The Journal July/August 2018 by Pharmacy Society of Wisconsin

Volume 21 THE JOURNAL OF THE PHARMACY SOCIETY OF WISCONSIN

RETURN S ERV ICE RE QUES TE D

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Issue 4 www.pswi.org

July/August 2018

JULY/AUGUST 2018 • VOLUME 21 • ISSUE 4

Population, Public, and Global Health

OPEN ACCESS

The Journal of the Pharmacy Society of Wisconsin is now open access for select articles! All original research, business and community member spotlights, as well as several other articles, will be available through the new JPSW website without a subscription. The vision of PSW is to serve the pharmacy profession as a professional resource, to create a unified voice to advocate for pharmacy practice advancement, and most importantly to enhance the lives of patients. It is our belief that providing the literature in The Journal as open access and accessible in Google will advance these goals, so please enjoy the new website for JPSW.

Visit the NEW open access website at www.jpswi.org

2018

July/August Continuing Education

CE for Pharmacists: The Use of Cannabinoids in Pharmacoresistant Epilepsy

Features

UpFront: Opportunities and Changes

WPQC Update: An Update on the Smart Meds Health System CMR Model

Preceptor Series: To Infinity...and Beyond! Pearls for Launching a Successful Career as a New Pharmacy Preceptor

ID Corner: New HIV Horizons: Advances in Antiretroviral Therapy

Original Work

Writing Club

Business Member Spotlight: Boscobel Pharmacy

PSW News

5 56

I am a Pharmacy Professional and a... Volunteer

Merging Passion and Population Health: Creating Better Health Through Pharmacist-Provided Care

Meeting Recap

2018 Educational Conference Recap

From Idea to Reality: The First Annual Wisconsin Pharmacy Residency Conference

Primary Care Pharmacists' Role and use of Technology in Diabetes Management in a Population Health Model within a Regional Health System

Adopting Patient-Centered Prescription Medication Labels in Wisconsin

Commentary: Population Health as the Pharmacy Profession's Value Proposition

The Utilization of Gabapentin in Alcohol Withdrawal Management at a Community Hospital

Improving Medication Access Through Partnership with Dispensary of Hope

Assessment of Potential Drug Interactions That May Increase the Rise of Major Bleeding Events in Patients on Warfarin Maintenance Therapy

A Physician Survey of Antimicrobial Stewardship Culture and Use of Antimicrobial Resistance Data and Resources

Pharmacy Reflections

The Journal of the Pharmacy Society of Wisconsin is a professional publication for original research, review, experience, and opinion articles that link science with contemporary pharmacy practice to improve patient care. Together we can inspire each other to advance our profession with the single purpose of enhancing the lives of our patients. Pharmacist Editor AMANDA MARGOLIS, PharmD, MS, BCACP Managing Editor & Creative Content Director MEGAN GRANT, mgrant@pswi.org Writing Club Editor ANGELA COLELLA, PharmD, BCPS CE Coordinator PATRICIA CARLSON, PharmD Peer Review Coordinator SHABNAM DABIRSHAHSAHEBI, PharmD, MS ID Corner Series Coordinator LYNNE FEHRENBACHER, PHARMD, BCPS-ID Precepting Series Coordinator MELISSA THEESFELD, PharmD

Editorial Advisory Board PATRICIA CARLSON, PharmD DCV Clinical Health Outcomes Director, Sanofi, St. Paul, MN

SUSIE MORONEY, PharmD, MS Regional Scientific Director in Immunology, Novartis, Fitchburg

LOREN CARRELL, PharmD Clinical Pharmacist/Pharmacist in Charge, Gundersen Health System, La Crosse

MICHAEL NAGY, PharmD Clinical Assistant Professor, Medical College of Wisconsin School of Pharmacy, Milwaukee

ANGELA COLELLA, PharmD, BCPS Drug Formulary Specialist, Drug Use Policy Aurora Healthcare, Milwaukee SHABNAM DABIRSHAHSAHEBI, PharmD, MS Drug Information Pharmacist Dean Clinic-Landmark Office, Madison LYNNE FEHRENBACHER, PharmD, BCPS-ID Associate Professor of Pharmacy Practice Concordia University School of Pharmacy, Mequon LYNNAE MAHANEY, MBA, BS PharmD Director, Pharmacy Accreditation American Society of Health-System Pharmacists NATHAN MENNINGA, PharmD Clinical Phamacist, William S. Middleton Memorial Veterans Hospital, Madison

MIKE OCHOWSKI, RPh, BBA Formulary Pharmacist, Group Health Cooperative of South Central Wisconsin, Madison TRISHA SEYS RANOLA, PharmD, CGP, CDE Clinical Phamacist, William S. Middleton Memorial Veterans Hospital, Madison SARA SMITH-SHULL, PharmD, MBA, BCPS Drug Policy Program, UW Health, Madison DIMMY SOKHAL, PharmD Clinical Pharmacist, Hayat Pharmacy, Milwaukee JULIE THIEL, PharmD, BCPP Clinical Pharmacist Winnebago Mental Health Institute, Winnebago

PSW Executive Board MICHELLE FARRELL, PharmD, BCACP Chairman of the Board

ALLAN LOEB, MS, RPh Treasurer

NICK OLSON, PharmD, BCACP, AAHIVP President

CHRISTOPHER DECKER, RPh Executive Vice President & CEO

MATTHEW MABIE, RPh President-Elect

PSW Board MIKE O’BRIEN. MS, RPh Region B Director 2016-18

MELISSA THEESFELD, PharmD Director-at-Large 2016-18

XIN RUPPEL, MBA, PharmD, BCPS, BCACP Region C Director 2017-19

ELLINA SECKEL, PharmD, BCACP Region A Director 2017-19

GEORGE GOSZ, RPh Region D Director 2016-18

KEN WALKER, RPh Director-at-Large 2017-19

ANGELA DE IANNI, RPh Region E Director 2017-19

DEAN ARNESON, PharmD, PhD Dean Concordia University Wisconsin SOP

MICHAEL GILLARD, PharmD, BCPS Region F Director 2016-18

STEVE SWANSON, PhD Dean UW School of Pharmacy

VANESSA FREITAG, PharmD Director-at-Large 2016-18

GEORGE MACKINNON, PhD, MS, RPh Dean Medical College of Wisconsin SOP

ARLENE IGLAR, MS, RPh, FASHP Director-at-Large 2017-19

MATTHEW PALMER, PharmD, CGP Senior & LTC Section Chair 2017-2018

JAKE OLSON, PharmD Director-at-Large 2016-18

CONNIE PEREZ, CPhT Technician Section President 2017-2018

RYAN MILLER, PharmD, BCPS Director-at-Large 2017-19

PSW Staff ELLEN BRUMMEL CHRISTOPHER DECKER, RPh MEGAN GRANT AMANDA MARGOLIS, PharmD, MS, BCACP ERICA MARTIN CHAD NECHVATAL, CPA

RYAN PSYCK KAY SCHELL SARAH SORUM, PharmD KARI TRAPSKIN, PharmD DANIELLE WOMACK, MPH

Send correspondence to: Megan Grant, Pharmacy Society of Wisconsin 701 Heartland Trail, Madison, WI 53717, phone: 608-827-9200, fax: 608-827-9292, thejournal@pswi.org Authors are encouraged to submit manuscripts to be considered for publication in The Journal. For Author Guidelines, see http://www.pswi.org/Get-Involved/Publish-articles-in-The-Journal Advertising inquiries: Megan Grant, Pharmacy Society of Wisconsin, 701 Heartland Trail, Madison, WI 53717, phone: 608-827-9200, fax: 608-827-9292, mgrant@pswi.org

The Journal of the Pharmacy Society of Wisconsin (ISSN 1098-1853) is the official publication of the Pharmacy Society of Wisconsin. Subscription included in membership dues. Non-member subscription $90 per year. Outside North America, add $60. Single copies $25 ($50 if outside North America). Periodical postage paid at Madison, WI and additional offices. Published bimonthly by the Pharmacy Society of Wisconsin, 701 Heartland Trail, Madison, WI 53717. Postmaster: Send address changes to PSW, 701 Heartland Trail, Madison, WI 53717. Opinions expressed by contributors do not necessarily reflect those of PSW.

2 The Journal July/August 2018 2 The Journal November/December 2015

www.pswi.org

Features

Up Front: Opportunities and Changes by Nick Olson, PharmD, BCACP, AAHIVP

ummer is a time of change for our profession. The beginning of summer marks the graduation ceremonies for schools of pharmacy. A new, young cohort of pharmacist professionals will enter the work force and infuse an invigorated

sense of purpose into our professional activities. The middle of the summer sees a turnover of our pharmacy residents. With this comes a fury of wrapping up old projects and the enthusiasm of initiating new ones. The end of summer sees the start of a new academic calendar, and with that a new set of professional learners will embark on their educational journey. As both PSW president and a pharmacist I have had the honor and great privilege of participating in many of the graduation, transition, and new change events our profession has hosted throughout this past summer. Though all these changes commence with their own style, and undoubtedly have different meanings for the professionals participating in them, there are several, very palpable, themes common across all of these change transitions: inspiration, enthusiasm, and uncertainty. Though I am some years removed from my early career, I found myself reflecting back to my time of change and transition in pharmacy. Through these reflections, I found myself viscerally reliving the sensations that those involved young professionals were experiencing and was struck how those feelings so eerily parallel the same feelings I now have as a professional when I am experiencing change at my practice site or change within the profession- inspiration, enthusiasm, and uncertainty. I was asked to prepare remarks and share any musings I thought would bear assistance to the professionals I was addressing regarding managing their changes and transitions. I chose to tell a

successful outcome of any change in oneâ&#x20AC;&#x2122;s life is dependent on how one harnesses, controls, and manages the inspiration, enthusiasm, and uncertainty surrounding the change. I then went on to confess that at the time that pearl of wisdom was shared with me, though I thought it sounded good, I felt it lacked any real tangible guidance in actually managing change. At that point in my career, I had no idea how to go about harnessing, controlling, or managing anything. I went on to further elaborate on how I developed a skill set in managing change and the role fellow pharmacists and PSW had in assisting me. PSW used to work with a speaker who would conduct a workshop for young leaders on how to lead change in their workplaces. His name was Harles Cone. He has long

story about a mentor of mine who once described to me that the www.pswi.org

July/August 2018

The Journal 3

since retired, but he was able to bring clarity to me as to how to

Is it measureable? Can education models be created to teach it?

effectively manage all of the emotions associated with change

How do we train our leaders to instill it? When it came down to

management. He stated that “You need to have the will to close

it we realized we were not going to answer all of those questions

the gap between what is and how you want it to be.” I find this

in one sitting. Understanding professional will is going to be a

mantra compelling - as important as the knowledge, expertise,

source of study and debate in the years to come for our profession.

and emotional balance of managing change is, so is having the

One thing we did realize is that we would know professional will

will to invoke the change - especially in the face of the obstacles

when we saw it. For again, it is professional will that has unified

preventing it.

our profession to successfully implement so many important

Change is hard and our profession has seen its share of

transformational changes.

it. Whether it was mandatory counseling, decentralization of

Given all of the change opportunity on the horizon for the

pharmacists, creation of residency programs, or WPQC, our

practice of pharmacy in Wisconsin, the question confronting our

profession has had the will to make the changes necessary to

profession is simple. Do we have the professional will necessary to

improve our practices and meet the needs required of us in the

invoke the changes needed to maximize patient care and further

healthcare system. As the healthcare system evolves, so will the

transform the role of pharmacy in the healthcare system?

roles that pharmacists need to play. This issue of The Journal

The answer to that question is intensely personal, but I submit

focuses on a series of changes and endeavors in our profession

to you that we do have the will required. We also have a wealth of

surrounding population, public, and global health. There will be

resources, from The Pharmacy Society of Wisconsin to professional

a discussion of the opportunities available to our profession to

partners and other stakeholders across the state and nation. These

improve the lives of patients on a population level. PSW members

entities act not only as a forum to develop and distribute the

will share their stories in these practice areas and you will read a

knowledge and tools to enact professional change, but also serve

compelling call to action for our entire profession to take on the

as a home to foster and unify the will required to close the gap

change our practice models require to affect the healthcare system

between where our practices are to where we want them to be.

on a global level. In addition to these opportunities, our profession is still engaging in practice change that comes along with ambulatory care, payment model reform, ‘provider status,’ and team-based

I hope you enjoy this issue of The Journal. May it help you inspire the will to manage change in your practice and improve the lives of the patients we serve.

care. Coupling these changes with the pressures of diminishing reimbursements, a job market growth regression back to the mean, and declining school of pharmacy enrollment, our profession’s capacity to handle change may seem a little stretched. I believe there is no better capacity-building mechanism for change than having a profession willing to take on the changes necessary.

— Nicholas Olson PharmD, BCACP, AAHIVP President, Pharmacy Society of Wisconsin

I met with a good colleague and friend recently, who through our conversation used the term “professional will” as a descriptor to how our profession invokes change. The concept intrigued me and we discussed it a bit. How do we define professional will?

Erratum: In the May/June issue of The Journal, the article titled: "Tobacco-Related Disparities Among Individuals Affected by Mental Illness" included an abstract that was added in error. We apologize to the author for this oversight. www.pswi.org

July/August 2018

The Journal 4

PSW News

I am a Pharmacy Professional and a...

Volunteer Sept/Oct Theme: I am a Pharmacy Professional and a... Chef/Baker Email your response to mgrant@pswi.org by July 21.

Nov/Dec Theme: I am a Pharmacy Professional and a... Pet Owner Email your response to mgrant@pswi.org by September 21. Responses should be <100 words and include a photo.

Shabnam (Shab) D. Sahebi, MS, PharmD, BCPS Pharmacy Practice Specialist SSM Health Dean Medical Group, Madison

More often than not, we get caught up in filling up our calendars with busy schedules that only revolves around us. However, there are many volunteering opportunities that are equally gratifying. I have volunteered in many capacities during my youth (following in my mom’s footsteps) and adult life. Having experienced many less than fortunate situations in my own life, I play it forward when I can, make new connections and put a smile on someone’s face. Those activities include anything from fundraising for American Family Children’s Hospital & Tri for Kids (e.g. triathlons and bike rides) interpreting for refugees, housing and conversation with international students to fostering kitties. Goodness is an investment that never fails! Photo: Jan 27th: Well EXPO-Healthy Living In Madison- Monona Terrace, Madison

Julie Thiel, PharmD, BCPP Pharmacy Director Winnebago Mental Health Institute, Winnebago

Our family volunteers as a weekend host family for A Better Chance program for highschool students and Lawrence University's Friendship Family program for international college students. We include them in our family activities like sporting events, concerts, or just hanging out at home. It has been wonderful to support our exchange students by attending their school events which has allowed our children to get a glimpse of highschool and college life!

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July/August 2018

The Journal 5

Continuing Education PHARMACIST CE:

The Use of Cannabinoids in Pharmacoresistant Epilepsy by Eric Friestrom, 2019 PharmD Candidate, Meredith Frey, 2019 PharmD Candidate, Kelsey Eickstaedt, 2019 PharmD Candidate, Alexander Gidal, 2019 PharmD Candidate, Adam Robb, 2019 PharmD Candidate, Matthew Williams, 2020 PharmD Candidate, Casey Gallimore, PharmD , Barry E Gidal, PharmD, FAES

mong the multitude of natural products used for the treatment of medical conditions, marijuana ranks amongst the oldest. Marijuana has been used and delivered in a variety of formulations dating back thousands of years. Interest in using cannabis for treatment of seizures can be found in reports from Asia, Europe and North America.1 During the past decade, there has been renewed interest by both consumers and health care practitioners in the use of cannabis for the treatment of several neurological disorders including most recently, epilepsy. Unfortunately, most evidence for cannabis has been limited to anecdotal reports, or small case series. This has left patients, caregivers and providers with a lack of data needed to inform clinical decisions. The reasons for this are multifactorial; but both basic and clinical research has been hampered by the U.S. federal regulatory status of cannabis, which is currently classified as a Schedule 1 substance. However, given the broad public interest, of late there have been considerable efforts to better understand the pharmacology of cannabis and develop an evidence-based approach to the clinical use of the natural product. The objective of this paper is to review the botany of marijuana, the presumed pharmacology of phytocannabinoids, and the current scientific and clinical evidence supporting the use of phytocannabinoids, specifically cannabidiol (CBD) for the treatment of the epilepsy syndromes, Lennox-Gastaut Syndrome (LGS) and Dravet (DS). 6 The Journal

July/August 2018

CE FOR PHARMACISTS

COMPLETE ARTICLE AND CE EXAM AVAILABLE ONLINE: WWW.PSWI.ORG

Learning Objectives • Describe the pharmacological and pharmacokinetic characteristics of cannabidiol • Know the current evidence supporting the use of cannabidiol in Epilepsy • Understand what factors contribute to the heterogeneity of commercially available cannabidiol products • Describe the current rules and regulations surrounding cannabidiol in Wisconsin and Federally

Botany: Marijuana, A Complex Plant The marijuana plant is part of the family Cannabaceae, which is one species with a number of varietals. For example, Cannabis sativa var. sativa is found in the warmer climates of Mexico, Africa and Thailand. The varitals indica and ruderalis are grown primarily in northern India and central Asia, respectively. These distinctions are important, as the distribution of the presumed pharmacologically active constituents can vary between varietals.2 Further, even within the same varietal, cannabinoid distribution and content will vary depending upon which part of the cannabis plant is assayed. For example, seeds, roots and stems contain virtually no cannabinoid as compared to leaves or buds. Even here, content will vary between seeded versus unseeded female buds. Growing conditions, including light, water and soil conditions, will also impact the cannabinoid content of any given plant. Cannabis sativa contains over 400 different chemical compounds including amino acids, terpenes, hydrocarbons,

fatty acids and various nitrogenous molecules.2 To date, over 100 different phytocannabinoids have been isolated from Cannabis sativa.3 It is these molecules in particular that are believed to be responsible for the psychoactive and non-psychoactive therapeutic actions of cannabis.

Pharmacology Relevant to Epilepsy Phytocannabinoids contained in the cannabis plant work through multiple cellular signaling networks. One such network is the endocannabinoid system (ECS), consisting of G-protein coupled receptors called cannabinoid (CB) receptors. Throughout the body these receptors are involved in regulation of the immune system, gastrointestinal tract, and central and peripheral nervous systems. The CB receptors are present in most vertebrate animals as a ubiquitous intracellular signaling system and can be differentiated into CB1 and CB2 receptors. CB1 receptors are found mainly at presynaptic neuronal terminals www.pswi.org

in central and peripheral neurons and reduce neurotransmitter release from nerve terminals by calcium blockade and opening of potassium channels.1 CB1 receptors are found in the hippocampus, basal ganglia and cerebellum. CB2 receptors are primarily expressed in the immune system, and to a lesser extent in neuronal tissue and gastrointestinal tract. The ECS and its endogenous ligands, 2-arachidonylglycerol (2-AG) and N-arachidonylethanolamine (AEA), are important in the regulation of numerous physiological processes, including memory, mood, energy, inflammation, immune function and brain reward systems. CB1 receptors modulate the release of both inhibitory (GABA) and excitatory (glutamate) neurotransmitters in a retrograde fashion. In essence, this means that these endogenous transmitters are synthesized “on-demand” in post-synaptic neuronal cells and flows back to presynaptic neuronal tissue, creating a feedback loop to regulate neural circuits.4 Of the over 100 currently identified molecules found in cannabis, the two phytocannabinoids most extensively studied are tetrahydrocannabinol (THC) and CBD, which have differing pharmacological actions. THC is responsible for majority of the psychoactive properties of cannabis, while CBD does not appear to possess psychoactive properties. Both THC and CBD have demonstrated efficacy in animal models of epilepsy, but work through different mechanisms.3 Unlike THC, whose action appears to be mediated by the CB1 receptor, CBD has minimal impact on the ECS and does not appear to bind to CB1 or CB2 receptors. While the antiseizure mechanism of CBD is unclear, CBD is thought to exert its antiseizure effects through a reduction in neuronal hyperexcitability and inflammation through modulation of intracellular calcium via several mechanisms in experimental models of epilepsy.5–7 Potential molecular targets to explain the actions of CBD in epilepsy include the orphan G protein-coupled receptor 55 (GPR55). Expression of this receptor increases following acute seizures and GPR55 modulation of excitatory neurotransmission is decreased www.pswi.org

BOX 1. Abbreviation List 2-AG

2-arachidonylglycerol

DSHEA

Dietary Supplement Health and Education Act of 1994

Adverse effect

ECS

Endocannabinoid system

AEA

N-arachidonylethanolamine

FDA

Food and Drug Administration

AED

Antiepileptic drug

GMP

Good Manufacturing Practices

ALT

Alanine transaminase

GPR55

G protein-coupled receptor 55

AST

Aspartate transaminase

Cannabinoid

N-CLB

N-desmethylclobazam

CBD

Cannabidiol

SUDEP

Sudden unexpected death in epilepsy

CBD-OS

CBD oral solution

DEA

Drug Enforcement Administration

Dravet Syndrome

in inhibitory cells in models of chronic seizures. This receptor system can modulate intracellular calcium, and therefore, neuronal excitability. CBD can block PR55 excitatory neurotransmission in epileptic tissue and conversely, the antiseizure effects are absent in animal models with no GPR55.8 CBD can also act as an agonist of transient receptor potential vanilloid receptor (TRPV1), resulting in receptor desensitization.9 This may be relevant because the non-selective TRPV1 cation receptor is increased in animal models and human temporal lobe epilepsy.10 Additional actions of CBD include enhanced activity of 5-HT1A and 5-HT2A receptors, α1 and α3 glycine receptors, and the transient receptor potential of ankyrin type 1 channel11, diminished rapid action potential firing through inhibition of T-type voltage gated calcium channels and the Nav1.6 voltage gated sodium channels12,13 as well as potential modulation of adenosine-mediated cellular signaling.14 Finally, although data is limited, there is a potential synergistic effect between THC and CBD, known as the entourage effect. This concept proposes that that there is a potentiating effect of endogenous cannabinoid receptor agonists when various cannabinoids are administered together. This hypothesis has led to the notion that the whole marijuana plant may have greater clinical effect as compared to administration of individual cannabinoids. The extent to which this effect actually contributes to antiseizure

LGS

TCH TRVP1 USP

Lennox-Gastaut Syndrome

Tetrahydrocannabinol Transient receptor potential vanilloid receptor U.S. Pharmacopedia Convention

effects of cannabis is unclear. Given the differing mechanisms of action of THC and CBD, it is reasonable to speculate that the combination may be useful in some patients.

Pharmacokinetics Absorption of CBD depends on the route of administration. When inhaled, CBD has a bioavailability of approximately 31%, and reaches peak plasma concentrations in under 10 minutes.11 For the purposes of this discussion, the pharmacokinetics of the most extensively studied formulation, CBD oral solution (CBD-OS, Epidiolex, GW Pharmaceuticals) will be referenced.15 The Investigative New Drug Application for CBD-OS was submitted in 2014, and this formulation has been granted Orphan Drug Designation and Rare Pediatric Designation for the treatment of LGS and DS and Fast-Track Designation for the treatment of DS. When taken orally, CBDOS has a very low bioavailability of 6% and undergoes high first pass metabolism, reaching peak plasma concentrations approximately 2 hours after administration. CBD-OS is highly lipophilic and readily crosses the blood brain barrier.14 CBD-OS is highly plasma protein bound (>90%, with the majority being bound to albumin, and 10% bound to erythrocytes) and has a large volume of distribution of 32 L/ kg, suggesting distribution into peripheral tissues.11 Due to the high lipophilicity of CBD, administration with food, July/August 2018

The Journal 7

TABLE 1. Summary of Trials Using CBD for Patients with Epilepsy Study

Compound

Study Type

Study Population

Study Duration

Primary Outcome

Mechoulam and Carlini (1978)27

CBD 200-300 mg/day

Prospective placebo controlled trial

n=9 (patient age not specified)

3 months

Cunha et al. (1980)28

CBD 200-300 mg/day

Prospective placebo controlled trial

n=16; adult patients aged 14-49 years old

8-18 weeks

Seizure freedom (25% CBD group vs. 6.25% placebo group)

Ames and Cridland (1986)29

CBD 200-300 mg/day

Prospective placebo controlled trial

n=12

3 weeks

No difference in seizure frequency for CBD group vs. placebo

Trembly and Sherman (1990)30

CBD 300 mg/day

Double-blind, placebo controlled trial

n=12

6 months

No difference in seizure pattern, character, and frequency for CBD group vs. placebo

Devinsky (2016)34

CBD 100 mg/mL, 2-5 mg/kg/day

Prospective open label trial

n=214; patients aged 1-30 years old

12 weeks

36.5% reduction in monthly seizure frequency (64% of subjects)

Szaflarski et al. (2016)35

CBD 100 mg/mL, 5-25 mg/kg/day

Prospective open label trial

n=51; pediatric patients (n=23), adult subjects (n=28)

6 months

50% or greater reduction in seizure frequency (49% of subjects)

Devinsky et al. (2017)33

CBD 100 mg/ml, 20 mg/kg/day

Double-blind, placebo controlled trial

n=120; children and young adults with DS

14 weeks

50% responder rate (43% CBD group vs. 27% placeboâ&#x20AC;&#x2122; p=0.08); seizure freedom (5% CBD group vs. 0% placebo group; p=0.08)

Thiele et al. (2018)31

CBD 100 mg/ml, 20 mg/kg/day

Double-blind, placebo controlled trial

n=171; patients aged 2-55 years old with LGS

14 weeks

Reduction in monthly drop attacks (44% CBD group vs. 22% placebo; p=0.0135)

Devinsky et al (2018)32

CBD 10-20mg/kg/day

Double-blind, placebo controlled trial

n=225, patients with LGS

14 weeks

37.2%-41.9% reduction in drop seizures vs 17.2% placebo

Seizure freedom (22% CBD group)

Abbreviations: CBD=Cannabidiol, DS=Dravet Syndrome, LGS= Lennox-Gastaut Syndrome

particularly high-fat meals will significantly increase extent of oral absorption, with no effect on either Tmax or T1/2. Given this effect, administration of CBD-OS with or without meals may represent a source variability in CBD absorption.14 Currently, CBD solution is being studied only following oral administration, and it will likely be suggested that patients take consistently with food in order to minimize this variability. CBD is metabolized extensively by the cytochrome P450 system in the liver, predominantly by CYP3A4, CYP2C9 and CYP2C19.14 The terminal elimination half-life is between 50-60 hours; however, given its multi-compartment elimination, terminal elinination half-life may not be the most appropriate parameter by which to construct dosing regimens in patients.14 In controlled clinical trials, CBD oral solution was given in two divided daily doses. Unchanged CBD and metabolites are excreted in both urine the feces11, with 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy CBD (7-COOH-CBD) as the primary metabolites found in humans after 8â&#x20AC;&#x192; The Journal

July/August 2018

oral administration. Animal data suggests that 7-OH-CBD given intraperitoneally can also exert antiseizure effects in at least one rodent model of epilepsy. Therefore, it is likely that both CBD and its metabolites contribute to efficacy in human patients.16 Further, an exposure-response analysis conducted in a group of n=360 patients with LGS, a typically pharmacoresistant epilepsy syndrome, found that there was a positive correlation between plasma CBD and 7-OH-CBD concentration and reduction in drop seizures.17

Drug Interactions There is currently lack of published, prospective evidence describing drug interactions with CBD; however, research in animal models and understanding of CYP metabolic pathways suggests clinically relevant interactions between CBD and several other drugs. Pharmacists and other health care providers must consider the implications of concurrent use of CBD and antiepileptic drug (AED) therapy when treating patients with epilepsy. Limited documented evidence

suggests that CBD can cause inhibition of CYP2C19, CYP2D6, CYP2C9, and other CYP3 family enzymes, implying potential drug interactions. In animal models, chronic CBD use induced CYP2B family enzymes.18 These observed and inferred drug interactions may affect coadministration of epileptic drugs such as carbamazepine, clonazepam, ethosuximide, topiramate, tiagabine, phenobarbital, and phenytoin.19 Other specific drug interactions may have implications for CBD use. Data from Geffrey et al, suggests CBD-OS interacts with clobazam via inhibition of CYP2C19, which metabolizes the active metabolite of clobazam, N-desmethylclobazam (N-CLB). Data from a healthy volunteer study suggested that N-CLB systemic exposure may increase 3-fold when clobazam is co-administered with CBD-OS.20 This study also noted a 1.5-fold increase in the concentration of 7-OH-CBD, possibly indicating inhibition by clobazam of CBDOS. These observations appear consistent across patient groups and may explain the efficacy of clobazam and CBD-OS www.pswi.org

co-administration and the increase in adverse effects, such as sedation. A recent case report noted a clinically significant drug interaction with a non-AED.21 An increase in the INR of a patient previously stabilized on warfarin seemed to correlate with increasing doses of CBD-OS and required warfarin dose modification. This observation is consistent with potential CBD-OS mediated inhibition of CYP2C9 and/or CYP2C19. A potential drug interaction of concern occurs when valproic acid is co-administered with CBD. Elevations in alanine transaminase (ALT) or aspartate transaminase (AST) levels increased to greater than three times the upper limit of normal in six patients with DS receiving both CBD-OS and valproic acid. Another randomized controlled trial in patients with LGS noted increased ALT or AST levels (without elevations of bilirubin) in 11 patients receiving 20 mg/kg CBD-OS and in two patients receiving 10 mg/kg CBD; ten of the 13 patients were also taking valproic acid. No patients met the criteria for drug-induced liver injury (Hy's Law) with concurrent elevated bilirubin, and all levels normalized after discontinuation. At present, the mechanism underlying this interaction is unknown, although it does not appear to be due to increases in valproic acid plasma concentrations. To date, no data are available regarding valproic acid metabolite kinetics in this population. In most cases, transaminase elevations were noted during the first 30 days of concomitant treatment, and appeared to be transient. Across studies, there does appear to be a greater incidence of transaminase elevations in patients receiving higher doses (i.e 20mg/kg/d) of CBD. These observations suggest a potential interaction with valproic acid, and periodic ALT and AST monitoring seems prudent for patients taking this combination.

