Louisiana Society of Health-System Pharmacists Board of Directors & Committee Chairs

Officers & Directors

Monica Dziuba - President Joseph “Gary” LeBlanc Jr. - Past President Kisha O’Neal Gant - President Elect Katherine Aymond - Secretary Tommy Mannino - Treasurer Elizabeth M. Lafitte - Director at Large Jill Comeau - Director at Large Jason Chou - Director at Large Jessica Brady - Director at Large Chapter Presidents

Olivia Antosz - NLSHP President Joseph “Gary” LeBlanc - CLSHP President Savannah Posey - NELSHP President Kristin Howell - SCLSHP President Fahamina Ahmed - SELSHP President Shane Domingue - SWLSHP President Committee Chairs

Michael Loftin, Scott Dantonio & Stephanie Thompson - Pharmacy Management & Practice Chairs Fancy Manton - Subcommittee on Antimicrobial Stewardship Lisa Ross - Membership & Marketing Chairs William Kirchain & Jeff Evans - Public Policy Chair Katherine Aymond - New Practitioner Committee Jennifer Smith - Programming & Practitioner Education Chair Katherine Aymond & Victoria Miller - Subcommittee on Publications Elizabeth Lafitte - Midyear Meeting Coordinator Iman Borghol - Annual Meeting Coordinator Jessica Brady - ULM Liaison Iman Borghol - Xavier Faculty Liaison Tuong –Vi Tran - Xavier Student Liaison Louisiana Society of Health-System Pharmacists Past Presidents

1944-45 Gracie A. Barr* 1984-85 T. Morris Rabb 1945-46 Hebert J. Mang* 1985-86 Paul S. Knecht 1946-47 Guy L. Leefe* 1986-87 F. B. “Brad” Belding 1947-48 John F. Thompson* 1987-88 Michael W. Walker 1948-51 Valerie C. Armbruster 1988-89 Malcolm J. Broussard (Bobear) 1989-90 Theresa M. Miller 1951-52 Troy L. Carter, Jr.* 1990-91 Ruth A.C. “Cookie” Jean 1952-53 William P. O’Brien* 1991-92 Darryl Gould 1953-54 Ernest B. Simnacher 1992-93 Myra Thomas 1954-55 Frances C. Pizzolato 1993-94 Susan Webber (Polizzi) 1994-95 Michael C. Loftin 1955-56 Herbert J. Mang* 1995-96 James Witchen 1956-57 Albert P. Lauve* 1996-97 Deborah U. Carpenter 1957-58 Joseph P. Crisalli* 1997-98 Janet B. Schmitt 1958-59 Joseph P. Crisalli*/ 1998-99 Charles W. Jastram Frank Hollister 1999-00 Helen M. Calmes 1959-60 Frank W. Hollister 2000-01 Ernest Terry 1960-62 Gladys M. Hebert 2001-02 Jay Schwab 1962-63 John F. Kellerman 2002-03 Mathew Thomas 1963-64 Malcolm Claus*/ 2003-04 David Loftin Henry Derewicz 2004-05 Tommy Mannino 1964-65 Henry J. Derewicz/ 2005-06 Michael Cockerham Lowell Pfau 2006-07 Christopher Betz 1965-66 Lowell Pfau 2007-08 Barries Leung 1966-67 Troy L. Carter, Jr.* 2008-09 Marty Steffenson 1967-68 Willard L. Harrison 2009-10 Keturah Robinson 1968-69 Joseph A. Maggio, Jr. 2010-11 Teresa Nash 1969-70 W. Clark Wherritt* 2011-12 Scott Dantonio 1970-71 Daniel H. Yeoman 2012-13 Roxie Stewart 1971-72 Thomas B. Himel* 2013-14 Edward Stemley 1972-73 W. James Inbau, Jr. 2014-15 Fancy Manton 1973-74 Jon J. Tanja 2015-16 Shawn Manor 1974-75 Paul J. Comeaux 2016-17 Jennifer Smith 1975-76 Charles G. Eberhardt 2017-18 Joseph “Gary” LeBlanc 1976-77 Thomas G. Alexander 2018-2019 Monica Dziuba 1977-78 JoBeth Baggett 1978-79 Wesley R. Gladhart, Jr.* 1979-80 Claudine J. Lackey 1980-81 Shelton E. McBride 1981-82 Michael L. Louviere 1982-83 John D. “Jack” Harris, III* 1983-84 Andrew L. Wilson

* Deceased Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Table of Contents

General Meeting Information & Activities………………………………………………………………...1 Hyatt Regency Layout……………………………………………………………………………………………….3 Annual Meeting Schedule………………………………………………………………………………………….5 Faculty……………………………………………………………………………………………………………………...7 Sponsors…………………………………………………………………………………………………………………..8 Exhibitor Layout……………………………………………………………………………………………………….9 Exhibitors by Booth Numbers………………………………………………………………………………….10 2019 Pharmacy Director’s Round Table Forum……………………………………………………….11 Jason Chou, PharmD The Pharmacist’s Role in Value Based Care……………………………………………………………..15 Brice Monhundro, PharmD,BCACP Hazardous Drugs……………………………………………………………………………………………………..37 Angie Choiniere, RPh Residency Director & Preceptor Round Table: Sharing Our Solutions……………………..41 Katie Aymond, PharmD, BCPS, BCCP & Kisha Gant, BCACP, BCGP, BCPS Opioid Stewardship…………………………………………………………………………………………………45 Thomas Webb, PharmD, BCPS Quiz Bowl 2019……………………………………………………………………………………………………….54 Katherine Aymond, PharmD, BCPS, BCCP Target Influenza by Maximizing Pharmacy –Based Immunization Services…………....55 Craig Martin, PharmD, BCPS, MBA This activity is jointly provided by UK CECentral and Vemco MedED and Supported by an educational grant from Sanofi Pasteur. Immunization Updates……………………………………………………………………………………………64 George Nawas, PharmD, BCPS Palliative Care and the Role of the Pharmacist…………………………………………………….....85 Sonia Malhotra, MD, MS, FAAP VTE in Cancer Patients………………………………………………………………………………………...…142 Jill Comeau, PharmD, BCOP Healthcare Burnout………………………………………………………………………………………………..154 Hannah Welch, PharmD & Alexis Horace, PharmD, BCACP, AAHIVP Comprehensive Medication Management………………………………………………………………165 Sarah Amering, PharmD, BCACP Sex, Drugs & Rock ‘N’ Roll…………………………………………………………………………………..….193 Joshua Gauthier, PharmD Newer Anti-Diabetes Drug Therapies & Cardiovascular Outcomes………………………..202 Christopher Gillard, PharmD, BCPS Trends in Health Policy and Pharmacy Law…………………………………………………………..213 William Kirchain, PharmD, CDE & Jeff Evans, PharmD Poster Presentations Abstract Listings………………………………………………………………….226 Notes……………………………………………………………………………………………………………………..250

General Meeting Information & Activities

Registration The Annual Meeting Registration and Information Desk is located on the third floor of the Hyatt Regency. Registration will be open Thursday from 1:00 - 5:30 PM, Friday from7:30 AM - 12:30 PM & 2:00 - 5:30 PM and Saturday from 7:30 AM - 12:30 PM.

Badges Badges must be worn at all times. Badges are required for admittance to all Annual Meeting functions. Registrants, Staff, guests and speakers have white badges. Exhibitors have blue badges.

Meeting Locations Most meeting sessions will be held in the Celestin Ballroom on the third floor of the Hyatt Regency. On Thursday, the Stu- dent Breakout Session will take place in

Welcome Reception Come join us for the Thursday Welcome Reception from 7:00 - 9:30 PM at Rock ‘N’ Bowl located at 3016 S. Carrollton Ave. New Orleans, LA 70118. Transportation will be provided. There will be a bus picking up at 6:30 PM at the rear entrance of the hotel.

Exhibit Program & Lunch The exhibit program is located in Storyville Hall on the third floor from 12:00 - 3:00 PM on Friday, May 24, 2019. Please take time to visit our exhibitors and express thanks for their participation. Additionally, please thank your local repre- sentatives. Friday’s lunch will be provided for all paid registrants. Lunch will be served in Storyville Hall for exhibitors only beginning at 11:00 AM. Lunch begins for registrants at 12:00 PM and ends at 1:00 PM. Please see the handouts in your packet for a list of exhibitors and exhibit hall layout.

Door Prize Drawings Cash Drawing - Four $50 cash drawings will be held throughout the exhibit hours on Friday. All registrants are automatically entered, but you must be present to win!

Exhibitor Drawings - A door prize drawing card can be found in your meeting packet. In order to qualify for the drawing, you must have an exhibitor from 32 of the attending companies sign or initial your exhibitor card on the appropriate space. After completing your card, sign it and return it to the registration desk. The drawing will be held at 2:45 PM on Friday in the Exhibit Hall. You must be present to win.

Poster Session Drawings - A door prize drawing card can be found in your meeting packet. In order to qualify for the drawing, you must have an author from 15 of the poster presentations sign or initial your poster session card on the ap- propriate space. After completing your card, sign it and return it to the registration desk. The drawing will be held at 2:45 PM on Friday in the Exhibit Hall. You must be present to win.

Awards All awards will be presented at the General Membership Meeting on Friday, May 24 from 11:00 AM - 12:00 PM.

Past President’s Breakfast The Past President’s Breakfast has been scheduled for Saturday from 7:00 - 8:00 AM in the Imperial 5 AB on the fourth floor. This event is by invitation only.

Activity Evaluations Activity evaluations are extremely important in the development of educational needs assessment for future activities. Please take a moment to evaluate each activity you attend; we appreciate and value your input. A booklet of evaluations was included in your registration packet. Please turn in your evaluation packet at the end of the activity, or after attend- ing your last activity. Please also fill out the Annual Meeting Survey, which helps us know what you did or did not enjoy about the meeting and facility. Thank you in advance for your participation! 1 General Meeting Information & Activities

Continuing Education Credit

The Louisiana Society of Health-System Pharmacists,, The Medical Learning Institute, Inc., and the Center for Independent Healthcare Education are accredited by the Accreditation Council for Pharmacy Education as providers of continuing pharmacy education.

Certification of Continuing Education Hours/ How to Receive Credit: To receive credit for continuing education activities at the Annual Meeting registrants must: 1. Register and pay all applicable fees. 2. Attend the activity. 3. Complete the Continuing Education Credit Report included in the registration packet. 4. Initial next to each activity that you attend. PARTIAL CREDIT WILL NOT BE GIVEN FOR ANY ACTIV- ITY. (For example, if you attended only 1 hour of a 2 hour activity, then you will not get any credit for it.) 5. Complete and sign the form and submit to the registration desk at the end of the conference or af- ter attending your last activity. Include on the form your month of birth in “MM” format (for exam- ple, January is “01”) and day of birth in “DD” format (for example, the 3rd of the month is “03”). Al- so include your NABP e-Profile ID.

Due to ACPE credit recordation requirements, LSHP no longer issues statements of credit. Your CE credit will be recorded by the LSHP office electronically via CPE Monitor (see details below) within 60 days after the meeting.

CPE Monitor is a national, collaborative effort by ACPE and the National Association of Boards of Phar- macy (NABP) to provide an electronic system for pharmacists and pharmacy technicians to track their completed continuing pharmacy education (CPE) credits. All pharmacists and pharmacy technicians must obtain their NABP e-Profile ID by going to www.nabp.net. Your NABP e-Profile ID is required to receive credit for the LSHP Annual Meeting. After the Annual Meeting, LSHP will send to NABP and ACPE (via the CPE Monitor) the amount of credit you received (using your e-Profile ID) at the Annual Meeting. Once this information is received by NABP, pharmacists and pharmacy technicians will be able to log in to access information about their completed CPE.

To receive credit, registrants must attend activities designated for their credential. Activities accepta- ble for pharmacists are indicated by a “P” suffix in the activity number. Programs acceptable for phar- macy technicians are indicated by a “T” suffix in the activity number.

ACPE credit will not be given by LSHP for the following activities. Information will be given to partici- pants at these sessions on how to receive credit.  Friday, May 24, 2019 from 9:00 - 10:00 AM: Targeting Influenza by Maximizing Pharmacy-Based Immunization Services (0022-9999-19-075-L06-P)

2 Hyatt Regency Layout

Second Floor Legend: Celestin C

♠ Celestin AB

Strand 13 ♠

Celestin Foyer ♥

♣ Storyville Hall

Third Floor ♣

♥

3 Hyatt Regency Layout

Legend:

Imperial 5 (fourth floor)

4 Annual Meeting Schedule

THURSDAY May 23, 2019 Time Event Information

1:00 - 5:30 PM Registration 1:00 - 5: 15 PM Pharmacy Director’s Forum & Reverse Expo For Pharmacy Directors and Clinical Managers only. If you are a Pharmacy Director or Clinical Manager and did not receive a separate registra- tion form for this event, please contact the LSHP office. 2:45 - 3:00 PM Welcome & Announcements 3:00 - 4:00 PM The Pharmacist’s Role in Value Based Care Brice Mohundro, PharmD, BCACP 0179-0000-19-025-L04-P/T 1.0 contact hour (0.1 CEU) Application-based activity 4:00 - 5:00 PM Hazardous Drugs Angie Choiniere RPh 0179-0000-19-016-L03-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity

5:00 - 6:00 PM Residency Director & Preceptor Round Table: Sharing Our Solutions Katherine Aymond, PharmD, BCPS, BCCP & Kisha Gant, PharmD, BCACP, BCGP, BCPS 0179-0000-19-024-L04-P 1.0 contact hour (0.1 CEU) Knowledge-based activity 7:00 - 9:30 PM Welcome Reception at Rock ‘N’ Bowl 3016 S. Carrollton Ave. New Orleans, LA 70118

FRIDAY May 24, 2019 Time Event Information

7:30 AM - 12:30 PM Registration 2:00 - 5:30 PM Registration 7:30 - 8:00 AM Continental Breakfast 8:00 - 9:00 AM Opioid Stewardship Thomas Webb, PharmD, BCPS 0179-0000-19-022-L01-P 1.0 contact hour (0.1 CEU) Knowledge-based activity 9:00 - 10:00 AM Quiz Bowl 2019 Katherine Aymond, PharmD, BCPS, BCCP 0179-0000-19-029-L01-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity 9:00 - 10:00 AM Targeting Influenza by Maximizing Pharmacy-Based Immunization Services Craig Martin, PharmD, BCPS, MBA 0022-9999-19-075-L06-P 1.0 contact hour (0.1 CEU) Knowledge-based activity

10:00 - 11:00 AM Immunization Update George Nawas, PharmD, BCPS 0179-0000-19-018-L01-P 1.0 contact hour (0.1 CEU) Knowledge-based activity 11:00 AM - 12:00 PM General Membership Meeting 5 12:00 - 1:00 PM Lunch Annual Meeting Schedule

FRIDAY May 24, 2019 continued Time Event Information

12:00 - 3:00 PM Exhibit Session 2:00 - 3:00 PM Poster Session: Innovations in Pharmacy Practice and Pharmaceutical Care 0179-0000-19-032-L05-P/T 1.0 contact hour (0.1 CEU) Knowledge based-activity

3:00 - 4:00 PM Palliative Care and the Role of the Pharmacist Sonia Malhotra, MD, MS, FAAP 0179-0000-19-031-L05-P 1.0 contact hour (0.1 CEU) Knowledge-based activity

4:00 - 5:00 PM VTE in Cancer Patients Jill Comeau, PharmD, BCOP 0179-0000-19-021-L01-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity 5:00 - 6:00 PM Healthcare Burnout Hanna Welch, PharmD & Alexis Horace, PharmD, BCACP, AAHIVP 0179-9999-19-028-L04-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity

SATURDAY May 25, 2019 Time Event Information

7:30 AM - 12:30 PM Registration 7:30 - 8:00 AM Continental Breakfast

7:00 - 8:00 AM Past President’s Breakfast 8:00 - 9:00 AM Comprehensive Medication Management (CMM) Sarah Amering, PharmD, BCACP 0179-0000-19-017-L04-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity 9:00 - 10:00 AM Sex, Drugs & Rock ‘N’ Roll: Pharmacotherapeutic Considerations of Arousal, Addiction and Regression Joshua Gauthier , PharmD 0179-0000-19-019-L01-P 1.0 contact hour (0.1 CEU) Knowledge-based activity 10:00 - 11:00 AM Newer Anti-Diabetes Drug Therapies & Cardiovascular Out- comes: A Heart Healthy Blueprint for the Management of Diabetes Christopher Gillard, PharmD, BCPS 0179-0000-19-026-L01-P/T 1.0 contact hour (0.1 CEU) Knowledge-based activity 11:00 AM - 12:30 PM Trends in Health Policy and Pharmacy Law William Kirchain, PharmD, CDE & Jeff Evans, PharmD 0179-0000-19-012-L03-P/T 1.5 contact hour (0.15 CEU) Knowledge-based activity 12:30 - 1:30 PM USP 800: Understanding & Preparing for a Change Neil Hunter, PharmD 1.0 contact hour (0.1 CEU) 0179-0000-19-023-L04-P Application-based activity

6 Faculty

Brice Monhundro, PharmD, BCACP lege of Health and Pharmaceutical Sciences Clinical Pharmacist—Population Management Shreveport, LA Blue Cross and Blue Shield of Louisiana Baton Rouge, Louisiana Hanna Welch, PharmD Angie Choinere, RPh Clinical Assistant Professor Accreditation and Regulatory Compliance University of Louisiana Monroe College of Pharmacy Ochsner Health System New Orleans, LA New Orleans, Louisiana Clinical Pharmacist, Ambulatory Care University Medical Center Primary Care Center Katherine Aymond, PharmD, BCPS, BCCP New Orleans, LA Assistant Professor of Clinical Sciences University of Louisiana Monroe Alexis Horace, PharmD, BCACP, AAHIVP New Orleans, LA Associate Professor Clinical Pharmacist, Cardiology University of Louisiana at Monroe College of Pharmacy University Medical Center Monroe, LA New Orleans, LA Sarah Amering, PharmD, BCACP Kisha Gant, PharmD, BCACP, BCGP, BCPS Clinical Assistant Professor PGY1 Pharmacy Residency Director Xavier University of Louisiana College of Pharmacy Clinical Coordinator, Pharmacy New Orleans, LA Slidell Memorial Hospital Slidell, LA Joshua Gauthier, PharmD Mental Health Clinical Pharmacist - Acute Psychiatry Thomas Webb, PharmD, BCPS Southeastern Louisiana Veterans Health Care System Clinical Pharmacy Specialist, Pain New Orleans, LA Southeast Louisiana Veterans Health Care System New Orleans, LA Christopher Gillard, PharmD, BCPS Clinical Associate Professor of Pharmacy Craig Martin, PharmD, BCPS, MBA Xavier University of Louisiana College of Pharmacy Director of Professional Practice Development New Orleans, LA University of Kentucky College of Pharmacy Clinical Assistant Professor of Pharmacy University of Kentucky HealthCare Pharmacy Services Xavier University of Louisiana College of Pharmacy New Orleans, LA George Nawas, PharmD, BCPS Internal Medicine Clinical Pharmacy Specialist Clinical Assistant Professor University Medical Center Xavier University of Louisiana College of Pharmacy New Orleans, LA New Orleans, LA Part Time Staff Pharmacist Floater CVS Pharmacy Sonia Malhotra, MD, MS, FAAP Baton Rouge, LA Director of Palliative Medicine and Supportive Care Assistant Professor of Medicine (Gratis) University Medical Center/Tulane University School of Medi- LSU School of Medicine cine New Orleans, LA New Orleans, LA Assistant Professor of Medicine and Pediatrics William Kirchain, PharmD, CDE Tulane University School of Medicine Clinical Associate Professor New Orleans, LA Xavier University of Louisiana Clinical Assistant Professor of Medicine and Pediatrics New Orleans, LA Louisiana State School of Medicine Wilber & Mildred Robichaux Professorship in Pharmacy New Orleans, LA Xavier University of Louisiana Faulty Director, Palliative Medicine Pathway New Orleans, LA Tulane University Internal Medicine Residency Program New Orleans, LA Neil Hunter, PharmD Assistant Director of Pharmacy Jill Comeau, PharmD, BCOP Ochsner Medical Center Associate Professor of Clinical Sciences New Orleans, LA University of Louisiana at Monroe College of Pharmacy, Col- 7 Faculty

The success of LSHP’s Annual Meeting depends, in large part, on the partic- ipation and support of pharmaceutical and related interests. LSHP is very appreciative of the companies listed below that have generously supposed the 2019 Annual Meeting by educational or event sponsorship.

8 2019 LSHP Annual Meeting Exhibitor Layout

FFF Enterprises 101 Pfizer, Inc. 100 Avella Pharmacy/Briova RX 314 Rare Disease Theapeutics, LLC 215 Janssen/Johnson & Johnson 303 Allergan Pharmaceuticals 116 Boehringer-Ingelheim CSL Behring 109 Leadiant Biosciences 316 Pharmaceuticals 200 Ipsen Biopharmaceuticals, Inc 205 Steri-Tamp by Allied Pharmacy Pentec Health 214 RXQ Compounding, LLC 300 Products 307 Abbvie 203 Heron Therapeutics 302 Janssen Pharmaceuticals 305 Slayback Pharma 115 Equashield, LLC 216 PharMEDium Services, LLC 406 SCA Pharma 202 Takeda 304 & 306 Merck 401 & 400 Octapharma USA 112 Cheisi 110 Omnicell 209 Fresenius Kabi 201 Vyera Pharmaceuticals LLC 113 Mylan, Inc. 321 Pfizer Biosimilars 103 Sanofi Pasteur 206 BD Pyxsis 119 Helmer Scientific 207 Proxsys RX 213 Grifols USA 107 Allergan Pharmaceuticals 212 CAPS/B. Braun Medical Inc. 217 Coherus Biosciences 402 NeoMed 204 Sanofi Genzyme 312 Pfizer, Inc. (1/2) 219 AuroMedics Pharma 102 BTG Internationals 104 Astra Zeneca 403 TEVA 114 Morris & Dicskon Co., LLC 105 Genentech (1/2) 219 Piramal Critical Care 117 Amag Pharmaceuticals 301 9 Exhibitors by Booth Numbers

100 Pfizer, Inc. 213 Proxsys RX 101 FFF Enterprises 214 Pentec Health 102 AuroMedics Pharma 215 Rare Disease Theapeutics, LLC 103 Pfizer Biosmiliars 216 Equashield, LLC 104 BTG Internationals 217 CAPS/B.Braun Medical Inc. 105 Morris & Dickson Co., LLC 219 Pfizer, Inc. 107 Grifols USA 219 Genentech 109 CSL Behring 300 RXQ Compounding, LLC 110 Cheisi 301 Amag Pharmaceuticals 112 Octapharma USA 302 Hero Therapeutics 113 Vyera Pharmaceuticals LLC 303 Janssen/Johnson & Johnson 114 TEVA 304 Takeda 115 Slayback Pharma 306 Takeda 116 Allergan Pharmaceuticals 305 Janssen Pharmaceuticals 117 Piramal Critical Care 307 Steri-Tamp by Allied Pharmacy Products 119 BD Pyxsis 312 Sanofi Genzyme 200 Boehringer-Ingelheim Pharmaceuticals 314 Avella Pharmacy/Briova RX 201 Fresenius Kabi 316 Leadiant Biosciences 202 SCA Pharma 317 203 Abbvie 321 Mylan, Inc. 204 NeoMed 400 Merck 205 Ipsen Biopharmaceuticals, Inc 401 Merck 206 Sanofi Pasteur 402 Coherus Biosciences 207 Helmer Scientific 403 Astra Zeneca 209 Omnicell 405 212 Allergan Pharmaceuticals 406 PharMEDium Services, LLC

10 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Thursday, May 23, 2019 1:00 - 3:00 PM

2019 Pharmacy Director’s Round Table Forum

0179-0000-19-033-L04-P

Jason Chou, PharmD Assistant Vice President, Pharmacy Services Ochsner Health System

2 Contact Hours (0.2 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Describe controlled substances management. 2. Discuss new technologies and innovation. 3. Discuss advanced clinical practice models. 4. Describe USP 800 and USP 797. 5. Discuss managing pharmacy financials. 6. Discuss shortage management. 7. Describe IDNs and Integration.

Speaker has disclosed that she has no relevant financial relationship. 11 5/20/2019

FACILITATORS

• Jason Chou, PharmD, MS 2019 LSHP • No pertinent disclosures • Michael Mohundro, PharmD DIRECTORS • No pertinent disclosures FORUM

OBJECTIVES FORUM EXPECTATIONS

• Interactive • Active discussion • Describe approaches to achieve USP 800 compliance. • Not a lecture • Describe opportunities for advancing clinical pharmacy practice models. • Discuss approaches for effective controlled substances management. • Primer questions are a starting point • Discuss best practices in managing pharmacy finances. • Let the discussion help guide us • Discuss methods for managing ongoing drug shortages. • Describe impact of integrated delivery networks in health systems on pharmacy practices. • Discuss new technologies and innovations that impact the practice of pharmacy. • Discuss new challenges for pharmacy leaders and practice.

USP 800 (…&795…&797) CLINICAL PHARMACY PRACTICE

• Practice model changes/shifts • Facilities • Funding and growth • Surveillance • Measures and metrics • Policies and procedures • Best practices • Training • Assessments of risk • 795 and 797

12 1 5/20/2019

CONTROLLED SUBSTANCES PHARMACY FINANCE AND SPEND MANAGEMENT • High cost drug oversight • Approaches to reducing diversion • Increasing overall drug costs • Policy and procedures • Utilization efforts and opportunities • Opportunity for multi-disciplinary teams • Use of data and measures • Utilization of data • Partnering with executive leadership • Best practices

DRUG SHORTAGES HEALTH SYSTEMS

• system vs. stand alone facility • Learnings over past several years • Challenges • Best practices/opportunities • Best practices discussion

CHALLENGES FOR PHARMACY LEADERS – TODAY AND FUTURE

TECHNOLOGY AND INNOVATION What is new and exciting?

13 2 5/20/2019

REFERENCES

• Usp.org. (n.d.). Updates on Compounding Standards. [online] Available at: https://www.usp.org/compounding/updates-on-standards [Accessed 20 May 2019]. • USP General Chapter <795> Pharmaceutical Compounding—Nonsterile Preparations. US Pharmacopeia 41-National Formulary 36 (online subscription). Accessed May 20, 2019 OPEN DISCUSSION • USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. US Pharmacopeia 41-National Formulary 36 (online subscription). Accessed May 20, 2019 • USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. US Pharmacopeia 41-National Formulary 36 2S (online subscription). Accessed May 20, 2019

14 3 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Thursday, May 23, 2019 3:00 - 4:00 PM

The Pharmacist’s Role in Value Based Care

0179-0000-19-025-L04-P/T

Brice Monhundro, PharmD, BCACP Clinical Pharmacist—Population Management Blue Cross and Blue Shield of Louisiana Baton Rouge, LA

1 Contact Hour (0.1 CEU) Application-based activity

Pharmacist Objectives: Pharmacy Technician Objectives: 1. Describe key elements included in value 1. Review value based care models. based care models. 2. List medication management approaches 2. Explain medication management used to achieve outcomes in value based approaches to improve clinical and financial arrangements. outcomes in value based arrangements. 3. Describe the role of the pharmacy 3. Create strategies to integrate pharmacists in technician in the value based care model the value based care model team. team.

Speaker has disclosed that she has no relevant financial relationship. 15 The Pharmacist’s Role in Value-Based Care Brice Labruzzo Mohundro, Pharm.D., BCACP Clinical Pharmacist– Population Management

1

Pharmacists • Describe key elements included in value­based care models • Explain medication management approaches to improve clinical and financial outcomes in value­based arrangements • Create strategies to integrate pharmacists in the value­based care model team OBJECTIVES Pharmacy Technicians • Review value­based care models • List medication management approaches used to achieve outcomes in value­based arrangements • Describe the role of the pharmacy technician in the value­based care model team

2

16 • Form of reimbursement that links care delivery payments to the quality of the care received VALUE-BASED CARE • Rewards providers for both efficient and efficacious care • Alternative payment model • Current model vs. fee­for­service replacement

3

Better Care

VALUE-BASED CARE: TRIPLE AIM Improved Reduced Total Population Health Cost of Care

4

17 1

Pay for Coordination • Primary care physician (PCP) is center of care and VALUE­BASED coordinates between multiple providers to improve CARE: efficiency and quality PAYMENT MODELS • Patient Centered Medical Home Model Pay for Performance • Physician reimbursement dependent on meeting quality and efficiency measures

5

2 Bundled Payments • Providers reimbursed a set amount to pay for specified care episodes (e.g., hip replacement, heart failure) VALUE­BASED CARE: Shared Savings Programs PAYMENT MODELS • Incentivize providers to improve quality and reduce costs for a defined patient population by rewarding the providers with a percentage of net savings achieved as a result of their efforts • Upside or Downside risk • Accountable Care Organizations

6

18 • Group of providers, systems and healthcare entities working collaboratively and sharing responsibility for the ACCOUNTABLE quality, cost and coordination of care for a defined CARE population ORGANIZATIONS • Small provider groups • Large integrated delivery systems • Works with a payer to achieve triple aim goals

7

Fragmented Care System Patients coordinate their own care between providers and services

TRADITIONAL CARE vs.vs ACOUNTABLE CARE

8

19 Accountable Care Organizations Improved coordination and communication between providers and patients

TRADITIONAL CARE vs.vs ACOUNTABLE CARE

9

Medicare • Pioneer ACO Model • Medicare Shared Savings Program • Next Generation ACO Model TYPES OF ACOs Medicaid • Varies from state to state

Commercial • Health plan partners with providers to form an ACO 10

20 • In 2017, the U.S. spent nearly $3.5 trillion on healthcare costs • 18% of the Gross Domestic Product • 75% of healthcare spend in the U.S. is attributed to chronic conditions and drugs used to treat them U.S. HEALTHCARE EXPENDITURES • $290 billion annually attributed to medication misuse • $150 billion spent on treating avoidable adverse events • 50% of chronically ill patients are non­adherent to medication regimens leading to $100 billion in costs annually

11

1

• Academy of Managed Care Pharmacy partnered with Hobart Innovations to perform an environmental assessment of pharmacy management in ACOs ACO MEDICATION MANAGEMENT • Assessment included entities with an affordable care component: • CMS Pioneer ACO Programs • Medicare Shared Savings Programs (MSSP) • Commercial ACOs

http://amcp.org/ACOs_Pharmacists/RoleofPharmacists/. Accessed May 15, 2019. 12

21 2 • 37% responding were involved in commercial ACO arrangements and 48% were in a MSSP

• 45% were at risk for medication costs (mostly commercial ACOs) ACO MEDICATION MANAGEMENT • When asked to rate the importance of medication management in 2014, 2015 and 2017, respondents communicated that medication management is currently moderately important, but would become increasingly important over the next 5 years

http://amcp.org/ACOs_Pharmacists/RoleofPharmacists/. Accessed May 15, 2019. 13

• Over half of ACOs do not have a formal strategy to manage drug costs • 63% ACOs employ and/or contract with PHARMACY pharmacists TRENDS IN ACOs • 38% providers not utilizing a pharmacist are extremely or somewhat interested in integrating them in the team

Pharmacy benefit management institute. Pharmacy trends in accountable care organizations. 2016.

14

22 • Commercial based ACOs may be at risk for medication costs MEDICATION • Most ACOs collect or monitor medication data MANAGEMENT • Underuse, overuse and misuse of medications can affect medical spending and healthcare outcomes

15

Population level • Manage an overall ACO population

PHARMACIST’S Provider level ROLE IN VALUE­ • Work with healthcare providers serving ACO BASED CONTRACTS population

Patient level • Provide individual patient care within ACO population

16

23 • Benefit provided for Medicare beneficiaries • Increase emphasis on wellness and preventative measures • Can be provided by “a physician, qualified nonphysician practitioner, medical professional (including a health educator, registered dietitian, nutrition professional, or MEDICARE ANNUAL other licensed practitioner), or team of such medical WELLNESS VISITS professionals who are working under the direct supervision of a physician.” • A pharmacist is considered a qualified nonphysician practitioner authorized to perform annual wellness visits • ACOs can increase shared savings by preventing or decreasing severity of illness

17

Medication Therapy Management Services within an ACO

18

24 • Develop and manage their own formulary FORMULARY • Rely on the formulary used by each insurer they have a OPTIMIZATION contract with • Use a combination of formulary management techniques

19

• Review prescribed medications, any over the counter medications and/or nutritional supplements COMPREHENSIVE • Assess medication efficacy MEDICATION • Identify drug interactions REVIEWS • Improve adherence • Identify gaps in care

20

25 Assessing medication appropriateness and potential safety concerns • Drug­disease contraindications • Drug­drug interactions • Inappropriate duration • Incorrect dose DRUG UTILIZATION REVIEWS • Over and under utilization • Therapy duplication

Data can be used to detect prescribing trends in a defined population, which would benefit from pharmacist intervention

21

Use quality measures to target patients not at goal • Improve disease management by using quality measures to target patients not at goal DISEASE • Work under collaborative agreements to adjust MANAGEMENT medications • Medication adherence initiatives • Identify medication management opportunities

22

26 • Identify medication management opportunities • Work under collaborative agreements to adjust medications DRUG THERAPY • Anticoagulation • COPD/Asthma MANAGEMENT • Diabetes • Smoking Cessation CLINICS • Hypertension • Hepatitis C • Lipid • HIV • Medication adherence initiatives

23

1 • Review discharge instructions and medications with patients and make sure they understand the changes within 7 days POST DISCHARGE • Can be performed telephonically or in person by a MEDICATION pharmacist RECONCILIATION • Note in medical record that discharge medications reconciled with current med list in outpatient medical record • Signed and dated current medication list

24

27 2 Community pharmacies can collaborate with hospitals within ACOs to provide medication reconciliation and reinforce discharge plan via bidirectional data flow • Patient demographics POST DISCHARGE • Contact information (PCP, hospital coordinator, caregiver) MEDICATION • Med list RECONCILIATION • Diagnosis list • Lab values • Hospital identified issues for resolution One transitional care pilot had pharmacists perform MTM visits 72 hours post discharge in heart failure patients • 50% reduction in preventable 30 day readmissions Prog cardiovasc dis. 2017 Sept-Oct, 60(2):249-258. 25

3 An integrated group practice and health plan with a patient centered medical home model decreased readmission rates at 7, 14 and 30 days post discharge after having a medication review performed by a pharmacist 3 to 7 days POST DISCHARGE post discharge MEDICATION • 80% of patients had at least one discrepancy when RECONCILIATION discharged • For every 100 patients who received medication reconciliation performed by a pharmacist, it was estimated $35,000 was saved

26

28 • Medication Reconciliation • Collect and verify medication history • Assist with prior authorization process to ROLE OF THE promote efficiencies in physician practices PHARMACY TECHNICIAN • Provide education on community resources and medication related financial assistance programs • Meds to Beds programs

27

1 • Technicians review reports of recently discharged patients and identify patients at high risk of having a readmission due to an adverse drug event • > 65 yo TELEPHONIC • 8 or more medications MEDICATION • prolonged hospital stay RECONCILIATION • cognitive impairment • patients with heart failure • Diabetes • Pneumonia • MI

28

29 2

• Prescribed anticoagulants, digoxin, potassium and/or sedatives TELEPHONIC • For high­risk members, certified pharmacy technician MEDICATION placed call 30 days after initial pharmacist call RECONCILIATION • Reduced overall readmissions and admissions due to adverse drug events • High level of patient satisfaction

29

• Medication adherence rates • Quality metrics (e.g., • Number of adjustments to HbA1c, blood pressure, medication regimens etc.) • Deprescribing rate (e.g., brand • Preventative care KEY PERFORMANCE to generic switches, activities (e.g., INDICATORS recommending clinically immunizations, effective, lower cost drug) diabetes screenings) • Decrease in physician time • Appropriate spent medication utilization on medication related issues • Avoidable hospital/ER • Avoided adverse drug events visits • Pharmacy spend • Quality payments achieved

30

30 1 Commercial Plan Funded Integrated Pharmacist Model • Large academic medical center integrated SUCCESSFUL pharmacist model at 15 primary care clinics and 4 MODELS specialty clinics INTEGRATING • Health Plan Support PHARMACISTS INTO • Initial funding provided by health plan to PCP PRACTICES develop patient­centered medical home • Codes created to reimburse non­physician providers for face­to­face and phone visits • Quality based financial incentives

Am J Health Syst Pharm. 2012 Jun 15;69(12):1063-71. 31

2

Center for Medicare and Medicaid Innovation Pilot SUCCESSFUL • Clinical pharmacy teams consisting of a clinical pharmacist, MODELS pharmacy resident and pharmacy technician INTEGRATING PHARMACISTS INTO • Use collaborative practice agreements to initiate, adjust PCP PRACTICES and discontinue medications for chronic conditions • An average of 10 medication related problems were identified and corrected for each patient enrolled

https://www.cdph.ca.gov/Programs/CCDPHP/DCDIC/CDCB/CDPH%20Document%20Libr ary/CMMWhitePaperCDPH2015Dec23FINALrev.pdf. Accessed May 15, 2019.

32

31 3

Pharmacists Integrated in Family Medicine Residency SUCCESSFUL Program MODELS • Pharmacists and pharmacy residents provide MTM INTEGRATING services and perform Medicare wellness visits PHARMACISTS INTO • Improved utilization of ACE inhibitors and beta blockers PCP PRACTICES in heart failure patients, inhaled steroids for asthma and DEXA screening rates

Advisory board. Integrated pharmacy models in primary care. December 2014.

33

SUPPORTING PHARMACIST INVOLVEMENT • 30% reduction in per­person total cost of care • Reduction in hospitalizations SUMMARY OF • 70% of quality metrics improved when pharmacists EVIDENCE fully integrated in primary care practices • After integration of pharmacists, physicians report • Increased time spent dedicated to patient care activities • Improved quality of care

34

32 • Culture of collaboration HEALTH SYSTEMS & • Sharing data PAYERS WORKING • Working toward the goal of providing quality care at an TOGETHER affordable cost • Improved outcomes for patients

35

MANAGE • Analyze pharmacy claims data MEDICATION USE • Monitor prescribing patterns WITH PAYER DATA • Monitor high cost drugs with low cost alternatives

36

33 Example of an ACO Managing Medication Costs

ACO was able to maintain a flat Per Member, Per Month (PMPM) pharmacy cost over time compared to an increase in PMPM for the plan & combined ACOs

ACO All ACOs Plan „ Budget Year 2016 „ Performance Year 7/17 – 6/18 37 BlueCross Blue Shield of Louisiana claims data 2017-2018.

