TSHP Journal - v18 (2019)

TSHP Journal

10 YEARS SHAPING THE FUTURE OF TEXAS PHARMACY

We’re celebrating the successes of the TSHP Mentorship Program Page 31 VOLUME 18

ADVANCING PHARMACY PRACTICE AND EDUCATION IN TEXAS

|

2019

Parenteral Nutrition Management in Adults: A Review for Pharmacists

Meagan Johns, PharmD, MBA, BCNSP, BCCCP, BCPS

The Evolving Role of Direct Oral Anticoagulants in Cardiovascular Disease: A Review of Recent Literature Caitlin M. Gibson, PharmD, BCPS, BCCP Meredith L. Howard, PharmD, BCPS

Guideline Updates: Review of 2018 Guidelines of Blood Cholesterol Management

Student Corner: A Pharmacy Student’s Role in Disaster Simulation

Drug-Induced Myopathies: A Systematic Review of the Combined Use of Daptomycin and Statins OFFICIAL JOURNAL OF THE TEXAS SOCIETY OF HEALTH-SYSTEM PHARMACISTS

Awards, Grants, Competitions, and Scholarships: 2019 Recipients & Winners

Advocacy Perspectives: Advocating for Our Profession: A Look at Pharmacy Legislation at the State Level Teaching Moments: An Examination of Eating Disorders

WWW.TSHP.ORG/JOURNAL

TSHP Journal TSHP Journal Official journal of the Texas Society of HealthSystem Pharmacists www.tshp.org/journal Stacey Mather, CAE Executive Director

Jenni Peters Membership & Communications Manager Leah Cody Professional Development Manager Katha Ferguson Office Manager/Bookkeeper

About TSHP The Texas Society of Health-System Pharmacists (TSHP) has been supporting health-system pharmacy in Texas since 1949, becoming one of the leading health-system pharmacy societies in the country that fosters leadership and education in pharmacy. What began as a small group of twenty-five dedicated hospital pharmacists coming together to learn and discuss professional issues, has grown to a dynamic health-system pharmacy organization that includes pharmacists, technicians, residents, students, retired pharmacists, educators, industry associates, and others passionate about the mission, vision, and core values of TSHP: Pharmacy Leaders. Transforming Patient Care. For more information on TSHP, please visit www.tshp.org.

TSHP Executive Committee: President Steven Knight, PharmD, BCPS, RPh, CMTM President-Elect Sarah Lake-Wallace, MS, PharmD, FTSHP

Immediate Past President Tammy Cohen, PharmD, MS, FACHE, FASHP, FTSHP Secretary Latresa Billings, PharmD, BCPS Treasurer Randy Martin, PharmD, BCCCP

President-Elect Designee Latresa Billings, PharmD, BCPS

Secretary-Elect Mallory Gessner-Wharton, PharmD, MS, BCPS A very special thank you to the authors and contributors of this special issue, the TSHP Board of Directors, and the members of the 2018-2020 TSHP Editorial Advisory Board for their time and expertise in helping bring back the TSHP Journal better than ever. It is because of you that we can truly advance pharmacy practice and education in Texas.

Pharmacy Leaders. Transforming Patient Care.

ISSN: 2325-2804

Copyright © 2019 Texas Society of Health-System Pharmacists (TSHP)

VOLUME 18 | 2019

TSHP Editorial Advisory Board & Peer Reviewers: E. Paul Holder, MS, PharmD, FTSHP (Chair/Editor) Saeed Alzghari, MS, MBA, PharmD, BCPS Tina Beck, PharmD, MSCR, BCPS Jacqueline Bozick, PharmD, BCPS Amy Buesing, BS-Pharm, MBA Todd W. Canada, PharmD, BCNSP, BCCCP, FASHP, FTSHP, FASPEN Abimbola Farinde, PharmD Caitlin Gibson, PharmD, BCPS Khanh-Hau Moss, MS, PharmD, BCPS Kimberly Nguyen, PharmD Kathryn Pidcock, PharmD, BCPS TSHP JOURNAL

2

Continuing Education Information The Texas Society of Health-System Pharmacists (TSHP) is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing education. To claim credit for CE, the participant must complete the course via the TSHP Education Portal (http://tshp.wcea.education/), pass an exam with a minimum score of 75%, and complete a session evaluation. Additional information on any available CE within this issue can be found at the end of each applicable article.

Completion of this course requires access to an internet-enabled computer. Mozilla Firefox is the preferred browser for the TSHP Education Portal. For information regarding TSHP’s privacy policy, please visit http://tshp.org/privacy-policy. html. To view the privacy policy specific to the TSHP Education Portal, visit https://tshp.wcea. education/default/privacy. Questions? Contact TSHP at tshp@tshp.org.

Hardware Requirements: Any computer capable of running an A-grade web browser. Typically, a minimum memory of 1GB, and a processor speed of 1Ghz

Software Requirements: Any of the following A-grade browsers: • Chrome 45+ • Edge 38+ • Firefox 40+ • Opera 15+ • Safari 7+ No other plugins are mandatory. Adobe Flash is recommended.

Connectivity: Minimum 1MB/s downstream, 512KB/s speed upstream

speed

For full CE information (UAN numbers, objectives, CEUs, type), see the end of the applicable article(s).

The TSHP Journal is the official publication of the Texas Society of Health-System Pharmacists (TSHP). TSHP is a membership-driven state society of pharmacists, technicians, students, and professional colleagues who advocate for optimized patient care, professional practice, and public health. Membership in TSHP is open to all pharmacists and others who support TSHP’s mission and values. Annual membership dues are $180, of which $30 is for a subscription to the TSHP Journal.

The annual subscription rate (minimum 2 issues) to non-members is $40. The cost for single copies is $25. Payments made to TSHP are not deductible as charitable contributions for federal income tax purposes. However, they may be deductible under other provisions of the IRS up to 33%. TSHP payment processing can be reached at (512) 9060546 Monday through Friday, 8:00 AM to 5:00 PM Central Time or by contacting tshp@tshp.org.

To view membership status, login at www.tshp. org/login or contact the TSHP office.

CONTENTS 5 6

Message from the TSHP President Steven Knight, PharmD, BCPS, RPh, CMTM

Review of 2018 Guideline of the Management of Blood Cholesterol Kathryn N. Pidcock, PharmD, BCPS & Steffany N. Nguyen, PharmD

12 The Evolving Role of Direct Oral Anticoagulants in

CPE

Cardiovascular Disease: A Review of Recent Literature

Caitlin M. Gibson, PharmD, BCPS, BCCP & Meredith L. Howard, PharmD, BCPS

17 Advocating for Our Profession: An Inside Look at Pharmacy Legislation at the State Level

12

18 A Pharmacy Student’s Role in Disaster Simulation

19 Attending a TSBP Board Meeting from the Pharmacy Students’ Perspectives

22 Parenteral Nutrition Management in Adults: A Review for Pharmacists (CPE)

CPE

Meagan Johns, PharmD, MBA, BCNSP, BCCCP, BCPS

31 10 Years Shaping the Future of Texas Pharmacy

32 Drug-Induced Myopathies: A Systematic Review of the

22

Combined Use of Daptomycin and Statins

Marian L. Gaviola, PharmD, BCCCP; Elizabeth Berihun, BS; Abigail Cole; Marc Esquivel, BS; Stephanie J. Cox, PharmD; Meredith L. Howard, PharmD, BCPS

38 An Examination of Eating Disorders Abimbola Farinde, PharmD, BCGP

TSHP Journal 3000 Joe DiMaggio Blvd., Ste. 30A Round Rock, Texas 78665-3920 (512) 906-0546

TSHP President Steven Knight, PharmD, BCPS, RPh, CMTM TSHP Journal Editor Paul Holder, MS, PharmD, FTSHP

11 19 28 37 40 42

2017 Grant Recipient Results 2019 Foundation Scholarships 2019 TSHP Awardees 2018 Grant Recipient 2019 Competition Winners 2019 Poster Winners

TSHP Journal Managing Editor Jenni Peters Questions/Comments journal@tshp.org

TSHP JOURNAL

3

32 VOLUME 18 | 2019

www.tshp.org/PAC

Authorship The Texas Society of Health-System Pharmacists Editorial Advisory Board welcomes manuscripts from any source that are pertinent to the practice of pharmacy in hospitals and health systems. Manuscripts are subject to review by the Editorial Advisory Board and Editor(s) and will be accepted for publication only if they are believed to represent an important contribution to the literature. Authors should follow the procedure checklist and submission instructions at www.tshp.org/journal. Authors without internet access may mail one (1) copy of their manuscript and a USB flash drive containing the manuscript file and supporting material to TSHP Journal, 3000 Joe DiMaggio Blvd, Ste 30A, Round Rock, Texas 78665-3920. Authors may call (512) 906-0546 for assistance.

Accepted materials may not be published elsewhere without written permission from both the author and TSHP. The Editor(s) reserve the right to revise all manuscripts submitted, if necessary. The publisher assumes no responsibility for the statements and opinions advanced by contributors to the TSHP Journal.

For guidance on style, authors should consult the manuscript checklist, recent issues of the TSHP Journal and American Journal of Health-System Pharmacy, and Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers, 6th edition. The AMA’s Manual of Style contain helpful advice on correct usage.

The views expressed by authors of contributions in the TSHP Journal do not necessarily reflect the policy of TSHP or the institution with which the author is affiliated, unless otherwise specified. Authors, reviewers, Editorial Board members, and TSHP Journal editors are required to declare potential conflicts of interest regarding manuscripts submitted for publication.

VOLUME 18 | 2019

TSHP JOURNAL

4

A MESSAGE FROM TSHP PRESIDENT

W

e are pleased to bring you the latest issue of the Texas Society of Health-System Pharmacists’ journal! TSHP Journal represents the pinnacle of the scholarly efforts to advance medical literature by pharmacists, residents, technicians, and students from across our great state and is one of many ways membership in the TSHP community opens doors to new thought provoking ideas. The journal’s Editorial Advisory Board has been judiciously working on selecting excellent content for this issue. We hope you enjoy exploring this latest issue!

The TSHP Board of Directors is excited to announce a change on the horizon. The TSHP Journal has been approved by the Board to be renamed to the Texas Journal of Health-System Pharmacy (TJHP). We look forward to this tremendous value for members to continue to be an excellent avenue for sharing clinical and scholarly work.

We are determined to continue to grow the value that being a member of TSHP brings, and the TJHP grants both members and potential members the ability to contribute to medical literature and share their bright ideas.

There are many, many ways you can continue to professionally grow yourself so that you are advancing patient care and the practice of pharmacy. It all starts from the beginning before you even set foot in your pharmacy. No one can run a pharmacy on their own. It truly takes a team effort to fill prescriptions in the retail practice setting or to distribute medications to automated dispensing cabinets in large institutional settings.

Surrounding yourself with high performing, positive-minded peers is one of the most advantageous positions you can place yourself in when choosing a practice site. Now, that is an important distinction to make when applying for positions. Although brief, the on-site interview is one of the best litmus tests to envision the possibility for you to grow as a professional within the culture of a practice site. Inserting yourself into an empowered, progressive team is like jumping into fast moving stream and swimming with the current. Truly a momentum builder for your early career, or a potential career accelerator for our peers seeking new job opportunities.

Once you have established your professional role in your site, one of the best ways you can start to advance patient care in your practice site is by building bridges with other practitioners. From interactions with bedside nurses to nurse practitioners to physicians, the more you are a resource to these providers, the more opportunities to be called upon in the future. Every interaction in front of or with the patient will further reinforce the role that you play in their life. When I was part of the bedside team as a transplant clinical pharmacist, I was amazed at how the patients and their family members asked questions related to their medications that they themselves admitted they would never ask their physicians. This truly demonstrates a way that we can all push practice in a positive light starting with every patient interaction. The simple act of identifying yourself as a pharmacy technician or pharmacist can tear down barriers of confusion and uncertainty, and let patients start to better understand their medications.

Contributing to patient care as part of a team of caregivers may be the most consistent opportunity we can contribute to practice advancement. Day-to-day activities in many practice settings grant the ability to demonstrate how all pharmacy technicians and pharmacists can practice at the upper limits of their

licenses. Whether your role is a clinical specialist in an intensive care unit recommending the addition of a new vasopressor, a technician compounding sterile compounds following highly stringent compounding standards, or an administrator implementing new sweeping workflow changes to increase interactions with patients, we can all find ways to contribute to the amount of time patients and their family members can interact with their pharmacists.

Exploring and pushing the limits of pharmacy practice is definitely a careerspanning endeavor and a calling we must all be willing and prepared to answer.

There are myriad ways to get involved in professional pharmacy organizations, and to put your skills to work to advance the care of our patients across the state and nation. From local chapter affiliates to statewide councils to national committees, your journey in practice advancement awaits. We look forward to hearing of the many ways you are contributing to and advancing the practice of pharmacy. Until the next issue of TJHP, the entire TSHP Board and Staff wishes you a very restful holiday season as the year ends and a wonderful start to a fruitful new year!

Steven Knight, PharmD, BCPS, RPh, CMTM TSHP President 2019-2020

TSHP President Steven Knight (center) celebrates with the newly installed 2019-2020 Technician Section Officers at the 2019 TSHP Annual Seminar at Embassy Suites by Hilton Dallas Frisco Hotel, Convention Center, & Spa. Officers pictured left to right: Leon Jacob, Serena Spurlock, Sam Tetteh, LiAnne Brown.

TSHP JOURNAL

5

VOLUME 18 | 2019

Guideline Update Review of the 2018 Guideline on the Management of Blood Cholesterol Purpose: This article provides a review of the 2018 Guideline of Management of Blood Cholesterol.

Kathryn N. Pidcock, PharmD, BCPS Houston Methodist Hospital Pharmacy Department Houston, TX Steffany N. Nguyen, PharmD Houston Methodist Hospital Pharmacy Department Houston, TX

S

ince the 2013 ACC/AHA guideline’s introduction of the four statin benefits groups, changes to monitoring parameters, and limited guidance regarding use of non-statin therapies, several focused updates have been published to address some of the gaps in hyperlipidemia management that were not previously addressed. Additional updates include those published from the National Lipid Association, the American Association of Clinical Endocrinologists, and the American College of Cardiology.1-4 A review of the 2018 Guideline of the Management of Blood Cholesterol5 is important because we feel that this latest guideline provides the most comprehensive approach to hyperlipidemia management and is valuable for pharmacy practitioners in both inpatient and outpatient settings.

The latest guideline provided additional recommendations for each of the four statin benefits groups first introduced in the 2013 ACC/AHA guideline, as well as recommendations for special populations not included in the previous guideline. Furthermore, the 2018 guideline was a collaborative effort by medical experts including cardiologists, internists, interventionists, a nurse practitioner, pharmacists, a physician assistant, a pediatrician, a nephrologist, and a patient representative. The writing committee in-

VOLUME 18 | 2019

Summary: The article discusses updated guideline recommendations on management of blood cholesterol in secondary prevention of ASCVD, severe hypercholesteremia, diabetes mellitus, as well as primary ASCVD prevention.

Discussion of lifestyle therapy, fixed dose statin therapy, and non-statin therapy is included. A review of the management of blood cholesterol in special patient populations such as elderly, young adults, children and adolescents, certain ethnicity groups, patients with hypertriglycer-

cluded representatives from the American Heart Association (AHA), American College of Cardiology (ACC), American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), American Association Academy of Physician Assistants (AAPA), Association of Black Cardiologists (ABC), American College of Preventive Medicine (ACPM), American Diabetes Association (ADA), American Geriatrics Society (AGS), American Pharmacists Association (APhA), American Society for Preventive Cardiology (ASPC), National Lipid Association (NLA), and Preventive Cardiovascular Nurses Association (PCNA).

The 2018 guideline did not change its recommendations from 2013 regarding the use of fixed-dose statins in the four statin benefits groups, importance of lifestyle changes, and monitoring of percentage LDL-C reduction as a measure of efficacy. However, the new guideline suggested LDL-C thresholds on when to consider adding non-statin therapies, recommendations on use of non-statin therapies, and additional risk factors to consider when evaluating atherosclerotic cardiovascular disease (ASCVD) risk and hyperlipidemia management.

TSHP JOURNAL

6

idemia, women, patients with chronic kidney disease, and patients with certain inflammatory disorders, is also provided. Lastly, statin-associated side effects as well as the economic value of PCSK9 inhibitors are briefly discussed.

Conclusion: This review article of the 2018 Guideline of Management of Blood Cholesterol provides pharmacists an opportunity for CE credits by reviewing the use of statins and addition of non-statin therapy for primary and secondary prevention of ASCVD, elements of lifestyle modification in hyperlipidemia patients, and how to manage potential statin-associated side effects.

Lifestyle Therapies

Patients should follow a diet consisting of vegetables, fruits, whole grains, legumes, healthy protein sources (low-fat dairy, lowfat poultry, fish/seafood, nuts), and non-tropical vegetable oils. Sweets, sugar-sweetened beverages, and red meats should be limited.

Caloric intake should be modified to avoid weight gain or promote weight loss in obese/ overweight patients. Other lifestyle therapies include at least 3 to 4 sessions of moderate to high intensity per week, with each session lasting at least 40 minutes. In patients with metabolic syndrome (defined as the presence of at least 3 of 5 risk factors: elevated waist circumference, elevated serum triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose), lifestyle changes are especially indicated since these patients are at increased risk for ASCVD, diabetes, and all-cause mortality.

Lipid-Lowering Drugs

Among lipid-lowering drugs, statins are the foundation of therapy along with therapeutic lifestyle changes. Other LDL-lowering drugs include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. Fibrates and niacin lower triglycerides with mild LDL reduction, but do not have substantial evidence to use as add on therapy for statins.

Guideline Update Fixed Dose Statin Therapy

Recommendations for the use of fixed doses of statins, based on the percentage of LDL-C reduction percentage observed in RCTs, remain in line with the 2013 guideline.

(Table 1) LDL-C should be ordered at baseline, and 4-12 weeks after initiation of fixed-dose statin therapy to monitor for response to therapy and reduction in LDL-C. Non-adherence to statin therapy and lifestyle changes may lead to suboptimal LDL-C reduction; therefore, the need for lab monitoring periodically remains emphasized.

Non-statin Therapies

In certain situations, non-statin therapies including ezetimibe, bile acid sequestrants, and PCSK9 inhibitors may be useful in combination with statins. Ezetimibe lowers LDL-C by 13%-20% and has a favorable adverse effect profile. Bile acid sequestrants (BAS) lower LDL-C by 15%-30% in a dose-dependent manner. These agents are not absorbed and therefore do not cause systemic side effects, but they are typically associated with gastrointestinal complaints such as constipation and bloating. BAS can also increase triglycerides in patients with baseline fasting triglycerides > 300 mg/dL. PCSK9 Inhibitors possess potent LDL-C reduction of up to an additional 43-64% when added onto statin therapy and are overall well-tolerated, however are limited by their cost and long-term safety data.

Patient Management Groups

Secondary ASCVD Prevention. Clinical ASCVD includes acute coronary syndrome (ACS), history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, peripheral arterial disease (PAD), aortic aneurysm, or transient ischemic attack (TIA). In patients with ASCVD, high-intensity statins are the preferred treatment to achieve at least 50% LDL-C reduction. Those with ASCVD who cannot tolerate high-intensity statins may receive moderate-intensity statin to achieve at least 30%-40% LDL-C reduction. In patients receiving maximally tolerated statin therapy, the recommended threshold for addition of non-statin therapies including ezetimibe is an LDL-C of 70 mg/dL or higher. In patients >75 years old with ASCVD, therapy initiation is dependent upon considerations weighing benefits versus

potential adverse effects from statin therapy. For patients considered “very high risk ASCVD� due to a history of multiple major ASCVD events or presence of high-risk conditions with elevated LDL-C or non-HDL-C while receiving maximally tolerated statin, ezetimibe should be added to statin therapy.

However, if LDL-C remains > 70 mg/dL or non-HDL-C level of > 100 mg/dL, adding a PCSK9 inhibitor is an additional option if the cost/benefit ratio is advantageous to the patient. In patients with heart failure with reduced ejection fraction who have a 3-5 years life expectancy and are not already on a statin for ASCVD, initiation of moderate-intensity statin therapy may help reduce occurrence of ASCVD events.

Severe Hypercholesteremia (Age 2075 with baseline LDL-C ≼ 190 mg/dL). In patients with severe hypercholesterolemia, high intensity statin therapy has the greatest risk reduction. The combination of ezetimibe and moderate intensity statin confers greater LDL-C reduction over statin monotherapy in patients with heterozygous familial hyperlipidemia and in patients with recent MI. For those with LDL-C not sufficiently reduced with pharmacologic therapy, LDL apheresis may be considered in conjunction with a conversation with a lipid specialist.

Diabetes Mellitus. In adult patients 4075 years of age with diabetes mellitus, use of the 10-year ASCVD risk evaluation may assist in lipid therapy decision-making. Moderate-intensity statin therapy is indicated in patients with a history of diabetes mellitus based on significant benefits shown in most primary prevention trials. As patients age or if they have additional risk modifiers such as long duration of diabetes (>10 years for type 2, >20 years for type 1), albuminuria >30 mcg of albumin/creatinine, eGFR <60 ml/ min/1.73 m2, retinopathy, neuropathy, or ABI < 0.9, high-intensity statin therapy is recommended. This recommendation is based on evidence supporting the benefit of primary prevention in older patients (men >50 years, women >60 years) as well the increased rates of morbidity and mortality associated with first ASCVD event in diabetes and residual risk in statin-treated groups. Adults 20-39 years of age with diabetes most likely have low 10-year ASCVD risk; however, in those with an extensive history of diabetes or additional risk modifiers, moderate-intensity statin therapy is a reasonable consideration.

Adults >75 years of age with diabetes are at high risk for complications from longstandTSHP JOURNAL

7

ing diabetes. Evidence from clinical trials indicate that these patients should be continued or initiated on statin therapy, with careful consideration of life expectancy and risk for treatment-related adverse effects.

Primary ASCVD Prevention. Adults 40-75 years of age, primary prevention may be initiated based on 10-year risk of ASCVD which may be classified as low-risk (<5%), borderline risk (5% to <7.5%), intermediate-risk (7.5% to <20%), and high-risk (> 20%). For intermediate-risk patients, moderate to high-intensity statin therapy should be discussed as options that will offer favorable long-term benefits. Other conditions supporting use of statins for primary prevention in intermediate-risk patients include certain factors that increase ASCVD risk (Table 2). Patients with higher baseline ASCVD risk obtain greater absolute benefit from more aggressive LDL-C reduction by at least 30% and more optimally by at least 50%, with evidence-based therapy. Further consideration of risk-enhancing factors should be considered when there is uncertainty on whether or not to initiate statin therapy, and the guidelines suggest that coronary artery calcium (CAC) scoring may be useful for guidance.

Select Special Populations

Primary Prevention in the Elderly.

Risk factors for ASCVD increases with age.

Data from primary literature are conflicting regarding the use of statins in older adults.

Furthermore, older adults are more at risk for statin-related adverse events due to age-related changes in pharmacokinetics and pharmacodynamics. Side effects from statins can also adversely impact older adults due to the presence of multiple comorbidities, multiple medications, deterioration in cognitive function, and nutritional status. Despite these factors, current guideline still recommend moderate-intensity statin therapy for adults >75 years of age with LDL-C 70-189 mg/dl.

However, it is reasonable to discontinue therapy in the settings of reduced life expectancy, functional decline, frailty, and multiple comorbidities. In older adults with CAC scores of zero, the risks and benefits of statin therapy are comparable; therefore, shared decision-making should be made before initiating therapy.

Young adults. Elevated LDL-C >190 mg/ dl in young adults poses long-term ASCVD risk; therefore, statin therapy is recommended. Secondary causes of elevated cholesterol VOLUME 18 | 2019

Guideline Update should be investigated, and if ruled out despite persistent LDL-C elevations, the possibility of genetic hypercholesterolemia should be considered. Intensive lifestyle changes offer lipid-lowering benefits as well as reduction in ASCVD risk factor burden. In young adults with persistent, moderately high LDL-C 160189 mg/dl, and other risk factors such as family history of early ASCVD, clinical judgment advocates for use of statin therapy in this high-risk group. In young adults without phenotypically severe hypercholesterolemia, risk assessment should start with estimation of lifetime risk. Lifestyle interventions are indicated when multiple risk factors are present. Of note, no long-term randomized trials have been conducted in patients 20-39 years of age. Furthermore, CAC scores can be used to detect coronary atherosclerosis and help identify those that would benefit from statin therapy, but absence of randomized data in this area have limited guideline recommendation at this time.

Children and adolescents. Confirmed lipid disorder can occur frequently in children and adolescents in the setting of obesity, with increased cardiovascular risk factors, and significantly increased risk of cardiovascular and metabolic morbidity and mortality.

Non-fasting lipid testing and non-HDL-C assessment are both effective for initial screening tests. Lifestyle changes can improve lipid levels without affecting growth and maturation; however, adherence may be difficult to maintain over time. Statins and non-statin therapy can lower total cholesterol and LDL-C with little adverse effects in children and adolescents with severe hypercholesterolemia. In children and adolescents > 10 years of age without response to 3-6 months of lifestyle therapy, who have persistent LDL-C > 190 mg/dl or > 160 mg/dl with familial hypercholesterolemia, initiation of statin therapy is recommended.

Ethnicity. Race/ethnicity, country of origin, and socioeconomic status can impact ASCVD risk estimates, intensity of treatment, and may guide use of lipid therapy. Examples include increased risk of ASCVD in South Asians, and increased statin sensitivity in East Asians. Native American/Alaskan natives also have high rates of risk factors for ASCVD compared to non-Hispanic whites.

The limitation of race/ethnicity-directed risk stratification includes lack of specificity in the classification of Hispanic/Latino in the US, thereby leading to issues in management of ASCVD risk.

VOLUME 18 | 2019

Hypertriglyceridemia (HTG). In all patients regardless of age, it is essential to first address lifestyle factors and comorbidities such as diabetes mellitus, chronic liver or kidney disease and/or nephrotic syndrome, hypothyroidism, and medications that can increase triglycerides. In adults 40-75 years of age with moderate or severe hypertriglyceridemia and ASCVD risk of 7.5% or higher, initiation or intensification of statin therapy may be considered after evaluating for lifestyle and other comorbidities as potential causes of elevated triglycerides. For those in this age group with triglycerides > 500 mg/dL and ASCVD risk 7.5% or higher, it is reasonable to initiate statin therapy. Finally, in adults with fasting TG > 500 mg/dL and those with TG > 1000 mg/dL, lifestyle changes including diet and exercise, eliminating trans-fatty acids, reducing simple carbohydrates, reducing or limiting alcohol should be discussed. If necessary, to avoid acute pancreatitis in these patients with severe hypertriglyceridemia, it is reasonable to start fibrate therapy.

Women. Cardiovascular disease remains the leading cause of death in women despite atherosclerosis occurring later in life. Statin therapy has been proven to reduce ASCVD events similarly in women as well as in men.