Clinical Evidence Most clinical trials with commonly available artisanal formulations and purified CBD oral solution have been conducted in patients with the typically pharmacoresistent epilepsy syndromes, LGS and DS. In these studies, CBD formulations are given as adjunctive www.pswi.org

treatment, meaning they are added onto existing AED regimens in patients who are continuing to have seizures. In both of these epilepsy syndromes, the most common antiepileptic drugs used include valproic acid, clobazam, levetiracetam, lamotrigine and topiramate. Unfortunately, many, if not most all patients have seizure types that are medically refractory, or resistant, to these or any other antiepileptic drug regimen.

formulations of CBD (where purity and content may be unclear) have been used. Many of these early studies were underpowered, and precise classification of seizure type and/or syndrome is lacking. Nevertheless, more contemporary retrospective chart reviews; open-label studies and randomized, controlled clinical trials have suggested clinical efficacy in seizure reduction and generally good tolerability (Table 1).25-35

Lennox-Gastaut (LGS) LGS is a rare, severe form of epileptic encephalopathy. The age of onset of LGS is typically between 3 to 5 years of age. Drop seizures, which include any seizure that causes a fall or head drop, are common and have the greatest clinical impact, often causing physical injury leading to increased morbidity and mortality. Significant cognitive impairment and psychiatric comorbidities are apparent in the majority of LGS patients within the first few years following syndrome onset. Patients with LGS also have an increased risk of death; epidemiological studies have suggested that mortality was 14 times greater among patients with LGS than in the general population.22,23

Early Clinical Experience

Dravet Syndrome (DS) Patients with DS, a relatively rare genetic syndrome also known as severe myoclonic epilepsy of infancy, experience a variety of drug- resistant seizures (febrile and afebrile, generalized clonic, absence, myoclonic or tonicâ&#x20AC;&#x201C;clonic) during the first year of life. Convulsive seizures such as generalized tonic-clonic seizures are more common, and likely are responsible for morbidity and mortality in these patients. This epileptic encephalopathy is believed to be primarily due to a loss-of-function mutation in the sodium channel, SCN1A gene. Long term outcomes for these patients are quite poor, with the majority of patients experiencing seizures that persist into adulthood. Death during childhood is common for patients with DS. Sudden unexplained death (SUDEP) and Status Epilepticus are the most common causes of death in DS.24 Until recently, the majority of clinical evidence has come from either uncontrolled studies, or anecdotal reports where artisanal

In an open-label study of 214 patients with severe, pharmacoresistant epilepsy, Devinsky and colleagues investigated the use of pure CBD oral solution (Epidiolex, 100mg/ml). Patients received oral CBD (2-5 mg/kg per day in three divided doses) in conjunction with various AED therapies. The primary endpoint was the reduction in median monthly seizure frequency, reported by subjects or caregivers using seizure diaries. At the conclusion of the 12-week treatment period, 137 subjects (64%) experienced a 36.5% reduced median monthly seizure frequency.34 Another open-label study by Szaflarski and colleagues evaluated the use of CBD in 23 pediatric and 28 adult patients with pharmacoresistant epilepsy.35 Patients received CBD oral solution (Epidiolex) at 5 mg/kg/day, titrated every two weeks to a maximum dose of 25 mg/kg/day. Over the six-month study period, 49% of subjects experienced 50% or greater seizure reduction. Clearly, open-label studies present

Four smaller studies included a total of 48 patients who experienced modest seizure reduction with CBD use. Mechoulam and Carlini found that two subjects experienced seizure freedom at the conclusion of the study; however, no baseline seizure measurement of the subjects was reported.27 Cuhna and colleagues found that 50% of subjects receiving CBD remained almost seizure-free during the treatment period, compared to seven of eight subjects receiving placebo who experienced no clinical improvement.28 The other two trials noted no difference in seizure reduction between CBD-OS and placebo.29,30

Open-Label Studies

July/August 2018

The Journal 9

FIGURE 1. Structure of Cannabidiol (CBD)

important limitations. However, based upon these promising initial findings, several large, multicenter, placebocontrolled trials were designed, and executed using a purified form of CBD (Epidiolex) in patients with pharmacoresistent epilepsy.

Controlled Studies In a placebo controlled trial of n=120 patients with DS, Devinsky and colleagues found that as compared to placebo, 20 mg/kg/day of CBD-OS added onto existing antiepileptic drug regimens, resulted in a significant difference in 50% responder rate (43% vs 27%), as well as 5% seizure freedom versus 0% in placebo treated patients.33 In the CBD-OS treated patients, monthly median seizure frequency decreased by 39%, versus 13% in the placebo group. Significant reductions were seen when calculating total convulsive seizures (primarily tonic-clonic). Significant reductions in non-convulsive seizure types was not evident. Thiele and colleagues31, found that adjunctive CBD-OS titrated to 20 mg/ kg/day orally resulted in a 44% reduction in monthly drop attacks, versus a 22% reduction in the placebo group in n=171 patients with LGS . In this trial, a drop attack was defined as a seizure such as atonic, tonic, or tonic-clonic that either resulted in a fall, or potentially could have led to a fall. Secondary analyses in this trial included 50% and 75% responder rates. Forty-four percent of patients in the CBDOS group had at least a 50% reduction in seizure frequency, as compared to 24% receiving placebo. Although as compared to 10â&#x20AC;&#x192; The Journal

July/August 2018

placebo, significantly more CBD treated patients had at least a 75% reduction in seizure frequency, none were free from drop seizures when considering the entire treatment period (titration + maintenance). Most recently, Devinsky et al reported a 37.2% and 41.9% median reduction in drop seizures in patients taking 10 mg/kg/d or 20 mg/kg/d CBD-OS versus a 17.2% reduction with placebo in n=225 patients with LGS.32 Thirty-six percent of patients receiving 10 mg/kg/day and 39% of patients receiving 20 mg/kg/day had at least a 50% reduction in seizure frequency, as compared to 14% in the placebo group. While no patients became seizure free during the total treatment period, up to 25% of patients receiving 20 mg/kg/day had at least a 75% reduction in seizures as compared to 3% in the placebo group. Adverse Effects Similar to other drugs, CBD has potential for adverse effects (AE). As discussed previously, although THC has potential benefit as an AED, it is also associated with psychoactive properties. Additionally, there is growing evidence that chronic use of cannabis may have longterm effects on cognition in the developing brain.1 Due to variation in cannabis-containing products and formulations, interpretation and prediction of AE is difficult. Many studies to date are open label or uncontrolled, which may influence the prevalence and reporting of AE. The most reliable evidence comes from the Phase III controlled studies using the purified form of CBD. In general, CBD-OS is well tolerated, and most reported AE are mild to moderate in severity. Most common AE associated with CBD-OS, in order of prevalence, included somnolence, diarrhea, and fatigue. During the controlled clinical trials for LGS and DS, somnolence was reported to be mild to moderate in severity

in most patients. It is important to note however, that across the most recently completed phase III studies, the incidence of somnolence appears to be increased in patients who are concomitantly receiving clobazam. Most likely, this is related to the CBD mediated increase in N-CLB, via CYP2C19 inhibition. Management of this adverse effect therefore may require reduction in clobazam dose, and caregivers/patients should be counseled to monitor for excessive sedation. Other common AEâ&#x20AC;&#x2122;s observed in CBD studies include: decreased appetite, fatigue, pyrexia, vomiting, ataxia, convulsion, and lethargy. As previously discussed, the combination of CBD-OS and valproic acid may result in a pharmacodynamic interaction resulting in increases in liver transaminases that occasionally may exceed 3-5 x upper limit of normal, and was one of the more common reasons for patient discontinuation from the trials.31-33 Additional evidence is needed to evaluate the safety profile of CBD, particularly when used in combination with other non-AED medications. Although long-term effects of CBD have not been studied, research on the safety and AE profile of recreational marijuana may provide some insight. Such studies examine cannabis as a whole, especially the effects of THC.27 Consequences of cannabis use may include psychosis and interruption of brain development during adolescence, leading to behavioral and cognitive changes. Research suggests that THC inhibits brain development; however, more research is needed to determine the exact effects of CBD on brain development.27

Barriers to Use Treatment with CBD is complicated by its ambiguous legal status in the United States. Patients and providers must navigate federal and state laws and procurement issues if choosing to use CBD therapy. In states where it is legal, CBD products can be purchased in-person at licensed dispensaries or from online retailers. Common forms include tinctures, capsules, topicals, edibles, and others, with each manufacturer claiming unique health benefits respective to the formulation. CBD products have different methods of www.pswi.org

preparation, causing extensive variation in CBD concentration, one example being the manufacturing of CBD oil. The variation in the product varies with the choice of plant. Both CBD and THC appear in the marijuana plant largely in acidic form, CBDa and THCa, which are differentiated by the enzymes that decarboxylate the acid. This process of decarboxylation is brought upon the plant through age and heating (e.g., heat lamps or smoking).36 Another variable introduced in the process is the choice of solvent for extraction of the chemical. In a recent 2016 study, oil was shown to result in lower degradation rates and higher potencies compared to other solvents, like ethyl alcohol.37 These are only two of the variables among many that impact the heterogeneity of the endproduct. Two studies performed in Italy have used liquid chromatography with tandem mass spectrometry and found wide variations of CBD concentrations in available products on the Italian market.38,39 In considering the use of CBD to treat epilepsy, therapeutic continuity is crucial. This continuity could be enforced with www.pswi.org

a standardized preparation protocol for the manufacturer to produce a more homogeneous product. In many states, CBD oil is treated similarly to a dietary supplement. The Federal Food and Drug Administration (FDA) regulates dietary supplements according to the Dietary Supplement Health and Education Act of 1994 (DSHEA).40 DSHEA delegates the evaluation of safety and labeling of supplements to manufacturers and distributors. The FDA will only intervene if a product is adulterated or misbranded. Verification of products is delegated to third parties, such as the U.S. Pharmacopeia Convention (USP). Products which pass USP Good Manufacturing Practices (GMP) audit, product testing, and manufacturing documentation are awarded a USP verification mark signifying to consumers that the product is legitimate.41 However, this process is optional, and no regulation is currently in place to avoid the entry of misbranded items onto the market. To date, there are no USP standards established for cannabis or cannabinoid derivatives. A research

letter published in 2017 details the online purchase of 84 CBD-containing products that were analyzed for CBD content. Of these products, 24.85% were underlabeled, 26.19% were over-labeled, and 30.95% were accurately labeled.42 To address this issue, the FDA has issued 44 warning letters between 2015-2017 to online CBD vendors suspected of misbranding products and offering medical claims. These letters specified that due to being studied as an investigational product in “substantial clinical investigations”, artisanal CBD products are excluded from the dietary supplement definition included in the Food and Drug Cosmetic Act.43 The Drug Enforcement Administration (DEA) classifies marijuana and THC as a Schedule I substance.44 The Controlled Substances Act further defines cannabis as “all parts of the plant cannabis sativa L., whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin”.45 CBD oil is included in this definition. CBD will not be a federally legal treatment option unless July/August 2018

The Journal 11

changes in schedule classification occur. In the state of Wisconsin, CBD in a form without psychoactive effect is exempt from this classification if certain criteria are met. In Wisconsin, under Lydiasâ&#x20AC;&#x2122; Law (enacted 2014), physicians and pharmacists approved by the Controlled Substance Board, could dispense CBD to patients or caregivers for the treatment of seizures. Recently, this law has been amended to expand access. 2017 Wisconsin Act 4 [2017 Senate Bill 10] provides that an individual may possess CBD if the individual has a certification (meaning a letter by the physician) or other appropriate documentation that the individual is using the CBD product to treat a medical condition, and that this certification has an issue date no more than 1 year prior to the possession. Under this Act, an approved pharmacy may dispense CBD without a psychoactive effect as a treatment for a medical condition. SB10 also provides that if cannabidiol is rescheduled, or deleted as a controlled substance under Federal Law, the Wisconsin Controlled Substance Board shall similarly treat this formulation. This change ensures that a prescription formulation of CBD will be rapidly rescheduled. Clearly, when considering a potential rescheduling of CBD, appropriate analyses of abuse potential need to be conducted. In a human abuse trial conducted in adult experienced recreational drug abusers, single doses of purified CBD given at presumably therapeutic doses (750 mg) as well as supratherapeutic oral doses (1500 mg and 4500 mg) showed only modest subjective effects. At oral doses of 750 mg, no significant abuse potential was noted. At higher doses, subjective effects were noticed, but appeared to be less common than with the control drugs including alprazolam and dronabinol. CBD administration had no observable effects in the battery of cognition tests including Digit Symbol Substitution Test and Divided Attention Test.46

Conclusions The past few years have seen a dramatic increase and improvement in the evidence supporting cannabinoids, and cannabidiol in particular, for the adjunctive treatment of severe seizure disorders. In addition 12â&#x20AC;&#x192; The Journal

July/August 2018

to animal data, the preponderance of clinical evidence supports the efficacy of CBD oral solution, and possibly THC. Data from Phase III clinical trials of CBD-OS suggest that likely therapeutic doses will range between 10-20 mg/kg/ day, given on a BID schedule. It is also clear that these compounds have complex pharmacokinetics and will most likely have pharmacokinetic and pharmacodynamic interactions with a variety of medications. Available data also suggests that purified CBD oral solution is likely to have a modest adverse effect profile that is not unlike many other AEDs. It is also important that we recognize that our strongest evidence to date comes from very severe epilepsy populations. At this time, it is not reasonable to extrapolate this evidence to other populations, such as patients with focal epilepsy. Additionally, there is concern regarding the continuity of supply of CBD products. Patients should be counseled that currently there are no established guidelines for purity or consistency of CBD formulations, outside of the formulations currently under clinical investigation. However, this intriguing family of molecules promises to provide an important addition to our current armamentarium in treating pharmacoresistent epilepsy in the most severely affected patients. Eric Friestrom, Meredith Frey, Kelsey Eickstaedt, Alexander Gidal, and Adam Robb are 4th year Doctor of Pharmacy Candidates at the University of Wisconsin-Madison School of Pharmacy in Madison, WI. Matthew Williams is a 3rd year Doctor of Pharmacy Candidates at the University of Wisconsin-Madison School of Pharmacy in Madison, WI. Casey Gallimore is an Associate Professor and Barry Gidal is a Professor of Pharmacy and Neurology at the University of Wisconsin-Madison School of Pharmacy in Madison, WI. Disclosure: Dr. Barry Gidal reports receiving consulting fees from Eisai, GW Pharmaceuticals, Sunovion, Lundbeck, Neurelis and fees for speaking from Eisai, Sunovion, Lundbeck.

References

1. Szaflarski JP, Martina Bebin E. Cannabis, cannabidiol, and epilepsy - from receptors to clinical response. Epilepsy Behav. 2014;41:277-282. 2. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers.

2007;4(8):1770-1804. 3. Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics. 2015;12(4):747-768. 4. Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature. 2001;410(6828):588-592. 5. Ryan D, Drysdale AJ, Lafourcade C, Pertwee RG, Platt B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci. 2009;29(7):2053-2063. 6. French JA, Koepp M, Naegelin Y, et al. Clinical studies and anti-inflammatory mechanisms of treatments. Epilepsia. 2017;58(suppl 3):69-82. 7. Iannotti FA, Hill CL, Leo A, et al. Nonpsychotropic plant cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), activate and desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-1141. 8. Bazelot M, Rosenberg EC, Gray R, Devinsky O, Whalley BJ TR. A role of GPR55 in the antiepileptic properties of cannabadiol. Abstract Presented at: American Epilepsy Society Annual Meeting, Washington DC. 2017. 9. Jones N, Stott C, Roberts E GR. Antiseizure properties of cannabadiol (CBD) are attenuated in the absence of transient receptor potential vanilloid (TRPV1) receptors. Abstract Presented at: American Epilepsy Annual Meeting, washington DC. 2017. 10. Sun F-J, Guo W, Zheng D-H, et al. Increased expression of TRPV1 in the cortex and hippocampus from patients with mesial temporal lobe epilepsy. J Mol Neurosci. 2013;49(1):182-193. 11. Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791-802. 12. Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem. 2008;283(23):16124-16134. 13. Patel RR, Barbosa C, Brustovetsky T, Brustovetsky N, Cummins TR. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol. Brain. 2016;139(8):2164-2181. 14. Gaston TE, Friedman D. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav. 2017;70:313-318. 15. CBD Products and Development Pipeline. Greenwich Biosciences, GW Pharmaceuticals. https://www.greenwichbiosciences.com/cbdproducts-development-pipeline. Published 2016. 16. Whalley BJ, Stott C, Gray RA JN. Human metabolite of cannabidiol, 7-hydroxy cannabidiol, but not 7-carboxy cannabidiol, is anticonvulsant in the maximal electroshock seizure threshold (mEST) test in mouse. Abstract Presented at: American Epilepsy Annual Meeting, Washington DC. 2017. 17. Morrison G, Sardu ML, Rasmussen CH, Sommerville K, Roberts C BG. Exposreresponse analysis of cannabidiol (CBD) for the treatment of Lennox-Gastaut Syndrome. Abstract Presented at: American Epilepsy Society www.pswi.org

Annual Meeting, Washington, DC. 2017. 18. Zendulka O, Dovrtelová G, Nosková K, et al. Cannabinoids and cytochrome P450 interactions. Curr Drug Metab. 2016;17(3):206-226. 19. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586-1592. 20. Sommerville K, Crockett J, Blakey G. Bidirectional drug-drug interaction with coadministration of cannabidiol and clobazam in a phase 1 healthy volunteer trial. Abstract Presented at: American Epilepsy Society. 2017;(2015):339322. 21. Grayson L, Vines B, Nichol K, Szaflarski JP. An Interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Reports. 2017;9:10-11 22. Camfield PR. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 2011;52(suppl 5):3-9. 23. Autry AR, Trevathan E, Van Naarden Braun K, Yeargin-Allsopp M. Increased risk of death among children with lennox-gastaut syndrome and infantile spasms. J Child Neurol. 2010;25(4):441-447. 24. Genton P, Velizarova R, Dravet C. Dravet syndrome: the long-term outcome. Epilepsia. 2011;52(suppl 2):44-49. 25. Porcari GS, Fu C, Doll ED, Carter EG, Carson RP. Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: practical experiences in a tertiary medical center. Epilepsy and Behavior. 2018;80:240-246. 26. Devinsky O, Patel AD, Thiele EA, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet Syndrome. Neurology 2018;90:e1204-e1211. 27. Mechoulam R, Carlini EA. Toward drugs derived from cannabis. Naturwissenschaften. 1978;65(4):174-179. 28. Cunha JM, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980;21(3):175-185. 29. Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. S Aft Med J. 1986;69(1):14. 30. Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. Marijuana ’90 Int Conf Cannabis Cannabinoids. 1990:Kolympari, Crete, July 8-11, 1990. 31. Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096. 32. Devinsky O, Patel A, Cross H, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut Syndrome. New Engl J Med. 2018;378(20):1888-1897. 33. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N Engl J Med. 2017;376(21):2011-2020. 34. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatmentresistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278. 35. Szaflarski J, Bebin E, DeWolfe J, et al. Seizure response to cannabidiol in a state-sponsored openlabel program. Neurology. 2016;86(suppl 16):S14.006. 36. Marks MD, Tian L, Wenger JP, et al. www.pswi.org

Identification of candidate genes affecting Delta9tetrahydrocannabinol biosynthesis in Cannabis sativa. J Exp Bot. 2009;60(13):3715-3726. 37. Citti C, Ciccarella G, Braghiroli D, Parenti C, Vandelli MA, Cannazza G. Medicinal cannabis: principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method. J Pharm Biomed Anal. 2016;128:201-209. 38. Carcieri C, Tomasello C, Simiele M, et al. Cannabinoids concentration variability in cannabis olive oil galenic preparations. J Pharm Pharmacol. 2018;70(1):143-149. 39. Pacifici R, Marchei E, Salvatore F, Guandalini L, Busardò FP, Pichini S. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry. Clin Chem Lab Med. 2017;55(10):1555-1563. 40. Dietary Supplements. U.S. Food and Drug Administration. https://www.fda.gov/Food/ DietarySupplements/default.htm. Published 2017. 41. Background on the Final Rule for Current Good Manufacturing Practices for Dietary Supplements. U.S. Food and Drug Administration. https://www.fda.gov/Food/GuidanceRegulation/ CGMP/ucm110863.htm. Published 2017. 42. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708-1709. 43. Warning Letters and Test Results for Cannabidiol Related Products. U.S. Food and Drug Administration2. https://www.fda.gov/ NewsEvents/PublicHealthFocus/ucm484109.htm. 44. Drug Scheduling. United States Drug Enforcement Administration. https:// www.dea.gov/druginfo/ds.shtml. 45. Controlled Substances Act of 2012, 21 U.S.C. 802(16). 46. Sommerville K, Etges T, Szeto I, et al. Assessment of the abuse potential of cannabidiol in recreational polydrug users: a randomized, double-blind, controlled trial. Abstract Presented at: American Epilepsy Society Annual Meeting, Washington DC. 2017.

Assessment Questions 1.

True or False: The content of pharmacologically active constituents are consistent between and among cannabis varietals. a. True b. False Which of the following statements is TRUE regarding cannabidiol (CBD)? a. Binds with high affinity to cannabinoid receptors CB1 and CB2 in the endocannabinoid system (ECS). b. Does not appear to possess psychoactive properties.

4. 5.

c. Has not demonstrated efficacy in animal models of epilepsy. d. All of the above. Which of the following accurately describes the pharmacokinetic properties of CBD when it is administered orally? a. High oral bioavailability. b. Hydrophilic c. Highly plasma protein bound d. Small volume of distribution CBD is thought to inhibit which of the following cytochrome P450 enzymes? a. 2C19 b. 2D6 c. 2C9 d. All of the above Which of the following statements is TRUE regarding the clinical efficacy of CBD in seizure disorders? a. CBD has only been studied in open- label, non-placebo controlled trials. b. CBD has mainly been studied in the treatment of pharmacoresistant epilepsy syndromes such as Lennox- Gastaut (LGS) and Dravet Syndrome (DS). c. CBD has only been studied as monotherapy for treatment of seizure disorders. d. All of the above. Which of the following is NOT a common adverse effect observed in controlled trials of CBD use? a. Insomnia b. Fatigue c. Ataxia d. Diarrhea Which of the following contributes to heterogeneity in the composition of CBD products? a. Choice of plant used in production b. Solevant used to extract CBD c. Treatment of cannabis as a dietary supplement in states that have legalized its use. d. All of the above

Which of the following is TRUE regarding current CBD regulation in Wisconsin? a. Under no circumstance can an individual possess CBD oil, even if it is used for a valid medical condition. b. An individual is allowed to possess CBD if that individual has a letter from their treating physician documenting use as treatment for a medical condition and the letter has been issued within the past 2 year period. July/August 2018

The Journal 13

c. Any physician or pharmacist in WI is automatically authorized to dispense CBD to patients or caregivers for the treatment of seizures. d. If CBD is rescheduled at the Federal level, the Wisconsin Controlled Substance Board will follow suit and treat CBD formulations in a similar fashion. 9.

Did the activity meet the stated learning objectives? (if you answer no, please email sarahs@pswi.org to explain) a. Yes b. No

10. On a scale of 1 – 10 (1-no impact; 10-strong impact), please rate how this program will impact the medication therapy management outcomes or safety of your patients.

11. On a scale of 1 – 10 (1-did not enhance; 10-greatly enhanced), please rate how this program enhanced your competence in the clinical areas covered. 12. On a scale of 1 – 10 (1-did not help; 10-great help), please rate how this program helped to build your management and leadership skills. 13.

How useful was the educational material? a. Very useful b. Somewhat useful c. Not useful

14. How effective were the learning methods used for this activity? a. Very effective b. Somewhat effective c. Not effective 15. Learning assessment questions were appropriate. a. Yes b. No

16. Were the authors free from bias? a. Yes b. No 17. If you answered “no” to question 16, please comment (email info@pswi.org). 18. Please indicate the amount of time it took you to read the article and complete the assessment questions.

CE FOR PHARMACISTS

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Continuing Education Credit Information The Pharmacy Society of Wisconsin is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Continuing education credit can be earned by completing the self assessment questions. Questions may be completed online at www. pswi.org or by mailing completed answer form to PSW, 701 Heartland Trail, Madison, WI 53717. Participants receiving a score of 70% or better will be granted 1 hour (0.1 CEU) credit through CPE Monitor within 60 day of quiz completion. Accurate birth date (MMDD) and CPE Monitor ID must be provided in order to receive this credit as required by ACPE. This CE offering is offered free-of-charge t o a l l P S W m e m b e r s . No n m e m b e r s a r e charged $20 for each exam submitted to cover administrative costs.

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July/August 2018 The Use of Cannabinoids in Pharmacoresistant Epilepsy

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ACPE Universal Activity Number: 0175-0000-18-101-H04-P

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Target Audience: Pharmacists Activity Type: Knowledge-based Release Date: July 1, 2018 (No longer valid for CE credit after July 1, 2021)

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July/August 2018

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Features WPQC UPDATE:

An Update on the Smart Meds Health System CMR Model by Sarah Lopina, 2019 PharmD Candidate, Katherine Hartkopf, PharmD, BCACP

n adverse drug event (ADE) is defined as harm experienced by a patient as a result of exposure to a medication.1 ADEs account for nearly 700,000 emergency department visits and 100,000 hospitalizations each year. Some factors put patients at greater risks of experiencing ADEs, such as complex medication regimens and older age.2 Patients aged 65 and older are twice as likely to be hospitalized due to ADEs than younger patients, for reasons including falls, orthostatic hypotension, heart failure, and delirium. In addition to complex medication regimens and older age, transitions of care are well-documented as a source of preventable harm related to medications.3 These events are potentially preventable up to 50% of the time through strategies such as discontinuing medications, prescribing new medications sparingly, and frequently assessing proper medication adherence.4

Pharmacists as a Potential Solution In 2006, Medicare Part D implemented a Medication Therapy Management (MTM) reimbursement program to reduce the risk of ADEs in older adults and ensure optimum therapeutic outcomes for beneficiaries through improved medication use.5 MTM services target patients with multiple conditions and multiple medications, and the services consist of comprehensive medication reviews (CMRs) by pharmacists. In 2011, the Wisconsin Pharmacy Quality Collaborative (WPQC) and United Way of Dane County (UWDC) adopted Medicare’s idea by performing CMRs at local senior/ community centers and pharmacies with the goal of reducing the number of falls and ADEs experienced by older adults in 16 The Journal

July/August 2018

Dane county. In 2017, the CMR program was extended to the health system with the addition of pharmacists providing medication reviews at UW Health primary care clinics. In this health system model, referred to as the Smart Meds program, CMRs are completed by primary care pharmacists for a subset of older adults discharged from the hospital.

The Smart Meds Program Update In the January/February 2018 issue of JPSW, the Smart Meds program was introduced as a health system model intended to provide CMRs to Dane County older adults in the primary care setting.6 Created collaboratively by UWDC, UW Health Pharmacy Services Department, UW-Madison School of Pharmacy and PSW, the program aims to reduce hospitalizations, falls, and ADEs while improving adherence to medication regimens. The program focuses efforts on older adults in Dane County who have been discharged from the hospital and have multiple chronic conditions and/or complex medication regimens. Since the program’s last update, two new clinics have been enrolled in the Smart Meds program for a total of ten UW Health primary care clinics: Arboretum, East, Fitchburg, Northeast, Odana Atrium, Oregon, Union Corners, University Station, Verona, and West Towne. Three UW-Madison pharmacy students have been hired as interns by UW Health to directly collaborate with the United Way Smart Meds Program Coordinator, Helene McDowell, and the UW Health primary care pharmacists providing the CMR services. The students identify eligible Smart Meds patients using the following criteria: patients are 60 years or older, have been discharged from the hospital in the previous 30 days, and were hospitalized

for a chronic condition or had significant changes made to their medication regimens. The eligible patients are communicated to the pharmacists onsite at collaborating clinics. The pharmacists then provide CMRs over the telephone or face-to-face with patients before or during their scheduled hospital followup appointments with their primary care providers. During the CMRs, pharmacists identify drug-related problems and make recommendations to both the patients and providers. From March 2017 to April 2018, a total of 98 Smart Meds CMRs were completed (Figure 1). On average, the older adults for which CMRs have been performed are 74 years-old and take 9 prescription medications and 5 over-thecounter medications, which puts them at great risk for experiencing ADEs. A total of 164 medication recommendations, or an average of 1.9 recommendations per patient, were made to providers with an 81% acceptance rate. Patients have been satisfied with the service overall, as indicated through followup telephone surveys completed by the pharmacy interns. A common statement made by patients is that they feel as though the pharmacists care about their well-being through the service. Some patients have recognized how the service assists their primary care providers with comments such as, “By calling me and going through my medications, it saved a lot of my doctor’s time in clinic.” Others are thankful for the service due to the ability to ask the pharmacist questions. One patient stated, “This was the first time I received a phone United Way Safe and Healthy Aging Initiative: https://ce.pharmacy.wisc.edu/ pd/united-way-safe-and-healthy-aginginitiative-creating-and-learning-from-smartmeds/ www.pswi.org

FIGURE 1. Progress of the Smart Meds program since its launch in March 2017

SmartMeds Program

SmartMeds Program Objectives Increase the number of referrals of high-risk older adults receiving a CMR through the SmartMeds program

A program to reduce falls and adverse drug events for UW Health patients aged 60 and older

Increase the number of medication recommendations made by the pharmacist at the initial CMR Increase the number of medication recommendations accepted by the primary care provider

Participating UW Health Clinics include: • East • Fitchburg • Odana Atrium • Oregon

• Union Corners • University Station • Verona • West Towne

To further expand the reach of comprehensive medication reviews, the SmartMeds Program embeds this valuable service in the health system. UW Health Primary Care Pharmacists provide comprehensive medication reviews to recently hospitalized older adults.

SmartMeds Program Impact 3/2017 to 4/2018 Rx

NEXT STEPS

98 comprehensive medication reviews completed

75%

Program funding supported by: • Wisconsin Partnership Program • The Retirement Research Foundation • Helen Daniels Bader Fund: A Bader Philanthropy

164 medication recommendations made to providers

81% of recommendations accepted by providers

of surveyed participants indicated the overall care they received from the pharmacist was very good or excellent (remaining 25% was good)

is the average age of program participants

medications per participant (9 prescription, 5 over-the-counter)

1.9

recommendations per participant

Assess the impact of CMRs on the falls & rehospitalization rates of vulnerable populations served by this program

Expand to additional UW Health Primary Care locations

Develop a model for disseminating SmartMeds in other healthcare systems

For more information about the SmartMeds Program, please contact Kate Hartkopf at KHartkopf@uwhealth.org

Graphic Credit: Sally Griffith-Oh, UW-Madison School of Pharmacy www.pswi.org

July/August 2018

The Journal 17

This was the first time I received a phone call from a pharmacist and she made me feel comfortable asking any question, which she answered thoroughly.

call from a pharmacist and she made me feel comfortable asking any question, which she answered thoroughly.” Going forward, the Smart Meds program aims to perform a retrospective analysis on hospital readmission rates, hospital admissions due to falls, and chronic condition factors such as A1c, cholesterol, and blood pressure before and after CMRs to assess how the program has benefited the patients in the health system model. Stay tuned for more updates on the Smart Meds program to discover how CMRs in the health system have helped the older adult community in Dane County. Sarah Lopina is a 4th year Doctor of Pharmacy candidate at the University of WisconsinMadison School of Pharmacy and was a UW Health Smart Meds Intern in Madison, WI at the time of writing this article. Katherine Hartkopf is a Pharmacy Manager of Ambulatory Care Services for UW Health in Madison, WI. Disclosure: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria

References

1. U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality, and Patient Safety Network. Medication errors. http://psnet.ahrq.gov/primers/primer/23/ medication-errors. Updated June 2017. 2. Beijer H, de Blaey C. Hospitalizations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm World Sci. 2002;24(2):46-54. 3. Coleman EA, Smith JD, Raha D, et

By calling me and going through my medications, it saved a lot of my doctor’s time in clinic.

