2016 Primary Care Update

The Northwest Ohio Osteopathic Association In Partnership with The University of Toledo, Center for Continuing Medical Education Present the:

2016 PRIMARY C ARE UPDATE

Friday, November 11 – Sunday November 13, 2016

Kalahari Resort and Conference Center 7000 Kalahari Dr Sandusky, OH 44870

NWOOA NORTHWEST OHIO OSTEOPATHIC ASSOCIATION

Treating our families and yours

Please be sure to visit our exhibitor booths:

PLANNING COMMITTEE MEMBERS Nicholas J. Pfleghaar, D.O. Program Director President, Northwest Ohio Osteopathic Association BG Family Physicians

Nicholas G. Espinoza, D.O. State Trustee, Northwest Ohio Osteopathic Association Dean of CORE St.Vincent’s Hosp., Toledo, OH Med Director, The Falcon Health Center, Bowling Green, OH

Kris L. Lindbloom, D.O. President Elect, Northwest Ohio Osteopathic Association Hospitalist, Firelands Hospital

Tracey O’Neal Hooker, D.O. Local Trustee, Northwest Ohio Osteopathic Association

Jennifer Pfleghaar, D.O. Local Trustee, Northwest Ohio Osteopathic Association

John T. Rooney, D.O. Secretary/Treasurer, Northwest Ohio Osteopathic Association Verde Valley Medical Center

Joy A. Studer, ED Executive Director, Northwest Ohio Osteopathic Association

Roger L. Wohlwend, D.O. Local Trustee, Northwest Ohio Osteopathic Association

William J. Davis, D.D.S., MS Associate Dean, CME The University of Toledo

Becky Roberts Sr. CME Coordinator The University of Toledo

FACULTY

Constance P. Cashen, DO, FACOS, FACS Gregory Kramp, PharmD, RPh Associate Professor, St George’s University; Pharmacy Manager, Rite Aid Pharmacy Director, Medical Education, Program Director Osteopathic General Surgery Residency Program, Carlos G. Lowell, DO Mercy St Vincent Medical Center; Chairperson Des Moines University, College of Osteopathic General Surgery, Clinical Professor, General Medicine; Firelands Regional Medical Center, DO Surgery Ohio University Heritage College of Rotating Internship; Medical College of Osteopathic Medicine Wisconsin, Psychiatric Residency; TMS Institute of Ohio, Medical Director Cleanne Cass, DO Director, Community Care and Physician George Thomas Magill, MD Education, Hospice of Dayton; Professor, Palliative Medical Director, Wound Care Services Medicine, Ohio University Heritage College of Osteopathic Medicine; Adjuvant Clinical Faculty, Richard M. Miller, DO, FAOAO Department of Family Medicine, Wright State Orthopaedic Surgery Residency Program Director, University Boonshoft College of Medicine Mercy St Vincent Hospital; Clinical Associate Professor, Orthopaedic Surgery, Ohio University Robert J. Cromley, DO Heritage College of Osteopathic Medicine Family Medicine Private Practice; Medical Director, Stein Hospice; Family Medicine Adjunct Nicholas M. Naudad, DPM Faculty, Ohio University Heritage College of Private Practice, Advanced Foot and Ankle of NW Osteopathic Medicine; Clinical Preceptor, Des Ohio Moines University College of Osteopathic Medicine Ajith K. Pai, MD, FACA, DABA Associate Professor, Anesthesiology and Pain A Thomas Dalagiannis, MD, FACS Medicine, Des Moines University; Associate Chief of Plastics, St Vincent Mercy Medical Professor, Anesthesiology, Ohio University Center. St Luke’s Hospital, Toledo Hospital; Private Practice, Arrowhead Plastic Surgeons Sarath K. Palakodeti, DO Attending General and Cosmetic Surgeon, Toledo David Degnan Clinic Instructor, American Heart Association, AHA Instructor Trainer, Promedica Fremont Memorial Sarah E. Pawlicki, Esq., SPHR, SHRM-SCP Hospital, Sandusky Fire Chief Eastman & Smith, Ltd.