Premature menopause in women younger than 40 years old and history of certain pregnancy-related problems (gestational diabetes, hypertension, preeclampsia, preterm deliveries, small for gestational-age infants) have been linked to increased ASCVD risk. Statin therapy, though effective in reducing ASCVD events, are not recommended in pregnancy. Women of childbearing age currently on statin therapy and are sexually active are encouraged to use a reliable form of contraception to avoid pregnancy. When planning to get pregnant, it is ideal to discontinue statin therapy 1-2 months before attempting conception. If an unplanned pregnancy happens, statins should be discontinued immediately.

Patients with genetic lipid disorders should consult with a lipid specialist prior to pregnancy, as both cholesterol and triglycerides are expected to increase during pregnancy.

Adults with CKD. As chronic kidney disease is a risk-enhancing factor for ASCVD, it is reasonable to initiate statin therapy in intermediate-risk patients with CKD. In adults with ESRD on dialysis, it is reasonable to continue statin therapy if patients have already been on treatment. However, it is not recommended to initiate statin therapy in adults with ESRD on dialysis.

TSHP JOURNAL

8

Chronic inflammatory disorders and HIV/AIDS. Inflammation and HIV infection both enhance the risk for ASCVD and therefore patients with these conditions may benefit from statin therapy. The 2018 guideline recommends screening for ASCVD in these patients via risk factor assessment and fasting lipid profile early and on a regular basis.

Before initiating therapy for ASCVD prevention, patients with HIV should be on antiretroviral therapy and counseled on modifiable risk factors. If the risk remains high, then moderate or high-intensity statin therapy is first line treatment. If the patient or clinician remains unsure about the need for statin therapy or if patient has had adverse effects from statin therapy in the past, using CAC score can help with risk assessment.

Statin Safety and Statin-Associated Side effects

Statin therapy is generally well tolerated and safe; however, associated side effects can be seen in certain patients. The present guideline recommends utilizing the terminology “statin-associated side effects” instead of “statin intolerance” as well as considering alternative etiologies for musculoskeletal symptoms prior to attributing to statin therapy such as drug-drug interactions, other disease states, and genetic reasons (SLCO1B1).

While literature has reported potential relationship between SLCO1B1 polymorphism and statin-related side effects, there are currently limited recommendations for pharmacogenomic testing as definitive conclusions regarding clinical decision-making have not been extensively evaluated.6-10 Most patients can tolerate another statin or alternative dosing regimen on re-challenge after a report of side effects. The most frequent reported statin associated side effects is statin-associated muscle symptoms (SAMS). SAMS can cause patients to become non-adherent to therapy and decrease the potential benefit on ASCVD outcomes. The majority of SAMS are subjective aches and pain without any other findings. Myalgia associated with statins are typically bilateral, involves proximal muscles, with onset weeks to months after initiation, and resolves after discontinuation. Small studies have suggested that management strategies for patients with SAMS can include discontinuation of statins until symptoms improve, re-challenging with lower dosing, switching to an alternative statin, or utilizing alternative dosing regimens, while continuing to monitor for recurring symptoms.

Guideline Update GAUSS-311 evaluated statin tolerability in patients with a history of muscle-related adverse effects and its findings highlighted the importance of patient perceptions on ability to tolerate statins. Although the reported rate of intolerance during atorvastatin administration was higher than that observed with placebo, these differences were minor, reflecting the significance of the “nocebo effect” (adverse effects during placebo administration) among patients with a history of statin intolerance. Zhang12 and colleagues evaluated reasons for statin discontinuation and the role of statin-related events in routine care settings. The authors concluded that statin discontinuation was common in routine care settings (1 in 5 patients), which is consistent with previously published studies. The rate of reported statin-related events was nearly 18%, higher than the previously described 5-10% rate in randomized placebo-controlled clinical trials. The majority of patients re-challenged with a statin after a statin-related event were ultimately able to tolerate therapy, whereas few others experienced another statin-related event and, rarely, serious reactions such as rhabdomyolysis. Lastly, a retrospective analysis study done by Mampuya and colleagues13 aimed towards intermittent statin dosing suggested that patients who underwent this treatment strategy had significantly lower LDL-C reduction compared to the daily dosing group. However, when compared to the group of patients who underwent statin discontinuation, patients with intermittent dosing had a significantly higher LDL-C reduction as well as trend towards decreased all-cause mortality at 8 years, and a significantly higher percentage of patients achieved their LDL goal.

fects including re-assessment, re-discussion, re-challenge unless side effects are severe.

Economic Value of PCSK9 Inhibitors

PCSK9 inhibitors reduce LDL-C further when combined with other LDL-lowering agents. The FOURIER14 trial evaluated LDL reduction with evolocumab 140 mg SC every 2 weeks or 420 mg SC once monthly vs placebo in patients with stable ASCVD and LDL levels > 70 mg/dL who were already receiving statin therapy. Compared to placebo, evolocumab treatment significantly reduced the risk of the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization by 15%. Secondary end point of cardiovascular death, myocardial infarction, or stroke risk were reduced by 20% compared to placebo.

ODYSSEY OUTCOMES15 evaluated the use of alirocumab 75 mg SC every 2 weeks vs placebo in patients who had an acute coronary syndrome within the past 12 months, LDL > 70 mg/dL, non−HDL > 100 mg/dL, or apolipoprotein B level > 80 mg/dL, and were receiving high-intensity or maximally tolerated statin therapy. The composite primary end point of death from coronary heart disease, nonfatal myocardial infarction, fatal

or nonfatal ischemic stroke, or unstable angina requiring hospitalization occurred in 9.5% in the alirocumab vs. 11.1% in placebo group.

Absolute benefit with alirocumab was greater in those with baseline LDL > 100 mg/dL compared to those with lower baseline LDL levels.

In published models, when compared with statin therapy for secondary prevention, PCSK9 inhibitors have an incremental cost-effectiveness ratio of $141,700 to $450,000 per quality-adjusted life year (QALY) added. None of the models show “good value” (<$50,000 per QALY added); all models mostly indicate “low value” >$150,000/QALY added). For PCSK9 inhibitors to be cost effective, the price would have to be reduced by 70-85%. The economic value of these agents will be enhanced if their use is limited to patients at very high risk for ASCVD events.16-18

Conclusion

Overall, we feel that the 2018 guideline is very comprehensive and provides further insight in the complexity of hyperlipidemia management. Compared to earlier published renditions, this guideline highly emphasized the importance of personalized care and creates a treatment road map for clinicians. The

Routine measurements of creatinine kinase (CK) and transaminases are not recommended after initial baseline. However, in cases of severe SAMS and objective muscle weakness, it is reasonable to measure CK and transaminases if there are signs and symptoms of hepatotoxicity. An increase in transaminases of 3 times the upper limit of normal occurs infrequently and often normalizes with dose reduction or re-challenging with alternative statins. Statins may also moderately increase the risk of diabetes in certain individuals, but this should not result in discontinuation of therapy nor be a contraindication to initiating statin therapy. The current guideline recommends a comprehensive approach to statin-associated side efTSHP JOURNAL

9

VOLUME 18 | 2019

Guideline Update guideline provided further risk assessment based on ASCVD score (low-risk, borderline-risk, intermediate-risk, high-risk) with specific recommendations for each and also considered additional “risk-enhancing” patient factors that are not incorporated in the population-based ASCVD risk equation.

Furthermore, LDL targets for high-risk patients were discussed compared to the 2013 guideline which had previously removed LDL targets. More specific recommendations for special patient populations as well as the incorporation of the 2017 focused updates regarding role of non-statin in clinical scenarios that may benefit from non-statin therapies were addressed. Detailed risk assessments were reviewed to help clinicians better determine individualized risk stratification and management strategies, with emphasis on healthy living, lifestyle modifications, and lifetime risks for cardiovascular disease. Lastly, recommendations for statin safety and statin-associated side effects were reviewed, which provides valuable insight for practitioners in management of adverse effects.

Current limitations and expectations listed for future guidelines include incorporation of additional evidence for non-statin therapies (including PCSK9 inhibitors) to determine their full scope of benefit in both primary and secondary prevention of ASCVD, short-term ASCVD risk and lifetime ASCVD risk algorithms for those 20 to 59 years of age, and lastly, the guidance of using calcium scoring for treatment decisions.

et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(Suppl 2):1-87.

5. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Circulation. 2018;000:e000–e000.

6. Ghatak A, Faheem O, Thompson PD. The genetics of statin-induced myopathy. Atherosclerosis. 2010;210(2):337-43.

7. Brunham LR, Baker S, Mammen A, et al.

Role of genetics in prediction of statin-associated muscle symptoms and optimization of statin use and adherence. Cardiovasc Res. 2018;114: 1073–81.

8. Niemi M. Transporter Pharmacogenetics and Statin Toxicity. Clin Pharmacol Ther.

2010;87(1):130-33.

9. Peyser B, Perry EP, Singh K, et al. Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings. Circ Genom Precis Med. 2018;11(9):e002228 10. 1Vrahblik M, Zhatohlavek L, Stulc T, et al.

Statin-associated myopathy: from genetic predisposition to clinical management.

Physiol Res. 2014;63(Suppl 3): S327-34.

11. Nissen SE, Stroes E, Dent-Acosta RE.

12.

13.

14.

15.

16.

17.

18.

Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance, the GAUSS-3 randomized clinical trial. JAMA. 2016;315(15):1580-90.

Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings. Ann Intern Med. 2013;158(7):526-34.

Mampuya WM, Frid D, Rocco M, et al.

Treatment strategies in patients with statin intolerance: the cleveland clinic experience.

Am Heart J. 2013;166(3):597-603.

Sabatine MS, Guigliano RP, Keech AC, et al. Evolucumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376;1713:22.

Schwartz GG, Steg G, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097-2107.

Kazi DS, Penko J, Coxson PG, et al. Updated cost-effectiveness analysis of PCSK9 inhibitors based on the results of the FOURIER trial. JAMA. 2017;318(8):748-50.

Fonarow GC, Keech AC, Pedersen TR, et al.

Cost-effectiveness of evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease.

JAMA Cardiol. 2017;2(10):1069-78.

Arrieta A, Hong JC, Khera R. Updated cost-effectiveness assessments of PCSK9 inhibitors from the perspectives of the health system and private payers: insights derived from the FOURIER trial. JAMA Cardiol.

2017;2(12):1369-74.

TSHP

Career Center

References 1.

2.

3.

4.

Bays HE, Jones PH, Brown WV, et al. National Lipid Association Annual Summary of Clinical Lipidology 2015. J Clin Lipido.

2014;8:S1-36.

Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016;68:92–125.

Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70:1785–822.

Jellinger PS, Handelsman Y, Rosenblit PD,

VOLUME 18 | 2019

Connecting Talent with Opportunity

www.tshp.org/cc TSHP JOURNAL

10

TSHP Research & Education Foundation Chester A. (CAB) Bond Memorial Research Grant

2017 Project Results Utilization of Robotic-assisted Video Conferencing to Extend Pharmacists’ Presence on Patient Care Floors to Provide Transition-ofCare Clinical Services in a Newly Opened Community Hospital M Nguyen, R Xu, K Emerson, K Rathmann Houston Methodist The Woodlands Hospital, Conroe, Texas Background: In newly opened hospitals, the pharmacy practice model is primarily centralized to allow the optimization of operational and clinical workflows. Consequently, the lack of the pharmacists’ presence on patient care floors poses unique challenges to provide clinical services and improve patient care, especially during transition of care. In this prospective observational study, the pharmacy staff utilizes a robotic-assisted video conferencing (RVC) device on patient care floors to provide virtual pharmacy services including discharge counseling and addressing patients’ medication questions.

Objective(s): The goal of this study is to assess patients’ acceptance towards the virtual interaction with pharmacy staff through the RVC interface by conducting anonymous internal patient surveys.

Method(s): The RVC device is used to conduct two-way video conferencing to provide medication education and perform discharge counseling. After each RVC encounter, four survey questions are presented to the patients to assess whether the interaction was smooth, easy to use, the purpose of the medications is understood, and the side effects of the medications are understood. Descriptive statistical analyses were performed.

Result(s): Among the patients surveyed, 75% were 50 years or older. Nearly all patients agreed or strongly agreed to the four questions designed to assess patient acceptance to the RVC encounters for medication counseling.

Conclusion(s): This study demonstrated general acceptance, interest, and appreciation of the virtual clinical services. Furthermore, patient’s age was not shown as a barrier for implementing a novel technology for pharmacy services. Future studies should focus on additional outcomes such as the impact on HCAHPS survey scores.

See page 48 for poster image and poster competition standing.

TSHP JOURNAL

Figure 1. Video conferencing device (iPad®) mounted on a Double® Robotics mobile device

11

VOLUME 18 | 2019

The Evolving Role of Direct Oral Anticoagulants in Cardiovascular Disease: A Review of Recent Literature CP

Caitlin M. Gibson, PharmD, BCPS, BCCP Associate Professor and Vice Chair University of North Texas System College of Pharmacy Department of Pharmacotherapy

cr E avai edit lable *

Meredith L. Howard, PharmD, BCPS Assistant Professor University of North Texas System College of Pharmacy Department of Pharmacotherapy

Introduction

Oral anticoagulants are among the most commonly prescribed medications in the United States. Prescribing patterns have shifted dramatically over the past decade following the advent of direct oral anticoagulants (DOACs). This drug class includes the direct thrombin inhibitor dabigatran, and the factor Xa inhibitors, apixaban, rivaroxaban, and edoxaban. The most common indications for DOACs are for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) and treatment or prevention of venous thromboembolism (VTE). Compared to vitamin K antagonists (VKA) such as warfarin, DOACs do not require routine monitoring, have fewer drug interactions, and do not require frequent dose adjustments. However, DOACs do require renal dose adjustments and are not well-studied in patients with low renal function. In landmark trials, DOACs are associated with similar or superior efficacy and similar or reduced rates of bleeding compared to VKA therapy.1-4 Because of these advantages, the medical community has recently engaged in research to expand the use of DOACs to other diseases and conditions. Here we review recent literature examining novel cardiovascular indications for DOACs.

Coronary Heart Disease

Up to 8% of patients who require percutaneous coronary intervention (PCI) for coronary heart disease (CHD) have concomitant VOLUME 18 | 2019

atrial fibrillation (AF).5 Patients who receive stents are often prescribed dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) to prevent thrombotic complications such as stent thrombosis, whereas patients with AF are often prescribed oral anticoagulants to reduce the risk of stroke or systemic embolism. Patients with both stents and AF traditionally received all three drugs in a treatment strategy known as triple therapy. However, triple therapy predictably results in a higher risk of bleeding events versus antiplatelet or anticoagulant therapy alone.6 Significant research has focused on novel methods for mitigating bleeding risk while maintaining antithrombotic efficacy.

The WOEST trial found higher rates of any bleeding among patients undergoing PCI and also requiring anticoagulation who received triple therapy (aspirin, clopidogrel, and warfarin) versus a clopidogrel and warfarin only regimen.7 More recent research has sought to identify a role for DOACs in concomitant CHD and AF, as DOACs are generally associated with lower rates of bleeding than warfarin.1-4 The 2018 Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report recommends incorporating an assessment of bleeding risk to guide decision-making regarding use and duration of triple therapy in stented patients with AF.8 The 2019 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) TSHP JOURNAL

12

Focused Update of the 2014 AHA/ACC/ HRS Guideline for the Management of Patients with Atrial Fibrillation prefers clopidogrel over prasugrel when triple therapy is warranted and gives consideration to double therapy with a P2Y12 receptor antagonist plus an anticoagulant: rivaroxaban 15 mg daily, dabigatran 150 mg twice daily, or warfarin.9 Three recent landmark trials have informed recommendations to consider DOACs in the management of patients requiring concomitant antiplatelet and anticoagulant therapy for overlapping coronary heart disease and NVAF. The PIONEER-AF trial randomized 2,124 patients with NVAF who had just undergone PCI to three arms: rivaroxaban 15 mg daily plus a P2Y12 receptor antagonist, rivaroxaban 2.5 mg twice daily plus DAPT, or VKA plus DAPT.10 There were no significant differences in baseline characteristics including P2Y12 antagonist selection between the arms. The primary endpoint of the trial, clinically significant bleeding, occurred less frequently in either rivaroxaban arm than the VKA arm. The rates of major adverse cardiovascular events were not higher in the rivaroxaban arms, but the trial was underpowered to detect these endpoints. As a result, the PIONEER-AF trial established a low dose rivaroxaban-containing regimen as a viable strategy to reduce bleeding risk among patients traditionally requiring triple therapy. The investigators estimated that in

order to establish non-inferiority or superiority for reduction in major adverse cardiovascular events, a trial would require enrollment of approximately 40,000 patients.

The RE-DUAL PCI trial randomized 2,725 patients with NVAF who had just undergone PCI to three arms: dabigatran 110 mg twice daily with a P2Y12 receptor antagonist, dabigatran 150 mg twice daily with a P2Y12 receptor antagonist, or VKA with DAPT.11 In the VKA plus DAPT arm, aspirin was discontinued 1-3 months after PCI. The primary endpoint of first major or clinically relevant nonmajor bleed occurred less frequently in both the dabigatran 110 mg and the dabigatran 150 mg arm than the VKA arm. Combining both dabigatran arms, dabigatran was non-inferior to the VKA arm in the primary efficacy outcome of composite of thromboembolic events, death, or unplanned revascularization, but the trial was underpowered to assess for efficacy of individual arms.

Although both studies above suggest DOAC-containing regimens reduce the risk of bleeding among patients with concomitant NVAF and coronary heart disease, neither study was designed to determine if this reduction is due to DOAC use, variable antiplatelet use or dose-reduction of DOACs. Most recently, the AUGUSTUS trial randomized patients with NVAF with recent acute coronary syndromes (ACS) or PCI and planned use of a P2Y12 receptor antagonist for at least six months in a two-by-two factorial design to receive either apixaban 5 mg twice daily or VKA therapy, and either aspirin or placebo.12 All patients received P2Y12 receptor antagonists for at least six months.

The primary endpoint of major or clinically relevant nonmajor bleeding occurred significantly less frequently in apixaban patients than VKA patients, and significantly more frequently in patients receiving DAPT than P2Y12 receptor antagonist monotherapy. The secondary efficacy outcome of the composite of death or hospitalization occurred less frequently among apixaban-treated patients than VKA-treated patients; this result was driven by reductions in hospitalizations. In the anti-platelet analysis, there was no significant difference between DAPT- and aspirin monotherapy-treated patients. The authors concluded that standard-dose apixaban plus P2Y12 receptor antagonist therapy without aspirin results in less bleeding and hospitalizations than VKA-containing regimens and DAPT-containing regimens. Detailed results

of these three studies are located in Table 1.

Valvular Heart Disease

In 2013, the RE-ALIGN trial was published demonstrating increased risks of both thromboembolism and bleeding with dabigatran compared with warfarin in patients with mechanical aortic or mitral valve replacement.13 Coupled with landmark DOAC trials excluding patients with valve replacements or moderate-to-severe mitral stenosis,1-4 the use of DOACs in valvular heart disease (VHD) and concomitant AF is not recommended.

Aligning with this data, the 2018 Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation have included an updated emphasis on valvular AF defined as mechanical valve replacement or moderate-to-severe mitral stenosis and recommend warfarin instead of DOACs.8,9 Although warfarin is recommended in the aforementioned specific subset of VHD, there is data investigating the use of DOACs in patients with other types of VHD, including prosthetic heart valves, trans-catheter aortic valve replacement (TAVR), and aortic or mitral regurgitation. Initial DOAC trials even included small numbers of some of these patients. In 2017, a meta-analysis of the four landmark DOAC trials in AF (ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY, and ROCKET AF) was conducted to evaluate the safety and efficacy of DOACs in VHD.14 There was an overall population of 13,585 patients across the four trials with VHD; the majority of patients had moderate-to-severe mitral regurgitation and smaller numbers of patients had mild mitral stenosis, moderate-to-severe aortic stenosis or tricuspid regurgitation, or valve surgery other than valve replacement with a mechanical valve. Patients with VHD were significantly older than the NVAF population and in ARISTOTLE and ENGAGE AF-TIMI 48 had significantly higher mean CHADS2 scores. Overall, amongst patients with concomitant VHD and AF the rate of stroke/systemic embolic events was lower with DOACs compared with warfarin (RR 0.84, 95% CI 0.58-0.86). Additionally, major bleeding rates were similar between DOACs and warfarin in the VHD population (RR: 0.93, 95% CI 0.68 to 1.27). No statistical heterogeneity was found between the trials.

TSHP JOURNAL

13

Each of the above landmark trials have separately published sub-analyses of patients with VHD which show similar results to the overall study populations. However, ARISTOTLE and ENGAGE AF-TIMI 48 sub-analyses specifically reviewed patients with bioprosthetic heart valves.15-18 A total of 191 patients in ENGAGE AF-TIMI 48 had bioprosthetic valves (0.9% of the total population).17 In this subgroup, patients receiving edoxaban 60 mg daily had significantly lower rates of combined stroke/systemic embolic events, major bleeding, and death compared with warfarin (HR 0.46, 95% CI 0.23â&#x20AC;&#x201C;0.91, P=0.03). Patients on edoxaban 30 mg daily also had significantly lower rates of the composite of combined outcomes or bleeding (HR, 0.12, 95% CI 0.01â&#x20AC;&#x201C;0.95, P=0.045). A sub-analysis of the ARISTOTLE trial was also completed in the 104 patients with bioprosthetic valves and 52 patients with histories of valve repair (0.85% of the total population).18 No significant differences in any of the clinical outcomes between apixaban and warfarin were found, including stroke/ systemic embolism, all cause death, major bleeding, or combined composite outcomes.

In addition to post-hoc analyses of the landmark trials, DOACs have also been prospectively investigated for AF in the setting of bioprosthetic valves and other VHD. The DAWA Pilot Study was a prospective, randomized, open label trial conducted to compare dabigatran with warfarin in patients with bioprosthetic valves and AF.19 While terminated early due to low enrollment, DAWA randomized and collected data on 27 patients over a 15-month time span. One patient in the dabigatran group developed an intracardiac thrombus, and one patient developed bleeding. In the warfarin group, one case of ischemic stroke and two cases of bleeding were reported. The trial was underpowered and no significant differences in any safety or efficacy endpoints between the two groups were found.

To investigate DOAC use in mitral stenosis and AF, a 2019 observational cohort study of South Korean patients from the national Health Insurance Review and Assessment Service database was conducted.20 Patients were included with any severity of mitral stenosis, including moderate-to-severe, and off-label DOAC use was matched to propensity-scored warfarin. Mitral valve surgery patients were excluded. A total of 2,230 patients were included with a mean CHA2DS2VOLUME 18 | 2019

VASc score of 5.2. The majority of patients (42.3%) received rivaroxaban, followed by dabigatran (32.9%), apixaban (17.2%), and edoxaban (7.5%). Severity of mitral stenosis was not reported. After a mean duration of follow-up of 27 months, there was less incidence of stroke or systemic embolism with DOACs compared with warfarin (HR 0.29, 95% CI 0.18-0.45). No difference was found in the incidence of intracranial hemorrhage.

Finally, numerous studies have been conducted or planned using DOACs in the setting of TAVR. The GALILEO trial was designed to evaluate rivaroxaban 10mg daily plus or minus aspirin versus DAPT (standard of care) post-TAVR outside the setting of AF. Although full results have not been published, GALILEO was halted early due to increase in all-cause mortality, thromboembolism, and bleeding in the rivaroxaban group.21 Apixaban was also evaluated post-TAVR. Patients who developed AF post-TAVR were initiated on either apixaban or warfarin in addition to standard antiplatelet therapy. Patients receiving apixaban had significantly lower rates of the composite safety endpoint which includ-

ed life-threatening bleeding, all-cause mortality, all-cause stroke (13.5% vs. 30.5%, p < 0.01), and had non-significantly lower rates of stroke at 30-days and 12-months compared with warfarin.22 Multiple trials are also underway evaluating edoxaban and apixaban post-TAVR.23,24

Discussion

in the setting of AF.25 Conversely, systemic anticoagulation is inferior to standard antiplatelet therapy in preventing thrombotic complications.26 Triple therapy with DAPT and warfarin has been the traditional treatment for patients with both disease states.

The DOACs, with lower bleeding rates than warfarin, have emerged as potential options for patients needing triple therapy.

In concomitant AF and CHD, reducing the risk of stent thrombosis and ischemic stroke must be balanced against the risk of bleeding. Dual antiplatelet therapy has previously been proven inferior to anticoagulation with warfarin for ischemic stroke prevention

The three major trials investigating regimens in patients with AF undergoing PCI with stenting outline various alternative anticoagulation/antiplatelet therapies. The PIONEER-AF and RE-DUAL PCI trials enrolled patients with ACS or stable ischemic heart disease receiving PCI with stents and found reduced rates of clinically relevant bleeding among patients receiving a DOAC plus P2Y12 antagonist versus DAPT plus VKA. The AUGUSTUS trial expanded enrollment to include ACS patients undergoing medical management and similarly found reduced rates of bleeding with DOAC plus P2Y12 antagonist therapy compared to VKA-based regimens or triple therapy. In all three studies, most patients received clopidogrel as the

Over the past decade, novel uses for DOACs outside of NVAF and venous thromboembolism have been investigated, including CHD with concurrent AF and VHD. The DOACs represent an attractive treatment option for many disease states requiring anticoagulation due to their ease of use, lower bleeding rates, and lack need for laboratory monitoring. Coronary heart disease and VHD represent two indications with increasing evidence for DOAC use.