18 The Journal

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al. Posthospital medication discrepancies: prevalence and contributing factors. Arch Intern Med. 2005;165(16):1842-1847. 4. Pretorius RW, Gataric G, Swedlund SK, et al. Reducing the risk of adverse drug events in older adults. Am Fam Physician. 2013;87(5):331-336. 5. Rucker NL, AARP Public Policy

Institute. Medicare Part D’s medication therapy management: shifting from neutral to drive. Insight on the Issues. 2012;64:1-12. 6. Martin A, Lopina S, Trapskin K. WPQC update: expansion of the United Way of Dane County Safe and Healthy Aging community-based program to the health system. J Pharm Soc Wis. 2018;21(1):15-17.

WPQC Updates Congratulations to First Quarter 2018 WPQC Top Performing Pharmacies! These 5 pharmacies billed the highest total number of CMR/A services (initial and follow up) for Medicaid members during January, February and March 2018! Congratulations on a job well done - KEEP IT UP! Life Change Pharmacy (Milwaukee)

113

Hayat Pharmacy #5 (Milwaukee)

Procare Pharmacy (Milwaukee)

Skywalk Pharmacy (Wauwatosa)

Hayat Pharmacy #7 (Villard Ave, Milwaukee)

2018-19 PSW CONFERENCE CALENDAR July 30, 2018 PSW Advanced Physical Assessment Workshop Medical College of Wisconsin, Milwaukee August 2–4, 2018 Leadership Pharmacy Conference Eagle Ridge Resort, Galena, IL August 23–25, 2018 PSW Annual Meeting Kalahari Theme Park & Convention Center, Wisconsin Dells October 26–27, 2018 PSW Technician Educational Forum Stoney Creek Hotel & Convention Center, Rothschild (near Wausau)

February 8-10, 2019 Midwest Pharmacy Expo Holiday Inn & Conference Center, Des Moines, IA March 13, 2019 PSW Legislative Day Monona Terrace, Madison April 9–10, 2019 PSW Educational Conference Monona Terrace, Madison May 16–17, 2019 PSW Senior Care Conference Lake Lawn Resort, Delavan, WI September 12–14, 2019 PSW Annual Meeting Hyatt Regency, Green Bay

www.pswi.org

What ONE thing can you do to help advance WPQC as we celebrate our 10th anniversary? • Complete one Comprehensive Medication Review (CMR) • Become a WPQC-accredited pharmacy (visit www.pswi.org/wpqc to learn more) For more information, contact Kari Trapskin at karit@pswi.org or (608) 827-9200.

• Connect with a fellow pharmacist or technician and encourage them to become WPQC-certified • Place free WPQC marketing materials in your pharmacy (available for order at www.pswi.org/wpqc)

1,800 CMRs in 30 Pharmacies in 2017. Working together, we can increase the annual number of CMRs by 10% during our WPQC 10-year anniversary year! If every WPQC pharmacy does just ONE MORE CMR in 2018, we will have reached a milestone of providing 10,000 CMRs to Medicaid members!

Features PRECEPTOR SERIES:

To Infinity…and Beyond! Pearls for Launching a Successful Career as a New Pharmacy Preceptor by Emily Bryant, PharmD, BCPS, Danielle Kroll, PharmD, James Lokken, PharmD, MS, MEd

recepting can be a daunting concept, especially for new practitioners. After getting assigned or volunteering to precept a rotation for the very first time, self-doubt can creep in. You might wonder “Am I qualified based on my limited experience?”, followed shortly afterwards by “What do I do now?”. As a new pharmacist, there can be a distinct advantage as a preceptor based on temporal proximity to the learner. This can be a powerful asset to planning a successful rotation, since Advanced Pharmacy Practice Experiences (APPEs) and/or residency may not have been completed too long ago. Preparation should leverage the freshness of those experiences to mimic and incorporate the activities that best promotes learning and engagement. Steps can be taken to optimize both your experience as a preceptor and the learner’s experience long before they ever arrive at the rotation site.

Prior to the Rotation

Activity Planning As with most things in life, a little planning can go a long way. This is especially true in developing a quality experiential rotation. A good place to start is to take inventory of the roles and responsibilities of your practice and consider categorizing them based on difficulty level (Table 1). For instance, it can be helpful to label each task as beginner, intermediate, or advanced.1 It is also important, as a new preceptor, to realize that each learner will arrive at their rotation with a different level of knowledge and abilities. A task that is at 20 The Journal

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the beginner level for one learner, may be an intermediate or advanced task for another learner. As a preceptor, you will need to adjust learners’ responsibilities based on their prior experiences. Having a complete and organized list of activities will make it much easier to sketch out a balanced blueprint and progressive schedule, to maximize what the learners are able to accomplish during their time on rotation. Activity Resources Once the activities list is developed and rotation outline is complete, it is much easier to map out what resources the learner will need to complete each task. This can include items like required readings, specific guidelines, sample forms or patient care templates, and policies and procedures.2 Resources should also be aligned with the rotation requirements set forth by the learner’s school of pharmacy or residency accreditation standards. Once the activities list is paired with the resources required, it is time to define the expectations for each task you anticipate the learner will complete. Activity Expectations Categorizing the difficulty level of each activity makes it much easier to assign expectations that are reasonable given a learner’s experience. The goal is to make each activity challenging for the learner, but not overwhelming. Once developed, the expectations for all activities should be shared with other pharmacy staff and the learner, so that everyone is aiming at the same target.2 In the end, having

an organized and matched list of tasks, resources, and expectations should help put you in the best position possible for the first day of the rotation

During the Rotation And so it begins… Day 1 of your first rotation as a preceptor. While you have done a lot of preparation work, it is important to be able to tailor the rotation to the learner. Having a plan is essential, yet it is just as important to be flexible and adjust the rotation to meet the needs of the learner.3 Many of the principles described here have been discussed in depth in other PSW articles for the preceptor series, but the repetition shows just how essential they are to building a successful rotation and a strong foundation as a new preceptor. Determining the Learner's Baseline Knowledge To start the rotation successfully, it is helpful to determine the learner's baseline knowledge of the content of your rotation. This comfort level will be very different for IPPE, APPE, and resident learners, so it is crucial to approach each learner individually - especially if you work with learners at each of these phases of their www.pswi.org

TABLE 1. Sample Categorization of Learner Activities Pharmacy Practice Setting

Learner Activity Level

Beginner

Intermediate

Advanced

Community • • • •

Patient education Medication histories Prescription processing & filling Product ordering or other inventory processes • Controlled substance inventory • Legal requirement evaluation for pharmacy and pharmacy practice • • • • • •

Prescription verification Insurance verification Prior authorization procedures Non-sterile compounding Pharmacy calculations Patient education material development • Therapeutic substitutions • Prescriber phone calls • Over-the-counter product recommendations for patients • Blood pressure screenings • Vaccine administration • Compounding • Transferring prescriptions • Billing insurance

career. The Aurora Cancer Care setting uses a survey that asks the learner to document several strengths, weaknesses, parts of oncology pharmacy they are comfortable with, parts they struggle with, and their goals for the rotation. On the first day of the rotation, a discussion of the learner's responses helps set the tone for the direction of the rotation. This information is useful in tailoring the rotation to build on the learner's strengths, while also focusing on improving the learner's areas of weakness. Understanding your learner's baseline knowledge will help you to develop realistic and reasonable expectations for the rotation. Setting Expectations One of the biggest frustrations in life is unmet expectations. The same is true for both learners and preceptors during experiential rotations. It is essential to discuss both preceptor and learner expectations at the beginning of the rotation to ensure a successful and healthy learning environment. Be specific and clear when you communicate your expectations. Encourage the learner to write down your expectations so they can refer to them during the rotation. Setting clear expectations up front helps to build the www.pswi.org

Ambulatory Care

Hospital

• Medication preparation, packaging, & delivery • Medication histories • Attending rounds • Electronic medical record navigation • Shadowing other health care providers • Policy review • Inventory management procedures

• Patient profile review • Collaborative practice agreement development or review • Patient education material development • Disease state or other guideline interpretation

• Patient education • Patient care interventions during rounds • Renal & hepatic dose adjustments • IV to PO conversions • Medication error identification and reporting • Drug information questions

• • • •

• • • • • • • •

Billing insurance Comprehensive medication management SOAP note documentation Patient work-up Point of care testing Vaccine administration Case presentations Business plan development for new or additional pharmacy services

foundation for feedback and evaluation as the rotation progresses.4 Providing Continual Feedback Receiving feedback – both positive and constructive – is fundamental to learners’ growth and advancement in their pharmacy career. Providing continual feedback allows for early identification of unmet expectations and lessens the likelihood of a difficult situation.5 Effective feedback provides the learner with an actionable plan to improve performance, while also acknowledging their strengths and aspects of the rotation in which they are excelling. Many feedback models are available and preceptors are encouraged to select and master a model that works best for their personal style.6 Providing effective feedback throughout the entire rotation will help to ensure that the rotation ends on a positive note, and allows the learner to leave with a sense of accomplishment and a plan for further development.

After the Rotation Upon successful completion of your very first student or resident rotation, you may feel that your work as a preceptor is done. Take time to breathe a sigh of relief! Afterwards, realize that you’ve just begun

• • • • • •

Pharmacokinetic monitoring Warfarin management TPN monitoring and/or preparation Sterile & nonsterile compounding Chart review Protocol & order set development

your journey. Just as learners are expected to self-reflect upon their performance, preceptors should pause to think about whether optimal precepting practices are being utilized. Feedback All preceptors should use feedback to evaluate and improve student performance, but it can be equally important to improving your own skills as a preceptor. Both informal and formal feedback provided by learners can provide valuable suggestions to improve your rotation.7 Four primary sources of feedback may be useful in continuous rotation improvement (see Figure 1).8 Informally, you as a preceptor may solicit feedback from your students and residents. This could happen during midpoint and final evaluations, or at any point during the rotation. Formal feedback is typically provided by the school/college of pharmacy or residency program and may be sent directly to the preceptor or require you to run an independent report. Results and comments are usually pooled to protect the identity of the learner, but they should be reviewed regularly and will likely provide strengths and opportunities for improvement. July/August 2018

The Journal 21

FIGURE 1. Sources of Feedback for Rotation and Preceptor Performance8

– starting before the rotation begins and ending after the learner’s rotation – will help to transform you from a novice into a precepting pro. Emily Bryant is a Clinical Pharmacist at Aurora St. Luke’s Medical Center in Milwaukee, WI. Danielle Kroll is a Clinical Pharmacist at Aurora Cancer Care Southern Lakes in Burlington, WI. James Lokken is a Clinical Pharmacist at Marshfield Clinic Health System in Marshfield, WI. Disclosures: The authors declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts and honoraria.

References

Self-Reflection Another key component of preceptor development is regular self-reflection. We expect learners to self-evaluate and preceptors should do the same! After compiling and reviewing feedback, consider completing a structured self-reflection exercise. Ask yourself, honestly, how the rotation went. Suggestions for questions to ask could include:8,9 • Was I prepared for the rotation? • Was it well-organized? • Did I act as a role model throughout? • Did I provide regular feedback? Was it both positive and constructive? • Did I encourage the learner to selfevaluate? • Were the methods I used to teach/ question the most effective? • Was student progress observed? • What steps can I take to improve as a preceptor? • What do I plan to do to address these areas for improvement and feedback received? A SWOT (strengths, weaknesses, opportunities, threats) analysis may be used to self-evaluate precepting abilities/ qualifications and aid in formation of 22 The Journal

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SMART (specific, measurable, attainable, relevant, time-bound) goals.7 Self-reflection and feedback should be used to write goals and create an overall plan for professional development. Continuing Preceptor Development Many resources exist for continuing preceptor development. A good place to start for members is the ASHP Preceptor Toolkit.10 Additionally, many colleges of pharmacy offer preceptor development programming and resources to their pharmacy preceptors. Consider attending professional local or national meetings such as the ASHP National Pharmacy Preceptors Conference. Lastly, never underestimate the value of mentorship! Finding an experienced preceptor to serve as a mentor can help to provide outside perspective, feedback, and an invaluable source of advice. Creating a sustainable model of continued self-evaluation and preceptor development will help you launch your lifelong journey in experiential education. Each learner will begin a cycle of preparation, action, and revision. Utilizing tips, tricks, and tried-and-true strategies throughout the entire precepting progress

1. Weitzel K. Preceptor CE: the power of planning: integrating learners into a busy practice setting. Pharmacist’s Letter. 2017. 2. Pharmacists Letter. A stepwise approach to incorporating learners into pharmacy or patient care services. http://pharmacistsletter. therapeuticresearch.com/ptrn/downloaditem. aspx?cs=PTRNONLY&s=PL&id=752. Published 2013. 3. Sheaffer SL, DeRemer CE, Yam NT. Precepting Fundamentals. In: Cuellar, LM, Ginsburg, DB. Preceptor’s Handbook for Pharmacists. Bethesda, MD: American Society of Health-System Pharmacists; 2009. 4. Theesfeld ML, Peppard SR. Great expectations: making sure you and your learner are on the same page. J Pharm Soc Wis. 2016;19(3):23-25. 5. Maynard RP. Preceptor CE: giving effective feedback to students and residents. Pharmacist's Letter. 2012. 6. Dworkin EE, Hager DR. Taking the fear out of feedback: models for success. J Pharm Soc Wis. 2016;19(2):22-25. 7. Soric, MM, Schneider SR, Wisneski S. The effective pharmacy preceptor. American Society of Health-System Pharmacists. https:// www.ashp.org/-/media/store-files/p5549frontmatter.ashx. Published 2017. 8. Doty RE. Getting Started as a Pharmacy Preceptor. American Pharmacists Association. 2011. 9. Vancouver Island Health Authority Pharmacy Residency Program. Preceptor self-evaluation & reflection. https://static1.squarespace.com/ static/51b156fee4b0d15df77a6385/t/51cb09d3e4 b09eb676a0e34d/1372260819880/Preceptor+SelfAssessment.pdf. Accessed 25 March 2018. 10. American Society of Health-System Pharmacists. Preceptor toolkit. https://www. ashp.org/Pharmacy-Practice/Resource-Centers/ Preceptor-Toolkit. Accessed 18 April 2018. 11. Pharmacist’s Letter. Preceptor training webinars & resources. http://pharmacistsletter. therapeuticresearch.com/content. aspx?page=PreceptorLiveOutside&xsl=PreceptorLive. Accessed 18 April 2018. www.pswi.org

Features

ID CORNER New HIV Horizons: Advances in Antiretroviral Therapy

ntiretroviral (ARV) therapy has advanced substantially over the past decade. Current guideline-directed regimens are highly efficacious and have favorable adverse effect profiles. In most cases, clinicians have the luxury of selecting regimens based largely on patient-specific factors. Care is taken to customize therapy to patients’ preferences, comorbid disease states, and other individual factors, in addition to routine HIV considerations, including drug resistance. Several notable additions to available ARVs have recently been approved. This article reviews three of these novel agents and/or regimens.

by Hailey E. Keeser, PharmD

Adherence A review of ARVs would be incomplete without mention of medication adherence. Successful HIV treatment requires excellent adherence, with a goal of taking medication greater than 95% of the time. People living with HIV (PLWH) can be nonadherent to their HIV medications for several reasons, including regimen complexity, pill burden, administration requirements, and adverse effects. Regimens should be individualized to each patient to achieve HIV viral suppression, defined by an undetectable viral load, typically defined as less than 20 copies per milliliter. Viral suppression results in decreased morbidity and mortality, mediated by improved immune system function, and decreases likelihood of transmission.1

Juluca™ The mainstay of HIV treatment has been a regimen that contains at least three active drugs. However, in November 2017, the first two-drug regimen was approved. Juluca™ (dolutegravir/rilpivirine (DTG/ RPV)) is a fixed dose combination tablet that contains an integrase inhibitor (INSTI), DTG, and a non-nucleoside reverse transcriptase inhibitor (NNRTI), RPV. Neither drug represents a novel compound, but their use in combination as a complete ARV regimen is the first of its kind. DTG/RPV is approved for use in adults with HIV who have been, and are currently suppressed, on a stable ARV regimen for six months or more. Patients must also have no history of virologic www.pswi.org

failure and no known resistance to the individual components. DTG/RPV was studied in two international, multicenter randomized controlled trials, SWORD-1 and SWORD-2, and in a pooled analysis.1,2 Each of these were non-inferiority studies with a duration of 48 weeks. DTG/RPV was compared to three-drug regimens, specifically, two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent (NNRTI, INSTI, or protease inhibitor) in patients with no known resistance to any ARVs or previous virologic failure. Eligibility criteria also specified that ARVs prior to randomization had to be either the patients’ first or second regimen. Up to 10% of patients were allowed prior exposure to one of the study drugs. The primary endpoint for each study was the proportion of patients reaching an undetectable viral load (less than 50 copies/mL) at week 48. The non-inferiority margin was set at 10% for the individual analyses, and eight percent for the pooled analysis. All three analyses met the criteria for non-inferiority.1 The pooled analysis of over 1,000 patients demonstrated a difference of -0.2% (DTG/RPV vs. three-drug regimen, 95% meeting the primary endpoint in both arms). From a safety perspective, adverse effects were reported at similar rates in both treatment arms. The most commonly reported adverse effects in the pooled analysis were nasopharyngitis (10% in the DTG/RPV arm) and headache (8% in the DTG/RPV arm).2 As with any ARV regimen, DTG/RPV has both advantages and disadvantages. Advantages include the convenience of a single tablet regimen and the ability to avoid short- and long-term toxicities by using less medication. Disadvantages include the administration requirements (i.e. food requirement for adequate absorption), and potential drug interactions with divalent cations and acid-suppressing agents. Additionally, available real-world data is limited, and existing data only extends to a 48 week time frame. The SWORD studies continue in open-label phases extending through 148 weeks to provide insight as to the long-term durability of a two-drug regimen.3 July/August 2018

The Journal 23

Biktarvy™ Another notable addition to ARV options is Biktarvy™ (bictegravir/ emtricitabine/tenofovir alafenamide (BIC/ FTC/TAF)), which contains the novel INSTI bictegravir as well as the NRTIs FTC/TAF within a single tablet regimen. BIC/FTC/TAF is approved for use in adults with HIV in two clinical scenarios: as initial therapy in treatment-naïve patients or in patients who have been and are currently suppressed on a stable ARV regimen for three months or more. Patients must also have no history of virologic failure and no known resistance to the individual components. BIC/FTC/TAF for treatment-naïve patients was studied in two international, multicenter randomized controlled trials. Each of these were non-inferiority studies with a duration of 48 weeks. Each study’s comparator arm differed, but both contained an INSTI with two NRTIs. The first study compared BIC/FTC/TAF to DTG with FTC/TAF in treatment-naïve patients. Eligibility criteria also specified that patients must have documentation of no resistance to FTC or TAF and an estimated glomerular filtration rate (GFR) greater than 30mL/min. The primary endpoint was the proportion of patients reaching an undetectable viral load (less than 50 copies/mL) at week 48, and the non-inferiority margin was set at 12%. The analysis of over 650 patients demonstrated a difference of -3.5% (89% meeting the primary endpoint in the BIC/FTC/TAF arm vs. 93% in the DTG plus FTC/TAF arm).4 A second study compared BIC/FTC/ TAF to DTG/abacavir/lamivudine (DTG/ ABC/3TC) in treatment-naïve patients. Eligibility criteria also specified that patients must have documentation of no resistance to any of the study drugs, HLAB*5701-negative, and have an estimated GFR greater than 50mL/min. The primary endpoint was the proportion of patients reaching an undetectable viral load (less than 50 copies/mL) at week 48, and the non-inferiority margin was set at 12%. The analysis of over 630 patients demonstrated a difference of -0.6% (92% meeting the primary endpoint in the BIC/FTC/TAF arm vs. 93% in the DTG/ABC/3TC arm).5 From a safety perspective, adverse 24 The Journal

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effects were reported at similar rates in both treatment arms of each study. Within both studies, the most commonly reported adverse effects were nausea (8-10% in the BIC/FTC/TAF arms), headache (11-13% in the BIC/FTC/TAF arms) and diarrhea (12-13% in the BIC/FTC/TAF arms).4,5 Similar to other ARV regimens, BIC/ FTC/TAF has both advantages and disadvantages. Advantages include the convenience of a single tablet regimen. Currently, INSTI-based regimens are recommended as first line treatment per Department of Health and Human Services (DHHS) HIV guidelines.1 Several other INSTI-containing single tablet regimens exist, each with their own set of advantages and disadvantages. One commonly used INSTI, elvitegravir, requires use of a pharmacokinetic booster, which poses drug interaction concerns.6 BIC/FTC/TAF provides a single tablet, INSTI-containing regimen free of this concern. Disadvantages include potential drug interactions, notably with divalent cations. Additionally, available real-world data is limited, and existing data only extends to a 48 week time frame. The studies discussed above are scheduled to continue through 144 weeks, which will provide further insight into the long-term efficacy and safety of this new INSTI.4,5

Trogarzo™ A unique addition to available ARVs is Trogarzo™ (ibalizumab), a monoclonal antibody with a novel mechanism of action. The antibody is directed against CD4 cells and blocks HIV from entering the cell. Ibalizumab is the first antibody for use in the treatment of HIV, and is approved for use in adults who are heavily treatmentexperienced, have multidrug resistance, and are failing their current regimen. Ibalizumab is administered via intravenous infusion. A loading dose is required, and maintenance doses are administered every 14 days. Given the risk for infusionassociated adverse reactions, patients must be observed after infusion completion. For initial doses, the observation period is one hour. If patients do not experience an adverse reaction following the first dose, subsequent observation periods are 15 minutes.7 Ibalizumab was studied in one small,

single-arm trial composed of 40 treatmentexperienced patients with multidrug resistance, some of whom had resistance to all approved ARVs. Over one quarter of enrolled patients had been previously treated with 10 or more ARVs. Patients continued an optimized background regimen (that could include investigational agents) that had failed to achieve viral suppression. The study’s primary endpoint was percentage of patients with a viral load decrease of greater than or equal to 0.5 log10 at day 14. At this time point, 55% of patients met the primary endpoint. At an extended time point of 24 weeks, 43% of patients had a suppressed viral load of less than 50 copies.8 Safety information was not presented at the time of writing, though adverse event rates and quality of life measures were collected.9 Ibalizumab has several notable advantages and disadvantages. As noted by the Food and Drug Administration upon approval, ibalizumab represents a major advancement for PLWH who have exhausted their treatment options. However, the benefits are accompanied by substantial challenges. The intravenous administration route and frequency of administration will likely limit use, due to logistical challenges for health care facilities and increased appointment frequency for patients. Additionally, the projected cost of the drug exceeds $100,000 annually. Finally, available data is limited, given the niche target population.

Future Advances Additional advancements in ARV therapy are anticipated in coming years, including new single tablet regimens, novel agents within existing drug classes, novel administration routes, and additional two-drug regimens.10-12 The future of ARV therapy is trending towards simplification, with a continued focus on medication adherence. To this point, a long-acting injectable product seems poised as the next major innovative therapy. This agent is currently in clinical trials as a two drug regimen (RPV plus another novel INSTI, cabotegravir), and will be dosed every 4 to 8 weeks.13

www.pswi.org

Conclusion PLWH can expect long and healthy lives, allowing for clinicians to focus more efforts on prevention and treatment of traditional chronic diseases such as diabetes and hypertension. For this reason, tailored and patient-centered ARV regimen selection is crucial. To facilitate this, advances in ARV therapy continue. The past twelve months have witnessed the approval of three novel agents and/or combinations, all of which appear to be both efficacious and well-tolerated based on current available data. HIV care team members should consider discussing these options with eligible patients. Wisconsin pharmacists in all settings will likely begin to see the novel agents discussed here, such as BIC, and novel two-drug regimens, such as DTG/RPV, and should be well versed on drug interactions and adverse effects that may accompany these. The pharmacist continues to play an important role in HIV care, in particular when monitoring and reinforcing medication adherence. Hailey Keeser is a PGY-1 Pharmacy Practice Resident at Concordia University Wisconsin School of Pharmacy & the AIDS Resource Center of Wisconsin in Mequon and Milwaukee,WI.

This article has been peer-reviewed. The contribution in reviewing is greatly appreciated!

Acknowledgements: The author would like to thank her preceptor, Nicholas Olson, PharmD, BCACP, AAHIVP for his expertise and guidance. Disclosures: The authors declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts and honoraria.

References

1. Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018; 391(10123):839-849. 2. ViiV Healthcare. Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-1). Available from: https://clinicaltrials. gov/ct2/show/NCT02429791. NLM identifier: www.pswi.org

NCT02429791. Accessed March 25, 2018. 3. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017; 390(10107):2073-2082. 4. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GSUS-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017; 390(10107):2063-2072. 5. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/ contentfiles/lvguidelines/AdultandAdolescentGL. pdf. Section accessed March 25,2018. 6. Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2015. 7. Trogarzo (ibalizumab-uiyk) [package insert]. Irvine, CA: TaiMed Biologics USA Corp.; 2018. 8. Weinheimer S et al. Ibalizumab susceptibility in patient HIV isolates resistant to antiretrovirals. 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018), Boston, abstract 561, 2018. 9. TaiMed Biologics Inc. Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV. Available from: https:// clinicaltrials.gov/ct2/show/NCT02475629. NLM identifier: NCT02475629. Accessed March 25,2018. 10. Huhn GD, Tebas P, Gallant J, et al. A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide Plus Darunavir in TreatmentExperienced HIV-1-Infected Adults. J Acquir Immune Defic Syndr. 2017;74(2):193-200. 11. Cahn P, RolĂłn MJ, Figueroa MI, Gun A, Patterson P, Sued O. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study. J Int AIDS Soc. 2017;20(1):21678. 12. ViiV Healthcare. An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/ Emtricitabine in Treatment naĂŻve HIV Infected Subjects (Gemini 1). Available from: https:// clinicaltrials.gov/ct2/show/NCT02831673. NLM identifier: NCT02831673. Accessed March 25, 2018. 13. Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499-1510.

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Original Work

Primary Care Pharmacists’ Role and Use of Technology in Diabetes Management in a Population Health Model within a Regional Health System by Jeff E. Freund, PharmD, BCACP, Mickey Hart, PharmD, Elyse Weitzman, PharmD, BCACP, Rachel L.C. Drury, PharmD, BCACP, and Erika E. Smith, PharmD, BCPS

pproximately 9.3% of the United States population (29.1 million people) has diabetes.1 The Centers for Disease Control and Prevention estimate that an additional 86 million adults in the U.S. have prediabetes and that as many as one out of every three adults in the U.S. could have diabetes by 2050.1 Diabetes is associated with significant rates of morbidity and mortality, leading to decreased quality of life and increased health care costs.1 The cost of care for patients with diabetes is high and increasing. As of 2012, annual costs associated with diabetes care in the U.S. total about $176 billion in direct medical costs and $69 billion in lost productivity; this equates to about one out of every 10 health care dollars.1,2 Patients with diabetes-associated complications have further increased costs when compared to those without complications.2 Improving glycemic control in patients with diabetes has been shown to reduce their risk of developing diabetesassociated microvascular complications, such as nephropathy, neuropathy, and retinopathy.3 The American Diabetes 26 The Journal

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Association recommends that diabetes care be provided by a multidisciplinary medical team that includes pharmacists, as this type of model has been shown to result in improved glycemic control when compared to provider-only care.4 Diabetes care team models that incorporate pharmacists consistently demonstrate a number of benefits, including improved glycemic control, reduced hospitalizations and emergency department visits for hyperglycemia and for hypoglycemia, reduced health care costs, and improved patient satisfaction.5-9 Froedtert & the Medical College of Wisconsin (F&MCW) is composed of Froedtert Hospital, a 585-bed academic medical center in urban Milwaukee, four community hospitals, and more than 45 primary and specialty health centers and clinics in southeastern Wisconsin. Twenty F&MCW health centers are recognized as patient centered medical homes by the National Committee for Quality Assurance (NCQA). F&MCW primary care physicians work closely with specialist physicians, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals to provide exceptional multidisciplinary team-based

care to patients. Inception Health was created by F&MCW to solve key health care problems, develop new ideas, and scale those solutions across the health network through successful collaboration with innovative external companies. Inception Health is the hub for the F&MCW health network’s digital health services. Through a close partnership with Inception Health, the primary care clinical pharmacists utilize technology to enhance disease state management through the use of digiceutical products Proteus Discover® and Glooko®.