PRESCRIBER EDUCATION

38

34 Payer working with Providers to Promote Cost Effective Care

$2.50 0.50

0.45 Dollars 0.44 0.44 Rx Count 0.43 0.41 $2.00 0.40 0.40 0.39 0.39 0.36 0.36 0.35 0.34 0.32 0.31 $1.50 0.30

0.25 0.24

$1.00 0.20

0.15 0.14

$0.50 0.10 0.09

0.05

$0.00 0.00 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar 2015 2016

39 BlueCross Blue Shield of Louisiana claims data 2015-2016.

• Integrating pharmacists as part of the healthcare team • Lack of awareness of pharmacist’s role in the ambulatory care setting CHALLENGES FOR • Pharmacists not recognized as healthcare providers PHARMACISTS • No compensation for pharmacist’s services • Complex regulations for clinical protocols • Collaborative practice agreements • Need to advocate a pharmacist’s value

40

35 41

36 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Thursday, May 23, 2019 4:00 - 5:00 PM

Hazardous Drugs

0179-0000-19-016-L03-P/T

Angie Choinere, RPh Accreditation and Regulatory Compliance Ochsner Health System New Orleans, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: Pharmacy Technician Objectives: 1. Recognize the difference between 1. Recognize the difference between hazardous drugs (USP 800) and Hazardous hazardous drugs (USP 800) and Hazardous Pharmaceutical waste. Pharmaceutical waste. 2. Define NIOSH category 1, 2 and 3 and how 2. Define NIOSH category 1, 2 and 3 and how NIOSH contributes to USP 800. NIOSH contributes to USP 800. 3. Identify the goal of USP 800 and measures 3. Identify the goal of USP 800 and measures for the goal. for the goal. 4. Outline an assessment of risk on a drug. 4. Outline an assessment of risk on a drug. 5. Determination of who within your facility 5. Determination of who within your facility must have USP 800 training. must have USP 800 training.

Speaker has disclosed that she has no relevant financial relationship. 37 5/17/2019

ProblemEffective Statement/Business December 1, 2019 The first federally enforceable standards that protect Casehealthcare workers from hazardous medications USP 800- Beyond the www.usp.org/compounding Pharmacy

Identified by the National Institute for Occupational Safety and Health (NIOSH), a department of the CDC, hazardous drugs can cause problems ranging from simple skin rash to reproductive toxicities and Angie Choiniere, RPh cancer.

Who does this apply to? Hazardous Drugs Risk

USP 800 Chapter • Healthcare workers may be exposed to HDs at many points during HD cycle “This chapter applies to all healthcare personnel who handle HD • One study of worker contact with preparations and all entities that store, prepare, transport, or surfaces contaminated with HDs identified a number of job administer HDs (e.g., pharmacies, hospitals and other healthcare categories not traditionally institutions, patient treatment clinics, physicians' practice facilities, or expected to be exposed. Unit veterinarians' offices). Personnel who may potentially be exposed to HDs clerks, transport workers, ward include, but are not limited to: pharmacists, pharmacy technicians, nurses, aides, dietitians, and oncologists physicians, physician assistants, home healthcare workers..” • Recent studies have also begun to examine the impact of HD exposure on healthcare workers’ families.

3 4

Who determines “Hazardous Drug”?

The National Institute for Occupational Safety and Health (NIOSH), part of the CDC, determines hazard. December 1, 2019 Goal Group 1. Antineoplastic drugs (+ BCG) Group 2. Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug Group 3. Non-antineoplastic drugs that primarily have adverse reproductive effects. www.cdc.gov/niosh Work Practices Education Characteristic Description Carcinogenic A substance or agent that can cause cancer USP 800 Teratogenic or developmental A substance or agent capable of producing fetal malformation toxicity Compliant Reproductive toxicity Adverse effects on the male and/or female reproductive systems caused by exposure to a toxic substance or an agent Documentation Monitoring Organ toxicity at low doses Toxicity of an organ by a pharmaceutical when it is administered in low doses Genotoxic A substance or agent causing deleterious action on a cell’s genetic material affecting its integrity; the degree to which something causes damage to or mutation of DNA

Similar drugs New drugs whose structure and toxicity are similar to existing drug 6 determined hazardous by above criteria

38 1 5/17/2019

Summary Charter Project Team: USP 800 Compliance Executive Sponsor: Project Lead: Angie Choiniere Cost of Not Complying PMO Resource: Business Case: USP Chapter 800 is a federally enforceable standard, containing both best practice recommendations and mandates for reducing the occupational exposure of healthcare workers who handle nonsterile and sterile hazardous drugs (HD). The standards set by USP Chapter 800 are applicable in all settings in which HDs are received, stored, transported, compounded, administered and disposed of and anywhere healthcare workers may contact HD residue. The FDA DOT DEA standards are in effect now and will be federally enforceable starting December 1st 2019. In Scope: All personnel working at Ochsner facilities- Ochsner employees, providers, contract workers, volunteers, EPA and Enforcing Bodies OSHA LA DEQ residents, fellows, and students in following areas: receiving, storage, transport (internal and between facilities), patient care areas, disposal, cleaning and sterile processing. LA Board LA Board Training (Training of contract workers), attestation, work practices, competency observation, PPE, Spill Kits, Surgical Kits, of of CMS Nursing Linen removal and laundering process, Haz. Comm Plan, Policy, Internal communication, Medical Surveillance, Internal Pharmacy Audit, Job Descriptions TJC Out of Scope: Visitors to Ochsner Facility Pharmacy Engineering Controls construction Cost of non‐compliance Expected Benefits: Ochsner System is fully compliant with USP 800 regulations. Metrics: 1. Lack of compliance, or even half‐hearted compliance will expose system • All personnel have completed appropriate OLN education and signed attestation, to risk of legal actions, adverse publicity and large awards. • Competency observation with documentation has been completed for each employee 1. Citations/ fines by governing bodies • Passing score on internal audits 2. Loss of accreditation and/or conditional accreditation • Surface wipe analysis shows no HD residue Items in red- to be All Job Descriptions updated • decided 7 Targeted Start Date: January 2018 Resources Needed: TBD Anticipated End Date: December 2019 Project Team Members: Next slide

USP 800 Project Team Other Areas Impacted

Project Team Member Department Title  Lab Services, Inpatient, Ambulatory, Outpatient Pharmacy VP-Pharmacy Services  Respiratory Therapy Center for Quality Medical Director for Regulatory Affairs

Pharmacy AVP- Pharmacy  Facilities Management

Nursing AVP-Clinical Informatics & Transformation  Environmental Services Nursing/ Supplies AVP-Nursing, Supply Chain  Food Services, Physical Therapy, others who enter Facilities Director of Facilities Management patient care areas and/or have physical contact with Supply Chain Dir-Ochsner Health System Purchasing patients Compliance Manager- Compliance  Patient transport, air transport, courier services Retail/Specialty Pharmacy AVP Retail Services

IS Pharmacy Dir-IS Epic Project  Rehab, Long Term Care, Home Nursing Employee Health Dir-Employee Health  Sterile Processing Department or Service Internal Communication Sr Internal Communications Specialist  Students, Residents, Volunteers Legal (HR) Dir-Associate General Counsel

IS VP Clinical Systems  Construction, repair and equipment servicing

OLN DIR Education Services 9 10 Contracting VP Vendor Management

Draft Project Dec 1st PlanMarch 1 April 1 May 1 July 1 Sept 1st Work that needs to be done

 Hazardous Communication Plan Reviewed Perform Internal Audit Establish Internal Audit and Monitoring Parameters and Ownership  Handling Options Master and Monitor Clean  Hazardous Drugs Labeled, IS build in Epic EPIC Alerts- In process- screenshots to be OLN MODULES Created OLN Modules included in OLN Modules  SDS Sheets Available Do we have USP800 Completed Epic Compliant Alerts  All employees confirmed in writing- acknowledge risk of HD handling the right SOPs Created Go- Supplies All Attestation Signed Live  ASTM rated PPE IdentifiedVizient people at the Catalog  Deactivation and Decontamination before Cleaning and Disinfecting SOPs table?  “Do Not Tube” list reviewed Competencies Observation Outline Competencies Observed  Administration SOPs (protective techniques, PPE)

 CSTD selected

Haz Comm Plan Updated  Patient Care SOPs (Identification, Excreta, Linens, Cleaning- Spill Kits) No Residue on Surfaces  Hospital Laundered Scrubs SOP

Policy  Alternative Duty (consistent accommodation outline- employees refuse HD handling, pregnant) Policy Review  Disposal SOPs

Accommodations  Outline Spill Control SOPs

 Eye Wash Areas Medical Surveillance  Environmental Monitoring (Baseline, every 6 month re-swab)

Assessment of Risk-  Medical Surveillance (Legal, HR decides how to track this) Vizient (Angie)  Personnel Training- annual, upon orientation- must be documented and competencies observed

 Exposure/ Near Miss Communication FormWeb updated 12

39 2 5/17/2019

Resources

 USP 800

 ASHP 2018 Hazardous Drug Guidelines

 ONS 4th Edition Hazardous Drug Handling

 NIOSH 2016 Hazardous Drug List

 Coming in June: NIOSH 2019 update USP 795 final version USP 797 final version

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40 3 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Thursday, May 23, 2019 5:00 - 6:00 PM

Residency Director & Preceptor Round Table: Sharing Our Solutions

0179-0000-19-024-L04-P

Katherine Aymond, PharmD, BCPS, BCCP Assistant Professor of Clinical Sciences University of Louisiana Monroe New Orleans, LA

Clinical Pharmacist, Cardiology University Medical Center New Orleans, LA

Kisha Gant, PharmD, BCACP, BCGP, BCPS PGY1 Pharmacy Residency Director Clinical Coordinator, Pharmacy Slidell Memorial Hospital Slidell, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Discuss the ASHP 2019 residency preceptor qualifications update. 2. Identify methods to improve preceptor engagement and education. 3. Explain strategies to mitigate issues related to managing residents. 4. Propose mechanisms that promote exchanges between Louisiana’s residency programs.

Speakers have disclosed that they have no relevant financial relationship. 41 5/17/2019

Objectives

1. Discuss the ASHP 2019 residency preceptor qualifications update. Residency Director & Preceptor Round Table: 2. Identify methods to improve preceptor Sharing Our Solutions engagement and education. 3. Explain strategies to mitigate issues related Katie Aymond, PharmD, BCPS, BCCP Assistant Clinical Professor to managing residents. University of Louisiana at Monroe 4. Propose mechanisms that promote Kisha O’Neal Gant, PharmD, BCACP, BCGP, BCPS PGY1 Residency Director exchanges between Louisiana's residency Clinical Coordinator, Pharmacy Slidell Memorial Hospital programs.

Recognition in the Area of Pharmacy Practice for Which They Serve as Preceptors (4.8.c) Preceptors must have one of the following: • BPS certification • Fellow at a state or national level organization • Post‐Graduate Fellowship in the advanced practice area or an advanced 4.8 PRECEPTORS’ QUALIFICATIONS degree beyond entry level pharmacy degree (e.g., MBA, MHA) • Formal recognition by peers as a model practitioner (PGY1 COMMUNITY-BASED - 4.3.B.3.) – Pharmacist of the year ‐ recognized at state, city or institutional level where only one individual is recognized – Patient care, quality, or teaching excellence – recognition at organization level (not internal to pharmacy department only) for an initiative that resulted in positive outcomes for all patients that either was operational, clinical or educational in nature) • Credentialing and privileging granted by the organization/practice/health system with ongoing process of evaluation and peer review • Subject matter expertise as demonstrated by ten or more years of practice experience in the area of practice in which they precept.

https://www.ashp.org/‐/media/assets/professional‐development/residencies/docs/pgy1‐and‐pgy2‐guidance‐document‐ summary‐of‐changes.ashx?la=en&hash=6929CA13ADC30F85D56F013283811287E3DE1699

Recognition in the Area of Pharmacy Practice Ongoing professionalism, Including . . . for Which They Serve as Preceptors (4.8.c) Advancing the Profession (4.8.f./4.3.b.6.) Preceptors must have one of the following: • Certificate of Completion from a state or nationally available‐program Ongoing professionalism is demonstrated by that relates to the area of practice in which they precept (e.g., Epic Willow certification, Six Sigma/LEAN Six Sigma certification, ISMP completing at least 3 activities in the last 5 sponsored Medication Safety certificate, ASHP sponsored year. certificates). Health‐system/local residency site based programs are excluded. • Active community service related to – Validated certification that results from an exam by the organization providing certification professional practice (e.g., Free Clinic, medical – Pharmacy related certification recognized by Council on mission trips) Credentialing in Pharmacy (CCP) http://www.pharmacycredentialing.org/Files/CertificationProgra • Active involvement on committees within an ms.pdf • Other examples include: Certified Professional in Patient Safety (CPPS), enterprise (e.g., work impacts more than one Certified Diabetes Educator(CDE) site across a health‐system) – Exceptions to the list that do not meet this domain are ACLS, PALS and BLS https://www.ashp.org/‐/media/assets/professional‐development/residencies/docs/pgy1‐and‐pgy2‐guidance‐document‐ https://www.ashp.org/‐/media/assets/professional‐development/residencies/docs/pgy1‐and‐pgy2‐guidance‐document‐ summary‐of‐changes.ashx?la=en&hash=6929CA13ADC30F85D56F013283811287E3DE1699 summary‐of‐changes.ashx?la=en&hash=6929CA13ADC30F85D56F013283811287E3DE1699

42 1 5/17/2019

What Are Your Thoughts?

PRECEPTOR ENGAGEMENT & EDUCATION

Image by OpenClipart‐Vectors from Pixabay

What Preceptor & Residents Think What Others Are Doing

Am J Health‐Syst Pharm. 2015; 72:1305‐ 14 Am J Health‐Syst Pharm. 2015; 72:1305‐ 14

What NMC Is Doing NEBRASKA MEDICAL CENTER (NMC)

https://flic.kr/p/P5wJEB

Am J Health‐Syst Pharm. 2013; 70:1605‐8

43 2 5/17/2019

What NMC Is Doing What Are You Doing ?

Image by Gerd Altmann from Pixabay

Am J Health‐Syst Pharm. 2013; 70:1605‐8

44 3 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 8:00 - 9:00 AM

Opioid Stewardship

0179-0000-19-022-L01-P

Thomas Webb, PharmD, BCPS Clinical Pharmacy Specialist, Pain Southeast Louisiana Veterans Health Care System New Orleans, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Identify variables affecting the current climate of opioid prescribing. 2. Recognized opportunities for intervening in settings where opioid use carries potential risk. 3. Recognize the role of opioids when indicated for use.

Speaker has disclosed that he has no relevant financial relationship. 45 5/17/2019

Disclosures

• Dr. Webb has no financial conflicts of interests to disclose. Brace For Impact: • The views expressed in this presentation are those of the author and do not necessarily reflect the official policy or position of any agency The Pharmacist’s Role Amid a of the United States government, including the Department of Veterans Affairs. The presentation was not prepared as part of official Reduced Reliance On Opioids government duties for Dr. Webb.

Thomas Webb, PharmD, BCPS May 24, 2019

Interactive Poll OBJECTIVES

1. Identify variables affecting the current climate of opioid prescribing. 2. Recognize opportunities for intervening in settings where opioid use carries potential risk. 3. Realize the role of opioids when indicated for use.

6 Objective 1

Identify variables affecting the prescribing of opioid medications.

‐CDC

46 1 5/17/2019

7 Drug Overdose Deaths 2013 Rates of Opioid Area 2014 2015 2016 2017** Prescribing Louisiana* 777 861 996 1108

United 47055 52404 63632 70237 States

LA: 108.9 prescriptions per 100 people *One of 23 states that had statistically significant increase in drug overdose death rates from 2016‐2017 **Opioids were involved in 47,600 overdose deaths in 2017 (67.8% of all drug overdose deaths) Note: Mainly synthetic opioids (other than methadone) are current main driver of drug overdose deaths Table adapted from: https://www.cdc.gov/drugoverdose/data/statedeaths.html (Accessed March 23, 2019)

CDC

2015 2017 Rates of Opioid Rates of Opioid Prescribing Prescribing

LA: 100.4 prescriptions per 100 people LA: 89.5 prescriptions per 100 people

CDC CDC

11 12 “New” Louisiana Laws for Opioid Prescribers The Opioid Pendulum in the United States

Prescribers are prohibited from issuing > 7 day supply opioid prescription if • First time opioid prescription for outpatient adult with acute condition, or • Growth of illicit Attempts to • Recipient is a “Minor” AND prescriber must discuss risk and necessity of opioid with a opioid market parent/tutor/guardian • OUD stigma CONTROL • Exceptions (based on prescriber medical judgement): • Sole reliance on the Crisis • The opioid is necessary to treat the acute medical condition, or opioids for pain • The opioid is necessary for the treatment of chronic pain, cancer‐related pain, or palliative care • Reducing use of illicit opioids When issuing an opioid, prescriber must discuss with patient: • Expanding treatment of • Patient’s option to fill lesser quantity than prescriber OUD • Risks associated with prescribed opioid use • Limiting use of opioids CRISIS for pain to exceptional PMP query must occur: circumstances • Initial prescription, and • Strengthening non‐ • At least every 90 days (if opioid treatment continues) opioid pain interventions

47 2 5/17/2019

14 Objective 2 Weighing the Analgesic Options

Recognize opportunities for clinical intervention in settings where “Nonpharmacologic therapy and nonopioid pharmacologic therapy opioids are avoided. are preferred for chronic pain.” ‐CDC, 2016

“What does the pharmacist with whom I’m speaking to recommend for this patient’s pain?"

15 16 Evidence‐Based Non‐Pharmacologic Options for Certain Pain Conditions Evidence‐Based Pharmacotherapeutic Options for Certain Pain Conditions

Recommending Indication Excerpted Non‐Pharmacologic Interventions Body Recommending Body Indication Excerpted Pharmacotherapeutic Interventions ACR (2012) Osteoarthritis • Hand OA (conditionally recommend): joint protection techniques, assistive devices to of hand, hip perform ADL, thermal modalities, splints when indicated ACR (2012) Osteoarthritis • Conditional: topical capsaicin, topical NSAID, oral NSAID, and knee (depending whether tramadol, acetaminophen, intra‐articular corticosteroid • Knee or hip OA (strongly recommend): cardiovascular and/or resistance land‐based hand, knee, or hip) exercise, aquatic exercise, weight loss (if overweight) IASP NeuPSIG Neuropathic pain • First line: duloxetine, venlafaxine ER, TCA, gabapentin, (2015) pregabalin EULAR (2016) Fibromyalgia • Aerobic and strengthening exercise (strong for) Second line: capsaicin patch, lidocaine patch, tramadol • CBT (weak for) • • Multi‐component therapies (weak for) • Acupuncture or hydrotherapy (weak for) EULAR (2016) Fibromyalgia • Weak for: amitriptyline (low dose), duloxetine, milnacipran, • Meditative movement therapies (qigong, yoga, tai chi) and mindfulness‐based stress tramadol, pregabalin, cyclobenzaprine reduction (weak for) ACP (2017) Chronic lower • Multiple, including but not limited to: ACP (2017) Chronic lower back pain • First line (weak recommendation): NSAIDs back pain • Exercise, multidisciplinary rehabilitation, mindfulness‐based stress reduction, acupuncture (moderate quality evidence) • Second line (weak recommendation): duloxetine, tramadol • Tai chi, yoga, progressive relaxation, CBT, spinal manipulation, etc… (low‐quality evidence)

18 POINT OF NO RETURN The Pharmacist’s “Corresponding Responsibility”

PHARMACIST Excerpt from the Controlled Substances Act • A prescription for a controlled substance to be effective must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of his professional practice. The responsibility for the proper prescribing and dispensing of controlled substances is upon the prescribing practitioner, but a corresponding responsibility rests with the pharmacist who fills the prescription.

Patient waiting on opioid prescription

48 3 5/17/2019

19 20 for Opioid Risk Mitigation Counseling Patients on Opioid Use Can the Pharmacist Intervene? unseling on Opioid Use YES

rine Drug Monitoring YES

Take as prescribed Caution about returning to high doses if DMP Querying YES • • • Expectations of Use (benefits vs risks) time has passed • Opioid tolerance can diminish • Possible risks when combined alcohol, pioid Overdose Education YES benzodiazepines, other sedatives • Naloxone dispensing if indicated Disposal of obsolete opioids • Constipation • • Take‐back events, flushing down toilet aloxone Access YES

Expectations of Opioid Use 21 22 Urine Drug Monitoring

• Opiates immunoassay (included in most urine drug screens) detects natural opiates: • Detects morphine, codeine, heroin, MAYBE oxycodone and hydrocodone at elevated doses • An opiate immunoassay will NOT detect methadone, fentanyl, tramadol

• Consider “window of detection” and limitations with samples

• Anticipate course of action/plan before results are obtained and analyzed

• UDM results may warrant stopping opioids, but should not dismiss care

CDC. Franklin GM.

23 24 Prescription Drug Monitoring Program Naloxone

CDC: • Mu opioid receptor antagonist (used to rapidly reverse opioid overdose) • For long‐term opioid therapy, consider checking PMP every 3 months or more frequently • Risk factors that may increase risk of opioid overdose (not inclusive list): • Discuss PDMP findings with patient • Prescribed Oral Morphine Equivalent Daily Dosage ≥ 50mg • History of Substance Use Disorder • Concurrent Benzodiazepine Use Louisiana Board of Pharmacy (as of March 2019): • Signs of opioid overdose • No legislative requirement for pharmacists to query PMP for opioid Not breathing prescriptions • • Not responsive to awaking despite appropriate attempts • However, before dispensing a legitimate marijuana product, pharmacist must • Fingernails and/or lips are blue/purple query PMP, review findings, and resolve any identified concerns when prescriber CDC.

49 4 5/17/2019

25 26 Naloxone – Louisiana Standing Order Naloxone nasal spray Naloxone auto‐injector Renewed for one year by LA Department of Health on 1/7/2019. Supplied in box of TWO sprays Supplied in box of TWO auto‐injectors

No electronic component Has electronic teaching voice component (not Pharmacist must: necessary for administration) 1. Secure a prescription or order from legitimate prescriber in order to dispense Spray dosage unit (4mg/0;.1 mL) in one nostril Inject one dosage unit (2mg/0.4mL) in outer thigh IM 2. Verify recipient’s understanding of use or subQ (+/‐ clothing) a. Recognizing signs of opioid‐related overdose Repeat other dosage unit in other nostril in 2‐3 b. Storage and administration of naloxone minutes if indicated Repeat other dosage unit in 2‐3 minutes if indicated c. Emergency procedure (i.e., seek medical assistance) 3. Attach Standing Order to invoice AND store with transaction documents at pharmacy MAY INDUCE SYMPTOMS OF OPIOID WITHDRAWAL (e.g. nausea, emesis, headache, stomach pain, change in blood pressure, tachycardia, sweating, tremors) Refills are permissible.

This standing order does not guarantee reimbursement from any payer source.

28 Objective 3 Excerpts from CDC Guideline

Realize the role of opioids when indicated for use. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient.

If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate.

29 30 Opioid Pharmacodynamics Mu Receptor Full Agonist Opioids

• An opioid is any chemical that acts on an opioid receptor. Potential adverse effects • The μ (mu) receptor is the primary target for opioid‐directed pain relief. • Tolerance‐related: sedation, nausea/vomiting, pruritus, respiratory depression, hyperalgesia Receptor Functions when agonized Subtype • Non‐remitting: constipation • Methadone and Buprenorphine: QTc prolongation Analgesia, sedation inhibition of respiration; μ (mu) slowing of GI tract, hormone modulation, neurotransmitter release modulation Organ impairment can increase risk of adverse effects Analgesia, hormone modulation, neurotransmitter δ (delta) depending on which opioid is used release modulation • Example: fentanyl may be safer than oxycodone or methadone in hepatic impairment κ (kappa) Analgesia, psychosis effects; slowing of GI tract

50 5 5/17/2019

31 IASP Statement on Opioids (February 2018) OPIOID for OPIOID for PAIN DEPENDENCE Excerpts: • “There may be a role for medium‐term, low‐dose opioid therapy in carefully selected patients with chronic pain who can be managed in a monitored setting.” • “However, with continuous longer‐term use, tolerance, dependence, and other neuroadaptations compromise both efficacy and safety.” • “Chronic pain treatment strategies that focus on improving the quality of life, especially those integrating behavioral and physical treatments, are preferred.”

33 34 Example criterions Medications for OUD Opioid Use Disorder (see DSM‐5 for full list) Considerations Buprenorphine Methadone Naltrexone Defined in DSM‐5 as “a problematic pattern of Craving or strong desire or opioid use leading to clinically significant Mechanism of Action Partial agonist Agonist Antagonist impairment or distress, manifested by at least urge to use opioids at mu‐Opioid Receptor two of eleven defined criteria occurring within a Route of Sublingual, buccal, Oral Oral, intramuscular year” Administration for OUD subdermal implant, extended‐release Important life activities subcutaneous are given up or reduced extended release because of opioid use Federal Regulations Schedule III; requires Schedule II; only Requires and waiver to prescribe available at federally prescription; office‐based outside OTPs certified OTPs and the treatment or Recurrent opioid use in Availability acute inpatient hospital specialty substance use Implant: REMS certification for setting for OUD treatment programs, situations in which it is prescriber treatment including OTPs physically hazardous Subcutaneous: REMS certification for pharmacy SAMHSA.

Useful Links Question #1

• GoodRx – pricing website Which below statement is true? One or more options may be correct. • https://www.goodrx.com/ A) Drug overdose deaths in Louisiana have declined in recent years. • DEA ‐ Controlled Substance Public Disposal Locations B) Drug overdose deaths in the U.S. have declined in recent years. • https://apps.deadiversion.usdoj.gov/pubdispsearch/spring/main?execution=e 1s1 C) Opioids were involved in most drug overdose deaths in the U.S. in 2017. D) The rate of opioid prescribing in Louisiana (in terms of per 100 residents) has decreased in recent years.

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Question #2 Case #1

Which below prescription reflects opioid prescribing that is acceptable LG is a 40 yo female patient with fibromyalgia and depression who comes to as deemed by Louisiana legislation? Consider the indication is for acute your pharmacy today. She is complaining of diffuse of pain “everywhere”. She pain and there may be no exceptional details related to the does not have any other pertinent medical history. She requests a pharmacist prescription. call her physician to recommend a medication. What are evidence‐based A) Oxycodone IR 5mg tab, one tab q6h prn pain, #120 tablets Known labs (collected within last month): interventions that may be BMP: no abnormalities appropriate to recommend? B) Tramadol 50mg tab, one tab q8h prn pain, #30 tablets CBC: no abnormalities C) Hydromorphone IR 2mg tab, one tab q8h prn pain, #10 tablets LFT: no abnormalities A) Oxycodone SCr: 0.7 mg/dL B) Aerobic exercise eGFR: ~95 mL/min C) Duloxetine D) Methadone

Case #2

RN is a 52 yo male patient with failed back syndrome who is picking up his routine pain prescription. You notice that it has been ~2 weeks since he last picked up a morphine prescription. RN says that his doctor is increasing the morphine dosage due to worsened back pain. During prescription counseling, RN says this morphine helps him to complete activities at home throughout the day. He has constipation often when taking morphine. He has old morphine pills from previous prescriptions and asks what he should do with them. Last filled prescription: What should be discussed with Questions? morphine IR 15mg tab, one tab PO RN right now? q12h prn pain, #60 tabs for 30 day supply A) Educating RN about naloxone New prescription: B) Take every prescribed dose of morphine IR 15mg tab, one tab PO morphine q6h prn pain, #120 tabs for 30 day C) Discuss laxative for prn use with supply RN’s opioid prescriber No prior naloxone prescription filled D) Keep old morphine in your cabinet

References

1. Understanding the Epidemic.. CDC. https://www.cdc.gov/drugoverdose/epidemic/index.html. Accessed March 23, 2019. 2. Drug Overdose Deaths. CDC. https://www.cdc.gov/drugoverdose/data/statedeaths.html. Accessed March 23, 2019. 3. Opioid Prescribing Laws ‐ Recent Changes. Louisiana State Board of Medical Examiners. Jan 2018. https://www.lsbme.la.gov/content/opioid‐prescribing‐laws‐recent‐changes. 4. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016;65(No. RR‐1):1–49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1https://www.cdc.gov/Other/disclaimer.html 5. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465‐74. 6. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318‐328. 7. Qaseem A, Wilt TJ, Mclean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166:514‐530. 8. Finnerup NB, Attai N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta‐analysis. Lancet. 2015;14:162‐173. 9. Title 21 U.S.C. §1306.04. 10. Franklin GM. Opioids for chronic noncancer pain: A position paper of the American Academy of Neurology. 2014. https://www.aan.com/uploadedFiles/Website_Library_Assets/Documents/6.Public_Policy/1.Stay_Informed/2.Position_Statements/3.PDFs_of_all_Position_Statements/Position%2 0and%20Policy%20Documents.pdf. 11. Laws and Regulations. Louisiana Board of Pharmacy. August 2018. Accessed March 23, 2019. http://www.pharmacy.la.gov/assets/docs/Laws/LB_2018‐0801‐S.pdf. 12. LA Health Alert Information‐‐2019 Renewed Standing Order for Naloxone. Louisiana State Board of Medical Examiners. Feb 2019. https://www.lsbme.la.gov/content/la‐health‐alert‐ information‐2019‐renewed‐standing‐order‐naloxone. 13. Schumacher MA, Basbaum AI, Naidu RK. Opioid Agonists & Antagonists. In: Katzung BG. eds. Basic & Clinical Pharmacology, 14e New York, NY: McGraw‐Hill; . http://accesspharmacy.mhmedical.com/content.aspx?bookid=2249§ionid=175220393. 14. IASP Statement on Opioids. February 2018. https://www.iasp‐pain.org/Advocacy/OpioidPositionStatement 15. Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63, Full Document. HHS Publication No. (SMA) 18‐5063FULLDOC. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2018.

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Question #1 Question #2

Which below statement is true? One or more options may be correct. Which below prescription reflects opioid prescribing that is acceptable as deemed by Louisiana legislation? Consider the indication is for acute pain and there may be no exceptional details related to the A) Drug overdose deaths in Louisiana have declined in recent years. prescription. B) Drug overdose deaths in the U.S. have declined in recent years. C) Opioids were involved in most drug overdose deaths in the U.S. in 2017. A) Oxycodone IR 5mg tab, one tab q6h prn pain, #120 tablets D) The rate of opioid prescribing in Louisiana (in terms of per 100 B) Tramadol 50mg tab, one tab q8h prn pain, #30 tablets residents) has decreased in recent years. C) Hydromorphone IR 2mg tab, one tab q8h prn pain, #10 tablets

Case #2 Case #1 RN is a 52 yo male patient with failed back syndrome who is picking up his routine pain prescription. You notice that it has been ~2 weeks since he last picked up a morphine prescription. RN says that LG is a 40 yo female patient with fibromyalgia and depression who comes to his doctor is increasing the morphine dosage due to worsened back pain. During prescription counseling, RN says this morphine helps him to complete activities at home throughout the day. He your pharmacy today. She is complaining of diffuse of pain “everywhere”. She has constipation often when taking morphine. He has old morphine pills from previous does not have any other pertinent medical history. She requests a pharmacist prescriptions and asks what he should do with them. call her physician to recommend a medication. Last filled prescription: What should be discussed with What are evidence‐based morphine IR 15mg tab, one tab PO RN right now? Known labs (collected within last month): interventions that may be q12h prn pain, #60 tabs for 30 day BMP: no abnormalities appropriate to recommend? supply A) Educating RN about naloxone CBC: no abnormalities New prescription: B) Take every prescribed dose of LFT: no abnormalities A) Oxycodone morphine IR 15mg tab, one tab PO morphine SCr: 0.7 mg/dL B) Aerobic exercise q6h prn pain, #120 tabs for 30 day C) Discuss laxative for prn use with eGFR: ~95 mL/min C) Duloxetine supply RN’s opioid prescriber D) Methadone No prior naloxone prescription filled D) Keep old morphine in your cabinet

53 1 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 9:00 - 10:00 AM

Quiz Bowl 2019

0179-0000-19-029-L01-P/T

Katherine Aymond, PharmD, BCPS, BCCP Assistant Professor of Clinical Sciences University of Louisiana Monroe New Orleans, LA

Clinical Pharmacist, Cardiology University Medical Center New Orleans, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Review clinical pearls within diabetes, cardiology and infectious diseases. 2. Discuss pharmacotherapy options for pain management. Pharmacy Technician Objectives: 3. Summarize recent guideline 1. Recognize pharmacotherapy options for recommendations across sub-specialties. diabetes, cardiac pathophysiology and

Speaker has disclosed that she has no relevant financial relationship. 54 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 9:00 - 10:00 AM

Targeting Influenza by Maximizing Pharmacy - Based Immunization Services

0022-0000-19-075-L06-P

Craig Martin, PharmD, BCPS, MBA Director of Professional Practice Development University of Kentucky College of Pharmacy University of Kentucky HealthCare Pharmacy Services

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Identify individuals who are at high risk of influenza or complications associated with influenza. 2. Recognize how patient factors and preferences can influence vaccine selection between the different, currently FDA - approved vaccines. 3. Evaluate strategies that can be utilized on an individual and institutional basis to overcome barriers to improve influenza vaccination rates.

This activity is jointly provided by UK CECentral and Vemco MedED and supported by an educational grant from Sanofi Pasteur. 55 5/17/2019

Faculty

Craig Martin, PharmD, BCPS, MBA Professor and Chief Operations Officer University of Kentucky College of Pharmacy Lexington, Kentucky

Disclosure of Relevant Financial Relationships with Commercial Interests No speaker or planners have any relevant financial relationships to disclose. Content review confirmed that the content was developed in a fair, balanced manner free from commercial bias. Disclosure of a relationship is not intended to suggest or condone commercial bias in any presentation, but it is made to provide participants with information that might be of potential importance to their evaluation of a presentation.

Accreditation Get Credit Instructions

Pharmacy Accreditation At the conclusion of the activity: The University of Kentucky College of Pharmacy is accredited by the Accreditation Council for Pharmacy 1. Go to www.CECentral.com/getcredit Education as a provider for continuing pharmacy education. 2. In the box marked ‘Activity Code’, enter PLN19135 and click 'Search' This knowledge-based activity has been assigned UAN 0022-9999-19-075-L06-P and will award 1.00 contact 3. The appropriate activity details will display; click ‘Proceed to Credit” on the right hand side. hour (0.100 CEU) of continuing pharmacy education credit in states that recognize ACPE providers. 4. If you are not signed into CECentral.com, you will either need to login or create an account (free of Statements of participation will indicate hours and CEUs based on participation and will be issued online at the charge) conclusion of the activity. Successful completion includes signing in at registration, attending the entire session for 5. Check all of the sessions for which you are requesting credit, check the certification statement, and which credit is claimed, completing the activity evaluation and requesting credit online at conclusion of the activity. click ‘Submit’ Credit will be uploaded to CPE Monitor, and participants may print a statement of credit or transcript from their NABP e-profile. The College complies with the Accreditation Standards for Continuing Pharmacy Education. 6. Complete the Evaluation and click ‘Submit’ 7. Your certificate will display; you can print it or view it later by clicking ‘Transcript’ in the blue bar at Other the top of the page UK Healthcare CECentral certifies this activity for 1.00 hour of participation. The deadline to claim credit online is July 23, 2019 The University of Kentucky is an Equal Opportunity University

Educational Need Practice Gap

Seasonal influenza remains a serious and life-threatening disease that can • Guidelines from ACIP recommend the flu vaccine for all individuals over cause serious complications in patients with various chronic health conditions, the age of 6 months. However, data from the CDC reveal that: such as asthma, diabetes, heart disease, and immunosuppression. The most • Only about half of the children from 6 months-17 years of age receive the flu vaccine effective approach to reduce the burden of seasonal influenza is through • Only about one-third of adults from 18-64 years of age receive the flu vaccine • In one study over five seasons at a large tertiary referral hospital, over 60% of patients admitted who vaccination. Yet, barriers to immunization have played a significant factor in were unvaccinated for influenza refused the vaccine while hospitalized. The most common reason given limiting vaccine use and their effectiveness. Pharmacists must continue to take was “believed not to be at risk.” • Though vaccination of healthcare providers (HCPs) is critical in preventing infection in vulnerable a proactive role in preventing influenza, particularly those patients at higher patients, nearly 1 in 4 HCPs are not vaccinated risk of serious complications from infection. Additionally, with the expansion of • The availability of new vaccines can add to the complexity of selecting the available influenza vaccines, selecting the most appropriate vaccine can be confusing. most appropriate vaccine for each patient type. • This complexity and confusion can augment barriers of improving vaccination rates within healthcare institutions.

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Learning Objectives Influenza: The Virus

• Identify individuals who are at high risk of influenza or • Orthomyxoviridae virus complications associated with influenza • Key components • Differentiate among the current FDA-approved influenza vaccines • Hemagglutinin and recognize how patient factors and preferences can influence . Viral attachment to cell vaccine selection . Membrane fusion • Neuraminidase • Evaluate strategies that can be utilized on an individual and . Facilitates virus movement institutional basis to overcome barriers to improve influenza . Prevents aggregation of newly-formed virus vaccination rates particles

Treanor JT. Influenza. In: Mandell GL, ed. Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2010: 2265-2288.

Epidemiological Terms Influenza Transmission

• Antigenic drift • Spread by contact with respiratory . Amino acid point mutations in secretions hemagglutinin or neuraminidase • Virus attaches to and penetrates . Seasonal epidemics columnar epithelial cells of • Antigenic shift respiratory tract . Large genetic changes lead to • Incubation period of 18‒72 hours emergence of serologically new • Virus remains detectable for 5‒10 viruses to which population has days no immunity . Pandemic flu CDC. MMWR Recomm Rep. 2013; 62(7): 1-43. Treanor JT. Influenza. In: Mandell GL, ed. Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2010: 2265-2288. Treanor JT. Influenza. In: Mandell GL, ed. Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2010: 2265-2288.

Major Influenza Pandemics

1920 1930 1940 1950 1960 1970 1980 1990 2000 2010

1918: Spanish influenza (H1N1) 50 million deaths worldwide

1957: Asian flu (H2N2) ~70,000 deaths in U.S.

1968: Hong Kong flu (H3N2) ~34, 000 deaths in U.S. 2009: Swine flu (H1N1) ~9,000-18,000 deaths

The College of Physicians of Philadelphia. Influenza Pandemics. Available at: https://www.historyofvaccines.org/index.php/content/articles/influenza-pandemics. CDC. Flu Symptoms & Complications. Available at: https://www.cdc.gov/flu/consumer/symptoms.htm.