Table 1: Landmark trials of DOACs in AF and CHD

Trial PIONEER AF6

Methods

Results

Inclusion criteria: adult patients with NVAF who had just undergone PCI Exclusion criteria: History of stroke or transient ischemic attack, CrCl <30 mL/min, or high-risk bleeding condition Three treatment arms: 1) RVX 15mg dailya + P2Y12 2) RVX 2.5mg BID + DAPTb 3) VKA + DAPTb

RE-DUAL

Inclusion criteria: Adult patients with NVAF who had just undergone PCI Exclusion criteria: valve replacement, CrCl <30 mL/min Three treatment arms: 1) DBG 110mg BID + P2Y12 2) DBG 150mg BID + P2Y12 3) VKA + DAPTb,c Primary outcome: first major or clinically relevant nonmajor bleed

AUGUSTUS8

Most patients were elderly white males Primary outcome occurred in 16.8% of Group 1, 18.0% of Group 2, and 17.4% of group 3 patients HR & 95% CI: Group 1 vs 3: 0.59 (0.47-0.75), p<0.001 Group 2 vs 3: 0.63 (0.50-0.80), p<0.001 Combined groups 1 & 2 vs. 3: 0.61 (0.50-0.75), <0.001

Primary outcome: clinically significant bleeding at 12 months

PCI7

Enrolled 2,124 patients in 1:1:1 fashion

Inclusion criteria: Adult patients with NVAF with recent ACS or PCI and planned use of P2Y12 antagonist for at least 6 months Exclusion criteria: valve replacement, severe renal insufficiency

Primary outcome: major or clinically relevant nonmajor bleeding

TTR = 65% More than 90% of P2Y12s selected were clopidogrel

No significant differences in MACE, but trial underpowered to study this endpoint Enrolled 2,725 patients

Not powered for efficacy analysis

Most patients were elderly males

88% of P2Y12s prescribed were clopidogrel

Primary outcome occurred in 15.4% of Group 1, 20.2% of Group 2, and 26.9% of Group 3 patients

TTR = 64%

HR & 95% CI: Group 1 vs. Group 3: 0.52 (0.42-0.63), p<0.001 for non-inferiority and superiority Group 2 vs. Group 3: 0.72 (0.58-0.88), p<0.001 for non-inferiority Composite of thromboembolic events occurred in 12.7% of combined Group 1 and Group 2 patients vs. 13.4% of Group 3 patients; HR 1.04 & 95% CI 0.84-1.29, p=0.005 for non-inferiority Enrolled 4,614 patients Most patients were elderly males Primary outcome occurred in 10.5% of apixaban patients and 14.7% of VKA patients: HR 0.69 (0.58-0.81), p<0.001 for superiority

Two-by-two factorial design: 1) APX 5mg BID or VKA 2) Aspirin or placebob All patients received P2Y12 antagonists

Notes DAPT duration was provider-driven and ranged from 1-12 months

Primary outcome occurred in 40.5% of aspirin vs. 21.0% of placebo patients: HR 1.89 (1.59-2.24); p<0.001 for superiority of placebo

No comparisons of dabigatran 110 mg vs 150 mg regimens Early discontinuation of aspirin compared to current practice guidelines Patients outside of the US were not eligible for enrollment into dabigatran 150mg arm due to approved dosing in those countries.

Twenty-four percent of patients had medically managed ACS; first trial to include this patient group TTR = 59% Anticoagulation randomization was open-label, antiplatelet randomization was double-blind

Composite of death or hospitalization occurred less commonly among apixaban than VKA patients (23.5% vs 27.4%, HR 0.83, 95% CI 0.74-0.93) Composite outcome occurred at similar rates between aspirin and placebo arms

APX = apixaban; CI = confidence interval; DAPT = dual antiplatelet therapy; DBG = dabigatran; HR = hazard ratio; MACE = major adverse cardiovascular events; NVAF = non-valvular atrial fibrillation; P2Y12 = P2Y12 receptor antagonist; RVX = rivaroxaban; TTR = time in therapeutic range (for warfarin patients); VKA = vitamin K antagonist (i.e. warfarin) a Rivaroxaban 15 mg was renally adjusted to 10 mg in patients with CrCl 30-49 mL/min b Aspirin dosing was 75-100 mg daily c Aspirin was discontinued at one month in patients who received bare metal stents and 3 months in patients who received drug-eluting stents

VOLUME 18 | 2019

TSHP JOURNAL

14

P2Y12 of choice. This selection is logical as clopidogrel confers a lower bleeding risk than newer, more potent P2Y12 antagonists. However, antiplatelet regimens in all three studies were of variable components and durations, so direct comparisons between studies is not possible. Additionally, trials were powered for safety results, not efficacy endpoints. A large, prospective, randomized trial adequately powered to assess efficacy endpoints is unlikely.

Use of DOACs in VHD is complicated by non-specific and inconsistent definitions of VHD in trials. Direct Oral Anticoagulants are also contraindicated in mechanical valve replacement following the RE-ALIGN trial.

The 2018 CHEST guidelines and 2019 AHA Focused Update have attempted to clarify some confusion by specifying VHD for the purpose of anticoagulation in AF to be moderate-to-severe mitral stenosis or mechanical valve replacement.8,9 CHEST guidance further recommends use of the functional EHRA (Evaluated Heart valves, Rheumatic or Artificial) categorization to be more specific, as endorsed by European guidelines.8 In patients with mechanical valves, mechanisms of thrombosis differ from those with AF alone. The artificial surface on mechanical valves in itself promotes thrombosis, platelet adhesion, and activation. The surgery involves local tissue injury, further activating the coagulation cascade. Finally, turbulence around the mechanical valve creates shearing and additional thrombosis. It is hypothesized that large concentrations of thrombin develop.27 With dabigatran, a direct thrombin inhibitor which failed in the RE-ALIGN trial, it is thought that impacting this single factor of the coagulation cascade may not be enough to overcome the high concentrations of thrombin found post-surgery. Conversely, warfarin, which acts on multiple areas of the coagulation cascade, is more efficacious in this setting. Direct factor Xa inhibitors may be more effective, based on successful use of enoxaparin in this setting for both bridging and long-term therapy in select patients.27 A case series of seven patients with mechanical mitral valves successfully receiving rivaroxaban 15mg BID may further validate this hypothesis.28 Regarding patients with VHD who do not have moderate-to-severe mitral stenosis or mechanical valve replacement, various studies demonstrate that DOACs may be safe

and effective. The meta-analysis of landmark DOAC trials specifically showed improved efficacy and similar bleeding rates.14 Despite this, the majority of patients included had moderate-to-severe mitral regurgitation, and only between 5.2% and 18.2% of patients in studies had bioprosthetic heart valves. Targeted sub-analyses of bioprosthetic valve patients in ARISTOTE and ENGAGE AF-TIMI 48 did show that apixaban and edoxaban are likely safe and effective as well.12,13 To date there is limited prospective data supplementing these meta-analysis and sub-analyses.19 Outside of AF with bioprosthetic valves, DOACs in TAVR is an emerging indication being investigated. Although the GALILEO trial was stopped early, other trials are currently planned and underway looking at apixaban and edoxaban.21 Potential reasons for poor outcomes in GALILEO could be related to the low dose of rivaroxaban used.

References 1.

2.

3.

4.

5.

6.

Limitations in data include use of DOACs in VHD outside the setting of AF. To date, almost all studies have investigated DOACs in VHD with concomitant AF. Prosthetic valve replacement (bioprosthetic or mechanical) in itself is an indication for anticoagulation, at least for the short-term in the case of bioprosthetic valves. Aside from GALILEO, current studies have only looked at bioprosthetic valves concomitantly with AF. Future studies are needed to further define the precise role of DOACs in the management of VHDs.

7.

Conclusion

10.

Although data are limited, it is reasonable to recommend a DOAC-based antithrombotic regimen including clopidogrel without aspirin in patients with NVAF requiring systemic anticoagulation and who would traditionally qualify for DAPT. Evidence-based DOAC recommendations include rivaroxaban 15 mg daily, dabigatran 150 mg twice daily, and apixaban 5 mg twice daily. Clopidogrel should be considered the P2Y12 antagonist of choice because the vast majority of patients in trials received this agent. It is also reasonable to utilize DOACs at standard dosing for AF in the setting of VHD with the exception of mechanical heart valves or moderate-to-severe mitral stenosis. The role of DOACs in specific subsets of VHD including TAVR, is still evolving with more studies on the horizon.

8.

9.

11.

12.

13.

14.

15.

16.

TSHP JOURNAL

15

Connolly SJ, Ezekowitz MD, Yusuf S, et al.

RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Eng J Med. 2009;361:1139-51.

Patel MR, Mahaffey KW, Garg J, et al.

ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Eng J Med. 2011;365:883-91.

Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Eng J Med. 2011; 15:365:981-92.

Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Eng J Med. 2013;369:2093-2104.

Rubboli A, Colletta M, Herzfeld J, et al.

Periprocedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coron Artery Dis. 2007;18(3):193-9.

Paikins JS, Wright DS, Crowther MA, et al.

Triple antithrombotic therapy in patients with atrial fibrillation and coronary artery stents. Circulation. 2010;121:2067-70.

Dewilde WJ, Oirbans T, Verheugt FW, et al.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomized, controlled trial. Lancet. 2013;281:1107-15.

Lip GYH, Banerjee A, Boriani G, et al.

Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report.

Chest. 2018;154:1121-1201.

January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation. Circulation. 2019. [Epub ahead of print]. doi: 10.1161/CIR.000000000000065.

Gibson CM, Mehran R, Bode C, et al.

Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Eng J Med. 2016;375(25):2423-34.

Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Eng J Med. 2017;377(16):1513-24.

Lopez RD, Heizer G, Aronson R, et al.

Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Eng J Med. 2019;380(16):1509-1524.

Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Eng J Med. 2013;369(13):1206-14.

Renda G, Ricci F, Giugliano RP, et al. Nonâ&#x20AC;&#x201C; Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease. J Am Coll Cardiol.

2017 Mar 21;69(11):1363-71.

Ezekowitz MD, Nagarakanti R, Noack H, et al. Comparison of dabigatran and warfarin in patients with atrial fibrillation and valvular hear disease: the RE-LY Trial (Randomized evaluation of long-term anticoagulant therapy). Circulation. 2016;134(8):589-98.

Breithardt G, Baumgartner H, Kerowitz SD, VOLUME 18 | 2019

et al. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

Eur Heart J. 2014;35(47):3377-85.

17. Carnicelli AP, De Caterina R, Halperin JL, et al. Edoxaban for the Prevention of Thromboembolism in Patients With Atrial Fibrillation and Bioprosthetic Valves. Circulation. 2017 Mar;135(13):1273-1275.

18. Guimarães PO, Pokorney SD, Lopes RD, et al. Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial. Clin Cardiol. 2019 Mar 24. [Epub ahead of print] doi: 10.1002/clc.23178.

19. Durães AR, de Souza Roriz P, de Almeida Nunes B, et al. Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively: DAWA pilot study. Drugs R D. 2016;16(2):149-54.

20. Kim JY, Kim SH, Myong JP, et al. Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis. J Am Coll Cardiol.

2019 Mar 19;73(10):1123-31.

21. Rivaroxaban (Xarelto): Increase in all-cause mortality, thromboembolic and bleeding events in patients after transcatheter aortic valve replacement in a prematurely stopped clinical trial. October 3, 2018. http://www. hpra.ie/docs/default-source/default-document-library/important-safety-information---xarelto-(rivaroxaban)-(oct-2018). pdf ?sfvrsn=0. Accessed May 22, 2019 22. Seeger J, Gonska B, Rodewald C, et al. Apixaban in Patients With Atrial Fibrillation After Transfemoral Aortic Valve Replacement.

JACC Cardiovasc Interv. 2017;10(1):66-74.

23. Van Mieghem NM, Unverdorben M, Calgimigli M, et al. Edoxaban versus standard of care and their effects on clinical outcomes in patients having undergone transcatheter aortic valve implantation in atrial fibrillation-Rationale and design of the ENVISAGE-TAVI AF trial. Am Hear J. 2018;205:63-9.

24. Collet JP, Berti S, Cequier A, et al. Oral anti-Xa anticoagulation after trans-aortic valve implantation for aortic stenosis: the randomized ATLANTIS trial. Am Heart J. 2018;200:44-50.

25. ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): A randomized controlled trial. Lancet. 2006;367:1903-12.

26. Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996;334(17):1084-9.

27. Aimo A, Giugliano RP, De Caterina R. Non-Vitamin K Antagonist Oral Anticoagulants for Mechanical Heart Valves. Circulation. 2018 Sep 25;138(13):1356-1365.

28. Durães AR, Bitar YSL, Lima MLG, et al.

Usefulness and safety of rivaroxaban in patients following isolated mitral valve replacement with a mechanical prosthesis. Am J Cardiol. 2018;122(6):1047-50.

To claim credit for this CE, the participant must complete the course via the TSHP Education Portal (http://tshp.wcea.education/), pass an exam with a minimum score of 75%, and complete a session evaluation.

See page 3 for additional information on claiming credit. *

The Evolving Role of Direct Oral Anticoagulants in Cardiovascular Disease: A Review of Recent Literature UAN: 0156-0000-19-195-H01-P Credit Hours: 0.5 (0.05 CEUs) Type: Knowledge-based Pharmacist Objectives: At the completion of this activity, the participant will be able to: 1. Formulate an evidence-based antithrombotic regimen for a patient with non-valvular atrial fibrillation and coronary heart disease with coronary stents 2. Review emerging evidence for use of direct oral anticoagulants in valvular heart disease 3. Identify valvular heart disease patients with concomitant atrial fibrillation in whom direct oral anticoagulants may be appropriate and design an evidence-based plan for anticoagulation These speakers have no relevant conflicts of interest to disclose.

The Texas Society of Health‐System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing education. Completion of this course requires access to an internet enabled computer. Mozilla Firefox is the preferred browser for the TSHP Education Portal. For information regarding TSHP’s privacy policy, please visit http://tshp.org/privacy‐ policy.html. To view the privacy policy specific to the TSHP Education Portal, visit https://tshp.wcea.education/default/privacy.

Questions? Contact tshp@tshp.org.

Thank you for being a TSHP Journal subscriber!

Use promo code JRNL1 to redeem this CE credit for FREE. See claiming instructions above.

VOLUME 18 | 2019

TSHP JOURNAL

16

Advocacy Perspectives Advocating for Our Profession: An Inside Look at Pharmacy Legislation at the State Level

P

harmacy Day at the Capitol was an incredible opportunity to see first-hand how pharmacists can have a direct impact on legislation at the level of state government. I decided to attend this event as a first-year pharmacy student because I did not have any legislative experience, and it seemed like a unique opportunity to learn how to advocate for pharmacy. My goal was to use my newfound knowledge to educate other pharmacy students about the importance of advancing our profession through advocacy and what we can do as students.

I remember arriving in Austin on February 26 and witnessing a sea of white coats all checking in for the morning briefing session. There were pharmacists from a plethora of different fields including ambulatory care, hospital, independent, and chain pharmacies, as well as students from various schools of pharmacy in Texas, all converging at the capitol to represent our profession. It was a little overwhelming at first since we were divided into small groups to meet with three Texas legislators to discuss priority issues for this legislative session. There were some issues that I was unfamiliar with, but all attendees were briefed, and every group was given a folder with descriptions of each issue.

Some business and professional issues currently being discussed include improving collaborative practice, enhancing pharmacy services to include “test and treat” for flu and strep (SB 835/HB1827), and ensuring payment parity between services offered by providers and these same services offered by pharmacists within our scope of practice.

When we were released into the capitol building, the goal was simple: to deliver a concise policy message that summarized the bills we wanted our legislator to support within a twenty-minute meeting. Our assigned list of legislators included Senator John Whitmire and Representatives Sarah Davis and Dwayne Bohac. I distinctly remember waiting anxiously to go into Senator Whitmire’s meeting room while attempting to recount each issue I wanted to discuss in my head. I was apprehensive because I did not want to make a mistake in front of my colleagues or the legislators I was tasked to influence. Being a first-year student made it difficult to deliver a succinct message to these legislators, but I was fortuitous in having second- and third-year pharmacy students aid my group from University of Texas at Tyler and University of Houston College of Pharmacy. We regrouped before the next meeting to discuss methods to deliver a clear and efficient message to our legislators. As a team, we extracted the main points from each bill and formulated a plan to have each member of our group elaborate on one issue at a time, then segue into the next. Our strategy proved successful and when I exited Representative Bohac’s office, I was brimming with confidence and felt exhilarated! Our legislator was astonished to learn that pharmacists played such a big role in these issues and that student pharmacists came to bring these issues to their attention. In the end, I was proud that I was able to tactfully address issues concerning pharmacists being able to “test and treat,” elaborating on the role of pharmacists in the current opioid epidemic, and the mandatory electronic prescribing of controlled substances. Upon learning that the mandatory electronic prescribing of controlled substances was recently enacted into law truly makes me feel successful, because I was able to voice my concerns regarding issues that are important to me with elegance and professionalism.

TSHP JOURNAL

I truly appreciate the University of Houston College of Pharmacy’s chapter of the American Pharmacist Association – Academy of Student Pharmacists for organizing my school’s participation at Pharmacy Day at the Capitol. I also want to thank all the professional pharmacy organizations that collaborated to successfully coordinate an event of this caliber. The experience I gained from attending Pharmacy Day at the Capitol is invaluable because I can use this knowledge to train other pharmacy students to spread awareness about the importance of advancing our profession through advocacy. The more students that become involved means that more information regarding current pharmacy issues can be disseminated to the public and hopefully one day a change can be enacted. As president-elect of a student organization, I plan to foster this trend of educating pharmacy students and the public in the long-term so that pharmacists can continue making steps toward achieving parity as healthcare providers. It is vital that every pharmacist understands the significance of advocating for our profession. These bills that the Texas Pharmacy Association stands behind will not only aid pharmacists in delivering a higher quality of patient care but will also help to further recognize pharmacists as healthcare providers. I would highly recommend anyone who is involved in the profession of pharmacy to attend the next Pharmacy Day at the Capitol event in two years.

In the meantime, pharmacists can continue to garner support for our profession in a variety of ways. Advocating through social media is an effective platform to spread awareness and inform the public that we can do much more than just dispense medications. Pharmacists can also write letters to their state legislators highlighting the services we can provide to the community and the bills we want them to support.

A list of current bills can be found on the Texas Pharmacy Association website, as well as a bill tracker to monitor their progress throughout the recent legislative session. There is also a toolkit available to members that offers tips on how to communicate with legislators. To determine which legislator to contact, visit the Texas House of Representatives website. So, gather your colleagues and utilize these invaluable resources to gain more knowledge regarding current pharmacy issues and become more politically involved. Pharmacists must stand united and be persistent in advocating for the advancement of our profession, because together, we can enlighten the public as to what pharmacists can do and further substantiate our claim that we are prominent healthcare providers.

Jason Levy PharmD Candidate, University of Houston College of Pharmacy Houston, TX BS Neuroscience The author has declared no potential conflicts of interest.

17

VOLUME 18 | 2019

Student Corner A Pharmacy Student’s Role in Disaster Simulation History of Disaster Day

Created by the Texas A&M College of Nursing in 2008, Disaster Day has evolved into the largest student-led interprofessional emergency response simulation in the nation. Past events have simulated mass casualties, resulting from hurricanes, train wrecks, wildfires, and tornadoes. The foundation of Texas A&M Disaster Day is dedicated to bringing interprofessional student teams from within the Health Science Center colleges together to diagnose, treat, and care for volunteer patients. This invaluable healthcare experience helps prepare students from all healthcare disciplines to better respond to emergencies once they have entered into their respective professions.

Evolution of College of Pharmacy Participation

Prior to 2012, Disaster Day only consisted of nursing students and community volunteers, with pharmacy roles being portrayed by future nurses. In 2012, the College of Pharmacy was invited to participate in this event. Fourth-year pharmacy students, who were assigned to the College Station area for advance clinical rotations, served as clinical pharmacists for the simulation. The College of Pharmacy expanded from its original facilities in Kingsville to the main campus of Texas A&M in College Station in 2014, allowing first-year pharmacy students to attend for the first time. Since that time, Disaster Day has developed into a more interprofessional event. Presently, all College of Pharmacy students are encouraged to attend and participate. First- and secondyear pharmacy students serve as simulated patients or pharmacy technicians, and third- and fourth-year students perform the duties of staff and clinical pharmacists. Pharmacy students also have the opportunity to help plan Disaster Day by fulfilling leadership positions on the Student Planning Committee. Each year, the committee is comprised of approximately fifty Health Science Center Students with usually two or three students representing the College of Pharmacy. For the 2018-2019 academic year, a third-year was selected by a committee of faculty members to serve as the Texas A&M Health Science Center Disaster Day Planning Director. Additionally, approximately 25% of the planning committee consisted of College of Pharmacy Students. To date, this is the largest pharmacy student leadership involvement.

11th Annual Disaster Day

Instrumental Interprofessional Training

Disaster Day offers future healthcare professionals with training experiences necessary to respond effectively to emergency situations.

Through this simulated disaster event, students from different healthcare disciplines are able to collaborate and demonstrate leadership skills by providing care based on real-life scenarios. Since interprofessional education is a required element for the accreditation of Health Science Center colleges, the continued growth of Disaster Day is inevitable. The role of Texas A&M College of Pharmacy’s role in Disaster Day has greatly progressed in the past 11 years. This event allows other healthcare professionals to better understand and appreciate the expertise pharmacists bring to interprofessional teams’ activities.

For additional information about Texas A&M Disaster Day, visit: https://www.tamhsc.edu/ipe/disaster-day/index.html

In February 2019, approximately 600 students from the Colleges of Medicine, Nursing, Pharmacy, Veterinary Medicine and Biomedical Sciences and the School of Public Health worked together to make Disaster Day another great success. Students were assigned to the role of a patient, provider, or observer before the event and were required to complete appropriate training to ensure proper safety training and understanding of role expectations. The event was held twice during the day, once in the morning and once in the afternoon. All participants were transported Disaster City, which is a 52-acre training facility with full-scale, collapsible structures that are customizable to the specific training needs of each group. While patients received moulage and were placed in either the simulated wreckage or field hospital, VOLUME 18 | 2019

interprofessional teams, consisting of nurses, doctors, pharmacists, and public health officials, met together and were informed of the Disaster Day scenario for the first time. Texas A&M Corps of Cadets and the National Guard collaborated with student healthcare teams to safely extract patients from the wreckage in a safe manner. After patients were removed from the collapsed building, triage occurred, and then patients were transported to the field hospital for further stabilization and care. The central pharmacy was located within the field hospital and had a limited medication formulary. Student pharmacists were responsible for ensuring patient safety by dispensing medications accurately and checking prescriptions and medication orders for proper dose and indication. At the end of the simulation, debriefing sessions, led by faculty observers, occurred amongst the interprofessional teams. Faculty members provided valuable, positive feedback to students, including constructive criticism. Furthermore, all Disaster Day participants, whether assigned to a patient, provider, or observer role, are required to complete a survey assessing their opinion of the massive event.

Acknowledgments

The author would like to sincerely thank the numerous faculty and students who participated in the event and the many hours of personal and professional time each volunteer dedicated to the success of this year’s event and to the growth and success of the Texas A&M Disaster Day event.

Caitlyn Iles Clifton PharmD Candidate, Texas A&M Irma Lerma Rangel College of Pharmacy

TSHP JOURNAL

18

Student Corner Attending a Texas State Board of Pharmacy Board Meeting from the Pharmacy Students’ Perspectives

T

he Texas State Board of Pharmacy (TSBP) was created in 1907 as a part of the Texas Pharmacy Act. TSBP is responsible for regulating the practice of pharmacy by proposing, formulating, and enacting new rules in order to promote the health, safety, and welfare of the public. Each of the 11 members of the Board are appointed by the Governor of Texas. Seven of the Board members are pharmacists, three members are public members, and one member is a pharmacy technician. It is important to have public members on the Board to ensure there is representation from all that are impacted by the profession of pharmacy. The Board meets quarterly on the first Tuesday of the month in Austin, Texas and posts agendas for each meeting two weeks before the meeting will occur on the Texas State Board of Pharmacy website. Public attendance at a Board meeting is permitted and welcomed, and as a first-year (P1) pharmacy student, it is exciting to be around all the successful people within the profession we are working to be apart of.

On February 5th, 2019, six Texas A&M first-year pharmacy students had the privilege of attending the TSBP Board Meeting with Texas A&M professor, Dr. Paul Holder. He explained that many people don’t get the chance to attend the Board meeting and he saw it as both an opportunity to learn more about the profession and to meet those both in attendance and on the board. For all of the students that attended the meeting, we had a common purpose for going - to observe the process by which rules are created and changed, and to learn about the plans for implementation of these rules. During these discussions, everyone is welcome to ask questions or make comments regarding the rules being discussed. Zachary Shenkir, one of P1 students in attendance, was able to ask his own question focused a decision made by the Board that could affect the workload in pharmacies in the future.

Zachary stated, “I was able to address the Board in a formal setting regarding rules. I learned that anyone, even a member of the public, can speak and have the ability to influence the introduction of rules.” The influence the public can have on these rules is impressive and it is encouraging to know that the public has a voice as the profession of pharmacy affects them as well as patients. The Board wants and encourages those who will be affected by these rules to speak up and voice their opinions. Jordan Hampton, another P1 student in attendance, stated that , “going to the Board meeting was an eye-opening experience for me because I didn’t realize how much influence the public has on the new rules and regulations enacted by TSBP. I learned that anyone can speak at the Board meeting and how important it is to advocate for what you want.” Advocating for the profession is key to making a true difference in the pharmacy world. Blaire Lankford, a P1 student who also attended the February 2019 TSBP Board meeting, described this experience as well by stating, “It’s encouraging to see how an individual’s suggestion could cause innovative changes in the pharmacy rules.”

This is especially important if you want to bring about changes within the rules of the profession.

Additionally, each of the students that attended the meeting possessed a similar interest in leadership that drove the desire to watch the interactions between those that led the profession in Texas. Faith Boone stated, “I have a desire to lead, so seeing the leaders of the Texas pharmacy world in action was a fascinating and rewarding experience.”

Each one of the students gained a new found respect for the processes TSHP JOURNAL

and effort that goes into making and agreeing upon new rules. Aron Gebremicael, a P1 student, has a new “awareness to what the board is currently working on,” and Sarah Schmidt, also a P1 student, have a better understanding of “the purpose and importance of the Texas State Board of Pharmacy.” We all agree on the importance of not only understanding what goes on within the Board, but also, if an individual truly wants to make a difference in the pharmacy profession, they must first understand what decisions are being made in addition to what it takes to make these decisions.

Attending a Board meeting as a student was an extremely unique and invaluable experience. Applying what you have learned about pharmacy, the knowledge of working in a pharmacy, and an interest in learning more about the profession are all reasons to attend a TSBP Board Meeting at least once in your career. Use your voice and personal experiences to help shape the profession of pharmacy into the future. It is so important to advocate for your profession, to learn about what goes into making the rules, to voice your opinions regarding these rules, and to make a difference. If you do not voice your opinions, who will?

February 2019 Texas State Board of Pharmacy Board meeting attendees (left to right): Dr. Paul Holder, Blaire Lankford, Sarah Schmidt, Jordan Hampton, Aron Gebremicael, Zachary Shenkir, and Faith Boone.

Texas State Board of Pharmacy Board Meeting Information: https://www. pharmacy.texas.gov/about/minute.asp Texas Pharmacy Laws and Rules: https://www.pharmacy.texas.gov/Rules/ index.asp Subscribe to the Texas State Board of Pharmacy Newsletter: https://us2.listmanage.com/subscribe?u=07a419d3bca3004ec8d19a43c&id=84ff257cde

Acknowledgments

We would like to thank Blaire Lankford, Aron Gebremicael, and Zachary Shenkir for their contributions. We would also like to thank our professor, Dr. Paul Holder, for the invitation and experience we had at the Board meeting and for encouraging us to document our thoughts and opinions in order to publish this paper.