Evolution of Primary Care Pharmacists at F&MCW into Population Health

Initial Pharmacist Involvement in Primary Care Primary care pharmacists have been an integral part of care at F&MCW Health Centers since 2013. Models have varied based on clinic needs and preferences and have continued to evolve. In July 2014, a Patient-Centered Medical Home Pharmacist began working collaboratively with a diabetes-focused Advanced www.pswi.org

Practice Nurse Practitioner at F&MCW Tosa Health Center. This pharmacist practiced under a Diabetes Management Collaborative Practice Agreement (CPA) with the F&MCW primary care physicians. This CPA allowed the pharmacist to independently assess patient progress towards diabetes-related goals, order and modify orders for medications and labs, and provide patient education regarding adherence to medications and lifestyle modifications. This model of care was developed with the primary purpose of increasing the quality of diabetes care at this clinic in a non-disruptive, financially sustainable way. A retrospective review of this co-management model in 2016 demonstrated an average change in A1c of -1.24% (p= 0.01) compared to prescriberonly management during an average of 73 days of engagement with the pharmacist, as well as statistically significant lowering of fasting and average blood sugars compared to baseline (p=0.003 for fasting blood sugars, p=0.001 for average).10 In April 2016, a F&MCW systemwide Diabetes Management CPA was approved and signed based on the F&MCW Tosa Health Center CPA. This CPA was a key component to the growth of the pharmacist’s role in primary care and diabetes management in the F&MCW system. With increased scope and autonomy, the primary care clinical pharmacists were able to more efficiently serve a larger patient population. Ambulatory Diabetes Outreach Program With data demonstrating the clinical benefits of the primary care pharmacist role in diabetes management along with physician feedback requesting additional resources within primary care, the Ambulatory Diabetes Outreach Program (ADOP) was approved by the F&MCW Ambulatory Quality subcommittee and officially started in August 2016. The primary purpose of ADOP was to help F&MCW Health Centers achieve the Wisconsin Collaborative for Healthcare Quality (WCHQ) diabetes bundle metrics for the managed care population. WCHQ publicly reports and brings meaning to performance measurement information that improves the quality and affordability of healthcare in Wisconsin, in turn improving the health of individuals and www.pswi.org

communities.11 The original ADOP team supported 19 clinics and was composed of five pharmacists and one certified diabetes educator (CDE) nurse. Each pharmacist supported a specific group of primary care clinics, whereas the CDE nurse was available to support patients at any of the clinics. As part of the Care Coordination department, the ADOP team also had access to a social worker and several care coordination nurses who were available to address barriers and provide patient care between follow-ups with the ADOP team. In addition to accepting referrals from primary care providers, the team utilized reports created from the electronic medical record (EMR) to identify patients within F&MCW’s managed care population. Eligible patients were those with type 2 diabetes, an A1c of ≥ 9%, not using U-500 insulin, and who were not being actively managed by endocrinology. Outreach to these patients was performed initially via a letter introducing the program to patients and providing the assigned ADOP team member’s contact information (Figure 1). The ADOP team member then provided an outreach call to each patient one to two weeks later. Upon the patient accepting participation in the program, management of the patient’s diabetes was provided primarily via telephone outreach, with office visits as needed, in collaboration with the patient’s primary care team until the patient achieved their diabetes-related goals. After meeting their diabetes-related goals while working with the ADOP team, patients returned to usual care with their primary care physicians. As the ADOP team developed, healthcare reimbursement models have continued to evolve from fee-for-service to pay-for-performance. Medicare's quality reporting programs and payment model are being consolidated and streamlined into one merit-based incentive payment system (MIPS). This consolidation has provided an opportunity to improve the existing Medicare programs and is focused on improved performance in four areas: quality (making up 50% of score), costs (10%), advancing care information (25%), and clinical practice improvement activities (15%). Under MIPS, clinicians and health systems are able to choose six measures on which they will be evaluated. One of

TABLE 1. Growth of Ambulatory Diabetes Outreach Program (ADOP) Year

Primary Care Clinical Pharmacist FTE

2014

2015

2016

Current state

FTE = Full Time Employee

the quality metrics F&MCW chose was Diabetes: Hemoglobin A1c under poor control (>9%), which aligns with the focus of ADOP.12 As the team found success in improving patient outcomes and with more emphasis being placed on quality of care, additional pharmacists were hired to meet increased demands through program expansion. The increase in primary care pharmacists on the ADOP team enabled the expansion of outreach to all patients, irrespective of insurance status, significantly increasing the number of patients supported. Currently, each of the pharmacists is actively managing between 80-100 patients, along with continued identification and outreach to eligible patients. Additionally, all pharmacists became embedded in their assigned primary care clinics throughout the F&MCW system, instead of some working from a central location. Having the pharmacists physically located in the clinics improves access for patients to have face-to-face pharmacist visits, enhances the collaboration with providers, and creates a stronger connection with the clinic-based care team. Lastly, an important factor in the growth of the primary care clinical pharmacist team is having a population (patients with uncontrolled type 2 diabetes) to which the pharmacists are accountable. This has allowed for data analysis of this population to indicate clear value in quality improvement and justification for continued growth (Table 1). Digiceutical Technology Having a pharmacist embedded in primary care clinics has also provided an opportunity to identify patients that may benefit from two digiceutical technologies, Proteus Discover® and Glooko®. Proteus Discover® is a digital medicine July/August 2018

The Journal 27

program designed specifically to provide feedback for medication adherence and other health behaviors to both patients and providers.13 It consists of an ingestible sensor, an adhesive wearable sensor patch, a patient mobile app, and a provider Web portal. After being swallowed, the ingestible sensor is activated and sends a brief signal with a specific code that is detected by the patch. The patch also measures physical activity, rest, heart rate, and step count to provide objective lifestyle information. Data from each patch are transmitted to a smart device (i.e., smartphone or tablet) and then to the secure portal. Patients can visualize the data on their smart device via an app. The patient is also able to enter blood glucose and blood pressure data into the app, and the app prompts the patient to take their medication doses as scheduled. Providers can view summaries of the data for their patients on a Web portal. The ultimate goal of Proteus Discover® is to improve clinical outcomes through better patient self-care, enhanced patient-provider dialogue, and data-driven optimization of therapy to help patients reach treatment goals more quickly.13 By utilizing electronic health record reports, patients have been identified for Proteus outreach through the ADOP team if they meet one of two criteria: 1. A1c >7% on only oral antidiabetic medications or, 2. Hypertension with concomitant type 2 diabetes with last two ambulatory BPs >140/90 or average ambulatory BP >140/90 over the past six months. Glooko® is a diabetes management healthcare tool that utilizes Bluetooth technology to support downloading of blood sugars from many different glucometers and continuous glucose monitors to a Web-based platform. This allows for more efficient, real-time assessment of individual patients’ diabetes control and enables the ADOP team to make medication adjustments quickly between a patient’s provider visits. The platform also has provided an avenue for patients to become more engaged in their care by allowing them to enter more specific data, including preprandial and postprandial blood sugars, when medication doses were missed or taken, 28 The Journal

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and eating habits. All patients enrolled in ADOP are eligible to sign up to use Glooko® while working with clinical pharmacists or certified diabetes educator on the ADOP team. Based on a cohort data review of patients enrolled in ADOP, those who used Glooko® demonstrated an average A1c lowering of 2.35% compared to 1.53% in those who did not use Glooko®(unpublished internal data).

Future Direction

Continued Evaluation of Effectiveness of Digiceutical Technologies Because the use of Proteus Discover® is a recent addition to ADOP, clinical outcomes to evaluate the effectiveness of the intervention, along with patient and other healthcare provider perspectives regarding the technology, are important areas of future research. Additionally, both digiceutical technologies will soon be integrated into the EMR platform, allowing providers to order the tool for patients who may or may not qualify for ADOP. This will allow the digiceuticals to be available to a wider population to include patients with diabetes and A1cs <9% and improve efficiency in the use of the digiceutical platforms. Focus on Additional Disease States Improved outcomes when expanding the care team to include clinical pharmacists in primary care at F&MCW have resulted in a desire to involve them in hypertension management and to provide comprehensive medication reviews for patients with complex medication regimens. This expansion of services is expected to further increase pharmacists’ value on the primary care team. Jeff Freund, Mickey Hart, and Elyse Weitzman are Primary Care Clinical Pharmacists at Froedtert and the Medical College of Wisconsin in Milwaukee, WI. Rachel Drury is Ambulatory Pharmacy Coordinator at Froedtert and the Medical College of Wisconsin in Milwaukee, WI. Erika Smith is Director, Enterprise Care Coordination and and Redesign at Froedtert and the Medical College of Wisconsin in Milwaukee, WI. Disclosure: The authors declare no real or potential conflicts or financial interest in any product or

service mentioned in the manuscript, including grants, equipment, medications, employment, gifts or honoraria.

This article has been peer-reviewed. The contribution in reviewing is greatly appreciated!

References

1. Centers for Disease Control and Prevention. Diabetes report card 2014. Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2015. 2. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033-1046. 3. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853. 4. American Diabetes Association. Foundations of care and comprehensive medical evaluation. Sec. 3. In Standards of Medical Care in Diabetes – 2016. Diabetes Care. 2016;39(Suppl. 1):S23–S35. 5. Bluml BM, Watson LL, Skelton JB, Manolakis PG, Brock KA. Improving outcomes for diverse populations disproportionately affected by diabetes: final results of Project IMPACT: Diabetes. J Am Pharm Assoc. 2014;54(5):477-485. 6. Ip EJ, Shah BM, Yu J, Chan J, Nguyen LT, Bhatt DC. Enhancing diabetes care by adding a pharmacist to the primary care team. Am J Health Syst Pharm. 2013;70(10):877-886. 7. Jameson JP, Baty PJ. Pharmacist collaborative management of poorly controlled diabetes mellitus: a randomized controlled trial. Am J Manag Care. 2010;16(4):250-255. 8. Johnson KA, Chen S, Cheng IN, et al. The impact of clinical pharmacy services integrated into medical homes on diabetes-related clinical outcomes. Ann Pharmacother. 2010;44(12):1877-1886. 9. Mccord AD. Clinical impact of a pharmacistmanaged diabetes mellitus drug therapy management service. Pharmacotherapy. 2006;26(2):248-253. 10. Hart M. Impact of a novel pharmacist and nurse practitioner diabetes co-management model. Oral Presentation at: Great Lakes Pharmacy Resident Conference; April, 2016; West Lafayette, IN. 11. Wisconsin Collaborative for Healthcare Quality. About WCHQ. https://www. wchq.org/about. Accessed 3/8/18. 12. The Merit Based Incentive Payment System (MIPS). https://www.cms.gov/Medicare/QualityInitiatives-Patient-Assessment-Instruments/ Value-Based-Programs/MACRA-MIPS-andAPMs/Quality-Payment-Program-MIPSNPRM-Slides.pdf. Accessed 3/8/18. 13. Frias J, Virdi N, Raja P, Kim Y, Savage G, Osterberg L. Effectiveness of digital medicines to improve clinical outcomes in patients with uncontrolled hypertension and type 2 diabetes: prospective, open-label, cluster-randomized pilot clinical trial. J Med Internet Res. 2017;19(7):e246.

www.pswi.org

FIGURE 1. ADOP Introduction and Outreach Letter

Dear XXX,

Managing diabetes can be a challenge, and sometimes you may need some extra help. You often cannot feel when your blood sugars are high and it is important to control your diabetes to avoid future health problems. You have been identified as being recommended for a FREE program for people with Type 2 Diabetes. At Froedtert, we have a team o experts as part of the Ambulatory Diabetes Outreach Program (ADOP) who want to help you control your diabetes by working together with you and your primary care doctor, @PCP@. We understand that making changes can be hard. We will work with you to help manage your sugars through food choices, activity, and medications. Working with an ADOP team member to manage your diabetes can be done over the phone at a time that is most convenient for you. It is a free service with a personalized approach to your care, working closely with your doctor and care team. Typically patients work with the ADOP team for 3-6 months AND as a part of this service, a tool called Glooko is available for free! Glooko is a diabetes management program to help you better manage your blood sugar levels and receive support as needed from the ADOP Care Team.

Using Glooko you will be able to: • • • •

Easily share data from your diabetes device(s) Quickly log carbs using our food database of 500,000+ foods and restaurant menus ceive support from your ADOP Care Team as needed Set medication reminders…and more!

**There are 2 ways to get started with the ADOP team**: 1. 2.

Call the pharmacist on your doctor’s care team at 414-777-5279 OR Follow instructions below to sign up for Glooko

If you are interested in signing up for Glooko, please follow the steps below:

1. On your computer or smart phone go to: join.glooko.com to claim your Welcome Kit. 2. Your unique activation code is the month, day and year of your birth along with the first two letters of your last name. For example 090386ta. 3. You will receive a shipping confirmation email to let you know your tracking information 4. Once you receive your Welcome Kit, follow the instructions in the box to sync your diabetes device(s) to Glooko and connect to your ADOP Care Team! 5. If you have any questions about Glooko setup, please contact the Glooko Support Team at 800-2066601 and press 1, or email support@glooko.com.”

We look forward to getting started together! Sincerely, XXX, Pharmacist PCP Phone: 414-777-5279 Froedtert *** Health Center

www.pswi.org

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The Journal 29

Original Work

Adopting Patient-Centered Prescription Medication Labels in Wisconsin by Steven W. Sparks, MS, Kenneth G. Schellhase, MD, MPH, Lauren B. Werner, MPH, David A. Mott, PhD, FAPhA, RPh, Paul D. Smith, MD, Henry N. Young, PhD, Michele B. Erikson, Kari N. LaScala, JD

hen Hayat Pharmacy owner Hashim Zaibak, PharmD, thinks about patientcentered prescription medication labels, one patient sticks in his mind. “I was going over all her medications after she was released from the hospital,” Zaibak said. “I asked her to show me how she used her Spiriva. The directions said, ‘Inhale the contents of one capsule once a day.’ She put the capsule in the inhaler. Then she inhaled but she never pierced the capsule. She was just getting plain air. Even though I thought the directions were clear, she was not taking the medicine properly.” This patient is not alone in her confusion. In one study, 3 in 5 persons with low health literacy incorrectly demonstrated use of a medication with instructions “take two tablets by mouth twice daily.” Even for those with adequate health literacy, 1 in 5 made mistakes.1 Communicating effectively about medications has long been a top priority for Wisconsin Health Literacy (WHL), a division of statewide nonprofit Wisconsin Literacy, Inc., located in Madison, WI. WHL’s mission is to improve communication between those who give and those who receive health communications. Patient misunderstanding about medication use has a high risk for adverse drug events. With existing evidence that patient-centered prescription medication labels improve understanding of medication instructions,2 WHL conducted a project to revise and implement prescription medication labels to conform to United States Pharmacopeia (USP) patient-centered medication label standards.3

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Abstract In 2013, the United States Pharmacopeia introduced new Patient-Centered Prescription Medication Label Standards. In 2014, Wisconsin Health Literacy (WHL) undertook a research project to determine if the standards could be successfully implemented in Wisconsin. Findings showed there was little awareness of the standards, but when they were explained, pharmacists and software vendors were in support of adopting them. In 2016-2017, WHL, in collaboration with an academic faculty partner from the Medical College of Wisconsin, completed a second phase of the project, working with 5 pilot pharmacy organizations to implement new labels based on the USP standards at 64 locations dispensing approximately 1.8 million prescriptions annually. Project Advisory and Patient Advisory Councils were formed to provide input for the project. Participating pharmacies worked with a WHL consultant to design new labels. Each pharmacy organization followed a different redesign process based on organizational structure and pharmacy software vendor. The new labels were well received by pharmacy managers, pharmacy staff and patients, based on surveys completed by over 500 patients and 92 pharmacists at participating organizations. Analysis of one organization’s prescription fill data showed improved adherence in 3 drug classifications after implementation of the new labels. Phase 3 began in January 2018, with a goal of expanding patient-centered labels to additional pharmacies across the state.

Background

Patient-Centered Labels Make a Difference The project began with evidence that patient-centered labels are effective. Multiple studies have shown positive results, especially for patients with limited health literacy and more complicated medication regimens: • A 2016 study reported redesign of patient-centered labels improved both medication adherence and when the medication was taken. The effect was stronger among patients with limited

literacy and more complex drug regimens.2 • Another 2016 study reported label redesign improved the comprehension and functional health literacy of older adults taking more than 2 prescription medications daily.4 • In 2011 the V.A. National Center for Patient Safety tested an evidencebased prescription label, finding it was preferred and improved comprehension in Veteran patients.5

www.pswi.org

USP Standards The path toward creating more patientcentered medication label standards nationally began in 2007, when the American College of Physicians Foundation issued a whitepaper, “Improving Prescription Drug Container Labeling in the United States.”6 The groundbreaking whitepaper reinforced the idea that the prescription label is the most tangible source of information about prescribed drugs and how to take them, and that the label is a crucial line of defense against medication errors and adverse drug events. The following year, the USP appointed a Health Literacy and Prescription Container Labeling Advisory Panel to develop prescription labeling standards. After extensive study, the USP developed a set of standards for patient-centered medication labeling as General Chapter 17 in USP’s National Formulary.3 The standards became official in April 2013 (Figure 1). A few years prior, in 2011, California became the first state to adopt its own standards to make labels easier to read. The standards included increasing font size and dedicating 50% of the label space to information intended for the patient. In 2013, prior to announcement of the USP Standards, the State of New York adopted supportive language for patient-centered labels.7 Late in 2013, Utah became the first and only state to formally adopt the USP standards when its Board of Pharmacy adopted rules that it was “unprofessional conduct” for a pharmacy or pharmacist to fail to comply with USP Chapter 17 standards.8 After much confusion from pharmacists on what was mandatory and what was optional related to the label rules, the Utah Board of Pharmacy made a decision to encourage use of the USP standards as a guide to help prevent medication misuse and not to enforce the standards.9 The USP has since made revisions to the standards in 2016 and 2017, and is now working on another update. Theory of Systems Change and Voluntary Approach This project and its continued expansion is based on Rogers’ Diffusion of Innovations Theory. The theory www.pswi.org

FIGURE 1. USP Standards in Brief 1. Emphasize instructions and other information important to patients; place less critical information away from dosing instructions a. Name, drug, directions at top b. Directions in simple language c. Sentence case (capital and lower case letters) 2. Improve readability – designed/formatted to be easy to read a. Contrast b. White space c. Large type d. Simple fonts 3. Give explicit instructions a. Numerals not spelled out (2, not “two”) b. Separate dose and timing c. Do not use “take as directed” or “take twice daily” d. Liquids-providing dosing device 4. Include purpose for use in clear language (if included on prescription and acceptable to patient) 5. Address limited English proficiency, in patient’s preferred language if possible 6. Address visual impairment; provide alternative access

describes the adoption of an innovation as following a pattern over time, gaining momentum and spreading as different groups adopt that innovation.10 The first phase of the project sought input from key pharmacy stakeholders regarding factors (i.e., attributes of the innovation) which could influence the adoption of patientcentered labels. Based on the interviews with pharmacy stakeholders, experiences of other states adopting patient-centered labels, and the advice of Pharmacy Society of Wisconsin and other key Wisconsin stakeholders, WHL decided to pursue a voluntary—not regulatory—approach to pharmacy redesign of labels and implementation. WHL staff believed the voluntary approach would be more successful to get the adoption process started. The pharmacies that implemented the USP standards in phase 2 of the project are serving as “innovators,” the first group to adopt an innovation under the Diffusion of Innovations Theory. The pharmacies who participate in phase 3 of the project will serve as the second group—or “early adopters” – under the theory. The project team anticipates that phase 3 will propel adoption of patient-centered medication labels to the tipping point when adoption becomes the norm for good customerfocused pharmacy practice in Wisconsin. While the focus of this project is the State of Wisconsin, it is anticipated that adoption of the USP standards may well extend to other states, as evidenced by interest already expressed. Wisconsin

Health Literacy will provide printed and web resources to help pharmacies outside the scope of the Wisconsin project.

Three Phase Project to Implement Patient-Centered Labels

Phase 1 The first of three phases in the project began in 2014 shortly after the USP standards were released. With grant funding from the Wisconsin Partnership Program of the University of WisconsinMadison, WHL staff interviewed Wisconsin pharmacists, pharmacy managers, physicians and pharmacy software vendors to examine the relative advantage, compatibility, complexity, trialability, and observability of the USP standards (patient-centered labels). These interviews provided information about facilitators and barriers that could impact the implementation of patient-centered labels in Wisconsin. Findings indicated that awareness of the standards was low. However, when interviewees learned more about the standards, they overwhelmingly supported implementing them, and felt they would fit into current pharmacy workflow. The results were published in a white paper, “Adopting an Easy-to-Read Medication Label in Wisconsin,”11 and led directly into the second phase of the project.

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FIGURE 2. Focus Group Participants Show Their Preferred Label Design (above) Phase 2 The second phase began in 2016 in collaboration with academic partner Kenneth Schellhase, MD, at the Medical College of Wisconsin Department of Family and Community Medicine. Phase 2 was a two-year project to implement the standards in pilot pharmacies. The Institutional Review Board of the Medical College of Wisconsin approved the project. The Advancing a Healthier Wisconsin endowment of the Medical College of Wisconsin provided grant funding. Phase 2 had five main components: 1) solicit stakeholder input; 2) recruit and engage pharmacy organizations; 3) revise medication labels; 4) implement revised labels and 5) evaluate stakeholder response. Stakeholder Input Wisconsin Health Literacy staff recruited a 17-member Project Advisory Council and 11-member Patient Advisory Council, conducted an email/internet survey of members of the Pharmacy Society of Wisconsin (PSW), coordinated patient semi-structured interviews and focus groups, and implemented a general public internet survey to obtain input about various aspects of the project. The Project Advisory Council included representatives from PSW, Medical College of Wisconsin, Epic Systems, USP, University of Wisconsin-Madison School of Pharmacy, a purposeful sample of pharmacists and Dr. Michael Wolf, nationally recognized medication label researcher. The group met quarterly to receive updates and to provide advice and recommendations to advance the project. 32 The Journal

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The Patient Advisory Council was recruited with advice from the Wisconsin Network for Research Support, whose staff has expertise in forming and operating advisory groups.12 A purposeful sample of participants was recruited with a diversity of age, race, geographic location, health status and literacy levels. The group met quarterly to review materials and project activities to ensure they were clear and understandable by patients of all literacy levels. The email/internet survey of PSW members included topics such as awareness of USP Patient-Centered Medication Label Standards, attitudes toward adoption of the standards, and barriers to adoption. Wisconsin Health Literacy staff conducted two individual semi-structured interviews and two focus groups of adults representing “patients.” A convenience sample of participants for the focus groups was recruited through a community center in Milwaukee, Wisconsin, which serves low literacy adults. The purpose was to discover what patients like and don’t like about labels. In a group exercise, WHL staff cut apart the different elements on a typical medication label and asked the participants to design their own labels (Figure 2). The project’s Patient Advisory Council was asked to go through the same exercise. The experience proved to be very enlightening and formed the basis for many of the format changes made by the pilot pharmacies. Feedback was consistent from the focus groups, individual interviews, and the Patient Advisory Council. Wisconsin Health Literacy also developed an internet survey called “Vote

for Your Favorite Label” to gain insight into patient label preferences. Through social media, the public was invited to select which of two labels they preferred and what they liked or didn’t like about each (Figure 3). They also answered a few label questions and had the opportunity to write about a medication label experience. The advice, recommendations, surveys and focus group information had substantial impact on the conduct of the project. Participating Pharmacies Three pharmacy organizations were recruited through personal contacts by project team members. 1. Hayat Pharmacy had 10 sites located mostly in low income areas in Milwaukee, WI. 2. UW Health Pharmacy Services had 14 locations in and around Madison. 3. Hometown Pharmacy had 44 sites in southern and eastern Wisconsin. The three pharmacy organizations were very different. Each used different pharmacy software vendors (Rx30, EnterpriseRx-McKesson, and PioneerRx), resulting in different processes for label change. Some pharmacies wanted to implement new labels at all sites at one time, while others chose to do one site at a time. Some pharmacies wanted to use up old label stock while others were willing to design something new. This diversity enriched the project by providing different routes to the same goal of redesigning labels. The only out-of-pocket cost for changing labels was purchasing new label stock for pharmacies opting to do this. Funds through the grant from the Advancing a Healthier Wisconsin endowment provided financial assistance for those who made this choice. The pharmacy staff time commitment varied greatly, depending on the pharmacy organization. The number of pharmacy sites involved in the project changed during the project. Hayat added two new locations. The ownership of several of the Hometown pharmacies changed as two new additional organizations were formed, Forward Pharmacy and Fitchburg Family Pharmacy. By the end of the project the number of participating organizations increased from www.pswi.org

three to five, with 64 sites implementing new labels. Nine sites have not yet changed labels: seven in one organization where printers would not accommodate the newly designed larger labels, and two in another organization where it plans to use up old label stock before starting the new labels. Leaders from all participating pharmacies said that they agreed to participate in the project because it was the right thing to do. Melissa Ngo, PharmD, BCACP, Manager of Community Pharmacy Services, UW Health Pharmacy Services, said, “We knew this was something really important. We hadn’t looked at our prescription labels in the last decade to address whether patients could understand them. This was a good way to get the label updated, make sure people understand how to take their medication and hopefully have better outcomes as a result.” Hashim Zaibak, PharmD, owner of Hayat Pharmacy agreed. “The number one reason patients don’t take their medicines properly is that they’re not understanding the label. If we can improve that, we can improve adherence, people taking their medications properly and, in the end, help make them healthier people.” Matt Mabie, RPh, previous co-owner of Hometown Pharmacy and current owner of Forward Pharmacy had similar thoughts. “Our motto at Hometown was ‘Our family caring for your family.’ We didn’t want barriers to patients understanding their label. Any time there are improvements, we’re going to jump on that to make the experience better for patients.”

participating pharmacies and other key pharmacy stakeholders also was important. The Phase 2 pharmacies were “innovators,” and able to be nimble, flexible and make quick decisions. Wisconsin Health Literacy recognized that it would be more effective to approach larger chains after having gone through the implementation experience with pharmacies that had a greater degree of flexibility to make prompt label and implementation decisions. The results and testimonials from Phase 2 innovators will be key as WHL communicates with potential Phase 3 pharmacy partners.

Results

PSW Survey Email invitations were sent to 3,879 PSW members, including mostly

pharmacists, along with some pharmacy technicians and students. Responses totaled 400 (10.3%). Key results were: • 59% were not familiar with the USP standards. • Given an explanation of the standards, 85% favored general adoption. • 61% said they would like to see the standards adopted in their pharmacy. • The biggest barrier to adoption of the standards was the perceived lack of space on the label. Patient Interviews and Focus Groups The two patient focus groups were comprised of 13 and 11 adults respectively. The first group included 9 women and 4 men, and the second included 9 women and 2 men. Participants were of mixed ages

FIGURE 3. Favorite Label Comparison

Communication and Engagement From the outset, WHL staff identified individuals and groups that should be informed of project updates. A quarterly e-newsletter was developed and distributed to pharmacy opinion leaders in the state and nationwide. Representatives from the Project Advisory Council gave an informational presentation to the Wisconsin Pharmacy Examining Board, which expressed interest in ongoing communication. Wisconsin Health Literacy staff also contacted key leaders at Walgreens, Roundy’s, CVS and Walmart to make sure they were aware of the project. Regular communication with the www.pswi.org

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TABLE 1. What Patients Like and Don’t Like about Prescription Labels Patients Like

Patients Don’t Like

Color, bolding, large font

Information only used by pharmacists

White space

Lots of confusing dates

Indication for drug use

Addresses

Most important info at top

Clutter

Name of medicine

Unclear directions (twice daily)

Prescriber name

All capital letters Pharmacy info at top

and all African-Americans. An additional two persons (1 man and 1 woman, both African Americans) were interviewed to determine if responses were different. Responses were consistent. The participants overwhelmingly said the top of the label should include patient name, medication name, and instructions for use, in that order. Less important to them were the prescription number and number of refills. They found multiple dates confusing and were adamant that the label should only include information important to the patient, not information used only by the pharmacist. Two observations from the focus groups were unexpected and eye-opening. Some of the focus group members with extremely low literacy struggled even to complete the exercise. That led to the realization that making an easier-to-read label was only part of the solution for them. Another interesting finding was a strong and widespread perception that generic drugs were less effective and that pharmacies give them to “poor” customers. General Public Internet Survey Nearly 1000 persons voted for which label they preferred, with 12% preferring label A and 88% label B (Figure 3). Of those responding to the survey questions, 88% said they found medication labels confusing and 23% said they had taken a medication wrong because the label was confusing. One of the most enjoyable—and at the same time frightening—aspects of this project was the collection of stories from 34 The Journal

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people who had found labels confusing. These stories also came through the Favorite Label website survey. Stories such as the following inspired WHL and pharmacy staff alike and reaffirmed the importance of this label initiative. “A woman I knew was rushed to the ER due to an overdose of diabetes medication. She later realized she was taking almost 3 times the recommended dosage because the instructions read, "take up to 3 tablets every 24 hours" and she understood it to be "3 tablets, 3 times a day every 24 hours." “My grandma accidentally took 3 times the daily dose of a medication for about 4 days due to a label that stated, “Take 1 1/2 pill twice daily.” She was actually just supposed to take a ½ pill two times a day, but with the “1” on the label before the 1/2, it made it look like she was supposed to take 1.5 pills twice a day.” The focus groups, the Patient Advisory Group, and the favorite label survey provided a wealth of guidance to create the redesigned labels (Table 1). Patients and Participating Pharmacy Staff Surveys The success of the project was measured in part by surveys of patients and pharmacy staff. Over 500 patient surveys were completed at multiple sites within the three original pharmacy partner organizations. Those surveys found: • 93% said it was important for medication labels to be easier to understand. • 83% like the new labels better or the same as the old label (only 13% said they liked the old label better). • Patients felt the greatest benefits were that the letters were larger, the labels were easy to understand, and important information was easy to find. A survey of pharmacy staff at the implementing organizations found that among 92 respondents: • 84% were aware of the change. • The greatest anticipated impact on patients was better adherence, fewer medication errors, and that patients were more likely to benefit from the

medication. Pilot Pharmacies’ Experience An estimated 1.8 million prescriptions dispensed from 64 sites annually will have easier-to-understand labels because of the collaboration between WHL and Phase 2 pharmacies. Wisconsin Health Literacy worked with each of the pharmacy partners to redesign labels based on the USP standards, feedback from the patient focus groups, analysis of other labels based on the USP standards, and extensive conversations with the pharmacies’ software vendors. Wisconsin Health Literacy created an online toolkit to educate pharmacy staff on the standards and to help them explain the label change to patients. Then the pharmacies introduced the new labels at various sites over a 14-month period (Figure 4). All participating pharmacies agreed that the experience was very positive. “Patients liked the new labels—having their name on top,” said Matt Mabie. “They liked the bigger font. After starting the new labels, we had dramatically fewer callbacks from patients who get home, looked at the bottle and had questions on what something means.” Melissa Ngo said, “Patients like the directions on the top, improved white space, and that the prescription number is close to the pharmacy number. Their one comment was that the medication name didn’t stand out, and we’ve worked on that.” Although all moving toward the same goal, each of the participating pharmacy organizations had a different experience based on organizational structure, previous labels, printers, prescription containers and software vendors. For example, all pharmacy locations at Hayat Pharmacy are located in relatively close proximity with a more uniform organizational structure. Hometown pharmacies, however, are located over a much wider geography and many come from a history of independent ownership with more individual site variations. UW Health pharmacies have a more complex decision-making process, given their position within a large health care system. Each pharmacy’s relationship with their pharmacy software vendor also varied. Some pharmacies could make label changes www.pswi.org

FIGURE 4. "Before" (left) and "After" (right) Labels at Hometown Pharmacy

themselves, while others had to work with a remote vendor to make every label change. Some vendors were not able to make the requested changes to comply with all the USP standards. For example, UW Health’s vendor was not able to change numbers into numerals within the directions for use, resulting in Melissa Ngo and her team having to change each manually. The varied vendor experience was a great benefit to the project, in that it has better prepared WHL to anticipate potential challenges and solutions with future pharmacy partners and their vendors. At the end of the project, all pharmacies implementing new labels committed to continue using them.

Dissemination

Medication Adherence The goal of Phase 2 of the project was implementation of the label and not to prove that patient-centered labels are effective, as this is already welldocumented. However, an opportunity presented itself to study adherence by patients before and after receiving new labels. Analysis was done of prescription refill information by Hayat Pharmacy patients who are members of Children’s Community Health Plan (an all-Medicaid plan). The average medication possession ratio (MPR) of these de-identified patients was calculated before and after the label change. The average MPR significantly improved after the label change for asthma medicines, anti-hypertensives, and oral contraceptives. Also, there was some evidence that MPRs improved the most for patients with very low MPRs before the label change.

Conclusions and Next Steps: Phase 3

www.pswi.org

The project included a unique Medication Label Summit, held April 3, 2017. One purpose was to share some of the recent research into patient-centered medication labeling. Another was to provide an opportunity for pharmacists from the pilot organizations to share experiences with other pharmacies who may want to participate in the future. Of 82 attendees emailed a survey after the event, 31 (38%) responded, with these key findings: • 82% would advocate for improving labels. • 54% plan to get involved in label redesign where they work.