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Impact of Influenza Recent Influenza Seasons

2017‒18 2018‒19 estimates ‒ • Since the 2010 2011 influenza season, annually incidence • ~80,000 deaths estimated (through April 6) of: • 180 pediatric deaths reported to the CDC • 32,900‒54,800 deaths • Symptomatic illnesses: ranged from 9.3 million (2011-12) to 49 . 80% were not vaccinated •35‒40 million cases million (2017-18) • Overall hospitalization rates (all ages) • 482,000‒585,000 hospitalizations • Medical visits: ranged from 4.3 million (2011-12) to 23 million were the highest ever recorded by CDC (2017-18) . Individuals age ≥65 years accounted for approximately 58% of reported flu- • Hospitalizations: ranged from 140,000 (2011-12) to 960,000 associated hospitalizations (2018-18) . 37.1% of adults vaccinated • Deaths: ranged from 12,000 (2011-12) to 79,000 (2017-18) . Lowest level since 2010-11 season

Garten R, et al. MMWR Recomm Rep. 2018;67(22):634-42. CDC. https://www.cdc.gov/flu/index.htm. CDC. Available at: https://www.cdc.gov/flu/about/burden/index.html.

Cumulative Hospitalizations, 2018-19 Influenza Vaccine Priorities

• ALL 6+ MONTHS WANTING TO PREVENT INFLUENZA • HEALTHCARE WORKERS • High risk for disease (symptomatic and asymptomatic) • High risk for transmission • If sick, not available to provide healthcare… • PATIENTS @ Highest Risk (severe illness/spread) • Pregnant women • Newborns and children • Elderly • “Medical Comorbidities” • Household contacts of high-risk • Long-term care, institutionalized, crowded living conditions CDC. https://www.cdc.gov/flu/about/burden/prelimi Does this sound like your patients? That’s why YOU need a vaccine. nary-in-season-estimates.htm. CDC. Available at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm?s_cid=rr6703a1_w.

Consequences and Complications Diagnosis

• Increased work/school absenteeism • When should we perform diagnostic testing? • Fever, cough, myalgia • Laryngotracheobronchitis • If results will influence clinical management • Secondary Bacterial Pneumonia: . Outpatients at high risk of complications • Uncomplicated influenza illness followed by 4‒14 days of improvement . • Recurrence of fever, cough, sputum production Immunocompromised patients with febrile respiratory • New consolidation on chest X-ray symptoms during influenza season • Likely pathogens: S. pneumoniae, H. influenzae, S. aureus . Inpatients with fever and respiratory symptoms during • Myositis: elevated creatine kinase and myoglobinuria influenza season • Myocarditis and pericarditis . • Reye’s syndrome: post-viral encephalopathy that occurs in children Elderly persons and infants with suspected sepsis or fever • Hospitalization and death of unknown origin during influenza season

Treanor JT. Influenza. In: Mandell GL, ed. Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2010: 2265-2288. Cate TR. Am J Med. 1987;82:15-19. Harper SA, et al. Clin Infect Dis. 2009;48:1003-1032.

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Influenza Testing Methods The Seasonal Influenza Vaccine Changes Annually

• Egg-based vaccine production: ~9 months • Strain choice (Feb) reflects antigenic drift [Prior season + Southern Hemisphere] • RIDT most commonly used in • US Vaccination season: Vaccine available to ‘disease passed’… ambulatory setting . More than 10 FDA cleared • 2019‒20 Vaccine strain composition: . Sensitivity generally 50‒100% Trivalent . Specificity generally >95% • A/Brisbane/02/2018 (H1N1)pdm09–like virus • A/Kansas/14/2017 (H3N2)–like virus • B/Colorado/06/2017–like virus (Victoria lineage) Quadrivalent • Same as trivalent plus B/Phuket/3073/2013–like virus (Yamagata lineage)

CDC. Available at: https://www.cdc.gov/flu/season/flu-season-2019-2020.htm.

Available Influenza Vaccine Types Influenza Vaccine Regular Dose

IIV3 or IIV4: ʻKilledʼ, injectable • Inactivated (IIV) • Inactivated cell culture-based • 6 months and older– Trivalent (IIV3) or Quadrivalent (IIV4) • Quadrivalent (IIV4) • Quadrivalent (ccIIV4) • FDA-indicated ages may vary by manufacturer: • Trivalent (IIV3) • Recombinant ‒ Practically speaking, these vaccines are for anyone who doesn’t have • Standard dose a contraindication to influenza vaccine • Trivalent (RIV4) • High dose ® • Adjuvanted (aIIV3) • Live Attenuated IIV4 Intradermal (Fluzone Intradermal) • Intradermal • Quadrivalent (LAIV4) • FDA approval for 18‒64 years • Manufacturer-supplied injection device (includes needle) ‒ 90% smaller needle; 9 mcg of each antigen (compared to 15 mcg of standard dose in IIV4) • Quadrivalent IIV, Inactivated Influenza vaccine CDC. Available at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm?s_cid=rr6703a1_w. Fluzone® Intradermal Quadrivalent (Influenza Vaccine) Prescribing Information. Sanofi Pasteur Inc., Swiftwater, PA. July 2017.

Influenza Vaccine High Dose Influenza Vaccine Adjuvanted Vaccine

® IIV3, high-dose (Fluzone High-Dose) aIIV3, adjuvanted vaccine (Fluad) • Contains 60 mcg each of the 3 influenza antigens (compared to 15 mcg • Trivalent inactivated influenza vaccine plus a proprietary adjuvant that is each for regular IIV3) proposed to recruit immune cells at the site of injection and enhance • Slightly higher rate of MILD reactions antigen uptake • Indications: Patients ≥65 years • Results in potentially greater immunogenic response in elderly patients • Clinical trial had shown high-dose vaccine was 24.2% more effective in • Indication: Patients ≥65 years preventing influenza in adults ≥65 than the standard vaccine. • Clinical trials show non-inferiority with IIV3 based on seroconversion and geometric mean titers • No data yet available that demonstrate decrease in influenza disease

Fluzone High-Dose (Influenza Vaccine) Prescribing Information. Sanofi Pasteur Inc. Swiftwater, PA. July 2017. DiazGranados CA, et al. N Engl J Med. 2014;371:635-45. Fluad™ (influenza vaccine, adjuvanted) Prescribing Information. Sequiris, Inc., Holly Springs, NC. March 2016.

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Influenza Vaccine Live Attenuated Influenza Vaccine Cell-Cultured and Recombinant Vaccines (LAIV4; FluMist®)

• ccIIV4 (Flucelvax® Quadrivalent) • In place of chicken eggs, uses animal cells (Canine Kidney) as host (reference strain • Cold-adapted nasal vaccine; quadrivalent obtained from virus originally grown in eggs); quadrivalent • Approved for ages ≥4 years • Licensed only for healthy people 2 through 49 years • Approved by ACIP for 2018‒19 flu season • RIV4 (Flublok®) • Recombinant vaccine— egg-free hemagglutinin influenza vaccine produced by • Not recommended for 2016‒17 and 2017‒18 flu seasons recombinant DNA technology using a baculovirus (a virus that infects insects) that produces virus-like particles, hemagglutinin (vaccine of choice for true egg allergy) • Not recommended as first-line vaccine by American Academy of • Approved for ages ≥18; only 16-week shelf-life; quadrivalent Pediatrics (IIV preferred) • Adverse events similar to other inactive vaccines

Flucelvax® Quadrivalent (influenza vaccine) Prescribing Information. Sequiris, Inc., Holly Springs, NC. July 2018. FluMist® Quadrivalent (influenza vaccine live, intranasal) Prescribing Information. MedImmune, LLC, Gaithersburg, MD. August 2018. Flublok® (influenza vaccine) Prescribing Information. Protein Sciences Corp., Meriden, CT. September 2016.

Alphabet Soup of Influenza Vaccines Vaccination: ACIP Recommendations

• 6 mos ‒ 3 yrs • IIV4: Quadrivalent Inactivated Influenza Vaccine • FluLaval Quadrivalent • ccIIV4: Cell culture-based • Fluarix Quadrivalent • Fluzone Quadrivalent • IIV3: Trivalent IIV (standard and high dose) • Afluria Quadrivalent • aIIV3 Adjuvanted Inactivated Influenza Vaccine • Pregnant Women (any trimester) • IIV or RIV4 RIV4 Recombinant Influenza Vaccine • • No LAIV • LAIV4 Live Attenuated Influenza Vaccine • Immune Compromised • No LAIV • Older Adults • Get the vaccine • Which one? It’s complicated…

CDC. Available at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm?s_cid=rr6703a1_w.

Vaccination: What About Egg Allergy? Universal Flu Vaccine

• Rationale: provides immunity against all influenza virus strains • Not a contraindication to any product regardless of virus subtype or antigenic drift • Recommendation • Will eliminate the need for annual vaccination, or at least require less • Any history of severe allergic reaction to eggs warrants frequent vaccination vaccination in a medical setting under the supervision of “a • BiondVax M-001 entered phase 3 trial in 2018 in Europe health care provider who is able to recognize and manage (results expected in late 2020) severe allergic conditions.” • Peptide vaccine (no virus) • A previous severe reaction to any influenza vaccine is a • Contains 9 highly-conserved viral epitopes common to 40,000 contraindication. influenza strains • Other vaccine candidates also in development

CDC. Available at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm?s_cid=rr6703a1_w.

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Prepare Yourself: The Pregnancy/Vaccine Brainstorming and Audience Participation Questions are Coming

• How do you choose a vaccine type? • Study published in the September 25, 2017 issue of Vaccine • Does it matter? • Case-control, covered two influenza seasons (2010‒11 and 2011‒12) • Spontaneous abortion was associated with receipt of influenza vaccination in the previous 28 days (adjusted OR 2.0 [95% CI, 1.1‒3.6]) • No causal relationship established due to study size • What has been established is the risk of severe influenza-related consequences to mother and fetus

Donahue JG, et al. Vaccine. 2017;35:5314-22.

Influenza Vaccine Supply Yes, vaccines may cause adverse effects

• Many issues in prior years • But the most common thing they cause is… • Current season projection • 163‒168 million doses • More than 80% of doses are thimerosal-free • More than 80% of doses are quadrivalent • 85% of doses are produced with eggs • Current status (as of 3/1/19) Adults • Approximately 169.1 million doses distributed

CDC. Available at: https://www.cdc.gov/flu/about/qa/vaxsupply.htm. CDC. Available at: https://www.cdc.gov/flu/about/qa/index.htm.

Case Exercise 1 Case Exercise 1 Which vaccine for: Which vaccine for:

A 67-year-old man with type 2 diabetes mellitus and no history A 67-year-old man with type 2 diabetes mellitus and no history of egg allergy? of egg allergy?

1. IIV3, standard 1. IIV3, standard 2. IIV3 high-dose (Fluzone High-Dose) 2. IIV3 high-dose (Fluzone High-Dose) 3. IIV4, intradermal (Fluzone Intradermal) 3. IIV4, intradermal (Fluzone Intradermal) 4. ccIIV4 (Flucelvax) 4. ccIIV4 (Flucelvax) 5. Any of the above 5. Any of the above 6. 1 and 2 only 6. 1 and 2 only

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Case Exercise 2 Case Exercise 2 Which vaccine for: Which vaccine for:

A 27-year-old woman with well-controlled asthma and hive- A 27-year-old woman with well-controlled asthma and hive- form reaction to eggs? form reaction to eggs?

1. No vaccine 1. No vaccine 2. IIV4, standard 2. IIV4, standard 3. aIIV3 (Fluad) 3. aIIV3 (Fluad) 4. RIV3 (Flublok) 4. RIV3 (Flublok) 5. 2, 3 or 4 5. 2, 3 or 4 6. 2 or 4 only 6. 2 or 4 only

Case Exercise 3 Case Exercise 3 Which vaccine for: Which vaccine for:

A 17-year-old with history of severe allergic reaction (i.e., A 17-year-old with history of severe allergic reaction (i.e., respiratory distress) to flu vaccine? respiratory distress) to flu vaccine?

1. IIV4, standard 1. IIV4, standard 2. LAIV4 2. LAIV4 3. RIV3 (Flublok) 3. RIV3 (Flublok) 4. ccIIV4 (Flucelvax) 4. ccIIV4 (Flucelvax) 5. No vaccine/refer to specialist 5. No vaccine/refer to specialist 6. 3 or 4 only 6. 3 or 4 only

Case Exercise 4 Case Exercise 4 Which vaccine for: Which vaccine for:

A 25-year-old woman in second trimester of pregnancy? A 25-year-old woman in second trimester of pregnancy?

1. IIV4, standard 1. IIV4, standard 2. LAIV4 2. LAIV4 3. No vaccine until after birth 3. No vaccine until after birth 4. A or B 4. 1 or 2

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Q and A

63 8 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 10:00 - 11:00 AM

Immunization Update

0179-0000-19-018-L01-P

George Nawas, PharmD, BCPS Clinical Assistant Professor Xavier University of Louisiana College of Pharmacy New Orleans, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacists Objectives: 1. Discuss the updated immunization recommendations for adults approved by the Centers for Disease Control and Prevention 2. Identify the appropriate vaccines for adults across their life span, including those who are at– risk and with special needs. 3. Understand the benefits of vaccines and dispel myths regarding their use.

Speakers has disclosed that he has no relevant financial relationship. 64 5/17/2019

Disclosures Immunization in the Modern World: Speaker: George Nawas, PharmD, BCPS ‐ Received a fee from LSHP for speaking at today’s educational 2019 Update activity

‐ No other financial disclosures or conflict of interest to disclose in relevance to this presentation George Nawas, PharmD, BCPS Clinical Assistant Professor Department of Clinical and Administrative Sciences Xavier University College of Pharmacy 1 2

Objectives Pre‐Assessment Questions

• Discuss the updated immunization recommendations for adults approved by the Centers for Disease Control and •To join – Prevention (CDC)

• Identify the appropriate vaccines for adults across their life span, including those who are at‐risk and with special needs

• Understand the benefits of vaccines and dispel myths regarding their use

3 4

Pre‐Assessment – Question #1 Pre‐Assessment – Question #2

5 6

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Pre‐Assessment – Question #3 Pre‐Assessment – Question #4

7 8

Immunization Outcomes

Cases Cases Cases Cases Cases Disease (US) 2013 2014 2015 2016 2017 Diphtheria 01000

Hib 31 40 29 30 22 Measles 187 667 188 85 122 Mumps 584 1,223 1329 6369 5629 Pertussis 28,639 32,971 20,762 17,972 15,808 Rubella 9 6 5 1 9

CRS 1 1 1 2 Tetanus 26 25 29 34 31 Varicella 11,359 10,172 9,789 8953 7059 9 10

MMWR. Weekly. January 5, 2018;66(52)

Vaccine Schedules

• Approved by the Advisory Committee on Immunization Practices (ACIP) in Fall 2019

• Released in January or February of each year • New editions on CDC website earlier if changed

• Separate childhood/adolescent and adult schedules

• Catch‐up schedules mentioned

11 12

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Grace Period

• Minimum interval on catch‐up schedule is 28 days

• Slightly earlier administration unlikely to interfere with antibody production KEY POINTS REGARDING IMMUNIZATION • ACIP grace period of 4 days

• Different live vaccines may have interference if interval less than 28 days

13 14

Minimal Intervals Between Vaccines and Other Products if not Administered Simultaneously General Rule in Immunization Regarding Intervals

Vaccines Minimum Interval • If interval between vaccine doses in a series is – Two inactivated vaccines No minimum Inactivated and live vaccines No minimum Two live vaccines, if not simultaneous 28-day minimum interval • Decreased Inactivated vaccines and antibodies No minimum • May interfere with antibody response and protection Live vaccines followed by blood products 2 weeks • Increased Blood product given before live vaccine Minimum interval varies (look • Delays protection for patient up) • Does not reduce vaccine effectiveness Live vaccine followed by PPD skin test 28-day minimum interval (or else false negative) PPD skin test followed by live vaccine Administer vaccine after PPD skin test has been read 15 16

American Academy of Pediatrics. Active Immunization. In: Pickering L, Baker C, Kimberlin D, Long S, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatric; 2012.

Contraindications Vaccines and Pregnancy

• General rules – • Encourage vaccination prior to pregnancy if possible • Do not vaccinate if will likely hurt patient • Do not vaccinate if patient has a history of a severe allergy to a vaccine component • Administer any deferred vaccines after pregnancy • Severe allergy – immediate & life‐threatening anaphylaxis • Indicated vaccines during pregnancy – • NOT considered contraindications – • Inactivated Influenza Vaccine (IIV) recommended – not LAIV • Allergies to components not available in vaccines (ex: penicillin, • Tdap: Administer EVERY pregnancy sulfa, etc..) • History of non‐serious allergic reactions to vaccines Avoid administering LIVE vaccines during pregnancy • Mildly sick with minor illnesses (ex: upper respiratory tract • infection, etc..) • Theoretical risks • Premature births 17 18 • Pregnancy ‘in the household’

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Vaccines and Immunosuppression Adverse Events Following Vaccination

• Can be very complicated • Decision should be made with a medical provider • Give vaccines 4 weeks BEFORE immunosuppression, if feasible • Immunize household contacts living with immunocompromised Live Attenuated Vaccines patients • Mild form of the natural illness • Concern with LIVE and INACTIVATED vaccines – Live vaccines Inactivated vaccines Inactivated Vaccines Concern for increased risk for adverse effects Concern for decreased • Injection site reactions due to uninhibited effectiveness (common) replication • May be with or without 19 fever 20

BUCKLE UP: IT’S TIME TO REVIEW THOSE FANCY VACCINE TABLES!

21 22 HOPE YOU’RE AS EXCITED AS I AM

INFLUENZA

23 24

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2018‒2019 Influenza Vaccines

Influenza Vaccine (manufacturer)* Approved Age Indications • Symptoms Inactivated Influenza Vaccine • High fever, cough (can be severe), fatigue, weakness, Fluzone (Sanofi Pasteur) IIV4 6 months and older headache, myalgia Fluvirin (Seqirus) IIV3 4 years and older • Different presentation than common cold Fluarix (GSK) IIV4 6 months and older FluLaval (GSK) IIV4 6 months and older Afluria (Seqirus) IIV3 6 months and older • Complications Afluria (Seqirus) IIV4 6 months and older Pneumonia, exacerbation of pulmonary and cardiac • Fluzone High-Dose (Sanofi Pasteur) IIV3 65 years and older conditions Flucelvax (Seqirus)–cell cultured (not eggs) ccIIV4 4 years and older Flublok (Sanofi Pasteur) RIV3/RIV4 18 years and older Fluad (Seqirus) IIV3** 65 years and older Live Attenuated InfluenzaVaccine*** 25 26 FluMist (MedImmune) LAIV4 2 years to 49 years

MMWR Morb Mortal Wkly Rep. 2015;64(RR30):818-825. Grohskopf LA et al. MMWR Morb Mortal Wkly Rep. 2014;63(32):691-697.

Influenza Vaccination Influenza Vaccination in Persons with Allergies

“Routine annual influenza vaccination is • ONLY contraindication recommended for all persons aged 6 months or older • If patient had a previous SEVERE allergic reaction to the who do not have contraindications.” influenza vaccine, regardless of the component suspected of being responsible

• If history of egg allergy • Hives or any other reaction that is less severe  should receive influenza vaccine

• If more severe than hives (e.g., angioedema, respiratory distress)  administer vaccine under the supervision of a provider who can 27 immediately recognize and manage severe allergic conditions 28

Centers for Disease Control and Prevention | Recommended Adult Immunization Schedule, United States, 2019

Tetanus

• Caused by Clostridium tetani • Spores found in soil, dust, feces • Toxin binds to CNS, prevents muscle relaxation TETANUS, DIPHTHERIA, & PERTUSSIS • Symptoms of trismus (lockjaw), muscle rigidity, and spasms • 10% case-fatality rate • Almost all cases of tetanus occur in patients not up to date with tetanus-containing vaccinations

29 30 Source: World Health Organization

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Tetanus Transmission Diphtheria

• How is tetanus transmitted? • Caused by Corynebacterium diphtheriae Rare in the US due to high vaccination rates • Puncture wounds (including • insect bites) ~37% • Widespread in other countries Other • Lacerations ~24% / abrasions 17% • Transmission respiratory or contact with ~6% / chronic wounds ~11% Puncture Chr 37% wound lesions • Injection drug use ~5% 11% • Amateur piercings and tattoos IDU 5% • Symptoms Abrasion Laceration 6% • May involve any mucus membrane (exudates can • Can occur indoors or 24% cause obstruction) or skin outdoors 31 • Complications due to absorbed toxin 32 • Myocarditis, neuritis, death CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington DC: Public Health Foundation; 2012. • Case fatality rate 5–10% https://healthand.com/us/topic/general‐report/diphtheria

Pertussis

• Caused by Bordetella pertussis • Very contagious

• Disease more severe among younger children

• Symptoms • Paroxysmal cough • Whooping caused by inspiration against a closed glottis

• Complications • Infants and children: • Teens and adults: 33 34 Pneumonia, seizures, Persistent cough, weight encephalopathy, hypoxia, loss, passing out, rib hospitalizations, death fractures

Differences Between DTaP and Tdap Tdap and Pregnancy

• Vaccination of mother transfers antibodies to fetus Adults Tetanus Diphtheria Pertussis Adacel® 11‐ • Provides protection until administration of first few doses of DTaP 64 years Td ap Boosterix® 1/3rd of dose Lesser dose ⩾10 years • One dose is indicated every pregnancy • Regardless of the interval since the last Td was given Tdap • Preferably at 27–36 weeks gestation • NEW DATA (Oct 2016): 28-32 weeks: higher titers in infants vs. 33-36 weeks • If not given in pregnancy, administer as soon as possible post- Diphtheria Tetanus Pertussis Children >7 partum years DT aP DTaP • Review vaccination of all family members and caregivers of 35 infant  administer Tdap if indicated 36

http://www.immunize.org/askexperts/experts_per.asp

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Tdap – Special Situations

Situation Recommendation If adult and 1 dose Tdap then 1 dose Td ⩾4 previously did not weeks later– receive primary and then another dose Td vaccination series for 6–12 months after last Td; then Td booster every 10 years thereafter MEASLES, MUMPS, & RUBELLA tetanus, diphtheria, and pertussis –

If pregnant – Give one dose of Tdap after 26 weeks of gestation (repeat every pregnancy) 37 38

Measles Measles • Paramyxovirus • Incidence • Roseola • Resurgence/outbreaks • hard measles • Caused by low • Complications • 7-day measles vaccination coverage • Hospitalization (18%) • Diarrhea (8%) Recent outbreaks • Clinical Features • • Otitis media (7%) • Autism myth Respiratory transmission (highly contagious) • Pneumonia (6%) • • Antivaccination groups 4 days before to 4 days after rash onset • • Low vaccination rates in • Encephalitis (0.1%) US and Europe • Death (0.2%) • Progression of a prodrome of – • high grade fever, cough and diarrhea 39 40 • blue white koplik spots on mucous membranes • hairline rash spreading downward/outward http://www.cdc.gov/vaccines/pubs/pinkbook/index.html

Mumps Mumps • Paramyxovirus • Can cause a painful swelling of salivary glands

• Clinical features • Usually self-treatable in ~10 days but in some • Respiratory transmission cases can cause complications

• Progression of a prodrome of – Complications Aseptic meningitis • Low-grade fever, headache, and malaise to unilateral or bilateral parotitis Orchitis Oophoritis • Asymptomatic in ~20% Deafness • Non-specific symptoms in 40%–50% 41 Myocarditis 42 Death

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Rubella Rubella • To g av i r u s German measles, 3-day measles • • Most dangerous for a • Considered no longer endemic in US in pregnant woman's baby 2004 • Cases in the US are mostly imported • Can cause miscarriage or birth defects • Clinical Features • Respiratory transmission • Prodrome (rare in children) • Complications • Low-grade fever, malaise, upper • Arthralgia or • Congenital rubella respiratory symptoms in adults arthritis in adult syndrome (CRS) • Rash women (50%-70%) Cataracts, heart defects, • Maculopapular – fairly mild compared to deafness, mental retardation, measles • Duration up to 1 miscarriage, liver and spleen 43 month 44 • Starts on face then spreads from head damage to foot (~3 days)

MMR Vaccine MMR Vaccine

• Live‐attenuated • Target groups for MMR vaccination • All children • Indication in adults – • Born in 1957 or later • Adults born in 1957 or later who have not been vaccinated with MMR • Dose: 0.5 mL SC • All susceptible people at high risk – • Contraindications • Health care personnel • Allergy to gelatin or neomycin, pregnancy, • College students immunosuppression, or person with passive immunity • International travelers to measles from a blood transfusion Non-pregnant women of childbearing age without 45 • 46 evidence of immunity to rubella • Patients with HIV (if CD4 count is adequate)

MMR: Frequently Asked Question

• Should a patient with provider-diagnosed measles, mumps, or rubella be considered immune?

Only if born before 1957 AND are not health care personnel

• For adults born in 1957 or later – • Laboratory evidence of immunity or documentation of vaccination required to be considered immune • Provider diagnosis  NOT adequate 47 48

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Applying Your Knowledge to Practice Third Dose of MMR Vaccine?

Target group How many doses of MMR should • Previously vaccinated with 2‐doses of a mumps‐containing vaccine these patients receive? AND identified at increased risk for mumps because of an outbreak All children 2 doses  should receive a 3rd dose of a mumps‐containing vaccine 1st dose: 12‐15 months 2nd dose: 4‐6 years Adults born in 1957 or later who have At least 1 dose; recommend a 2nd not been vaccinated with MMR • At risk populations – dose if patient has a risk factor • Those in close contact settings such as schools, colleges, camps, playing on the same sport team Health care personnel born before Consider 2 doses 1957 (without evidence of immunity) • Living with someone else who has mumps or any behavior that All susceptible patients at high risk for would exchange saliva with another person disease (college students, international 2 doses (4 weeks apart) 49 50 travelers, etc..)

Albertson JP et al. MMWR, 2016, 65(26):731-4.

Varicella • Varicella zoster virus (VZV) • Primary infection: varicella (i.e., chickenpox)

• Transmission • Via respiratory droplets or VARICELLA contact with lesions • Very contagious http://www.healthvermont.gov/immuni zations‐infectious‐disease/other‐ reportable‐diseases/varicella‐ chickenpox‐and‐shingles • Clinical features • Mild prodrome • Fever, headache, tiredness • Rash • Head first 51 52 • Concentrates on trunk • Duration 5–10 days

Varicella

• Complications • Encephalitis • Secondary bacterial infection • Pneumonia • Hospitalization • Death

53 54

http://www.healthvermont.gov/immunizations‐infectious‐ disease/other‐reportable‐diseases/varicella‐chickenpox‐and‐shingles

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Varicella Vaccination Varicella: Frequently Asked Questions • Varivax® (Merck) • Should a patient who provides a verbal history of • Live‐attenuated virus vaccine chickenpox be considered immune? • No longer considered sufficient evidence of immunity • 2 doses are about 98% effective • How can a patient demonstrate immunity? • Dose: 0.5 mL SC • Documentation of age-appropriate vaccination • Laboratory confirmation after natural infection • All adults without evidence of immunity to varicella • Birth in the United States before 1980 should receive 2 doses at least 4 weeks apart • Excluding pregnant women and health care providers • Diagnosis or verification of history of varicella disease or • Reported adverse events herpes zoster by health care provider 55 • Instead of relying on parental or self-reporting 56 • Local injection site reactions and varicella‐like rash at injection site

Varicella: Special Situations CI: contraindicated Pregnancy Health care personnel VAR CI during Vaccinate (regardless pregnancy of year born) if no HIV infection evidence of CD4 count ≥200 Severely immunity: cells/µL (with no immunocompromised Indicated after •1 dose if evidence HERPES ZOSTER pregnancy previously ofsupressed VAR CI (before discharge received immunity): from healthcare varicella‐ Consider 2‐dose facility regardless containing series VAR 3 months vaccine: apart based on of whether born individual clinical before 1980) OR decision • 2‐dose series if not previously VAR CI in HIV vaccinated (~4‐8 infection with 57 58 weeks apart) CD4 count <200 cells/μL

Herpes Zoster

• Herpes‐zoster virus establishes latency in cells of dorsal root ganglia

• Reactivates and travels along neuronal cell axons • Often associated with advancing age or a weakened immune system

• Appears as localized rash in dermatomes

• Can cause the following complications: • Post‐herpetic neuralgia (PHN) • Scarring • Bacterial infection 59 60 • Ocular abnormalities

https://www.bmj.com/content/364/bmj.k5095

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Recombinant Zoster Vaccine (RZV) Zoster Vaccine Live (ZVL)

• Shingrix® (GSK) • Zostavax® (Merck) Live attenuated virus vaccine • Recombinant, adjuvanted zoster vaccine • • Higher strength (much higher antigen amount) than varicella vaccine • Lyophilized gE antigen (powder) • AS01B adjuvant suspension • ~50% effective (but is less effective with advancing age)

• 2-dose series spaced 2-6 months apart • ACIP target group for vaccination: adults ≥60 years

• A single dose after reconstitution is 0.5 mL (IM) • FDA approved for prevention in: • Adults aged ≥50 years • Antigen and adjuvant stored refrigerated between 2°C - 8°C • Dose and route: 0.65 mL (entire contents of vial) SC (1 dose)

61 • Reduced incidence of post-herpetic neuralgia (PHN) by ~39% 62 • FDA approved for prevention in adults ≥ 50 years in those who actually develop zoster

Zoster Vaccine Indications 1 dose ZVL

Age ⩾ 60

years OR Age⩾ 50

years 2‐dose series RZV 2–6 months apart regardless of previous herpes zoster infection or previously 2‐dose series RZV 2–6 received ZVL months apart (regardless of previous herpes zoster infection or if previously 64 received ZVL) PREFERRED!!!

Zoster ‐ Special Situations

Severe immunocompromising Pregnancy conditions (including HIV infection with CD4 count <200 cells/μL) HUMAN PAPILLOMAVIRUS (HPV) • ZVL contraindicated • ZVL contraindicated

• Consider delaying RZV • Recommended use until after pregnancy, if of RZV: under review indicated 65 66

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Human Papillomavirus Infection Human Papillomavirus Infection

• In the US in 2012, >20 million people infected with HPV • Human papillomavirus (HPV) • Rate of HPV infection in sexually active adults is extremely high • Lifetime risk for sexually active adults is >50% • Types (more than 100) • High‐risk types 16*, 18*, 31, 33, 39, 45, 51, 52, 58 • Most HPV infections resolve spontaneously • Cancers • Small proportion of infected persons become persistently infected • Low‐risk types 6*, 11*, 40, 42, 43, 44, 54 • Low‐grade Pap smear abnormalities, warts • High-risk types found in 99% of cervical cancers *Most common types • Infection with one type does not prevent infection with another 67 68

http://www.ashasexualhealth.org/stdsstis/hpv/fast‐facts/ CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington DC: Public Health Foundation; 2012.

Pathogenesis of HPV HPV Vaccines

® CIN = Cervical intraepithelial neoplasia Cervarix® (GSK) • Gardasil 9 (Merck) – 9 • valent

• Bivalent • Quadrivalent, alum‐adjuvanted High‐grade CIN (up to • Protects against • Protects against serotypes serotypes 6, 11, 16, 18 6, 11, 16, 18, 31, 33, 45, 52, 58 Persistent 20 years) HPV CANCER • Approved for the prevention of • Covers ~70% of cervical cervical, vulvar, vaginal, anal infection cancers  Low‐ cancers and genital warts Initial HPV grade CIN infection • Covers 90% of cervical cancers (1 year) (up to 6 69 70 years) • Covers 90% of genital warts

HPV Vaccination – Indication HPV Vaccination – Indication

• Routine vaccination indicated –

• For females through age 26 years • For males through age 21 years • Males 22-26 years may be vaccinated based on individual clinical decision

71 72 • HPV vaccination routinely recommended by ACIP at age 11–12 years https://www.gardasil9.com/about‐gardasil9/schedule/

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HPV Vaccine – Special Situations

Pregnancy Immunocom- Men who have through age 26 sex with men promising years conditions (MSM) and PNEUMOCOCCAL DISEASE (including HIV transgender •Not persons through recommended infection): age 26 years  through age until after 2- or 3-dose series pregnancy 26 years depending on age  3-dose series at initial vaccination

73 74

Pneumococcal Disease Pneumococcal Disease

• Caused by Streptococcus pneumoniae • Gram-positive coccobacillus with a polysaccharide cellular capsule • Colonizes upper respiratory tract as part of normal flora

• Leading cause of vaccine-preventable illness and death in the US

• Threat exists year-round (not just in winter)

• Frequent cause of secondary bacterial pneumonia following influenza

• Antibiotic resistance is common 75 76

Pneumococcal Vaccines Pneumococcal Disease

Routine vaccination in immunocompetent individuals ≥65 years: • For adults (19‐64 years of age)

77 78

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm?s_cid=mm6434a4_x https://www.pharmacist.com/focus‐pneumococcal‐vaccines‐adults?is_sso_called=1

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Pneumococcal Disease Pneumococcal Polysaccharide Vaccine 23‐valent (PPSV23)

• Pneumovax 23® (Merck) Vaccination (in immunocompromised individuals): • Polysaccharide vaccine • Contains 11 serotypes not found in PCV13 • More efficacious against bacteremia than pneumonia • Not adequately effective in children <2 years • Dose and route: 0.5 mL IM (or SC)

Vaccinate people whenever they first become eligible for this vaccine, before advancing age impairs their immune response 79 80

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm?s_cid=mm6434a4_x

Pneumococcal Conjugate Vaccine 13‐valent Quick Recap: (PCV13) • Prevnar 13® (Pfizer) • 12 serotypes same as PPSV23 • 1 serotype not in PPSV23 (6A)

• ACIP recommended in all adults >65 years and in patients with: x2 • Cochlear implants x1 • CSF leaks • Immunosuppression • Asplenia (includes sickle cell disease)

• No additional PCV13 needed if dose given before age of 65 81 82 • PCV13 recommendation to be re-evaluated by ACIP in 2019 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm?s_cid=mm6434a4_x

Hepatitis A

• Virus – Picornavirus • Humans only natural host • Stable in environment for months

• Disease HEPATITIS A • Fecal-oral transmission • Viral shedding from 10 days post-exposure to 3 weeks post- onset of symptoms • Symptoms • Abrupt onset of fever, malaise, nausea, anorexia • Abdominal discomfort, dark urine, jaundice 83 • Duration up to 2 months (with relapses up to 6 months) 84

https://www.rivm.nl/en/hepatitis‐a

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Hepatitis A Indication

• Routine vaccination indicated –

• All children 1-2 years old

• Adults if risk factors are present

• Any person for whom immunity against hepA is desired • Identification of risk factor not required

85 New recommendation! 86

Hepatitis A Target Groups for Vaccination Hepatitis A Vaccines

Close personal Travel in countries • 2-dose series HepA 3-dose series HepA-HepB At risk for hepA contact with with high or • Havrix® (GSK): 6–12 months apart • Tw i n r i x ® at 0, 1, 6 months viral infection: international intermediate • Vaqta ® (Merck): 6–18 months apart 2‐dose series adoptee endemic hepA • HepA (pediatric dose) + • Brands are interchangeable HepB (adult dose)

Men who have sex Injection or non- Homelessness • Minimum interval: 6 months • Minimum intervals – with men injection drug use (new) • Between doses 1 & 2 – • Dosing – 1month • 18 years and younger: 0.5 mL IM Between doses 2 & 3 – • 19 years and older: 1.0 mL IM • Work with hepA 5 months Chronic liver virus in research Clotting factor 88 laboratory disease disorders

Hepatitis A Vaccine – Pre & Post‐exposure Prophylaxis

Age group Risk Category/Health Condition HAV IG*

Postexposure Prophylaxis *IG: Immune Globulin <6 mos Healthy IG 12 mos- 40 yrs Healthy 1 dose >40 yrs Healthy 1 dose IG >12 mos Immunocompromised/Chronic Liver 1 dose IG Disease >12 mos HAV contraindicated IG HEPATITIS B Preexposure Prophylaxis <6 mos Healthy IG 6 mos-40 yrs Healthy 1 dose >40 yrs Healthy 1 dose All ages Immunocompromised/Chronic Liver 1 dose IG Disease 89 90 >6 mos HAV contraindicated/Refuse HAV IG

MMWR Morb Mortal Wkly Rep. 2018;67(RR43):1216-20

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Hepatitis B Hepatitis B • Virus – Hepadnaviridae • Virus – Hepadnaviridae • Humans only known host • Humans only known host • Stable on environmental surfaces for 7 days • Stable on environmental surfaces for 7 days • Disease • Disease • Blood-borne pathogen • Blood-borne pathogen • More common in adults versus children • 50% of adults remain asymptomatic • ~50% of adults remain asymptomatic • Clinical features – progression from a prodrome of: • Complications Malaise, nausea and • Acute: fulminant hepatitis (1%–2%) vomiting, fever, right Jaundice, 91 92 Chronic hepatitis upper quadrant pain, hepatomegaly • Chronic (10%): cirrhosis, liver cancer, death

rash, dark urine https://www.cdc.gov/hepatitis/hbv/index.htm

Hepatitis B Target Groups for Hep B Vaccination • All infants • All adolescents who have not been previously vaccinated • All high-risk adults • Risk factors – • Multiple sex partners

Other • Patients seeking treatment for STIs 5% Unknown • Patients with HIV infection 16% Heterosexual Injection drug users Encounters • 39% • Patients on dialysis MSM • Patients with chronic liver disease 24% Injection- drug use • Health care providers 16% • Patients with diabetes 19 to 59 years old (permissive if 60 years and older) Photograph courtesy of Patricia 93 Walker, MD Ramsey Clinic 94 Associates, St. Paul, MN

CDC. MMWR. 2006:55(RR-16):6-7. https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm

Hepatitis B Vaccines Hepatitis B Vaccine

® ® • Recombivax HB and Engerix-B • Duration • After seroconversion, protection appears to persist indefinitely • Adolescents and adults • 3 doses (no boosters): 0, 1, 6 months • Adult formulation of Recombivax® licensed for a 2-dose schedule for adolescents 11 to 15 y/o separated by 4-6 • What if a heath care months provider’s titer is zero? • For patients on hemodialysis: 4 doses of Engerix-B® needed • Give one dose, wait 1 month and repeat titer • Do not administer in gluteus – poor immune response!! • If high, no more doses needed

® • If low or none, complete • HEPLISAV-B (Dynavax) series, then repeat titer • 2 doses 1 month apart • Approved by FDA in November 2017 for adults >18 years 95 96 • 1st new HepB vaccine in >25 years http://www.immunize.org/catg.d/p2110.pdf

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Meningococcal Disease

• Caused by Neisseria meningitidis

• In the US, 5 specific serogroups cause almost all invasive meningococcal disease: A, B, C, Y, and W • Serogroups B, C and Y account for most disease MENINGOCOCCAL DISEASE • Serogroups C, Y and W (>70% of meningococcal disease in >11 y)

• Incidence declining for all serotypes • Most cases are sporadic, but outbreaks continue

97 98

CDC.MMWR 2013;62(RR02):1-22 https://en.wikipedia.org/wiki/Meningococcal_disease

Meningococcal Vaccines: A, C, W, Y Meningococcal Disease • Polysaccharide (MPSV4) • Symptoms • Removed from the market in 2017 • Meningitis • Pain, headache, neck stiffness • Conjugate (MCV4) • Bacteremia • Menactra® (Sanofi Pasteur) (MenACWY‐D); • Sepsis and rash • Age 9 months – 55 years • Bacteremic pneumonia • 9‐23 months: 2‐dose series • 2–55 years: single dose • Spreads through the exchange of respiratory and throat secretions like spit (e.g., by living in close quarters, kissing) • Menveo ® (Novartis) (MenACWY‐CRM); • Age 2 months – 55 years • Case fatality rate:10%–15% 99 • 2–23 months: 4‐dose series 100 • 11%–19% survivors have long-term sequelae • 2–55 years: single dose

Photograph courtesy of CDC Public Health Image Library https://www.cdc.gov/vaccines/hcp/acip‐recs/vacc‐specific/mening.html

Meningococcal B Vaccines Meningococcal Disease

Two new Men B vaccines –

• Trumenba® (Pfizer) • Choice depends upon risk of exposure and patient’s susceptibility to MenB disease Important to remember –

• 3-dose series (0, 1-2, 6 months) OR • Must complete the series with the same vaccine • 2-dose series (0, 6 months)

® • May be given at the same • Bexsero (Novartis) time with other vaccines • 2-dose series (0, 1-6 months) (different sites) 101 102

MMWR Morb Mortal Wkly Rep. June 12, 2015/64(22);608‐12

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HAEMOPHILUS INFLUENZAE TYPE B (HIB)

103 104

Haemophilus influenzae Type B (Hib) Hib Vaccines

Photographs courtesy of Children’s Immunization Added to the adult schedule in 2014 – Project St. Paul, Minnesota

• Three conjugated vaccines • Gram-negative coccobacillus (polysaccharide capsule) • ActHIB® (Sanofi Pasteur) • Respiratory Spread 4‐dose series at • Hiberix® (GSK) 2, 4, 6, 12–15 • Enters nasopharynx (some become asymptomatic carriers) Pentacel® (Sanofi Pasteur Limited) months • Invades bloodstream and causes disease • • Not common after age 5 years • Clinical Features • PedvaxHIB® (Merck) 3-dose series at 2, 4, • Causes meningitis, pneumonia, arthritis, cellulitis 12–15 months • Hearing impairment or neurological sequelae in 15-30% • Case fatality rate 2-5% 105 106 • Incidence • Decreased 99% since vaccine (1985)

Hib Vaccine Indications in Adults Hib Vaccine Indications

• Routine • Infants and young children

• High‐risk persons • People without spleens (anatomic or functional): 1 dose • Sickle cell disease • Undergoing elective splenectomy (14 or more days before splenectomy)

• Recipients of hematopoietic stem cell transplant (6‐12 107 months after transplant): 3 doses 108

Centers for Disease Control and Prevention | Recommended Adult Immunization Schedule, United States, 2019

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HiB Vaccine – Special Situations

Hematopoietic Starting 6-12 m 3-dose series stem cell after successful 4 weeks apart transplant transplant

Anatomic or functional Unvaccinated asplenia persons age 5 1 dose (including sickle years or older cell disease)

Unvaccinated 1 dose Elective persons age 15 (preferably at least 14 days splenectomy months or before older procedure)

Unvaccinated 1 dose (not indicated HIV infection persons age 5– in adults>18y w/ 109 110 18 years HIV)

Centers for Disease Control and Prevention | Recommended Adult Immunization Schedule, United States, 2019

References

• Adult Immunization Schedule by Vaccine and Age Group. CDC. Centers for Disease Control and Prevention, 2019. www.cdc.gov/vaccines/schedules/hcp/imz/adult.html. Post‐Assessment Questions • American Academy of Pediatrics. Active Immunization. In: Pickering L, Baker C, Kimberlin D, Long S, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatric; 2012.