Brent C. DeVries, DO Laura T. Phillipps, RN, MSN, CHPN ProMedica Physicians Cardiology Nurse Educator, Hospice of Northwest Ohio;

Terry Mark Gibbs, DO, NCMP James E. Preston, DO, FAODME Promedica Obstetrics, Gynecology, Robotic Senior Medical Director, Stein Hospice and Surgery Palliative Care Inc.; Assistant Dean, Clinical Affairs, Ohio University Heritage College of Erin Hennessey, DNP, APRN, FNP Osteopathic Medicine; Program Director, Firelands Director, RN/BSN Program, Mercy College of Regional Medical Center; Fellowship, Hospice and Northwest Ohio Palliative Medicine

Tracy A. Karolyi, DO, FACOP Todd Rambasek, MD, FAAAAI Clinical Assistant Professor of Pediatrics, Ohio Clinical Allergist/Immunologist University College of Osteoapathic Medicine Judge Jodi Debbrecht Switalski C. Jeff Kesler, MD FACS Attorney, Family Law, Criminal Municipal and Private Practice, Plastic, Cosmetic and Medical Malpractice, Giarmarco, Mullins & Reconstructive Surgery, Head and Neck Surgery, Horton P.C.; Judge, Waterford District Court Hand Surgery, Arrowhead Plastic Surgeons Robert M. Stutman The Stutman Switalski Group, LLC

DISCLOSURES

FACULTY DISCLOSURES Dr. Gibbs discloses he is a speaker and receives honorarium from Pfizer.

Dr. Rambasek discloses he is a speaker and receives honorarium from Mylan.

Robert Stutman discloses he is a speaker and receives honorarium from Quest Diagnostics, Linden Care and Solo Technologies.

Jodi Debbrecht Switalski discloses she is a speaker and receives honorarium from Quest Diagnostics, Linden Care and Solo Technologies.

Drs. Cashen, Cass, Cromley, Dalagiannis, Karolyi, Kesler, Lowell, Miller, Nadaud, Pai, Palakodeti, Preston nor David Degnan, Brent DeVries, Erin Hennessey, Gregory Kramp, Laura Phillips, George Magill, or Sarah Pawlicki do not have any financial interest or other relationship with any manufacturer of commercial product or service to disclose.

PLANNERS

Drs. Davis, Espinoza, Lindbloom, Jennifer Pfleghaar, Nicholas Pfleghaar, O’Neal Hooker, Rooney, Joy Studer and Becky Roberts do not have any financial interest or other relationship with any manufacturer of commercial product or service to disclose.

ACCREDITATIONS

AOA AACCREDITATIONS The NWOOA certifies credit hours in conjunction with the OOA, directly to the AOA with the requirements and policies of the AOA. A total of up to 23 Category 1A credits will be requested from the American Osteopathic Association.

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Toledo and Northwest Ohio Osteopathic Association. The University of Toledo is accredited by ACCME to provide continuing medical education for physicians. The University of Toledo designates this live activity for a maximum of 23 AMA PRA Category 1 CreditsTM. Physicians should claim only credit commensurate with the extent of their participation in the activity.

This Live activity, 2016 NWOOA Primary Care Update 2016, with a beginning date of 11/11/2016, has been reviewed and is acceptable for up to 22.75 Prescribed credit(s) by the American Academy of Family Physicians. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The Ohio Board of Nursing will accept, at face value, the number of hours awarded for an educational activity that has been approved for CE, provided it was approved by a nationally accredited system of CE approval.

The AAPA accepts certificates of participation for educational activities, certified for Category 1 credit from AOACCME, Prescribed credit from AAFP, and AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

EVALUATION/CERTIFICATE Evaluations will be readily available online daily at the start of the program. Evaluation is an important component of continuing education programs. In addition to providing feedback to the program planners and faculty, it provides information to improve future programs. The evaluation is an integral part of your participation in this meeting.

TO OBTAIN YOUR CME CREDIT Evaluations will be readily available each day after the program, and MUST be completed for all days you attend order to receive a certificate. Certificates will be available online on Monday, November 14, 2016 after 12 noon. Follow the instructions below:  Go to website cme.utoledo.edu  Click on Direct Link to Login

 Login: lastnamefirstname (no commas, no spaces)

Password: zip code (unless you have changed in our system previously)  If you have not completed your online evaluations: You will be immediately directed to an “Online Forms Inbox” o Click on the evaluation form for the activity, Complete every field and hit “Submit” o You will be directed to view/print your certificate  If you have completed your online evaluations: o Choose “Credit Transcript” in the left side margin o Next to the activity, will be a certificate icon, click it and print your certificate o Remember each day has a certificate

FRIDAY, NOVEMBER 11, 2016 9 credits

7:00 a.m. -7:55 a.m. Registration/Breakfast - West Pathway

Moderator: Nicholas J. Pfleghaar, D.O.