Phases 1 and 2 resulted in a wealth of information being used to compile an Implementation Guide for new pharmacies implementing patient-centered labels in the future. Some of the most impactful learnings are: • Pharmacists have an intense desire to help their patients, which is a very strong driver to make the change to patient-centered labels. • Patient involvement during the project was critical to assure that label changes with the most potential impact were emphasized. • Every pharmacy is different, requiring flexibility during label redesign and implementation. • Software vendors need to be involved all along the way. Some “impossible” changes ended up being possible with

perseverance. • Pharmacies should be recognized for their commitment to making labels easier to read. • Education about the research behind the standards, e.g., the benefit of not using all capital letters, is important to help pharmacists understand and accept the changes. • Stories are vital to motivating staff. Citing statistics about medication errors is much more effective when also telling stories about patients misunderstanding label instructions and taking medications incorrectly.13 Phase 3 Phase 3 began in January 2018 and is focused on leveraging experiences of the pilot pharmacies with the primary goal of expanding patient-centered labels to additional pharmacies across the state of Wisconsin. This phase also is supported by grant funds from the Advancing a Heathier Wisconsin endowment of the Medical College of Wisconsin. Readers interested in learning more about Phase 3 should contact the authors. As of this writing, three health systems, one small pharmacy network, and one independent pharmacy have committed to working with WHL in phase 3 to improve their labels. Representatives of the Phase 2 pharmacies have agreed to share their experience with new pharmacies beginning the patient-centered label journey. In addition to implementing new labels at more pharmacies, WHL is also addressing modifying the “sigs,” or directions for use. In Phase 2, there July/August 2018

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Interested in working with Wisconsin Health Literacy to implement patient-centered labels in your Wisconsin pharmacy? • Benefit from free consultation throughout the guided process • Receive financial assistance available to purchase (optional) new label stock • Join and connect with an ever-growing number of nationally recognized Wisconsin pharmacies making this change. To find out more, contact Kari LaScala, Wisconsin Health Literacy, (608) 257-1655, ext. 5, or email kari@wisconsliteracy.org.

was a clear desire among pharmacies to improve the sig, but it is an incredibly complex matter and was beyond the scope of that project. In Phase 3, WHL will bring many stakeholders, including Epic Systems representatives, together in a “Sig Improvement Task Force.” The task force’s goal will be development of recommendations to help organizations improve their directions for use to meet the USP standards. In the final year of Phase 3, systems and resources will be put in place so future pharmacies have step-by-step directions for implementing patient-centered labels on their own. What would those pharmacists who already have adopted the patient-centered labels say to new pharmacies considering redesign? Hashim Zaibak says it’s good for patients and for business. “Helping patients better understand their labels will make them more adherent to their medications, love their pharmacy more and hopefully stay with that pharmacy as customers for a long time.” For Melissa Ngo, the answer is “Why wouldn’t you?” She added, “Why wouldn’t you take the time to think about what your label looks like and if your family or friends would be able to understand what’s on that label.” Relatively small changes on a prescription label can significantly improve patients’ effective use of medications. With the introduction of patientcentered labels into more pharmacies, millions more patients can experience safer medication use and better health outcomes. For more information on the 36 The Journal

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project or how you can be part of this expanded effort in Wisconsin at no cost, contact Kari LaScala, Wisconsin Health Literacy, (608) 257-1655, ext. 5, or email kari@wisconsinliteracy.org. Steven Sparks is the Health Literacy Director at Wisconsin Health Literacy in Madison, WI. Kenneth Schellhase is a Professor of Family Medicine at the Medical College of Wisconsin and the Medical Director at Children’s Community Health Plan in Milwaukee, WI. Lauren Werner was formerly tge Project Coordinator at Wisconsin Health Literacy in Madison, WI. David Mott is the Chair of the Social and Administrative Sciences Division at the University of Wisconsin-Madison School of Pharmacy in Madison, WI. Paul Smith is a Professor in the Department of Family Medicine at the University of Wisconsin-Madison, and Medical Advisor at Wisconsin Health Literacy in Madison, WI. Henry Young is an Associate Professor at the University of Georgia College of Pharmacy in Augusta, GA. Michele Erikson is the Executive Director of Wisconsin Literacy, Inc. in Madison, WI. Kari LaScala is the Project Manager at Wisconsin Health Literacy in Madison, WI. The authors would like to thank the following for the assistance they provided during the project: Beth Gaytan, Wisconsin Health Literacy; Pharmacy Society of Wisconsin; Wisconsin Network for Research Support; University of WisconsinMadison School of Pharmacy, and Children’s Community Health Plan. Special thanks also go to the members of the Steering Team, Project Advisory Council, and Patient Advisory Council which provided invaluable contributions to the project.

6, 2018; Institute for Health Care Advancement 17th Annual Health Literacy Conference May 10, 2018; and Academy of Communication in Healthcare ENRICH Communication Course & Research Forum, May 31-June 3, 2018.

References

1. Davis TP, Wolf MS, Bass PF 3rd, et al. Literacy and misunderstanding prescription drug labels. Ann Intern Med. 2006;145(12):888-894. 2. Wolf MS, Davis TC, Curtis LM, et al. A patient-centered prescription drug label to promote appropriate medication use and adherence. J Gen Intern Med. 2016;31(12):1482-1489. 3. United States Pharmacopeia. USP-NF General Chapter <17> Prescription Container Labeling. http://www.usp.org/health-quality-safety/ usp-nf-general-chapter-prescription-containerlabeling. Published October 9, 2012. Updated November 13, 2012. Accessed May 2, 2018. 4. Tai B-WB, Baei YH, LaRue CE, Law AV. Putting words into action: a simple focused education improves prescription label comprehension and functional health literacy. J Am Pharm Assoc. 2016;56(2):145-152. 5. Trettin KW. Implementation of VA patientcentered prescription label and patient medication information. Procedia Manufacturing. 2015;3:1-5. 6. National Academies of Science, Engineering and Medicine. Improving Prescription Drug Container Labeling in the United States. http:// www.nationalacademies.org/hmd/~/media/Files/ Activity%20Files/PublicHealth/HealthLiteracy/ Commissioned-Papers/Improving%20 Prescription%20Drug%20Container%20 Labeling%20in%20the%20United%20States.pdf. Published October 12, 2007. Accessed May 2, 2018. 7. Herold, Virginia, (Executive Officer, California Board of Pharmacy). Telephone interview by Steven Sparks. May 11, 2015. 8. Garn, Derek (Chair, Utah Board of Pharmacy). Telephone interview by Steven Sparks. June 11, 2015. 9. Utah – DOPL Label Requirements Dropped. Foundation Systems Support website. Accessed July 8, 2015. 10. Boston University School of Public Health. Diffusion of Innovations Theory. http://sphweb.bumc.bu.edu/otlt/MPHModules/SB/BehavioralChangeTheories/ BehavioralChangeTheories4.html. Published April 28, 2016. Accessed May 2, 2018. 11. Sparks S, Mott, D, Young H, Mansukhani S, Erikson M. Adopting an easy-to-read medication label in Wisconsin. http://wisconsinliteracy. org/health-literacy/what-we-do/medicationlabel-improvement.html. September 2015. 12. Wisconsin Network for Research Support. https://winrs.nursing.wisc. edu/. Accessed May 2, 2018. 13. Heath C, Heath D. Switch: How to Change Things When Change Is Hard. Random House Business Books, 2010.

Some of the information included in this manuscript has been presented at the Pharmacy Society of Wisconsin Educational Conference April www.pswi.org

Original Work

The Utilization of Gabapentin in Alcohol Withdrawal Management at a Community Hospital by Christopher T. Leuenberger, PharmD, David G. Galbis-Reig, MD, DFASAM, Steven J. Suokko, PharmD, Biniam G. Berhane, PharmD, and George I. Honein, PharmD

he alcohol withdrawal syndrome is a pathophysiological response to long-term alcohol use, that when severe, is most effectively managed in an inpatient medically managed detoxification setting to ensure adequate symptom control and prevent the worst consequences of alcohol withdrawal: seizures, delirium, or death.1 Proper management of the alcohol withdrawal syndrome can improve engagement in long-term treatment for addiction to alcohol. Complications associated with alcohol withdrawal, however, are estimated to still occur in approximately 500,000 individuals in the United States annually, making it an important clinical concern.1 It is known that neurons producing gammaaminobutyric acid (GABA), which is the primary inhibitory neurotransmitter in the central nervous system, play a crucial role in the development of the alcohol withdrawal syndrome via a host of neuronal adaptations that lead to excessive neuronal excitation with the abrupt cessation of alcohol use. While the following explanation is an oversimplification of the neuroadaptive changes that occur, the long-term ingestion of high amounts of alcohol produces desensitization and downregulation of the GABA receptors. This causes a commensurate upregulation of the excitatory neurotransmitter system via an increase in the number of N-Methyl-D-Aspartate receptors that have an increased affinity and sensitivity to glutamate (what is clinically described as “tolerance.”)2 Abrupt discontinuation of alcohol, therefore, produces a sudden disequilibrium in this adaptive system resulting in an abrupt reduction in GABA www.pswi.org

Abstract Objectives: Recent literature suggests that gabapentin may be an alternative treatment to standard management of the alcohol withdrawal syndrome (AWS). At All Saints hospital it was anecdotally observed that the addiction medicine physician managing patients on the Medically Managed Detoxification Unit (MMDU) utilized lower doses of benzodiazepines than did physicians on the General Medical Units (GMU). This was accomplished by using scheduled gabapentin as adjunctive therapy. The objective of this retrospective outcome study was to compare benzodiazepine usage between the MMDU and the GMU to describe if there exists a difference in treatment outcomes. Methods: A retrospective chart review was conducted in order to describe the use of gabapentin in patients, meeting inclusion criteria, being treated for alcohol withdrawal between the study timeframe of January 1st, 2016 thru October 31st, 2016. The primary outcome of interest was the time it took for patients to reach a Clinical Institute Withdrawal Assessment for Alcohol (CIWA-ar) score of 7 or less for 24 hours. Secondary outcome measures included total average benzodiazepine and gabapentin dosage used during hospitalization and the development of severe complications of withdrawal including seizures or delirium. Results: The gabapentin protocol utilized in the MMDU was similar to that of the GMU (mean time to the primary outcome of interest between both groups was non-significant with a p-value of 0.87). This was despite a statistically significant difference in total benzodiazepine dosage among the two groups with much lower benzodiazepine doses in the MMDU than in the GMU (P-Value < 0.0001). Conclusions: The results of this study support further investigation into the use of a scheduled gabapentin protocol to decrease utilization of benzodiazepines during management of AWS in hospitalized patients.

activity with increased, and immediately unopposed, glutamatergic action that leads to excessive central nervous system excitation that is observed clinically as AWS. The current “gold standard” treatment

for the AWS has been the use of benzodiazepines, a class of substances that produce their clinical effects by sensitizing and stimulating the GABA A subunit of the GABA receptor in a fashion similar to alcohol. As a result, benzodiazepines July/August 2018

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TABLE 1. ICD-10 Diagnostic Codes Used to Generate Patient Lists for the Study F10.20

Alcohol dependence

F10.129

Alcohol abuse with intoxication

F10.21

Alcohol dependence (remission)

F10.229

Alcohol dependence with intoxication

F10.231

Alcohol dependence with withdrawal delirium

F10.221

Alcohol dependence with intoxication delirium

F10.921

Alcohol use with intoxication delirium

F10.220

Alcohol dependence with intoxication

F10.121

Alcohol abuse with delirium

F10.120

Alcohol abuse with intoxication

F10.221

Alcohol dependence with intoxication delirium

F10.239

Alcohol dependence with withdrawal

maintain the neuroadaptive changes produced by long-term use of alcohol and help alleviate the symptoms associated with the AWS.3 In clinical practice there are several benzodiazepines that are utilized interchangeably, most commonly, chlordiazepoxide, diazepam, and lorazepam. During the past several decades, additional studies have demonstrated that several anticonvulsant medications, including gabapentin, carbamazepine, and valproic acid may also be effective at suppressing the AWS.4 These medications appear to play a role in inhibitory neurotransmission via direct and indirect effects on the GABA receptor, and perhaps via modulation of the excitatory pathways. Interest in utilizing some of these agents, especially gabapentin, to support treatment during alcohol withdrawal have grown over the past decade. While the primary advantage of utilizing gabapentin now appears to be in outpatient settings for individuals with mild to moderate AWS5, the literature also demonstrates that the use of gabapentin may be effective in the treatment of seizures associated with AWS6, a reduction in CIWA scores (in head-to-head trials versus lorazepam)7, and in the long-term treatment of addiction to alcohol by preventing relapse.8-10 Gabapentin has been shown to decrease rates of sedation, anxiety, and craving when compared with detoxification using a benzodiazepine.7 Gabapentin use also increases abstinence rates versus traditional detoxification using only a benzodiazepine. In addition, when used in combination with symptomtriggered benzodiazepine AWS protocols, the anticonvulsants may reduce the overall dosage of benzodiazepines required. While gabapentin is used most often for this purpose (due to its favorable side effect profile), other anticonvulsants including carbamazepine and zonisamide can 38 The Journal

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play an important role in managing the AWS.4,11,12 In addition to benzodiazepines and anticonvulsants, alpha-2 agonists can play an important role as adjunctive treatment for patients with a significant hyperautonomic response (hypertension, tachycardia, severe diaphoresis) associated with their alcohol withdrawal.13 The Ascension Wisconsin All Saints hospital system in Racine, WI has two campuses located within the city of Racine. The Saint Mary’s Medical Center facility represents the primary hospital campus and houses most medical specialties including the general medical units, hematologyoncology units, surgical units, intensive care units, cardiovascular services, orthopedic services, an emergency department, and Women’s Health (including labor and delivery). The St. Luke’s Medical Center facility (approximately 3 miles from the primary hospital campus) houses a Skilled Nursing Facility and the Behavioral Health and Addiction Units (including the state certified MMDU). Both facilities admit and manage patients undergoing alcohol withdrawal symptoms using the same system-wide alcohol withdrawal protocol which permits providers to choose either lorazepam or chlordiazepoxide

for symptom-triggered therapy. It was anecdotally noted that higher doses of benzodiazepines were being utilized on the GMU than on the MMDU where scheduled gabapentin was used on a routine basis by the addiction medicine attending. The purpose of this retrospective outcome study was to describe the anecdotal finding that the MMDU was utilizing significantly lower total doses of benzodiazepines (standardized to a milligram dosage equivalent) than the GMU service while not compromising outcomes through augmentation of the alcohol withdrawal protocol by including a scheduled standard dose of gabapentin for all patients admitted for alcohol detoxification. The goal of this study was also to obtain data that will support the standardized application of the scheduled gabapentin protocol utilized by the Addiction Medicine Specialist throughout the Ascension Wisconsin All Saints system (and perhaps throughout Ascension Wisconsin).

Methods The study utilized a retrospective naturalistic outcome study design to compare differences between alcohol withdrawal management on the GMU

TABLE 2. Baseline Characteristics General Medical Unit

Medically Managed Detox Unit

P-value

Age (years)

49.5

0.56

Blood alcohol concentration on admit (average)

0.23

0.22

0.71

Seizures pre-admit (# of patients)

0.02

Initial CIWA-ar score (average)

7.88

6.6

0.17

5.0

4.3

0.02

Male: 43, Female: 8

Male:70, Female: 17

PAWSS score (average) Gender

www.pswi.org

TABLE 3. Summary of Results

Against medical advice discharge (# of patients) Length of stay (average days) Incidence of seizures (# of patients)

General Medical Unit

Medically Managed Detox Unit

P-value

0.06

2.4

3.1

0.01

400 mg

140 mg

<0.0001

Total gabapentin dose used (average)

1565 mg

3890 mg

<0.0001

Average time (hrs) until patients achieved a CIWA-ar score of 7 or less for at least 24 hrs

20.9 hrs

19.8 hrs

0.87

0.03

7.88

6.6

0.17

0.56

Total chlordiazepoxide equivalent dose used (average)

Delirium during treatment (# of patients) Initial CIWA-ar score (average) Max CIWA-ar score (average)

and the addiction medicine service MMDU. The study design was reviewed by the Institutional Review Board (IRB) at Ascension Wisconsin All Saints. The IRB did not feel that the study required formal review because the study did not involve an intervention that would otherwise not have occurred in the routine care of patients at each facility. Also, because the nature of the data being collected did not include any patient-specific identifiers. Potential patient date for inclusion into the study was identified via an electronic medical record search of The International Classification of Diseases (ICD-10) diagnostic codes (See Table 1) for alcohol use disorders, alcohol abuse, or alcohol withdrawal syndrome for all patients admitted to either the GMU or the MMDS. Inclusion criteria were as follows: all patients 18 years of age or older with a diagnosis of a moderate to severe alcohol use disorder who were primarily being admitted for the treatment of the (AWS). The data was collected and de-identified following chart review of all patient admitted for alcohol detoxification meeting inclusion criteria from Jan 1, 2016 thru Oct 31, 2016. Datum for patients was excluded if they met any of the following criteria: 1) A diagnosis of end stage liver disease as defined by a Model for End-stage Liver Disease score of 30 or greater, 2) A diagnosis of end stage renal disease, 3) Post organ transplant patients, 4) Patients admitted for treatment of a primary diagnosis other than an alcohol use disorder www.pswi.org

yet still needing alcohol withdrawal management, and 5) Patients who were initially admitted directly to the intensive care unit. The study assessed treatment regimens in a naturalistic setting to compare outcomes between a moderate-intensity gabapentin dose schedule (300 mg capsules four times per day with rapid titration to 600 mg three to four times per day as necessary) in conjunction with an alcohol withdrawal protocol utilizing a symptom-triggered benzodiazepine, versus management with lower dose (or no dose) gabapentin in conjunction with an alcohol withdrawal protocol utilizing symptomtriggered benzodiazepines in order to demonstrate the feasibility and efficacy of using gabapentin to reduce overall benzodiazepine dose without affecting primary outcomes. The primary endpoints included: total dosage of benzodiazepine used (calculated as a chlordiazepoxide dose equivalent); total dosage of gabapentin used; development of delirium or seizures during the withdrawal process after treatment was initiated; initial and maximum CIWA-ar scores; and the time (in hours) until the patient achieved a CIWA-ar score of 7 or below maintained for 24 hrs. The secondary endpoints included: actual length of stay and rate of “against medical advice” discharges. With respect to benzodiazepine dose equivalency all benzodiazepines utilized were converted to the equivalent chlordiazepoxide dose. This was accomplished using the following relationship - 100 mg of oral

chlordiazepoxide is equivalent to 4 mg of oral lorazepam.14 Patients with the highest risk for severe withdrawal are typically admitted to the GMU due to availability of monitoring equipment (such as telemetry, which is not available on the MMDU). In order to capture risk of withdrawal severity patients were risk stratified using the Prediction of Alcohol Withdrawal Severity Score (PAWSS), a predictive tool utilized to predict the severity of alcohol withdrawal.15,16 In this study, the investigators used the PAWSS scoring system in a retrospective manner to stratify patients to account for any difference in the risk of alcohol withdrawal severity among the two sites. Those individuals who scored a 3 or less were deemed to be at “low risk” for severe alcohol withdrawal and those that scored a 4 or greater were deemed to be at “high risk” for severe alcohol withdrawal. The average PAWSS score for each site was calculated and compared. In addition to risk stratification using the PAWSS scoring tool, the average initial blood alcohol level, patient age, and the average initial CIWA-ar score were compared between the two treatment sites to ensure that there was not a statistically significant difference in these measurements that could lead to confounding of the results. In regards to the statistical analysis the alpha level was set to 0.05 for the determination of significance. The gabapentin treatment protocol utilized on the MMDU was as follows: gabapentin started at a scheduled dose of 300 mg every 6 hours and titrated rapidly to 600 mg every 6-8 hours for symptom July/August 2018

The Journal 39

control over 24 hours in conjunction with symptom-triggered chlordiazepoxide 25-50 mg per hour based on the patients CIWAar score. No medication for CIWA-ar score < 8. Chlordiazepoxide 25 mg for a CIWAar score 8-12. Chlordiazepoxide 50 mg for a CIWA-ar score > 12. Clonidine 0.1 mg for systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg, with hold parameters for Heart Rate < 55 bpm. If patients were 65 years of age or older, or had renal insufficiency, then the chlordiazepoxide dosing was lowered to 5-10 mg. The gabapentin was adjusted per renal function by the physician on a case-by-case basis.

Results Using the ICD-10 Codes in Table 1, 66 patients admitted to the GMU group and 94 patients admitted to the MMDU group initially meet the inclusion criteria. However, 15 out of 66 patients in the GMU group and 7 out of 94 patients in the MMDU group were excluded due to having met one or more of the exclusion criteria. Baseline characteristics are shown in Table 2. Analysis of the data demonstrated that patients admitted to both treatment sites shared some similar characteristics including age (p-value 0.56), initial blood alcohol level (p-value 0.71), and initial CIWA-ar score (p-value 0.17). There was a difference in pre-admit seizures between the two groups with the GMU showing 9 and the MMDU showing 4 (p-value 0.02). The average PAWSS score on admission was also different with a score of 5 for the GMU group and 4.3 for the MMDU group. Both groups scored in the “high risk” category (PAWSS score 4 or greater) for alcohol withdrawal. However, the GMU group (score of 5) had a greater PAWSS score than the MMDU group (score of 4.3) with a p-value of 0.02. The total chlordiazepoxide equivalent dose used on average was 400 mg in the GMU group and 140 mg in the MMDU group, a difference that was statistically significant with a p-value of < 0.0001. As expected, the total gabapentin dose on average was lower in the GMU group than it was in the MMDU group, a difference that was also statistically significant with a p-value of <0.0001. The difference 40 The Journal

July/August 2018

between average length of time (in hours) until patients achieved a CIWA-ar score of 7 or less that was maintained for 24 hours was statistically non-significant (GMU group 20.9 hours, MMDU group 19.8 hours, p-value 0.87). A total of six patients experienced alcohol withdrawal delirium in the GMU group while only two patients experienced delirium in the MMDU Group, a difference that was statistically significant with a p-value of 0.03. No other medication usage data were collected for this study. A summary of all results are shown in table 3.

Discussion Alcohol withdrawal is an extremely unpleasant, and potentially life-threatening, experience for patients affected. It is a difficult and challenging acute condition that requires vigilant monitoring and appropriate pharmacologic interventions to prevent complications. The intervention for the MMDU group involved the use of the scheduled gabapentin along with as needed chlordiazepoxide protocol described earlier. The interventions used for the GMU group involved the utilization of lorazepam for symptom control based on physician specified parameters that varied based on the patient’s individual needs. The study was carried out to determine if the GMU group was in fact utilizing much higher doses of benzodiazepine than the MMDU group. This was confirmed by the finding that the difference between the two groups in this study was statistically significant favoring much lower average benzodiazepine dose utilization in the MMDU group. The study was also carried out to demonstrate that despite utilizing lower doses of benzodiazepines, the MMDU group’s outcome was similar to that of the GMU group. Not only did the study confirm similarity with the addition of scheduled gabapentin, but the rates of delirium were also statistically significantly lower in the MMDU group, a finding that was not expected. Generalizability of the study results may be limited by the study’s design and the presence of confounding variables. These confounding variables largely derive from the different unit locations. Nursing staff on the MMDU are more specialized in handling treatment of AWS compared to

those on the GMU and therefore affecting overall benzodiazepine utilization. However due to the fact that both groups use the same scoring tool for assessing CIWA-ar scores, it was felt that this variable was at least somewhat lessened. Due to the absence of any supporting data; however, this remains as a potential confounding variable. Additionally, the patients on the GMU had more medical comorbidities which could have played a role in overall treatment and affected the study results. However, it is not known the extent in which it was affected, which is why good clinical judgment remains important to overall treatment. Despite attempts to address confounding variables the design of the study does not allow one to make clear cause and effect assumptions regarding the use of gabapentin and the decrease in benzodiazepine utilization in the MMDU group. Other factors (including the higher PAWSS score in the GMU group) could have accounted for the difference in benzodiazepine use. While the difference in the PAWSS score between the groups was statistically significant favoring higher risk for severe alcohol withdrawal in the GMU Group, both groups had an average score of over 4 that was felt to be indicative of severe withdrawal risk. Another factor may include greater discrimination in CIWA-ar scoring by the nursing staff on the MMDU versus the GMU. Though this factor seems unlikely given that the average initial CIWA-ar score and the time to CIWA-ar less than 7 are statistically nonsignificant between the two groups.

Conclusion Based on the results of this study, it is appropriate to conclude that the use of scheduled gabapentin in conjunction with symptom-triggered chlordiazepoxide may decrease overall benzodiazepine utilization during alcohol withdrawal management without affecting outcomes. This is important because studies have demonstrated that gabapentin may improve rates of abstinence over use of benzodiazepines during detoxification in an outpatient setting. Additionally, further benefits from using gabapentin instead of benzodiazepines is the avoidance of the adverse drug reactions such as respiratory depression, increased fall risk, www.pswi.org

and increased confusion/delirium seen with many benzodiazepines. The results of this study do support the utilization of gabapentin for the treatment of more severe alcohol withdrawal. It is yet to be determined whether use of scheduled gabapentin, as is routine on the MMDU, would also lead to improved abstinence rates versus a traditional benzodiazepinesonly withdrawal protocol. Future research regarding the use of anticonvulsants, particularly gabapentin, should focus attention on this important question. In addition, this study suggests that the use of gabapentin was associated with a lower risk of delirium which should prompt further investigation into its use. Christopher Leuenberger is a former PGY-1 resident from Ascension Wisconsin - All Saints Hospital in Racine, WI. David Galbis-Reig is an Addiction Medicine Physician at Ascension Wisconsin - St. Luke's Hospital in Racine, WI. Steven Suokko is a Clinical Pharmacist at Ascnesion Wisconsin - All Saints Hospital in Racine, WI. Biniam Berhane is a former Clinical Pharmacist from Ascension Wisconsin - All Saints Hospital in Racine, WI . George Honein is a Clinical Pharmacist at Ascension Wisconsin - All Saints Hospital in Racine, WI. Disclosures: The author(s) declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript,

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including grants, equipment, medications, employment, gifts, and honoraria.

This article has been peer-reviewed. The contribution in reviewing is greatly appreciated!

References

1. Kosten T, O'Connor P. Management of drug and alcohol withdrawal. N Engl J Med 2003;348(18):1786-1795. 2. Hoffman P, Grant K, Snell L, et al. NMDA receptors: role in ethanol withdrawal seizures. Ann N Y Acad Sci. 1992;654:52-60. 3. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev.2010;(3):CD005063. 4. Hammond C, Niciu M, Drew S, Arias A. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorder. CNS Drugs. 2015;29(4):293-311. 5. Leung J, Hall-Flavin D, Nelson S, et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015;49(8):897-906. 6. Rustembegovic A, Sofic E, Tahirovic I, Kundurovic Z. A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome. Med Arh. 2004;58:5-6. 7. Myrick H, Malcolm R, Randall P, Boyle E, et al. A double-blind trial of gabapentin vs lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 2009;33(9):1582-1588. 8. Brower K, Kim M, Strobbe S, KaramHage M, et al. A Randomized double-blind pilot trial of gabapentin vs. placebo to treat alcohol dependence and comorbid insomnia. Alcohol Clin Exp Res. 2008;32(8):1429-1438.

9. Sachdeva A, Choudhary M, Chandra M. Alcohol withdrawal syndrome: benzodiazepines and beyond. Journal of Clinical and Diagnostic Research. 2015;9(9):1-6. 10. Barbara J, Susan Q, Vivian G, Farhad S, et at. Gabapentin treatment for alcohol dependence: a randomized controlled trial. JAMA Intern Med. 2014;174(1):70-77. 11. Rubio G, López-Muñoz F, Ponce G, et al. Zonisamide versus diazepam in the treatment of alcohol withdrawal syndrome. Pharmacopsychiatry. 2010;43(7):257-262. 12. Barrons R, Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther. 2010;35(2):153-167. 13. Muzyk A, Fowler J, Norwood D, Chilipko A. Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011;45(5):649-657. 14. Kane SP. Benzodiazepine Equivalents Conversion Calculator. ClinCalc: http://clincalc. com/Benzodiazepine/default.aspx. Updated June 3, 2017. Accessed December 2016. 15. Maldonado J, Sher Y, Das S, et al. Prospective validation study of the prediction of alcohol withdrawal severity scale (PAWSS) in medically ill inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2015;50(5):509-518. 16. Maldonado J, Sher Y, Ashouri J, Hills-Evans K, et al. The “prediction of alcohol withdrawal severity scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375-390.

July/August 2018

The Journal 41

2018

PSW Annual Meeting SAVE THE DATE August, 23-25, 2018 Kalahari Resort, Wisconsin Dells

42â&#x20AC;&#x192; The Journal

July/August 2018

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Registration PSW Annual Meeting • August 23-25, 2018

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Original Work

Assessment of Potential Drug Interactions That May Increase the Risk of Major Bleeding Events in Patients on Warfarin Maintenance Therapy by Meredith Kean, PharmD, Kori K. Krueger, MD, Brandon L. Parkhurst, MD, Richard L. Berg, MS, and Sara Griesbach, PharmD

Abstract Objectives: To assess whether drug interactions were present in patients on warfarin maintenance therapy who experienced a major bleeding event and assess which medications may increase the incidence of major bleeds. This information will be used to enhance prescription and monitoring protocols within the Marshfield Clinic Anticoagulation Service (ACS). Methods: A retrospective electronic record review of patients enrolled in the ACS on maintenance warfarin therapy between March 1, 2011 and September 30, 2014 was conducted to analyze adverse bleeding events. Cases were patients on warfarin therapy who experienced major bleeding events. Date of major bleeding event was used as a reference date to evaluate interaction potential of medications taken 30 days before the major bleeding event. Results: From a total of 115 drugs analyzed, 34 were significantly associated with major bleeding events with concurrent warfarin treatment (p < 0.05); 17 medications had previously documented warfarin drug interaction in MicromedexÂŽ. Analyses of medications initiated within 14 days before major bleeding event reference date identified furosemide, hydrocodone-acetaminophen, amoxicillin-clavulanate, acetaminophen, docusate, and metoprolol tartrate as significantly associated with major bleeding events (p < 0.05). Conclusions: Even when closely managed by an anticoagulation service, patients can experience major bleeding events due to potentially unknown/unrecognized drug interactions with warfarin. Further analysis of individual drug interactions with warfarin will determine if current protocols regarding warfarin medication management should be altered in relation to various drugs. 44â&#x20AC;&#x192; The Journal

July/August 2018

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arfarin is an anticoagulant that inhibits vitamin K epoxide reductase to prevent the synthesis of coagulation factors.1,2 Warfarin is highly bound to plasma proteins and has a half-life of 36 to 42 hours.3 Multiple cytochrome P450 (CYP) enzymes including CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4 metabolize warfarin in the liver.1 Warfarin is a racemic mixture of R and S enantiomers, of which the S enantiomer is approximately three times more potent in terms of anticoagulant properties than the R enantiomer.3 The S enantiomer is primarily metabolized by the CYP2C9 enzyme and to a lesser extent CYP3A4, while the R enantiomer is primarily metabolized by CYP1A2 and CYP3A4 and to a lesser extent by CYP2C19.3 Medications that increase bleeding on their own can cause pharmacodynamic interactions with warfarin. In addition to drug interactions, pharmacogenetics, variation in a patient’s diet and drugdisease interactions can also increase risk of major bleeding events.1 Warfarin has multiple documented pharmacokinetic and pharmacodynamic drug interactions that lead to increased bleeding risk.1,3 Medications that inhibit or induce CYP2C9, CYP1A2, and CYP3A4 can potentially cause drug interactions with warfarin.1 Inhibitors of one or more of these CYP enzymes increase patient risk for bleeding during warfarin treatment, while inducers of one or more of these enzymes increase patient risk for thromboembolism with concurrent warfarin treatment. Previous studies have demonstrated the importance of monitoring potential drug interactions with respect to risk management during warfarin therapy.4,5 However, it is unclear how much impact these potential interactions have with respect to bleeding risk in a well-managed patient population, where healthcare providers are actively monitoring for such interactions. The Marshfield Clinic Anticoagulation Service (ACS) manages approximately 10,000 to 11,000 patients on warfarin per 12 month period with a protocol driven service. Micromedex® is the drug database used most frequently to identify potential drug interactions. www.pswi.org

The goal of this study was to evaluate a population of patients enrolled in the Marshfield Clinic Anticoagulation Service (ACS) who experienced a major bleeding event while on warfarin and to assess the risk of an adverse bleeding event in the presence of drug interactions with warfarin.