• Broder KR, Cortese MM, Iskander JK, et al; Advisory Committee on Immunization Practices (ACIP). Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis •To join – vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR‐ 3):1–34pmid:16557217.

• Centers for Disease Control and Prevention (CDC). Updated recommendations for use of meningococcal conjugate vaccines— Advisory Committee on Immunization Practices (ACIP), 2010.MMWR Morb Mortal Wkly Rep. 2011;60(3):72– 76pmid:21270745.

• Centers for Disease Control and Prevention (CDC). Use of 13‐valent pneumococcal conjugate vaccine and 23‐valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816–9.

• Markowitz LE, Dunne EF, Saraiya M, et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR‐05):1–30pmid:25167164.

• Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and children—use of 13‐valent pneumococcal conjugate vaccine and 23‐valent pneumococcal polysaccharide vaccine— recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010;59(No. RR‐11):1–18. 111 112 • Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13‐valent pneumococcal conjugate vaccine and 23‐valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63:822–5.

Post‐Assessment – Question #1 Post‐Assessment – Question #2

113 114

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Post‐Assessment – Question #3 Post‐Assessment – Question #4

115 116

8420 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 3:00 - 4:00 PM

Palliative Care and the Role of the Pharmacist

0179-0000-19-031-L05-P

Sonia Malhotra, MD, MS, FAAP Director of Palliative Medicine and Supportive Care University Medical Center/Tulane University School of Medicine New Orleans, LA

Assistant Professor of Medicine and Pediatrics Tulane University School of Medicine New Orleans, LA

Clinical Assistant Professor of Medicine and Pediatrics Louisiana State School of Medicine New Orleans, LA

Faulty Director, Palliative Medicine Pathway Tulane University Internal Medicine Residency Program New Orleans, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: 1. Define palliative medicine versus hospice care. 2. Identify at least 3 misconceptions about palliative care. 3. Outline at least 3 topics of interest that bridge palliative medicine and pharmacy.

Speaker has disclosed that they have no relevant financial relationships. 85 Topics in Palliative Pharmacy

Sonia Malhotra, MD, MS, FAAP Internal Medicine, Pediatrics, Hospice & Palliative Medicine Director, Palliative Medicine & Supportive Care – UMC New Orleans Assistant Professor of Medicine & Pediatrics - Tulane SOM Clinical Assistant Professor of Medicine & Pediatrics – LSU SOM Senior Lecturer – University of Queensland/Ochsner Clinical School

Louisiana System of Health-System Pharmacists Annual Conference Friday, May 24, 2019

86 Disclosure

• I am a contributing author for the American Academy of Hospice and Palliative Medicine (AAHPM) UNIPAC and Online Module Series

87 The Social Media Piece!

• FOLLOW ME ON TWITTER: @SoniaMKhunkhun

• If you post a slide, TAG ME ON IT!

• Hashtags: #PalliativeCare #hpm #pedpc #Palligator #CriticalCare #DiversityandInclusion

88 Objectives

1. To define Palliative Medicine vs. Hospice care

2. To identify and clarify at least 3 misconceptions about Palliative Medicine

3. To outline at least 3 topics of interest that bridge Palliative Medicine and Pharmacy

89 Palliative Medicine vs. Hospice Care

Objective: To define Palliative Care vs. Hospice care 90 Americans Want Palliative Care Telephone survey of 800 Americans

• 92% of respondents say they would seek Palliative Care for a loved one if they had a serious illness

• 92% of respondents say Palliative Care services should be available at all hospitals

• BUT…Only 8% were knowledgeable about Palliative Care at the start of the survey

Public Opinion Strategies/CAPC/ACS Consumer Poll, 2011 91 The Changing Face of Illness

• 1 in 4 Americans will live until the age of 90 • Millions of older adults with multiple chronic illnesses • COPD • CHF • Dementia • Cancer • DM • Etc • Etc • Etc

92 What is Palliative Medicine?

• Manages needs of patients and families living with progressive illnesses -Patient AND Family Centered

• Focuses on the burden of illness rather than the illness itself

• Willingness to address issues of life completion and closure if the patient wants to

• Continuum of care, offered with curative and life prolonging treatment

93 Domains of Palliative Care What Do Palliative Care Teams Do? • Relieve /Symptom Management • Pain and other symptoms • Distress- emotional, spiritual, social, practical • Uncertainty

• Communicate • What to expect • Treatments that match person and family priorities

• Coordinate /Support • Medical and practical needs across settings 94 Issues We Can Help With Symptoms Communication a) Pain a) Goals of Care b) Nausea/Vomiting b) Making Recommendations c) Constipation c) Team Cohesion d) Anxiety/Depression d) Addressing Code Status e) Fatigue e) Revisiting and Readdressing f) Poor Appetite g) Dysphagia f) Ethics h) Dyspnea i) Delirium j) Secretions k) Neuroirritability/Dysautonomia Emotional Support Coordination of Care a) Patients a) Home palliative care b) Families b) Hospice c) Physicians and Other Clinicians c) AIM programs

d) Placement issues 95 e) Medical Equipment Domains of Palliative Care: Dispositional Issues • Where to go from here? • Home • Home with home care/home palliative care • Home with hospice • SNF with hospice philosophy • Inpatient hospice facility

96 Palliative Medicine & Hospice

Palliative Medicine

Hospice

97 Hospice Care • Prognosis less than 6 months to be eligible

• Philosophy of care and insurance benefit

• Interdisciplinary model: SW, RN, PT, chaplain, MD

• Focus is comfort, maximizing time out of the hospital • Does not exclude clinic visits

50% of patients are dead in two weeks ntdead in two weeks

98 Inpatient vs Home/Nursing Home with Hospice?

• Inpatient Hospice Criteria • Symptom management • Imminent death with active symptoms • Respite care • Medicaid rules on length of stay

• Home Hospice: Care provided by family

• Artificial Nutrition

• Hemodialysis

99 Misconceptions in Palliative Medicine

Objective: To identify and clarify at least 3 misconceptions about Palliative

Medicine 100 Misconception: Palliative Medicine Grandfathering • Boarded specialty • Now requires fellowship training • Prior to 2013: “Grandfathering” allowed

101 University of California, San Francisco Hospice & Palliative Medicine Fellowship Misconception: Every Hospital Provides Palliative Care • National survey of all hospitals in the United States providing medical/surgical care to adults

• Data linked to American Hospital Association Annual Survey, Dartmouth Atlas of Healthcare, U.S. Census Data

Center to Advance Palliative Care, 2015

102 >80% of hospitals with palliative care programs A 61-80% of hospitals with palliative care programs B 41-60% of hospitals with palliative care programs C 103 21-40% of hospitals with palliative care programs D Where is Palliative Care being provided?

• 90% of hospitals with 300 or more beds

• 97% of teaching hospitals

• 90% of Catholic Church operated hospitals

• 77% of nonprofit hospitals

104 Where are the gaps? • Geography: the South

• Ownership: For Profits • All hospitals: 23% of for-profits vs. 67% of nonprofits • 300 or more bed hospitals: 54% of for-profits vs. 94% of nonprofits

• Hospital size: Smaller hospitals • <100 beds: 44% vs. >300 beds: 90%

105 The Workforce

• 1 Palliative Medicine MD for every 1,700 persons with serious illness

• Fellowship trained Palliative Medicine physicians • Most fellowships in academic medical centers are supported through philanthropy, not GME

• Training for front-line doctors and nurses

106 Audience Question on Palliative Medicine and Mortality In patients with life-limiting illnesses, is there a difference in mortality between those receiving standard of care and those receiving palliative care? *Standard care = Oncologic treatments alone *Palliative care = Oncologic treatments + palliative care

A) Yes, standard of care pts live longer

B) Yes, palliative care pts live longer

C) No, there’s no difference in mortality

D) I have no clue (there’s no evidence)

107 108 109 Temel, JS et al. NEJM. 2010 Early Palliative Care: Study Design

• 107/150 adult patients with newly diagnosed NSCLC randomized with baseline & 12 week assessments • FACT-L • Mood Assessment • HADS-D • HADS-A • PHQ-9

• Primary Outcome: • Change in QOL at 12 weeks

110 Early Palliative Care: The Evidence

111 Temel, JS et al. NEJM. 2010 Misconception: Palliative Care Hastens Death

Median Survival

Palliative Care = 11.6 mo

Standard Care = 8.9 mo

p=0.02

***Palliative Care can extend survival and decrease symptom burden

112 Temel, JS et al. NEJM. 2010 Misconception: Palliative Care is Hospice Care

Life Prolonging Therapy

Dx of Death serious illness

Palliative Care Medicare Hospice Benefit 113 Misconception: Every Patient Benefits from Enteral Nutrition • Life Prolongation: Who benefits the most? 1. Short bowel syndrome​ • Often require parenteral nutrition due to nonfunctioning gut​ 2. Acute phase – CVA/Head Injury 3. Short term critical care stays - Sepsis​ 4. Proximal GI obstruction secondary to cancer​ • Patients receiving XRT/Chemo​ • Must have good functional status 5. ALS​ 6. Head and Neck Cancer

114 Patients that do not Benefit

1. Dementia 2. HIV 3. Advanced Cancer

115 Misconception: Dehydration/”Starvation” is Uncomfortable

• Dehydration • Anesthetic at the end of life • Benefit: May improve delirium • “Starvation” • Sensation for an intact brain Issues with Fluids at the EOL: Prolongs the Increased • Pleasure feeds dying process secretions = • Oral Swabs increased cough Increased urine = Increased increased use of edema/ascites catheters Increased Limits patients Fainsinger R, Fast Facts and Concepts #133 nausea/vomiting mobility 116 Misconception: “It’s Just Semantics” Common Phrases Used: Alternatives: 1. “Withdrawal of Care” 1. “Withdrawal of ventilation” -We withdraw interventions, not care for our pataients 2. “What do you want us to do?” 2. “Based on my understanding of your goals, I would recommend…” -Elicit hopes/expectations/goals, prior to making a recommendation 3. “The patient is DNR.” 3. “A resuscitation order was placed in the chart.” -DNR is about resuscitation in the event of a CARDIAC ARREST, NOT overall care 4. Narcotics 4. Opioids Pain Medications -Negative, legal implication 5. Competency 5. Capacity 117 -Legal term, NOT a medical term The Intersection of Palliative Medicine & Pharmacy

Objective: 118 To outline at least 3 topics of interest that bridge Palliative Medicine and Pharmacy Types of Pain

• 1. Nociceptive a) Somatic b) Visceral

• 2. Neuropathic

• 3. Bony/Musculoskeletal

• 4. Other a) Chronic b) Psychosomatic

119 Why Does Cancer Cause Pain?

The Main Culprits: TNF-alpha, TNF-beta IL-1, IL-6 Cytokines

Prostaglandins 120 Substance P It’s NOT Just Semantics:

• OPIOIDS, NOT NARCOTICS!!

• Narcotics  Legal, negative implication

• **LANGUAGE MATTERS!!**

Mangione MP, Crowley-Matoka M. J Gen Int Med; 2008 Wallace L et al. Pain Practice; 2012

121 Misconception: “It’s Just Semantics”

Common Phrases Used: Alternatives: 1. “Withdrawal of Care” 1. “Withdrawal of ventilation” -We withdraw interventions, not care for our pataients 2. “What do you want us to do?” 2. “Based on my understanding of your goals, I would recommend…” -Elicit hopes/expectations/goals, prior to making a recommendation 3. “The patient is DNR.” 3. “A resuscitation order was placed in the chart.” -DNR is about resuscitation in the event of a CARDIAC ARREST, NOT overall care 4. Narcotics 4. Opioids Pain Medications -Negative, legal implication 5. Competency 5. Capacity 122 -Legal term, NOT a medical term Why Do Opioids Help Cancer Related Pain?

123 Where are my Surgical Pharmacists at?? Why are Opioids Used in Postoperative Pain? • Same mechanism… INFLAMMATION!!!

• Shorter duration of use • Inflammation expected to improve

124 Not Every Opioid is Created Equally!

• Using the Equianalgesic Table:

125 1 mg IV Dilaudid DOES NOT EQUAL 1 mg IV Morphine

1 mg IV Dilaudid EQUALS 6.67 mg IV Morphine

126 Renal vs GI vs Liver Excretion

• NOT safe in renal failure • Morphine (by-products M3G & M6G) • Oxycodone okay but not great

• NOT safe in liver failure • Fentanyl • Methadone okay but not great

• Gut primarily • Methadone

127 Trashbox of Opioids

•Demerol •Soma •Tramadol •Codeine

128 The Ceiling Effect

• Pain relief by some analgesics which have no further effect on pain above a particular dose level

• Certain drugs limited by the ceiling on how often(duration) they can be prescribed

129 PCA Settings

• Continuous rate • Patient administered bolus • Lockout interval • Can be anywhere from 6-30 minutes • RN administered bolus • Hourly max • Not really required

130 Quick Facts About Acute Pain Management

• CALCULATE OME’S if a patient is on opioids at home • Don’t be afraid of PCA’s! • Transition as quick to orals when possible • Don’t forget adjuvant agents

131 Key Management Points in Chronic Pain

• Opioids are NOT mainstay of treatment • Can be used sparingly in certain situations

• Use adjuvant agents • Gabapentin, TCA’s, SNRI’s • Acetaminophen/NSAID’s • Muscle relaxants

• Use complementary methods • Accupuncture/Needling, TENS units • Physical therapy

• Don’t forget that mental health often plays a large role • CBT/DBT, visits with a psychologist/psychiatrist

132 Adjuvant Agents & Why We Choose Them

• Gabapentin/Pregablin • Ca/Cl Channel Mediation; 3-5 days to work • SE’s: Sedation, weight gain, constipation • Was used as a mood stabilizer • Tricyclic Antidepressants (Amitriptyline, Nortriptyline) • Na/Cl Channel mediation; 3-5 days to work • SE’s: Sedation, urinary retention, constipation • Used as an anti-depressant • SNRI’s (Venlafaxine, Duloxetine) • Serotonin/NE mediation; 7-10 days to work • SE’s: Activation, nausea, weight gain • Used as an anti-depressant/anxiolytic

133 Look for the Red Flags…

• Multiple allergies to different opioids

• Multiple prescribers/”Doctor shopping” • CHECK THE PMP (PRESCRIPTION MONITORING PROGRAM)

• Unwilling to try multimodal therapies

• Multiple ER Visits/Admissions for Pain

134 Misconception: Long Term Opioid Use Leads to Addiction • If patient brings up worry, less reason to worry • Patients with cancer = Legitimate pain • Substance abuse hx = Higher risk • Opioid contracts NOT ALWAYS helpful!!!

Reisfield GM, Paulian GD, and Wilson GR, Fast Facts and Concepts, #127

135 NOT Every Dying Patient Should Be on a Continuous Infusion of Morphine

• Bolus Doses • More effective for immediate symptom relief • Continuous Infusion • Should be started based on oral morphine equivalent calculation (OME) • When started, bolus doses should still be provided • Titration should ONLY occur 2-3 times/day at most

Patient A: Morphine 2mg IVq1 PRN Used 10 doses in 24 hours OME = 60

To Start Continuous Infusion: -2/3 of total OME in long 60 x 2/3 = 40 CI = 1.6mg/hr acting form 40 Divided by 24 hours -Bolus dose 5-15% of total 60 x 0.05 Bolus dose = 3 mg IV q15 OME min PRN 136 Weissman D, Fast Facts and Concepts, #72 Dying Patients Need More Than Just Opioids

• EOL Symptoms:

Pain Dyspnea Secretions Nausea Constipation

Opioids Opioids Positioning Zofran Suppository Adjuvant Agents Benzos Anticholinergics Dopa agents a) Neurontin a) Robinul a) Haldol b) TCA’s b) Scopalamine b) Reglan c) SNRI’s c) Atropine c) Compazine drops Oxygen Opioids Steroids

Benzos Suctioning

Agitation Haldol/Benzos Depression Ritalin 137 Pearls/Summary

• Palliative medicine can be provided simultaneously with therapy of curative/life-prolonging intent • Hospice is a branch of palliative medicine • Many misconceptions exist and need clarification in the world of Palliative Medicine

• Knowledge of opioids leads to effective use and prescribing patterns

• Chronic pain should be managed with a multimodal approach

138 Special Shotouts

• University Medical Center, New Orleans Pharmacists!! • Dr. Helen Calmes • Dr. Fatima Brakta • Dr. Ellen Austin • Dr. Charles Jastram

• Dr. Mary Lynn McPherson (Univ of Maryland)

• Dr. Jennifer Pruskowski (Univ of Pittsburgh)

139 • Center to Advance Palliative Care

• www.capc.org

• American Academy of Hospice and Palliative Medicine

• www.aahpm.org

• National Palliative Care Research Center

References http://www.npcrc.org/

• EPERC Fast Facts

• https://www.capc.org/fast-facts/

• Commission on Cancer

www.facs.org

• National Hospice and Palliative Care Organization Facts and Figures

http://www.nhpco.org/sites/default/files/public/quality/Pediatric_Facts-Figures.pdf

• Otolaryngology Clinics of North America 2009;42:1-13

• Attal N, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurology. 2006; 13:1153-1169.

• Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005454. DOI: 10.1002/14651858.CD005454.pub2.

• Moulin DE, et al. Pharmacological management of chronic neuropathic pain. Consensus statement and guidelines from the Canadian Pain Society. Pain Res Manage. 2007; 12(1):13-21.

• Rowbotham MC, et al. Venlafaxine extended release in the treatment of painful diabetic neuropathy: A double-blind, placebo-controlled study. Pain. 2004; 110:697-706. (Erratum in 2005; 113:248).

• Durand JP, Alexandre J, et al. Clinical activity of venlafaxine and topiramate against oxaliplatin-induced disabling permanent neuropathy. Anticancer Drugs 2005; 16:587-591.

• Durand JP, Deplanque G. Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo- controlled phase III trial. Ann Oncol 2012 23 (1):200-205.

• Sindrup SH, et al. Venlafaxine vs imipramine in painful polyneuropathy. A randomized, controlled trial. Neurology. 2003; 60:1284-1289.

• Goldstein DJ, et al. Duloxetine vs placebo in patients with painful diabetic neuropathy. Pain. 2005; 116:109-18.

• Lavoie Smith EM, Pang H, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA 2013; 309:1359-1367.

• Bomholt SF, Mikkelse JD, Blackburn-Munro G. Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain., Neuropharmacology. 2005; 48(2):252-263.

• Semenchuk MR, Sherman S, Davis B. A double blind randomized controlled trial of buproprion SR for the treatment of neuropathic pain. Neurology. 2001; 57(9):1583-8.

• Edlund MJ et al; Trends in use of opioids for chronic non-cancer pain among individuals with mental health and substance use disorders: The TROUP study; Clin J Pain. 2010 January ; 26(1): 1–8. doi:10.1097/AJP.0b013e3181b99f35.

• Back, Arnold and Tulsky. Mastering communication with seriously ill patients. Cambridge University Press, 2009

• Temel, J et al; Early Palliative Care for Patients with Metastatic Non-Small-Cell Lung Cancer; N Engl J Med 2010;363:733-42

• Mangione MP, Crowley-Matoka M. Improving Pain Management Communication: How Patients Understand the Terms “Opioid” and “Narcotic.” J Gen Int Med. 2008;23(9):1336-1338 140 • Wallace LS, Keenum AJ, AbdurRaqeeb O, et al. Terminology Matters: Patient Understanding of “Opioids” and “Narcotics”. Pain Practice. 2012(Jun 4)

• Jordan A, Malhotra S, et al; Depression in Older Adults: A Palliative Medicine Perspective; Harvard Review of Psychiatry; 2014 For More Information

[email protected] [email protected]

FOLLOW ME ON TWITTER! @SoniaMKhunkhun

141 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 4:00 - 5:00 PM

VTE in Cancer Patients

0179-0000-19-021-L01-P/T

Jill Comeau, PharmD, BCOP Associate Professor of Clinical Sciences University of Louisiana at Monroe College of Pharmacy, College of Health and Pharmaceutical Sciences Shreveport, LA

1 Contact Hour (0.1 CEU) Knowledge-based activity

.Pharmacist Objectives: Pharmacy Technician Objectives: 1. Identify the pathophysiologic process and 1. Identify the risk factors in cancer patients risk factors for venous thromboembolisms that cause VTEs. (VTEs) of malignancy. 2. List the different classes of anticoagulants 2. Discuss the current practice guideline and used in the patient population to treat or recommendations regarding prevent VTEs. anticoagulation in patients with cancer. 3. Discuss the mechanisms of action, dosing, 3. Review the current literature addressing length or therapy, drug interactions and the use of direct oral anticoagulants side effects of these medications. (DOACs) in the prevention and treatment of cancer-induced VTEs. 4. Identify pertinent clinical pearls that can be utilized in pharmacy practice, including but not limited to, frequency, schedule, drug interactions and cost. 5. Choose appropriate therapy and monitoring parameters in a patient case regarding VTEs of malignancy.

Speaker has disclosed that they have no relevant financial relationships. 142 5/17/2019

DISCLOSURES

KEEP CALM AND ANTICOAGULATE! AN UPDATE OF THE PREVENTION AND  Nothing to disclose TREATMENT OF CANCER-ASSOCIATED VENOUS THROMBOEMBOLISMS

Jill M. Comeau, PharmD, BCOP Associate Professor of Clinical Sciences, ULM College of Pharmacy Gratis Assistant Professor, Dept. of Internal Medicine and Feist- Weiller Cancer Center, LSU-Health Shreveport May 24, 2019

PHARMACIST OBJECTIVES PHARMACIST OBJECTIVES

 Identify the pathophysiologic process and risk  Identify pertinent clinical pearls that can be utilized factors for venous thromboembolisms (VTE) of in pharmacy practice including but not limited to malignancy frequency, schedule, drug interactions and cost of  Discuss the current practice guideline these medications recommendations regarding anticoagulation in  Choose appropriate therapy and monitoring patients with cancer parameters in a patient case regarding VTEs of  Review the current literature addressing the use of malignancy direct oral anticoagulants (DOACs) in the prevention and treatment of cancer-associated VTEs

TECHNICIAN OBJECTIVES CANCER AND VTES

 Identify the risk factors in cancer patients that  Over 1.7 million people will be diagnosed with cause VTEs cancer in 2019 in the United States  List the different classes of anticoagulants used in  LA: 26,800 this patient population to treat and prevent VTEs  Discuss the mechanisms of action, dosing, length  15 million people living with cancer in 2017 of therapy, drug interactions, and side effects of these medications  2-year risk of VTEs: 0.6%-7.8%

 6-7x with start of chemotherapy

 Increased risk of bleeding American Cancer Society. Cancer Facts & Figures 2019. Heit et al. Arch Intern Med. 2000;160:809-15. Khorana et al. Cancer. 2013;119:648-55.

143 1 5/17/2019

VTE OF MALIGNANCY COAGULATION CASCADE PATHOPHYSIOLOGY

 Hypercoagulable state Activates Tissue Factors IX Deposits Factor VIIa Factor + and X Fibrin Cancer Platelets and Procoagulant Factor X Cancer Procoagulant

 Tumor + Endothelium → Cytokine production  Hyperviscosity  Thrombophilic state  Upregulation of COX-2 → tissue factor, thromboxanes, and prostaglandins  Disseminated intravascular coagulopathy (DIC)

Dipasco et al. J Surg Oncol. 2011;104:316-22. http://err.ersjournals.com/content/24/137/392

INCIDENCE OF VTES BASED ON CANCER TIMING OF VTES RELATED TO START OF DIAGNOSIS CANCER TREATMENT

Khorana et al. Cancer. 2013;119:648-55. Khorana et al. Cancer. 2013;119:648-55.

KHORANA CHEMOTHERAPY-ASSOCIATED INCIDENCE AND RISK FACTORS FOR VTE SCORE BLEEDING

Characteristic Score Incidence Cancer Incidence Control Type of Bleeding Cohort (%) Cohort (%) Site of Cancer All 17.7 7 • Stomach or pancreas 2 Major 0.9 0.1 • Bladder, gynecologic, lung, lymphoma, or testicular 1 Minor 16.8 6.9 Prechemotherapy platelets 350,000 cells/mm3 1 Hemoglobin (Hb) < 10 g/dL or use of erythropoietin 1 Characteristic Odds Ratio (OR) stimulating agents (ESA) Body mass index 35 kg/m2 1 Bladder Cancer 4.09 Gastric Cancer 2.16 Score Risk of VTE (%) Atrial Fibrillation or Flutter 1.46 00.3 ESA 1.6 1-2 2 Cetuximab 1.47 36.7 Bevacizumab 1.39

Khorana et al. Blood. 2008;111:4902-7. Khorana et al. Cancer. 2013;119:648-55.

144 2 5/17/2019

CONTRAINDICATIONS TO ANTICOAGULATION

 CNS bleed or hemorrhage from metastases VTE TREATMENT  Major bleed requiring > 2 units of packed red blood GUIDELINES cells in 24 hours

 Relative  CNS metastases  Platelets < 50,000 cells/mm3  Procedures with a high risk for bleeding  Surgery: intracranial, spinal, urologic, cardiac, etc.  Lumbar puncture  Interventional pain procedures  Long-term antiplatelet therapy

NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

ASCO GUIDELINES NCCN GUIDELINES VTE TREATMENT 2007 2019

 Agent Category 1 Category 2A  LMWH preferred  LMWH with warfarin acceptable if long-term LMWH cannot be  Dalteparin  Enoxaparin utilized  LMWH and edoxaban  Fondaparinux  Can use inferior vena cava (IVC) filter if recurrent VTE with LMWH or contraindication to LMWH  Apixaban  Rivaroxaban  Length of therapy  Warfarin with UFH,  Minimum of 6 months LMWH, or  Continue if receiving chemotherapy or metastatic fondaparinux disease  Dabigatran with UFH or LMWH LMWH: low-molecular-weight heparin, UFH: unfractionated heparin Lyman et al. J Clin Oncol. 2007;25:5490-505. NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

NCCN GUIDELINES VTE TREATMENT LENGTH OF THERAPY

 Minimum of 3 months TREATMENT OF VTESOF MALIGNANCY  Indefinite while PRIMARY LITERATURE  Active cancer  Receiving treatment  Risk factor(s) for VTE exists  Catheter

NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

145 3 5/17/2019

CLOT TRIAL CLOT TRIAL DALTEPARIN OUTCOMES

 Population, n=676 6-month recurrence rate: 17% vs. 9%  Active cancer  Newly diagnosed symptomatic DVT and/or PE  Excluded  Active or serious bleed within 2 weeks  Platelets ≤ 75,000 cells/mm3  Treatment arms  Dalteparin 200 IU/kg SC once daily with warfarin starting within 24 hours from randomization  Goal INR 2.5 (2-3)  Dalteparin ≥ 5 days and INR > 2 for 2 days  Dalteparin 200 IU/kg SC once daily x 1 month, then 150 IU/kg x 5 months

Lee et al. N Engl J Med. 2003;349:146-53. Lee et al. N Engl J Med. 2003;349:146-53.

HOKUSAI VTE TRIAL HOKUSAI VTE TRIAL PRIMARY OUTCOME

 Non-inferiority trial  Shown to be non-inferior  n=1050  DVT or PE, either symptomatic or incidental  Active cancer or diagnosed within 2 years  Excluded: active bleeding, chronic treatment with NSAIDS for ≥ 4 days, aspirin > 100 mg/day  Treatment arms (6-12 months)  Edoxaban 60 mg orally once daily  LMWH for 5 days  Dalteparin  Primary outcome  Recurrent VTE or major bleeding  Non-inferiority margin: 1.5

Raskob et al. N Engl J Med. 2018;378:615-24. Raskob et al. N Engl J Med. 2018;378:615-24.

HOKUSAI VTE TRIAL SELECT-D TRIAL SECONDARY OUTCOMES RIVAROXABAN TREATMENT

 Population n=406 Edoxaban Dalteparin Outcome pvalue (n=522) (n=524)  Active cancer  Recurrent VTE (%) 7.9 11.3 0.09 DVT or PE, symptomatic or incidental Statistically  Exclusion Recurrent DVT (%) 3.6 6.7 significant  > 75 mg aspirin per day Not statistically  Active or high risk of bleeding Recurrent PE (%) 5.2 5.3 significant  Medications that cause significant drug-drug interactions Major bleed (%) 6.9 4 0.04  Treatment arms  Dalteparin at standard dose Major bleeding with GI Cancers: 13.2% vs. 2.4%,  Rivaroxaban 15 mg PO BID x 3 weeks, then 20 mg PO p=0.0169 daily for a total of 6 months

Raskob et al. N Engl J Med. 2018;378:615-24. Young et al. J Clin Oncol. 2018;36:2017-23.

146 4 5/17/2019

SELECT-D SELECT-D PRIMARY OUTCOME: VTE RECURRENCE BLEEDING RISK

Outcome Dalteparin Rivaroxaban Most Common Location 11% vs. Major Bleed (%) 3 5.4 GI 4% Clinically Relevant 3.4 12.3 GI or urologic Nonmajor Bleeding (%)

Young et al. J Clin Oncol. 2018;36:2017-23. Young et al. J Clin Oncol. 2018;36:2017-23.

PATIENT CASE 1 PATIENT CASE 1 QUESTION 1

 RP is a 54-year-old male with metastatic pancreatic Based on the patient case and primary literature, cancer. He was planning to start treatment with which treatment is most appropriate for RP? FOLFIRINOX today, but presents with unilateral swelling in his right leg. An ultrasound was a. Apixaban performed which confirmed a DVT. b. Dalteparin c. Edoxaban d. Unfractionated heparin

PATIENT CASE 1 QUESTION 1

How long should RP’s anticoagulant be continued? VTE PROPHYLAXIS GUIDELINES a. 3 months b. 6 months c. 9 months d. Indefinitely

147 5 5/17/2019

ASCO GUIDELINES NCCN GUIDELINES OUTPATIENT VTE PROPHYLAXIS OUTPATIENT VTE PROPHYLAXIS

Surgical Surgical Medical Medical (7-10 days) (up to 4 weeks)

 Laparotomy,  Multiple myeloma  High risk abdominal or  Multiple myeloma laparoscopy or receiving IMID with pelvic receiving IMIDs thoracotomy > 30 chemotherapy or  Gastrointestinal  Thalidomide minutes dexamethasone malignancies  Lenalidomide  High risk abdominal or  Thalidomide  Previous VTE  Pomalidomide pelvic for up to 4 weeks  Lenalidomide  Anesthesia > 2 hours  Residual disease  Immobile ≥ 4 days  Previous VTE  Advanced disease  Obese  > 60-years-old

Lyman et al. J Clin Oncol. 2007;25:5490-505. NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

RISK FACTORS FOR VTESWITHIMIDES RECOMMENDED PROPHYLAXIS

 Diagnosis of multiple myeloma ≤ 1 Risk Factor ≥ 2 Risk Factors  Obesity ≥ 30 kg/m2  Prior VTE  Central venous access device or pacemaker  Aspirin 81 or 325 mg  LMWH at prophylactic  Comorbidities  Cardiac disease daily dose  Chronic renal disease   Diabetes Warfarin  Immobilization  Goal INR 2-3  Infection  Surgery  General  Anesthesia use  Trauma  Use of ESAs  Blood clotting disorders  Hyperviscosity  Combination with high-dose dexamethasone or chemotherapy (rare)

NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019). NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

PALUMBO ET AL. IMID VTE PROPHYLAXIS

PROPHYLAXIS FOR VTESOF  n=667 MALIGNANCY  Substudy of 2 myeloma studies including PRIMARY LITERATURE population who received thalidomide  Study arms  Aspirin 100 mg PO daily  Enoxaparin 40 mg SC daily  Warfarin 1.25 mg PO daily (INR ≤ 3)

Palumbo et al. J Clin Oncol. 2011;29:986-93.

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PALUMBO ET AL. CASSINI TRIAL PRIMARY OUTCOME RIVAROXABAN PROPHYLAXIS

Composite of: Incidence  Population  Solid tumor or lymphoma  Symptomatic DVT  No difference was  ≥ 2 Khorana score  PE found  Start new treatment ≤ 1 week  Aspirin 6.4%   Arterial thrombosis Exclude: active bleeding or at risk for bleeding  LMWH 5%  Acute cardiovascular  Warfarin 8.2% event  Treatment arms  Rivaroxaban 10 mg orally daily x 180 days  Sudden death  Placebo No difference in incidence of bleeds

Palumbo et al. J Clin Oncol. 2011;29:986-93. Khorana et al. N Engl J Med. 2019;380:720-8.

CASSINI TRIAL CASSINI TRIAL PRIMARY OUTCOME PRIMARY OUTCOME UP TO DAY 180

 Composite up to day 180  DVTs  Asymptomatic or symptomatic proximal lower limb  Symptomatic upper limb  Symptomatic distal lower limb

 PE  Symptomatic or incidental

 Death from VTE

Khorana et al. N Engl J Med. 2019;380:720-8. Khorana et al. N Engl J Med. 2019;380:720-8.

CASSINI TRIAL AVERT TRIAL PRIMARY OUTCOME DURING STUDY APIXABAN PROPHYLAXIS

 Population  Active cancer  New diagnosis or progression AND start treatment within 3 months  Excluded: increased risk of clinically significant bleeding, platelets < 50,000 cells/mm3  Khorana score ≥ 2

 Treatment arms  Apixaban 2.5 mg PO BID x 180 days  Placebo

 Primary Outcome: first major VTE within 180 days (± 3 days)

Khorana et al. N Engl J Med. 2019;380:720-8. Carrier et al. N Engl J Med. 2019;380:711-9.

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AVERT TRIAL AVERT TRIAL PRIMARY OUTCOME MAJOR BLEEDING

4.2% vs. 10.2%, p<0.001 3.5% vs. 1.8%, p=0.046

Carrier et al. N Engl J Med. 2019;380:711-9. Carrier et al. N Engl J Med. 2019;380:711-9.

CASE 2 CASE 2 QUESTION 3

 PR is a 65-year-old female who was recently  Based on the current primary literature and patient diagnosed with ovarian cancer. Today, she will be case, what prophylaxis should PR receive to starting chemotherapy treatment with carboplatin prevent a VTE? and paclitaxel. She has no history of VTEs. Her BMI is 32 kg/m2. a. abixaban  Lab values b. aspirin 3 3 Date WBC (cells/mm ) Hb (g/dL) Plt (cells/mm ) c. rivaroxaban 05/24/19 5,200 12.1 300,000 d. no prophylaxis is needed  Home medications: amlopidine 10 mg daily, Calcium and vitamin D 600mg/400 IU BID, lisinopril 20 mg daily, rosuvastatin 20 mg daily

ANTICOAGULANTS TO DISCUSS

HARMACOLOGY OF DOAC P LMWH ANTICOAGULANTS COMMONLY USED Anti-Xa FOR VTESOFMALIGNANCY  Dalteparin  Edoxaban  Rivaroxaban  Apixaban

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COAGULATION CASCADE DOSING REVIEW ANTI XA FOR TREATMENT

 Dalteparin Dose First Month Five Months 200 IU/kg 150 IU/kg  Edoxaban

Dose First 5 days Up to 6 months LMWH Treatment Dose Edoxaban 60 mg daily 60 mg daily

LMWH  Rivaroxaban

Dose 21 days Up to 6 months 15 mg BID 20 mg daily

Fragmin (R) [package insert]. New York, NY: Pfizer, Inc.; 2010. http://err.ersjournals.com/content/24/137/392 Savaysa (R) [package insert]. Tokyo, Japan: Daiichi Sankyo Co. LTD; 2015. Xarelto (R) [package insert]. Titusville, NJ: Jansen Pharmaceuticals, Inc.;2016.