8:00 a.m.-9:00 a.m. Diabetic Lower Extremity Health Nicholas M. Nadaud, DPM

9:00 a.m.-10:00 a.m. Hormone Therapy: Past, Present, Future Terry Mark Gibbs, D.O., NCMP

10:00-10:30 a.m. Break/View Exhibits - West Pathway

10:30-11:30 a.m. Colorectal Cancer: Hitting Your Screening Target Constance P Cashen, D.O. FACOS, FACS

11:30 a.m.-12:30 p.m. Ohio’s Opioid Guidelines, Laws and Rules: Protecting the Patient and the Prescriber Cleanne Cass, D.O.

12:30 p.m.-12:45 p.m. Lunch Buffet Line (Lunch and Learn)

12:45 p.m.-1:45 p.m. The Five Common Disorders of the Hand Seen by PCP’s C. Jeff Kesler, M.D., FACS

1:45 p.m.-2:45 p.m. See Spot Change: Identification and Management in Primary Care Erin Hennessey, DNP, APRN, FNP-C

2:45 p.m.-3:00 p.m Break /View Exhibits-West Pathway

3:00 p.m.-4:00 p.m. Plastic Surgery Overview for the PCP A. Thomas Dalagiannis, M.D., FACS

4:00 p.m.-5:00 p.m. Common Pediatric Sightings Tracy A. Karolyi, D.O., FACOP

5:00 p.m.-6:00 p.m. Angioedema Todd Rambasek, M.D., FAAAAI

SATURDAY, NOVEMBER 12, 2016 9 credits

7:30 a.m.-7:55a.m. Registration/Breakfast - West Pathway

Moderator: Nicholas G. Espinoza, DO

8:00 a.m.-9:00 a.m. Issues in Pain Management Ajith K. Pai, M.D., FACA, DABA

9:00 a.m.-10:00 a.m. Workplace Issues Associated with Legalized Medical Marijuana Sarah E. Pawlicki, Esq., SPHR, SHRM-SCP

10:00 a.m.-10:30 a.m. Break /View Exhibits - West Pathway

10:30 a.m.-11:30 a.m. Prescribing Naloxone and Management of Chronic Non-Cancer Pain Gregory Kramp, PharmD, RPh

11:30 a.m.-12:30 p.m. Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioids James E. Preston D.O., FAODME

12:30 p.m.-12:45 p.m. Lunch Buffet (lunch and Learn)

Moderator: Jennifer Pfleghaar, D.O.

12:45 p.m.-1:45 p.m. Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioids James E. Preston D.O., FAODME

1:45 p.m.-3:45 p.m. Osteopathic Manipulation in a Busy Practice Robert J. Cromley, D.O.

3:45 p.m.-4:00 p.m. Break/View Exhibits – West Pathway

4:00 p.m.-6:00 p.m. Drugs in America 2016 Robert M. Stutman & Judge Jodi Debbrecht Switalski

SUNDAY, NOVEMBER 13, 2016 5 credits

7:00 a.m. Breakfast Buffet - West Pathway

Moderator: Roger L. Wohlwend, D.O.

7:00 a.m.-9:00 a.m. Breakfast Buffet Served

8:00 a.m.-9:00 a.m. Breast Cancer Update 2016: The Latest in Diagnosis and Treatment Sarath K. Palakodeti, D.O.

9:00 a.m.-10:00 a.m. Young , Healthy…and Immortal: Discussing Advance Directives with Patients Who Don’t Think They Need Them Laura T. Phillipps, RN, MSN, CHPN

10:00 a.m.-11:00 a.m. The Basic Principles and History of Hyperbaric Oxygen Therapy George Thomas Magill, M.D.

11:00 a.m.-12:00 p.m. TMS Therapy: A Unique and Proven Approach to Treating Depression Carlos G. Lowell, D.O.