Methods This retrospective study was approved by the Marshfield Clinic Institutional Review Board. The study included patients over the age of 18 years enrolled in the Marshfield Clinic ACS on maintenance warfarin therapy between March 1, 2011 and September 30, 2014. Maintenance therapy was defined as more than 30 days of warfarin therapy, and case subjects were those patients who experienced major bleeding events while taking warfarin. For this study, major bleeding events were defined as bleeding events resulting in hospitalization, blood transfusion, or death. The date of the major bleeding event was used as the reference date for evaluating the interaction potential of medications taken within 30 days prior to the major bleeding event. A frequency-matched group of control subjects was randomly selected from the same ACS population. Matching criteria included gender, age, and duration of warfarin therapy; the matching groups included five age categories (18–54 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years), two gender categories (male and female), and four categories for year of initial exposure to warfarin (before 2002, 2003–2007, 2008–2011, 2012–2014). In addition, a counterfactual event date was assigned to each control subject by randomly sampling (with replacement) the actual event dates of matched case subjects who experienced their major bleeding event at a time when both case and control patients were managed by the ACS. This method of assigning reference event dates was used to ensure comparable distributions of dates for the two groups. Patients who were bridged on enoxaparin within 2 weeks before the reference date were ineligible for either group. A list of newly prescribed medications within 2 weeks from the reference date was retrieved from the electronic health record (EHR) for all study subjects.

The start date for each newly prescribed medication was identified to verify the patient had not previously been on the medication. To determine which drugs could have contributed to the major bleeding event, all medications recorded in each patient's medication list within 30 days of the major bleeding event reference date were also abstracted from the EHR. The last International Normalized Ratio (INR) before the reference date was abstracted electronically for both case and control patient groups. The electronic data (including information for all bleeding events during the 30-day time period preceding the major bleeding event) were validated by manual review. In addition, patients were randomly selected for manual review of their eligibility and medication information. The criteria for the electronic retrievals were iteratively adjusted based on the manual review. Full manual review was performed for 70 case and 70 control subjects included in the final analysis. Potential warfarin drug interactions while taking oral medications was the primary focus this study. Of the generic name medications found during manual chart review, 85% were found both electronically and manually which was deemed acceptable. Other routes of administration for medications, such as transdermal, ophthalmic, or inhaled were not analyzed or included when assessing the total number of drugs the patient was taking 30 days prior to the reference date. Prescriptions for enoxaparin and phytonadione were not included in the final analysis of drug interactions with warfarin due to the use of these medications as a part of warfarin anticoagulation management. For example, if phytonadione was included in the study, it would have likely shown up in the analysis as a potential drug interaction, when in fact it is used as a reversal agent to warfarin. However, the patients that took phytonadione were included in the study. The primary statistical analyses were based on multiple logistic regression models with the case/control indicator as a binary response. These models included the matching criteria and the exact age as covariates with a drug indicator as the predictor of primary interest. To prevent convergence problems and to limit spurious July/August 2018

The Journal 45

TABLE 1. Drugs on Medication List in Order of Descending Odds Ratio Generic Drug Name

No. of Case Group Patients on Drug (%)

No. of Control Group Patients on Drug (%)

Odds Ratio (95% Confidence Interval)

P-value

A. 30 days prior to the reference date Oxycodone

62 (8.1)

15 (2)

4.5 (2.6-8.2)

<0.001

Prochlorperazine

37 (4.8)

12 (1.6)

3.4 (1.8-6.8)

<0.001

Levofloxacin*

41 (5.3)

13 (1.7)

3.3 (1.8-6.6)

<0.001

Dextromethorphan-guaifenesin

23 (3.0)

7 (0.9)

3.3 (1.5-8.3)

0.007

Clopidogrel*

16 (2.1)

5 (0.7)

3.3 (1.3-10.1)

0.022

Oxybutynin chloride

36 (4.7)

12 (1.6)

3.1 (1.7-6.3)

<0.001

Pregabalin

15 (2.0)

5 (0.7)

3.1 (1.2-9.7)

0.029

Gemfibrozil*

26 (3.4)

9 (1.2)

3.0 (1.4-6.7)

0.006

Baclofen

15 (2.0)

6 (0.8)

2.8 (1.1-8.1)

0.037

Calcitriol

17 (2.2)

6 (0.8)

2.8 (1.2-7.9)

0.031

Metolazone

32 (4.2)

12 (1.6)

2.7 (1.4-5.6)

0.003

Amoxicillin-clavulanate*

30 (3.9)

12 (1.6)

2.6 (1.4-5.4)

0.005

Ferrous sulfate

120 (16)

53 (6.9)

2.5 (1.8-3.6)

<0.001

Ibuprofen*

17 (2.2)

7 (0.9)

2.4 (1.1-6.4)

0.049

Diphenhydramine-acetaminophen*

25 (3.3)

12 (1.6)

2.2 (1.1-4.5)

0.029

Hydrocodone-acetaminophen*

167 (22)

88 (11)

2.2 (1.6-2.9)

<0.001

Cephalexin*

30 (3.9)

14 (1.8)

2.2 (1.2-4.3)

0.018

Ondansetron

40 (5.2)

20 (2.6)

2.1 (1.2-3.7)

0.010

Glimepiride*

34 (4.4)

17 (2.2)

2.0 (1.1-3.8)

0.019

Paroxetine*

28 (3.6)

14 (1.8)

2.0 (1.1-4.0)

0.034

Amoxicillin*

73 (9.5)

41 (5.3)

1.9 (1.3-2.9)

0.001

Amiodarone*

38 (4.9)

20 (2.6)

1.9 (1.1-3.4)

0.021

Loperamide

42 (5.5)

23 (3.0)

1.9 (1.1-3.2)

0.019

Acetaminophen*

373 (49)

267 (35)

1.8 (1.5-2.3)

<0.001

Citalopram*

66 (8.6)

39 (5.1)

1.8 (1.2-2.7)

0.006

Polyethylene glycol 3350

57 (7.4)

34 (4.4)

1.7 (1.1-2.7)

0.017

Furosemide

397 (52)

299 (39)

1.7 (1.4-2.1)

<0.001

Isosorbide mononitrate

89 (12)

56 (7.3)

1.7 (1.2-2.4)

0.006

Omeprazole*

259 (34)

190 (25)

1.6 (1.2-1.9)

<0.001

Allopurinol*

73 (9.5)

49 (6.4)

1.5 (1.1-2.3)

0.027

Gabapentin

97 (13)

67 (8.7)

1.5 (1.1-2.1)

0.015

Aspirin*

194 (25)

144 (19)

1.5 (1.2-1.9)

0.002

Amlodipine

129 (17)

99 (13)

1.4 (1.0-1.8)

0.039

Metoprolol tartrate

209 (27)

167 (22)

1.3 (1.1-1.7)

0.014

Furosemide

11 (1.4)

2 (0.1)

11.4 (2.2-208.2)

0.020

Hydrocodone-acetaminophen*

17 (2.2)

3 (0.4)

5.8 (1.9-25.0)

0.005

Amoxicillin-clavulanate*

10 (1.3)

2 (0.3)

5.6 (1.5-36.7)

0.028

Docusate sodium

11 (1.4)

2 (0.3)

5.4 (1.4-35.0)

0.029

Acetaminophen*

16 ( 2.1)

3 (0.4)

5.3 (1.8-23.1)

0.008

Metoprolol tartrate

11 (1.4)

3 (0.4)

3.7 (1.1-16.4)

0.047

B. Within 14 days of the reference date

*Documented as a drug interaction with warfarin in MicromedexÂŽ

46â&#x20AC;&#x192; The Journal

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associations based on few observations, analyses of drugs in the 30-day period prior to the reference date were limited to those drugs reported for at least 20 of the 1,538 total subjects, while analyses of drug changes in the prior 14 days were limited to those with at least 10 subjects. Results from the logistic regression models were summarized with adjusted odds ratios and confidence limits for each drug of interest. These analyses represent preliminary screening for a large number of potential drug interactions, and the results were not adjusted for multiple comparisons. As such, although the results are presented at the nominal 5% level of statistical significance (p < 0.05, per drug), the overall rate of false positive associations may be substantially higher.

Results The final study population included 769 validated case subjects with major bleeding events and 769 matched control subjects. Each group included 404 males (52.5%), and the mean age in years at the reference date was 76.8 (SD 11.6) and 76.5 (SD 12.3) in the case and control groups, respectively. The study population was almost exclusively Caucasian (only two case subjects and one control subject were identified as African-American), which is consistent with the general population of the health system. From a total of 115 drugs analyzed from patient electronic medication lists 30 days prior to the major bleeding event reference date, 34 drugs were significantly associated with major bleeding events with concurrent warfarin treatment (p < 0.05). Of these 34 drugs, 17 had a previously documented drug interaction with warfarin in the Micromedex® drug information database (Table 1a).6 Further analysis of medications initiated within 14 days before the major bleeding event reference date identified six medications from among 12 total medications analyzed that had significant associations with major bleeding events ( p < 0.05; Table 1b). Three of the six medications have documented drug-drug interactions with warfarin according to the Micromedex® database.6 The case group (N=769), on average, had more oral medications on their www.pswi.org

TABLE 2. Most Recent INR* Result Prior to the Reference Date INR* Range

No. of Case Group Patients (%) N=769

No. of Control Group Patients (%) N=769

Total (%) N=1538

≤1.5

29 (3.8)

24 (3.1)

53 (3.4)

1.6-1.9

77 (10.0)

92 (12.0)

169 (11.0)

2.0-3.0

465 (60.5)

556 (72.3)

1021 (66.4)

3.1-3.9

107 (13.9)

74 (9.6)

181 (11.8)

4.0-4.9

52 (6.8)

18 (2.3)

70 (4.6)

5.0-8.9

29 (3.8)

5 (0.7)

34 (2.2)

≥9

10 (1.3)

0 (0)

10 (0.7)

*INR = International Normalized Ratio

medication list and higher INRs prior to the reference date than the control group (N=769). The mean total number of drugs identified per patient was 10.5 drugs in the case group (median 10.0; range 1.0-27.0), compared to 8.2 drugs in the control group (median 8.0; range 0.0-22.0; p<0.001). The mean number of drugs on the medication list associated with major bleeding (those shown to be statistically significant) in the case group was 3.9 (median 4.0; range 0.0-12.0), compared to 2.4 drugs in the control group (median 2.0; range 0.0-10.0; p<0.001). The patients in the case group also had a higher frequency of INRs ≥3.0, including ten patients with an INR ≥9.0. No patients in the control group had an INR >9.0 (Table 2).

Discussion Even though warfarin is closely monitored by many health systems, major bleeding events still occur in patients on warfarin. More attention may be required for a variety of medications that have the potential to interact with warfarin. For starters, when looking at medications that may acutely increase bleeding risk, each of the six medications found to have statistical significance when initiated within 14 days of the reference date could be examined further. For example, although acetaminophen has a documented drug interaction with warfarin, it may be beneficial to place additional focus on assessing potential risk factors, number of medications, patient education and INR monitoring. The same applies for the other documented interactions previously

described. As far as the medications considered as undocumented interactions with warfarin in Micromedix®, further research will be needed to determine their clinical significance.6 Accessing a second drug information database as a standard of practice may also be recommended. For patients that experience a major bleed, not only individual drugs, but also the number of potentially interacting medications should receive attention. The drugs found to be on the patient’s medication list 30 days before the major bleeding event should be further analyzed. In the meantime, this study attempts to raise awareness of other medications on the market that may need to be considered when a patient is on warfarin, especially if the patient is on several of the medications in this study. Of the 34 medications in this study associated with major bleeding events in conjunction with warfarin maintenance therapy, 17 were documented as having drug interactions with warfarin in the Micromedex® drug information database. However, not all drug information databases list the same drug interactions. It is possible there are more drug interactions with warfarin that could increase risk of bleeding than currently documented in the Micromedex® database and using more than one drug knowledge database may be beneficial. Another possible explanation for the apparent discrepancy between the listed drug-warfarin interactions could be due, in part, to procedural and statistical limitations of this study. When conducting a single institution July/August 2018

The Journal 47

medication assessment study with limited demographics (mostly Caucasian patients) and many medications, there is an increased risk for falsely detecting medication interactions. Our ability to statistically evaluate meaningful adverse drug interactions with warfarin was limited by the number of patients exposed to a particular drug and to the observed events attributable to that drug. In a system where a patient’s warfarin therapy is closely managed, as in this study, the warfarin dose could be proactively lowered to prevent a thromboembolic event in response to a drug that is well-known to adversely interact with warfarin or increase INR values, perhaps reducing the likelihood that well-recognized drug interactions will show significant associations with bleeding. There is also the chance that the disease state itself could increase a patient’s risk for a major bleeding event. For example, anemia is a known risk factor for increased bleeding risk.7 Another example is furosemide, where the interaction could be due to worsening heart failure increasing the patient’s sensitivity to warfarin, thereby increasing bleeding risk.8 However, these medications can still be important in managing warfarin in that they can serve as an indicator of a compounding drugdisease interaction that may need to be assessed. The number of medications can also represent the number of compounding diseases a patient may have. In addition to this, pharmacogenomics may also impact the patient’s bleeding risk. Given the large number of drugs observed, limited sample demographics, and the possibility of confounding variables such as disease state or diet with respect to increasing INR values, we are cautious in our interpretation of statistical analysis for this study. In addition to statistical limitations, there are also some procedural limitations with this study, including the inability to assess for medication adherence. In addition, some of the case patients may have had a recent non-major bleeding event and therefore been more likely to have been evaluated by a healthcare provider recently and may have received more medications and monitoring in the 14 day period preceding the major bleeding event. When determining if a major adverse bleeding event initially entered into the ACS database was an actual 48 The Journal

July/August 2018

major adverse bleeding event (as defined by a hospitalization, blood transfusion, or death) there is a chance for human error in data entry as well as classification bias. Since only patients with adverse bleeding events treated at Marshfield Clinic were included in this study, all major bleeding events may not have been reported to the Marshfield Clinic ACS if a patient went to an outside facility. Medication changes from non-Marshfield Clinic providers may not be reflected in the medication database, or these providers may not adhere to the same procedures and monitoring practices as Marshfield Clinic ACS personnel. Future directions include further assessment of individual medications without a currently documented interaction with warfarin and potential confounders based on worsening disease states. Additional drug information databases could be used to further define documented interactions. Also, a goal would be to collect more information and compare disease states between the case and the control group. Due to limited resources and what was accessible in the medical record, we were limited on what characteristics patients could be case matched on. In a future study matching patients based on other bleed risk factors such as HASBLED or ATRIA scores may be beneficial.

Conclusion Even when patients are closely managed by an anticoagulation service, major bleeding events may still occur due to potentially unknown/unrecognized drug interactions with warfarin. Although the patients in this study were monitored for thromboembolic risk, patients in the case group had somewhat higher INRs as compared to the control group. Further analysis of individual drug interactions with warfarin will determine if current protocols regarding warfarin medication management should be altered in relation to various drugs. The results of this and future studies will be used to review the current protocols for managing warfarin drug interactions. Meredith Kean conducted this project during her PGY1 pharmacy residency at Marshfield Clinic. She currently works as a pharmacist at Family Health Center, Marshfield Clinic Health System in Marshfield, WI. Kori Krueger and

Brandon Parkhurst are Doctors at Marshfield Clinic in Marshfield, WI. Richard Berg is a Senior Biostatistician at the Marshfield Clinic Research Institute, Marshfield, WI. Sara Griesbach is a Clinical Pharmacist at Marshfield Clinic in Marshfield, WI.

This article has been peer-reviewed. The contribution in reviewing is greatly appreciated!

Disclosures: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Funding: Funding for this study was provided by Marshfield Clinic’s Division of Education Resident Research Program. Acknowledgements: The authors would like to acknowledge Debra Kempf, Marshfield Clinic Resident Research Facilitator, Connie Folz, Marshfield Clinic Investigational Drug Pharmacy, Melissa Mikelson, Marshfield Clinic Anticoagulation Service, and Marie Fleisner, Marshfield Clinic Research Foundation Office of Scientific Writing and Publication.

References

1. Coumadin® (warfarin sodium) [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2011. 2. Hauta-Aho M, Tirkkonen T, Vahlberg T, Laine K. The effect of drug interactions on bleeding risk associated with warfarin therapy in hospitalized patients. Ann Med. 2009;41(8):619-628. 3. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G; American College of Chest Physicians. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. 4. Gasse C, Hollowell J, Meier C, Haefeli W. Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin. Thromb Haemost. 2005;94(3):537-543. 5. Snipelisky D, Kusumoto F. Current strategies to minimize the bleeding risk of warfarin. J Blood Med. 2013;4:89-99. 6. Warfarin. Micromedex [Internet database]. Tampa (FL): 2014. Available with subscription from: www.micromedexsolutions.com. 7. Westenbrink BD, Alings M, Connolly SJ, et al. Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE-LY trial. J Thromb Haemost. 2015;13(5):699-707. 8. del Campo M, Roberts G. Changes in warfarin sensitivity during decompensated heart failure and chronic obstructive pulmonary disease. Ann Pharmacother. 2015;49(9):962-968.

www.pswi.org

Original Work

A Physician Survey of Antimicrobial Stewardship Culture and Use of Antimicrobial Resistance Data and Resources by Laurel M. Legenza, PharmD, MS, Susanne G. Barnett, PharmD, BCPS, and Warren E. Rose, PharmD, MPH

ntimicrobial resistance (AMR) is a serious threat to global public health according to the World Health Organization.1 If existing trends are not disrupted, AMR estimated deaths could total 10 million globally per year, with $100 trillion dollars in lost productivity by 2050.2 Variations in AMR occur globally, nationally and locally due to multiple patient, social, and system factors. In a surveillance study across Wisconsin, regional and organism variations in antibiotic resistance were observed near urban centers.3 Antibiotics are key in treating bacterial infections, but they are commonly misused and unnecessarily prescribed.4 According to the Centers of Disease Control (CDC) and a recent study of 184,032 outpatient visits, opportunity exists to improve the appropriate prescribing patterns of antibiotics in both inpatient and outpatient healthcare settings.4,5 Pharmacists are pivotal to ensuring appropriate use of antimicrobials and are often key contributors to and leaders of stewardship programs.6 The CDC’s Core Elements of Hospital Antibiotic Stewardship Programs include appointing a single pharmacist leader responsible for working to improve antibiotic use.7 Progressive antimicrobial stewardship teams are increasingly interdisciplinary, including front-line staff, and shifting from a raising awareness approach to a shared responsibility approach for improved antibiotic use.8-10 Many health systems document local AMR in the form of an antibiogram displaying bacterial susceptibility to select antibiotics.11 Antibiograms are essential for antimicrobial stewardship, and they serve as a local resource to practitioners to facilitate www.pswi.org

Abstract Objectives: To describe the physician-perceived functionality of antimicrobial resistance (AMR) data resources and use in practice by identifying (1) the types and quality of AMR resources and frequency of use in practice and (2) the current antibiotic stewardship culture across the state of Wisconsin. Methods: An online survey evaluating physician use of AMR data resources and stewardship culture was distributed to Wisconsin Medical Society members. Results: Online resources were the most commonly used AMR resource, with 38% of antibiotic prescribers reporting at least weekly use (n=16). Antibiograms, reference books, and literature searches were only used at least weekly by 13% of respondents. Respondent ranking (1=not at all, 7=very) for AMR data accessibility (mean 4.3±2.1), availability (4.4±2.2), functionality (4.8± 2.1), and interpretability (4.9± 2.0) averaged slightly above ‘somewhat’. ‘Antibiotic use monitoring’ was the most recognized stewardship intervention, being employed often or always in 57% (n=12) of respondent’s practice sites. Of antimicrobial stewardship interventions, both sample taken for culture before antibiotic treatment and de-escalation were reported by 53% of respondents as being present often or always. ‘Prospective audit and feedback’ and ‘antibiotic use data reported to clinicians’ were the least common stewardship interventions. Conclusions: Opportunities exist for improving accessibility and quality of AMR resources in Wisconsin. Strengthening of prospective audit and feedback interventions and antibiotic use data provided to clinicians is needed. Pharmacists should be key contributors to antimicrobial stewardship efforts across practice settings.

empiric antibiotic selection.12 However, functionality and practice gaps may exist in the availability and use of antibiogram data by practitioners. The objective of this study was to describe the physicianperceived functionality of AMR data resources and use in practice by identifying (1) the types and quality of AMR

resources and frequency of use in practice, (2) the current antibiotic stewardship culture across the state of Wisconsin, including common stewardship strategies implemented in practice, and opportunities for improvement in current AMR resources and its use. July/August 2018

The Journal 49

TABLE 1. Survey Respondent Demographics and Characteristics

Variable

Survey Question Respondents (%)*

Number of Respondenets

Frequency of Prescribing Systemic Antibiotic

Rarely, 0-2 Times Per Week

Occasionally, 3-4 Times Per Week

A Least Daily, 5-30 Times Per Week

Frequently, 30+ Times Per Week

Never

Total (n)

25-34 years

35-44 years

19%

45-54 years

25%

55-64 years

38%

65 years or older

13%

Number of Respondenets

Time with electronic medical record (EMR) open during patient visits Yes - always

67%

Yes - >50% of the time

Sometimes, <50% of the time

27%

No EMR use during visits Number of Respondenets

Type of antibiograms available at respondents' health system (if available) Inpatient

69%

Outpatient

38%

ICU

31%

Transplant

Pediatrics ICU

Emergency Department

Trauma and life support

No antibiogram at health system

19%

16*

Number of respondents (n=16)

Respondent practice areas: general/internal/family medicine (n=7), emergency medicine (n=2), hospitalist (n=1), otolaryngology and allergy (n=1), private practice (n=1), occupational medicine (n=1). *Percentages rounded to whole number may total >100%. *Multiple types of antibiograms were reported by the sixteen respondents.

Methods This study is a survey of Wisconsin physicians regarding current availability and use of AMR resources, and practice site culture of antimicrobial stewardship. The University of Wisconsin-Madison Health Sciences Institutional Review Board exempted the study from further ethical approval. Survey Questions Survey questions were developed by the pharmacists conducting this antimicrobial stewardship research with input from a small, multidisciplinary group of infectious diseases healthcare providers (infectious 50 The Journal

July/August 2018

disease physicians, fellows, residents, a nurse practitioner, and a medical student). Survey questions included 5-point and 7-point unipolar scales as determined to be appropriate by survey developers. An individual not involved with the design of the survey reviewed the survey to identify any items that needed further clarification. The survey collected information about 1) respondent demographics, 2) knowledge of AMR, 3) the use and availability of AMR resources (type and frequency of use), 4) quality of available AMR data, 5) antimicrobial stewardship culture and activities present at the participant's practice. This study defines antimicrobial

stewardship culture as the antimicrobial stewardship attitudes and practices that characterize a healthcare setting. Questions asked about a participant’s individual workplace setting, such as a practice site and their health system as a whole (ex. system hospitals and clinics). The survey was designed to be completed by physicians who prescribe antibiotics, with branch logic to customize a respondent’s path through the survey (Online Supplement). The survey totaled 24 questions with a five to ten minutes estimated completion time. An initial survey question asked participants how frequently he/she prescribes antibiotics. www.pswi.org

FIGURE 1. Reported Frequency of Resources Used Over Previous Twelve Months (n=16)

Respondents who reported he/she never prescribe antibiotics were directed to questions about antimicrobial stewardship culture and AMR knowledge at their workplace and were not asked specific questions about resources used when prescribing antibiotics. Questions about use of AMR resources, specifically antibiograms, were not displayed for a participant if he/she indicated their health system did not have an antibiogram. Survey Recruitment and Participants Wisconsin Medical Society members were invited to participate in a voluntary, electronic Qualtrics® survey distributed via email in the Wisconsin Medical Society newsletter, ‘Medigram’, on June 2, 2016, with a reminder being sent on June 23, 2016. The survey remained open for four weeks following the initial invitation. The Online Supplement can be found here: https://www.jpswi.org/jpswja18_supplement. html

Statistical Analysis Demographic data were summarized with Excel and Qualtrics® as observed frequencies and percentages. Descriptive statistics were calculated for questions that have range responses (ex. 1-7). Multiple choice options were summarized as percentages of respondents for each question. Data was also summarized by practice area and frequency of prescribed antibiotics. Types of resources available www.pswi.org

were reported as the percent of respondents who had access to each type of resource, and the frequency of use from those who had access.

Results Twenty-one Wisconsin physicians provided survey responses, including 16 antibiotic prescribing respondents. Sixteen respondents, including two of the non-antibiotic prescribing physicians, completed the demographics section (Table 1). Sample size varied for each question as a response was not required for every question to complete the survey. The most common age group reported was 55-64 years (38%) with 75% of respondents being male. The majority of respondents (67%) kept an electronic medical record (EMR) open during patient visits. When asked about knowledge of AMR on a unipolar 5-point awareness scale (1=not at all, 3=somewhat, 5=extremely aware), awareness was highest for incidence of resistance of common pathogens (mean 3.1±1.3), followed by antibiotic specific resistance patterns (mean 3.0±1.2), pathogen specific resistance trends (mean 2.8±1.3), local changes in resistance by county (mean 2.7±1.3), and incidence of resistance for less common pathogens (mean 2.7±1.2); statewide distribution of antibiotic resistance had the lowest average awareness rating (mean 2.5±1.3, n=21). Online resources were the most commonly used type or AMR resource, with 38% of antibiotic prescribing respondents reporting at least weekly use

(Figure 1). Antibiograms, reference books, and literature searches (an alternative to a specific resource) were only used at least weekly by 13% of the respondents. Antibiograms were available to 69% of antibiotic prescribing respondents, of whom 36% estimated use of 1-2 times per month and another 36% estimated use of 0-2 times per year. Respondents were reportedly either self-taught (47%, n=7) or untrained (20%, n=3) in the use of antibiogram data; 33% (n=5) received training from someone else. When asked to describe their training one respondent stated their ID rotation in medical school was very helpful, while another respondent stated they would greatly appreciate training on AMR data. An independent provider added they no longer have access to AMR data since leaving a practice within a health system with a hospital. Antibiotic prescribing respondents (n=16) were asked to consider the quality of AMR data in their practice environment in terms of accessibility, availability, functionality, and interpretability on a 7-point unipolar scale (1=not at all, 4=somewhat, 7=very). Data interpretability (mean 4.9± 2.0) and functionality (mean 4.8± 2.1) ranked more favorably than data availability (mean 4.4±2.2) and accessibility (mean 4.3±2.1). When asked how much the respondent’s health system or practice maintains a culture of antimicrobial stewardship (5-point unipolar scale: 1 = not at all, 3 = a moderate amount, 5 = a great deal), the fourth option, ‘quite a lot’, was the most common response (33%, n=7/21). ‘Antibiotic use monitoring’ was the most recognized stewardship intervention, being employed often or always in 57% (n=12) of respondent’s practice sites (Figure 2). Both sample taken for culture before antibiotic treatment and de-escalation were also reported by 53% of respondents as being present often or always. ‘Prospective audit and feedback’ and ‘antibiotic use data reported to clinicians’ were the least common stewardship interventions. When asked how much changing the presentation of AMR data with visualizations would improve the translation of AMR data into practice on a 5-point scale (0 = not at all, 3 = somewhat, 5 = a great deal), the majority July/August 2018

The Journal 51

FIGURE 2. Reported Responses to Type(s) of Antimicrobial Stewardship Components Present? (n=21)

of respondents indicated ‘a great deal’ (57%, n=12). Discussion The results of our survey identify an opportunity to improve frequency of AMR data use in practice and AMR data quality, especially improving data access and availability. The physicians surveyed used online resources more frequently than local antibiograms for AMR data. Use of local AMR data, including antibiogram data, may be improved with a clear pathway for online access. Education on interpretation of antibiogram data may facilitate increased frequency of use and appropriate antibiotic prescribing considering local antibiotic resistance. These results and the survey comments also identified an opportunity to improve knowledge of AMR resource availability. The results of this study are consistent with a survey to spinal cord injury physicians finding deficits in antibiogram access and awareness.13 The 2016 guidelines for implementing an antibiotic stewardship program recommend the development of stratified antibiograms (e.g. by age or location) to reveal susceptibility differences.12 Educating clinicians about AMR and optimal prescribing is also one of the CDC Core Elements of Hospital Antibiotic Stewardship, now required 52 The Journal

July/August 2018

for reimbursement from the Centers for Medicare and Medicaid Services and included in the Joint Commission Antimicrobial Stewardship Standard.7,14 Regular reporting of antibiotic resistance to providers is also a CDC Core Element that could be achieved with improved AMR data resources. This regulatory climate necessitates pharmacist leadership within antimicrobial stewardship teams to achieve the Core Elements and provide needed education. The extent of antimicrobial stewardship culture and strategies implemented are variable across Wisconsin. Achievements include high reporting of antibiotic use monitoring, samples taken for culture before antibiotic treatment, and the use of de-escalation. Similar to a national antibiotic stewardship survey, prospective audit and feedback remains the area of greatest opportunity in antimicrobial stewardship program implementation.15 Pharmacists are the drivers of antimicrobial stewardship interventions. The survey developed and results could be a valuable tool for pharmacy departments to benchmark currently available AMR resources and stewardship strategies and may provide justification for adding or expanding an antimicrobial stewardship program. A low response rate may have

confounded the data. The survey was expected to reach 14,000 Wisconsin Medical Society members. Practitioners involved in antimicrobial stewardship initiatives or interested in antibiotic resistance potentially were biased toward favorable results by their propensity to respond to the focused survey. Although the response rate was low, physician satisfaction with AMR data resources varied greatly among respondents, suggesting diversity in the respondent AMR expertise and resource access. For example, responses to data availability included both ‘not at all’ and ‘very’. More than 50% of respondents stated they worked in general, internal, or family medicine, and were current antibiotic prescribers (Table 1). The survey results and answers are subject to interpretation by the respondents. The survey questions were developed by the research team due to a lack of AMR resource surveys published in the literature. Therefore, these results need further validation through additional distributions, including to pharmacists and other healthcare professionals. We subsequently scaled this initial pilot survey in Wisconsin to a multidisciplinary national distribution.