DOSING REVIEW MONITORING PARAMETERS PROPHYLAXIS FOR 180 DAYS

 Rivaroxaban 10 mg PO daily  Hb, hematocrit, and platelet count  Baseline  Apixaban 2.5 mg PO BID  Q2-3 days x 14 days  Q2 weeks thereafter  As needed  Renal function  Closely if receiving nephrotoxic chemotherapy  Hepatic function  Closely if receiving hepatotoxic chemotherapy  Initiation of new medications  Evaluate for drug-drug interactions

Eliquis (R) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2016. Xarelto (R) [package insert]. Titusville, NJ: Jansen Pharmaceuticals, Inc.;2016. NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease (version 1.2019).

DALTEPARIN DALTEPARIN ADVERSE DRUG EVENTS (ADE) AND MONITORING

 Other ADEs Pharmacokinetics Drug-drug Interactions  Injection site pain: ≤ 12%  Heparin-induced thrombocytopenia (HIT): < 1%  Onset of action: 1-2  Decrease efficacy  Contraindicated with history of HIT hours  Estrogens/Progestins  Half-life elimination: 3-5  Increase toxicity  Monitoring: not universally recommended for efficacy hours  Anticoagulants  Can monitor anti- factor Xa level: 0.5-1 anti-Xa units/mL  Hold dose prior to  Herbal products  Measure 4-6 hours post injection procedure  Nonselective NSAIDs  Consider in obesity, renal impairment, pregnancy, and urgent  Excretion: renal procedures

 Reversal: protamine 1 mg/100 U of dalteparin  Does not rid of anti-Xa activity

Fragmin (R) [package insert]. New York, NY: Pfizer, Inc.; 2010. Fragmin (R) [package insert]. New York, NY: Pfizer, Inc.; 2010.

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DOAC MONITORING DOAC PHARMACOKINETICS

Renal  None recommended Onset Half-life Clearance Renal Liver Medications (hours) (hours) (% drug Impairment Impairment affected) Avoid if Apixaban 1-3 12 25 Controversial Severe Avoid if Avoid if CrCl Edoxaban 1-2 10-14 50 Moderate- < 15 mL/min Severe Avoid if Avoid if CrCl Rivaroxaban 2-3 7-11 35 Moderate- < 30 mL/min Severe

Hold 2-3 days before surgery Resume 24-72 hours after surgery Eliquis (R) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2016. Savaysa (R) [package insert]. Tokyo, Japan: Daiichi Sankyo Co. LTD; 2015. Xarelto (R) [package insert]. Titusville, NJ: Jansen Pharmaceuticals, Inc.;2016.

DDI WITH CANCER MEDICATIONS DOAC DDI CYP 3A4 (APIXABAN AND RIVAROXABAN)

Strong and Moderate Inducers (Avoid) Medication Indication

Medications CYP 3A4 Substrate P-gp Substrate Apalutamide Prostate Cancer Apixaban X X Enzalutamide Melanoma Edoxaban X Dabrafenib Non-small-cell Lung Cancer Rivaroxaban X X Lorlatinib Non-small-cell Lung Cancer Strong Inhibitor (Monitor)

Medication Indication Chronic lymphocytic leukemia Idelalisib Follicular B-cell Lymphoma

Eliquis (R) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2016. Savaysa (R) [package insert]. Tokyo, Japan: Daiichi Sankyo Co. LTD; 2015. Xarelto (R) [package insert]. Titusville, NJ: Jansen Pharmaceuticals, Inc.;2016. Lexicomp. https://www-uptodate-com.ulm.idm.oclc.org/contents/search. Accessed April 23, 2019.

DDI WITH CANCER MEDICATIONS DOAC XA INHIBITOR REVERSAL P-GP ANDEXANET ALFA  Mechanism of action: binds and neutralizes factor Inducer (Monitor) Xa inhibitors  Dosing Medication Indication  Low dose: 400 mg IV bolus, 4 mg/minute IV infusion up Apalutamide Prostate Cancer to 120 minutes  High dose: 800 mg IV bolus, 8 mg/minute IV infusion up Inhibitors (Avoid) to 120 minutes Taken < 8 hours Taken ≥ 8 Medication Indication Medication Dose or unknown hours Lapatinib Breast Cancer ≤ 5 mg Low dose Neratinib Apixaban > 5 mg or High dose Rolapitant Nausea and Vomiting unknown Low dose Melanoma Vemurafenib ≤ 10 mg Low dose Colorectal Rivaroxaban > 10 mg or High dose unknown Lexicomp. https://www-uptodate-com.ulm.idm.oclc.org/contents/search. Accessed April 23, 2019. Andexxa (R) [package insert]. South San Francisco, CA: Portola Pharmaceuticals , Inc..; 2018.

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COST FOR 6 MONTHS OF THERAPY QUESTION 4

Treatment What medication can cause HIT? Medication Cost ($) Dalteparin (70 kg) 22,899.90 a. apixaban Edoxaban with 5 days of dalteparin 3,355.85 Rivaroxaban 3,601.92 b. dalteparin c. edoxaban Prophylaxis d. rivaroxaban

Medication Cost ($) Apixaban 3,196.80 Rivaroxaban 3,225.60

Lexicomp. https://www-uptodate-com.ulm.idm.oclc.org/contents/search. Accessed March 31, 2019.

QUESTION 5 CONCLUSIONS

What medication is contraindicated in a patient with a  Even though cancer is a hypercoagulable state, the CrCl of 25 mL/min? risk of VTEs is patient specific

a. apixaban  Anticoagulants currently recommended and b. dalteparin preferred in the guidelines c. edoxaban  Treatment: dalteparin and edoxaban  Prophylaxis: none except for patients taking IMIDs d. rivaroxaban

 New data has emerged that will most likely change the guidelines recommendations

CONCLUSIONS

 Close monitoring is needed of these patients due to an increased risk for bleeding, especially those with GI cancers and those receiving medications that will decrease platelet counts

 Pharmacists have an important role in choosing appropriate therapy as well as optimizing the dose, monitoring laboratory values, and preventing drug- drug interactions

15311 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 5:00 - 6:00 PM

Healthcare Burnout

0179-0000-19-028-L04-P/T

Hanna Welch, PharmD Clinical Assistant Professor University of Louisiana Monroe College of Pharmacy New Orleans, LA

Clinical Pharmacist, Ambulatory Care University Medical Center Primary Care Center New Orleans, LA

Alexis Horace, PharmD, BCACP, AAHIVP Associate Professor University of Louisiana at Monroe College of Pharmacy Monroe, LA

.Pharmacist Objectives: Pharmacy Technician Objectives: 1. Define the 3 components of burnout. 1. Define the 3 components of burnout. 2. Discuss factors contributing to burnout in 2. Discuss factors contributing to burnout in pharmacy practice. pharmacy practice. 3. Describe individual and organizational 3. Describe individual and organizational strategies to reduce burnout. strategies to reduce burnout.

Speakers have disclosed that they have no relevant financial relationships. 154 5/17/2019

Disclosure

We have no conflicts of interest to disclose.

Alexis Horace, PharmD, BCACP & Hanna Welch, PharmD

Objectives

• Define the 3 components of burnout • Discuss factors contributing to burnout in pharmacy practice • Describe individual and organizational strategies to reduce burnout

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https://i.pinimg.com/originals/1b/06/3d/1b063d3edd568abbd395f33484d91b9f.gif https://corkpsychotherapyandtraumacentre.ie/wp‐content/uploads/2018/10/Burn‐out.jpg

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Case Question 1:

• HA is a 36 year of AA female who has • Lately, HA feels overwhelmed with her practiced as a critical care pharmacist at a daily responsibilities and guilty for not community hospital for the past 10 years. having enough time with her kids. She sometimes has tension with the other Daily Work Responsibilities clinical pharmacists who she perceives Do any of the above slides feel are pawning their work onto her. In Rounding Order Verification committee meetings, she rarely Antibiotic Stewardship Addressing Drug speaks up and feels detached from familiar to you? Shortages any new initiatives that are promoted, Administrative Meetings Formulary Reviews because she feels there’s been no Precepting residents Assisting with Codes progress on old ones. • She also staffs every third weekend. On average, she works 50 hours per week • Recently her boss has approached her with little time devoted to research or about accepting pharmacy students teaching. She is also a single mother with on rotation at least 3 blocks per year. 2 kids in elementary school.

Which of the of follow components of What is Burnout? burnout is HA experiencing? • Context of physical and behavioral symptoms • Emotional Exhaustion** • Depersonalization • Decreased Sense of Accomplishment Increased Frustration Suspicion anger

Appearance Paranoia Inflexibility of depression

Freudenberger HJ. Staff burn‐out. J Soc Issues. 1974;30:159‐65.

What is Burnout? Emotional Exhaustion

• A culmination of the effects of professional responsibilities and work • Feeling of emotional strain and environment physical depletion

• Feel apathetic and indifferent about work Decreased sense Emotional Depersonalization of exhaustion accomplishment • No longer invested in situations that arise during the work day http://thecontextofthings.com/wp‐content/uploads/2017/04/emotional‐ exhaustion.jpg

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Depersonalization Decreased Sense of Accomplishment

• Developing a negative attitude • Feeling of incompetence and toward his/her job decreased work productivity • Feeling detached from the work • The gerbil on the wheel • An example is dehumanizing or • No matter what you do, there’s removing human characteristics more to be done of patients to make it easier to • Start to loath your job and cope or not care about the usually start looking for new outcome opportunities

https://blog.freelancersunion.org/content/images/OLRNPCJ4.png

https://files.adme.ru/files/news/part_172/1726215/13610365‐ Exhaustedmatchcharacter‐1521544130‐650‐be17a78e8d‐1521894066.jpg

How Common is Burnout? Workplace Consequences of Burnout

Physicians Nurses Pharmacists Increased Medical errors Staff turnover healthcare cost 30‐ 10‐ 40‐

50% 70% 60% Costs Decreased associated with patient staff turnover satisfaction

Bridgeman PJ, Bridgeman MB, Barone J. Am J Health Syst Pharm 2018;75:147‐52. El‐Ibiary SY, Yam L, Lee KC. Am J Pharm Educ 2017;81:75. Jones GM, Roe NA, Louden L, Tubbs CR. Hosp Pharm 2017;52:742‐51. Williams E, Martin SL, Fabrikant A, Wang A, Pojasek M. Am J Health Syst Pharm 2018;75:292‐7.

Health Consequences of Burnout Burnout and Depression

Depression

Helplessness Hopelessness Powerlessness

Salvagioni DAJ, Melanda FN, Mesas AE, Gonzalez AD, Gabani FL, Andrade SM. Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies. PLoS One 2017;12:e0185781. Bridgeman PJ, Bridgeman MB, Barone J. Burnout syndrome among healthcare professionals. Am J Health Syst Pharm 2018;75:147‐52.

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Difference Between Stress & Burnout

Stress Burnout

Characterized by over‐engagement Characterized by disengagement

Emotions are overreactive Emotions are blunted

Produces urgency and hyperactivity Produces helplessness and hopelessness

Loss of energy Loss of motivation, ideals, and hope

Leads to anxiety disorders Leads to detachment and depression

Primary damage is physical Primary damage is emotional

May kill you prematurely May make life seem not worth living

https://img.huffingtonpost.com/asset/5894f1062800001f00996c5f.jpeg?ops=scalefit_960_noupscale https://www.helpguide.org/articles/stress/burnout‐prevention‐and‐recovery.htm/

How do we assess burnout? How do we objectively assess burnout?

• Maslach Burnout Inventory • Self‐Administered • Divided into three domains • 22 questions • 15 minutes

http://weknowmemes.com/wp‐content/uploads/2013/02/i‐feel‐it‐dog‐meme.jpg

Do you feel you suffer from burnout in your current position? 7 risk Workload Job demands exceed human limits • Yes factors Control Role Conflict • No for Reward Inadequate financial, institutional, or social burnout reward Community Lack of quality social interaction at work

Fairness Perception of equity from an organization

Organizational values are incongruous with Values an individual's personal values or beliefs

Personality doesn't fit or misaligned with Job‐person‐incongruity job expectations

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Case question 2 Burnout in Pharmacy Practice

• WH, a 29‐year‐old male, is a PGY2 Emergency Medicine Pharmacy Resident at an academic medical center. He works long hours and feels bogged down by his residency responsibilities. When he goes Clinical Pharmacists home, he feels drained from working and has no interest in his hobbies. He sleeps long hours on the weekends and rarely leaves his apartment. He used to enjoy going out to eat with friends, but Residents recently started to decline their invitations even when his schedule allows. Pharmacy Faculty

Factors Associated with Burnout Among US Hospital Clinical Pharmacy Burnout in Pharmacy Practice Practitioners: Results of a Nationwide Survey

• Surveyed 1,256 clinical pharmacists (14.7% response rate) Clinical Pharmacists 97.4% worked full‐time (~48 Majority female (69.5%) hours a week) Residents Demographics

46.9% in academic teaching Pharmacy Faculty BPS (73.0%), Residency hospital, 30.0% in training (58.1%) community hospital

Jones GM, Roe NA, Louden L, and Tubbs CR. Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Survey. Hospital Pharmacy. 2017:52(11):724‐751.

Factors Associated with Burnout Among US Hospital Clinical Pharmacy Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Survey Practitioners: Results of a Nationwide Survey

• Factors independently linked to Burnout Emotional Personal • Too many non‐clinical responsibilities (OR: 2.3) Depersonalization Burnout! Exhaustion Accomplishment • Uncertainty regarding healthcare reform (OR: 2.0) • Inadequate time for teaching (OR: 1.8) • Administrative activities (OR: 1.9) HW1 • Difficult pharmacist colleagues (OR: 2.1) 52.9% 32.6% 10.3% 61.2% • Feeling that one’s contributions were unappreciated by others (OR: 2.2)

• Factor protective against Burnout • Age (39 +/‐ 10.6 years)

Jones GM, Roe NA, Louden L, and Tubbs CR. Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Jones GM, Roe NA, Louden L, and Tubbs CR. Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Survey. Hospital Pharmacy. 2017:52(11):724‐751. Survey. Hospital Pharmacy. 2017:52(11):724‐751.

159 5 Slide 29

HW1 Although this study doesn't state explicitly, I think this subscale is the opposite of the others in that high scores=good. So not a good finding that only 10.3% reported high personal accomplishment :(. Hanna Welch, 3/20/2019

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Factors Associated with Burnout Among US Hospital Clinical Pharmacy Burnout in Pharmacy Practice Practitioners: Results of a Nationwide Survey

Career Satisfaction 83.7% Clinical Pharmacists

Residents Conclusion: The rate of burnout among US clinical pharmacists is high. The response rate of this survey is low, and therefore cannot be extrapolated to to clinical pharmacists as a whole. Hopefully this information will spur further research on rates of burnout on the lives of clinical pharmacists and the outcomes regarding medication errors. Pharmacy Faculty

Jones GM, Roe NA, Louden L, and Tubbs CR. Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide Survey. Hospital Pharmacy. 2017:52(11):724‐751.

Rates of Depressive Symptoms Among Pharmacy Residents Rates of Depressive Symptoms Among Pharmacy Residents

• Surveyed 678 PGY1 and PGY2 residents (20.5% response rate) PHQ‐9 Survey Survey Score Result Average 57.6 work hours a <4 No depression Majority female (72.8%) week, 5.5 hours spent outside of work 5‐9 Mild depression 10‐14 Moderate depression Demographics 15‐19 Moderately‐severe depression ≥20 Severe Depression A score of ≥10 has been shown to have an 88% sensitivity and specificity for 73.2% in In‐patient • PGY1 (72%) major depression. residency program

Williams E, Martin SL, Fabrinkant A, Wang A, et al. Rates of depressive symptoms among pharmacy residents. Am J Health‐Syst Pharm. 2018; 75(5): 292‐297 Williams E, Martin SL, Fabrinkant A, Wang A, et al. Rates of depressive symptoms among pharmacy residents. Am J Health‐Syst Pharm. 2018; 75(5): 292‐297

Rates of Depressive Symptoms Among Pharmacy Residents Rates of Depressive Symptoms Among Pharmacy Residents

PGY1 & PGY2 Residents • Thoughts 40% • Symptoms of depression may be unrelated to residency Scored ≥10 n = 280 • Treatment of depression was not evaluated

US General Population Rates: 6.6 – 6.7% • How does this link to burnout? • What activities are linked to burnout for pharmacy residents? • What can be done about this? Start of Survey End of Survey Rated of PHQ‐9 ≥20

2.9% 7.3% p < 0.05

Williams E, Martin SL, Fabrinkant A, Wang A, et al. Rates of depressive symptoms among pharmacy residents. Am J Health‐Syst Pharm. 2018; 75(5): 292‐297 Williams E, Martin SL, Fabrinkant A, Wang A, et al. Rates of depressive symptoms among pharmacy residents. Am J Health‐Syst Pharm. 2018; 75(5): 292‐297

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Burnout in Pharmacy Practice Assessment of Burnout and Associated Risk Factors Among Pharmacy Practice Faculty in the United States

• Surveyed 758 faculty members (32.7% response rate) Clinical Pharmacists Mean 15.1 years worked Majority female (68.2%) since graduation, 8.9 years at current institution Residents Demographics

Pharmacy Faculty Majority non‐tenure track Majority with clinical (69.3%) practice site (77.6%)

El‐Ibiary SY, Yam L, Lee KC. Assessment of Burnout and Associated Risk Factors Among Pharmacy Practice Faculty in the United States. Am J Pharm Educ 2017;81:75.

Assessment of Burnout and Associated Risk Factors Among Pharmacy Assessment of Burnout and Associated Risk Factors Among Pharmacy Practice Faculty in the United States Practice Faculty in the United States

• Factors predictive of burnout Emotional Low Personal • Female Exhaustion Depersonalization Accomplishment • Children <12 years old • Working at newer college/school of pharmacy • Working >50 hours per week • Lower rank 41.3% 10.4% 23.9% • No hobby • No mentor

Jones GM, Roe NA, Louden L, and Tubbs CR. Factors Associated with Burnout Among US Hospital Clinical Pharmacy Practitioners: Results of a Nationwide El‐Ibiary SY, Yam L, Lee KC. Assessment of Burnout and Associated Risk Factors Among Pharmacy Practice Faculty in the United States. Am J Pharm Educ 2017;81:75. Survey. Hospital Pharmacy. 2017:52(11):724‐751.

Assessment of Burnout and Associated Risk Factors Among Pharmacy Which component of burnout is most prevalent Practice Faculty in the United States among pharmacists based on these studies? • A 2015 study of pharmacy faculty found • Emotional Exhaustion • Depersonalization High Career Satisfaction 63.7% • Low Personal Accomplishment

High Satisfaction with 36.9% Work‐Life Balance

• Poor work‐life balance  emotional exhaustion

Lindfelt TA, Ip EJ, Barnett MJ. Survey of career satisfaction, lifestyle, and stress levels among pharmacy school faculty. Am J Health Syst Pharm. 2015;72(18):1573‐8.

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Solutions: How to Cope?

• First is to identify Burnout within yourself • Reach out to those closest to you – try to communicate with your supervisor • Become more “selfish” or say “No” • Find ways to make work more interesting • Work away from your desk / change of scenery • Get plenty of sleep, exercise, eat well • Ask for different responsibilities / check your job responsibilities • Take a break from caffeine or alcohol use

• QUIT! https://cdn.shopify.com/s/files/1/0612/1109/products/612 ‐mom‐burnout‐cartoon_300x300.gif?v=1539717589

https://www.thebalancecareers.com/how‐to‐deal‐with‐work‐burnout‐4142144 https://www.inc.com/john‐rampton/8‐ways‐to‐get‐over‐job‐burnout‐without‐leaving.html

Burnout Interventions Brainstorm: Ideas for system‐wide change

• Individual‐focused • Examples: stress management, mindfulness training • May target trainees or practitioners • Generally positive results in short term

• Organization‐focused • Examples: rescheduling shifts, decreasing workload • More likely to reduce burnout

Panagioti M, Panagopoulou E, Bower P et al. Controlled Interventions to Reduce Burnout in Physicians: A Systematic Review and Meta‐analysis. JAMA Intern Med 2017; 177: 195‐205.

Which of these domains most contributes to Organizational Change your feeling of burnout? “Burnout is not a problem of people but of the social environment in which they work.” Workload Control Reward Community Fairness Values

Maslach C, Leiter MP. New insights into burnout and health care: Strategies for improving civility and alleviating burnout. Med Teach 2017; 39: 160‐163.

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Organizational Change Organizational Change Workload • Efficient work processes • Time to recover from stress • Improves patient outcomes Control • Clearly defined roles and expectations across practice environments • Employee control over workplace issues and disease states Reward • Culture of appreciation and recognition Team‐Based • Teamwork  less burnout • Opportunities for advancement Care Team culture predicts Community • Structured mentor programs • • Personal contact from management emotional exhaustion more reliably than structure Fairness • Equitable and transparent policies Values • Identifying misalignments between individual expectations and organizational goals

Bridgeman PJ, Bridgeman MB, Barone J. Burnout syndrome among healthcare professionals. Am J Health Syst Pharm 2018; 75: 147‐152. Smith CD, Balatbat C, Corbridge S, Dopp AL, Fried J, Harter R, Landefeld S, Martin C, Opelka F, Sandy L, Sato L, Sinsky C. 2018. Implementing optimal Maslach C, Leiter MP. New insights into burnout and health care: Strategies for improving civility and alleviating burnout. Med Teach 2017; 39: 160‐163. team‐based care to reduce clinician burnout. NAM Perspectives. Discussion Paper, National Academy of Medicine, Washington, DC.

What is one change in your workplace that Conclusion has helped or could help to reduce burnout? • Burnout is common in health care and pharmacy practice • Burnout has pervasive negative effects on health, workplace, and patient care • Positive lifestyle changes can help to overcome burnout • Organizational change is necessary to prevent and reduce burnout

164 9 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Saturday, May 25, 2019 8:00 - 9:00 AM

Comprehensive Medication Management (CMM)

0179-0000-19-017-L04-P/T

Sarah Amering, PharmD, BCACP Clinical Assistant Professor Xavier University of Louisiana College of Pharmacy New Orleans, LA

.Pharmacist Objectives: Pharmacy Technician Objectives: 1. Review key components of Comprehensive 1. Define Comprehensive Medication Medication Management. Management. 2. Discuss CMM and previous iterations of 2. Compare Comprehensive Medication pharmacotherapy. Management to Medication Therapy 3. Explain integration of CMM into Management. Pharmacist’s Patient Care Process.

165 CMM: Speaking the Same Language

Sarah Amering, PharmD, BCACP

Clinical Assistant Professor

Xavier University of Louisiana

College of Pharmacy

New Orleans, LA

166 Objectives

 Review key components of Comprehensive Medication Management (CMM)

 Compare and contrast CMM and previous iterations of pharmacotherapy

 Evaluate integration of CMM into the Pharmacists’ Patient Care Process (PPCP)

167 Scope of issue

Spending on healthcare in US in 2017 $3.5 trillion dollars

Medication related issues $500 billion

Diabetes Care in US in 2017 $327 million

SpaceX Falcon 9 program $90 million per mission

Mueller investigation $25.2 million

168

Politifact, Money.com, Diabetes.org, CMS.gov, hpi.Georgetown.edu/rxdrugs Poll

 What do you call what you do?

169 170 What’s in a name?

Nurses  Nursing process  Assessment  Diagnosis  Outcomes/planning  Implementation  Evaluation

171 ANA. The Nursing Process. Web accessed 5/1/2019 What’s in a name?

Nurse Practitioner’s Practice model  Process of care  Assessment of health status  Diagnosis  Development of treatment plan  Implementation of plan  Follow-up and evaluation

AANP. AANP Standards of Practice for Nurse Practitioners. Web accessed 5/2/2019. 172 History

Patient- Medication centered Management Primary Care Task Force CMM Collaborative

173 Pharmacotherapy 2015;35(4):e39–e50 History

Pharmaceutical CareMedication Therapy ManagementIndividualized (MTM) Medication Assessment and PlanningSHPA standards (iMAP of) practice for clinicalComprehensive pharmacy medication services management in the PCMH

174 Pharmacotherapy 2014;34(8):e133–e148 Comparison

Pharmaceutical MTM iMAP SHPA Care Collect, analyze, Assess med Ten step process Focused on identify med therapy and reviewing medical overall patient related develop list of record and identifying and specific problems (MRPs) MRPs MRPs clinical outcomes • Indication • Indication • Drug therapy needed • Drug selection • Effectiveness • Effectiveness • Suboptimal dosing • Over/underdose • ADRs • ADRs • Monitoring needed • Compliance • Adherence • Compliance • Suboptimal drug • Undertreated • ADE condition • Suboptimal • Monitoring duration/frequency needed • Nonadherence • Education • Non-classifiable • Toxicity/allergy/A DR 175 Pharmacotherapy 2014;34(8):e133–e148 CMM components

 Standard of care to ensure each patients medications are assessed to determine  Appropriateness  Efficacy  Safety  Adherence

Pharmacotherapy 2015;35(4):e39–e50 176 CMM process

 Assessment of medication related needs  Includes clinical assessment of patient’s conditions

 Identification of medication related problems  Appropriateness of medication  Evidence-based  Personalized  Effectiveness of medication  Achieving goals of therapy  Safety of medication  ADRs  Drug interactions  Adherence

PCPCC 2012. Integrating Comprehensive Medication Management to Optimize Patient 177 Outcomes Who provides MTM?

178 Key differences between MTM and CMM

CMM MTM

 Process of care  Part D benefit

 Requires collaborative  No formal agreement agreement between pharmacist and prescriber  Evaluate clinical status  Provided in any setting  Clinical follow-up to determine progress  Specific plan criteria must be met  Specific to pharmacists  Can be performed by any healthcare team member

179 Pharmacotherapy 2015;35(4):e39–e50 MTM included in CMM

Appropriateness Adequacy Safety

• Unnecessary • Ineffective • ADR drug therapy medication • Dose too high • Needs • Dose too low • Drug additional interaction therapy

The Patient Care Process for Delivering Comprehensive Medication Management(CMM): Optimizing Medication 180 Use in Patient-Centered, Team-Based Care Settings. CMM in Primary Care Research Team. July 2018. Available at http://www.accp.com/cmm_care_process CMM is a process of care

Patient care Process

Practice Philosophy Management Systems of Care

181 Why is this important?

 Advocacy  Consistency in message

 Patient care  Consistency in care

 Value  Consistency in coding

182 Poll

 How many subjects have you had in a research study you have completed?

183 184 Terminology used in practice

Citation Terms used

Garcia-Cardenas, et al Patient Care Management, Drug Therapy, Eur Respir J 2016; 47: Outcome and Process Assessment, Preventative 1134–1143 Health Services, Pharmaceutical Services Bukhsh A, et al. Front. Pharmaceutical Care, Clinical pharmacy, Pharmacol 2018; 9:339. Pharmaceutical Services or Education or Intervention, Medication Management, Delpeuch A, et al. Drug Management, Clinical pharmacy services, ANTICANCER RESEARCH Medication review, 2015; 35: 457-460. Polgreen L, et al. Pharmacist-physician collaborative intervention Hypertension. 2015;66:1145-1151 185 Consequences of inconsistency

Documentation

Billing

Practice advancement

186 Advocacy

Pharmacy and Medically Underserved Areas Enhancement Act (Pharmacist provider status)  S. 109 – Senator Grassley (R‐Iowa); 53 cosponsors  H.R. 592 – Rep. Guthrie (R‐Kentucky); 291 cosponsors  Congressional Budget Office  Does it really solve the important issues?

Kelly PT. ACCP 2018 Annual Meeting. Making the Case: Advocating for Patients Across the Health 187 Care Spectrum Looking Beyond “Provider Status” Moving pharmacy practice forward

Comprehensive Medicare Management  Not introduced in Congress ‐‐ yet  Policymakers need “data” to provide rationale  Need to demonstrate value and define what we do  CMM fits perfectly into value‐based, collaborative health reform

Kelly PT. ACCP 2018 Annual Meeting. Making the Case: Advocating for Patients Across the Health 188 Care Spectrum Looking Beyond “Provider Status” Teaching CMM

Consistency in documentation Appropriateness Adequacy Safety Adherence

189 CMM and the PPCP

Joint Commission of Pharmacy Practitioners. Pharmacists’ Patient Care Process. May 29, 2014; The Patient Care Process for Delivering 190 Comprehensive Medication Management(CMM): Optimizing Medication Use in Patient-Centered, Team-Based Care Settings. CMM in Primary Care Research Team. July 2018. Available at http://www.accp.com/cmm_care_process Benefits of speaking the same language

 Research  Collaborate with peers  Allow for larger studies to better demonstrate value

 Value  Create consistent terms used in billing similar to other professions

 Advocacy  Consistency in message to legislators

191 What questions do you have?

Courtesy GitHub 192 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Saturday, May 25, 2019 9:00 - 10:00 AM

Sex, Drugs & Rock ‘N’ Roll: Pharmacotherapeutic Considerations of Arousal, Addiction and Regression

0179-0000-19-019-L01-P

Joshua Gauthier, PharmD Mental Health Clinical Pharmacist - Acute Psychiatry Southeastern Louisiana Veterans Health Care System New Orleans, LA

Pharmacist Objectives: 1. Describe neuropsychiatric physiology of arousal, aggression and addiction. 2. Discuss diagnosis and pathology of behavioral disorders. 3. Detail evidence-based guideline drive treatment for behavioral disorders (pharmacologic and non-pharmacologic) 4. Discuss social implications and stigma associated with behavioral disorders. 5. Describe potential role for clinical pharmacist providers in behavioral disorder recovery.

Speaker has disclosed that he has no relevant financial relationships. 193 5/17/2019

Pre‐Test

1. Healthcare providers may identify or relate to behavioral disorders by 4. Which agent is least likely to be effective for long‐term treatment of ◦ A. Stigmatizing impulsive aggressive behaviors? ◦ B. Normalizing A. Alprazolam ◦ C. Romanticizing B. Naltrexone ◦ D. All of the above C. Fluoxetine Sex, Drugs and Rock 'n’ Roll: D. Phenytoin 2. Impulsive and compulsive disorders are similar in that ◦ A. Signaling from the pre‐frontal cortex to the limbic system is muted 5. Which agent has good evidence for benefit across multiple Pharmacotherapeutic considerations of ◦ B. Signaling from the limbic system to the pre‐frontal cortex is amplified substance use disorders, impulse‐control disorders and is available as a ◦ C. Involve an injury or lesion within the prefrontal cortex monthly long‐acting injectable? ◦ D. Involve an injury or lesion within the limbic system A. Acamprosate arousal, addiction and aggression B. Naltrexone 3. Chemical castration with a GNRH such as leuprolide requires which during initiation to prevent recidivism? C. Buprenorphine‐naloxone ◦ A. Concommitant administration with ascorbic acid to assure D. Topiramate JOSHUA D GAUTHIER PHARMD absorption ◦ B. Therapeutic drug monitoring of GNRH agonist levels ◦ C. Concommitant administration of an anti‐androgen such as flutamide to block an initial increase in testosterone ◦ D. Supplementation with estrogen to ensure aberrant thoughts do not return

Objectives .Describe neuropsychiatric physiology of arousal, aggression and “I hate to advocate drugs, alcohol, violence, or insanity to addiction anyone, but they've always worked for me.” . Discuss diagnosis and pathology of behavioral disorders ‐Dr. Hunter S. Thompson .Detail evidence‐based, guideline driven treatment for behavioral disorders (pharmacologic and non‐pharmacologic) Note: Dr. Thompson was found in his Woody Creek, Colorado home, dead of an apparent self‐ .Discuss social implications and stigma associated with behavioral inflicted gunshot wound February 20, 2005. Dr. Thompson was 67 years old. disorders .Describe potential role for clinical pharmacist providers in behavioral disorder recovery

Beer Street and Gin Lane (1751) Impulsive vs Compulsive Impulsive – difficulty resisting urges to engage in behaviors that are excessive and/or harmful to self or others

Impulse‐Control Disorders • Repetition despite adverse consequences • Diminished control • Cravings or urges • Pleasure

https://en.wikipedia.org/wiki/Beer_Street_and_Gin_Lane#/media/File:Beer‐street‐and‐Gin‐lane.jpg

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Impulsive vs Compulsive Sex associated Impulsive‐compulsive disorders Compulsive – difficulty terminating a repetitive ritual or behavioral pattern Paraphilic disorders • Sexual behaviors which are generally not accepted by society • May or may not be compulsive Compulsive Disorders • Stereotypic behaviors • Ego‐dystonic Non‐paraphilic disorders • Harm avoidance • Compulsive behaviors • The frequency of behavior results in the disorder

Stahl, S. M. (2013). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.

Sex ‐ Physiology Neuro‐active steroids

•Gonadal hormones – Synergistic asymmetry of male/female hormones 5α – R: 5 alpha reductase • Androgen – male • Finasteride • Estrogen – female • Dutasteride •Arousal requires both hormones, however relative concentration ratios must be either High estrogen and low testosterone AROM: Aromatase ‐OR‐ • Anastrozole High testosterone and low estrogen • Exemestane •Potential pharmacologic targets • Letrozole • 5‐Alpha reductase – converts testosterone to dihydrotestosterone (DHT) • Although DHT is more potent than testosterone, testosterone has a stronger effect on sexual response to stimuli • Aromatase

• Converts testosterone to estrogen although is unable to act on DHT Cai H, Cao T, Zhou X, et al. Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications. Front Psychiatry. 2018 Mar 8;9:73. doi: 10.3389/fpsyt.2018.00073. eCollection 2018

Sex – Physiology (cont.) Relationships ‐ Physiology •More robust evidence describing •The Oxytocin – Vasopressin Pathway process in males • Greek for ‘Rapid birth’ • Concomitant activation of antagonistic • Inherently pro‐social hormone processes in both cerebral and spinal tracts • Suppression of inhibitory interneurons • Works with serotonin to reinforce pleasurable social experiences • Sympathetic system – Subjective arousal • Oxytocin has been found to • Parasympathetic – Physiological response • Increase ability to infer emotional state from expression • Promote monogamous relationships •Implications – sequence effects • Promote mother‐infant bonding • Male – Engorgement, erection, secretion, • Disorders associated with pathologic oxytocin activity ejaculation/orgasm • Autism – subset with hypothalamic oxytocin deficiency • Female – Secretion, engorgement, orgasm • Prader‐Willi – associated with hypothalamic oxytocin deficiency • Generally, in a series of orgasms, men • 2017 study ‐ low dose intranasal oxytocin result in reduction of experience diminishing intensity whereas Appetite drive, Anxiety and Repetitive behaviors women experience increasing intensity Carter, C. The Oxytocin–Vasopressin Pathway in the Context of Love and Fear. Front Endocrinol (Lausanne). 2017; 8: 356. Motofei IG, Rowland DL. The physiological basis of human sexual arousal: • Vasopressin promotes defense of self and family neuroendocrine sexual asymmetry. Int J Androl. 2005 Apr;28(2):78‐87.

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Paraphilia and associated disorders Paraphilia Epidemiology Intense and persistent sexual interest Paraphilia Description The most common: Recidivism rates ‐ Most data for pedophilia in non‐human or non‐consenting Exhibitionism Exposure of genitals to unsuspecting strangers • Voyeurism – 12% male, 4% female • Homosexual and bisexual pedophiles – 50% targets Heterosexual pedophilia – 25% Fetishism Use of nonliving objects (e.g. leather goods, clothing, undergarments, fabrics, shoes) • Pedophilia – 3 to 5% male • • Exhibitionism – 2 to 4% male • Incestuous pedophilia has lowest rates Frotteurism Touching and rubbing against a non‐consenting person Anomalous activity Pedophilia Children are the sexual target Paraphilic disorders are Risk factors for recidivism • Courtship significantly more preponderant in • Deviant sexual practices • Algolagnic Sexual masochism Receipt of humiliation/suffering from partner males except for Sexual Masochism • Attraction to younger children Sexual sadism Inflicts humiliation/suffering on partner • Sociopathic or antisocial personality traits Transvestic Wearing clothing of the other sex Common comorbidity Anomalous target fetishism • Treatment non adherence • Children • Sexual dysfunction disorder, Voyeurism Observing sexual activity or naked/disrobing individuals personality disorder and depression • Objects Coprophilia (feces/defecation); klismaphilia (enema use); mysophilia (filth); Paraphilia NOS narratophilia (erotic talk); telephone scatalogia (obscene telephone calls); urophilia (urine/urination); zoophilia (animals); and necrophilia (dead persons).