Faith Boone, Jordan Hampton, Sarah Schmidt PharmD Candidate, Texas A&M University Irma Lerma Rangel College of Pharmacy 19

VOLUME 18 | 2019

Early Connections

Technicians

s

Internship

2020 TSHP 2020 Annual Seminar

Texas Career & Residency Showcase Friday, April 17 1:00 PM - 3:00 PM | Galveston, TX

CONNECT VOLUME 18 | 2019

EXPLORE

PREPARE

www.tshp.org/showcase TSHP JOURNAL

20

TSHP Research & Education Foundation

2019 Scholarship Recipients

Valerie Yuenger University of Texas College of Pharmacy Austin Area Society of HealthSystem Pharmacists Scholarship

Tasha Roshan Texas Southern University College of Pharmacy & Health Sciences Grace Dyan Coggin MSHP Memorial Scholarship

Susie Park Texas Tech University Health Science Center School of Pharmacy Michael Patry/Texas Tech University Health Sciences Center School of Pharmacy EPASHP Memorial Scholarship

Lindsey Taylor Groff University of Texas College of Pharmacy Celso and Matiana M. CuĂŠllar Sr. Scholarship and Central Texas Society of Health-System Pharmacists Scholarship

Aimen Naveed University of Houston College of Pharmacy Gulf Coast Society of HealthSystem Pharmacists Leadership Scholarship

Laura Roccograndi University of Texas College of Pharmacy Micheline & Bourjois Abboud Scholarship

Geannette Green University of Texas College of Pharmacy Eustacio Galvan Memorial Scholarship

Uzoamaka Abajue Texas Southern University College of Pharmacy & Health Sciences James T. Doluisio Scholarship

Audrey Anderson Texas A&M University Health Science Center Irma Lerma Rangel College of Pharmacy Phyllis B. Ginsburg Memorial Scholarship

Christina Hansen Texas Tech University Health Science Center School of Pharmacy Gene Lake Scholarship

Heily Pham University of North Texas Health Science Center College of Pharmacy Jon Peyton Hudlow & Mark Tamble Memorial Scholarship

Ashley Cubley University of Texas College of Pharmacy Robert G. Leonard Memorial Scholarship

Kevin Chan Texas A&M University Health Science Center Irma Lerma Rangel College of Pharmacy Glenda Lawson McRee Scholarship

Irvin Alvarez Texas Tech University Health Science Center School of Pharmacy Metroplex Society of HealthSystem Pharmacists Scholarship

Jesus Camacho University of Texas at El Paso School of Pharmacy The University of Texas at El Paso School of Pharmacy/EPASHP Scholarship

Fiona Imarhia, PharmD PGY1 Pharmacy Resident, Michael E. DeBakey VA Medical Center Richard Cadle Mentoring Scholarship for Pharmacy Leadership

TSHP JOURNAL

21

VOLUME 18 | 2019

Parenteral Nutrition Management in Adults: A Review for Pharmacists Purpose: Parenteral nutrition (PN) support therapy is a high-alert medication that has the potential to result in significant patient harm when used in error.1 Clinical pharmacists play an important role in the provision of parenteral nutrition support in hospitalized patients.2 This review provides an overview of the basic elements of PN management for health-system pharmacists that write or review PN orders, or monitor patients on PN therapy.

Summary: Standardized competencies are available from the American Society for Parenteral and Enteral Nutrition (ASPEN) that identify core skills necessary for safe prescribing of PN therapy for various healthcare professionals, including pharmacists.3 Pharmacists writing or reviewing PN orders, or monitoring patients on PN therapy, should have a clear understanding of PN indications and risks, be able to assess fluid and electrolyte balance, calculate macronutrient requirements, and be able to assess the compatibility and stability of PN admixtures.3 Meagan Johns, PharmD, MBA, BCNSP, BCCCP, BCPS Department of Pharmacy, William P. Clements Jr. University Hospital University of Texas Southwestern Medical Center Dallas, Texas

CrPedEit

* c le ilab a v a

Key Words • • • • • •

Nutrition support Parenteral nutrition training TPN Pharmacist Competencies Parenteral nutrition education

VOLUME 18 | 2019

Conclusion: This review will provide a summary of these key clinical competencies and serve as a primer for health-system pharmacists involved in PN management in adult patients.

Introduction

Parenteral nutrition (PN) support therapy is a high-alert medication that has the potential to result in significant harm when used in error1. Based on a survey conducted by the American Society for Parenteral and Enteral Nutrition (ASPEN) in 2011, pharmacists play an important role in PN management.2 In this survey, 28.3% of respondents stated that pharmacists write PN orders in their respective institutions.2 Standardized processes, as well as initial and ongoing clinical competency and skills assessments are important for high-alert medications. Standardized competencies are available from ASPEN that identify the skills necessary for safe prescribing of PN for various healthcare professionals, including pharmacists.3 According to ASPEN consensus recommendations and clinical guidelines, hospital providers who write PN orders should either be certified as a nutrition support clinician (e.g., Board of Pharmacy Specialties [BPS]), or should complete a didactic and interactive course on PN with a skills test and ongoing competency assessment.3 ASPEN offers TSHP JOURNAL

22

pharmacist continuing education on PN as well as a PN Safety Series and a Certificate of Training Program. Additionally, a Nutrition Support Certificate Program is also offered for pharmacists by the American Society of Health-System Pharmacists. Pharmacists writing or reviewing PN orders, or monitoring patients on PN therapy, should have an understanding of PN indications and risks, be able to assess fluid and electrolyte balance, calculate macronutrient requirements, and be able to assess the compatibility and stability of PN admixtures.3

Parenteral Nutrition Indications and Risks When to Initiate Parenteral Nutrition Support. In 2017, ASPEN published recommendations on the appropriate use of PN support.4 According to these recommendations, PN should be initiated in the following situations: 1. After 7 days for well-nourished, stable adult patients who have been unable to receive significant enteral nutrition (EN) or oral intake (50% or more of requirements).

2. Within 3 to 5 days in patients that are nutritionally-at-risk and unlikely to achieve desired oral intake or EN. 3. As soon as possible in those with moderate or severe malnutrition when oral intake or EN is not possible or does not meet requirements.4 To determine the appropriateness of PN therapy, the provider must assess if the patient is malnourished and/or nutritionally-at-risk. Nutritional risk may be assessed by tools such as the Nutritional Risk Screening 2002 (NRS 2002), the Nutritional Risk in Critically Ill (NUTRIC) Score, or the modified Nutritional Risk in Critically Ill (mNUTRIC) score.5 Adults with two of the six criteria below meet the criteria as defined by ASPEN for a diagnosis of malnutrition:6 • Insufficient energy intake • Weight loss • Loss of muscle mass • Loss of subcutaneous fat tissue • Localized or generalized fluid accumulation that may mask weight loss • Diminished functional status (handgrip strength) Complications of Parenteral Nutrition.

PN is associated with infectious comorbidities, such as pneumonia and central line-associated bloodstream infections (CLABSIs).

PN is also associated with hepatobiliary complications, such as hepatic cholestasis.

Hepatobiliary complications can be prevented and/or mitigated by decreasing the intravenous (IV) fat dose to 1 g/kg/day or less, avoiding overfeeding and providing balanced nutrition, using a cyclic PN infusion, and/or maximizing EN, even if only providing trophic feeds (e.g., 10 to 20 kcal/hr). Maximizing EN can also help prevent villous atrophy and bacterial translocation from the gut that is associated with PN use.7 Metabolic bone disease (MBD) is also a complication associated with the use of long-term PN therapy. Patients on long-term PN therapy need calcium and phosphate supplementation.

Serum calcium may be normal; however, 10 to 15 mEq of calcium daily is needed in PN to prevent MBD when it is compatible in the PN solution. Additionally, both vitamin D and vitamin K play an important role in bone metabolism, and are provided in adult parenteral multiple vitamins.

Benefits of Early Enteral Nutrition

Support. The gastrointestinal (GI) tract is the body’s first line of defense for infection.9 EN supports the intestinal mucosal barrier through stimulation, and in critically ill patients, EN modulates the stress response and can mitigate disease severity.5,8 It is recommended that early EN be initiated within 24 to 48 hours in critically ill patients that are hemodynamically stable and/or adequately resuscitated, and are unable to maintain sufficient intake.5 Trophic feeding, or EN provided at low rates such as 10 to 20 kcal/hr, with adequate protein should be initiated in these critically ill patients and advanced based on nutritional risk and tolerance.5

derly female = 0.45 x IBW) º Use Actual Body Weight if less than IBW • Change in serum Na per liter of IV fluid = (Infusate Na + K) - Serum Na / (TBW + 1)

Fluid Balance Assessment. When writing or reviewing PN orders, it is critical that all sources of fluid intake be considered when determining PN admixture volume. Initially, an assessment of the type of fluid and the total volume the patient is already receiving from all sources (enteral and parenteral) should be considered. Additionally, output from all sources (e.g., urine, stool, wound vacs, drains, enteral tubes, and fistulas) must be considered. Daily fluid needs can be determined by a variety of methods, such as 1 mL per calorie of EN, or 1500 mL for the first 20 kg of total body weight plus an additional 20 mL/kg for each kg over 20 kg of total body weight, or the 4-2-1 method (4 ml/kg/hr for the initial 10 kg body weight (BW), 2 ml/kg/hr for the second 10 kg BW, and 1 ml/kg/hr for each kg greater than 20 kg).9 A simple calculation for daily fluid requirements in adults is:9 • 30-35 mL/kg: 18-54 years • 30 mL/kg: 55-65 years • 25 mL/kg: >65 years

Hypovolemia can also be identified by high serum osmolality (serum osmolality greater than 295 mOsm/kg H20), blood urea nitrogen (BUN)/creatinine ratio greater than 20:1, or urine sodium less than 15 mEq/L, and/or a fractional excretion of sodium (FeNa) of less than 1%.10 Daily patient body weights can also be used to assess fluid balance. A daily weight change of 1 kg in an adult is often indicative of a 1L fluid balance change. Hypovolemia or hypernatremia should be corrected slowly, typically over at least 48 hours, unless the patient is hemodynamically unstable. Serum sodium should not be corrected faster than 8 to 12 mEq/L in 24 hours, or 18 mEq/L in 48 hours.10 In patients at a higher risk with rapid correction, such as in the case of alcoholism, advanced liver disease, malnutrition or serum sodium less than 105 mEq/L, serum sodium should not be corrected faster than 8 mEq/L in 24 hours.10 A general rule is that only around half of the free water deficit should be replaced in 24 hours, unless the patient is hemodynamically unstable.10 Remember that in the case of hemodynamic instability, isotonic solutions, such as lactated ringers (LR) or normal saline (NS), should be used as they replete the intravascular fluid space more effectively. For example, if 1L of 5% dextrose in water (D5W) is utilized for fluid replacement, only around 83 mL stays in the intravascular space, as opposed to 250 mL of 1L of NS.9

Sodium and Volume Assessment. Hypernatremia is often reflective of the water content of the extracellular fluid and not of sodium balance.10 Each liter of free water loss results in around a 3 to 5 mEq/L increase in serum sodium concentration.10 The equations below can be used in the case of hypernatremia to determine free water replacement needs and the rate of serum sodium correction:10 • Free Water Deficit = Total Body Water (TBW) x (serum sodium-140)/(140) • TBW male = 0.6 x Ideal Body Weight (IBW), (elderly male = 0.5 x IBW) º Use Actual Body Weight if less than IBW • TBW female = 0.5 x IBW, (el-

Clinical Case Example • PT is a 42 year old female (40 kg, 63 inches) post-operative day 2 for extensive lysis of adhesions and small bowel resection. She now has 100 cm of small bowel remaining. She has a nasogastric tube (NGT) to suction, and she is nil per os (NPO) starting on PN tonight.

• NGT output was 1700 mL in the last 24 hours.

• Labs: Na 151 mEq/L, K 3.1 mEq/L, Cl 115 mEq/L, CO2 18 mEq/L, BUN 40 mg/dL, • Cr 1.5 mg/dL (baseline = 0.8 mg/dL), blood glucose 162 mg/dL, serum osmolality 325 mOsm/kg H20 • LR is currently infusing at 60 mL/hr.

Fluid and Electrolyte Balance Assessment

TSHP JOURNAL

23

VOLUME 18 | 2019

Table 1. Parenteral Nutrition Electrolyte Requirements in Adults10 Electrolyte

Maintenance Range Requirements in PN

Maximum Recommended Intake in PN

Sodium

1-2 mEq/kg (77-130 mEq/L for most)

154 mEq/L (NS)

Potassium

1-2 mEq/kg

See non-linear increases in serum K with doses ≥2 mEq/kg

Calcium

10-15 mEq/day

Based on Ca/Phos solubility Ca+Mg sum should be ≤20 mEq/L when in 3-in-1 TPN

Magnesium

8-20 mEq/day

Based on Ca+Mg sum ≤20 mEq/L when in 3-in-1 TPN

Phosphorus

20-40 mmol/day

Based on Ca/Phos solubility

Chloride/Acetate Ratio

Typical Chloride:Acetate ratio is 2:1 (mEq)

Based on patient acid/base balance Commercial amino acids contain acetate primarily. Depending on the amino acid manufacturer, the content can range from approximately 0.7 to 1.47 mEq acetate per gram of amino acid.

Her urine output was around 50 mL/ hr, and now it has been 150 mL in the last 12 hours.

1. What is her free water deficit?

Free Water Deficit = (0.5 x 40 kg) x (151-140)/(140) = around 1.6 L 2. How would you replace the free water deficit from NGT losses? a. Start PN with no sodium at 50 ml/hr tonight, and add D5W at 65 mL/hr. b. Start PN with no sodium at 100 ml/hr tonight. c. Start LR at 65 ml/hr, hold PN for now. d. Start ½ NS at 50 ml/hr along with PN with 92 mEq total Na (½ NS) at 50 ml/hr The best answer is to start ½ NS at 50 ml/hr along with PN with 92 mEq total Na (½ NS) at 50 ml/hr. The content of gastric secretions is around ½ NS, so ½ NS can be used to replace these losses. She is intravascularly depleted because her serum creatinine has increased and her urine output is now less than 0.5 ml/kg/hr, indicating she has pre-renal acute kidney injury (AKI) due to volume depletion likely due to a large amount of NGT output for her weight (~ 37.5 ml/kg in losses from NGT in the last day).

3. How much would her serum sodium decrease in 24 hours with ½ NS at 50 mL/hr, and PN with 92 mEq Na (~½ NS) + 40 mEq K at 50 mL/hr?

• Change in serum Na per liter of IV fluid = (Infusate Na + K) - Serum Na / (TBW + 1) = (77 mEq Na/L + 17 mEq K/L) -

151 mEq/(40 kg x 0.5)+ 1

= -2.7 mEq/1L of fluid x 2.4 L/day

= - 6.5 mEq/L change in serum

sodium in 24 hr • This is within the appropriate VOLUME 18 | 2019

range of serum sodium correction of ~ 8-10 meq/L in 24 hr 4. What would the change in her serum sodium be if PN with no sodium and 40 mEq potassium at 50 ml/hr was started, and D5W at 65 mL/hr was also infused?

• Change in serum Na per liter of IVF = (Infusate Na + K)- Serum Na / (TBW + 1) = (0 mEq Na/L + 14.5 mEq K/L)

- 151 mEq/L/(40 kg x 0.5) + 1

= -6.5 mEq/L of fluid x 2.76 L/day

= -17.94 mEq/L change in serum

sodium in 24 hr • 17.5 mEq/L decrease in serum

sodium in 24 hr is too fast of a correction Electrolyte Requirements. When determining electrolyte provision in PN, it is important to remember the components of human plasma. The sodium content of human plasma is 135 to 145 mEq/L, chloride is 94 to 111 mEq/L, and bicarbonate is 24 to 32 mEq/L.9 It is also critical to assess the electrolyte content of GI fluid losses to assess replacement needs. For example, if a patient is losing fluid from an NGT, the content of gastric fluid is sodium 60 mEq/L, potassium 10 mEq/L, and chloride 130 mEq/L, so replacing these losses with ½ NS would likely be appropriate.9 Conversely, a patient with significant output from an ileostomy may need LR for fluid replacement since the sodium content is 140 mEq/L, chloride 104 mEq/L, and bicarbonate is 30 mEq/L from ileal secretions.9 Table 1 shows the typical electrolyte requirements for adults in PN. When determining the sodium content in PN formulations, look at the total concentration (mEq/L) of sodium provided to make assessments. If the PN volume changes and TSHP JOURNAL

24

serum sodium is appropriate, keep the total sodium concentration (mEq/L) in the PN admixture the same. Always evaluate trends in serum electrolytes to make adjustments.

Serum magnesium and phosphorus take longer to replete, so large changes in serum levels typically do not occur quickly from repletion in PN.

Assessing the Stability of PN Admixtures

The content of calcium and phosphate should always be assessed using published calcium and phosphate solubility curves along with consideration of PN volume at the time of calcium addition.11 The calcium and phosphate solubility curves are available from amino acid manufacturers, or available with many PN software packages. Quick assessments at the point of ordering, such as the 45 Rule, where calcium (mEq/L) plus phosphate (mmol/L) is less than or equal to 45 can be used if the specific brand of amino acid is known; however, solubility should always be assessed using published curves before admixture of the final PN solution.12 These curves are developed based on the concentration of calcium gluconate and phosphate, as well as the final concentration of dextrose and amino acids of the specific PN solution.11 The solubility curves are typically developed with calcium gluconate, as calcium chloride easily dissociates and precipitates with phosphate, and generally should not be used in PN admixtures.

When a total nutrient admixture (TNA) or a 3-in-1 PN admixture is utilized, IV lipid emulsion is mixed with dextrose, amino acids, and micronutrients. Preparation of this formulation requires specific assessments to ensure the stability of the lipid emulsion.13 The final contents of a TNA should be at least 4% amino acids, at least 10% dextrose, and at least 2% lipid emulsion to ensure the stability of the lipid emulsion in the final admixture.13 In addition, divalent cations (calcium and magnesium) can destabilize the lipid emulsion; therefore, the calcium and magnesium sum should be 20 mEq/L or less in a TNA.13 Monovalent cations also influence the stability of the lipid emulsion, and most studies evaluating TNA stability included admixtures with total sodium and potassium concentration of 150 mEq/L or less.13 Iron should not be used in a TNA, as it can destabilize the lipid emulsion. Typically, stability issues will arise with TNAs in the initial 24 to 72 hours of PN use when dextrose concentrations are

not high due to low initial glucose infusion rates when calories are being advanced. If values close to these concentration ranges cannot be achieved, it is safer to Y-site the IV lipid emulsion, using a 2-in-1 PN solution.

The final osmolarity of the PN formulation should be assessed when infusing through a peripheral venous access site. The final osmolarity of peripheral PN formulations should be no greater than 900 mOsm/L.13 Typically, dextrose should be 12.5% or less, potassium 40 mEq/L or less, and calcium 5 mEq/L or less in peripheral PN solutions.11

Macronutrient Requirements

Calculation of Caloric Needs. Various methods can be utilized to determine caloric requirements in adults. The most appropriate equations used to determine the caloric needs of hospitalized patients continues to be debated.14 Indirect calorimetry (IC) is the gold standard for estimation of caloric needs.5 Indirect calorimetry estimates energy expenditure from measures of carbon dioxide production and oxygen consumption; however, it is not available at many institutions.5 This methodology can be summarized by the respiratory quotient (RQ ), where RQ is CO2 eliminated/O2 consumed.5 The goal RQ is 0.85, indicative of mixed substrate oxidation.15 An RQ of 1 to 1.2 is indicative of overfeeding and lipogenesis.15 Predictive equations such as the Harris-Benedict Equation, the Penn State Equation, or the Mifflin St Jeor equation among others, range in accuracy of 40% to 75% when compared to IC measured energy expenditure.16 Simplistic formulas, such as the provision of 25 to 30 kcal/kg/day are also appropriate to determine caloric needs in adults.

General Adult Macronutrient Requirements. It is important to provide balanced nutrition support, with adjustments based on patient tolerance. Macronutrients should be ordered as total grams per day based on ASPEN recommendations for safe practices for PN orders.11 General adult PN macronutrient requirements are summarized in Table 2. General adult PN daily energy and protein requirements are summarized in Table 3.

Protein. Protein is provided as a 4 kcal/g amino acid solution in PN admixtures. The goal of protein provision is not only to provide calories, but also to minimize the loss of lean body mass.5 Typically, hospitalized

Table 2. General Adult Parenteral Nutrition Macronutrient Requirements14 Initiation

Advance By

Goal

Protein

0.8 to 2 g/kg/day

Start at Goal Day 1

0.8 to 2 g/kg/day

Dextrose as Glucose Infusion Rate (GIR)

1 to 2.5 mg/kg/min

1 to 2 mg/kg/min

4 to 5 mg/kg/min Max 5 mg/kg/min (for noncyclic PN over 24 hr)

Fat (dosing based on 100% soybean oil-based lipid emulsion)

1 g/kg/day

0.5 to 1 g/kg/day

1 to 2 g/kg/day

patients need at least 1 to 1.5 g/kg/day of protein in PN solutions to meet this goal, with critically ill patients, or those on continuous renal replacement therapy (CRRT) having higher requirements.14 Protein can be provided at full requirements the first day of PN administration in the absence of hepatic encephalopathy. Protein is usually around 20 to 25% of total calories in adult PN admixtures.14 Carbohydrates. Carbohydrate calories are provided as a 3.4 kcal/g dextrose solution in PN admixtures. Dextrose is initiated and advanced over a few days to goal depending on the patientâ&#x20AC;&#x2122;s tolerance. The infusion of dextrose is calculated as the glucose infusion rate (GIR) in mg/kg/min. A lower initial GIR of 1 to 1.5 mg/kg/min, or dextrose of 100 to 150 grams/day, should be provided in patients at higher risk of intolerance, such as those with severe malnutrition, diabetics, critically ill patients, those with baseline hyperglycemia, hypokalemia, and/or hypophosphatemia. Dextrose calories should be advanced to goal when electrolytes are stable, and blood glucose is controlled at 180 mg/dL or less. The maximum recommended GIR in adult patients is 5 mg/kg/min in uncycled PN (e.g., over 24 hours). Typically, around 60 to 70% of non-protein calories are provided as dextrose in adult PN solutions.14 In patients with hyperglycemia with consistent correctional insulin dosing requirements, or baseline insulin requirements before PN initiation, regular human insulin may be added to PN. For patients that are clinically unstable with fluctuating blood glucose values, or transient risk factors for hyperglycemia such as increasing vasopressor dose requirements, an insulin drip is a safer option for blood glucose control to allow more rapid dose changes.

Lipid Emulsion. Adult patients on PN for 2 weeks or longer need at least 100 g/week of a 100% soybean oil-based IV lipid emulTSHP JOURNAL

25

sion to prevent Essential Fatty Acid Deficiency (EFAD). SmoflipidÂŽ (Fresenius Kabi), an IV lipid emulsion comprised of 30 % soybean oil, 30% medium chain triglycerides, 25% olive oil, and 15% fish oil, may be utilized to prevent EFAD.18 However, higher doses are required with this formulation to supply the necessary amount of omega-6 fatty acids to prevent EFAD, as the content is around onethird that of soybean oil-based IV lipid emulsion.17 The caloric content of 20% IV lipid emulsion is 10 kcal/g. A 30% soybean oil-based lipid emulsion is available and should only be utilized to compound a 3-in-1 PN admixture, and not infused directly to a patient. Baseline and at least weekly serum triglycerides should be monitored in patients on IV lipid emulsion. More frequent monitoring may be required in patients with high baseline triglycerides, alcoholism, obesity, or liver disease. Intravenous lipid emulsion should be held and reassessed when serum triglycerides exceed 400 mg/dL in adults, except in pregnancy where baseline triglycerides are higher and critical to fetal lung surfactant development.

The maximum rate of lipid emulsion administration is 0.12 g/kg/hour when provided in PN. Lipid emulsion in PN is typically provided as 20% to 30% of total calories.14 In some situations, 35% to 45% of total calories may be provided to decrease the production of carbon dioxide by minimizing dextrose. This strategy may be used in hyperglycemic patients. Typically it is more important to assess the provision of total calories and prevent overfeeding in these situations rather than to provide more calories as lipid emulsion. Carbon dioxide production is driven more by overfeeding, rather than by the provision of dextrose.

It is also important to account for the caloric content of medications when calcuVOLUME 18 | 2019

lating calories in PN. For example, propofol is a 10% lipid emulsion, supplying 1.1 kcal/ mL, and clevidipine is a 20% lipid emulsion, supplying 2 kcal/mL. Low quality evidence exists to support holding or limiting soybean oil-based IV lipid emulsion during the first week of a patient’s intensive care unit stay.5 This formulation of IV lipid emulsion has a higher ratio of omega-6 to omega-3 fatty acids, making it pro-inflammatory and potentiating the systemic inflammatory response in critically ill patients.5 Monitoring PN Caloric Provision. Serum albumin and prealbumin will be low in acute illness or inflammatory states, so they typically are not an accurate measure of nutritional status in hospitalized patients. If prealbumin is monitored, it should be interpreted along with other markers of inflammation, such as C-reactive protein (CRP). As the CRP decreases, and the acute illness is resolved, prealbumin should increase in the setting of adequate hepatic function.

Nitrogen balance studies can also be utilized to assess for adequate protein provision.18 The goal is to have a positive nitrogen balance, which is indicative of anabolism. A nitrogen balance of -4 g/day to +4 g/day is indicative of nitrogen equilibrium. Exceptions are unstable renal function or renal replacement therapy (RRT); however, adjustment factors are available for these states.

Typical protein losses in stool, skin and nonurea losses of nitrogen in the urine are accounted for by adding 4 to the measured 24 hour urine urea nitrogen (UUN).18 • Nitrogen Balance (grams)= [pro-

tein intake (grams)/6] – [UUN (grams)+4) Other clinical assessments can guide the clinician to determine if protein and caloric provision is appropriate, such as adequate wound healing, weight loss or gain, fistula closure, or overall clinical status and the ability to wean mechanical ventilation settings.

PN Management in Special Populations

Critically Ill. Protein catabolism is a typical metabolic response in critical illness that can result in the loss of lean tissue.19 Provision of adequate protein (>80% goal protein requirements) and calories as opposed to adequate total calories alone has been associated with reduced mortality in critically ill patients.20 Protein doses in PN should be at least 1.5 g/kg/day in most critically ill patients, with the goal range of 1.2 to 2.5 g/kg/ day.5,19 Higher protein goals in PN are needed in patients with burns, multi-trauma, on CRRT, or in the elderly.5,19 It is equally important to avoid overfeeding, as it can worsen hypercapnia, making it more difficult to wean mechanical ventilation, particularly in obese patients.5 Obesity. Hospitalized obese patients are at an increased risk for experiencing metabolic complications from PN, such as hyperglycemia and hypercapnia.21 Hypocaloric, high protein feeding is recommended in obese hospitalized patients as it is associated with similar outcomes as eucaloric, high protein feeding, and can help mobilize and decrease adipose stores, while preserving lean

body mass.5,21 If indirect calorimetry is unavailable, then the simple formulas in Table 3 can be used to estimate caloric requirements in obese patients.