Conclusion As national efforts accumulate to address the threat of AMR, the results www.pswi.org

of this survey identified a lag in access to AMR quality data. Results of this survey support improving the availability and quality of online AMR data resources and education about interpretation or translation of data into practice. High quality AMR resources should be available to all healthcare providers across the continuum of care. Pharmacists have a responsibility to ensure appropriate antimicrobial use in all practice settings. Pharmacists can also be instrumental in antimicrobial stewardship education efforts now mandated by multiple regulatory agencies. The results identify areas of opportunity for pharmacists in increasing stewardship strategies, such as prospective audit and feedback. These efforts may increase appropriate antibiotic prescribing and strengthen antimicrobial stewardship across Wisconsin. Laurel Legenza is a Comparative Health Systems Global Pharmacy Fellow at the University of Wisconsin-Madison School of Pharmacy in Madison,WI. Susanne Barnett and Warren Rose are Associate Professors (CHS) at the University of Wisconsin-Madison School of Pharmacy in Madison,WI.

This article has been peer-reviewed. The contribution in reviewing is greatly appreciated!

www.pswi.org

Disclosures: The authors declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Acknowledgements: We appreciated the opportunity to present survey results at the Pharmacy Society of Wisconsin Annual (PSW) Meeting, Waves of Change, in Wisconsin Dells, Wisconsin on August 26, 2016. We thank the Wisconsin Medical Society for their collaboration to conduct this research. Legenza had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

References

1. World Health Organization. Antimicrobial Resistance Fact Sheet. Avaiable at: http://www. who.int/mediacentre/factsheets/fs194/en/ Updated February, 15 2018. Accessed May 18, 2018. 2. Oâ&#x20AC;&#x2122;Neill J. Review on antimicrobial resistance: tackling a global health crisis initial steps. https://amr-review.org/sites/default/files/ Report-52.15.pdf. Published February 2015. 3. Munson E, Block TK, Bowles EJ, et al. Surveillance of Wisconsin antibacterial susceptibility patterns. WMJ. 2016;115(1):29-36. 4. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17):1864-1873. 5. Fridkin S, Baggs J, Fagan R, et al. Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014;63(9):194-200. 6. ASHP statement on the pharmacist's role in antimicrobial stewardship and infection prevention and control. Am J Health Syst Pharm. 2010;67(7):575-577.

7. Pollack LA, Srinivasan A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis. 2014;59(Suppl 3):S97-100. 8. Kapadia SN, Abramson EL, Carter EJ, et al. The expanding role of antimicrobial stewardship programs in hospitals in the United States: lessons learned from a multisite qualitative study. Jt Comm J Qual Patient Saf. 2018;44(2):68-74. 9. Haas MK, Dalton K, Knepper BC, et al. Effects of a syndrome-specific antibiotic stewardship intervention for inpatient community-acquired pneumonia. Open Forum Infect Dis. 2016;3(4):ofw186. 10. Srinivasan A. Antibiotic stewardship grows up. Jt Comm J Qual Patient Saf. 2018;44(2):65-67. 11. Zapantis A, Lacy MK, Horvat RT, et al. Nationwide antibiogram analysis using NCCLS M39-A guidelines. J Clin Microbiol. 2005;43(6):2629-34. 12. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-77. 13. Evans CT, Rogers TJ, Burns SP, et al. Knowledge and use of antimicrobial stewardship resources by spinal cord injury providers. PM R 2011;3(7):619-623. 14. Joint Commission on Hospital Accreditation. APPROVED: new antimicrobial stewardship standard. Jt Comm Perspect. 2016;36(7):1, 3-4, 8. 15. The Advisory Board Company. Survey of antibiotic stewardship programs. Accessed January 2016.

July/August 2018

The Journal 53

Writing Club

Spotlight

UNIVERSITY OF WISCONSIN-MADISON SCHOOL OF PHARMACY STUDENT WRITING CLUB:

Business Member Spotlight: Boscobel Pharmacy by Alanna Benaszeski, 2019 PharmD Candidate, Andrea Grey, 2020 PharmD Candidate, Michael D Heltne, 2020 PharmD Candidate, and Musetta Steinbach, 2020 PharmD Candidate

Day to Day Practice Boscobel Pharmacy is a full-service pharmacy, committed to offering a consistent care process to each patient who walks through the door. Services offered range from dispensing, medication flavoring, and compounding, to offering durable medical equipment, nebulizers, sleep apnea supplies, portable oxygen, and hospital beds. The pharmacists take pride in meeting patient and community needs, and having the supplies to do so. The day-to-day work environment is best described as dynamic, with staff maintaining the flexibility to crossover between departments in emergencies or staffing challenges. Along with the three staff pharmacists, Boscobel Pharmacy employs seven pharmacy technician full time equivalents (FTEs), five pharmacy assistant FTEs, and two bookkeeping FTEs. The bookkeeping department is tasked with issues that take longer to resolve. Some examples include prior authorizations or insurance complications that are outside of the technician workflow. This allows technicians to spend more time focusing directly on patient needs. Pharmacy assistants conduct over-thecounter product and gift merchandising as well as marketing activities. Boscobel Pharmacy believes that having many “prongs in the wheel” improves the patient care process. Michelle Farrell, PharmD, BCACP, began her career as a pharmacist at Boscobel pharmacy in 2000, and became owner of the pharmacy in 2011. Dr. Farrell grew up in a nearby community, and finds her practice especially rewarding due to the relationships she is able to establish with her patients. She remains active on the Boscobel Chamber of Commerce, is a former President of the Pharmacy Society of Wisconsin (PSW), and current Chairman of the Board. Her membership and involvement with PSW 54 The Journal

July/August 2018

has shaped and informed her pharmacy practice throughout the years. For example, Dr. Farrell recalls the movement toward immunization legislation when she graduated from pharmacy school. Since that time, PSW has progressed to dialogue concerning collaborative practice and non-vaccine injectables. Ideas and implementation designs for many of Boscobel Pharmacy’s programs including medication synchronization, immunization protocols, refill agreements, therapeutic substitution agreements, and most recently a tobacco cessation collaborative practice agreement, were provided by PSW. Additionally, the Wisconsin Pharmacy Quality Collaborative (WPQC) program has shaped the patient care process, improved transitions of care and comprehensive medication reviews, and enhanced safety in Boscobel Pharmacy. Finally, Dr. Farrell particularly values the networking opportunities and awareness that PSW has provided her practice.

Raising the Bar Dr. Farrell and her team at Boscobel Pharmacy are improving patient care in many ways and exploring new pharmacy practice models. Currently, they are participating in the PSW pilot program: Tech-Check-Tech. Over the past year, two pharmacy technicians have become TechCheck-Tech certified, and four additional technicians are completing requirements. By implementing Tech-Check-Tech, it has allowed the pharmacists at Boscobel Pharmacy to focus on and expand patient care programs like the comprehensive medication reviews, immunizations, and medication synchronization. Besides working on internal projects, Boscobel pharmacy has maintained a strong connection with local hospitals and clinics to further improve the patient experience. The relationship established with Gundersen Boscobel Area Health

Care allows the pharmacy Epic link access, ensuring smooth transitions of care. The pharmacy team works with clinic nurses to coordinate adherence issues and medical equipment needs. Collaboration with physicians involves three currently established protocols. Other ties to the community include a scholarship offered for high school seniors and shadowing opportunities designed with the hopes of increasing interest in rural health care careers.

Bumps in the Road Boscobel Pharmacy has implemented many successful practice model changes; however, making effective changes requires effort. For successful change, Dr. Farrell realizes the need for open discussion and a staff willing to embrace change and try new approaches. When incorporating new care models, a consistent message is important so that all staff members are aware of the terminology, the perception of what is being offered, and what the new process involves. Dr. Farrell has learned with experience that there will be gaps in knowledge that need to be addressed. She now incorporates monthly staff meetings over lunch to talk about new services and problems as they arise. The pharmacy strives to offer services longitudinally such as immunization reviews and nicotine cessation, and staff education on how to incorporate these services into the patient encounter is highly valued and prioritized. Finding time and resources to ensure consistent training and implementation takes place while continuing to offer the established level of care is very challenging. Practice advancement and project management can be difficult to fit into a busy pharmacist’s schedule. Dr. Farrell has addressed this through involvement in the University of Wisconsin Community Pharmacy Residency Program. The skills needed to implement novel patient care www.pswi.org

Above: Boscobel Pharmacy Staff

services are evolving and residents are at the cutting edge from both a clinical and technological standpoint. Dr. Farrell believes that Community Pharmacy residents are uniquely poised to drive innovation. Another challenge faced by Boscobel Pharmacy is the threat of losing patients due to Medicare Part D preferred provider policies. This obstacle initially seemed insurmountable as financial impact is a powerful motivator for patients to go elsewhere. Boscobel Pharmacy has faced this issue directly by affirming commitment to operating as a full service pharmacy that provides comprehensive care. By providing services and consultations in a consistent manner, Dr. Farrell has seen patients return to Boscobel Pharmacy after trying a preferred provider and missing the conveniences and services offered through Boscobel. Dr. Farrell admits her biggest fear when implementing new services is how to offer a uniform and dependable service that will be welcomed by the community and work in synchrony with the existing health care resources. The strategies she has developed to address this fear allow Boscobel Pharmacy to move forward and face new challenges. www.pswi.org

Moving Forward Boscobel Pharmacy is optimistic about the future. Due to a successful practice model, prescription volume continues to rise, which is a boost to the pharmacy. The pharmacy is also seeking out more opportunities to expand into the pharmacy services sector. In 2012, the pharmacy was remodeled to include two sit down areas for immunizations, medication reviews, and counseling on Continuous Positive Airway Pressure (CPAP) machines. The possibility of provider status, combined with these patient care services, will help the pharmacy evolve to meet patient needs and be part of a value-based care model. To foster communication with customers and patients, the pharmacy is fully embracing technology using Facebook, a mobile app, their website, and email. Transitioning from a more traditional pharmacy to one with advanced practices is challenging. In giving advice to other pharmacies that want to implement more services, Dr. Farrell suggests finding the biggest “headache” within your day – whether that be prescription workflow, or a person that calls the pharmacy multiple times a day. After that, develop a strategy to address this problem with everyone's input, so all staff are on board with the change.

As part of the remodel, Boscobel Pharmacy addressed a relevant issue of location of prescriptions and prescription bags. This may sound simple, but even a new bagging system can lead to a big impact and reduce stress for staff. These changes lead to a “buy in” for others, moving the pharmacy forward. Dr. Farrell sees the future of the pharmacy, and pharmacy as a whole, as a culture that takes care of the whole patient, not just refills. No one has said that the transformation of pharmacy practice would be easy, as there are and will be stresses, but the process should be embraced. Dr. Farrell sees exciting things in the future of pharmacy and by embracing that belief, she is advancing pharmacy practice and improving patient care. Alanna Benaszeski is a 4th Year Doctor of Pharmacy Candidate and Andrea Grey, Michael Heltne, and Musetta Steinbach are 3rd Year Doctor of Pharmacy Candidates at the University of Wisconsin-Madison School of Pharmacy in Madison, WI. Disclosures: The authors declare no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. July/August 2018

The Journal 55

PSW News

Merging Passion and Population Health: Creating Better Health Through PharmacistProvided Care by Erica Martin, BS, Jonathan Meiman, MD, and Charles Vear, MPH

hy do you do what you do?1 It seems like a simple question. But, take a moment to really

think, “why?” You didn’t land where you are today by happenstance. You are there because you followed your passion and your strengths. You practice pharmacy because you love helping your patients live better lives. Your passion aligns with the Pharmacy Society of Wisconsin’s (PSW) vision, “together we can inspire each other to advance our profession with the single purpose of enhancing the lives of our patients.2” There are many ways pharmacists and technicians can enhance the lives of patients. Specifically, pharmacists and technicians can play a role in improving population health.

Population Health - What is it? The terms, “public health” and “population health” bounce around in conversation a lot. Similar to “there, they’re, and their” or “affect and effect”, these terms are (accidentally) used interchangeably but are different by definition. The American Public Health Association defines “public health” as the space were people live, learn, work, and play.3 However, often in health care jargon, the term, “public health” is specifically referring to county health departments. Population health is less defined. If you did a quick search online, you’d find varying definitions. One defines, “Population health is a holistic focus that requires the consideration of a broader array of the determinants of health than is typical in either health care or public health and recognizes shared responsibility for population health outcomes with diffuse accountability.3” Population health includes examining 56 The Journal

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clinical and non-clinical factors that may affect a person or communities' health, such as access to healthy foods, transportation, and care, and holding steady employment. That’s a tall order and pharmacists may feel the need to “drink the ocean” by themselves. Therefore, to achieve population health, shared responsibility and accountability are key. If we all, pharmacy professionals and non-pharmacy professionals, work collaboratively, we can make large impacts together. So, what can you as a pharmacist or technician do to improve population health and care? Well, PSW has ideas for you! PSW has taken a focus on health care initiatives that pharmacists and technicians can make big waves to improve patients’ access, care, and health, specifically by addressing preventative care. This includes focusing on immunizations and non-vaccine injections; tobacco cessation; naloxone and safe use of opioids; antimicrobial stewardship; and enhanced practice models.

Immunizations and Non-Vaccine Injections Did you know, according to the 2017 America’s Health Rankings, Wisconsin ranks 41st in number of pertussis cases, a vaccine-preventable disease and outside the top ten best states for in adolescent vaccinations, rates including meningococcal, HPV, and Tdap vaccines?4 Further, in 2016, all 72 Wisconsin counties fell below Healthy People 2020’s influenza vaccination rate goal of 70% for children, adolescents, and adults under age 65.5 Complimentary to PSW’s vision, PSW aims to expand patient access to recommended vaccines with the aim of improving immunization rates. The Centers for Disease Control and Prevention (CDC) recommend expanding access

as an evidence-based way of increasing immunization rates.6 PSW, the Medical College of Wisconsin (MCW) Pharmacy School, and the MCW Medical School are pleased to announce a partnership to expand vaccine access by addressing system and policy barriers to vaccine administration by Wisconsin pharmacists. Access will be expanded by exploring the creation of a consistent vaccination protocol, updating vaccine administration training, addressing financial sustainability, partnering with the Wisconsin Immunization Program and immunization coalitions, and engaging patients and communities. This project is funded in whole by the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin. PSW and MCW are eager to get underway with this work and will be providing frequent updates on how access can be expanded in your practices. Furthermore, in 2016, pharmacists gained the authority to administer nonvaccine injections. PSW and the University of Wisconsin-Madison (UW) Division of Pharmacy Professional Development partnered to create three trainings available online. To receive the required training to provide non-vaccine injections, pharmacists must complete the “Administration” module (approximately one hour in length). Additional modules for “Inpatient” and “Long Acting Naltrexone and AntiPsychotic Drugs” are also available.

Tobacco Cessation PSW launched a Tobacco Cessation Initiative in 2017. As part of the Initiative, a survey was sent out to PSW membership to better understand how pharmacists’ interests and current tobacco cessation practices. The results are very promising to helping patients quit or reduce tobacco www.pswi.org

FIGURE 2. Antibiotics Before Dental Procedures Patient-Facing Flyer

ANTIBIOTICS BEFORE DENTAL PROCEDURES Do I need to take antibiotics before dental procedures?

How has using antibiotics before dental procedures changed?

You may need to take antibiotics before a dental procedure if you have one of the following HEART conditions: An artificial heart valve or other artificial material in your heart

A history of a heart infection called infective endocarditis

TAKING ANTIBIOTICS prior to dental procedures used to be recommended more often for people with heart conditions or after joint replacement surgery.

RESEARCH has now shown that antibiotic use before dental procedures was more harmful than helpful for many of these people.

UPDATED GUIDELINES now recommend that fewer groups of patients require an antibiotic before a dental procedures.

Unrepaired congenital heart disease conditions

Antibiotic use is not needed before all dental procedures. Your DENTIST will tell you if the procedure requires you to take your antibiotics beforehand.

You may need to take antibiotics before a dental procedure if you have had serious complications with a knee or hip replacement surgery. Ask your ORTHOPEDIC SURGEON if you need antibiotics before dental procedures. Then be sure to talk with your DENTIST.

Ask your CARDIOLOGIST or primary care doctor if you need an antibiotic before a dental procedure. Then be sure to talk with your DENTIST.

What harm could come from taking antibiotics? When antibiotics are used too often, bacteria can become resistant to them and the antibiotics no longer work.

When antibiotics are used inappropriately, they can cause unnecessary side effects.

What else can I do? If you have been using an antibiotic before a dental procedure, discuss it with your medical and dental providers. Since recommendations have changed, you may no longer need it. The most effective way to prevent infections is to maintain good oral health. Make sure to: 1. Get professional cleanings every 6 months or as recommended by your dentist 2. Brush twice daily 3. Floss daily For questions, please contact the Wisconsin Department of Health Services Oral Health Program at dhsdphoralhealth@wisconsin.gov www.pswi.org July/August 2018 The Journal

FIGURE 1. Total Number of Pharmacies that Signed Naloxone Statewide Standing Order by Month

use. Nearly all pharmacists said it was their professional responsibility to counsel patients on tobacco use. A large majority of pharmacists were very interested, interested, or neutral about prescribing, showing a large opportunity to expand access and advance the profession. To move toward our goal of increasing the provision of tobacco cessation services performed by pharmacists and improving patient outcomes, PSW has partnered with different organizations to create resources to continue to expand tobacco cessation access, coverage, and training opportunities. This includes a partnership with the UW Center for Tobacco Research and Intervention (CTRI). CTRI has many resources on their website that could be useful to your practice, including the Wisconsin Quit Line, a support line you could refer your patients to. CTRI has also contributed articles to The Journal of the Pharmacy Society of Wisconsin. PSW has a tobacco cessation clinical pocket toolkit that includes information on medication and counseling techniques. To augment this toolkit, a new supplemental toolkit will be available later in 2018 to provide information on implementing a tobacco cessation program in your practice, financial sustainability guidance, and motivational interviewing techniques.

Naloxone and Safe Use of Opioids PSW has been an active participant 58 The Journal

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in addressing the opioid epidemic and is participating in several key initiatives. One of the most influential ways pharmacists can reduce opioid-related deaths is through the dispensing of naloxone under the statewide standing order. The statewide standing order aims to increase access to life-saving naloxone. The order allows pharmacists to dispense naloxone to patients receiving high doses of prescribed opioids or others at risk of overdose. It also allows individuals to acquire naloxone for a close friend or family member who is at risk. The statewide standing order for naloxone was signed by Dr. Jonathan Meiman and observed by Governor Scott Walker at PSW’s Annual Meeting in 2016. Today, 254 pharmacies have signed the statewide standing order (Figure 1) and more than 600 doses of naloxone were dispensed statewide from October to December 2017. Of these, 64% were dispensed under the statewide standing order.7 PSW and the Department of Health Services (DHS) aim to increase pharmacy participation along with patient awareness and utilization of the statewide standing order. While improved access is helping save lives, dispensing remains below optimal levels. PSW and DHS highly encourage pharmacies to utilize the statewide standing order. If you are interested in dispensing naloxone, the statewide standing order is available on the DHS website and requires a one-hour

online training. DHS also provides a naloxone directory map on their website which allows members of the public to locate pharmacies able to dispense naloxone under a standing order. Over 330 pharmacies throughout the state are shown on the map and it has been viewed over 3,800 times.7 If you are interested in having your pharmacy on the map, contact PSW so your name can be relayed to DHS. PSW has also participated in teambased care initiatives, including the Governor’s Task Force on Opioid Abuse chaired by Lieutenant Governor Rebecca Kleefisch and the Safe Communities Dane County Stop the Overdose Healthcare Task Force. In partnership with the Office of the Attorney General, PSW hosts a pharmacy robbery training online, describing prevention and robbery response.

Antimicrobial Stewardship Antimicrobial resistance is a growing concern and PSW wants to continue to support initiatives aiding antimicrobial stewardship. Guidelines related to antibiotics before dental procedures recently changed. PSW, DHS, Concordia University Wisconsin School of Pharmacy, and Marquette University School of Dentistry created an eye-catching flyer for patients (Figure 2). This flyer reviews whether antibiotics are appropriate or not before a dental procedure. It is developed for interprofessional use both by pharmacists and dentists. This flyer is available on the DHS website to be printed and handed out to your patients. Additionally, PSW has worked with other partners on various antimicrobial stewardship initiatives, including supporting the implementation of the CDC Core Elements of Outpatient Antibiotic Stewardship in community pharmacies and increasing pharmacy participation in study of antimicrobial stewardship in the intensive care unit to reduce C. diff. infections. Studies have shown point-of-care testing at pharmacies has contributed to antimicrobial stewardship. PSW continues to explore the expansion of point-of-care testing, specifically influenza and group A streptococcus testing. These tests could www.pswi.org

then be paired with a collaborative practice agreement to issue the proper therapy.

Technician Product Verification You’re probably thinking, these initiatives interest me, but how on earth do I have the time to do this? Que the “technician product verification model.” A technician product verification model improves patient care by allowing pharmacist more time to spend with patients by leveraging technicians to complete the final product verification. Pharmacists complete the clinical reviews of a patient’s history and their prescription, but technicians are utilized to complete the technical task of verifying the product. In sum, technician roles advance and teambased care expands. Wisconsin pharmacists have said the model has helped them spend more time with their patients. Pharmacists shared are they scheduled more comprehensive medication review appointments in the first months of implementing a technician product verification model than they had done in the entire year prior, their technicians feel empowered, pharmacists feel less stressed; and they completed hundreds of influenza and zoster vaccinations with ease. If you are interested in bringing a technician product verification model to your practice, PSW can help you. PSW, with the assistance of the PSW Practice Advancement Leadership Team (PALT), created two toolkits to implement this model (Figure 3). The institutional toolkit is intended for inpatient and long-term care setting and the community toolkit is for outpatient pharmacies. Both can be found on PSW’s website. They include directions, trainings, and templates to make it relatively turnkey to implement.

www.pswi.org

What's Next? After hearing all this information, what’s next? What can you do today? Take a minute and think about where are you now? Then, where do you want to be? What practices do you wish you could provide to your patients? Now, why do you want to be there? It’s probably because you love what you do. You love helping your patients. You love making them live healthier and happier lives. And you wish you could do even more for them but you just need to figure out the first step. With PSW’s help we can all do what we love to do, which is create better lives for Wisconsinites. Erica Martin is the Manager, Practice and Population Health Initiatives at the Pharmacy Society of Wisconsin in Madison, WI. Jonathan Meiman, MD is a Chief Medical Officer and State Occupational and Environmental Disease Epidemiologist at the Wisconsin Department of Health Services, Wisconsin Division of Public Health in Madison, WI. Charles R. Vear, MPH is an Applied Epidemiology Fellow with the Wisconsin Department of Health Services, Opioid Harm Prevention Program in Madison, WI. Disclosures: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medication, employment, gifts, and honoraria.

References

FIGURE 3. Technician Product Verification Toolkit IMPLEMENTATION TOOLKIT

WISCONSIN TECH-CHECK-TECH

DECEMBER 2016

TechCheckTech Advancing Pharmacy Quality

wisconsin. Published 2018. Accessed May 17, 2018. 5. Wisconsin Department of Health Services. https://www.dhs.wisconsin.gov/publications/ p01609.pdf. Influenza vaccination rates by age and county, Wisconsin 2015-2016. https://www.dhs. wisconsin.gov/publications/p01609.pdf. Published October 2016. Accessed May 25, 2018. 6. Task Force on Community Preventive Services. Recommendations regarding interventions to improve vaccination coverage in children, adolescents, and adults. Am J Prev Med. 2000;18(1):92–96. 7. Naloxone Statewide Standing Order Database, 2017-2018, Division of Public Health, Wisconsin Department of Health Services.

1. Swanson J. Advancing a Healthier Wisconsin Endowment’s (AHW) Storytelling for PSE Change Learning Series. 2018. 2. About PSW. Pharmacy Society of Wisconsin. http://www.pswi.org/about. Accessed May 25, 2018. 3. Swarthout M, Bishop MA. Population health management: review of concepts and definitions. Am J Health-Syst Pharm. 2017;74(18):1405-1411. 4. America's Health Rankings. Wisconsin. https://www.americashealthrankings.org/learn/ reports/2017-annual-report/state-summaries-

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The Journal 59

INSPIRE TODAY

2018 PSW Educational

60â&#x20AC;&#x192; The Journal

July/August 2018

www.pswi.org

TRANSFORM TOMORROW

www.pswi.org

Conference Recap July/August 2018

The Journal 61

Meeting Recap

Inspire Today. Transform Tomorrow. Learning from the 2018 PSW Educational Conference by Ryan Simonet, 2019 PharmD Candidate

he 2018 Pharmacy Society of Wisconsin (PSW) Educational Conference took place April 5-6 at the Monona Terrace in Madison, Wisconsin. Pharmacists, pharmacy residents, student pharmacists, and pharmacy technicians gathered to present, share ideas, and learn from one another at the conference. Featured events included continuing education opportunities, the Educational Conference & Wisconsin Residency Conference Reception, exhibit showcase, poster presentations, and the Wisconsin Pharmacy Residency Conference platform presentations. PSW continued its partnership with Pharm to Tables to host a food donation drive at the Educational Conference. Pharm to Tables is not-forprofit organization that brings those in the pharmacy profession together to combat hunger in the state of Wisconsin. This year, the University of Wisconsin – Madison, Concordia, and Medical College of Wisconsin Schools of Pharmacy participated in a friendly competition, appropriately titled “Pharm Phood Phight,” to donate the greatest amount of nonperishable food and monetary donations. Concordia defended their title! In total, the three schools combined for over 1,800 lbs of food and over $2,700 in donations. Donations from the schools of pharmacy and the PSW Educational Conference will help provide food to the hungry in the local communities of Wisconsin. The conference began Thursday with an invigorating first general session entitled “Inspire Today. Transform Tomorrow.” in which Kelly Sheffield, head coach of the University of Wisconsin – Madison volleyball team reinforced the power of positivity and its impact on a team’s success. The second general session given in tandem by Philip Brummond, PharmD, MS, Director of Pharmacy 62 The Journal

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at Froedtert & the Medical College of Wisconsin, Milwaukee, and David Hager, PharmD, BCPS, Director of Clinical Pharmacy Services at UW Health, Madison, along with Kristin O’Reilly, PharmD, PGY2 Health-System Pharmacy Administration Resident at Froedtert & the Medical College of Wisconsin, Milwaukee, and Rachel Nass, PharmD, PGY2 Health-System Pharmacy Resident at Aurora Health Care, Milwaukee. The group discussed the growth of residency programs, including the breakdown of PGY1, PGY2, and PGY1/2 combined programs with a 30% increase in total programs. Additionally, the distribution of PGY2 programs was discussed, with the three largest areas being critical care, ambulatory care, and oncology. As of 2017, there were an estimated 190 residents in the state of Wisconsin! New this year, the Wisconsin Pharmacy Residency Conference (WPRC) was introduced along with the Practice Advancement Initiative and PSW Partnership. This partnership’s mission is to advance patient-centered care and pharmacy practice in Wisconsin through the growth of innovative programs and the development of professional and technical pharmacy workforces. This effort is being led by the Practice Advancement Leadership Team (PALT), consisting of state leaders in the pharmacy profession. Two of the many initiatives PALT seeks to advance is Community Tech-Check-Tech and recruitment and retention of pharmacy technicians. Thursdays sessions included a wide variety of topics that were focused on clinical intensive programming, including Building a Framework for Insulin Safety in Hospitals, Clinical Projects – WPRC Star Research Podium Session, and Infections and Injection Drug Users: An Opportunity for Harm Reduction. Several conference sessions also focused on ambulatory care, such as the ambulatory care networking session and Ambulatory Care Advancements

– WPRC Star Research Podium Session. The conference also offered programming specifically to benefit pharmacy technicians, such as the technician luncheon and technician friendly sessions including Workshop: Implementing USP <797>, Expanding Technician Roles – WPRC Star Research Podium Session, and Features in Practice: IV Workflow Technologies. Other featured session types included WPQC/MTM features, Informatics and Technology, and population health. The WPRC Meeting events concurrently offered attendees a plethora of events and sessions to attend throughout Thursday and Friday. The WPRC Platform Presentations provided residents the opportunity to present their residency projects on a wide variety of subjects including disease state management and health-system process improvement. The day wrapped up Thursday evening with the Wisconsin Pharmacy Residency Conference Reception to socialize and celebrate the inaugural WPRC Meeting. Friday began bright and early with the continental breakfast as well as the Christian Pharmacists Fellowship International Breakfast – “Be Still”, featuring Eva Vivian, PharmD, MS, CDE, BC-ADM, FAADE, in which students and pharmacists from UW-Madison, Concordia, and MCW enjoyed breakfast, fellowship, and reflection together. After breakfast, the conference hit the ground running with three featured sessions, beginning with Transforming Health-System Management of Populations Using TeamBased Care featuring John Fangman, MD, Senior Medical Director, Ambulatory, Froedtert & the Medical College of Wisconsin, Milwaukee and Associate Professor of Medicine, Infectious Disease. He made a popular comparison of health care teams to the Green Bay Packers, The Ritz Carlton, and Southwest Airlines. By comparing the health care team model to leading teams in other industries, www.pswi.org

Above Left: Congratulations to the recipients of this year's Curtis A. Johnson Award for their consistent article contributions over the last few years and, in particular, their recent article entitled: Active Observation in Pharmacy Precepting. Pictured Left to Right: Mindy Bauer, Kate Rotzenberg, and Shab Dabirshahsahebi. Above Right: Congratulations to this year's Cardinal Generation RX Award recipient, Doug Englebert. The Cardinal Health Generation Rx Champions Award was established in 2011 to recognize a pharmacist that has demonstrated a commitment to the mission of substance abuse education.

valuable lessons can be drawn, such as the importance of leadership, each team member knowing their responsibilities and executing consistently, anticipating and complying with needs, and having fun working together. Overall as a health care team, the focus of care should be placed on safe, effective, efficient, personalized, timely, and equitable care. Making time to create and develop teams will enhance the care delivered to patients and improve careers in healthcare. Dr. Fangman is confident that together we can build and develop strong healthcare teams across the state and further improve how healthcare is delivered to patients. Following the next two general sessions, Forcasting for the Future: Leveraging the Pharmacy Forecast to Plan, and PSW Membership Briefing, the meeting broke for lunch and the poster session. The poster session featured 69 posters from pharmacists, pharmacy residents, and pharmacy students from across the state. Afternoon programming included several WPQC/MTM features, including Practice Change Features: How to Advance Ambulatory Care in 3 Months or Less. This session featured a large panel of pharmacists, residents, and students including Andy Cannon, PharmD, Katie Keucker, PharmD, Dan Cunningham, PharmD, Emily Bollom, BS, DPH-4, Khyati Patel, PharmD, BCPS, Michelle Farrell, PharmD, BCACP, and Steffen Matijevich, PharmD. Each of them shared their stories and unique experiences as well www.pswi.org

as how attendees could make their own impact on ambulatory care at their practice sites. The afternoon also included technicianfocused programming, including Improving Adherence through Patient-Centered Prescription Medication Labels. The panel of speakers, consisting of Dave Mott, RPh, PhD, FAPhA, Hashim Zaibak, PharmD, Matt Mabie, RPh, Melissa Ngo, PharmD, BCACP, and Steve Sparks, MS, discussed recent medication label changes their various pharmacy sites underwent as well as the process and challenges behind developing a more patient-friendly label. The second and final day wrapped up with two sessions including Bridging Warfarin Therapy in the Periprocedural and Surgical Setting presented by Emily Rahn, PharmD discussing the recent findings of new literature and re-evaluation of bridging anticoagulation and Cancer Therapy Side Effects led by Jennie Piccolo, PharmD, BCOP in which the management of chemotherapy induced nausea and vomiting (CINV), dermatologic toxicity associated with epithelial growth factor receptor (EGFR) inhibitors, and immune related toxicities utilizing the most current and up-to-date guidelines in the oncologic and hematologic setting. This yearâ&#x20AC;&#x2122;s PSW Educational Conference was an excellent opportunity for pharmacists, residents, student pharmacists, and technicians to collaborate and learn from numerous keynote speakers, educational sessions, and residency project

presentations and posters as part of the WPRC and Educational Conference. PSW appreciates the members, staff, sponsors, and presenters for once again making the Educational Conference a collaborative success to share knowledge and advance pharmacy practice and patient care in Wisconsin. PSW invites you to mark your calendars and attend the upcoming 2018 PSW Annual Meeting which will be held at the Kalahari Resort, Wisconsin Dells on August, 23-25! Ryan Simonet is a 4th year Doctor of Pharmacy Candidate at the University of WisconsinMadison School of Pharmacy in Madison, WI.