Paraphilia Pathology Paraphilia treatment Addiction vs compulsion debate • Hormones Non‐pharmacologic Cross‐cultural normative ambiguity • • Testosterone/dihydrotestosterone • Surgical castration • Diverse manifestations – paraphilic vs non‐paraphilic • Estrogen/progesterone • Reduces recidivism however, • Disorder vs Syndrome • Prolactin • Up to one third of castrated males • Lack of empirical evidence • Neuropeptides can still engage in intercourse Exogenous testosterone replacement Chemicals associated with normal • Gonadotropin‐releasing hormone • physiologic functioning [GnRH] • Neurotransmitters • Follicle‐stimulating hormone [FSH] • Cognitive‐behavioral therapy • Dopamine • Luteinizing hormone [LH] • Norepinephrine Paraphilia often emerge secondary to • Masturbatory conditioning https://tvtropes.org/pmwiki/pmwiki.php/Main/TheLudov • Acetylcholine sexual dysfunction icoTechnique • Serotonin • Huntington’s

http://news.bbc.co.uk/2/hi/uk_news/magazin e/4853432.stm

Algorithm of pharmacological treatment of paraphilias LEVEL 1 • Aim: control of behaviors without impact on • Psychotherapy (preferentially cognitive behavioral Paraphilia conventional sexual activity and on sexual desire therapy if available (Level C), no level of evidence for other forms of psychotherapy) LEVEL 2 • Aim: control of behaviors with minor impact on • SSRIs: increase the dosage at the same level as treatment conventional sexual activity and on sexual desire prescribed in OCD (e.g., fluoxetine 40–60 mg/day or Luteinizing Hormone‐Releasing Hormone Agonists • “Hands off” paraphilia paroxetine 40 mg/day (Level C) • No satisfactory results at level 1 Pharmacologic LEVEL 3 Chemical castration • Aim: control of behaviors with a moderate reduction • Add a low dose antiandrogen (e.g., cyproterone acetate • Antidepressants of conventional sexual activity and sexual desire 50–100 mg/day) to SSRIs (Level D) • Release of LH and FSH initially stimulates • Fondling without penetration or sexual sadism • Decrease testosterone • No satisfactory results at level 2 after 4–6 weeks of increasing sex hormones Increase oxytocin high dose SSRIs • LEVEL 4 • Gonadotrope responsiveness to endogenous •Aim: control of behaviors with a substantial reduction • First choice: cyproterone acetate (CPA): oral, 200–300 LHRH is eventually suppressed • Naltrexone of sexual activity and desire mg/day (full dose) or i.m. 200–400 mg once weekly or • Non‐paraphilic compulsive behaviors •Sexual violence, intrusive fondling, victimization of every 2 weeks (Level C) • LH and FSH secretion and thus sex hormones others • Second choice: medroxyprogesterone acetate: 50–300 mg/day or i.m. 300–500 mg/week are reduced • Anticonvulsants/mood • If sexual sadism fantasies or behavior: go to level 5 stabilizers • If non‐compliant: use IM formulation or go to level 5 • Pure antiandrogen is used during the initial 1‐2 • No satisfactory results at level 3 LEVEL 5 months • Antipsychotics • Aim: control of behaviors with an almost complete • Long acting GnRH agonists, i.e. triptorelin or leuprolide suppression of sexual desire and activity acetate 3 mg/month or 11‐25 mg i.m. every 3 months • Adverse events • Hormones (Level C) • Sexual Sadism • Hypogonadism with erectile failure • Estrogen • Non‐compliance or no satisfactory results at level 4 • Cyproterone acetate may be added to GnRH agonist (one week before and during the first month) to prevent • Decreased pubic/facial hair growth • Progestin the androgen flare up effect and reduce risk for relapse LEVEL 6 • Hot flashes Luteinizing Hormone‐Releasing • Aim: control of behaviors with a complete suppression • Use antiandrogen treatment, i.e. cyproteroneacetate • Adatpted from Bertoni Lopes de Andrade, Italo & Souza, Nathália & Mattos Pascotto, Viviane. (2017). Hormone Agonists of sexual desire and activity (200–400 mg once weekly or every 2 weeks i.m.) or, Cypermethrin exposure and effects on the reproductive male system: a literature review. Revista Intertox de • Most severe paraphilia (catastrophic cases) medroxyprogesterone acetate (300–500 mg/week i.m.) in Toxicologia, Risco Ambiental e Sociedade. 10. 10.22280/revintervol10ed3.293. • No satisfactory results at level 5 addition to GnRH agonists (Level D)

Thibaut F, De La Barra F, Gordon H, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the biological treatment of paraphilias. World J Biol Psychiatry. 2010 Jun;11(4):604‐55. doi: 10.3109/15622971003671628.

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Cyproterone Acetate Medroxyprogesterone Acetate •Testosterone antagonist and also blocks •More progestin‐like than anti‐ testosterone synthesis androgenic •Progestin activity blocks the compensatory rise • Less potent androgen antagonist in gonadotropins after a decrease in than cyproterone acetate testosterone levels • Unlike antiandrogen flutamide •Adverse effects •Adverse effects • Reduced bone mineral density • Malaise • Weight gain • Flushing • Headache • Dizziness • Malaise • Depression • Dyspepsia • Venous thromboembolism (VTE) • VTE • Decreased pubic/facial hair growth • Muscle cramps • Psychotic reactions • Gallstones • Increased body weight • Diabetes mellitus https://courses.washington.edu/conj/bess/contraception/contraception.htm

Compulsive Sexual Behavior (CSB) Sex and Violence Pattern of failure to control intense sexual impulses or urges resulting in repetitive Physiologic associations sexual behavior and causes marked distress or significant impairment in functioning • Testosterone • Sympathetic systems “Other unspecified impulse control disorders” • Male preponderance of sexually violent disorders • Aggression is associated w/ flight‐or‐fight systems • Evidence correlating testosterone levels with which decreases penile tumescence • Some advocate for an addiction classification violent sexual behavior is mixed • However, arousal and orgasm requires sympathetic • The debate regarding sexual addiction/CSB classification highlights how little is known about • However, significant association with activation impulsive/compulsive behaviors and corresponding pathology • Social dominance – high levels • Norepinephrine levels increase 12x from baseline during male orgasm • Lack of social reciprocity – low levels Treatment Pharmacotherapy • When sympathetic deficiency leads to dysfunction, in Antidepressants • High testosterone levels associated with anti‐ order to heighten norepinephrine release, some might • Cognitive behavioral therapy (CBT) • social behavior SSRIs – Paroxetine engage in risky behaviors such as: • Increasing socio‐economic status may moderate this • Cognitive analytic therapy (CAT) • Self‐asphyxia • TCAs – Clomipramine, Desipramine effect • • Mindfulness • Exhibitionism • Naltrexone Temporal‐Limbic pathways are involved Self‐Help groups ‐ 12‐step programs • • • Antiepileptics in both arousal and aggression Sexual victimization is often less about arousal and more about control of another person • Temporal‐Frontal lobe abnormalities

Aggression Physiology Aggression Pathology Anger and fear Impulsive aggressive behavior • Subcortical source – Limbic system • Reduced top‐down inhibition • Amygdala • Cortical impairment • Cortical inhibition • Phineas Gage • Increased bottom‐up signaling Types of aggression • Hyperactive limbic system • Impulsive Amygdala’s Weaknesses • Associated with anger/fear as indicated by autonomic Mental Illness • Prone to violent fits of rage arousal in response to stress • When medicated, he is Kindling theory usually quite docile • Pre‐meditated Diminished Intellect • Similar sensitizing process described • Intellect is similar to that of a • Also, Predatory, Instrumental, Proactive young child for seizure and bipolar disorders • Not necessarily associated with autonomic response • Violent outbursts are like a child throwing a temper tantrum, although more Siever LJ. Neurobiology of aggression and violence. Am J Psychiatry. 2008;165(4):429‐42. • Mode dangerous • Verbal or physical, direct or indirect

http://dc.wikia.com/wiki/Aaron_Helzinger_(New_Earth)

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Aggression Pathology (cont.) Aggression Treatment Complexity of impulsive aggression Acute phase • Diverse pathological processes associated with aggressive behavior • Benzodiazepines in several psychiatric disorders • Antipsychotics Neuromodulators Maintenance phase Serotonin • • Dementia Catecholamines • • SSRIs effective and fewer side effects • Acetylcholine • Several antipsychotics showed benefit, but • GABA/Glutamate quetiapine did not – presumably due to anticholinergic effects • Vasopressin/Oxytocin • Psychosis • Opiates • Clozapine showed benefit independent of sedation • Testosterone • Lithium • Cortisol • Anticonvulsants – mixed evidence Siever LJ. Neurobiology of aggression and violence. Am J Psychiatry. 2008;165(4):429‐42. • Sterols/Fatty acids Siever LJ. Neurobiology of aggression and violence. Am J Psychiatry. 2008;165(4):429‐42. • Phenytoin, Depakote, Carbamazepine

Impulse‐Control Disorders (ICD) Substance Use Disorder (SUD)

Note: For DSM 5, Trichotillomania and Skin Picking Disorders Formerly separated into two diagnoses in DSM‐IV Evidence for Pharmacologic Treatment Benefit with ICDs were moved from ICD to Obsessive‐Compulsive and Related Antidepressants Anticonvulsant/mood stabilizers Opioid antagonist Antipsychotics Disorders . Gambling Disorder was moved to Addiction • Substance abuse – mild to moderate SUD Disorders. Compulsive Buying and Sexual Behavior have not Fluvoxamine ‐ mixed Lithium ‐ benefit Naltrexone ‐ benefit Olanzapine ‐ none been explicitly recognized/defined. • Substance dependence – moderate to severe SUD Paroxetine ‐ mixed Nalmafene ‐ benefit Pathological Escitalopram ‐ benefit gambling Sertraline ‐ none Conclusions regarding For the first time non‐substance related addiction Bupropion ‐ none pharmacologic treatment for ICDs: has been described in the DSM 5 Kleptomania Escitalopram ‐ none Naltrexone ‐ benefit • SSRIs have the most evidence • Gambling Disorder Fluoxetine ‐ benefit Divalproex ‐ benefit (w/ Cluster B for benefit across disorders • Conditions for Further Study Intermittent PD dx only) Explosive Levetiracetam ‐ none • Naltrexone has the strongest • Caffeine use disorder disorder evidence for benefit with • Internet gaming disorder Pyromania gambling and kleptomania Fluvoxamine ‐ mixed Non‐therapeutic use of psychotropic drugs – issues? • High rates of co‐morbidity and Compulsive Citalopram ‐ benefit • Cultural or ritualistic purposes buying Escitalopram ‐ none variability in treatment efficacy highlight the importance of • Recreation Compulsive Citalopram ‐ benefit • Dietary – difference between drugs and food sexual behavior patient assessment and • Silicon Valley innovators Schreiber L, Odlaug BL, Grant JE. Impulse Control Disorders: Updated Review of Clinical Characteristics and Pharmacological Management. Frontiers in individualized care Psychiatry. 2011;2:1. doi:10.3389/fpsyt.2011.00001.

SUD Features SUD Epidemiology

Behaviors characterized by Prevalence Risk decreases as • Impaired control 12‐month – 3.9% Income increases • Attempts to refrain are unsuccessful • • • Excessive effort to obtain a substance, engage in use • Lifetime – 9.9% • Education increases and/or recover from the effects • Triggers lead to urges/cravings – generally associated Co‐morbid SUD and psychiatric with previous use disorder risk • Social impairment Demographic characteristics at risk • Employment • Male • Depression • Relationships • White and Native American • Anxiety • Risky use • Youth • PTSD • Use despite association with recurrent negative physical or psychological effects • Bipolar • Personality disorder • Pharmacologic criteria http://www.helnwein.com/press/international_press/article_5151‐Boulevard‐of‐Broken‐ • Tolerance Dreams;jsessionid=52A7B814A81F728E2D1E9EC4E25D24BC • Schizophrenia • Dependence/Withdrawal

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Alcohol Use Disorder (AUD) Alcohol Withdrawal Epidemiology Seizure Risk Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWAS‐Ar) • Lifetime prevalence – 4.0% • Most evidence for benzodiazepines • 51.8% report using alcohol at least once in their lifetime • Long‐acting vs Short‐acting • AUD represents just under half of all SUD • Fixed dose vs Symptom triggered diagnoses • Lack of evidence or shown to be ineffective as monotherapy Pathology • Anticonvulsants • Gamma amino butyric acid (GABA) potentiation • Carbamazepine, levetiracetam and phenytoin • Chronic alcohol use • Alpha‐2 agonists Significant adaptation of GABAergic transmission in the central • • Clonidine, dexmedetomidine, lofexidine nucleus of the amygdala resulting in disinhibition Beta‐blockers • Acute NMDA antagonism prevents long‐term plasticity resulting in • adaptations such as NMDA receptor upregulation • Propranolol • Increase endorphin activation of μ and δ opioid receptors of • Baclofen GABAergic interneurons resulting in disinhibition of dopaminergic Lovinger, DM. Communication Networks in the Brain: Neurons, Receptors, Neurotransmitters, and tracts in the Ventral Tegmental Area (VTA) Alcohol. https://pubs.niaaa.nih.gov/publications/arh313/196‐214.htm

AUD Treatment Opioid Use Disorder (OUD) Naltrexone ‐ mu‐opioid receptor antagonist Alcohol Use Disorder Recommendation Strength Category Epidemiology • Meta‐analysis of 50 randomized trials (2010) For patients with moderate‐severe alcohol • Reduced the risk of heavy drinking (RR 0.83, 95% CI 0.76‐0.90) and use disorder, we recommend offering one • US in 2015 – of those 12 years or older of the following medications: decreased drinking days Reviewed, • Acamprosate Strong New‐ • 20.5 million with SUD diagnosis • Well tolerated • Disulfiram For replaced • Depot available • Naltrexone‐ oral or extended release • 2 million with SUD involving prescription pain Pharmacotherapy • Topiramate relievers Acamprosate – NMDA receptor modulator For patients with moderate‐severe alcohol use disorder for whom first‐line • 21,101 overdoses related to pain medication • Meta‐analysis of 24 randomized trials (2010) Reviewed, pharmacotherapy is contraindicated or Weak for New‐ • Reduced rate of relapse (RR 0.86, 95% CI 0.81‐0.91) and increased ineffective, we suggest offering replaced • 591,000 with SUD involving heroin abstinence duration gabapentin. • 12,990 overdoses due to heroin • Well tolerated For patients with alcohol use disorder we recommend offering one or more of the • 80% of heroin users started with prescription opioids • Renal dose adjustment following interventions considering patient preference and provider • 23% of those who try heroin develop an OUD Disulfiram – acetaldehyde metabolism inhibitor training/competence: • Behavioral Couples Therapy for alcohol Reviewed, Psychosocial Strong • 2014 meta‐analysis use disorder New‐ • Compare to around 10% of those who try alcohol or Interventions For • No difference between disulfiram and placebo in return to any drinking • Cognitive Behavioral Therapy for replaced cannabis develop a SUD or other primary SUD outcomes substance use disorders • Community Reinforcement Approach • Efficacy found in trials that force adherence • Motivational Enhancement Therapy • Aversion therapy • 12‐Step Facilitation

VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders. https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf

OUD Physiology OUD Physiology (cont.) Opioid receptors – G protein Peripheral opioid receptors • μ(Mu) ‐MOR • GI tract • Most expressed in the caudate nucleus and the nucleus accumbens • Myenteric plexus • Associated with euphoria and dopamine disinhibition in these areas • Inhibits acetylcholine and Vasoactive Intestinal Peptide (VIP) resulting in reduced contraction, • δ (Delta) ‐ DOR impaired peristalsis and reduced GI secretion • Most expressed in the cortex, hippocampus, temporal lobe, caudate nucleus and nucleus accumbens • κ(Kappa) ‐KOR Oligomerization • Most expressed in the peripheral nerves and epidermal • Receptors can combine with other opioid keratinocytes AMG, amygdala; Arc, arcuate receptors and even other receptor types to nucleus, hypothalamus; CPu, caudate putamen; DMH, Multiple ligands in addition to endorphins produce functional dimers, heterodimers and dorsomedial hypothalamus; oligomers LH, lateral hypothalamus; • β‐arrestin, calmodulin, calnexin, filamin A, periplakin, NAc, nucleus accumbens; NTS, RGS4, ribophorin I or ubiquitin nucleus tractus solitarius; Sobczak M, Sałaga M, Storr MA, Fichna J. Physiology, signaling, and pharmacology of opioid • Example: analgesic effects of morphine are PAG, periaqueductal gray; receptors and their ligands in the gastrointestinal tract: current concepts and future PBN, parabrachial nucleus; perspectives. J Gastroenterol. 2013;49(1):24‐45 Analgesic action at descending pathways enhanced when administered with 9‐ PVN, paraventricular tetrahydrocannabinol (THC) due to formation hypothalamus; VP, ventral involving locus coeruleus, medulla and the pallidum; VTA, ventral periaqueductal gray area of MOR/CB1 complex tegmental area. Le Merrer J, Becker JA, Befort K, et al. Reward processing by the opioid system in the brain. Physiol Rev. 2009 Oct;89(4):1379‐412. doi: 10.1152/physrev.00005.2009.

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Opioids and Reward Opioid Dependence/Withdrawal Presentation • Anything that can run, will run Schematic representation of the brain • Lacrimation, diarrhea, rhinorrhea, sweating, vomiting reinforcement circuit. Brain sites of • Hyper‐analgesic reaction with anxiety/agitation reinforcement are integrated in a circuit based • Increased blood pressure and pulse on their connectivity and putative functional • All over muscle aches roles. Pathology BNST, bed nucleus of the stria terminalis; CPu, caudate putamen; LH, lateral hypothalamus; • Physical symptoms associated with reduced activation or mPFC, medial prefrontal cortex; NAc, nucleus antagonism of opioids in the periaqueductal gray area accumbens; PAG, periaqueductal gray; POA, • Anxiety/agitation symptoms associated with reduced opioid preoptic area; VP, ventral pallidum; VTA, activity in the VTA and NAC ventral tegmental area. Severity of withdrawal is associated with potency and receptor affinity whereas duration of withdrawal is related to half‐life Le Merrer J, Becker JA, Befort K, et al. Reward processing by the opioid system in the brain. Physiol Rev. 2009 Oct;89(4):1379‐412. doi: https://americanaddictioncenters.org/withdrawal‐timelines‐treatments/opiate/ 10.1152/physrev.00005.2009. • Methadone and buprenorphine withdrawal are often described as worse than heroin

Opioid Withdrawal Management Morphine Milligram Equivalent (MME)

Buprenorphine Opioid Withdrawal Management Standardized assessment of opioid utilization • Induction required to prevent withdrawal 2009 precipitation Recommendation Grade Strength Category • Caveats/Considerations For patients not yet stabilized from B Strong Against Reviewed, • 8 hours since last use of heroin or other short‐acting opioid opioid use disorder, we recommend New‐ • Buprenorphine – extremely high conversion factor due • 24 and preferably at least 48 hours have elapsed since the last to very high affinity for receptor, however partial agonist use of methadone or other long‐acting opioid against withdrawal management alone Replaced due to high risk of relapse and mechanism could result in withdrawal • Stabilize within 1‐3 days and taper over 5‐7 days overdose Methadone – the conversion factor is dependent upon Among patients with opioid use None Strong For Reviewed, • Methadone disorder for whom maintenance New‐ dose, so when converting high MME regimen to • Requires participation in a federally licensed opioid agonist treatment is contraindicated, replaced methadone, less methadone is required treatment program unacceptable, or unavailable, we • When Converting from methadone to other opioids there is recommend using a methadone (in less variance in the conversion factor • Initiate 5‐30mg daily to stabilize and taper over Opioid Treatment Program only) or several weeks buprenorphine taper for opioid • Reducing perceived opioid use across a facility/system by withdrawal management switching high MME patients to methadone Clonidine For patients with opioid use disorder None Strong For Reviewed, • Patches in mcg/h • For autonomic symptoms for whom methadone and New‐ buprenorphine are contraindicated, replaced • Buprenorphine – 1mg IV = 75mg PO morphine unacceptable, or unavailable, we • Fentanyl – 1mg IV = 100mg PO morphine Symptom management recommend offering clonidine as a • Residual symptoms, muscle aches, second‐line agent for opioid anxiety/agitation, withdrawal management https://www.cms.gov/Medicare/Prescription‐Drug‐ https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf Coverage/PrescriptionDrugCovContra/Downloads/Opioid‐Morphine‐EQ‐Conversion‐Factors‐April‐2017.pdf

OUD Management Impulsive vs Compulsive (revisited)

OUD Management Methadone Four major circuits Comparison of food and drugs as reinforcers 2009 1. Reward/Saliency Food Drug • Benefit for reduced illicit opioid use and reduced Grade Recommendation Strength Category 2. Inhibitory Control/Emotional Reactivity attrition For patients with opioid use disorder, AStrong ForReviewed, Potency as a ⁺⁺ Oral, ++ Snorted, +++ Smoked, Injected ++++ we recommend offering one of the New‐ 3. Motivation/Drive reinforcer following medications considering Replaced 4. Learning/Memory Delivery Oral Oral, Snorted, Smoked, Injected Buprenorphine patient preferences: • Buprenorphine/naloxone Mechanisms reward Somatosensory (palatability) Chemical (drug) • Suboxone vs Subutex Disordered behaviors associated with Chemical (glucose) • Methadone in an Opioid Treatment food consumption offer insight into the • Film vs tablet Program evolutionary function of habit formation Relevance of kinetics Not investigated The faster the stimulation the more • Advantages over methadone powerful its reinforcing effects For patients with opioid use disorder None Strong For Reviewed, Findings for whom opioid agonist treatment is New‐ Regulation of intake Peripheral and central factors Mostly central factors Naltrexone Long‐acting injection (LAI) contraindicated, unacceptable, replaced • Fewer striatal D2 receptors with SUD and Adaptations Physiologic Supraphysiologic • 12 week open label randomized Norwegian study of unavailable, or discontinued and who obesity – insensitivity to reward 232 outpatients with opioid dependence (DSM IV) have established abstinence for a • OCD and SUD patients s/p detox are Physiological role Necessary for survival Unnecessary sufficient period of time, we associated with orbitofrontal cortex (OFC) recommend offering: Learning Habits conditioned responses Habits conditioned responses • Intention‐to‐treat analysis •Extended‐release injectable hypofunctioning • Conclusion: naltrexone LAI was as effective as naltrexone • Urges/Cravings are associated with Role of stress ⁺⁺⁺ ⁺⁺⁺ buprenorphine‐naloxone in maintaining short‐term increased OFC activity in addicts as with Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R obese subjects exposed to a meal Soc Lond B Biol Sci. 2008;363(1507):3191‐200. abstinence from heroin and other illicit substances https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf

200 7 5/17/2019

Impulsive vs Compulsive (revisited) Conclusion Twinkie trial takeaways •Habit formation serves to facilitate our survival • Two groups • Food consumption, procreation and defense of self/family occurs without much deliberation • In the absence of behavioral reinforcement processes, we would constantly feel overwhelmed without any ability to • Obese multitask • Not obese • Unfortunately our ability to discover and/or invent pleasurable experiences has, in many instances (e.g. diabetes, SUD and other addictive disorders) outpaced the development of negative feedback processes that might limit excessive pleasure • Two phases seeking • Show them the Twinkie •Disordered behavior can be viewed across a spectrum between impulsivity and compulsivity, however this is a • Give them the Twinkie somewhat fluid process • Imaging of the four circuits • When impulsive behavior is rewarded repeatedly, over time the behavior transitions toward compulsivity for both groups during both • After years of abstinence, a relapse may be impulsive, however with an addiction history, the conversion to compulsivity may phases would reveal what for be almost instantaneous the: •Addiction is characterized by amplification of our motivation as the experience of reward fades resulting in a 1. Not obese – Show ‘em? profound thirst/hunger that becomes increasingly difficult to satisfy 2. Obese – Show ‘em? Zhang Y, Liu J, Yao J, et al. Obesity: pathophysiology and intervention. Nutrients. 2014 Nov 18;6(11):5153‐83. doi: •Controlling compulsive behaviors is almost impossible because our ability to render judgement is bypassed 3. Not obese – Let ‘em have it? 10.3390/nu6115153. altogether – and yet for the most part we are held responsible for all our behaviors – compulsive or not Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping 4. Obese – Let ‘em have it? neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. •Habit formation may be permanent, but since we know how it happens, we can imprint good habits over bad 2008;363(1507):3191‐200. ones (e.g. exercise)

Sources Post‐Test

1. Schreiber L, Odlaug BL, Grant JE. Impulse Control Disorders: Updated Review of Clinical Characteristics and Pharmacological Management. Frontiers in Psychiatry. 2011;2:1. doi:10.3389/fpsyt.2011.00001. 1. Healthcare providers may identify or relate to behavioral disorders by 4. Which agent is least likely to be effective for long‐term treatment of ◦ A. Stigmatizing 2. Chamberlain SR, Leppink EW, Redden SA, et al. Are obsessive‐compulsive symptoms impulsive, compulsive or both? Compr Psychiatry. 2016 Jul;68:111‐8. doi: 10.1016/j.comppsych.2016.04.010. Epub 2016 impulsive aggressive behaviors? Apr 15. ◦ B. Normalizing A. Alprazolam 3. Kim M, Lee TH, Choi JS, et al. Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive‐compulsive disorder: Perspectives from impulsivity and compulsivity. Sci ◦ C. Romanticizing B. Naltrexone Rep. 2017 Jan 30;7:41742. doi: 10.1038/srep41742. ◦ D. All of the above C. Fluoxetine 4. Cai H, Cao T, Zhou X, Yao JK. Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications. Frontiers in Psychiatry. 2018;9:73. doi:10.3389/fpsyt.2018.00073. D. Phenytoin 2. Impulsive and compulsive disorders are similar in that 5. Shen H. Neuroscience: The hard science of oxytocin. Nature. 2015 Jun 25;522(7557):410‐2. doi: 10.1038/522410a. ◦ A. Signaling from the pre‐frontal cortex to the limbic system is muted 5. Which agent has good evidence for benefit across multiple 6. Miller JL, Tamura R, Butler MG, et al. Oxytocin treatment in children with Prader‐Willi syndrome: A double‐blind, placebo‐controlled, crossover study. Am J Med Genet A. 2017 May;173(5):1243‐1250 ◦ B. Signaling from the limbic system to the pre‐frontal cortex is amplified substance use disorders, impulse‐control disorders and is available as a ◦ C. Involve an injury or lesion within the prefrontal cortex monthly long‐acting injectable? 7. Guay DR. Drug treatment of paraphilic and nonparaphilic sexual disorders. Clin Ther. 2009 Jan;31(1):1‐31 ◦ D. Involve an injury or lesion within the limbic system A. Acamprosate 8. Efrati, Yaniv & Gola, Mateusz. (2018). Treating Compulsive Sexual Behavior. Current Sexual Health Reports. 10.1007/s11930‐018‐0143‐8 B. Naltrexone 3. Chemical castration with a GNRH such as leuprolide requires which during C. Buprenorphine‐naloxone 9. Grant BF, Saha TD, Ruan WJ, et al. Epidemiology of DSM‐5 Drug Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions‐III. JAMA Psychiatry. 2016;73(1):39‐47. initiation to prevent recidivism? ◦ A. Concommitant administration with ascorbic acid to assure D. Topiramate 10. American Society of Addiction Medicine (ASAM). Opioid Addiction 2016 Facts and Figures. https://www.asam.org/docs/default‐source/advocacy/opioid‐addiction‐disease‐facts‐figures.pdf absorption

11. Sobczak M, Sałaga M, Storr MA, Fichna J. Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives. J Gastroenterol. ◦ B. Therapeutic drug monitoring of GNRH agonist levels 2013;49(1):24‐45. ◦ C. Concommitant administration of an anti‐androgen such as flutamide to block an initial increase in testosterone 12. Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. 2008;363(1507):3191‐200. ◦ D. Supplementation with estrogen to ensure aberrant thoughts do not 13. Zhang Y, Liu J, Yao J, et al. Obesity: pathophysiology and intervention. Nutrients. 2014 Nov 18;6(11):5153‐83. doi: 10.3390/nu6115153. return

14. Motofei IG, Rowland DL. The physiological basis of human sexual arousal: neuroendocrine sexual asymmetry. Int J Androl. 2005 Apr;28(2):78‐87.

Post‐Test

1. Healthcare providers may identify or relate to behavioral disorders by 4. Which agent is least likely to be effective for long‐term treatment of ◦ A. Stigmatizing impulsive aggressive behaviors? ◦ B. Normalizing A. Alprazolam ◦ C. Romanticizing B. Naltrexone ◦ D. All of the above C. Fluoxetine D. Phenytoin 2. Impulsive and compulsive disorders are similar in that ◦ A. Signaling from the pre‐frontal cortex to the limbic system is muted 5. Which agent has good evidence for benefit across multiple Questions? ◦ B. Signaling from the limbic system to the pre‐frontal cortex is amplified substance use disorders, impulse‐control disorders and is available as a ◦ C. Involve an injury or lesion within the prefrontal cortex monthly long‐acting injectable? ◦ D. Involve an injury or lesion within the limbic system A. Acamprosate B. Naltrexone 3. Chemical castration with a GNRH such as leuprolide requires which during initiation to prevent recidivism? C. Buprenorphine‐naloxone ◦ A. Concommitant administration with ascorbic acid to assure D. Topiramate absorption ◦ B. Therapeutic drug monitoring of GNRH agonist levels ◦ C. Concommitant administration of an anti‐androgen such as flutamide to block an initial increase in testosterone ◦ D. Supplementation with estrogen to ensure aberrant thoughts do not return

201 8 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Saturday, May 25, 2019 10:00 - 11:00 AM

Newer Anti-Diabetes Drug Therapies & Cardiovascular Outcomes: A Heart Healthy Blueprint for the Management of Diabetes

0179-0000-19-026-L01P/T

Christopher Gillard, PharmD, BCPS Clinical Associate Professor of Pharmacy Xavier University of Louisiana College of Pharmacy New Orleans, LA

Clinical Assistant Professor of Pharmacy Xavier University of Louisiana College of Pharmacy New Orleans, LA

Internal Medicine Clinical Pharmacy Specialist University Medical Center New Orleans, LA

Part Time Staff Pharmacist Floater CVS Pharmacy Baton Rouge, LA

Assistant Professor of Medicine (Gratis) LSU School of Medicine New Orleans, LA

.Pharmacist Objectives: Pharmacy Technician Objectives: 1. Discuss the macrovascular complications 1. Understand the macrovascular complications of associated with diabetes and the incidence of diabetes and associated cardiovascular risks. adverse cardiovascular events in diabetic patients. 2. Discuss the mechanism of action and indications 2. Review recent cardiovascular outcomes trials for new diabetes therapies, DPP-4 inhibitors, SGLT- (CVOT) of the new diabetes therapies, DPP-4 2 inhibitors, and GLP-1 agnostics. inhibitors, SGLT– 2 inhibitors and GLP-1 agnostics. 3. Describe the recent American Diabetes Association (ADA) Guideline Updates for Cardiovascular Risk Management in diabetic patients. 4. Apply the clinical evidence and ADA guidelines in the management of a patient with Type 2 Diabetes and Cardiovascular Disease.

Speaker has disclosed that he has no relevant financial relationships. 202 5/17/2019

1 2 Pharmacist Objectives Newer Diabetes Therapies & Cardiovascular  Discuss the macrovascular complications associated with diabetes and the Outcomes: A Heart Healthy Blueprint for the incidence of adverse cardiovascular events in diabetic patients. Management of Diabetes  Review recent cardiovascular outcomes trials (CVOT) of the newer diabetes therapies, DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists.

 Describe the recent American Diabetes Association (ADA) Guidelines updates for . Christopher J. Gillard, Pharm.D., BCPS Cardiovascular Risk Management in diabetic patients. . Clinical Associate Professor of Pharmacy-- Xavier University of Louisiana . LSHP Annual Meeting May 2019  Apply the clinical evidence and ADA guidelines in the management of a patient with Type 2 Diabetes and Cardiovascular Disease.

3 4 Technician Objectives Diabetes

 30.3 million US adults have diabetes  1 in 4 patients not diagnosed  Understand the macrovascular complications of diabetes and associated cardiovascular risk.  Seventh leading cause of death in the United States

 Discuss the mechanism of action and indications for newer diabetes therapies newer diabetes therapies, DPP-4 inhibitors, SGLT-2 inhibitors,  No. 1 cause of kidney failure, lower-limb amputations, and and GLP-1 agonists. adult blindness

 In the last 20 years, the number of adults diagnosed with diabetes has more than tripled

Center for Disease Control. Diabetes Statistics https://www.cdc.gov/diabetes/data/center/slides.html Image Credit: http://healthintotality.blogspot.com/

5 6 Diabetes Diabetes Related Complications

 Microvascular Complications  Diabetic Neuropathy  Diabetic Retinopathy  Diabetic Nephropathy

 Macrovascular Complications  Myocardial Infarction  Coronary Heart Disease  Stroke  Heart Failure  Peripheral Vascular Disease

Clinical Diabetes. Vol 26, Number 2 2008. Image Credit: https://cdn.rcsb.org/pdb101/global-health/diabetes-mellitus/files/DM-Micro-Macro-Complicns.png

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7 8 Diabetes Macrovascular Prevalence of Macrovascular Complications Complications

Pathophysiology  Patients with type 2 diabetes have a much higher risk of stroke, with an increased  Increased inflammation and risk of 150-400%. atherosclerosis in diabetes  Risk of stroke-related dementia and recurrence, as well as stroke-related mortality, is elevated in patients with diabetes  Insulin resistance leading to endothelial dysfunction  Prevalence of peripheral vascular disease in patients with diabetes aged 30 years or older is 26%  Byproducts of glucose lead to cellular injury  Two- to four-fold increased risk of coronary artery disease (CAD), peripheral arterial disease, and cerebrovascular disease

Clinical Diabetes. Vol 26, Number 2 2008. Diabetes Prevalence. Cleveland Clinic 2016 Diabetic Macrovascular Disease, Volume: 106, Issue: 22, Pages: 2760-2763. Diabetes Care 1980; 3:650–654.

9 10 Diabetes Management & Assessment Question 1 Cardiovascular Outcomes

Which of the following below is a macrovascular complication of  Prevalence of macrovascular complications well established Diabetes?

 Clinicians should weigh cardiovascular risks against the potential benefits of prescribing diabetes therapies A. Peripheral Neuropathy B. Diabetic Retinopathy  Benefits and risk of anti-diabetic agents needs to be clearly defined C. Stroke

D. All of the above  Therapies should not exacerbate cardiovascular complications of diabetes

Diabetes Care 2008 Feb; 31(Supplement 2): S215-S221.

11 12 Diabetes Cardiovascular Trials Diabetes Cardiovascular Trials Historical Perspectives Historical Perspectives

Rosiglitazone Evaluated for Cardiac University Group Diabetes UK Prospective Diabetes Study 2007 Meta Analysis of 47 Trials Outcomes in Diabetes (RECORD Program (UGDP) (UKPDS) (NEJM) Study)

 Conducted in 1961; N=200  Conducted in 1976; N=7600  Rosiglitazone was associated with  Inconclusive findings for adverse increased risk of heart attacks and cardiovascular outcomes & mortality  Type 2 DM on insulin, tolbutamide or placebo  Type 2 DM patients to determine the effect of cardiovascular related death intensive glycemic control on the incidence of  Patients with the poorest glycemic control CV complications showed an excess of cardiovascular deaths  Rosiglitazone eventually eliminated  Intensive glycemic control reduced the rate  Led to Rosiglitazone withdrawn in from REMS category in 2014 of MI by 16% Europe and restricted under REMS by the FDA in 2010

Diabetes. 1972 Sep;21(9):976-9. N Engl J Med 2007; 356:2522-2524. Lancet. 1998 Sep 12;352(9131):854-65. N Engl J Med 2007; 357:28-38.

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13 14 CVOT Trials & MACE for Diabetes 2008 FDA Mandate Therapies

 FDA issued guidance to the pharmaceutical industry setting new expectations for  CVOT the development of antidiabetic drugs for type 2 diabetes  Aim to demonstrate that the addition of the diabetic agent is as safe as usual care and non-inferior with regard to cardiovascular outcomes  Mandates long term cardiovascular outcomes trials (CVOTs) for safety  Minimum of 2 years of safety data from clinical studies  MACE (Major adverse cardiovascular events)  Cardiovascular Death  Purpose to demonstrate no increase in CV risk and include analysis on the risk of  Myocardial Infarction Cardiovascular death , Myocardial Infarction, and Stroke  Stroke

Diabetes Care 2018 Jan; 41(1): 14-31. Diabetes Care 2018 Jan; 41(1): 14-31. U.S. Food and Drug Administration. Guidance for industry: diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 Eur Heart J Cardiovasc Pharmacother. 2016 Jan;2(1):32-43. diabetes.

15 History of Diabetes Medications 16 Diabetic Management Today & Development Treatment Considerations

 Diabetes continues to be difficult to manage

 Large armory of anti-diabetic drugs to use in patient care

 Treatment guidelines provide goals to be achieved and offer alternatives to treatment  Medical decision making has to be made on an individualized basis

 Important to understand the cardiovascular safety of antidiabetic therapies

White, J. History of the Development of Diabetes Medications. 2014 Diabetes Spectrum

Newer Diabetes Therapies & 17 18 Cardiovascular Outcomes Trials (CVOTs) DPP-IV Inhibitors

 Indication: Management of adults with type 2 diabetes mellitus as an adjunct to diet and exercise  DPP-IV Inhibitors as monotherapy or in combination therapy  GLP-1 Agonists  Mechanism of Action:  SGLT-2 Inhibitors  Prolongs incretin levels and inhibits the breaking down of GLP-1 secreted during meals, which in turn increases pancreatic insulin secretion, limits glucagon secretion, slows gastric emptying and promotes satiety  Currently Approved: Sitaliptin, Saxagliptin, Linagliptin, Alogliptin

Image Credit: https://kauhdic.files.wordpress.com/2017/12/14-1.jpg?w=759 Cardiovascular Pharmacotherapy (2016) 2, 32–43. Clin Pharmacol Ther 2007;81:761 –767.

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19 DPP-IV Inhibitor CVOT Trials 20 Role in Diabetes Therapy & Efficacy EXAMINE

Examination of Cardiovascular Outcomes with Alogliptin versus standard Care in patients with  Reduced fasting and post-prandial Type 2 Diabetes & Acute Coronary Syndromes hyperglycemia Objective . To determine whether alogliptin is noninferior to placebo with respect to major cardiovascular events in type 2 diabetes patients .  Low risk of hypoglycemia Primary Composite of death from cardiovascular causes, nonfatal myocardial infarction, Endpoint or nonfatal stroke Study Design . N= 5380 Patients  Overall 0.5-1% reduction in A1C . On alogliptin compared to placebo and followed for 1.5 years

Results . A primary end-point event occurred in alogliptin (11.3%) and placebo (11.8%)  Considered weight neutral (hazard ratio, 0.96; CI, 1.16; P<0.001 for noninferiority).