Renal Replacement Therapy. CRRT therapy is associated with significant protein losses; estimated to be around 10 to 15 g/day depending on the rates.5 Therefore, protein goals in critically ill patients on CRRT are 2 to 2.5 g/kg/day to ensure a positive nitrogen balance and preservation of lean body mass.5 Additionally, CRRT can also cause micronutrient deficiencies, particularly of water-soluble vitamins and trace elements.22 Supplementation of additional thiamine 100 to 200 mg, folic acid 1 mg, and selenium 75 to 100 mcg daily are recommended in PN to replace losses with CRRT.22 Cases of severe copper deficiency have also been reported with prolonged CRRT, and patients on this therapy should be monitored.23 Protein requirements in patients on intermittent hemodialysis are typically 1.2 to 1.5 g/kg/day.

Conclusion

PN therapy is a high-alert medication that is likely to result in significant patient harm if used in error. Pharmacists are often involved in writing or reviewing PN orders in hospitalized patients. To ensure optimal patient outcomes, pharmacists involved in PN management should have a clear understanding of PN indications and risks, fluid and electrolyte balance assessment, macronutrient requirements, PN stability and compatibility assessment, and appropriate provision of PN in special populations.

Table 3. Approximate Adult Parenteral Nutrition Daily Energy and Protein Requirementsa,14 Patient Type

Energy (kcal/kg)

Protein (g/kg/day)

Well nourished, healthy

20 to 25

0.8 to 1

Critically ill, metabolic stress, trauma, undernourished

25 to 30 (up to 35 in certain cases)

1.5 to 2 (up to 2.5 in certain cases)

Critically ill obese (BMIa ≥30 kg/m2)

BMI 30-50 kg/m2: 11-14 of Actual BW BMI >50 kg/m2: 22-25 of IBW

BMI 30-40 kg/m2: ≥2 g/kg IBW BMI >40 kg/m2: ≥2.5 g/kg IBW

AKI, CKD

25 to 30 (up to 35 in certain cases)

No dialysis: 0.8 to 1.2 HD: 1.2 to 1.5 (may depend on frequency of HD) CRRT: 1.5 to 2.5 PD: 1.2 to 1.4

a BMI=

Body Mass Index, IBW= Ideal Body Weight, AKI= Acute Kidney Injury, CKD= Chronic Kidney Disease, HD=Hemodialysis, CRRT= Continuous Renal Replacement Therapy, PD=Peritoneal Dialysis, BW= Body Weight

VOLUME 18 | 2019

TSHP JOURNAL

26

References 1.

Institute for Safe Medication Practices (ISMP). ISMP’s list of high-alert medications in acute care settings (2018). https:// www.ismp.org/recommendations/highalert-medications-acute-list (accessed 2019 May 19).

Boullata JI, Guenter P, Mirtallo JM. A parenteral nutrition use survey with gap analysis. JPEN. 2013;38:212-22.

Guenter, P, Boullata JI, Ayers, P, et al.

Standardized competencies for parenteral nutrition prescribing: the American Society for Parenteral and Enteral Nutrition model.

Nutri Clin Pract. 2015; 30:570-76.

Worthington P, Becktold M, Bingham A, et al. When is parenteral nutrition appropriate?

JPEN. 2017; 41:324-77.

McClave SA, Taylor BE, Martindale RG et al. Society for Critical Care Medicine, American Society for Parenteral and Enteral Nutrition. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN. 2016; 40:159-211.

White JV, Guenter P, Jensen G, et al. Academy Malnutrition Work Group. American Society for Parenteral and Enteral Nutrition Malnutrition Task Force. ASPEN Board of Directors. Consensus Statement: Academy of Nutrition and Dietetics and ASPEN: Characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). JPEN. 2012; 36:275-83.

Jabbar A, Chang WK, Dryden GW, McClave SA. Gut immunology and the differential

2.

3.

4.

5.

6.

7.

*

8.

9.

10.

11.

12.

13.

14.

15.

response to feeding and starvation. Nutri Clin Pract. 2003; 18:461-82.

Kudsk KA. Current aspects of mucosal immunology and its influence by nutrition.

Am J Surg. 2002; 183:390-98.

Canada TW, Tajchman SK, Tucker AM, Ybarra JB. Regulation of water and electrolyte balance. In: Canada TW, Tajchman SK, Tucker AM, Ybarra JB. ASPEN fluids, electrolytes, and acid-base disorders handbook.

Silver Spring: ASPEN; 2015:9.

Canada TW, Tajchman SK, Tucker AM, Ybarra JB. Electrolyte disorders. In: Canada TW, Tajchman SK, Tucker AM, Ybarra JB. ASPEN fluids, electrolytes, and acid-base disorders handbook. Silver Spring: ASPEN; 2015:11.

Mirtallo JM, Canada TW, Johnson D, et al.

Safe practices for parenteral nutrition. JPEN. 2004; 28:S39-70.

Cober MP, Derenski K, Malone A, Monczka J. Appendix C: tables and figures. In: Cober MP, Derenski K, Malone A, Monczka J. ASPEN Adult parenteral nutrition workbook: cases and worksheets for adult, pediatric, and neonatal patients. Silver Spring: ASPEN; 2016:11.

Boullata JI, Gilbert K, Sacks G, et al.

ASPEN Clinical Guidelines: Parenteral nutrition ordering, order review, compounding, labeling, and dispensing. JPEN. 2014; 38:334-77.

Mundi MS, Nystrom EM, Hurley DL, McMahon MM. Management of parenteral nutrition in hospitalized adult patients.

JPEN. 2017; 41:535-49.

Ireton-Jones C, Turner WW Jr. The use of respiratory quotient to determine the effica-

16.

17.

18.

19.

20.

21.

22.

23.

cy of nutrition support regimens. J Am Diet Assoc. 1987; 87:180-3.

Derenski K, Catlin J, Allen L. Parenteral Nutrition Basics for the Clinician Caring for the Adult Patient. Nutri Clin Pract. 2016; 31:578-95.

Fresenius Kabi. Smoflipid. (IV fat emulsion 20%). http://smoflipid.com/all-smoflipid-clinical-information/ (accessed 2019 May 19).

Dickerson RN, Tidwell AC, Minard G et al.

Predicting total urinary nitrogen excretion from urinary urea nitrogen excretion in multiple-trauma patients receiving specialized nutrition support. Nutrition. 2005; 21:332-38.

Hurt RT, McClave SA, Martindale RG, et al.

Summary points and consensus recommendations from the International Protein Summit. Nutr Clin Pract. 2017; 32:142S-151S. Nicolo M, Heyland DK, Chittams J, et al.

Clinical outcomes related to protein delivery in a critically ill population: a multi-center, multinational, observational study. JPEN. 2016; 40:45-51.

Choban P, Dickerson R, Malone A, et al.

ASPEN Clinical Guidelines: Nutrition support of hospitalized adult patients with obesity. JPEN. 2013; 37:714-44.

Gervasio, JM, Garmon WP, Holowatyj M. Nutrition support in acute kidney injury, Nutri Clin Pract. 2011; 26:374-81.

Ben-Hamouda N, Charriere M, Voirol P, Berger MM. Massive copper and selenium losses causing life-threatening deficiencies during prolonged continuous renal replacement. Nutrition. 2017; 34:71-5.

To claim credit for this CE, the participant must complete the course via the TSHP Education Portal (http://tshp.wcea.education/), pass an exam with a minimum score of 75%, and complete a session evaluation. See page 3 for additional information on claiming credit.

Parenteral Nutrition Support in Adults: A Review for Pharmacists UAN: 0156-0000-19-196-H01-P Credit Hours: 0.75 (0.075 CEUs) Type: Knowledge-based Pharmacist Objectives: At the completion of this activity, the participant will be able to: 1. Calculate protein, carbohydrate, and fat intake goals for adults on parenteral nutrition support based on clinical status and nutrition risk.

2. Discuss fluid and electrolyte balance considerations based on clinical status for patients on parenteral nutrition support.

3. Identify parenteral nutrition monitoring parameters.

These speakers have no relevant conflicts of interest to disclose.

The Texas Society of Health‐System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing education. Completion of this course requires access to an internet enabled computer. Mozilla Firefox is the preferred browser for the TSHP Education Portal. For information regarding TSHP’s privacy policy, please visit http://tshp.org/privacy‐ policy.html. To view the privacy policy specific to the TSHP Education Portal, visit https://tshp.wcea.education/default/privacy.

Questions? Contact tshp@tshp.org.

Thank you for being a TSHP Journal subscriber!

Use promo code JRNL1 to redeem this CE credit for FREE. See claiming instructions above.

TSHP JOURNAL

27

VOLUME 18 | 2019

TSHP Member Recognition

2019 Award Recipients MIKE KNAPP PHARMACY TECHNICIAN AWARD

INDUSTRY SERVICE AWARD

Bradley Miller, PhTR

With a strong passion for operational excellence and patient care, Jon brings more than twelve years of experience and leadership to the industry side of acute care pharmacy.

Joining PharMEDium Services (an AmerisourceBergen subsidiary) in 2011, Jon actively engages in TSHP and MSHP activities.

Jon has had a strong devotion for the sterile compounding industry and has been a great asset and resource regarding industry and compliance related information. As a recognized partner and leader on both the state and regional level, Jon also brings an unparalleled wealth of knowledge from his past studies. Jon holds a bachelor’s degree in the study of business from Purdue University, an MBA in Healthcare Administration from Indiana Wesleyan, and is currently enrolled at Liberty University in chase of his Doctorate degree in Healthcare Leadership. Coupling his educational curriculum with real-life experiences, Jon continues to provide value to both his clients and the entire acute-care pharmacy industry. Jon was just re-elected as an Industry liaison for the MSHP. As each new year brings its own set of challenges, Jon pledges to continue his ever-growing support for the pharmaceutical industry and all of the key stake holders that rely on his support.

Bradley is the Supervisor of Pharmacy Technicians at Dell Seton Medical Center at The University of Texas (DSMC-UT), in Austin, TX, a Level 1 trauma and teaching hospital.

Quickly approaching 38 years as a technician, his experiences include all aspects of the pharmacy department, including the outpatient area. Since August 2013, he has been serving as the first technician appointed to the Texas State Board of Pharmacy (TSBP) as a Board member and is currently serving as the Vice President. He previously served as Treasurer. He is currently a member of NABP, TSHP, AASHP, TPA, and CAPA for many years, serving on various Boards, Committees, and Task Forces. He provides the University of Texas College of Pharmacy and the McComb’s School of Business, mock interviews, to better prepare students for their future careers. Bradley enjoys recreational kayaking, landscaping, and architecture.

LEO F. & ANNE GODLEY RESIDENCY FELLOWSHIP AWARD

An Nguyen, PharmD

An obtained her Bachelor of Science in Biology at the University of Texas at Arlington.

She received her Doctor of Pharmacy degree from the University of Saint Joseph College of Pharmacy in Hartford, Connecticut. After graduating, she worked for a short period as a staff pharmacist at Methodist Charlton, however, decided to then pursue a residency a PGY-1 residency at John Peter Smith Hospital in Fort Worth, Texas. She just accepted a position as the Internal Medicine Pharmacy Specialist at Methodist Charlton, where she will return this Summer upon completion of her residency training. She is also finishing up her two-year term as the Education Chair for MSHP, and has now accepted a new position as their Treasurer for the upcoming year.

Outside of pharmacy, she enjoys spending time with her husband Chris and her 6-year old daughter, Madelyn.

VOLUME 18 | 2019

Jon Eaton

GLENDA LAWSON MCREE PHARMACY STUDENT AWARD

Hannah Gaylord

Hannah received her Bachelor of Science Degree in Chemistry from Texas State University where she was introduced to research in semiconducting polymers. Hannah continued research during pharmacy school at The University of Texas at Austin and has been involved in many research projects during this time. She recently presented a poster on one of these projects, in collaboration with Dusten Rose, PharmD, BCPS (AQ-ID), AAHIVP, on ESBL risk factors at ASHP Midyear in December 2018. In addition to her extensive research work, Hannah also prides herself in community service and enjoys volunteering at several local organizations such as Austin Smiles, Dell Children’s Medical Center, and the SAFE alliance. After graduating in May, Hannah will pursue a PGY-1 residency with Seton Healthcare Family in Austin.

TSHP JOURNAL

28

RESIDENCY PROGRAM EXCELLENCE AWARD Houston Methodist Hospital PGY2 Critical Care Residency

The PGY2 Critical Care Residency Program at Houston Methodist Hospital (HMH) is proud to accept the 2019 TSHP Residency Excellence Award. The program was started in 2005 under the vision and direction of Dr. Michael Liebl and has been led by Dr. Michael Sirimaturos since 2013.

Since its inception, the HMH PGY2 Critical Care Residency Program has demonstrated a significant track record of excellence in training highly successful pharmacy residents.

The program has graduated 24 exceptional critical care residents whom have gone on to receive 50+ awards including 10 Preceptor of the Year awards, 7 Teacher of the Year awards, and 9 Society of Critical Care Medicine (SCCM) Presidential Citations. Other notable accomplishments from the program include 3 Fellows of Critical Care Medicine, 4 Residency/Fellowship Program Directors, 60+ significant presentations at regional/ national/international venues, and 2 Past Presidents of the SCCM Texas Chapter. The 24 PGY2 Critical Care graduates have 90+ publications of which they are first or anchor author on over 50% of the publications. The graduates also have a publication rate more than double the national average for residency research projects. Seventy nine percent of graduates hold board certification and 17% of graduates are board certified in more than one specialty.

The training environment for the PGY2 Critical Care Residency Program at HMH is also exceptional for learning. The hospital has approximately 150 ICU beds amongst 5 unique ICUs, 10 dedicated ICU clinical specialists with over 110 years of combined ICU experience, and 24/7 in-house ICU coverage. The success of the program would not be possible without the time and dedication from all of the clinical pharmacist preceptors that support the residents academically and professionally throughout the year. The residents successes are also enriched by the supportive collaboration and exceptional HMH work environment of the multidisciplinary ICU team of physicians, nurses, NPs/PAs, dietitians, physical therapists, and respiratory therapists that work together to provide optimal care for critically ill patients.

TSHP Member Recognition

2019 Award Recipients INNOVATIVE COLLABORATIVE PRACTICE AWARD UNT Health Clinical Practice Group Advancing Pharmacy Services in Primary Care

UNT Health Clinical Practice Group is an academic medical practice that delivers primary and specialty care to 37,000 patients in the Greater Fort Worth Area. As part of the interprofessional care team, pharmacists provide direct patient care through face-to-face and telephone encounters using the comprehensive medication management (CMM) framework. Under a universal collaborative practice agreement that includes 38 physicians, pharmacists are authorized to provide clinical pharmacy services, including prescriptive authority, for over 40 disease states.

As part of a replicable sustainability plan, the pharmacy division at UNT Health has developed a revenue cycle model that includes feefor-service reimbursement and value-based care programs. The program continues to work toward a sustainable model for ambulatory pharmacists that can be replicated in non-academic primary care practices. Pharmacy team members include: Randy Martin, Katura Bullock, Shara Elrod, Jennifer Fix, Jessica Gardea, Alicia Harris, Crystal Simmons, Megan Wesling, and Cheng Yuet.

PHARMACY LEADERSHIP AWARD

Tricia A. Meyer, PharmD, MS, FASHP, FTSHP

Tricia is the Regional Director for the Department of Pharmacy at Baylor Scott and White Health in Temple, Texas. She is an Associate Professor of Anesthesiology for the Texas A&M College of Medicine and Adjunct Associate Professor for the Texas A&M Rangel College of Pharmacy. Dr. Meyer is a member of TSHP and served as chair of the Educational Affairs Committee, delegate to ASHP, and was recognized as a Fellow for TSHP. She has served as the Heart of Texas chapter president. Tricia is an active member of ASHP, having served as Director-at-Large for the Section for Clinical Specialists and Scientists (SCSS). She represented the SCSS

on the Joint Section/Forum PPMI Coordinating Committee. Dr. Meyer was also appointed to the 2014 & 2015 ASHP Council on Pharmacy Management. Dr. Meyer was involved in the ASHP Section Advisory Group for Investigational Drug Services. She served as a judge for the ASHP Literature Awards, Best Practices Award and was also awarded the Best Practices Award in 2000. She is participating in the revision of the ASHP Guidelines on Surgery and Anesthesiology Pharmaceutical Services. She received the Abbott National Quality Award in 1998, 1999 and the Organon Leadership Award in Hospital Pharmacy in 1998. Dr. Meyer is recognized as an ASHP Fellow. Dr. Meyer’s clinical interest is in the field of anesthesiology where she has published and conducted numerous research studies. She was appointed as the first pharmacist to the Anesthesia Patient Safety Foundation and currently serves on the Education and Training Committee. She regularly contributes to the Anesthesia Patient Safety Foundation Newsletter on perioperative medication safety. She served as the co-chair for the 2003, 2007 & 2019 Consensus Panel on the Guidelines for Management of Postoperative Nausea and Vomiting. The guidelines, endorsed by the Society of Ambulatory Anesthesia, were updated and the 3rd guidelines were published in Anesthesia & Analgesia in Jan. 2014. Dr. Meyer was recommended by ASHP and appointed by CMS to a Technical Expert Panel Member for Ambulatory Surgery Measure development.

NEW PHARMACIST AWARD

Justin D. Shanks, PharmD

Justin graduated from Texas A&M Rangel College of Pharmacy in 2016 where he had the privilege of serving as the Texas A&M Student Society of Health-System Pharmacy President. While a P4 student he served as the TSHP Student Section Executive Committee Chair. He went on to complete a PGY-1 Pharmacotherapy Residency at Baylor Scott & White Medical Center – Temple. While a resident he remained involved in TSHP in the New Practitioner Section Executive Committee (NPEC). Justin is currently employed as a clinical pharmacist primarily in the intensive care unit at Kingwood Medical Center in Kingwood, Texas. In addition to working in the ICU he is actively involved in the antimicrobial stewardship committee, process development committee, and is an active preceptor at Kingwood Medical Center. In April of 2018 he was sworn in as the TSHP NPEC Chair-Elect.

TSHP JOURNAL

29

LEWIS S. SMITH PHARMACY PRACTITIONER AWARD

Melissa Reyes, PharmD, BCPP

Melissa is a clinical pharmacy specialist in psychiatry at Dell Children’s Medical Center in Austin, TX. She received her Doctor of Pharmacy degree at the University of New Mexico in her home town of Albuquerque. After school she moved to Washington, Texas and Minnesota for residencies and first jobs, then moved back to Austin in 2013. Melissa is thrilled to be practicing pharmacy and precepting students and residents at Seton Healthcare Family and The University of Texas where she trained for her PGY2. She recently moved to the children’s hospital and established psychiatry pharmacy services for the new pediatric behavioral health unit. She works as an interprofessional team member optimizing psychopharmacology regimens and providing education to patients, trainees and staff to optimize patient outcomes. Melissa is also an active member of the Austin Area Society of Health-Systems Pharmacists and volunteers in her community.

PHARMACY MENTOR AWARD

Phuoc Anh (Anne) Nguyen, PharmD, MS, BCPS

Anne is a native Houstonian and a proud Austinite where she received her Bachelor of Arts in Biology and Doctor of Pharmacy degree from the University of Texas at Austin.

She completed a PGY1/PGY2/MS in Health Systems Pharmacy Administration Residency at Michael E Debakey VA Medical Center and obtained a Master’s degree in Pharmacy Administration from the University of Houston College of Pharmacy. After residency, she worked for several years as a clinical pharmacy specialist in transitions of care and internal medicine at the University of Texas MD Anderson Cancer Center. She is currently working as a pharmacy manager at Houston Methodist West, overseeing a wonderful team of 40 team members and assisting with operational and clinical initiatives. Her professional interests include leadership development, transition of care initiatives, and patient safety. She has a strong passion in public health, pharmacy, and management and plan to integrate them in her career to optimize patient care and enhance the profession of pharmacy as well as our healthcare system.

VOLUME 18 | 2019

TSHP Member Recognition

2019 Award Recipients TSHP PHARMACIST PRACTITIONER RECOGNITION FELLOWS PROGRAM In 2012, the TSHP Board of Directors approved establishment of a unique Practitioner Recognition Program modeled after the ASHP Fellows program to recognize pharmacists who have made significant and sustained contributions to the Texas Society of Health-System Pharmacists and the profession. Through these presentations, we hope to honor excellence in health-system pharmacy practice and promote public awareness of pharmacists who have distinguished themselves in practice. At the 2013 Annual Seminar, the initial class of TSHP Fellows was recognized. A list of all past recipients can be found at www.tshp.org/fellows. At the 2018 TSHP Annual Seminar, we recognized our 2018 Class of TSHP Fellows.

FTSHP CLASS OF 2019 Maumi C. Villarreal, PharmD, MS, CDE, ANP

Dr. Villarreal is a graduate of the University of Texas College of Pharmacy (BS, MS) and the University of Colorado School of Pharmacy (PharmD).

She is currently a Senior Medical Li-

aison with Novo Nordisk, Inc in the Diabetes & Research Division. Her experiences include hospital Pharmacy, from staff pharmacist to Director of Pharmacy, authorized nuclear pharmacist, and Assistant Professor of Pharmacy Practice and Chief of Patient Care Services with the Texas Tech Health Sciences Center Schools of Pharmacy/Medicine, where she earned her Certified Diabetes Educator designation. She served as President of the El Paso Area Society of Health System Pharmacist numerous times and is currently serving as Chair of the EPASHP Educational Committee. She has also served as Secretary and PAC Chair of TSHP

as well as served on many community Boards of Directors.(El Paso Diabetes Association VP, El Paso Symphony Debutante Chair, volunteer at Abundant Living Faith Center and Faith Christian Academy, etc.)

Dr Villarreal makes her home in El Paso with husband of 32 years, Daniel, and black standard poodle, Belle.

She has 2 daughters who reside in the Pacific Northwest where she and her husband now vacation as much as possible. Dr. Villarreal is very thankful to have been able to participate in the noble profession of pharmacy where she has been blessed to make life-long friends and memories.

TSHP Webinar Series Online and Home-study CPE Courses on Essential & Emerging Topics ÂŤ Presented FREE to TSHP members Âť www.tshp.org/webinars VOLUME 18 | 2019

TSHP JOURNAL

30

YEARS

10

Where are they now?

Mentees from the first TSHP Mentorship Program offer what the program has meant to them.

“For me, participating in the Mentorship Program 10 years ago allowed me to connect with a mentor who completed a similar career path in pharmacy leadership and helped me build my personal and professional connections that have continued in my career. My mentor provided great tips on how to stand out as a resident candidate, we discussed my CV, and he wrote my recommendation letters. Our mentor/mentee relationship continued after pharmacy school. My mentor helped me find my first management job when I completed residency. We are close friends today who I still reach out to ten years later!”

Jerry James, PharmD, MS Director of Pharmacy | Dallas, TX “Being a part of the TSHP mentorship program has been a valuable experience for me to personally and professionally grow as an individual and a leader. My mentors help me to successfully navigate my journey. My way of giving back to my mentors and TSHP is that I have become a mentor to pay it forward to others.”

Phuoc Anh (Anne) Nguyen, PharmD, MS, BCPS 2019 TSHP Pharmacy Mentor Award Recipient Pharmacy Manager | Houston, TX “I owe my mentor a big debt of gratitude! He was an informatics pharmacist so he was able to explain, in great detail, about the job and how the work he did was greatly beneficial for not only the healthsystem, but for the patients as well—you could really tell he was proud of the work he did. I’m an Informatics Pharmacist now myself. It didn’t happen right away though. I graduated, completed a PGY1-residency, and became a clinical pharmacist, but always had our conversations in the back of my mind. Fast forward a few years, I gravitated toward work on an upgrade from EHR to Epic and became a Super User, because my mentor told me what was possible. When a position came open on the Epic build team I jumped at the opportunity. If I never signed up for the TSHP Mentorship Program, I don’t think I would be in the position I am today. I want to tell my mentor, Thank You!” Brett R. Noteware, PharmD, MBA, BCPS Pharmacist Informatics & Information Management | Tyler, TX

TSHP Mentorship Program www.tshp.org/mentorship

Drug-Induced Myopathies: A Systematic Review of the Combined Use of Daptomycin and Statins Marian L. Gaviola, PharmD, BCCCP Assistant Professor of Pharmacotherapy, University of North Texas System College of Pharmacy Elizabeth Berihun, BS Student Pharmacist, University of North Texas System College of Pharmacy Abigail Cole Student Pharmacist, University of North Texas System College of Pharmacy Marc Esquivel, BS Student Pharmacist, University of North Texas System College of Pharmacy Stephanie J. Cox, PharmD PGY1 Pharmacy Practice Resident, John Peter Smith Health Network Meredith L. Howard, PharmD, BCPS Assistant Professor of Pharmacotherapy, University of North Texas System College of Pharmacy

Introduction

Drug-induced myopathies have been associated with a wide array of medications, but with unclear incidence.1 Myopathies can include muscle weakness, myalgias, and elevations in creatine phosphokinase (CPK) concentrations, an enzyme found in heart, brain, and skeletal muscle that may increase with muscle damage.1 Myalgias alone may be troubling to patients but are usually not life-threatening. More severe muscle breakdown may lead to potentially fatal complications such as rhabdomyolysis, a necrotizing myopathy often accompanied by CPK elevations of up to 2,000 times the upper limit of normal (ULN). In rhabdomyolysis, damaged skeletal muscle is catabolized at a rapid rate, releasing byproducts, such as myoglobin, into the bloodstream. Myoglobin excreted through the kidneys may lead to acute kidney injury (AKI) and possible renal failure.2 One of the most common classes of medications VOLUME 18 | 2019

Purpose: Drug-induced myopathies have been associated with the use of daptomycin and statins. These have both independently been associated with creatine phosphokinase (CPK) elevations, myopathies, and rhabdomyolysis. However, it remains unclear if the concomitant use of statins and daptomycin exacerbates this risk. We conducted a systematic review to summarize the available evidence regarding the incidence, degree, and management of muscle-related adverse effects that occur with the concomitant use of daptomycin and statins.

Summary: An English-language PubMed and Medline search was conducted from 1964 through April 2019. Results were limited to case reports and human studies evaluating the effects of the concomitant use of statins and daptomycin on muscle-related outcomes. Nine studies and reports were included for review.

All studies reported on and demonstrated elevations in CPK concentrations. In studies that reported myalgias and myopathies as outcomes, the incidence of these outcomes were reported in 4.2%-6.1% of patients receiving concomitant daptomycin and statin. The occurrence of rhabdomyolysis was rare. Conflicting data on the association between concomitant use and muscle-related adverse events were found.

Conclusion: While concomitant use of daptomycin and statins may lead to elevated CPK concentrations, further research should be conducted to evaluate outcomes in the development of this drug-induced myopathy and to identify additive risk factors.

implicated in drug-induced myopathies is 3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA) reductase inhibitors, or statins. Another medication with increasing reports of CPK elevations and myopathies is daptomycin.