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Meeting Recap

From Idea to Reality: The First Annual Wisconsin Pharmacy Residency Conference by Julie K. Dagam, PharmD, BCPS, Craig R. Grzendzielewski, PharmD, MBA, BCPS, and Sarah E. Sorum, PharmD

hursday April 5 and Friday April 6 marked the beginning of a new tradition in residency training in the state of Wisconsin when the first ever Wisconsin Pharmacy Residency Conference (WPRC) was held concurrent to the 2018 PSW Educational Conference. Throughout the two days, conference attendees were treated to resident platform and poster presentations, each highlighting significant projects conducted over the course of their programs. Residents received honest verbal and written feedback on their projects and presentations, and everyone had the unique opportunity to take advantage of valuable interaction and networking. Thursday morning, general sessions set the stage for WPRC breakout sessions by touching on the impact of residency training. Thursday afternoon brought the opportunity for conference participants to hear about residents’ specific projects during concurrent breakout sessions. Each session featured 3-4 resident platform presentations and focused on specific topics or themes. Themes included cardiology, infectious diseases, pain and opioids, oncology, women’s and men’s health, insulin-related clinical projects, patient services in a variety of disease states and settings, and practice management topics. Featured “STAR” presentations on the themes of expanding technician roles, clinical projects, ambulatory care, and informatics were among additional options for attendees. Friday brought the opportunity for residents and attendees to engage on a more individual level during the poster session. As attendees learned more about each participant’s specific project, the Community Terrace provided a beautiful backdrop of Lake Monona. Friday afternoon brought more concurrent 64 The Journal

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breakout session options. This time, presentations on the themes of medication safety, informatics, and ambulatory care were among the choices. During the conference, energy and excitement was palatable. Feedback from resident participants, program directors, preceptors, and conference attendees indicated overall success, and supported the exciting decision to continue this endeavor annually. But how did WPRC begin? It all started with a simple idea: How can an avenue for residents to present their work at a statewide level to promote idea sharing, best practices, and practice advancement be created? And so began the evolution of WPRC.

The Idea Takes Shape The initial idea gained momentum in July 2017, when several members came together at the PSW headquarters for a brainstorming session. Because utilizing the resources of an existing

conference took advantage of established conference structure, support, and logistics, preliminary plans for piloting residencyspecific sessions at the PSW Educational Conference were discussed. Utilizing the PSW Educational Conference specifically was also attractive due to appropriate timing within the residency year. Finally, adding resident-presented educational content would provide programming variety for attendees, add to the energy of the existing conference, and be consistent with the conference’s focus on education. In follow-up to this initial discussion, PSW conducted a survey of Wisconsin program directors to obtain initial feedback and preliminary interest in participating in this developing initiative. In September 2017, seven PSW members were invited to come together via teleconference with the mission of using the survey results to make the pilot a reality. These seven members, comprised of residency program directors, a current

TABLE 1. Summary WPRC Timeline Time

Action

October

Establish WPRC format

November

• Determine participant commitment (through communication with WI residency program directors • Determine number of resident presentation slots available based on room availability, participant commitment, and PSW Educational Conference programming

December

Communicate session format to participants based on number of attendees

January

• Advertise conference information in Fast Facts • Solicit interest for preceptor volunteers

February

• Resident abstract submissions due (for presentation, poster, or both) • WPRC Planning Committee in-person meeting to group presentations into sessions based on topic/theme • Resident presenters notified of acceptance

March

• Volunteers notified of role • Instructions and training communicated to preceptor evaluators and to room proctors

April

PSW Educational Conference/Wisconsin Pharmacy Residency Conference! www.pswi.org

FIGURE 1. Sample WPRC Resident Presentation Feedback Form

WPRC Resident Presentation Feedback Form Presenter Name: Awesome Resident Title: Completion of the WPRC evaluation form: a stepwise approach. Evaluator Name/Organization: Perfect Preceptor / PSW 1. Strongly Disagree

2. Disagree

3. Neutral

4. Agree

Date: 4/5/18

5. Strongly Agree

Scale

Comments

Presentation Content Presentation topic was current and relevant to the audience

Interesting topic - applicable to other organizations.

Background (and rationale) effectively articulated

Too much time on background â&#x20AC;&#x201C; spend more time on the project itself.

Project objective(s) effectively articulated

Yes.

Steps in methods are clearly articulated

Yes, I clearly understood the step by step approach you took.

Results are effectively articulated

Results were clear and directly tied to your project objective.

Discussion points (summary of results, other findings, limitations, future direction) are appropriately articulated

What happens to your project when you are no longer a resident?

Given the information presented, the conclusion (if applicable) is appropriate

Conclusion restated project objectives. Be bold with your conclusions.

Yes.

I gained new information and knowledge on the subject presented

Yes

The presentation was free from bias

Yes

Presentation Quality Presentation was organized in a logical order

Presentation subject and detail were appropriate for allotted time and audience

As above, consider spending majority of presentation on project content rather than background.

Presentation slides were easy to read and visually appealing

See below.

Speaker Assessment Presenter was prepared and had comprehensive knowledge of their topic

I clearly understood your involvement with the project.

Presenter had effective presentation delivery skills (ex: eye contact, volume, slide transition, does not read from slides)

Was dependent on notes for majority of the presentation.

Presenter engaged the audience and answered questions appropriately

Yes

Answered questions appropriately - consider restating the question before answering to ensure entire audience hears the question.

General Comments (strengths and areas for improvement): Great job outlining a rather complicated methodology in a way the audience could follow. Slides contained too many words. In the future, consider using slides to support what you are saying rather than as a script. Thank you and good luck! www.pswi.org

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FIGURE 2. WPRC Planning Committee at the First Annual WPRC

Above: Pictured Left to Right: Mike Gillard, Maria Wopat, Julie Dagam (co-chair), Craig Grzendzielewski (co-chair), Diane Erdman, Sarah Sorum. Not pictured: Richard Arndt.

Post Graduate Year Two (PGY2) resident, and PSW leadership, ultimately became the WPRC Planning Committee. Based on the survey results, the WPRC Planning Committee determined that it was important to: • provide an opportunity for every interested resident to participate while still insuring quality content for attendees • incorporate a method for residents to receive direct, robust feedback • consider resource and space availability Using these parameters, as well as giving consideration to managing potential future growth, the WPRC Planning Committee established a preliminary conference format.

WPRC Format and Timeline One step in establishing the WPRC format included evaluating conference capacity. Preliminary models of conference capacity that included scheduling and available resources indicated it was possible to accommodate resident presentations in a formal “platform” presentation style. This presentation style was consistent with program director preference. Alternative styles, such as shorter presentations, were 66 The Journal

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less desirable, but could be considered if the number of presenters exceeded space and time availability. Another step in establishing the WPRC format was determining how to integrate the WPRC sessions with existing PSW conference programming and design. Consideration was given to how the WPRC sessions would be scheduled relative to PSW Educational Conference programming. The WPRC Planning Committee realized that conference attendees would need the flexibility to be able to attend both WPRC sessions and conference programming. In order to allow for this flexibility, it was decided to schedule WPRC presentations in 1-hour sessions. This allowed for: • scheduling 3 resident presentations (15 min each) plus allotting 15 minutes for questions and feedback into each 1-hour WPRC session • grouping resident presentations based on similar topic or theme into the same session when possible • providing continuing education for attendees of each session • aligning start and end times of WPRC sessions with PSW Conference sessions when possible

Further, grouping the WPRC presentations into 1-hour sessions by theme helped to keep each session stay on time by decreasing attendee travel time between individual 15 minute presentations. It also allowed for questions for each resident to be handled in a single question and answer panel with all resident presenters at the end of each session. Finally, time for robust verbal and written feedback in each session could be accommodated using this model. Once the initial format was determined, the WPRC Planning Committee acknowledged that a broad base of support would be necessary to execute the design. Because it would be critical to engage residency programs, preceptors, and residents early in the process, the WPRC Planning Committee developed a timeline. Key components of the timeline are listed in Table 1.

Engaging Preceptors and Residents As conference planning progressed, the WPRC Planning Committee identified several key areas for resource development and engagement. In order to ensure quality content for attendees, residents were asked to submit their project as an abstract, and indicate whether they www.pswi.org

Wisconsin Pharmacy Residency Conference… at a glance: • 100 resident platform presentations • 50 resident posters • 41 residency programs in 14 Health Care organizations represented • 66 volunteer room proctors and preceptor evaluators

planned to participate in the platform presentation sessions, the poster session, or both. Members of the WPRC Planning Committee, along with two additional resident volunteers, met in early February to review each abstract, group presentations together based on similar topics/themes, and identify the featured “STAR” presentations. In order to ensure consistency in resident presentations and promote quality content, the WPRC Planning Committee also developed a standardized slide deck. This slide deck was provided to each resident to use as a template to develop their presentation. Key elements of the slide deck included: • background template • style and content tips • presentation format and expectations, including title slide, disclosure, learning objectives, background, project objective, methods, results, discussion, conclusion, and learning assessment A fundamental element of the conference identified early in the planning was incorporating a method of providing direct, robust verbal and written feedback to each resident presenter. Time for feedback within each session had been allotted during conference format development, but that left the need to develop the mechanism for feedback. In order to accomplish this, the WPRC Planning Committee drafted a feedback form to be used at the conference (Figure 1). Residency preceptors were solicited to volunteer to provide feedback. Those selected were assigned to a breakout session www.pswi.org

and given instructions regarding their expectations. It was also important to develop a method of insuring each breakout session ran smoothly and according to schedule. In order to aid in this, the WPRC Planning Committee solicited resident and preceptor volunteers to serve as room proctors. A training video was developed that described room proctor duties and expectations, which was a convenient and effective way to help room proctors understand their expectations prior to the conference. Upon conference check-in, residents, WPRC evaluators, and room proctors were given a packet of information summarizing their roles and expectations. In addition, WPRC Planning Committee members were available onsite for trouble shooting (Figure 2).

Plans for the 2nd Annual WPRC As described above, the first WPRC was truly a success. It was very exciting to see the WPRC evolve from an idea to a reality! There is always room for adjustments, and the WPRC Planning Committee will begin evaluating suggestions and implementing necessary changes. Going forward, a formal WPRC governance document that clearly outlines the WPRC Planning Committee duties and how its members are selected and supported will be developed. Finally, the WPRC Planning Committee will consider how to best handle expansion based on interest. The WPRC Planning Committee is very excited to begin planning for the PSW Educational Conference/2nd Annual WPRC, which will be held April 9-10, 2019. We hope to see you there!

Julie Dagam is the Residency Program Director for the PGY1 Pharmacy Residency program at Aurora Health Care in Milwaukee, WI. Craig Grzendzielewski, at the time of publication, is the Director of Pharmacy at Aurora St. Luke’s South Shore in Cudahy, WI. Sarah Sorum is the Senior Vice President of Professional Services at the Pharmacy Society of Wisconsin in Madison, WI. Acknowledgments : The authors would like to acknowledge the members of the 2018 WPRC Planning Committee: Richard Arndt, Julie Dagam (co-chair), Diane Erdman, Mike Gillard, Craig Grzendzielewski (co-chair), Diane Erdman, Sarah Sorum, and Maria Wopat, as well as the resident presenters, program directors, preceptors, PSW staff, and volunteers who contributed to the success of the 2018 WPRC. Disclosures: Julie Dagam: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Craig Grzendzielewski: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Sarah Sorum: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria.

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Pharmacy Reflections

Commentary: Population Health as the Pharmacy Profession’s Value Proposition by Christopher J. Barron RPh, BS Pharm

recently attended the Pharmacy Society of Wisconsin HealthSystem Pharmacy Advisory Board meeting (PSW HPAB). There we have the ”lightning round,” where participants go around the table commenting on what keeps us up at night. This is usually something health-system pharmacy related. As a former director of pharmacy, I can empathize with my peers; Joint Commission, USP <797>, USP <800>, mergers and acquisitions, staffing shortages, medication shortages, and information technology challenges all are common topics, and I have lived most of those. The knowledge and leadership in the room is impressive. Wisconsin pharmacy is fortunate to have such a valuable forum organized by PSW. I would encourage eligible PSW members to seek membership on this board as seats become available. As the Executive Director of Population Health at Fort HealthCare, I now have a different perspective than many of my health-system pharmacy peers at the table. Population health is defined as the health outcomes of a group of individuals, including the distribution of such outcomes within the group. This includes health outcomes, patterns of determinants, and policies and interventions that link these two.1 Population health is more than just clinical outcomes of a patient population, sometimes described as population health management, it encompasses the broader community health where non-clinical interventions may be required to impact health determinants and health disparities of a broader geographic population. As a healthcare executive leading a population health initiative, I am now an outsider 68 The Journal

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looking in at my former pharmacy profession. What keeps me up at night is different than what most of my peers mentioned at the PSW HPAB lightning round. Gone are my sleepless nights thinking about Joint Commission or USP <797>. Instead, what keeps me up at night, is the idea of professional relevance. A preoccupation with professional relevance is not new to me. As a pharmacist, particularly as a Director of Pharmacy, I was driven by relevance. I sought and continue to seek to keep myself, my department, my organization, and my profession relevant. Through my years as a Director of Pharmacy this idea drove continuous change and innovation both in my department and at my organization. It made pharmacists at my organization indispensable. It elevated pharmacy’s status at my organization, ultimately leading to two pharmacists moving into senior executive roles at Fort HealthCare. What makes pharmacists relevant? The answer today is likely not the same as it was a few years ago and will likely change into the future. I even like to quiz pharmacy students, residents, and even pharmacist applicants, “why do we need pharmacists?” When I think about relevance, I think about value. In business terms, value equals quality divided by cost. Do pharmacists deliver value? What value do pharmacists bring and to whom? Does the pharmacy profession tell our story well enough to those (outside of our profession) so stakeholders and decision-makers recognize the value pharmacists provide? This introspection on professional relevance brings me to population health. The Pharmacy Forecast 2018

calls population health management a community imperative.2 I see it as even more than that. It is our profession’s imperative to make a measurable difference in the lives of patients, improving the health of populations, asserting pharmacy’s relevance by delivering measurable quality at reduced overall cost. I was at a recent Wisconsin Hospital Association Advocacy Day with my colleagues from Fort HealthCare. In the meeting packet was a paper stating, “Wisconsin Healthcare best in nation” referring to Wisconsin’s ranking with the federal Agency for Healthcare Research and Quality (AHRQ).3 I wondered, do others in this room recognize pharmacists as part of this story? I am certain the pharmacy profession contributes to Wisconsin’s #1 ranking, but do the people that need to know this know that pharmacists are part of the story? Have we proven ourselves to be indispensable? Have we proven our value with stakeholders and decisionmakers? In my population health role I attend numerous non-pharmacy conferences; whether it is the recent WHA Advocacy Day, the Population Health Colloquium in Philadelphia, or various regional Wisconsin Collaborative for HealthCare Quality (WCHQ) meetings. At these meetings I encounter opportunities too numerous to count for the pharmacy profession to bring solutions to complex healthcare issues, but I frequently do not see pharmacist representation at the table. Many times, I am the only pharmacist in the room (and not present in a pharmacy capacity). I see many missed opportunities for pharmacy www.pswi.org

to be part of large scale population health improvements. Imagine if stakeholders and decision-makers could say Wisconsin has the best healthcare in the nation at the lowest cost because of the value the pharmacy profession delivers. Pharmacists are accessible and knowledgeable, uniquely qualified to impact both health outcomes and determinants of health. I see this as our value proposition, but we need to challenge ourselves to tell our story better, outside of our profession, both as a profession and as individual pharmacy professionals. There are many great things happening in the pharmacy profession, especially in a wonderfully progressive state like Wisconsin. We have a lot to be proud of. Nationally, I think we are nearing provider status, but no matter what happens we must prove our value, effectively telling the story of the value we provide. Pharmacists also need to be at the table to recognize new opportunities and become involved, becoming a bigger part of the great stories that are unfolding in Wisconsin healthcare. What are some ways the pharmacy profession can impact population health? I think an easy place to look is to not only leverage our expertise but also leverage our accessibility. Pharmacists are one of the

www.pswi.org

most accessible healthcare providers. How might we use our interactions differently to impact broader health? There are many great examples such as the PSW Adherence Competence Collaborative (PACC) and Tobacco Cessation Initiatives but I think we are barely scratching the surface. Another obvious opportunity is to fully connect our inpatient and outpatient practices, ensuring safe transitions of care. A great deal of exceptional work is happening here, and I applaud those involved in those efforts. Pharmacists also have the potential to relieve burden from primary care providers. As more workload is put on primary care providers with new payment models, such as the Merit-Based Incentive Payment System (MIPS), pharmacists should be ready to jump in and be part of the solution, but we must be at the table to recognize those opportunities. Pharmacists must also be serious about opioid abuse, working outside the walls of our businesses, partnering with others in the communities we serve, and impacting prescribing behaviors. We must be committed patient advocates and be committed to overall health and wellness. Finally, to really impact population health, we need to not only be involved with population health management but

also community health, identifying and addressing health disparities and social determinants of health through a variety of means. All of this requires population health, and not just population health management, to be part of the strategic planning for our practice sites, professional organizations, and schools of pharmacy. This is what keeps me up at night. Christopher Barron is Executive Director of Population Health for Fort HealthCare and a member of the PSW Health-System Advisory Board, Madison, WI. Disclosures: The author declares no real or potential conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medication, employment, gifts, and honoraria.

References

1. Kindig D, Stoddart G. What is population health? Am J Public Health. 2003;93(3):380-383. 2. Devereux D, Zilz D. Population health management: a community imperative. Am J Health-Syst Phar. 2018;75(2):46-48. 3. Grasmick, MK. Wisconsin Health Care Best in Nation. Wisconsin Hospital Association News. http://www.wha.org/Data/Sites/1/pubarchive/ news_releases/WHAnr-WIhealthcareNo1-8-22-2017. pdf Accessed March 30, 2018.

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Pharmacy Reflections

Improving Medication Access Through Partnership with Dispensary of Hope by Jonathan Koehler, PharmD, Katie Scarpace, PharmD, BCACP and Joshua Coffey, 2018 PharmD Candidate

harmacists and pharmacy technicians specialize in ensuring medication therapy is safe and effective for patients. As medication costs continue to rise, pharmacists and technicians are challenged to not only make sure medications are safe and effective but affordable for patients! This article will review financial barriers to medication access and share one solution pharmacies can employ to overcome financial barriers.

Financial Barrier to Medication Access Although rates of uninsured patients have declined annually since passing the 2010 Affordable Care Act, a large segment of the population remains uninsured. A 2016 report by the Department of Health and Human Services estimated that the rate of uninsured individuals under the age of 65 was 10.6% encompassing an estimated 28.7 million people.1 Analysis of the same data set found that 16.2% of families

Abstract Pharmacists and pharmacy technicians specialize in ensuring medication therapy is safe and effective for patients. As medication costs continue to rise, pharmacists and technicians are challenged to not only make sure medications are safe and effective, but affordable for patients. For patients without prescription insurance, financial barriers can make it challenging to adhere to drug therapy regimens. Dispensary of Hope is a charitable medication distributor that provides participating pharmacies and clinics with access to medications donated by pharmaceutical manufacturers. Ascension Wisconsin's retail pharmacies have partnered with Dispensary of Hope to create a patient assistance program to provide eligible patients medications at no charge. This article reviews how two Ascension pharmacies in Wisconsin have created programs to improve medication access.

reported problems paying medical bills in the previous year, having an impact on 43.8 million people.2 In Wisconsin, many of these patients exceed the state Medicaid income threshold but do not make enough to afford monthly insurance premiums. For these patients, it can be challenging to

Below: Christine Brown, pharmacy technician, pulling Dispensary of Hope inventory to fill a prescription. Pharmacies must keep Dispensary of Hope inventory separate.

adhere to drug therapy regimens. Inability to maintain drug coverage and afford medications can have significant negative impacts on patient quality of life and outcomes. Self-reported data demonstrates the negative impact of high out-of-pocket costs on an individual’s perceptions on their ability to afford medications, adherence, and quality of life.3,4 Additional research reveals quantifiable examples exist beyond the realm of patient perceptions. Comparing groups with differences in cost sharing burden has shown increased drug costs to be associated with higher rates of disease symptoms, adverse events, emergency room visits, hospitalizations, and key lab values like A1C.5-7

One Solution to Improve Access Ascension Wisconsin has partnered with Dispensary of Hope, a charitable medication distributor, to help patients without insurance meet prescription drug needs. Dispensary of Hope was founded to help patients without insurance meet prescription drug needs. Dispensary of Hope's mission is “transforming lives through the 70 The Journal

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www.pswi.org

TABLE 1. Federal Poverty Guidelines 20188 Household Size

100% Poverty 200% Poverty Guidelines Guidelines

$12,140

$24,280

$16,460

$32,920

$20,780

$41,560

$25,100

$50,200

*48 contiguous states and the District of Columbia

philanthropic donation and distribution of medicine.â&#x20AC;? Through innovative stewardship of the pharmaceutical supply chain, the Dispensary of Hope collects and distributes millions of dollars of pharmaceuticals annually to pharmacies and safety-net clinics to dispense to low income, chronically ill patients. Through meaningful partnerships, pharmacies and clinics nationwide can utilize Dispensary of Hope medication to impact the health of their communities by improving access to affordable medication. Dispensary of Hope has established partnerships across the country including the practice sites of the authors of this article.

Who Qualifies for Ascension Wisconsin's Medication Assistance Program

medications. Before completing an order, Ascension Wisconsin pharmacies are able to confirm the product, pack size, and expiration dating. Once the order is completed, most Ascension Wisconsin pharmacies receive the order within one week. Each Ascension Wisconsin pharmacy site in partnership with Dispensary of Hope, creates a standard formulary of medications that are readily available. Examples include commonly used drugs like metoprolol tartrate and atorvastatin. Providing medications to a patient frequently involves collaboration with the patient's primary care provider to make therapeutic interchanges that match the medication formulary. Using formulary medications helps to ensure patients have the best chance for continuing medication access to manage their conditions. Some programs provide one-time access to drugs or require the patient to make frequent changes in therapy to utilize available products. The use of a formulary ensures consistent availability of medications resulting in fewer drug changes and less confusion for patients.

Dispensary of Hope in Practice at Two Ascension Wisconsin Outpatient Pharmacies In Wisconsin, we often think of rural and urban healthcare as looking vastly different. The state consists of wide variations in population density and city structures; however, the struggles of uninsured patients are the same. Whether it is transportation issues or provider shortages, uninsured patients in all practice settings face similar barriers. Ascension Wisconsinâ&#x20AC;&#x2122;s retail pharmacy sites have faced similar challenges in implementing access programs in urban and rural practice settings. Many patients qualifying for medication assistance programs have a difficult time maintaining consistent addresses and telephone numbers due to changes such as employment status and relocation. As a result of these challenges, patients are provided as much information about the program as possible during the first encounter. For example, patients are provided an informational hand-out containing contact information for specific pharmacy staff. Ascension Wisconsin pharmacies have created informational flyers describing the

Below: Joshua Coffey, PharmD Candidate, filling out Dispensary of Hope eligibility attestation with potential patient.

For a patient to qualify to receive medication through Ascension Wisconsin's medication assistance program, an eligibility form is completed at the pharmacy by trained pharmacy staff. The patient must attest to their household income and insurance status. Patients without prescription insurance and a household income at or below 200% of the 2018 Federal Poverty Guidelines are qualified (Table 1). Patients with any form of government funded insurance including Medicaid, Medicare, or VA coverage are not eligible. Once qualified, patients receive available medication free of charge.

Which Medications are Available? Ascension Wisconsin utilizes Dispensary of Hope to provide the core of the charitable medication inventory. Dispensary of Hope provides a website to allow partners to view available www.pswi.org

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program to provide to the patient’s primary care provider. To overcome challenges, sites have needed to be creative in their approach to follow-up care with enrolled patients.

Urban Setting Ascension WI retail pharmacy at St. Joseph's hospital in Milwaukee is one practice location addressing access barriers in an urban healthcare setting. Their outpatient pharmacy sees many patients from the community not yet connected to a primary care team. A lack of consistent medication access and insurance coverage complicates this problem. Even for patients with established primary care providers, running out of medications often leads to hospital and emergency department admissions. Pharmacy staff works side by side with care managers and hospital staff, frequently during the pharmacy discharge education program, to identify eligible patients. Enrollment is done in tandem with the pharmacy discharge education program. Medications are provided at bedside along with information on how to access medication resources after discharge. Dispensary of Hope medication is often used as a monthly resource, as well as a temporary bridge for patients whose insurance enrollment may be pending.

Rural Setting Medication access in north central Wisconsin is not just limited by cost but, also location. Ascension WI Retail Pharmacy in Wausau receives referrals for eligible patients from case management departments throughout Ascension Wisconsin’s north and central regions. The pharmacy utilizes technology to manage enrollment and medication therapies. Patients may live miles away and travel costs can prohibit a patient from coming to the pharmacy. To overcome this barrier, the pharmacy uses inter-department shipping or mailing services to deliver medications directly to the patient. This team-based approach to care has allowed the pharmacy to provide affordable medication access to patients throughout north central Wisconsin.

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Above: Katie Scarpace, pharmacist, reviewing Dispensary of Hope website to see available medications with primary care team.

Community Impact Partnering patient assistance programs with Dispensary of Hope impacts patients as well as health systems. In 2016, the Advisory Board studied Dispensary of Hope data from several participating health systems. This data demonstrated reductions in number of total encounters, length of stay per encounters, and direct variable cost per encounter.9 By offering this charitible service in their facilities, participating healthcare systems were able to avoid costs estimated at $650,000 per 1000 patients.9 Dispensary of Hope’s presence continues to grow and establish in Wisconsin. The power of patient access programs lies in their utilization. Networking opportunities exist in reaching out to community partners and physician groups. The more our underserved communities are made aware of programs like this, the easier it will be to connect vulnerable patients to these resources. Our pharmacies’ hope is to provide consistent medication access and improve patient outcomes by removing barriers to successful therapies. Jonathan Koehler is a Discharge Pharmacist at Ascension-Wheaton Franciscan PharmacySt. Joseph Campus in Milwaukee, WI. Katie Scarpace is the Lead Pharmacist at Ascension WI Retail Pharmacy in Wausau, WI. Joshua Coffey is a 4th year Doctor of Pharmacy Candidate at the University of WisconsinMadison School of Pharmacy in Madison, WI.

Disclosures: The authors of this article are employed by Ascension WI. Their pharmacies are participants in the Dispensary of Hope medication access program, but have no financial arrangements or responsibilities to the organization.

References

1. Center for Disease Control and Prevention website. Table 105. no health insurance coverage among persons under age 65, by selected characteristics: United States, selected years 1984-2015. https:// www.cdc.gov/nchs/hus/contents2016.htm#105. Published 2016. Accessed March 08, 2018. 2. Cohen R, Zammitti E. Problems paying medical bills among persons under age 65: early release of estimates from the National Health Interview Survey, 2011-June 2016. U.S. National Center for Health Statistics. 2016;1-10. 3. Steinman M, Sands L, Covinsky K. Self-restriction of medications due to cost in seniors without prescription coverage. J Gen Intern Med. 2001;16(12):793-799. 4. Mojtabal R, Olfson M. Medication costs, adherence, and health outcomes among Medicare beneficiaries. Health Affairs. 2003;22(4):220-229. 5. Tamblyn R, Laprise R, Hanley J, et al. Adverse events associated with prescription drug cost-sharing among poor and elderly persons. JAMA. 2001;285(4):421-429. 6. Piette J, Wagner T, Potter M, Schillinger D. Health insurance status, cost-related medication underuse, and outcomes among diabetes patients in three systems of care. Med Care. 2004;42(2):102-109. 7. Fung V, Price M, Busch A, et al. Adverse clinical events among Medicare beneficiaries using antipsychotic drugs: linking health insurance benefits and clinical needs. Med Care. 2013;51(7):614-621. 8. U.S. Department of Health and Human Services. U.S. poverty guidelines used to determine financial eligibility for certain federal programs. https://aspe.hhs.gov/poverty-guidelines. Published January 18, 2018. Accessed March 23, 2018. 9. Advisory Board Company. Dispensary of HopeAdvisory Board Evaluation White Paper. 2016;19-20.

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Volume 21 THE JOURNAL OF THE PHARMACY SOCIETY OF WISCONSIN

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Issue 4 www.pswi.org

July/August 2018

JULY/AUGUST 2018 • VOLUME 21 • ISSUE 4

Population, Public, and Global Health