. Trend toward increase hospitalization for heart failure (HR 1.07, p=n.s) Cardiovascular Pharmacotherapy (2016) 2, 32–43. Clin Pharmacol Ther 2007;81:761 –767 N Engl J Med 2013; 369:1327-1335 Image Credit: https://globalrph.com/drugs/diabetes-dpp-4-inhibitors/

DPP-IV Inhibitor CVOT Trials 21 DPP-IV Inhibitor CVOT Trials 22 SAVOR TIMI TECOS

Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)–Thrombolysis in Myocardial Infarction (TIMI) Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) Objective . Evaluate the safety and efficacy of saxagliptin with respect to cardiovascular Objective . To assess the long-term cardiovascular safety Of sitagliptin compared to usual care outcomes in patients with diabetes Primary . Composite of death from cardiovascular causes, nonfatal myocardial infarction, or Primary . Composite of death from cardiovascular causes, nonfatal myocardial infarction, Endpoint nonfatal stroke Endpoint stroke, or hospitalization for angina Study . N= 16,492 Patients Study Design . N= 14,671 Patients Design . On saxagliptin compared to placebo and followed for 2 years . Sitagliptin compared to placebo and followed for 3 years Results . Primary end-point event similar in both groups (7.3% vs. 7.2%, respectively, HR Results . Sitagliptin was noninferior to placebo for the primary composite cardiovascular 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for outcome (HR, 0.98; 95% CI, 0.88 to 1.09; P<0.001). noninferiority) . Rates of hospitalization for heart failure did not differ between the two groups . Subgroup analysis showed trend toward higher rates of hospitalizations for heart (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). failure (HR 1.27, p<0.007)

N Engl J Med 2013; 369:1317-1326 N Engl J Med 2015; 373:232-242

23 24 DPP-IV inhibitors & Heart Failure DPP-IV Inhibitors CVOT’s Summary

 Three major trials suggest DPP-IV inhibitors are safe from a cardiovascular standpoint

 However, they do not improve cardiovascular endpoints at least in the short term

 SAVOR-TIMI & EXAMINE indicate increased risk of heart failure hospitalizations  Mechanism not fully understood  FDA Warning for increased risk of heart failure hospitalizations with saxagliptin and alogliptin

FDA Drug Safety Communication. Saxagliption & Alogliptin. April 2016 Diabetes Care 2016;39(Suppl. 2):S210–S218

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25 26 GLP-1 Agonists Role in Diabetes Therapy & Efficacy

 Indication: Management of adults with type 2 diabetes mellitus as an adjunct to diet and  Works better to reduce postprandial exercise as monotherapy or in combination therapy hyperglycemia than fasting glucose

 Low risk of hypoglycemia  Mechanism of Action:  Binds to GLP-1 receptors resulting in glucose-dependent insulin secretion, reduction in glucagon secretion, reduced gastric emptying, and promotes satiety  Overall 0.5-1.5% reduction in A1C

 Currently Approved: Exenatide, Liraglutide, Dulaglutide, Semaglutide, Lixisenatide  Associated with modest weight loss

Cardiovascular Pharmacotherapy (2016) 2, 32–43. Cardiovascular Pharmacotherapy (2016) 2, 32–43. Am J Physiol Endocrinol Metab 2000;278: E1010– E1018. Am J Physiol Endocrinol Metab 2000;278: E1010– E1018. Image Credit: https://labiotech.eu/medical/sanofi-novonordisk-fda-insulin-glp-1-combination

GLP-1 Agonist CVOT Trials 27 GLP-1 Agonists CVOT Trials 28 ELIXA SUSTAIN-6

Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes Objective . To assess the effects of lixisenatide on cardiovascular morbidity and mortality. Objective . To assess the noninferiority of semaglutide vs. placebo for cardiovascular safety in Primary . Time to event analysis of a composite of death from cardiovascular causes, nonfatal patients with type 2 diabetes. Endpoint myocardial infarction, or nonfatal stroke Primary . First occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal Endpoint stroke. Study Design . N= 6068; Patients with a recent coronary event . On Lixisenatide compared to placebo and followed for 2 years Study . N= 3297; Diabetic patients with a recent coronary event Design . On semaglutide compared to placebo and followed for 2 years Results . Primary outcome occurred (13.4%) in the lixisenatide group vs. (13.2%) in the Results . Primary outcome occurred in (6.6%) in the semaglutide group and (8.9%) in the placebo group (HR, 1.02; 95% [CI], 0.89 to 1.17), which showed the noninferiority of placebo group (HR, 0.74; 95% [CI], 0.58 to 0.95; P<0.001 for noninferiority) lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81) . All components of the primary endpoint occurred less in the semaglutide group

N Engl J Med 2015; 373:2247-2257 N Engl J Med 2016; 375:1834-1844

GLP-1 Agonists CVOT Trials 29 GLP-1 Agonists CVOT Trials 30 LEADER EXSCEL

Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) Exenatide Study of Cardiovascular Event Lowering (EXSCEL) Trial Trial Objective . To assess the cardiovascular safety and efficacy of exenatide, administered once Objective . To assess the long-term effects of liraglutide on cardiovascular outcomes weekly, in patients with type 2 diabetes with CV risk . Primary . Time-to-event analysis first occurrence of death from cardiovascular causes, nonfatal Primary First occurrence of death from cardiovascular causes, nonfatal myocardial infarction, Endpoint myocardial infarction, or nonfatal stroke. Endpoint or nonfatal stroke. Study . N= 9340; Diabetic patients with high cardiovascular risk Study Design . N= 14,752; Diabetic patients with CV risk Design . On liraglutide compared to placebo and followed for 3.8 years . Exenatide compared to placebo and followed for 3.2 years Results . Primary outcome occurred in fewer patients in the liraglutide group (13.0%) than in the Results . Primary composite outcome event occurred in (11.4%) in the exenatide vs. 12.2%) in placebo group (14.9%) (HR, 0.87; 95% [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 the placebo group (HR, 0.91; 95% confidence interval [CI], 0.83 to 1.00) for superiority). . Results showed non-inferiority but not superiority . All components of the primary endpoint occurred less in the liraglutide group; rate of cardiovascular death statistically significant (HR 0.78, 95 CI 0.66-0.93)

N Engl J Med 2016; 375:311-322 N Engl J Med 2017; 377:1228-1239

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31 32 GLP-1 Agonist CVOT’s Summary SGLT-2 Inhibitors

 Four major trials suggest GLP-1 Agonists are safe from a cardiovascular standpoint  Indication: Treatment of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise to improve glycemic control  Two studies indicate improved cardiovascular outcomes  SUSTAIN-6 & LEADER  Mechanism of Action:  2017 Liraglutide gains FDA approval for the reduction in cardiovascular outcomes in  Increases urinary glucose excretion by blocking normal reabsorption in the proximal Type 2 Diabetic Patients convoluted tubule; mild effect of delaying GI glucose absorption  Recognized in the ADA Treatment Guidelines

 Currently Approved: Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin  Rationale for better cardiovascular outcomes not fully understood  Potentially because of decrease in weight and BMI Cardiovascular Pharmacotherapy (2016) 2, 32–43. Diab Care 2015;38: 1730 –1735. Diabetes Care 2019;42(Suppl. 1):S103–S123

33 SGLT-2 Inhibitors CVOT Trials 34 Role in Diabetes Therapy & Efficacy CANVAS

Canagliflozin Cardiovascular Assessment Study (CANVAS)  Reduces fasting and post-prandial hyperglycemia Objective . To assess the cardiovascular safety and renal outcomes of canagliflozin  MOA does not depend on insulin secretion Primary . Composite of death from cardiovascular causes, nonfatal myocardial infarction, or  Low risk of hypoglycemia Endpoint nonfatal stroke.  Overall 0.3%-1.0% reduction in A1c Study . N= 10,142; Diabetic patients with high CV risk  Modest Weight Loss Design . On Canagliflozin compared to placebo and followed for 3.6 years  Decreases in systolic and diastolic blood pressure Results . The rate of the primary outcome was lower with canagliflozin than with placebo (HR, seen in studies 0.86; 95% [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority).

. Lower rate of progression to albuminuria, decreased HF hospitalization, but higher rate of amputations in patients

Cardiovascular Pharmacotherapy (2016) 2, 32–43. Diabetes Care 38.3 (2015): 420-428 Image Credit: https://meddataspeaks.files.wordpress.com/2014/01/2014-1-121.jpg N Engl J Med 2017; 377:644-657.

35 SGLT-2 Inhibitors CVOT Trials 36 SGLT-2 Inhibitors CVOT Trials EMPA-REG CANVAS Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

Objective . To assess the cardiovascular safety and renal outcomes of empaglifozin Primary . Composite of death from cardiovascular causes, nonfatal myocardial infarction, or Endpoint nonfatal stroke.

Study Design . N= 7,020; Diabetic patients with high CV risk . On empagliflozin compared to placebo and followed for 3.1 years

Results . Primary outcome occurred (10.5%) in the pooled empagliflozin group and (12.1%) in the placebo group (HR 0.86; 95% CI 0.74 to 0.99; P=0.04 for superiority).

. Secondary endpoints indicate decrease in CV death and also heart failure hospitalizations

N Engl J Med 2017; 377:644-657 Image Credit: https://twitter.com/edgarvlermamd/status/877338681169915904 N Engl J Med 2015; 373:2117-2128

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SGLT-2 Inhibitors CVOT Trials 37 38 EMPA-REG (CV Death & HF) SGLT-2 Inhibitor CVOT’s Summary

 Reduction in cardiovascular mortality demonstrated by major trials

 Decreased heart failure hospitalizations seen in study outcomes  FDA approves empagliflozin to reduce cardiovascular outcomes in patients with Type 2 Diabetes

 Canagliflozin associated with significantly higher rates of amputations in diabetic patients  2017 FDA issues a drug safety communication warning  Mechanism not fully understood, unclear if a class effect

FDA Drug Safety Communication 2017 Canagliflozin. N Engl J Med 2015; 373:2117-2128 FDA News Release 2016 Empagliflozin. Image Credit: http://img.medscape.com/article/851/470/Slide23.png

39 Completed & Ongoing CVOTs 40 Limitations to CVOT Trials for Diabetes Therapies

 Heterogenous Study Populations between trials  Baseline A1c  Duration of Diabetes  Previous HF

 Different Criteria & Endpoints

 Difficult to determine if cardiovascular outcomes are a class effect

2017 American College of Cardiology Middle East Conference https://img.medscapestatic.com/article/872/903/Slide4.png Cefalu & Associates. Diabetes Care 2018;41:14–31

41 Type 2 Diabetes & Cardiovascular 42 Key CVOT Studies in Progress Disease Treatment Algorithm

CARMELINA (Linagliptin vs. Standard Therapy)

CAROLINA (Linagliptin vs. Glimeperide)

REWIND (Dulaglutide vs. Standard Therapy)

Cefalu & Associates. Diabetes Care 2018;41:14–31. Journal of the American College of Cardiology. 69, No. 21, 2017

209 7 5/17/2019

ADA Treatment Algorithm 43 Impact of CVOT on ADA Treatment Guidelines

 ADA 2018 Standards of Medical Care in Diabetes  Updated Type 2 Diabetes Treatment Algorithm

 Need to Assess Diabetic Patients for ASCVD Risk

 When beginning dual therapy add antidiabetic agent to reduce major cardiovascular events and cardiovascular mortality

Diabetes Care 2018;42(Suppl. 1):S103–S123 Diabetes Care 2018;42(Suppl. 1):S103–S123

Cardiovascular Disease and Risk Management: 45 46 Standards of Medical Care in Diabetes—2019 Pharmacist’s Role in Type 2 DM Management & Reducing CV Risk Summary of Recommendations for Blood Pressure & Lipid Control in Adult Diabetic Patients  Recognize diabetic patients with risk of Hypertension/BP . Diabetes & HTN with low ASCVD risk Goal BP <140/90 Cardiovascular Disease Control  Primary Prevention & Secondary Prevention . High ASCVD Risk Goal BP <130/80  Benefits and Risk of Antidiabetic Therapies . First line agents: Ace-I/ARB +Thiazide OR CCB  Side Effect Profile Dyslipidemia . Intensive lifestyle therapy and glycemic control for hypertriglyceridemia  Contraindications  CVOT Outcome Data . Lipid lowering therapy with a moderate or high intensity statin based on 10 yr ASCVD Risk  Focus on reaching glycemic control, blood Antiplatelet . Aspirin for secondary prevention of CV disease pressure, cholesterol targets Therapy  Lifestyle modifications and weight loss . Primary prevention in high risk Type 2 DM patients Image Credit: http://www.familypharmacybh.com/wp- content/uploads/2016/09/diabetes2.jpg Diabetes Care 2019;42(Suppl. 1):S103–S123

47 48 Summary Assessment Question 2

 Cardiovascular Outcomes Trials now required for Antidiabetic Therapies  Have to assess any major adverse CV outcomes Which of the following FDA approved agents for the management of Type 2 Diabetes has been associated with an increase rate of limb  Some newer drug classes have been associated with positive cardiovascular outcomes amputations in CVOTs?  SGLT-2 inhibitors (Empaglifozin-FDA Approval)  GLP-1 Agonists (Liraglutide-FDA Approval) A. Saxagliptin  Careful selection of drug therapy paying particular attention to cardiovascular safety is important to optimize B. Empagliflozin diabetic therapy C. Exentatide  Clinicians (pharmacist, physicians, etc.) should be aware of efficacy and safety of anti-diabetic drug therapies D. Canagliflozin

210 8 5/17/2019

49 50 Assessment Question 3 Assessment Question 4

Which of the following agents below is now approved to reduce the A 57 year old man with a past medical history of Type 2 Diabetes, NYHA Class III Systolic Heart risk of major cardiovascular events such as heart attack, stroke, or Failure (Ejection Fraction 30%), hypertension, and dyslipidemia presents to the diabetes clinic. death in adults with type 2 diabetes based on evidence from His A1C is 8.5% and all of his labs are within normal limits. He currently is taking metformin cardiovascular outcomes evidence trials (CVOT’s)? 1000 mg twice daily for his diabetes therapy. After consulting with the physician, you decide to start an additional therapy for management of his diabetes. Which of the following would be the most appropriate to start at this time. A. Linagliptin B. Dapaglifozin A. Insulin Glargine 10 units at bedtime C. Rosiglitiazone B. Empagliflozin D. Liraglutide C. Pioglitazone D. Alogliptin

51 52 Questions? Newer Diabetes Therapies & Cardiovascular Outcomes: A Heart Healthy Blueprint for the Management of Diabetes

. Christopher J. Gillard, Pharm.D., BCPS . Clinical Associate Professor of Pharmacy-- Xavier University of Louisiana . LSHP Annual Meeting May 2019

References References 53 54

 Center for Disease Control. Diabetes Statistics https://www.cdc.gov/diabetes/data/center/slides.html  U.S. Food and Drug Administration. Guidance for industry: diabetes mellitus—evaluating cardiovascular  Fowler, M. Microvascular and Macrovascular Complications of Diabetes Clinical Diabetes. Vol 26, Number 2 2008. risk in new antidiabetic therapies to treat type 2 diabetes  Libby P, Plutzky J.Diabetic macrovascular disease: the glucose paradox Diabetic Macrovascular Disease, Volume: 106,  Kumar R, Kerins D,Cardiovascular safety of anti-diabetic drugs. Eur Heart J Cardiovasc Pharmacother. Issue: 22, Pages: 2760-2763. 2016 Jan;2(1):32-43  Melton L, Macken K. Incidence and prevalence of clinical peripheral vascular disease in a population-based cohort of  White, J. History of the Development of Diabetes Medications. 2014 Diabetes Spectrum diabetic patients. Diabetes Care 1980; 3:650–654.  Cardiovascular Pharmacotherapy (2016) 2, 32–43.  Diabetes Prevalence. Cleveland Clinic 2016  Herman G, Stein P. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: focus on  Stirban, A. Tschoepe D. Cardiovascular Complications in Diabetes. Diabetes Care 2008 Feb; 31(Supplement 2): S215- sitagliptin. Clin Pharmacol Ther 2007;81:761 –767. S221.  White W, Cannon C. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J  Seltzer H. A summary of criticisms of the findings and conclusions of the University Group Diabetes Program Med 2013; 369:1327-1335. (UGDP).Diabetes. 1972 Sep;21(9):976-9.  Scirica B, Bhatt D. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N  Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes Engl J Med 2013; 369:1317-1326. (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.  Green J, Bethel M. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med  Psaty B, Furberg C.Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 356:2522-2524 2015; 373:232-242.  Home P, Pocock S. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med 2007; 357:28-  Schernthaner G, Cahn A. Is the Use of DPP-4 Inhibitors Associated With an Increased Risk for Heart 38. Failure? Lessons From EXAMINE, SAVOR-TIMI 53, and TECOS. Diabetes Care 2016;39(Suppl. 2):S210– S218.  Cefalu W, Kaul S.,Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a Diabetes Care Editors' Expert Forum. Diabetes Care 2018 Jan; 41(1): 14-31.  FDA Drug Safety Communication. Saxagliption & Alogliptin. April 2016

211 9 5/17/2019

References 55

 Pfeffer M, Claggett B. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med 2015; 373:2247-2257

 Marso S, Bain S Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375:1834-1844.

 Marso S, Daniels G. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375:311-322.

 Holman R, Bethel M. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:1228- 1239.

 American Diabetes Association. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42(Suppl. 1):S103–S123

 Ferrannini G, Hach T. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diab Care 2015;38: 1730 –1735.

 Neal B, Perkovic V. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377:644-657

 Zinman B, Wanner C. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med 2015; 373:2117-2128.

 FDA Drug Safety Communication 2017 Canagliflozin. FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin

 FDA News Release 2016 Empagliflozin. FDA approves Jardiance to reduce cardiovascular death in adults with type 2 diabetes.

 Atallah, Bassam. Diabetes Drugs & Cardiovascular Outcomes. 2017 American College of Cardiology Middle East Conference

 Naveed Sattar, Mark C. Petrie Novel Diabetes Drugs and the Cardiovascular Specialist. Journal of the American College of Cardiology. 69, No. 21, 2017.

 Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42(Suppl. 1):S103–S123

212 10 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Saturday, May 25, 2019 11:00 AM - 12:30 PM

Trends in Health Policy and Pharmacy Law

0179-0000-19-012-L03-P/T

William Kirchain, PharmD, CDE Clinical Associate Professor Xavier University of Louisiana New Orleans, LA

Wilber & Mildred Robichaux Professorship in Pharmacy Xavier University of Louisiana New Orleans, LA

Jeff Evans, PharmD

.Pharmacist Objectives: Pharmacy Technician Objectives: 1. Discuss the opportunities and risks 1. List recent changes in State and Federal associated with recent changes in State and controlled substance regulations. Federal controlled substance regulations. 2. Discuss potential changes that will follow 2. Formulate an informed opinion about the state and national trends presented. potential changes in scope of practice; site 3. List the new policies and procedures that accreditation; liability risks and other near- recent changes in laws and regulations will term issues. mandate. 3. List the new policies and procedures that recent changes in laws and regulations will mandate.

Speakers have disclosed that that they have no relevant financial relationships. 213 5/17/2019

egal pdates & Trends 2019 A Quick Review…

William R. Kirchain, PharmD, CDE Jeffery D. Evans, PharmD

Title 40 § Chapter 4 § Part X § 978. Prescriptions Title 40 § Chapter 4 § Part X § 978. Prescriptions Title 46 § Part LIII § 2745. Prescriptions  C‐II expires in 90 days  Partially fill a C‐II if requested (30 days)  Out‐of‐State Rx’ers (not listed in PMP) Actual dispensed amount  the PMP. C‐II (not C‐IIN) –10 day supply; wait 60 days Unless Rx “Dx of cancer or terminal illness” The pharmacist (in 7 days) note in EHR  Issuance of Multiple Prescriptions  First Time Rx – Limited to 7 day supply a. 3 Rx; collectively total ≤ 90 day supply Unlesss more is needed for the injury b. Earliest date to dispense or the Rx is for Cancer Pain, Palliative c. Does not encourage diversion Care or Chronic Pain Management d. All 3 Rx must have the same DOI

Substance Use‐Disorder Prevention Federal Legislation … that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018

214 1 5/17/2019

Substance Use‐Disorder Prevention that Promotes Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Patients and Communities Act of 2018 Medicaid (October 1, 2019) Medicaid (October 2019) Mandates the creation of…  Requires Prescribers to Check PMP 1. Safety Edits for Opioid Refills linked to ICD 10 Codes  Mandates AHRQ & SAMHSA: demonstration 2. Safety Edits for MME per Day project to expand Medication Assisted SUD 3. Audit Process for Opioids + Benzodiazepines Treatment 4. Audit Process for Opioids + Antipsychotics  Mandates Drug Management (“lock‐ins”) for 5. Monitoring Program for Antipsychotic Use in Children at‐risk beneficiaries (January 2022) … Except for Hospice, Palliative Care, Cancer & LTC Patients

Substance Use‐Disorder Prevention that Promotes Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Patients and Communities Act of 2018 Funds the Expansion and Continuation of Tx for Other State Activity (October 2019) Mother/Child with SUD at birth Requires CDC support for enhancing PMP Mandates Telehealth‐based Mental Health Services 1. Universal use of PMP for… (Medicare & Medicaid) 2. Timely Data Entry 1. American Indians & Alaskan Natives 3. Active Management of the PMP 2. Adults < 40 4. Ease of Use 3. Anyone post‐OD 4. Anyone with Dual Diagnosis

Substance Use‐Disorder Prevention that Promotes Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Patients and Communities Act of 2018 Other State Activity (October 2019) Medicare National Coordinator for Health Information Technology to  Prior authorization for Opioids (2021) improve interoperability of PMP.  Integrating PMP with EHR  Require an Assessment of SUD and OD risk on  Linking PMP data to other data systems (PBM, Coroners, CMS, Enrollment & at Wellness Visits (2020) Worker’s Comp, VA, IHS)  Beneficiaries deemed at risk for SUD or OD:  Sharing PMP data in Near‐Real Time eligible for MTM under Part D (2021)  Automation of Queries  MTM to address cost‐effective disposal (2021)  Automation of Analytics into Clinical Workflow  Mandates Drug Management (“lock‐ins”) (2022)  Including Treatment Referral Capabilities within PMP

215 2 5/17/2019

Substance Use‐Disorder Prevention that Promotes Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Patients and Communities Act of 2018 Medicare FDA  Update the biometric component of  FDA (with Pharmacists) to Author EBM Opioid Rx multifactor authentication for e‐Scripts Guidelines for Indication‐Specific Tx of Acute Pain  Requires Suspension of Payments Pending  Empowers FDA to Initiate Recalls of CS & Imposes a Investigation Allegations of Fraud by 10 day Response Time Pharmacies  Assigns Homeland Security, U.S. Customs & Border  Requires Identification of Prescribers that Protection to Assist FDA and Postmaster General in Over Prescribe as Compared to Others of the Inspecting & Securing Imported Drug Products. Same Specialty and Location.

Substance Use‐Disorder Prevention that Promotes Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Patients and Communities Act of 2018 REMS – disposal regulations including; the Medication‐assisted Treatment for OUD (SUD) required inclusion of safe disposal packaging or Allows certification to provide MAT to 30 patients safe disposal system at dispensing. Securing Nurse Practitioner Opioids and Unused Narcotics with Deliberate Clinical Nurse Specialist (SOUND) Disposal and Packaging Act of 2018 Certified Registered Nurse Anesthetist (within the SUPPORT Act) Certified Nurse Midwife Physician Assistant Allows Physician certification to be included in Medical Training

Substance Use‐Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018 Medication‐assisted Treatment for OUD (SUD) Comptroller General shall conduct a study of the following models of distribution of SUD medications, buprenorphine, Last Session… naltrexone, and buprenorphine‐naloxone combos: (a) Purchase of SUD meds by providers directly. (b) Purchase of SUD meds on demand from specialty pharmacies by providers. (c) Dispensing of SUD meds by pharmacists.

216 3 5/17/2019

ACT 548… Authorizes GOHSEP to ACT 423 …establish a registry of emergency Requires LBOP & LSBME develop a volunteers & to provide credentials Uniform Rx PA Form for volunteers. Prohibits PBM requiring a license, … Indirectly establishes 5 days as a accreditation, affiliation, or “protected” leave of absence from registration NOT required by the work. Government.

ACT 146 Adds “drugs whose use requires tracking for public health Current Session… purposes” to PMP

HB 101 Harris HB 207 Amedee Requires provision of information prior to vaccination… Requires the LSP to create the (1)Diseases the vaccine targets LA Voluntary Do Not Sell List (2)The effectiveness of immunization (3)Contraindications, Adverse Reactions (4)Ingredients (5)Info on submitting AE to VAERS

217 4 5/17/2019

SB 169 Barrow

Officially changes LINKS to an immunization registry for both children and adults PBM Related

HB 119 Bishop HB 370 Stokes

Requires a PBM that denies a drug Prohibits a PBM from using “step‐ based on a “step‐therapy” or other therapy” or protocol as the basis to protocol basis to provide the restrict any benefit for a person prescriber with a list of alternatives with advanced metastatic cancer in writing.

HB 424 Stagni HB 432 Jordan Requires PSAO operating to be licensed with DoI. When claims denials are based Requires PSAO to disclose to DoI, pharmacies and PBM ownership by any parent company that provides pharmacy services or sells, upon an interpretation of a drugs, biologicals, or devices. Further prohibits insider sales or special discounts. regulation, policy or medical Requires all remittances submitted by a PBM or third‐party payer on behalf of a pharmacy to the PSAO to be passed through to the guideline, then the MCO shall pharmacy within a reasonable amount of time after receipt of the provide either instructions for remittance. Requires a PSAO that provides, accepts, or processes discounts to accessing the source or a copy provide to DoI an annual report that includes: (1) All transactions, by pharmacy AND (2) Payments received for processing discounts within 3 business days. on behalf of a pharmacy.

218 5 5/17/2019

SB 41 Mills SB 48 Mills "Pharmacy Benefit Manager Licensing Law" to Prohibits Medicaid PBM from providing recipient PHI provide requirements for obtaining and maintaining to subsidiaries of PBM, unless authorized by LDH licensure to operate in LA. Forbids (a) patient steering; (b) denial of a pharmacist the right to be a provider in network if he Requires PBM to be licensed and regulated by DoI, or she meets the requirements of participation in LSBME, LBOP collectively. Medicaid; (c) the deduction of provider fees due from any reimbursement to a pharmacist and (d) the Establishes the PBM has a fiduciary duty to deduction of sales taxes owed. beneficiaries and to the pharmacists who provide pharmacy services. Mandates Medicaid MCO create a single preferred drug list that includes all therapeutic classes that are Provides a listing of unfair trade practices. subject to PA.

HB 434 Magee HB 374 Thomas Establishes public notice Medicaid MCO Requires the LDH ensure that Medicaid adheres to: (1) Payments follow a "money follows the person" contract amendments model. LDH to publish the proposed amendment (2) Payments are value‐based/tied to clinical and provide a comment period ≥ 30 days. outcomes. (3) Medicaid adequately funds the cost of care Also requires any policy or procedure provided. proposed by the MCO not be implemented (4) Payments are equitable across all hospitals. without written approval by LDH (5) The system promotes access to care.

HB 433 LeBas HB 538 LeBas

Authorizes a pharmacist to decline Requires pharmacy audits be to dispense a covered Rx if the conducted by pharmacists. PBM reimburses the pharmacy in Requires that recoupment occur at an amount < acquisition cost POS and limited to actual financial harm. Requires that the beneficiary of a discount pay the recoupment.

219 6 5/17/2019

HB 278 Abraham

Adds to current law: when > 7‐day supply the prescriber shall indicate on the Rx the quantity of the Opioid Related opioid needed to treat the patient's condition

HB 243 Miller HB 250 Davis

Require “real‐time” reporting of Requires residential behavioral opioid‐related overdoses by ED health facilities offer MAT to and First Responders to LDH patients

SB 160 Boudreaux HB 526 Hoffman

Changes Nursing and Physician (a) Prohibits PA for MAT Assistant Practice Acts to align (b) Prohibits “step‐therapy” them with the scope of practice (c) Require “ALL” (buprenorphine/naloxone) in the buprenorphine/naloxone Federal SUPPORT Act formulations on State Drug Lists

220 7 5/17/2019

HB 276 Johnson

Grants APRN signature authority over activities within their scope of practice PA and APRN

SB 166 LaFleur HB 280 McFarland

Changes the relationship between Authorizes an income tax credit up Physician and Physician Assistant to $3,600 for 5 years for PA who from supervisory to collaborative practice in rural areas Changes the liability between them from Agency to Independent Practitioners

SB 177 White Adds to current prohibitions on agreements which restrain the exercise of a lawful profession; limits to non‐compete and non‐solicitation Medical Cannabis clauses of 5 years in the same area for MD, RN, APRN, and PA

221 8 5/17/2019

HB 138 Connick HB 169 Hoffman

Aligns LA definition of Hemp with Mandates that LSBME maintain a the latest Federal Agriculture Act… database on the health effects and Δ9THC < 0.3% outcomes associated with medical And cannabis Adds synthetic fentanyls to C‐I

HB 358 James HB 503 Edmunds

Allows “inhaled” cannabis Creates the Fresh Start Act of 2019 preparations and opens cannabis to enable persons with a criminal recommendations to Out‐of‐State record to obtain occupational and Telemedicine practitioners licenses

HB 509 Bagneris HB 579 Connick

Creates a pathway for recreational cannabis Authorizes hemp farming and use. Allows adults to possess up to 1 oz. provides for regulation by the LDAF Requires LDAF to issue licenses for the cannabis cultivation, manufacturing and testing facilities. Requires LBOP to issue licenses for retail stores. Creates a 15% tax on cannabis products for personal use.

222 9 5/17/2019

SB 61 Boudreaux HB 272 Brown Creates Louisiana Commission on Medicinal Plants within LDAF for the purpose of advising on Requires coverage for acupuncture the regulation of medicinal plants to protect the health, safety, and welfare of citizens. The membership: 1 farmer; 1 member from the state at large; 1 physician (LSBME); 1 pharmacist (LBOP); 1 law enforcement officer (LSA); 1 attorney (LDAA); and Secretary of LDH/designee

2018‐A ~ Immunization reporting 2018‐B ~ To permit returns for destruction 2018‐C ~ Investigational Drugs in Hospital Board of Pharmacy … 2018‐D ~ New PIC Responsibility 2018‐F ~ Creates Subchapter F. PBM 2018‐N ~ FDA Guidance Document January 2018 2018‐R ~ CPT Licensed in Other States 2019‐A ~

2018‐B: 46§2503. Drug Returns 2018‐A: 46§521. Rx Orders to Administer Medications A. … unchanged. F. Vaccines. 1… B. When a patient or his designee wishes to return previously 2. The immunizing pharmacist or his designee dispensed prescription drugs or devices to a pharmacy for shall report the immunization to the state destruction, the pharmacy shall accept such products previously immunization registry within 24 hours of the dispensed by that pharmacy and may accept such products administration of the immunization. In the event previously dispensed by another pharmacy, but only for destruction. the immunization was performed as part of a mass immunization event, the required report 1. From the time of receipt of such products until the time of to the state immunization registry shall be made destruction, the pharmacy shall quarantine such products to keep them separate from its active dispensing stock and shall within 72 hours of the administration of the take appropriate security measures to prevent the theft or immunization. diversion of such products.

22310 5/17/2019

2018‐C: Investigational Drugs 2018‐F: PBM 46§1529: A. Where the hospital pharmacy is a Any pharmacy benefit manager who, pursuant participant in one or more investigational drug to a contract or under an employment studies, the pharmacy may dispense investigational relationship with a carrier, health benefit plan drug products as well as commercially available drug products to patients enrolled in a study, whether or sponsor, or other third‐party payer, either not the patient is a registered patient of the hospital. directly or through an intermediary, manages the drug or device coverage or other pharmacy 46§2505: The pharmacist shall conduct, participate in, and support medical and pharmaceutical research benefits provided by the carrier, plan sponsor, appropriate to the goals, objectives, and resources of or other third‐party payer, shall be permitted the facility. by the board.

2018‐N: Compounding 46§2535 A.2.a. – E.4. … unchanged Prescription Adaptation F. Compounding Copies of Commercial Drug Products… 1. Copies of commercial drug products contain the same active pharmaceutical ingredient(s) in the same, similar, or easily substitutable dosage strength which can be Pharmacist changes the dose, interval used by the same route of administration. In the event a prescriber determines a change in the formulation of a commercial drug product is necessary to produce a significant clinical difference for the patient and documents that determination on the or formulation on an existing Rx when… prescription, the pharmacy may prepare the copy of the commercial drug product, provided: a. The prescriber’s determination shall identify both the relevant change requested and a. During shortage / when unavailable the clinically significant difference the change will produce for the patient; b. Changes in strength < 10% from the commercial drug product shall not be considered significant enough to warrant the preparation of a copy of a commercial b. To improve adherence drug product; and c. The pharmacy does not prepare copies of commercial drug products regularly or in inordinate amounts. c. To deal with a formulary issue 2. A pharmacy may prepare a copy of a commercial drug product when that product has been discontinued and is no longer marketed, or the drug product appears on the drug shortage list maintained by the federal Food and Drug Administration (FDA). d. To address a dose‐related ADR

“Over the long term, the big question for pharmacy is whether the profession will be able to develop a role in which its… knowledge can be brought to bear where it is most needed Hopes & Dreams ‐ at the point where decisions about drug usage are made…… the ultimate goal should be to give the pharmacist the responsibility for (or nightmares) prescribing medication and monitoring.”

Commission on Pharmaceutical Services. Pharmacy in a new age: report of the Commission on Pharmaceutical Services. CPhA, Toronto 1971.

22411 5/17/2019

Bills Introduced, 2019‐2020

Medicare Buy‐in for Older Individuals The Medicare at 55 Act ‐ Stabenow, S. 1742 Medicare Buy‐In & Health Care Stabilization Act ‐ Higgins, H.R. 3748

Medicare for All S. 1804 ‐ Sanders H.R. 676 ‐ Ellison

Medicare‐based Public Plan Option through an Expanded ACA Marketplace (HIE) The Choice Act ‐ [Schakowsky, H.R. 635, Whitehouse, S. 194] The Medicare‐X Choice Act ‐ [Bennett, S. 1970, Higgins, H.R. 4094] The Choose Medicare Act ‐ [Merkley, S. 2708 Richmond, H.R. 6117]

Medicaid Buy‐in through the ACA Marketplace State Public Option Act ‐ Schatz, S. 2001 ‐ Luján, H.R. 4129

22512 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Friday, May 24, 2019 2:00 - 3:00 PM

Poster Session: Innovations in Pharmacy Practice and Pharmaceutical Care

0179-0000-19-032-L05-P/T

1 Contact Hour (0.1 CEU) Knowledge-based activity

Pharmacist Objectives: Pharmacy Technician Objectives: 1. Describe the concepts of patient safety. 1. Describe the concept of patient safety. 2. Review outstanding health-system 2. Recognize what the high-risk drugs are and pharmacy practices or best practices in how to handle them throughout the health-system pharmacy. continuum of care. 3. List the impact of patient safety and safe 3. Review programs in insulin, chemotherapy, medication practices. anticoagulation and sedatives and 4. Discuss Continuous Quality Improvement introduce the safety practices into your and processes utilized to achieve quality practice setting. Pharmaceutical Care. 4. Outline how technicians may assist the 5. Utilize national standards, evidence-based pharmacist in identifying opportunities to medicine and pharmacy literature to improve medication safety. improve safety and efficacy. 6. List the ways that national accreditation agencies may positively impact the overall practice of pharmacy in heath-systems. 7. Recognize what the high-risk drugs are and how to handle them throughout the continuum care. 8. List the impact of educational programs on safety and pharmacy practice improvement. 9. Review the impact pharmacist, pharmacy students or pharmacy technicians may have in patient safety.

226 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting Poster Session Poster Titles and Participants

1 A Description of Antipsychotic Prescribing Patterns Based on Race in a Culturally Diverse Population Thomas Maestri, Taylor Waguespack, David Anderson, Margarita Echeverri, Jose Calderon-Albo Xavier University, New Orleans, LA

2 Implementation of an Electronic Narcotic Administration Record (eNAR) in a Large Health System John Lee, Alexandre Raymond Ochsner Health System

3 Student Perceptions Concerning the Use of Simulated Medications in a Pharmaceutical Care Lab Hardin M, Smart C, Elsayed RK, Starks S, Walker A University of Louisiana Monroe (ULM) College of Pharmacy

4 Evaluation of the Effect of Slow IV Push Administration of Antibiotics on Clinical Outcomes Gania G, Fabre’ - Lacoste N, Prabhu E, Odinet J, King ST, Stewart K, Supan E Ochsner Medical Center

5 Intravenous Lorazepam Storage and Replenishment Efficiencies in a Large Academic Medical Center Christine Pham, Alex Raymond Department of Pharmacy Ochsner Clinic Foundation, New Orleans, LA

6 Evaluating the Estrogen Activity of Over-the-Counter Medications Containing Parabens Caroline Baer, Emily Ragland, Peng Ma, Thomas Weise Xavier University of Louisiana, New Orleans, LA

7 Comparison of Acute Kidney Injury (AKI) Incidence and Risk Factors in Patients Receiving Cancomycin and Cefepime Versus Vancomycin and Piperacillin-Tazobactam Amanda Stevens Miller, Fatima Brakta, Ellen Austin, Kirbie St. James, Julio Figueroa, Amne Borghol, Ifeanyi Onor, Jayla Thompson University Medical Center, New Orleans, LA

8 Perceived Benefit of Electronic Medical Records in Preparing Pharmacy Students for Institutional Pharmacy Practice Experiences Stelly AM, Sealy CM, Hatcher AA, Park HQ, Donald BJ University of Louisiana Monroe College of Pharmacy

9 Aspirin Use as Primary Prevention in Elderly Patients Allison Graffeo and Michele McCloskey Xavier University of Louisiana College of Pharmacy, New Orleans, LA

10 Effect of Procalcitonin Protocol on Discontinuation of Antibiotics in Septic and Septic Shock Patients at University Medical Center Bilbe S, Azhar A, Brakta F, Figueroa J, Aymond K University Medical Center, New Orleans and Louisiana State University Science Center, New Orleans, LA

227 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting Poster Session Poster Titles and Participants

11 Evaluation of Direct Oral Anticoagulations in Obese and Extremely Obese Patients Kelvin Tran, Kristina Dupre, Stephanie Yousef-Elagizi, Yana Bukovskaya, Lauren A. Fuller Ochsner Foundation Hospital, Pharmacy Department

12 To Evaluate and Assess Acute Kidney Injury in Adult Hospitalized Patients Receiving the Combination on Vancomycin and Piperacillin/Tazabactam for More than 48 Hours Morrison PM, Gerard T, Davis A, Le A, Parker L East Jefferson General Hospital, Metairie, LA

13 Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA- MB-231 Breast Cancer Cells Chandler Schexnayder, Kiera Broussard, Demitrius Onuaguluchi, Anthony Poche, Moamen Ismail, Lefantae McAtee, Shawn Llopis, Amber Keizerweerd, Harris McFerrin and Christopher Williams Xavier University of Louisiana College of Pharmacy

14 The Assessment of the APhA Immunization Course at ULM COP Through Student Self-Assessment Pecora R, Griggs T, Ortego H, Crew C University of Louisiana at Monroe College of Pharmacy

15 Relative Risk for Acute Kidney Injury When Using ACE-Inhibitor or ARB Therapy Versus Sacubitril/Valsartan Vega A, Miller V Ocshner LSU Health - Shreveport, LA

16 The Impact of A Pharmacy-Based Transitions of Care Program on the Heath Failure 30-Day Readmission Rates in a Community Hospital Eman Al-Bassisi, Ernest Terry, Kisha Gant Slidell Memorial Hospital - Slidell, LA

17 Pharmacokinetic Comparison of Pharmacist-Managed Versus Traditional Vancomycin Dosing and Monitoring in Two Community Hospitals Wu N, Bohan JG, Stewart K, King ST, Burton J, Gastanduy M Ocshner Medical Center - New Orleans, LA

18 The Appropriate Use of Statins in Patients with Diabetes of Hyperlipidemia Lewis PB, Ahmed F East Jefferson General Hospital - Metairie, LA

19 Comparison of Pre and Post Implementation of a Clinical Protocol Allowing Pharmacists to Initiate Universal MRSA Decolonization Orders for Patients Admitted to an Adult ICU Jameshia A. Below, Gretchen Blondeau, Kisha Gant Slidell Memorial Hospital - Slidell, LA

20 Evaluation of Antibiotic Administration Timing and Patient Outcomes Post-Implementation of Code Sepsis Ly M, Morales C, Lee S, Sloan W, Shreves A Ochsner Medical Center, New Orleans, LA

21 Short Versus Prolonged Course of Antibiotic Treatment of Gram-Negative Blood Stream Infections Elle Kline, Samuel King, Kyana Stewart, Jefferson Bohan, Jonathon H Ochsner Medical Center 228 Poster Abstract #1

A Description of Antipsychotic Prescribing Patterns Based on Race in a Culturally- Diverse Population

Thomas Maestri, Pharm D, BCPP [1], Taylor Waguespack [1], Margarita Echeverri, M.Sc, PhD [1], Jose Calderon-Abbo, MD [2], David Anderson, PhD [1]. 1 . Xavier University of Louisiana, New Orleans, LA, 2. Optum/United Healthcare, LA

Abstract Psychosocial factors including cultural beliefs and socioeconomic status can have a large impact on accessibility to treatment in mental illness. Considering the various perceptions of mental health across cultures and stigmatization of health care providers, minority populations can potentially be prone to health disparities in regards to the treatment of mental health conditions. This pilot study will provide new data regarding drug selection of antipsychotic medications based on race/ethnicity, as well as, other individual characteristics and how it relates to possible unnecessary antipsychotic exposure. The study describes the prescribing patterns of antipsychotic medications in patients from different racial/ethnic backgrounds and explores appropriateness to therapy, targeting potential mental health disparities related to antipsychotic medication exposure. A single-centered, retrospective chart review was conducted at the inpatient behavioral health center of an academic hospital. To be included, patients had to have been discharged with a prescription for an oral antipsychotic or be administered a long-acting injectable antipsychotic prior to discharge for a diagnosis of a formal mood or thought disorder. The study enrolled 400 patients discharged from October 1, 2015 – December 31, 2017. Descriptive in nature, the study relates the antipsychotics prescribed at discharge to race/ethnicity of the patient. Demographical information including socioeconomic status, healthcare coverage, past psychiatric and medication history was collected. We reported the prescribing patterns of antipsychotics based on race/ethnicity to better target health disparities in the treatment of mental illness in future studies. Patients who were involuntarily admitted to the behavioral health unit and patients with more past antipsychotic trials had a highly significant dose increase of Thorazine upon discharge. Also, appropriateness of antipsychotic medications was reported based on guideline recommendations in relationship to the patients’ individual demographical information, socioeconomic status, psychiatric history and previous treatment approaches. The study found a trend towards significance in appropriateness of therapy based on race. African American patients were three times more likely to receive inappropriate medications compared to the White population.