Daptomycin is a broad-spectrum, cyclic, lipopeptide antibiotic indicated for the treatment of complicated skin and skin structure infections, in addition to other infections. It has antimicrobial activity against many aerobic gram positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus (VRE).3,4 Daptomycin inserts the lipid portion of its molecule into bacterial cell membranes, thus creating a channel that allows for an influx of cations. This leads to depolarization of the cellular membrane and eventual death of the bacterium.5 In addition to antibacterial effects, daptomycin has been TSHP JOURNAL

32

associated with increases in CPK concentrations.5,6 Although the exact mechanism is unknown, increased CPK is thought to be related to daptomycinâ&#x20AC;&#x2122;s pore-forming ability.7 Measurement of serum CPK concentrations may provide a reliable biomarker for muscle-related injury, including myopathy and rhabdomyolysis.2 Given daptomycinâ&#x20AC;&#x2122;s ability to increase CPK and cause muscle injury, there may be concern for its use alongside the highly-used statin medications. Between 2012 to 2013, statins were used by an estimated 39.2 million adults in the United States primarily to treat dyslipidemia and prevent atherosclerotic cardiovascular events.8 Statins are generally well tolerated, however, they are also associated with myopathies and rhabdomyolysis.9 According to the Food and Drug Administration (FDA) Adverse Event Reporting System database, between 1998 to 2004, rates of sta-

tin-induced rhabdomyolysis occurred in 0.3 to 13.5 cases per 1,000,000 statin prescriptions.10 The mechanism of statin-induced myopathies is not well known, but is thought to be related to the inhibition of isoprenoids and coenzyme Q10. The incidence of statin-induced myopathies may be influenced by drug-drug interactions, dose, and the degree of lipophilicity of the prescribed statin.11,12 It is unknown whether the concomitant use of statins and daptomycin may increase the risk of developing myopathy and rhabdomyolysis.

The prevalence of statin therapy and the increasing use of daptomycin have led to studies investigating the link between the two and the development of myopathies or rhabdomyolysis. To date, clear recommendations on concomitant use of these two agents do not exist. We have conducted a systematic review of published articles pertaining to the combined use of statins and daptomycin with resulting muscle-related adverse events. The purpose of this review is to summarize the available evidence regarding the incidence, degree, and management of muscle-related adverse effects that occur with the concomitant use of daptomycin and statin therapy.

Methods

An English-language PubMed and MEDLINE search was conducted through April 2019 using the following search terms alone or in combination: statins, HMG-CoA inhibitors, daptomycin, rhabdomyolysis, muscle pain, CPK elevations, and the individual specific generic names of available statin drugs.

References of relevant articles were also reviewed for qualifying studies. Results were limited to clinical studies and reports evaluating statin and daptomycin effects on rhabdomyolysis and muscle-related outcomes. Studies that failed to report outcomes associated with concomitant statin and daptomycin use were excluded.

Results

A total of nine studies and reports were identified for inclusion. All studies were retrospective in nature and a summary of results can be found in Tables 1 and 2.6,13-20 Of the included studies, six studies were observational cohort studies, one was a case-control study, and two were case reports.

Characteristics of statin and daptomycin therapy. The specific statins used differed among the studies included in this review. All retrospective, observational studies reported

simvastatin as the most prevalent statin used, except for the studies by Parra-Ruiz and Lehman et al., which did not provide a list of specific statins included in these studies.6,13-19 The next most commonly studied statins included atorvastatin and rosuvastatin, although pravastatin and lovastatin use were also reported.14-17,19,20 Specific doses were not provided for each statin except in the Golightly et al study.14 The two case reports within this review included patients who experienced rhabdomyolysis and were exposed to simvastatin at doses greater than or equal to 40 mg.6,20 Additionally, Berg et al. reported that the patient who experienced the singular case of rhabdomyolysis in their trial was receiving simvastatin 80 mg.15 The mean doses of daptomycin administered in the retrospective trials were greater than 4 mg/kg in all retrospective trials and ranged from 5.3 mg/kg to 6.78 mg/kg. The duration of daptomycin use was generally extended, ranging from 16 to 40 days. The two most common indications for daptomycin were bone and joint infections and bacteremia.13-19 In the two case reports included, the daptomycin doses administered were 7.2 mg/kg in Odero et al. and 8 mg/kg in Bland et al. with a duration of at least 16 and 18 days, respectively.6,20

were used as markers for myopathy and CPK concentrations of greater than 2,000 units/L used as markers for rhabdomyolysis.19 Timing of CPK measurements also differed among the studies, ranging from 72 hours to 90 days. Three studies reported time to CPK elevation with a median range of 11.5 to 28 days.16,17,19 In the two case reports, CPK elevations occurred at day 9 and day 16 after the initiation of concurrent daptomycin and statin therapy.6,20 The reported mean elevations of CPK ranged from 99 to greater than 1,000 units/L, but case reports described CPK elevations greater than 10,000 units/L. Three of the seven studies excluded patients with baseline CPK elevations and McConnell et al. required a higher CPK elevation of at least 5 times the baseline concentration for those with elevated baseline CPK.14,15,17,19 Only the study by Dare et al. found a statistically significant increase in the risk of CPK elevations with concomitant statin and daptomycin use (odds ratio [OR] = 2.60, p=0.03), while other studies reported an increased trend towards risk that was not statistically significant.15-17,19

Studies did not provide detailed data on the duration of overlap between daptomycin and statin therapy. The duration of concomitant daptomycin and statin therapy required for trial inclusion ranged from one to seven days.

Myalgias or myopathies were measured in four of the studies. Criteria for identifying myalgias or myopathies differed in these studies as well with some using CPK as a surrogate marker, while others relied on symptom documentation. Muscle disease occurred at incidence rates ranging from 4.2% to 6.1%.1416,19 Creatine phosphokinase concentrations did not necessarily correlate with symptoms.

For example, Berg et al. reported only 5 of the 13 patients in their study that experienced myalgia symptoms also had CPK elevations.15

Characteristics of adverse effects.

Three pertinent adverse effects were explored amongst the literature: serum CPK concentration elevations, myopathies, and rhabdomyolysis. Serum CPK concentrations were measured in all nine studies and was used as a surrogate outcome for muscle-related adverse effects; however, the threshold for identifying CPK elevations differed in each study, ranging from 200 units/L to 2,000 units/L. In the seven retrospective studies, CPK elevations occurred in patients on concomitant daptomycin and statin therapy at an incidence rate ranging from 2.89% to 10.2%, although one study reported results as hazard ratio (HR = 1.75, p=0.32) in this population.13-19 One study by Dare et al. used serum CPK concentrations to stratify myopathy severity. Creatine phosphokinase concentrations of greater than 200 units/L

Rhabdomyolysis was reported in three of the studies and in both case reports. Rhabdomyolysis was a rare occurrence and, similar to myalgia and myopathy, varying definitions were used. In the study by Berg et al., rhabdomyolysis was defined as symptomatic muscle pain associated with an elevated CPK; only 1 out of 486 patients experienced this outcome.15 No cases of rhabdomyolysis were reported by Golightly et al.14 In the case-control study by Dare et al., rhabdomyolysis was defined as a CPK elevation of greater than 2,000 units/L, and only 25 patients were identified which corresponded to an incidence rate of 0.8%.19 Both case reports reported the occurrence of rhabdomyolysis. In the case report

by Odero et al., the patient developed AKI with an increase in serum creatinine from 1.5 mg/dL to 3.4 mg/dL.6 The patient experienced albuminuria and an elevated CPK

TSHP JOURNAL

33

VOLUME 18 | 2019

Table 1. Studies evaluating patient outcomes with concomitant daptomycin and statin use Study author, year (n)

Study design

Daptomycin Dose

Statin(s) and Doses

Duration of Concomitant Therapy

Infection Site

Patient Population and Treatment groups

Primary Outcome

Results

Agent Discontinued

Parra-Ruiz, 201213 (n=36 concomitant therapy; 68 comparator arm)

Retrospective, two-center study

>6 mg/kg (median 7.8 mg/kg) *IBWa used for morbidly obese patients

Not described (35% of patients receiving statin therapy)

> 7 days (mean 17 days)

Prosthetic joint infection (41%), bacteremia (26%), diabetic foot infection (24%), endocarditis (9%)

Patients on daptomycin + statin vs daptomycin alone

CPKb elevation (>2.5 times the ULNc)

8% of patients in combination group developed CPK elevation compared to 10% of daptomycin alone (p=0.746). No signs or symptoms of myopathy noted.

Neither therapy discontinued or dose-adjusted

Golightly, 201314 (n=52 concomitant therapy; 690 comparator arm)

Retrospective, single-center, cohort study

6 mg/kg (70%)

Simvastatin (20 mg, 36%; 40 mg 30%), rosuvastatin

At least 1 dose concomitantly

Bone and joint infections (58%), bloodstream (31%), abscess (17%)

Patients on daptomycin + statin vs statin alone

Diagnosis of myopathy, myalgia, myositis, or rhabdomyolysis

9% of patients in combination group had CPK elevations without symptoms compared to 21% of statin alone group (p=0.135)

Not reported

Berg, 201415 (n=63 concomitant therapy; 384 daptomycin alone; 51 statin held)

Retrospective, single-center, cohort study

Mean 5.3 mg/kg

Atorvastatin (40%), simvastatin (40%), pravastatin (7.9%), rosuvastatin (7.9%), lovastatin (4.8%)

> 72 hours

Bone and joint (28.7%), soft tissue/urinary (22.1%), bacteremia/ neutropenic fever (21.1%), abdominal (15.3%), and others

Patients on daptomycin vs daptomycin + statin vs daptomycin (statin held)

CPK elevation (any and >5 times baseline)

8% of total patients on daptomycin develop any CPK elevation and 5% >5 times baseline. Only 5/13 patients with myalgias also had CPK elevations. 3/5 patients on concomitant therapy. Trend towards increased risk of CPK elevation in concomitant group but did not reach significance. 1 patient developed rhabdomyolysis while on simvastatin 80 mg

Daptomycin discontinued in 21/498 patients (3/63 concomitant therapy group).

9% of patients in statin-held group never resumed statin in 1-year follow-up.

Bland, 201416 (n=49 concomitant therapy; 171 comparator arm)

Retrospective, multicenter, cohort study

Mean 6.78 mg/kg

Simvastatin (44.9%), atorvastatin (28.57%), pravastatin (14.29%), rosuvastatin (6.12%), lovastatin (4.08%), unknown (2.04%)

> 24 hours (at least 7 days of daptomycin)

Bacteremia/ endocarditis (48.2%), skin and soft tissue (15%), bone and joint (14.5%)

Daptomycin + statin vs daptomycin alone for 7 days

CPK elevation >1,000 units/L, myalgias, and therapy discontinuation

CPK elevations in 10.2% of combination group vs 5.3% in daptomycin alone (p=0.32); Myalgias in 6.1% of combination group vs 2.9% of daptomycin alone (p=0.38); Median time to CPK elevation was 11.5 days.

Daptomycin discontinued in 3/5 patients with myalgias or CPK elevations.

McConnell, 201417 (n=53 concomitant therapy; 180 comparator arm)

Retrospective cohort study

Median 6 mg/kg

Simvastatin (58.5%), atorvastatin (17%), pravastatin (13.2%), rosuvastatin (11.3%)

Not reported (at least 48 hours of daptomycin)

Bacteremia (34%), skin/soft tissue (32.1%), osteomyelitis (17%), endocarditis (15.1%)

Daptomycin + statin vs statin alone

CPK elevation (if CPK normal at baseline, >3 ULN; if elevated at baseline >5 ULN)

CPK elevation in 5.75% patients in combination group vs 1.1% on statins alone (p=0.08). Median time to elevation was 28 days

Not reported

Lehman, 201618 (n=902 concomitant therapy; 3,471 comparator arm)

Retrospective, multisite study

Not reported

Not reported

Not reported

Not reported

Daptomycin + statin vs daptomycin alone

CPK elevation (not defined)

CPK elevation in 2.89% patients in combination group vs 4.4% in daptomycin alone. Daptomycin alone group was found to be 1.63 times more likely to develop CPK elevation.

Not reported

Dare, 201819 (n=128 myopathy; 25 rhabdomyolysis; 228 controls)

Single-center, retrospective, matched casecontrol risk factor analysis

Mean 6.3 mg/kg

Simvastatin, atorvastatin, pravastatin, rosuvastatin, lovastatin

Not reported (at least 3 days of daptomycin)

Bacteremia (42.2%), osteomyelitis (40.6%)

Myopathy patients matched 1:1 with controls; Rhabdomyolysis matched 1:4 with controls

Myopathy (CPK >200 units/L [ULN]), rhabdomyolysis (CPK >2,000 units/L)

4.2% of patients developed daptomycin-associated myopathy, 0.8% rhabdomyolysis, and 2.3% CPK elevation >2.5 times ULN. Statin coadministration independently associated with myopathy and rhabdomyolysis (p=0.03). Mean time to CPK elevation 16.7 days

46.9% patients discontinued daptomycin

aIBW=

ideal body weight; bCPK= creatinine phosphokinase; cULN=upper limit of normal

which peaked at 8,995 units/L and reported muscle weakness and aches in the extremities. Bland et al., described a patient who also experienced AKI with a serum creatinine elevation from 1.0 to 1.6 mg/dL, a peak CPK of 7,916 units/L, and hyperkalemia with a serum potassium of 6 mmol/L. The patient was admitted for rhabdomyolysis with a CPK concentration greater than 10,000 units/L. Despite this, the patient denied symptoms of musculoskeletal pain.20

initiation of daptomycin and found that 9% of patients never resumed their statin therapy.15 Daptomycin was also discontinued in both case reports. In the case report by Odero et al., only daptomycin was stopped while simvastatin and niacin were continued.6 In the case report by Bland et al., initially daptomycin and simvastatin were discontinued. The patient was subsequently re-challenged with daptomycin alone at a lower dose of 6 mg/kg without recurrence of rhabdomyolysis.20

Agent Discontinuation. The rate of daptomycin discontinuation was reported in three of the seven retrospective trials listed. Rates of discontinuation varied widely from 3.5% to 4.8% of the total number of patients.15,16 Daptomycin was discontinued in patients for either CPK elevations or myalgias.15,16,19 Parra-Ruiz et al. reported no efforts to discontinue statin or daptomycin therapy when adverse effects were seen. While CPK elevations were reported in this study, no signs or symptoms of myopathy were noted.13 Berg et al. also reported on patients who had their statin therapy discontinued prior to the

Discussion

VOLUME 18 | 2019

Daptomycin and statins have been associated with adverse effects including myalgias and rhabdomyolysis independently and when concomitantly used. While associated with elevations in CPK, this does not necessarily correlate with myopathies or muscle damage. Literature investigating this phenomenon varied widely in drug doses used, outcomes reported, and management of the concomitant medications.

The mechanism by which daptomycin and statins cause these adverse effects also TSHP JOURNAL

34

remains unclear; however, previous studies of the medications independently suggest there is a dose and frequency-related association.21,22 In the studies included in this review, no clear stratification of doses and frequencies that might be related to adverse events were found. Most studies included a mean daptomycin dose at or above 6 mg/ kg daily. It may be hypothesized that as the dose of daptomycin is increased for treatment of more severe infections the risk for adverse events may also increase. In relation to statins, simvastatin was the most commonly used statin and its use has been associated with increased myopathy-related adverse events compared to other statins, such as atorvastatin and pravastatin.23 Myalgia was most prevalent in patients taking simvastatin, but this could be due to the high prevalence of simvastatin use in the studies.14-17,19 Conversely, Dare et al. found that patients using pravastatin in combination with daptomycin had the greatest risk of developing rhabdomyolysis, but only five patients taking pravastatin were included in the study.19 Patients were found to be at an increased risk

Table 2. Case reports evaluating patient outcomes with concomitant daptomycin and statin use Report author, year (n)

Study design

Daptomycin Dose

Statin(s) and Doses

Duration of Concomitant Therapy

Infection Site

Patient Population and Treatment groups

Primary Outcome

Results

Agent Discontinued

Odero, 20096 (n=1)

Case report; letter

7.2 mg/kg

Simvastatin 80 mg (additionally, niacin ER 500 mg)

16 days

Bone and joint infection (vancomycin failure?)

Unknown

Development of rhabdomyolysis with symptoms

6 days after discontinuation, aSCr returned to normal; 7 days after discontinuation b CPK decreased to 125 international units/L

Daptomycin discontinued

Bland, 201120 (n=1)

Case report; letter

8 mg/kg (6 mg/kg on restart)

Simvastatin 40 mg

9 days

Bone and joint infection (cutaneous reaction to vancomycin)

69-year-old male

Recurrence of rhabdomyolysis if rechallenged with daptomycin alone

Rhabdomyolysis did not reoccur when daptomycin was give alone for 18 days at 6 mg/kg

Initially both agents discontinued (statin not restarted upon daptomycin rechallenge)

SCr = serum creatinine; bCPK= creatinine phosphokinase

a

and more likely to develop rhabdomyolysis within about 2 weeks of starting treatment, but elevations have been reported as late as 40 days after starting therapy.15 While not clearly delineated in concomitant daptomycin and statin use, patients with body mass index (BMI) > 30 kg/m2 may generally be at higher risk of adverse effects and should be monitored more closely.

All studies reported CPK concentrations, however, not all patients with elevations in CPK experienced myalgias or rhabdomyolysis. Rhabdomyolysis is defined as myonecrosis with myoglobinuria or acute renal failure with an increase in serum creatinine of at least 0.5 mg/dL from baseline.24 Although CPK is a surrogate marker for muscle breakdown and our results suggest that CPK can be a trigger for further workup in patients experiencing muscle-related adverse events, it should not a be used as the sole diagnostic marker.24 Many factors may impact serum CPK concentrations which may subsequently lead to false positives. For instance, individuals may have genetic or idiosyncratic disorders, which can cause hyperCKemia and highly active individuals may have elevated CPK concentrations prior to initiating treatment.23,25 As discussed previously, not all studies included in this review excluded patients with baseline CPK elevations. Furthermore, CPK elevations greater than 2,000 international units/L (e.g., CPK > 10x ULN) do not necessarily predict rhabdomyolysis or myalgias.

Additional factors such as thyroid disorders, hepatic dysfunction, and renal disease may increase a patientâ&#x20AC;&#x2122;s risk of developing CPK elevations. This may potentially contribute to the diagnosis of myalgia and rhab-

domyolysis during statin and daptomycin therapy, especially depending upon the CPK threshold utilized.1 Golightly et al. noted that of the four patients with CPK elevations in their study, two had recent surgery while the other two had CPK elevations at baseline.14 Therefore, it is imperative that clinicians be aware of risk factors that can exacerbate muscle catabolism and monitor for subsequent CPK elevations when starting concomitant therapy with daptomycin and statins.

Based on the current body of literature, there is no clear recommendation on how to manage medication therapy when CPK elevations, myopathies, or rhabdomyolysis occur. Multiple factors should be kept in mind when deciding management, including the severity of the myopathy, and the need for statin and daptomycin therapy. Statins are imperative in reducing cardiovascular events in high-risk patients (e.g., those who have had a previous cardiovascular event) and previous trials have demonstrated an increased risk of cardiovascular events within a week of discontinuing statin therapy.26,27 In contrast, low cardiovascular risk patients have not shown an increased risk of acute coronary syndromes after short-term, abrupt discontinuation of statin therapy.28 Therefore, the degree of cardiovascular disease may guide clinicians as to which medication should be discontinued. Berg et al. also highlighted that 9% of patients who discontinued statin therapy never reinitiated therapy.15 Given the wide array of benefits of statin therapy, especially in high risk patients, it is vital that statins are restarted in patients when feasible.

Conversely, daptomycin is traditionally used in infections as a second line agent when patients are either resistant to the genTSHP JOURNAL

35

eral standard of care, vancomycin, and/or cannot tolerate long-term adverse effects of other agents, such as linezolid.29,30 The majority of patients in the included trials were being treated for bone and joint infections or bacteremia which require longer durations of therapy.30 Patients who are started on daptomycin may have few alternative antibiotic options remaining.

Unfortunately, little research is available to help clinicians identify patients who may be at an increased risk of myopathies when daptomycin and statins are used together. In the multivariate analysis performed by Dare et al., patients receiving daptomycin were found to be at an increased risk of myopathies if receiving therapy for deep abscess infections, using antihistamines, and using statins. Obesity, defined as BMI > 30 kg/ m2, and statin use were also associated with an increased risk of rhabdomyolysis while older age was seen to be protective. These results contradicted previous studies on statin monotherapy which found that older age was associated with an increased risk of rhabdomyolysis.19 Additionally, Dare et al. reported using actual body weight instead of ideal body weight for daptomycin dosing in obese patients, possibly explaining the increased risk observed. Dare et al. ultimately recommended monitoring CPK elevations twice weekly in patients taking concomitant daptomycin and statin therapy and in obese patients, but this recommendation has not been evaluated.19 If a patient does develop CPK elevations in the absence of myopathy or rhabdomyolysis, clinicians should first identify cardiovascular risk and the indication for daptomycin.

It may be reasonable to continue both mediVOLUME 18 | 2019

cations, at lower doses if possible, and monitor CPK concentrations more often than once a week in patients with obesity or daptomycin duration of therapy greater than 7 days.

Daptomycin doses reported in the included studies were typical and careful monitoring should be considered if higher than usual doses are given. If myopathies occur, risks versus benefits of both medications need to be weighed carefully and one or both agents may need to be discontinued. Of note, Dare et al. reported rates of daptomycin discontinuation of 46.9% in patients who developed myopathies.19 In the setting of rhabdomyolysis, specific treatment, including intravenous fluids, should be initiated, and both daptomycin and the statin should be stopped.31 Re-challenge with either agent in the future may be considered on a case-by-case basis.

4.

5.

6.

7.

8.

9.

Conclusion

Concomitant use of daptomycin and statins may increase patient risk of developing CPK elevations, myopathies, and rhabdomyolysis. The actual incidence of severe or life-threatening manifestations of muscle damage is overall low. Statin therapy likely does not need to be discontinued when daptomycin is initiated; however, CPK and muscle-related symptoms should be monitored more often than once weekly especially if duration of daptomycin therapy is greater than 7 days or if the patient has a BMI > 30 kg/m2. Although definitive management of daptomycin and statin-induced myopathies remains unclear, clinicians must weigh the risks versus benefits and alternatives of each medication as well as the degree of muscle damage. It is reasonable to discontinue either daptomycin or the statin depending on patient-specific factors. More studies evaluating treatment options and outcomes following development of this drug-induced myopathy while clearly delineating any additive risk factors for myopathies are needed.

10.

11.

12.

13.

14.

15.

16.

References: 1.

2.

3.

Williams C. Myopathy. In: Tisdale JE, Miller DA, eds. Drug-Induced Diseases.

2nd ed. Bethesda, MD: American Society of Health-System Pharmacists; 2010. 1017-26.

Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve.

2015;51(6):793-810.

Cubicin (daptomycin) injection [package insert]. Lexington, MA: Cubist Pharmaceuticals, 2005.

VOLUME 18 | 2019

17.

Papadopoulos S, Ball AM, Liewer SE, Martin CA, Winstead PS, Murphy BS. Rhabdomyolysis during therapy with daptomycin.

Clin Infect Dis. 2006;42(12):e108-10.

Zhang T, Muraih JK, Maccormick B, Silverman J, Palmer M. Daptomycin forms cation- and size-selective pores in model membranes. Biochim Biophys Acta.

2014;1838(10):2425-30.

Odero RO, Cleveland KO, Gelfand MS. Rhabdomyolysis and acute renal failure associated with the co-administration of daptomycin and an HMG-CoA reductase inhibitor. J Antimicrob Chemother.

2009;63(6):1299-300.

Hohenegger M. Drug induced rhabdomyolysis. Curr Opin Pharmacol. 2012;12(3):33539.

Salami JA, Warraich H, Valero-elizondo J, et al. National trends in statin use and expenditures in the US adult population from 2002 to 2013: Insights from the medical expenditure panel survey. JAMA Cardiol.

2017;2(1):56-65 Valiyil R, Christopher-stine L. Drug-related myopathies of which the clinician should be aware. Curr Rheumatol Rep. 2010;12(3):21320.

Davidson MH, Clark JA, Glass LM, Kanumalla A. Statin safety: an appraisal from the adverse event reporting system. Am J Cardiol. 2006;97(8A):32C-43C. Paiva H, Thelen KM, Van CR, et al. High dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.

Clin Pharm Ther. 2005; 78:60–68.

Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: Mechanisms and management. Diabetes Care.2013;36(Suppl 2):S325-S330.

Parra-Ruiz J, Dueñas-Gutiérrez C, Tomás-Jiménez C, Linares-Palomino JP, Garrido-Gomez J, Hernández-Quero J. Safety analysis of high dose (>6 mg/kg/day) daptomycin in patients with concomitant statin therapy. Eur J Clin Microbiol Infect Dis. 2012;31(8):1771-4.

Golightly LK, Barber GR, Barron MA, Page RL. Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability. Drug Metabol Drug Interact. 2013;28(1):49-58.

Berg ML, Estes LL, Dierkhising RA, Curran B, Enzler MJ. Evaluation of impact of statin use on development of CPK elevation during daptomycin therapy. Ann Pharmacother.

2014;48(3):320-7.

Bland CM, Bookstaver PB, Lu ZK, Dunn BL, Rumley KF. Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors. Antimicrob Agents Chemother. 2014;58(10):5726-31.

McConnell HL, Perris ET, Lowry C, Lodise T, Patel N. Effect of concomitant 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor therapy on creatine phosphokinase levels and mortality among patients receiving daptomycin: Retrospective cohort study.

Infect Dis Ther. 2014;3(2):225-33.

TSHP JOURNAL

36

18. Lehman B, Neuner E, Isada C. A multisite review of concomitant use of daptomycin and statins and the effect on CPK. Abstract presented at: ID Week 2016. New Orleans, LA; 2016 Oct. Open Forum Infect Dis. 2016;3(1).

19. Dare RK, Tewell C, Harris B, et al. Effect of statin coadministration on the risk of daptomycin-associated myopathy. Clin Infect Dis. 2018; 67(9):1356-63.

20. Bland CM, Bookstaver PB, Thomas S. Successful re-challenge of daptomycin therapy after initial rhabdomyolysis with co-administration of simvastatin. Int J Antimicrob Agents. 2011;38(6):549-50.

21. Cziraky MJ, Willey VJ, Mckenney JM, et al. Risk of hospitalized rhabdomyolysis associated with lipid-lowering drugs in a real-world clinical setting. J Clin Lipidol.

2013;7(2):102-8.

22. Armitage J, Bowman L, Wallendszus K, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet.

2010;376(9753):1658-69.

23. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-410.

24. Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA, The national lipid association’s muscle safety expert panel. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S58-71.

25. Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008;359(8):789-99.

26. Heeschen C, Hamm CW, Laufs U, et al.

Withdrawal of statins increases event rates in patients with acute coronary syndromes. i.

2002;105(12):1446-52.

27. Spencer FA, Fonarow GC, Frederick PD, et al. Early withdrawal of statin therapy in patients with non–ST-segment elevation myocardial infarction national registry of myocardial infarction. Arch Intern Med. 2004;164(19):2162–2168.

28. Mcgowan MP. There is no evidence for an increase in acute coronary syndromes after short-term abrupt discontinuation of statins in stable cardiac patients. Circulation.

2004;110(16):2333-5.

29. Humphries RM, Pollett S, Sakoulas G. A current perspective on daptomycin for the clinical microbiologist. Clin Microbiol Rev. 2013;26(4)759-80.

30. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-55.

31. Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015;15(1)5869.

TSHP Research & Education Foundation Chester A. (CAB) Bond Memorial Research Grant

2018 Grant Recipient Impact of Patient Education on Knowledge and Practices Relating to Sharps Disposal Rachel Basinger, PharmD, BCPS, CTTS Assistant Professor, Division of Ambulatory Care Texas Tech University Health Science Center School of Pharmacy Amarillo, TX Purpose of the Project: The adequate disposal of sharps is a critical factor in the reduction of blood borne diseases such as HIV, Hepatitis B, and Hepatitis C.1 Although sharps disposal recommendations from the federal and state level are available to the public online, it still appears that a large majority of patients with diabetes are unaware of the proper procedures for disposal of sharps.

A survey of 50 patients in an outpatient pharmacy conducted by Musselman and colleagues in 2010 showed only 40% of patients stated they received education on how to dispose of their needles and 50% reported throwing their needles directly in the trash after use.2 A 2013 article published in the Journal of General Internal Medicine details this lack of patient knowledge regarding the safe disposal of sharps.3 Providers surveyed 44 patients with diabetes within their own clinic, with 86% of patients reporting improper disposal and only 16% of those patients reported receiving education from their providers about how to correctly dispose of sharps.

Although both studies had a small sample size of patients, it can be inferred that a lack of knowledge regarding proper disposal is prevalent.

References 1.

2.

3.

Safely Using Sharps (Needles and Syringes) at Home, at Work and on Travel. U.S. Food and Drug Administration website. https://www. fda.gov/MedicalDevices/ProductsandMedicalProcedures/HomeHealthandConsumer/ConsumerProducts/Sharps/ucm20025647.html.

Updated March 3, 2016. Accessed October 15, 2017.

Musselman KT, Sicat BL, Thomas MH, Harpe SE. Patientâ&#x20AC;&#x2122;s knowledge of and practices relating to the disposal of used insulin needles. Inov Pharm. 2010;1(2): Article 20.

Costello J, Parikh A. The sticking point: diabetic sharps disposal practices in the community. J Gen Intern Med. 2013;28(7):868-869.

Results will be published upon completion of the project.

TSHP JOURNAL

37

VOLUME 18 | 2019

Teaching Moments An Examination of Eating Disorders

A

ccording to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, there are categories for an eating disorder diagnosis which include anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified, and binge-eating disorder.3 All four categories for an eating disorder are generally considered to be a disturbance in an individual’s eating pattern and behavior that eventually leads to significant impairments in a person’s life and ability to perform normal activities of daily living as a result of the preoccupation with their weight.

In current western culture, the development of eating disorders is an ever growing occurrence that is generally marked by disturbances in eating behavior.1 It is estimated that about 4 out of 5 females in the United States are utterly dissatisfied with their appearance and about 40% usually succumb to an eating disorder in order to achieve what is considered to be the perfect body.2 For the most part, the development of an eating disorder has generally been associated with the female gender, and has become a major public health concern. Greater focus has been placed on this growing issue as it is becoming more of a widespread epidemic among even younger females (age less than 16 years).The focus of women’s health has been actively taking steps towards educating the public about the detrimental and often times irreversible effects of the disorder. Women can experience both systemic and external effects related to the practice of self-deprivation or the development of unhealthy eating habits but systemic effects are typically more prevalent.

Systemic effects can range from infertility to complete organ dysfunction.2,3 In terms of the more predominant eating disorder, bulimia is recognized as being more common than anorexia nervosa. The characteristics of bulimia consists of four key symptoms that clinicians attempt to look for when performing an assessment: (i) over-concern with weight and body shape, (ii) recurrent episodes of binge eating, (iii) recurring subsequent purging, restriction, or excessive exercise, and (iv) binge eating and subsequent inappropriate compensatory behaviors, occurring a minimum average of twice a week for at least three months.1,3 In contrast to women with anorexia, women with bulimia can typically be within the normal weight VOLUME 18 | 2019

range, although recurrent weight changes can frequently be observed in this population.

The majority of female patients with eating disorders can be treated in the outpatient setting. Hospitalization is usually reserved for severely symptomatic patients such as women who present with extremely low body weight (75% or less of expected body weight) whose condition must be hemodynamically stabilized, or those with medical problems requiring intensive monitoring such as patients with electrolyte imbalances, cardiac arrhythmias, profound hypoglycemia, self-mutilation, impaired capacity for self-care, or active suicidal ideation.2,3,4 Also, the failure of outpatient treatment may serve as a valid reason for an individual to receive inpatient treatment. It should be noted that women with a diagnosis of bulimia rarely need hospitalization unless the binge-purge cycle has led to anorexia resulting in severe metabolic deficiencies such as severe electrolyte imbalances, or suicidal depression is present.

Some of the treatments for eating disorders consist of the choice of pharmacotherapy (i.e., antidepressants or low dose antipsychotics) and/or psychotherapy (i.e., cognitive behavioral therapy, interpersonal therapy, psychodynamic therapy, family therapy)).

Psychotherapy has been shown to have the best improvement on symptoms, and the combination of both pharmacotherapy and psychotherapy has been shown to produce some benefits if the dose and duration of therapy is optimal.1,4 While pharmacotherapy has been shown to play a significant role in improving the symptoms of anorexia nervosa, it only provides modest benefit for bulimia nervosa, while cognitive behavioral therapy is recognized as the most effective treatment intervention for bulimia nervosa.4 The use of pharmacotherapy has been shown to be modestly effective in the treatment of treating bulimia. For example, fluoxetine (Prozac®) can be given as 60 mg orally once daily in the morning; may initiate at a lower dose and titrate up over several days.

Other selective serotonin reuptake inhibitors such as trazodone (Desyrel®) at doses of doses of 200 mg/day to 400 mg/day have also been shown to assist with the management of bulimia symptoms. Another class of antidepressants, namely tricyclic antidepressants such as imipramine (Tofranil®) and desipraTSHP JOURNAL

38

mine (Norpramin®) can be used to reduce binge eating and vomiting in bulimic patients.

On the other hand, bupropion (Zyban®, Wellbutrin®, Budeprion®) is one antidepressant that is known to be contraindicated in the treatment of bulimia due to an increased risk of seizures and weight loss. Weight restoration is the ultimate goal of treating anorexia nervosa. A serious medical complication of anorexia nervosa is the development of osteopenia, since peak bone mass is achieved during puberty.

In adolescents with anorexia nervosa, weight restoration was determined to be the most important factor of bone mineral density, but treatment with alendronate did increase the bone mineral densities of the lumbar spine and femoral neck over a year compared with placebo (p=0.02).5 Until additional studies have demonstrated efficacy and long-term safety beyond one year given the risk of teratogenicity, the use of alendronate in this population should be reserved for those with nutritional rehabilitation and severe osteopenia. Transdermal estrogen may also be more effective in adolescent females. Dietary supplements are usually not recommended for anorexia. In a randomized controlled study, Barbarich, et al. (2004) concluded that supplement strategies are not a substitute for proper nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight anorexia nervosa subjects.6 The implementation of enteral or parenteral feeding is rarely needed or recommended unless the patient’s condition is considered to be life threatening due to severe malnourishment. Eating disorders continue to be viewed as a major public health issue and the different forms of treatment available can assist with long-term management. The advent of pharmacotherapy combined with psychotherapy has the ability to manage symptoms and improve the condition of many women who currently suffer with an eating disorder.

Abimbola Farinde, PharmD, BCGP Professor, Columbia Southern University Pharmacist, Cornerstone Hospital References continued on page 40.

Leave Your Student Loans Behind TSHP members receive a 0.125% rate discount when they refinance with Laurel Road.1

What is Student Loan Refinancing and Who is Eligible TSHP members can choose to refinance all or some of their federal and private loans from bachelor, and/or graduate degree programs. Laurel Road refinances student loans by paying off a customer's current student loans and issuing them a new loan.

Laurel Road refinances student loans for pharmacists with degrees from accredited schools.

Borrowers must be U.S. citizens or permanent residents. Loan eligibility depends on lending criteria such as your credit profile, monthly income, and monthly debt payments.

Why refinance?

Student loan refinancing is an opportunity to: • Lower interest rate(s) and save money • Pay off loans faster • Lower monthly payments • Move from a fixed rate to a variable rate (or vice versa) • Reduce number of loans in repayment

Member Benefit TSHP members receive a 0.125% rate discount when refinancing their student loans1

To learn more and apply, visit www.tshp.org/laurelroad

TSHP Competition Winners 2019 Leadership Challenge Competition Van Nguyen, Eileell Alin Nguyen, Amilda Medina PharmD Candidates, University of Houston College of Pharmacy Team Proposal: The goal of our plan is to reduce and eliminate drug diversion to improve the safety of the staff and the patient. To achieve this and regarding this specific case, we prioritized access, workflow, and response time as the main issues, which is best presented in Plan 1. Metrics that will be used to determine if plan is successful consists of override, diversion, and incident reports, which would all be presented at the monthly Controlled Substance Committee (CSC) meetings. Monthly CSC meetings would be held to review plan with feedbacks from nursing, pharmacy, and all relevant staff following modifications if necessary. The meeting with the key players would establish an interdisciplinary understanding of the new workflow. All nursing supervisors would be e-mailed with new information on the workflow with www.tshp.org/competitions the access form attached. Under the assumption that all financial and personnel resources are available, achieving this goal should not be a problem, and it is projected to take about a month to start. With Pyxis ES Server currently already in use, altering access and workflow would be feasible in a health system setting. Plan 1 will help address current issues due to the recent drug diversion case. This is the right time to implement this plan to prevent any future incidents. To address access, Plan 1 proposes that automated dispensing cabinet (ADC) access by nurses should be more strictly - nurses cannot pull controlled substances (CS) unless the medication is linked to their patient’s profile. However, an override can be done in the event of an emergency with the caveat of supplemental personnel requiring a witness for the process. Additionally, nurses are granted access to the ADC by pharmacists through fax to limit the nurses’ access to specific units they cover. By limiting certain pharmacy technicians from unloading controlled substances, it prevents diversion on the pharmacy end, but narcotic technicians have full access to the ADC, allowing them to resolve any discrepancy and work flow issues.

View the teams full proposal | View the 2019 Competition Case

2019 Clinical Skills Competition

Article continued from page 38

P1 Winners: Ricky Huynh‐Phan & Duc Huynh

University of Houston College of Pharmacy P2 Winners: Leia Gaddis & Princy John

Texas Tech University Health Science Center School of Pharmacy Honorable Mention: Kevin Burnham & Kevin Varughese

University of Texas College of Pharmacy – Tyler P3 Winners: Alana Coleman & Hanna Kim

University of Texas College of Pharmacy – Austin Honorable Mention: Jenny Lee & Tarak Patel

Texas Tech University Health Science Center School of Pharmacy

2019 Disease State Management Competition Winner:

Honorable Mention:

VOLUME 18 | 2019

Anna Bozhkova University of the Incarnate Word Feik School of Pharmacy Jennifer Dela Pena University of Houston College of Pharmacy TSHP JOURNAL

40

References 1.

2.

3.

4.

5.

6.

Hersen M, Turner S. & Beidel D. (Eds.).

Adult psychopathology and diagnosis. (5th ed.) Hoboken, NJ: John Wiley & Sons, 2007.

Schaffner A. & Buchanan L. EvidenceBased Practices in Outpatient Treatment for Eating Disorders. International Journal of Behavioral Consultation & Therapy, 2010; 6(1): 35-44.

American Psychiatric Association.

Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. Text citation: (American Psychiatric Association, 2013).

Hahn RK, Albers LJ, & Reist C.Psychiatry.

Blue Jay, California: Current Clinical Strategies Publishing, 2008.

Golden NH, Iglesias EA, Jacobson MS, et al.

Alendronate for the treatment of osteopenia in anorexia nervosa: A randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2005;90(6):3179-3185.

Barbarich NC, McConaha CW, Halmi KA, et al. Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. Int J Eat Disord. 2004;35(1):10-15.

TSHP Interact is an exclusive benefit for TSHP members,

a place to connect, ask questions, find resources, and participate in conversations.

How do I interact?

Go to interact.tshp.org.

What is my username and password?

It is the same as your member login.

How can I contribute?

Submit a question or give a possible solution to somebodyâ&#x20AC;&#x2122;s problem. Go beyond by sharing new perspectives, your experiences, or data from your own research!

Can I search community members?

Using the Directory tool, you can search by name, title, or company.

For , ns Texa ans ex

By T

Free.

Online.

Community.

Log on now @ interact.tshp.org

TSHP Research & Education Foundation Poster Competition

2019 Winners VOLUME 18 | 2019

TSHP JOURNAL

42

E

very year, the Texas Society of Health-System Pharmacists Research & Education Foundation holds a poster competition during the TSHP Annual Seminar. The Competition is an opportunity for new practitioners, students, technicians, and practitioners to submit and display original scholarly work in poster format in one of the followings seven categories: Resident/Fellow/Post-Graduate category includes posters submitted by pharmacists enrolled in a post-graduate residency, fellowship or other post-graduate educational programs. The category is divided into two sub-groups: PGY1 and PGY2.

Student category includes posters submitted by students enrolled in pharmacy academic programs.

Technician category is for posters submitted by practicing pharmacy technicians and technician students.

Practitioner category is for posters submitted by registered pharmacists in one of three categories: • Administrative/Practice Management is related to professional practice management issues and leadership.

• Clinical is related to patient care delivery, therapy and outcomes.

• Education is related to patient, healthcare practitioner and community education and/or educational planning, development and conduct for professional practice.

The 2019 TSHP Research & Education Foundation Poster Competition took place at the 2019 Annual Seminar in Frisco, TX, April 12-13. The Foundation is proud to offer abstracts for the seven 2019 winning posters. Click on each poster image to view larger.

The 2020 Call for Posters will open December 2019. For full competition details, visit www.tshp. org/poster.

PRACTITIONER – CLINICAL The Impact of a Transitional Care Management Pharmacist on Medication-Related Readmissions L Paul, M De La Garza, S Le, K Purcell Baptist Health System, San Antonio, TX Background: Ineffective transitions of care lead to poor patient outcomes, increased expenses, and higher hospital readmission rates. Baptist Health System implemented a transitional care management (TCM) program to prevent future readmissions. A TCM pharmacist was added to focus on reducing medication-related readmissions.

Objective(s): The primary objective was to evaluate the impact of the TCM pharmacist on medication-related readmissions. The secondary objective was to evaluate the overall impact of pharmacist interventions on patient outcomes.

Method(s): A retrospective evaluation was conducted on all patients who were consulted by the TCM pharmacist from April 1 to December 31, 2018 for the 6 Baptist hospitals in the San Antonio market of Tenet Healthcare.

Results(s): The TCM pharmacist was able to identify discrepancies on 47% of the discharge medication lists. The most common discrepancies were incomplete medication reconciliation due to missing frequency (46%), medication omission (16%), incorrect dose (14%), and duplication of therapy (14%).

Approximately 200 interventions were made during the day 3 post-discharge follow-up phone calls.

The most common interventions included patient education on new and discontinued medications, non-medication related issues such as scheduling a follow-up appointment with primary care or specialist physicians, and communication with hospital case managers on problems encountered. The medication-related readmission rate was reduced by 80% when the TCM pharmacist was involved.

Conclusion(s): The TCM pharmacist was able to improve transitions of care and reduce medication-related readmissions by 80% through making post-discharge follow-up phone calls, identifying and resolving discrepancies on the discharge medication list, and intervening on medication-related issues.

Disclosure(s): None.

THE IMPACT OF A TRANSITIONAL CARE MANAGEMENT PHARMACIST ON MEDICATION-RELATED READMISSIONS Linda Paul, PharmD, BCPS, Merissa De La Garza, PharmD, Samantha Le, Kevin Purcell, MD, PharmD, MHA Baptist Health System, San Antonio, TX

BACKGROUND o Transitions of care are defined as the movement of patients between various providers and settings o Ineffective transitions of care lead to adverse events, higher hospital readmission rates, and increased cost o In 2012, The Joint Commission and Centers for Medicare and Medicaid Services established hospital readmission reduction programs to address gaps in patient care o Hospitals are faced with the challenge of providing optimal and cost-effective transitions of care o In an effort to prevent and reduce readmissions, Baptist Health System (BHS) implemented a transitional care management (TCM) program o A TCM pharmacist was added to focus on reducing medication-related readmissions o TCM pharmacist services were to include medication reconciliation, day 3 post-discharge follow-up phone calls, interventions, and case manager referrals for problems encountered

OBJECTIVES Primary: o Determine the impact of the transitional care pharmacist on medication-related admissions Secondary: o Evaluate the overall impact of pharmacist interventions on patient outcomes

METHODS

METHODS (CONT.) o Patients referred to the TCM pharmacist for consultation included Medicare patients discharged home or home with home health AND with >1 of the following qualifying diagnoses: o Congestive heart failure, acute myocardial infarction, coronary artery bypass graft, cardiac arrhythmias, percutaneous coronary intervention, cardiac defibrillator, pacemaker, renal failure, urinary tract infection, sepsis, gastrointestinal hemorrhage, pneumonia, chronic obstructive pulmonary disease, and stroke

o 528 patients (60%) were reached by the TCM pharmacist and 200 interventions were made during the day 3 post-discharge follow-up phone calls

Other 10%

Dose 14%

Duplication 14%

Frequency 46%

Figure 3. Interventions at Follow up Call Recommendation 18%

Communication 6%

o 248 (47%) of the discharge medication lists had discrepancies o Common discrepancies were incomplete medication reconciliation due to missing frequency (46%), omission of medications (16%), incorrect dose (14%), and duplication of therapy (14%) (Figure 2) o Common interventions were patient education on new and discontinued medications, non-medication related issues such as scheduling a follow-up appointment with primary care or specialist physicians, and communication with hospital case managers about problems found (Figure 3)

Education 23% PCP refferal 18%

Other 23%

Failure to pick up rx 6% No PCP 6%

o Medication-related readmissions were reduced by 80% (Figure 1)

CONCLUSIONS

Figure 1: Flow Diagram

o The TCM pharmacist was able to improve transitions of care and reduce medication-related readmissions by 80% through making day 3 post-discharge follow-up phone calls, identifying and resolving discrepancies on the discharge medication lists, and intervening on medication-related issues

Medicare pt. discharged home/home with home health (n= 897)

o Patients were from al 6 Baptist hospitals in the San Antonio market of Tenet Healthcare

RPH not contacted (n=369, 41%)

RPH contacted (n=528; 59%)

o The time period was April 1 to December 31, 2018

Not readmitted (n=503; 95%)

Readmitted (n=25, 5%)

Med-Related (n=1; 0.2%)

For more information or a reprint of the poster, please contact Linda Paul (lindacpaul@gmail.com)

TSHP JOURNAL

Omission 16%

RESULTS o The TCM pharmacist was consulted on 897 patients from April 1 to December 31, 2018 (Figure 1)

o A retrospective evaluation was conducted on all patients who were consulted by the TCM pharmacist

o Data was collected from the Cerner and AllScripts electronic health records and the MIDAS system, which documents pharmacist-directed interventions on patient outcomes

Figure 2. Errors on Discharge Medication Reconciliation

43

Not Readmitted (n = 331, 90%)

Readmitted (n=38, 10%)

o Coordination of care across the health care continuum is crucial to ensure continuity and promote successful treatment and prevent readmissions

Med-Related (n=4; 1%)

Texas Society of Health-System Pharmacists, April 12-14, 2019. Frisco, TX

VOLUME 18 | 2019

TSHP Research & Education Foundation

2018 Poster Competition Winners PRACTITIONER – EDUCATION Experiential Education’s Role in a Successful Residency Interview JT Copeland, JC Fazio-Gosser, CM Long University of the Incarnate Word, Feik School of Pharmacy, San Antonio, Texas

Background: Completion of a pharmacy residency continues preparation for practice by providing opportunities to apply knowledge learned in school to various patients while enhancing essential career skills. The value of these training programs has prompted an employment advantage and, consequently, acquiring a residency position has become increasingly competitive.

Objective(s): The Experiential Education (EE) department at the Feik School of Pharmacy (FSOP) is making efforts to provide residency-seeking students with rotations that will improve their success as a residency applicant.

Method(s): EE has worked to optimize the timing and availability of direct patient care advanced pharmacy practice experiences (APPEs) for students interested in residency. It is our hope that completion of these rotations prior to the American Society of Health-System Pharmacists Midyear Clinical Meeting will enhance interview performance as a result of strengthened clinical knowledge as well as an improved capacity to discuss their experiences providing patient care and being a healthcare team member.

Result(s): Longitudinal APPE (LAPPE) programs at local hospitals were developed with priority given to residency-seeking students in order to provide additional direct patient care experiences and to provide them earlier in the year. These programs will enable 13 (15%) P3 students at FSOP pursuing residency to complete direct patient care rotations and possibly longitudinal projects prior to recruiting events, thus strengthening their residency candidacy.

Conclusion(s): The development of LAPPE programs is one strategy EE departments can implement to improve the ability for students pursuing residency to obtain learning experiences critical to successful residency interviews.

Disclosure(s): None.

Experiential Education’s Role in a Successful Residency Interview Jeffrey T. Copeland PharmD, Joanne C. Fazio-Gosser RPh, Christina M. Long PharmD, BCPS University of the Incarnate Word Feik School of Pharmacy San Antonio, TX

Background

Methods

Results

Completion of a pharmacy residency program continues preparation for practice by providing opportunities to apply knowledge learned in pharmacy school to various types of patients and in variety of settings while enhancing essential career skills, such as project and time management, research, networking, and professional development, under the mentorship and guidance of established pharmacists in the field. The value of these training programs has prompted an employment advantage and, consequently, acquiring a residency position has become increasingly competitive and challenging. Pharmacy students seeking a postgraduate year one (PGY1) residency must apply and consequently interview midway through their final year of pharmacy school.

The EE department has worked to optimize the timing and availability of direct patient care APPEs for students interested in residency. It is our hope that completion of these rotations prior to the American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting (the largest residency recruiting event of the year) and subsequent residency interviews will enhance performance at these events as a result of strengthened clinical knowledge as well as an improved capacity to discuss their experiences providing patient care and being a healthcare team member.

Longitudinal APPE (LAPPE) programs at local hospitals were developed with priority given to residency-seeking students in order to provide additional direct patient care experiences and to provide them earlier in the year, prior to the ASHP Midyear Clinical Meeting and residency interviews. This year, these programs will enable 13 (15%) of all P3 students at FSOP and all of those currently interested in pursuing residency to complete direct patient care rotations and possibly longitudinal projects prior to recruiting events, thus strengthening their residency candidacy.

Conclusions The development of LAPPE programs is one strategy EE departments can implement to improve the ability for students pursuing residency to obtain learning experiences critical to successful residency interviews. In the future, the EE department at FSOP will continue to search for strategies to improve students’ level of career readiness.

Objective The Experiential Education (EE) department at the Feik School of Pharmacy (FSOP) is making efforts to provide residency-seeking students with advanced pharmacy practice (APPE) rotations in their fourth year that will improve their success as a residency applicant.

For more information, contact JTCopela@uiwtx.edu The authors have nothing to disclose.

VOLUME 18 | 2019

TSHP JOURNAL

44

TSHP Research & Education Foundation

2018 Poster Competition Winners

STUDENT Medication Use Evaluation of Vaginal Misoprostol vs Intravaginal Dinoprostone Insert for Labor Induction S Nim, H Christian, A Graves Memorial Hermann The Woodlands Medical Center, The Woodlands, Texas Background: Labor induction rate has doubled over the past three decades to about one in five births.

Even though dinoprostone is FDA approved for labor induction, misoprostol is still used as a lower cost alternative. Per American Congress of Obstetricians (ACOG), there are currently no strong recommendations to choose one agent over the other.

Objective(s): To evaluate the efficacy of utilizing vaginal misoprostol versus intravaginal dinoprostone insert as cervical ripening agents, their differences in safety, and cost savings potential at Memorial Hermann The Woodlands Medical Center.

Method(s): This will be a single-center retrospective chart review of pregnant patients receiving vaginal misoprostol or intravaginal dinoprostone for labor induction from January 2016 to September 2018.

Result(s): Data from present up to 2016 shows 872 eligible patient chart documenting 341 vaginal misoprostol and 531 dinoprostone use. Maternal and neonatal characteristics were nonsignificant.

Delivery within 24 hours were %62.1 (95%CI 57.0-67.3) and %55.2 (95%CI 50.9-59.4) for misoprostol and dinoprostone respectively. This is a difference of 7.0% (0.3 to ∞, 97.5% non-inferiority CI). Other significant findings were increase rate of tachysystole in misoprostol, %29.6 (95%CI 24.7-34.5), versus dinoprostone, %21.8 (95%CI 18.3-25.4) and subsequent terbutaline use. There was no significance in birth-related complications.

Conclusion(s): Vaginal misoprostol is non-inferior to dinoprostone with similar safety profiles with an exception to increase tachysystole and terbutaline use. Annually, $217,780.64 of resource can be allocated to other areas of the hospital if a major switch to misoprostol is made.

Disclosure(s): None.

Chemical Synthesis of Flexible Antitumor Agents using 1H imidazole-4-carbonitrile Joseph I Nnani, Ifeyinwa B Nwolisa, Hamed I Ali Ph. D. Texas A&M Irma Lerma Rangel College of Pharmacy

Background • Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells.

Cancer is the second most common cause of death in the US, exceeded only by heart disease.1 •

Method • Our chemical synthesis is only the initial stage of an ongoing research by Dr. Ali in his lab at Texas A&M College of pharmacy. The method was adapted from Sleebs et al 2010.

• There were 3 major steps in this phase of the research that we were responsible for: • Addition reaction: major reactants- MeOH (anhydrous), NaOMe, NH4CL , heat • Cyclization reaction: Major reactants- Diethyl malonate, NaOMe, heat

In 2018, the FDA approved over 100 new cancer drugs. About 20% of these were kinase inhibitors.2

• Kinase Inhibitors have the advantage of providing targeted cancer therapy which reduces collateral damage to other healthy cells in the patient’s body.

• However, there is still a challenge of constant mutation of cancer cells which creates resistance to cancer therapy including the kinase inhibitors.

• Chlorination reaction: Major reactants- Toluene (anhydrous), POCL3, trimethylamine, • After each step, the resulting compound was analyzed using TLC and NMR.

• The results were compared to computer generated expected results and the success of each step was based on that comparison.

• The summary of the steps in the synthesis and results are shown below.

Chemical Synthesis Objective

Step 1 - Addition

• This research was aimed at synthesizing a flexible kinase inhibitor antitumor agent aided by computational design and to optimize their potencies by structural optimization • A flexible kinase inhibitor will combine targeted tumor therapy with the ability to change conformation in response to any mutations at the cancer cell receptor site.

•

Result Step 1 - Addition • TLC: The original compound rose a bit higher than the salt product and this was the expected outcome.

• The NMR result from the first step showed the correct predicted peaks. There were five distinct peaks. Two peaks were at 8, one was at 7.5. A peak at 3.5 which was the water peak, and a final peak at 2.5 was for the NMR reagent used - DMSO. Step 2 – Cyclization • TLC: The cyclized product from step 2 rose higher than the salt from step 1.

Step 3 - Chlorination • TLC: A 1:1 mixture MeOH: EtoAC did not show any movement for the chlorinated product. A 2:1 solvent mixture showed the chlorinated product rose a bit higher than the cyclized product.

• NMR: The result gotten from the NMR was not what was expected. The peak expected at position 5.0 was not found.

Conclusion

Step 2 – Cyclization

• The 5-year relative survival rate of all cancers combined has improved due largely to advances in treatment.

• Creating a flexible kinase inhibitor antitumor agent will further improve survival by delivering targeted cancer cell therapy and circumventing cancer cell resistance due to gene/receptor site mutation.

• The use of an imidazole analogue shows some promising results .

• Further work varying the synthesis parameters is needed and if this imidazole analogue does not produce a final favorable result, a different imidazole analogue could be used.

Step 3 - Chlorination

Our role in this multi-step research is to identify a plausible imidazole analogue and carry out the initial stages of the chemical synthesis.

• We used 1H imidazole-4-carbonitrile as our imidazole analogue starting compound.

1. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf 2. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm 3. Sleebs BE, Street IP, Bu X and Baell JB. De Novo Synthesis of a Potent LIMK1 Inhibitor. Synthesis. 2010; 7: 1091-96.

4. Kosisek M, Stepanek O, Parkan K et al. Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly. Bioorg Med Chem Lett. 2016; 26 (15): 3487-90.

TSHP JOURNAL

45

VOLUME 18 | 2019

TSHP Research & Education Foundation

2018 Poster Competition Winners TECHNICIAN A Journey Towards Zero Pyxis Stock Outs: A Patient Centered Approach S Cooper, D Nyakundi, S Parekh, M Ouma, T Roduta, R Cox Memorial Hermann Memorial City Medical Center, Houston, TX

Background: In both decentralized distribution systems and combinations of both centralized and decentralized pharmacy distribution, automated dispensing cabinets (ADCs) serve as a dispensing technology within a majority of hospitals across the country. Post-implementation optimization is necessary to maximize the benefits of ADC technology. Pharmacy technician labor requirements (such as number of refills) and ADC inventory stock out percentages are useful metrics to justify ADC optimization efforts. Memorial Hermann Memorial City Medical Center utilizes Pyxis® automated dispensing cabinets.

In an effort to move to a more patient-centered approach, various improvements to the Pyxis® hardware, education to the staff, and reset of medication distribution culture is necessary.

Objective(s): To increase availability of medications through optimization of ADCs. Method(s): Many strategies were deployed to optimize Pyxis and move toward a goal of zero stock outs: 1) development of a Pyxis refresher for education and review of difficult topics/functionalities; 2) development of a standardized approach to loading new medications in Pyxis including identifying loading/unloading drawers, standardizing pocket sizes, and identifying appropriate min/max levels; 3) review of stock outs daily and updating par levels based on patterns; and 4) deployment of hardware changes for space optimization.

Result(s)/Conclusion(s): Through different optimization strategies, education, and a resetting of the pharmacy distribution culture, the percentage of stock out per number of vends decreased. Additionally, the ratio number of vends per number of refills increased. Despite loading more medications in Pyxis and increasing the vend to refill ratio, the amount spent on inventory loaded in Pyxis did not increase.

Disclosure(s): None.

A Journey Towards Zero Pyxis Stock Outs: A Patient Centered Approach Steven Cooper, CPhT; Daniel Nyakundi, CPhT; Shreya Parekh, PharmD, MS, BCPS, Martha Ouma, Msc, PMP; Thomas Roduta, PharmD, MS; Rodney Cox, BSPharm, MS Memorial Hermann Memorial City Medical Center, Houston, Texas

BACKGROUND

METHODS

• In both decentralized distribution systems and combinations of both centralized and decentralized pharmacy distribution, automated dispensing cabinets (ADCs) serve as a dispensing technology within a majority of hospitals across the country1 • Post-implementation optimization is necessary to maximize the benefits of ADC technology • Optimization strategies have improved medication inventory, par level determination, and availability of medications for nurses when they are needed for patient administration2 • Pharmacy technician labor requirements (such as number of refills) and ADC inventory stock out percentages are useful metrics to justify ADC optimization efforts3 • Memorial Hermann Memorial City Medical Center utilizes Pyxis® automated dispensing cabinets • In an effort to move to a more patient-centered approach, various improvements to the Pyxis® hardware, education to the staff, and reset of medication distribution culture is necessary

MEASURES OF SUCCESS

1600

% Stock Outs per Number of Vends

Vend to Refill Ratio

10 9.8

200,000

9.6

150,000

Scheduled multimodal 100,000 pain therapy within 48 hours of admission 50,000

• • • •

Length of stay 30-day readmission Pain scores Pharmacy pain consult

-

9.4 9.2 9 8.8 8.6

Number of Vends

$600,000.00

Vend to Refill Ratio

Linear (Vend to Refill Ratio)

Inventory Value

$500,000.00 $400,000.00 $300,000.00 $200,000.00 $100,000.00 $0.00

DISCUSSION 100% 90%

1400

80%

1200

70%

1000

60%

800

50% 40%

600

• Percentage of stock outs per number of vends in the ADC • Ratio of number of vends per number of refills in the ADC • Inventory value within the ADC

250,000

RESULTS

PURPOSE • To increase availability of medications through optimization of the ADCs • To move from a nurse-centered medication delivery system to a more patient-centered approach

RESULTS CONT.

• Annual strategic plan set a vision for pharmacy to move from a nurse-centered medication delivery system to a more patient-centered approach • Development of a Pyxis® refresher for education • Pyxis ES system manager reviewed the top three questions that were marked incorrectly with the staff • Development of a standardized approach to loading new medications into the Pyxis® • Identified loading/unloading drawers • Standardized pocket sizes • Identified appropriate min/max levels based on dose frequency • Review of stock outs daily • Updated min/max levels based on patterns and repeated trends • Deployment of hardware changes for space optimizations • Changed matrix drawers to cubie pockets

30%

400

20%

200

10%

0

0%

Number of Stockouts Linear (% Stockout per Vend)

% Stockout per Vend

• Pyxis® optimization, hardware upgrades/ standardization, and staff education produced positive results towards the goal of zero stock outs • Despite loading more in Pyxis® and increasing the vend to refill ratio, inventory value did not increase

References 1. McCarthy BC, et al. Implementation and optimization of automated dispensing cabinet technology. American Journal of Health System Pharmacy.

2014; 73(19): 1531-1536.

2. Kelm M, et al. Improved arrangement and capacity for medication transactions: a pilot study to determine the impact of new technology on medication storage and accessibility. Hospital Pharmacy. 2018; 53(5): 338– 343.

3. O’Neil DP, et al. A comparison of automated dispensing cabinet optimization methods. American Journal of Health System Pharmacy. 2016; 73(13): 975980.

DISCLOSURE: Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have direct or indirect interest in the subject matter of the presentation.

VOLUME 18 | 2019

TSHP JOURNAL

46

TSHP Research & Education Foundation

2018 Poster Competition Winners

RESIDENT/FELLOW/POST-GRADUATE - PGY1 Heparin Requirements in Patients with Impella® and TandemHeart® Support Devices RP Kessinger, MC Mousavi, EB Yin CHI Baylor St. Luke’s Medical Center, Houston, Texas Background: Devices such the Impella® and TandemHeart® provide support to patients with refractory cardiogenic shock. Patients are managed with local heparin flowing through the device as well as systemic heparin to prevent thrombus formation. Managing multiple heparin infusions can be challenging, and the device manufacturers provide limited guidance.

Objective(s): The objective is to examine safety and efficacy outcomes and heparin requirements for the current TandemHeart® and Impella® heparin protocols in order to determine what improvements can be made.

Method(s): This is a retrospective chart review of 47 patients from January 2018 to December 2018.

Heparin requirements were assessed from post-operative hours 6 to 48 for each device.

Result(s): For the Impella®, the average device heparin rate was 360 units/hour (45% of the total) and the average systemic heparin rate was 452 units/hour (55% of the total); 48% of the patients had a systemic heparin rate of 0 units/hour at 6 hours post-implant. For the TandemHeart®, the average device heparin rate was 829 units/hour (81% of the total) and the average systemic heparin rate was 239 units/hour (19% of the total); 89% of patients had a systemic heparin rate of 0 units/hour at 6 hours post-implant.

TandemHeart® patients had a higher rate of supra-therapeutic activated partial thromboplastin times even when no systemic heparin was started.

Conclusion(s): The current order set has a higher initial rate for systemic heparin than is seen in practice. In addition, a TandemHeart® infusate protocol would allow easier adjustment of device heparin concentration.

Disclosure(s): None.

Heparin requirements in patients with Impella® and TandemHeart® support devices

Rebecca Kessinger, PharmD; Mariam Mousavi, PharmD; Ellen Yin, PharmD, BCCP, BCPS CHI St. Luke’s Health Baylor St. Luke’s Medical Center, Houston, Texas

BACKGROUND

RESULTS

• Temporary mechanical circulatory support devices such as the Impella® and TandemHeart® systems provide support to patients with severe refractory cardiogenic shock

Figure 1. aPTTs from 6-48hr – All devices

• Local anticoagulation flowing through the device, often in addition to systemic anticoagulation, prevents pump thrombosis and systemic embolization

Table 2. Outcomes – Anticoagulation TandemHeart®

• Both the fixed rate infusate and the variable rate purge solution present challenges, and anticoagulation management in these patients is very complex • The device manufacturers provide limited guidance on the best method for anticoagulation management • At Baylor St. Luke’s Medical Center, we use a low intensity heparin order set with a starting rate of 500-1000 units/hr and a typical activated partial thromboplastin time (aPTT) goal of 65-85 for the systemic component of device anticoagulation

54% 40%

Examine safety and efficacy outcomes and heparin requirements for patients using the current heparin protocol for Impella® or TandemHeart® anticoagulation in order to determine what improvements can be made

METHODS • This retrospective chart review included 47 patients that received an Impella® or TandemHeart® device from January 2018 to December 2018

Impella®

18%

TandemHeart®

Systemic heparin to meet goal aPTT 65-85

Sub-therapeutic

Therapeutic

Supra-therapeutic

TandemHeart®

Age – yr (mean ± SD) Male sex, n (%) Weight – kg (mean ± SD) Race, n (%) Caucasian African American Hispanic Asian Other Indication for support, n (%) Ischemic Non-ischemic Duration of support, hr (median, range) Devices placed, n

10 (34) 13 (45) 4 (14) 0 (0) 2 (7)

10 (56) 6 (33) 1 (6) 1 (6) 0 (0)

13 (45) 16 (55)

9 (50) 9 (50)

177, 23-772

145, 65-1159

40

18

0 units/hr

19 (48)

16 (89)

> 0 units/hr

21 (53)

2 (11)

Outcome 50%

33%

31%

17%

Sub-therapeutic

17%

Therapeutic

Supra-therapeutic

83

779

750

6 (15)

4 (22)

Impella® Patients (n=29)

TandemHeart® Patients (n=18)

Minor bleeding, n (%)

6 (21)

4 (22)

Major bleeding, n (%)

20 (69)

10 (56)

Hgb drop ≥ 4 g/dL

13 (45)

5 (28)

> 2 pRBC units/day

13 (45)

6 (33)

Retroperitoneal

1 (3)

0 (0)

Pulmonary

4 (14)

CNS bleed

1 (3)

0 (0)

Procedural intervention required

7 (24)

2 (11)

3 (10)

1 (6)

DVT/PE

1 (3)

0 (0)

Ischemic stroke

2 (7)

1 (6)

8 (28)

0 (0)

Thrombosis, n (%)

Figure 3. aPTTs from 6-48hr – Initial systemic heparin at > 0 units/hr

Device exchange

0 (0)

CONCLUSIONS

58%

• While the order set used for these device patients states to start systemic heparin at a rate of 500-1000 units/hr in addition to the infusate or purge solution heparin, patients often have initial rates of 0 units/hr at 6 hours post-device implantation

41% 31%

• TandemHeart® patients frequently have a supra-therapeutic aPTT even when systemic heparin is started at 0 units/hr, most likely because of the high average rate of heparin from the fixed rate infusate (~830 units/hr)

28% 21%

452

Table 3. Outcomes – Bleeding and Thrombosis

53%

TandemHeart®

TandemHeart® Patients (n=18) 59±15 16 (89) 97±25

11.5

Devices with 0 units/hr systemic heparin for duration (6-48hr), n (%)

Impella®

Table 1. Baseline Characteristics Impella® Patients (n=29) 59±14 24 (83) 91±19

1068

8.9

Average initial systemic heparin for those started at > 0, units/hr

Figure 2. aPTTs from 6-48hr – Initial systemic heparin at 0 units/hr

Impella®

Characteristic

239 (19)

812

Average initial systemic heparin, units/hr

Systemic heparin to meet goal aPTT 65-85

Heparinized infusate – fixed rate 10 ml/hr

452 (55)

Initial rate for systemic heparin, n (%) 23%

• Bleeding and thrombosis outcomes were assessed for each patient for the duration of device support

Heparinized purge – variable flow rate 230 ml/hr

829 (81)

Average systemic heparin, units/hr (% from total)

Average total heparin, units/kg/hr

37%

• Heparin requirements and aPTT monitoring were assessed from post-op hours 6-48 for each device

• Patients were excluded if they received device support for less than 24 hours, used anticoagulation other than heparin, or were less than 18 years of age

TandemHeart® Devices (n=18)

360 (45)

Average total heparin, units/hr

29%

OBJECTIVE •

Impella® Devices (n=40)

Average device heparin, units/hr (% from total)

Outcome

Impella®

21%

• In reviewing heparin orders, we also found a wide variety of aPTT goals and inconsistencies between stated goals and the ordered goal Sub-therapeutic

Therapeutic

Supra-therapeutic

DISCLOSURES The authors of this presentation have no disclosures concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation

TSHP JOURNAL

• Suggested adjustments to the protocol include:  Lower initial systemic heparin rates to more closely reflect the current practice  Addition of higher and a lower aPTT goals in the systemic heparin order set with matching heparin adjustment protocol for each goal  Addition of a device heparin adjustment protocol in order to more easily change the device heparin concentration when aPTTs are supra-therapeutic

47

VOLUME 18 | 2019

TSHP Research & Education Foundation

2018 Poster Competition Winners RESIDENT/FELLOW/POST-GRADUATE - PGY2 The Use of Lean, Six Sigma Methodology to Optimize Expiration Dating in the Automated Dispensing Cabinet EM Villanueva, A Couriel, OO Eshleman, DE Wilson, S Varghese, T Huerta, E Barrera, O Oriakhi Harris Health System, Houston, Texas

Background: Audits performed during the months of May and June of 2018 at Ben Taub Hospital, found approximately 15% of Automated Dispensing Cabinet (ADC) pockets containing inaccurate dates for medications, defined as the medication expiration before the date on the machine. This presented an opportunity to improve inventory management and accuracy for proper outdated medication removal. In this study, we examined our workflow to optimize our processes.

Objective(s): Reduce the percentage of ADC pockets at Ben Taub Hospital containing inaccurate recorded expiration date to 10% or less.

Method(s): We evaluated 328 pockets to determine the number of pockets with inaccurate recorded expiration date at baseline. Lean Six Sigma methodology was used to analyze and improve the evening batch replenishment workflow. Workflow modifications were implemented as follows: the number of batch pulls was reduced with the smallest batch to be performed separately; two technicians were selected to manage ADC par levels and which medications to stock in ADC. A post-implementation audit was conducted to determine the success of our interventions.

Result(s): The post-implementation audit examined 299 pockets and found eleven pockets contained medication expiring before the recorded date. Overall, 3.6% of the examined ADC pockets contained medication expiring before the date recorded on the machine post-implementation, a p-value less than 0.05. Additionally, a workload reduction in the number of medications pulled during the evening batch replenishment decreased by 25% from 800 to 600.

Conclusion(s): The new process decreased the number of medications expiring before the date recorded on the ADC. Disclosure(s): None.

The Use of Lean, Six Sigma Methodology to Optimize Expiration Dating in the Automated Dispensing Cabinet Elizabeth M Villanueva, PharmD, Ana Couriel, PharmD, BCPS, Shaji Varghese, RPh, MBA , Ogechi O Eshleman, PharmD, BCPS, David E Wilson, PharmD, MBA, BCPS, Tracy Huerta BS, Estevan Barrera, and Ogbevoen Oriakhi, PharmD, MBA Harris Health System, Houston, Texas

WORKFLOW

BACKGROUND • Ben Taub Hospital has 13,871 pockets in automated dispensing cabinets (ADC).

• We audited 328 pockets, and found 49 (15%) pockets containing inaccurate dates for medications, defined as the medication expiration before the date recorded on the machine.

• Approximately 78% of pockets audited contained the correct quantity of medication recorded on the machine.

Expiration Date Discrepancies Expired Medication

Inventory Quantity Discrepancies

Expires Before the date

Blind Stockout

Incorrect quantity

Correct/expires after the date 4.1%

Correct quantity

RESULTS

Pre-Implementation:

Expiration Date Discrepancies

Expired Medication Correct/expires after the date

PM Shift

Batch 1 (14:30)

Inventory Quantity Discrepancies Blind Stockout

Incorrect quantity

1.0% 2.7%

Correct quantity

1% 9%

Batch 2 (16:30)

Batch 3 (19:30)

1%

10.3%

Expires Before the date

96.3%

90%

Post-Implementation:

21%

950

Total Number of Medcarousel Pulls by Day

900

Pharmacy

OBJECTIVES

VOLUME 18 | 2019

Analysis • Root causes: • Par levels • Process for returning med • Time constraints

700

Batch 2 and 3 combined (14:30)

650

Batch 1 (05:30)

Improve • Adjust Batch time • ADC technician roles

Optimize par levels

Reduce outdates and stock outs

Control • Conduct follow up Audit

550 500

Date Medications Pulled

Reduce medication without removal

• Time study

750

1-Jan 2-Jan 3-Jan 4-Jan 5-Jan 6-Jan 7-Jan 8-Jan 9-Jan 10-Jan 11-Jan 12-Jan 13-Jan 14-Jan 15-Jan 16-Jan 17-Jan 18-Jan 19-Jan 20-Jan 21-Jan 22-Jan 23-Jan 24-Jan 25-Jan 26-Jan 27-Jan 28-Jan 29-Jan 30-Jan 31-Jan 1-Feb 2-Feb 3-Feb 4-Feb 5-Feb 6-Feb 7-Feb 8-Feb 9-Feb 10-Feb 11-Feb 12-Feb 13-Feb 14-Feb

Tech delivers Batch 1

ADC tech manage par levels

ADC Maintenance Technicians:

METHODS

Measure

Night Shift

800

600

Reduce the percentage of automated dispensing cabinet (ADC) pockets at Ben Taub Hospital containing inaccurate recorded expiration date to 10% or less.

• Create a team • Process map • Spaghetti Diagram

PM shift

Number of Medication Pulls

AM shift

Define

850

78%

85.5%

CONCLUSION 77.8%

REFERENCES

• The new process has helped to optimize expiration dating.

• Separating batch 1 and consolidating batch 2 and 3 to one large batch in the evening provided technicians with more time to replenish the machine.

• Distributing the work between all three shifts and the addition of two technicians to maintain par levels also contributed to a reduction in expired or expiring medications.

TSHP JOURNAL

• Post-implementation audit examined 299 pockets and found 11 (3.6%) pockets containing inaccurate dates for medications; Reduction from 15% at baseline (p-value < 0.05).

• 90% of pockets audited contained the correct quantity of medication recorded on the machine.

• Additionally, the number of medications pulled during the evening batch replenishment decreased from 800 to 600.

48

American Society of Health-System Pharmacists. ASHP guidelines on the safe use of automated dispensing devices. Am J Health-Syst Pharm. 2010; 67:483–90.

DISCLOSURE Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this poster presentation.

TSHP Research & Education Foundation

2018 Poster Competition Winners

PRACTITIONER – ADMINISTRATIVE/PRACTICE MANAGEMENT Utilization of Robotic-assisted Video Conferencing to Extend Pharmacists’ Presence on Patient Care Floors to Provide Transition-of-Care Clinical Services in a Newly Opened Community Hospital M Nguyen, R Xu, K Emerson, K Rathmann Houston Methodist The Woodlands Hospital, Conroe, Texas Disclosure: Ran Xu received Chester A. Bond (CAB) Memorial Grant for this project from Texas Society of Health-System Pharmacists Research & Education Foundation.

See page 11 for full project information and results.

Utilization of Robotic-assisted Video Conferencing to Extend Pharmacists’ Presence on Patient Care Floors to Provide Transitionof-Care Clinical Services in a Newly Opened Community Hospital Monique Nguyen, PharmD; Ran Xu, PhD, PharmD, BCPS, BCCCP, BCIDP; Kayleigh Emerson, PharmD, BCPS, BCCCP; Kaye Rathmann, BS, RPh Houston Methodist The Woodlands Hospital

Background

Objectives

An important phase of care transition is at the time of discharge from the hospital. Discharge medication counseling has been associated with reduced readmission rates in published literature.1 Additionally, hospital patients who have been discharged home are requested to answer questions pertaining to patients’ understanding of medications in a standardized survey administered by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS), as required by the Centers for Medicare and Medicaid Services. Many patients have indicated that they have received insufficient information from hospital staff regarding medications. Thus, the presence of pharmacists is integral to a seamless discharge workflow in order to improve the quality of care and patient satisfaction.

Houston Methodist The Woodlands Hospital, is an acute care community hospital that opened in June 2017. In the newly opened hospitals, the pharmacy practice model is primarily centralized to allow the optimization of operational and clinical workflows. Consequently, the lack of the pharmacists’ presence on patient care floors poses unique challenges to provide clinical services and improve patient care, especially during transition of care.

Based on a previous study where pharmacists utilized video conferencing to provide medication counseling and successfully improved patient satisfaction,2,3 a robotic-assisted video conferencing (RVC) device that can be driven remotely has been set up for the pharmacy department in the newly opened hospital. In this prospective observational study, the pharmacy staff utilizes the RVC technology on patient care floors to provide virtual pharmacy services including discharge counseling and addressing patients’ medication questions.

The goal of this study is to assess patients’ acceptance towards the virtual interaction with pharmacy staff through the RVC interface by conducting anonymous internal patient surveys.

Methods Study design: Prospective observational study approved by Houston Methodist Research Institute Internal Review Board Inclusion and Exclusion Criteria: Patients older than 18 years of age who have been admitted to Houston Methodist The Woodlands Hospital medical-surgical floors.

Interventions: A two-way video conferencing device (iPad®, Apple) is mounted on a stable robotic mobile device (Double®, Double Robotics Inc.), which can be controlled and driven by user via computer keyboard or an app. The content of video conferencing is encrypted and has been approved by the institutional information technology department as secure communication and compliant with HIPPA requirements.

The surface of the RVC device can be cleaned by alcohol-containing disinfectant to meet the requirements from infection control. The RVC device is used to provide medication education and perform discharge counseling.

Primary outcome: After each RVC encounter, four survey questions (Figure 1) are presented to the patients, and patients can choose one of the interval scale answers as following: strongly agree, agree, neutral, disagree, and strongly disagree.

Statistical analysis: Descriptive statistical analyses were performed. Patient-specific comments were also documented.

Results Figure 1. Patient responses after RVC encounter for medication counseling.

Strongly Agree

Neutral

The interaction with your virtual pharmacist is smooth.

The video conferencing is easy to use.

References 1. Still KL, Davis AK, Chilipko AA, Jenkosol A, Norwood DK, Evaluation of a pharmacy-driven inpatient discharge counseling service: impact on 30-day readmission rates. Consult Pharm. 2013 Dec. 28(12): 775-85 2. Price-Pierre C, Harvey-Traylor C, Reinhold, M, Xu R, Rathmann K. Improved patient satisfaction associated with discharge medication counseling via multimedia teleconferencing. The 50th American Society of Health- System Pharmacists Midyear Clinical Meeting; New Orleans, Louisiana, December 2015.

3. Reinhold MM, Rathmann K, Price-Pierre C, Xu R. The Talking Head-Video Teleconferencing Connects Patients and Pharmacists for Medication Counseling. ANCC Pathway to Excellence Conference, Louisville, Kentucky, May 2015

Agree

• • • • •

0% 0%

Disagree

6%

Strongly Disagree

0% 0% 0%

After talking with your pharmacist on the video call, you have recognized the possible side effects of your new medications.

0% 0% 0%

68%

32%

41%

59%

Examples of Patient-specific Responses “Robot was cool” “Neat and modern” “Enjoyed speaking to the robot” “10 out of 10 cute” and patient wanted to take a picture with the robot.

Family members recorded a video of robot.

TSHP JOURNAL

Conclusions

53% 47%

0% 0% 0%

After talking with your pharmacist on the video call, you have understood the purpose of taking each of your medications.

56%

38%

49

Patient demographics: • Age: Median: 66.5 Range: 30-93; IQR: 50-72 • Gender: 47% male • Nearly all patients agreed or strongly agreed to the four questions designed to assess patient acceptance to the RVC encounters for medication counseling, demonstrating general acceptance of the virtual clinical services.

• Among the patients surveyed, 75% are 50 years or older, showing that patient’s age is not a major barrier for implementing a novel technology for pharmacy services, although some of the responses reflected the view of patient’s family or caretaker.

• Multiple patients and family requested to take picture or video of or with the robot, conveying their interest and appreciation of the virtual pharmacy approach.

• Future studies should focus on additional outcomes such as the impact on HCAHPS survey scores.

Disclosures Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation: Ran Xu received Chester A Bond (CAB) Memorial Grant for this project from Texas Society of Health-System Pharmacists.

VOLUME 18 | 2019

SAVE THE DATE 2020 TSHP 2020 Annual Seminar April 17-19 Moody Gardens | Galveston, TX ®

www.tshp.org/seminar #tshp2020

#PharmacyStrong