229 Poster Abstract #2

Implementation of an Electronic Narcotic Administration Record (eNAR) in a large health system

John Lee, Pharm.D., Alexandre Raymond, Pharm.D., MS Ochsner Health System

Abstract: Historically, controlled substance transactions that occur outside of automated dispensing cabinets (ADCs) have been documented on paper narcotic administration records (NAR). On the inpatient side, nurses documented narcotic waste on paper NAR when patients were discharged or changed locations, and either returned/tubed the paper forms to phar- macy for manual audits. Additionally, in the ambulatory clinics without ADCs, nurses documented all controlled sub- stance transactions including receipt, daily inventory count, administration, and waste on the paper NARs, which were faxed to pharmacy at the end of each month for audits. To mitigate the risk of drug diversion due to the limitations of paper forms (delay in audits, potential for fabrication), pharmacy leadership proposed an electronic narcotic administration record. A few notable features of the eNAR are:  Witness receives an email to approve/deny witnessing the transaction  Witness receives reminder emails if the transaction is not approved within 12 and 24 hours  Email alert to pharmacy leadership if a nurse has not attested witnessing a transaction within 48 hours  Email alert to pharmacy leadership if a nurse denies witnessing a transaction  Enhanced and continuous visibility of narcotic usage/waste practice At Ochsner Medical Center – Jeff Hwy, the eNAR was implemented and went live in February 2019 on one of the inpatient nursing units, pediatric intensive care, and in March 2019 for all of hospital-based clinics. Key performance indicators (KPIs) for the eNAR included following: Total #s of dispenses, wastes, and counts documented, audit turnaround time, total #s of dispenses vs. total #s of administrations, % of discrepancies, and % of transactions approved within 24 hours. Table 1: Non-ADC Controlled Substance Transactions at Ochsner Medical Center – Jeff Hwy Inpatient Nursing Unit Hospital-based Clinics # Administrations 118 581 # Wastes 2 378 # Counts 95 600 # Receipt N/A 30

Table 2: Pre- vs. post-implementation on an inpatient nursing unit Pre-Implementation Post Audit Turnaround Time 5 days Real-time % Discrepancies N/A 1.1% % of transactions approved N/A 79% within 24 hours

Table 3: Pre- vs. post-implementation in hospital-based clinics Pre-Implementation Post-Implementation Audit Turnaround Time 30 days Real-time % Discrepancies N/A 0.69% % of transactions approved N/A 92% within 24 hours

Given the results, the implementation of an electronic narcotic administration record increased pharmacy’s visibility into the controlled substance usage that occur outside of ADCs and streamlined the process to allow more convenient docu- mentation for the nurses/providers. 230 Poster Abstract #3

Student Perceptions Concerning the Use of Simulated Medications in a Pharmaceutical Care Lab

Hardin M*,1 Smart C,1 Elsayed RK,2 Starks S,3 Walker A.1 1University of Louisiana Monroe (ULM) College of Pharmacy; Monroe, Louisiana; 2St. Francis Medical Center; Monroe, Louisiana; 3ULM College of Health Sciences; Monroe, Louisiana.

Abstract

This study assesses student perceptions regarding the substitution of in-house prepared, simu- lated medications for commercial, active medications in pharmacy school practice labs as a fol- low-up to a pilot study.1 An IRB-approved, voluntary, electronic survey was administered. The survey was used to assess perceived benefits and challenges of using simulated medications in- cluding amoxicillin suspension, ampicillin and ceftazidime powders, and Tamiflu capsules pre- pared in-house at the College of Pharmacy. Survey question types were dichotomous, multiple- choice, and Likert-scale questions that evaluated students’ opinions of in-house simulated med- ications compared to commercial active medications used in previous labs. An open-ended question was included to obtain student perceptions on the overall advantages and disad- vantages of using simulated medications. One hundred (100) student pharmacists completed the survey. The survey revealed a majority of the students (97%) understood the simulated products’ educational intentions and purpose in their practice labs. There was a diverse re- sponse in relation to simulated Tamiflu capsules providing adequate substitution for commer- cial Tamiflu capsules. Overall, for future labs, simulated lab products were preferred (43%) over commercial drugs (23%) and no opinion (34%). Safety concerns and cost efficacy were ad- dressed in the open-ended responses given by the students. This project relates to students’ perceptions concerning the use of in-house prepared, simulated medications versus commer- cial, active medications in pharmacy practice labs and the impact that it has had, if any, during their academic career. Limitations to data analysis included lack of thorough student de- mographics and sampling size, which will warrant further studies. Our findings suggest that im- plementing simulated medications was accepted by students, and will help with the advance- ment of future practice lab courses.

Acknowledgements: 1. Walker, A., Elsayed, R., Hill, S. (2018). Reducing costs by using simulated medications instead of commercial products in a pharmaceutical care lab. American Journal of Pharmaceutical Edu- cation: Abstract for Volume 82, Issue 5, page 529.

231 Poster Abstract #4

Evaluation of the Effect of Slow IV Push Administration of Antibiotics on Clinical Out- comes

Gania G, Fabre’-LaCoste N, Prabhu E, Odinet J, King ST, Stewart K, Supan E, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121

Abstract In the wake of the Hurricane Maria-induced fluid shortage of 2017, our institution implemented an intravenous push (IVP) protocol for many beta-lactams. Given that prolonged infusions of these time-dependent agents have demonstrated greater efficacy for many infections over short (30 minute) infusions, we sought to determine if IVP administration of beta-lactams impacted early patient outcomes. This was a retrospective cohort study that included patients who received select beta-lactam antimicrobials (aztreonam, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, and meropenem) during a hospital admission between January 1, 2017 and June 30, 2018. Patients were excluded for the following reasons: documented allergy to the adminis- tered antimicrobial, active outpatient antimicrobial therapy, receiving antimicrobial prophylax- is. To address the primary outcome of clinical improvement at 48 hours, patients receiving in- termittent or continuous infusion antimicrobials from January 1, 2017 to June 30, 2017 were compared to patients receiving IVP antimicrobials from January 1, 2018 to June 30, 2018. Sec- ondary endpoints include time to clinical improvement, antimicrobial-associated adverse events, and drug expenditures. Categorical variables will be analyzed with a Chi-squared test; continuous variables will be analyzed with either a Student’s t-test or Mann-Whitney U test. A total of 200 patients were included in this study; 100 patients in the IV push group and 100 in the intermittent or continuous IV infusion group. Data analysis is currently in progress. Conclu- sions to be presented following completion of data analysis.

232 Poster Abstract #5

Intravenous Lorazepam Storage and Replenishment Efficiencies in a Large Academic Medical Center

Christine Pham, PharmD Candidate, Class of 2020; Alex Raymond, PharmD, MS Department of Pharmacy Ochsner Clinic Foundation, New Orleans, Louisiana

Abstract: Ochsner Medical Center currently stores Lorazepam 2 mg/mL vials one of two ways: in a lock box in the refrigerator, or in the pyxis at room temperature. Both storage methods have their benefits and disadvantages. Refrigerated storages allows the pharmacy to utilize the manufac- tures expiration date yet, can result in delays in accessing a key. Room temperature storage al- lows efficient access yet, results is frequent outdates due to the manufactures 30 day beyond use date. The purpose of this project is to determine which method of storing Lorazepam pro- vides the most operational efficiencies. This will be achieved by analyzing the data collected Pyxis reports from January 1, 2018 to December 31, 2018. Data collection includes: expired vi- als, refills, and vends of Lorazepam recorded from all of the Pyxis machines . The data will be used to calculate the percentages of expired, refills, and vends from the units that store Loraze- pam in a lockbox and the units that store Lorazepam in the Pyxis. In addition, the data will be used to determine the refill to vend ratio and the vend to expired ratio. Descriptional statistics will be used to analyze the data to determine which units generate the most waste. A total of 10,387 Lorazepam 2mg/mL vials were stored on the floors within the timeframe. Out of the to- tal Lorazepam vials, 31% (3,200 vials) were stored at room temperature in the Pyxis and 69% (7,187 vials) were stored in a refrigerated lock box. Out of the lorazepam vials that were stored in the Pyxis, 9.34% (299) were expired. Out of the lorazepam vials that were stored in the re- frigerated lock box, 1% (74) were expired. The results show that most of the expired vials were stored at room temperature in the Pyxis.

233 Poster Abstract #6

Evaluating the Estrogen Activity of Over-the-Counter Medications Containing Parabens

Caroline Baer, Emily Ragland, Peng Ma2, Thomas Wiese1 1College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 2RCMI Cell and Molecular Biology (CMB) Core, Xavier University of Louisiana, New Orleans, LA

Abstract: Parabens such as methylparaben, ethylparaben, and propylparaben are widely used in food products, cosmetics, and pharmaceuticals as preservatives. Many products contain multiple parabens to enhance the preservative effect. Parabens have been shown to be weak estrogens with alkyl chain length directly related to activity. In this study, we test the hypothesis that extracts of over-the-counter (OTC) medications containing paraben preservatives will induce estrogen activity in human breast cancer cells in culture. Five frequently used OTC medications were selected where equivalent pairs of products with the same active pharmaceutical ingredient were available, one with and one without paraben preservatives in the formulation. Ethanol extracts and dilutions were prepared of OTC preparations of: Calcium Carbonate, Bisacodyl, Ibuprofen, Diphenhydramine, and Benzoyl Peroxide (1 unit:1 mL). The estrogen agonist and antagonist activity of each extract was determined using the T47dkbluc estrogen reporter gene and the MCF-7 E3 estrogen responsive proliferation assays. Estrogen agonist activity was observed after treatment with extracts from Bisacodyl and Benzoyl Peroxide preparations. Formulations of Bisacodyl with and without parabens both induced estrogen agonist activity. The Bisacodyl structure suggests some features of the estrogen pharmacophore, and estrogen activity has been reported in the literature. Thus, observed Bisacodyl extract estrogen effects are likely due to the active ingredient. Estrogen activity of Benzoyl Peroxide extracts was only observed in the extract deriving from the formulation that contained parabens and thus activity is likely due to the paraben preservative. While Ibuprofen and Diphenhydramine extracts with and without parabens did not induce significant estrogen activity in the bioassays, extracts from these products induced estrogen activity when combined with fulvestrant. The cause for this apparent potentiation of estrogen activity in an antiestrogen is not clear. This study highlights the potential for paraben preservatives in OTC medications to induce observable estrogen activity. The importance of determining the estrogen activity of OTC medications in general is also illustrated. While the capacity for OTC preparations containing parabens or other estrogenic substances to induce estrogen activity in individuals using the medications is unclear, consumers may want to know about the presence of estrogenic components.

234 Poster Abstract #7

Comparison of Acute Kidney Injury (AKI) Incidence and Risk Factors in Patients Receiv- ing Vancomycin and Cefepime Versus Vancomycin and Piperacillin-Tazobactam

Amanda Stevens Miller, Fatima Brakta, Ellen Austin, Kirbie St. James, Julio Figueroa, Amne Bor- ghol, Ifeanyi Onor, Jayla Thompson; University Medical Center of New Orleans, New Orleans LA.

Abstract: The incidence of vancomycin-induced nephrotoxicity (VIN) when used in combination with oth- er nephrotoxic antibiotics have been explored by various studies. Navalkele et. al. compared the risk of AKI between patients on concomitant vancomycin and piperacillin-tazobactam versus vancomycin and cefepime. The AKI rate was significantly higher in the concomitant vancomycin and piperacillin-tazobactam than the vancomycin and cefepime (81/270 [29%] vs 31/279 [11%]). The purpose of this study is to determine the incidence of AKI associated with vanco- mycin and cefepime (group 1) versus vancomycin and piperacillin-tazobactam (group 2) in both trauma and non-trauma patients at University Medical Center New Orleans. A retrospec- tive chart review of adult patients receiving vancomycin and piperacillin-tazobactam or cefepime from July 1st 2017 to December 31st 2017 will be conducted at the University Medical Center New Orleans. The primary objective of this study is to compare the incidence of AKI in patients receiving vancomycin and piperacillin-tazobactam versus vancomycin and cefepime. The secondary objectives of this study are to evaluate the following clinical outcomes: length of stay, effect of additional nephrotoxic agents and time to AKI. All patient data will be collected via auto-generated reports from EPIC. The following demographic data will be collected for each patient: age, gender, weight, height, patient’s baseline Serum creatinine, patient’s serum creatinine at time of AKI, and diagnosis of shock if present. Other data points that will be col- lected are dates of first administration of each agent together, date of AKI, and documentation of patient receiving any other nephrotoxic drugs. Nephrotoxic drugs included will be IV con- trast 72 hours before IV antibiotics, Furosemide, Angiotensin converting enzyme inhibitors, an- giotensin receptor blockers, calcium channel blockers, thiazides, and nonsteroidal anti- inflammatory drugs. There was no difference in incidence of AKI between the two groups (p=0.056). There was no difference in time to AKI or length of stay between the groups (p=0.754 and p=0.485). Of the nephrotoxic agents examined in the study, thiazide diuretics were the only medications shown to put a patient at an increased risk of AKI (OR=0.806, CI 0.732 to 0.888). In conclusion, we found no difference in the incidence of AKI between the pi- perazillin-tazobactam and vancomycin and the cefepime and vancomycin group.

235 Poster Abstract #8

Perceived Benefit of Electronic Medical Records in Preparing Pharmacy Students for Institu- tional Pharmacy Practice Experiences

Stelly AM, Sealy CM, Hatcher AA, Park HQ, Donald BJ and the University of Louisiana Monroe, College of Pharmacy

Abstract To determine if the utilization of an electronic medical record (EMR) versus usage of paper medical charts in the curriculum will better prepare pharmacy students for Institutional Practice Experiences. After completing their Institutional rotation, P3 students were asked to complete an academic exercise using an EMR. These students had not been exposed to an EMR prior to their Institutional rotation and were only given practice with paper charts. P3 students were given access to the EMR and asked to identify as many medical errors within the charts as possible within a time period. After the exercise, students were then surveyed using kert scale on their opinion of if they had exposure to an EMR prior to their Institutional rotation would have been helpful. Conversely, prior to their institutional rotation, P2 students were given the same academic exercise and survey. Data was collected on their opinion of the effect of EMRs in the pharmacy curriculum for future institutional experience preparedness. Students responded that exposure to an EMR prior to an Institutional rotation would have better prepared them for their IPPE and that it was an effective method of learning pharmacotherapeutic material. P3 students agreed with P2 students that usage of the EMR will better prepare students for their institutional IPPE (Likert score 4.06 vs. 4.18). Our team finds that incorporation of the use of an EMR into the pharmacy curriculum has positive impacts on students' perceived readiness for institutional practice experiences.

236 Poster Abstract #9

Aspirin Use as Primary Prevention in Elderly Patients

Allison Graffeo and Michele McCloskey Xavier University of Louisiana College of Pharmacy, New Orleans, LA

Abstract: The frequency of prescriptions for low-dose aspirin is significant; but physicians regularly dis- regard the overall appropriateness for each patient, specifically the elderly, and their cardiovas- cular and bleeding risk factors. Are all patients at risk for atherosclerotic cardiovascular disease (ASCVD) or is the recurrent use of antiplatelets a greater risk for those older patients with low- er percentages for ASCVD and bleeding risk? Clinicians should be calculating each patient’s 10- year ASCVD risk and assessing their past medical history to ensure individualized and safer de- cision-making regarding medication selection and dosage. In 2016, JAMA recommended giving low-dose aspirin to patients between the ages 50-59 who have a 10% or greater 10-year ASCVD risk. When increasing to ages 60-69 with a 10% or greater 10-year ASCVD risk, they decided it ultimately becomes individualized and specific to each patient case. In a placebo-controlled study during 2010-2014 by the National Institute of Aging, the results concluded that in healthy elderly patients using low-dose aspirin as a prevention strategy proved a significantly higher risk of major hemorrhage and did not result in lower cardiovascular disease in comparison to the placebo patients P<0.001. There are numerous trials and articles regarding the dispensable use of low-dose aspirin in patients, yet patients continue to overuse it. The purpose of this post- er is to discuss the risk and benefits and appropriateness of using daily low-dose aspirin. As a pharmacy student, we are the next generation and will need to make these vital changes in our healthcare system by providing new research and studies into clinical practice.

237 Poster Abstract #10

Effect of procalcitonin protocol on discontinuation of antibiotics in septic and sep- tic shock patients at University Medical Center – New Orleans

Bilbe S, Azhar A, Brakta F, Figueroa J, and Aymond K; University Medical Center New Orle- ans and Louisiana State University Health Science Center, New Orleans, LA

Abstract Procalcitonin is a biomarker produced by the thyroid that increases acutely as an indica- tor of bacterial infection. University Medical Center New Orleans (UMCNO) developed a procalcitonin protocol in November 2017 that is used to guide antibiotic discontinuation in sepsis and septic shock. The objective of the study was to compare antibiotic days of therapy in septic patients in which the procalcitonin protocol was followed to septic pa- tients in which procalcitonin levels were not taken. A retrospective chart review was per- formed from January 2018 to July 2018. ICD 9 and 10 codes were used to generate a list of patients with sepsis and septic shock. A procalcitonin lab value report was generated to identify patients in which a procalcitonin level was collected. Septic and septic shock patients with procalcitonin values showed a significant decrease in antibiotic days of therapy (6.25 days vs 10.74 days, p = 0.006) and decrease length of stay (7.45 days vs 14.11 days, p = 0.006). In patients in whom the UMCNO protocol was followed, there was a significant decrease in antibiotic days of therapy (2.33 days vs 6.87 days, p = 0.013). There was no difference in mean total days of broad spectrum antibiotic therapy (3.93 days vs 2.66 days, p = 0.077) or all-cause mortality at 28 days (OR 0.433, 0.128 to 1.466 (95% CI)). In conclusion, patients in which a procalcitonin value was collected during ad- mission had a decrease in antibiotic days of therapy and decreased length of stay. Educa- tion for providers regarding procalcitonin and development of a more extensive procalci- tonin protocol is in process at UMCNO.

238 Poster Abstract #11

Evaluation of Direct Oral Anticoagulations in Obese and Extremely Obese Patients

Kelvin Tran, PharmD; Kristina Dupre , PharmD; Stephanie Youssef-Elagizi, PharmD, BCPS; Yana Bukovskaya, PharmD, BCPS; Laura A. Fuller, PharmD, BCPS, BCCP, Ochsner Foundation Hospital, Pharmacy Department, 1516 Jefferson Highway, New Orleans, LA 70121

Abstract Despite the high prevalence of obesity, there has yet to be a large, prospective, a priori analysis assessing the efficacy and safety of direct oral anticoagulants (DOACs) in this population. Post- hoc data from the venous thromboembolic (VTE) phase III trials use inconsistent body mass in- dex stratification and weight categories, with even less representation of patients who are ex- tremely obese (BMI ≥ 40 kg/m2). In addition, pharmacokinetic and pharmacodynamic studies have suggested that obese patients may be under-dosed, although these studies did not provide clinical outcomes. A retrospective cohort of patients receiving DOACs in patients who are normal or overweight compared to patients who are obese and extremely obese for the treatment of an index VTE from January 2013 to November 2017 was conducted. The primary outcome of the study is to assess the rate of recurrent VTE over 12 months from the time of DOAC initiation. The percent recurrence of VTE 12 months from the time of DOAC initiation, was 11.1% in the control group, 8.3% in the obese group, and 0% in the extremely obese group (p=0.004). Major bleeds occurred in 8.3%, 5.6%, and 2.8% in the control, obese, and extremely obese groups, respective- ly (p=0.59). The study did not find an increased risk of bleeding or VTE recurrence in the obese and extremely obese groups compared to the control, although larger trials are needed.

239 Poster Abstract #12

To Evaluate and Assess Acute Kidney Injury in Adult Hospitalized Patients Receiving the Combination of Vancomycin and Piperacillin/Tazobactam for More than 48 Hours

Morrison PM*, Gerard T, Davis A, Le A, Parker L, East Jefferson General Hospital Metairie, Loui- siana.

Abstract This study discusses factors affecting the incidences and severity of acute injury post concomi- tant vancomycin and piperacillin/tazobactam therapy. We will also discuss confounding varia- bles that may increase renal toxicity. The method used for the study design was a single center retrospective chart review. The timeline of the charts reviewed was January 2017- December 2017. Acute kidney injury incidence was assessed at baseline, 48 hours, and 96 hours. At the conclusion of this study our result showed combination therapy did not appear to increase the risk of acute kidney injury and that confounding variables, such as nephrotoxic agents and sep- sis were associated with higher rates of acute kidney injury.

240 Poster Abstract #13

Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells

Chandler Schexnayder, Kiera Broussard, Demitrius Onuaguluchi, Anthony Poche, Moamen Ismail, LeFontae McAtee, Shawn Llopis, Amber Keizerweerd, Harris McFerrin, and Christopher Williams Xavier University of Louisiana College of Pharmacy, 1 Drexel Drive, New Orleans, LA 70125

Abstract Background: Several mechanisms of action have been proposed to explain the apparent antineoplastic functions of metformin, many of which are observed at high concentrations that may not be reflective of achievable tissue concentrations. We propose that metformin at low concentrations functions to inhibit ROS production and inflammatory signaling in breast cancer, thereby reducing metastasis. Methods: Using the highly invasive MDA-MB-231 breast carcinoma model, we ascertained the impact of metformin on cell viability by DNA content analysis and fluorescent dye exclusion. Migration and invasion assays were performed using a modified Boyden chamber assay and metastasis was ascertained using the chorioallantoic membrane (CAM) assay. PGE2 production was measured by Enzyme-Linked Immunosorbent Assay (ELISA). COX2 and ICAM1 levels were determined by flow cytometry immunoassay. Results: Metformin acutely decreased cell viability and caused G2 cell cycle arrest only at high concentrations (10 mM). At 100 μM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS produc- tion while failing to significantly impact cell viability. Consequently, metformin inhibited migra- tion, invasion in vitro and PGE2-dependent metastasis in CAM assays. Conclusion: At pharmacologically achievable concentrations, metformin does not drastically impact cell viability, but inhibits inflammatory signaling and metastatic progression in breast cancer cells.

241 Poster Abstract #14

Assessment of the APhA Immunization course at ULM COP through student self-assessment

Pecora R, Griggs T, Ortego H, Crew C. University of Louisiana at Monroe College of Pharmacy, 1800 Bienville Drive, Monroe, LA 71201

Abstract The purpose of this study was to assess student perception on the placement and class structure setup of the APhA immunization course in the ULM College of Pharmacy curriculum. A voluntary survey was used to gather data in different areas of immunization competency among the P1, P2, and P3 classes. The assessment of student confidence revealed 58% of the P1, 60% of the P2, and 78% of the P3 classes were at least confident in their ability to administer vaccinations. For the placement of the course in the curriculum, implementation of the course during P1 year was preferred by the P1 and P2 participants at 91% and 83%, respectively, while 91% of the P3 participants preferred the course be implemented before P3 year. Roughly the same percentage of study participants in the P1, P2, and P3 class liked the independent self study set up of the immunization course at 40%, 42%, and 42%, respectively. Furthermore, 57% of the P1 participants and 40% of the P2 participants desired the course structure setup to be a small in-class module throughout the semester. Additionally, 30% of the P3 class participants desired a small in-class module, while yet another 30% preferred pre-readings with in-class application. From the data collected, the majority of students who participated in the surveys were at least confident in their ability to administer vaccinations, and preferred the course remain in P1 year of the curriculum. However, data indicates that the students may prefer a different class structure of the immunization course.

242 Poster Abstract #15

Relative Risk for Acute Kidney Injury When Using Age-Inhibitor or ARB Therapy Versus Sacubitril/Valsartan

Vega A, Miller V; Ochsner LSU Health – Shreveport; Shreveport, LA

Abstract This study evaluated the relative risk of acute kidney injury (AKI) in Heart Failure Clinic patients receiving prior treatment with an ACE-inhibitor or angiotensin II receptor blocker (ARB) versus current sacubitril/valsartan therapy. The secondary objective of the study was to compare the incidence of hospitalizations due to AKI between the ACE-inhibitor or ARB and sacubitril/valsartan time periods. This is a retrospective chart review which looked at Heart Failure Clinic patients transitioning from an ACE-inhibitor or ARB to sacubitril/valsartan from April 2017 to December 2018. The data collected for each patient spanned from 6 months prior to and after the first prescription of sacubitril/valsartan. Patients were included if they were adults between 18-89 years of age, enrolled in the Heart Failure Clinic at Ochsner LSU Health – Shreveport, prescribed sacubitril/valsartan and were previously on an ACE-inhibitor or ARB, and had serum creatinine (SCr) results available. Patients were excluded if they were prisoners, pregnant, had end-stage renal disease on dialysis, or had severe hepatic impairment. During the study time period, 90 patients received a prescription for sacubitril/valsartan. There were 15 patients excluded due to insufficient laboratory data, 2 patients excluded due to severe hepatic impairment, and 55 patients excluded due to insufficient data within the time period. There were 18 patients included and assessed according to the protocol. Pertinent results include: 7 patients (39%) had an AKI while on an ACE-inhibitor or ARB in the six months prior to being switched to sacubitril/valsartan, and 9 patients (50%) had an AKI during the first six months of sacubitril/valsartan treatment. Of note, 5 patients (28%) experienced an AKI both during the ACE-inhibitor or ARB time period as well as the sacubitril/valsartan time period. Based on these results, there was a relative risk of 1.28 for developing an AKI on sacubitril/valsartan versus during treatment with an ACE-inhibitor or ARB. There were no hospitalizations directly attributed to AKI during this time period so a comparison could not be assessed. The results of this study suggest a higher incidence of AKI when using sacubitril/valsartan as compared to an ACEinhibitor or ARB. However, a low sample size and possible confounding factors limits the power of the study. It would be beneficial to extend this project and assess a larger number of patients to determine if there truly is a higher risk for AKI when using sacubitril/valsartan since this medication will be highly utilized in the heart failure patient population.

243 Poster Abstract #16

The Impact of a Pharmacy-Based Transitions of Care Program on Heart Failure 30-Day Readmission Rates in a Community Hospital

Eman Al-Bassisi, Ernest Terry, Kisha Gant, Slidell Memorial Hospital, Slidell, LA.

Abstract Heart failure affects approximately 6.5 million Americans 20 of years of age and older and is projected to increase to more than 8 million people 18 years of age and older between 2012 and 2030. It costs the nation approximately $30.7 billion annually. This includes the cost of health care, medications, and loss of productivity. By 2030, this amount is expected to grow to $69.7 billion. According to the Agency for Healthcare Research and Quality, the national 30-day readmission rate for heart failure was 23.2% in 2014 making it the leading cause of hospital re- admissions. Factors that contribute to early readmission rates include low rates of medication adherence, self-monitoring, and follow-up. The primary objective of this study is to determine the impact of a pharmacy-based transitions of care program on 30-day heart failure readmis- sion rates.

In this retrospective study, the hospital’s electronic medical record system was used to identify all patients readmitted for heart failure within 30 days. Data collected prior to the start of the transitions of care program (January 2015 to April 2016) will be used as a baseline and com- pared to data collected from program implementation in May 2016 through December 2018.The program initially consisted of a pharmacist assisted by pharmacy students, but it evolved to include a nurse case manager in March 2018. Prior to program implementation, the 30-day readmission rate for heart failure in 2015 was 28.9%. There was a slight decrease in the 2016 30-day heart failure readmission rates (25.3%) following the implementation of the pro- gram in April 2016. A continuous downward trend in the 30-day heart failure readmission rates was noted in 2017 and 2018, which were 24.7% and 17.9%, respectively.

A pharmacy-based transitions of care program demonstrated positive outcomes on 30-day heart failure readmission rates. An addition of a nurse case manager may have continued to promote a further decrease in 30-day heart failure readmission rates. This program may serve as a potential mechanism to combat early readmissions.

244 Poster Abstract #17

Pharmacokinetic Comparison of Pharmacist-Managed Versus Traditional Vancomycin Dosing and Monitoring in Two Community Hospitals

Wu, N; Bohan, JG; Stewart, K; King, ST; Burton, J; Gastanaduy, M; Ochsner Medical Center, New Orleans, LA

Abstract Pharmacists are the best-equipped medical professionals to manage vancomycin dosing due to their extensive medication knowledge and education. The primary objective of this study is to establish a difference between provider-managed and pharmacy-to-dose vancomycin therapy effectiveness.

This is a retrospective, matched 1:1, case-control study comparing vancomycin dosing practices at two community hospitals within a health system from January to June 2018. Hospital A (control arm) em- ploys traditional, non-pharmacist-managed vancomycin dosing and monitoring. Hospital B (case arm) employs a wide-spread pharmacist-managed vancomycin dosing consult program. Patients were matched based on dosing frequency and obesity status. All patients age 18 or older, admitted to Hospi- tals A or B, and receiving at least 3 consecutive doses of intravenous vancomycin on a scheduled dos- ing frequency of every 8, 12, or 24 hours with at least one trough collected before at least the third dose will be included in this study.

The co-primary outcomes include proportion of patients attaining first goal trough and AUC. Second- ary outcomes include goal trough or AUC attainment at any time in the first 7 days of vancomycin ther- apy with safety outcomes evaluating rates of AKI and supratherapeutic levels of vancomycin serum trough or AUC levels in each group. A total of 399 patient admissions were screened, resulting in 68 patients included in each study arm. A higher proportion of patients achieved goal trough and AUC goal in the provider-managed arm compared to the pharmacy-to-dose arm (trough: 41.2% vs. 30.9%, p = 0.211; AUC: 73.5% vs. 67.7%, p = 0.452). However, these results were not statistically significant, and we cannot conclude that either group was more effective at managing vancomycin therapy com- pared to the other.

245 Poster Abstract #18

The Appropriate Use of Statins in Patients with Diabetes or Hyperlipidemia

Lewis PB, Ahmed F, East Jefferson General Hospital, 4200 Houma Blvd, Metairie, LA 70006

Abstract The objective of the study was to assess how well patients with diabetes and hyper- lipidemia were being optimized on statin therapy. This was a single-center, retrospective chart review of patients between the ages of 40 and 75 years old that were seen in the Family Prac- tice Clinic between 1/1/2015 and 11/27/2018. The patients had either a recorded LDL value greater than 190 mg/dL or had both an LDL value between 70 mg/dL and 189 mg/dL and an HbA1C value greater than 6.5%. The primary endpoints were the percentage of patients in each group that were on the appropriate intensity statin. Data collected included age, gender, LDL value, the calculated ASCVD risk, whether or not the patient was put on a statin initially, wheth- er or not the patient is on a statin currently, what the statin intensities were, what the desired statin intensities were, and whether or not the patient was on the appropriate statin intensity initially and currently. Descriptive statistics were used to determine rates of appropriate statin use. A total of 100 patient charts were reviewed, and there were 50 patients in each group. We found that 58% of patients with LDL>190 mg/dL were on a statin, and 36% were on a statin of appropriate intensity. In contrast, 84% of patients in the diabetes group were on a statin, and 66% were on a statin of appropriate intensity. The data shows that fewer patients with LDL values greater than 190 mg/dL are on the appropriate statin than patients with diabetes and LDL between 70 and 189 mg/dL. Both groups have a lower percentage of patients on the ap- propriate statin than we would like. We can use this information to educate providers and pa- tients in the clinic going forward to better optimize patient care.

246 Poster Abstract #19

Comparison of Pre and Post Implementation of a Clinical Protocol Allowing Pharmacists to Ini- tiate Universal MRSA Decolonization Orders for Patients Admitted to an Adult ICU

Jameshia A. Below, Gretchen Blondeau, Kisha Gant, Slidell Memorial Hospital, Pharmacy Department, 1001 Gause Blvd, Slidell, LA.

Abstract Healthcare acquired infections (HAI) are now the fifth leading cause of death in U.S. acute-care hospi- tals with the highest incidence being in intensive care units (ICU). Decolonization is an evidencebased intervention that can be used to prevent HAI. Studies show that decolonization procedures are effective in reducing colonization rates and controlling MRSA. As a result, MRSA decolonization protocols are implemented to eliminate MRSA and reduce infections. Currently, there are no studies evaluating pharmacist initiated decolonization orders. This study was to identify the percentage of patients with universal MRSA decolonization orders initiated post-implementation of a clinical proto- col allowing pharmacist to initiate the orders in comparison to pre-implementation of the protocol. This is a retrospective analysis of patients admitted to an adult ICU between March 1, 2018 and September 30, 2018. On June 19, 2018, a protocol permitting pharmacists to initiate universal MRSA decolonization orders for adult ICU patients. Prior to this intervention, only physicians, nurse practitioners, and physician assistants entered these orders. Data was collected using the institution’s electronic medical records of all patients admitted to an adult intensive care units three months before and three months after the implementation of the protocol. The primary outcome was the per- cent of patients with MRSA decolonization orders initiated during pre-implementation and post- implementation of the protocol. The secondary outcome was the percent of orders initiated by non- pharmacist versus pharmacist post-implementation of the protocol. There were 1503 patients admit- ted into the ICU during the study period with an average of 188 patients per month. Prior to imple- mentation of the protocol 33%-56% of the patients in the ICU had MRSA Decolonization orders. After implementation of the protocol, the amount of patients receiving MRSA Decolonization increased to 79%-88%.

247 Poster Abstract #20

Evaluation of Antibiotic Administration Timing and Patient Outcomes Post- Implementation of Code Sepsis

Ly M, Morales C, Lee S, Sloan W, and Shreves A. Ochsner Medical Center, 1514 Jefferson High- way, New Orleans, LA 70121.

Abstract "Code Sepsis" was implemented to improve management of septic shock in the Ochsner Medical Center Emergency Department. This study evaluated the timing of antibiotic administration and patient outcomes before and after implementing Code Sepsis. This retrospective, single- center, cohort study included patients who presented to the ED with septic shock. The primary endpoint assessed the timing of antibiotic administration from sepsis time zero. Secondary endpoints were length of hospitalization, 30- and 60-day mortality, 30-day readmission, and pa- tients requiring intensive care unit (ICU) admission, vasopressor administration, mechanical ventilation, and renal replacement therapy. Three hundred fifty-four patients were included with 151 patients and 203 patients in the pre- and post-implementation group, respectively. The median timing of antibiotic administration from sepsis time zero improved after imple- menting Code Sepsis from 85 to 57 minutes (p < 0.001). The median length of hospitalization was 5.2 days for both groups (p = 0.873). The percentage of 30- and 60-day mortality increased (30-day mortality: 27.2% vs 28.6%, p = 0.77; 60-day mortality: 4% vs 8.9%, p = 0.07). Readmis- sion within 30 days was higher in the post-implementation group (21.9% vs 30.5%, p = 0.07). There were no statistically significant differences seen in patients requiring ICU admission, vas- opressor administration, mechanical ventilation, or renal replacement therapy between the groups. Implementation of Code Sepsis decreased the timing to antibiotic administration in pa- tients with septic shock that presented to the emergency department. However, there were no statistically significant differences seen with patient outcomes. Further research with a larger sample is warranted to assess patient outcomes.

248 Poster Abstract #21

Short Versus Prolonged Course of Antibiotic Treatment for Gram-Negative Blood Stream Infections

Elle Kline, PharmD; Samuel King, PharmD, BCPS-AQ ID; Kyana Stewart, PharmD, BCPS; Jefferson Bohan, PharmD, BCPS; Jonathan Hand, MD

Abstract Gram-negative bacteria is a major cause of morbidity and mortality in hospitalized patients and there is limited guidance and consensus on the optimal duration of antibiotic therapy for these infections. Retrospective chart review was conducted in patients admitted to the Ochsner Medi- cal Health System who had a positive blood culture with a gram-negative bacteria between July 14th, 2018 to January 14th, 2019. We compared outcomes in patients receiving a short duration of therapy (<11 days) to those receiving a prolonged duration of antibiotic therapy (>11 days). The primary outcome was a composite of 30-day readmission, all-cause mortality, and recur- rent infection. Secondary outcomes included emergence of multidrug resistance and clostridi- um difficile infections within 30 days of completion of therapy. There were 79 patients who met criteria and were included in the study. Twenty patients received a short course and 59 re- ceived a prolonged duration of antibiotics. There was no difference found in primary or second- ary outcomes between the 2 groups. Shorter courses of antibiotics appear to have non-inferior outcomes to prolonged duration of antibiotics.

249 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Notes

250 Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Notes Louisiana Society of Health-System Pharmacists 2019 Annual Meeting

Notes