12:00 pm.-1:00 p.m. The Anterior Approach to Hip Replacement Richard M. Miller, D.O., FAOAO

8:00 a.m.-1:00 p.m. ACLS Recertification - Tamarind Room Brent C. DeVries, D.O. & Captain DavidDegnan, Fire Chief

COME AND JOIN US FOR A PIZZA PARTY

SPONSORED BY THE:

NORTHWEST OHIO OSTEOPATHIC ASSOCIATION

Saturday, November 12, 2016 BEGINNING AT 6:30 PM IN ZAMBESI ROOM

FRIDAY, NOVEMBER 11, 2016 9 credits

7:00 a.m. -7:55 a.m. Registration/Breakfast - West Pathway

Moderator: Nicholas J. Pfleghaar, D.O.

8:00 a.m.-9:00 a.m. Diabetic Lower Extremity Health Nicholas M. Nadaud, DPM

9:00 a.m.-10:00 a.m. Hormone Therapy: Past, Present, Future Terry Mark Gibbs, D.O., NCMP

10:00-10:30 a.m. Break/View Exhibits - West Pathway

10:30-11:30 a.m. Colorectal Cancer: Hitting Your Screening Target Constance P Cashen, D.O. FACOS, FACS

11:30 a.m.-12:30 p.m. Ohio’s Opioid Guidelines, Laws and Rules: Protecting the Patient and the Prescriber Cleanne Cass, D.O.

12:30 p.m.-12:45 p.m. Lunch Buffet Line (Lunch and Learn)

12:45 p.m.-1:45 p.m. The Five Common Disorders of the Hand Seen by PCP’s C. Jeff Kesler, M.D., FACS

1:45 p.m.-2:45 p.m. See Spot Change: Identification and Management in Primary Care Erin Hennessey, DNP, APRN, FNP-C

2:45 p.m.-3:00 p.m Break /View Exhibits-West Pathway

3:00 p.m.-4:00 p.m. Plastic Surgery Overview for the PCP A. Thomas Dalagiannis, M.D., FACS

4:00 p.m.-5:00 p.m. Common Pediatric Sightings Tracy A. Karolyi, D.O., FACOP

5:00 p.m.-6:00 p.m. Angioedema Todd Rambasek, M.D., FAAAAI

Diabetic Lower Extremity Health

Nicholas M. Nadaud, DPM

Learning Objectives:

Outline how to perform foot screening effectively using accepted screening tools Describe foot ulcer risk following foot screening. Identify referral pathways and describe when, where and who to refer. Discuss effective and targeted foot health education for people with diabetes.

10/31/2016

Diabetic Lower Extremity Health

Nicholas Nadaud DPM Advanced Foot and Ankle of NW Ohio Toledo Ohio

Diabetes Impact

• Nearly 24 million people, or 8 percent of the U.S. population, have diabetes

• 17.9 million people have been diagnosed

• 5.7 million people are still undiagnosed

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Risk Factors for Ulceration  Social / cultural habits  Mobility  Deformities  Vascular status  Neurological status  Skin lesions: ulcers, callus, blisters  Footwear  Compliance & understanding

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Risk Factors

• Ethnicity plays a large factor in developing diabetes. The following groups are at an increased risk: African‐American American Indian/Alaskan Native Asian‐American Pacific Islander Hispanic‐American/Latino • Overweight or obese • A family history of diabetes or gestational diabetes raises the risk

Signs & Symptoms

Diabetes warning signs in the feet:

• Redness • Numbness • Swelling • Cold to touch • Inflammation • Decrease hair growth

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Diabetes’ Impact on the Feet

• Neuropathy ‐ causes numbness, burning or tingling and diminishes sensation in the feet.

• Ulcers ‐ a breakdown of skin on the foot that is difficult to heal and often leads to infection.

• Amputations ‐ occur as a result of foot wounds and ulcers that do not heal.

Diabetes is a biochemical disease

• “Diabetes mellitus is a biochemical disease, but a large number of lower extremity complications of the disorder are due to biomechanical dysfunction.” (Source: Payne, 1998.) • Diabetics may have altered biomechanics; or • Present with a complication of any pre‐existing neurovascular or biomechanical dysfunction.

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Foot Ulceration

• Approximately 85% of diabetes‐related amputations start off with a foot ulcer that deteriorates, becomes infected & gangrenous!

Most foot ulceration CAN be avoided /prevented

Risk Factors for Ulceration • Peripheral neuropathy – Sensory – Autonomic – Motor • Risk factors for neuropathy include: hyperglycemia, elevated triglycerides, high BMI, smoking & hypertension.

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Risk Factors for Ulceration

Sensory Neuropathy • Largest single risk factor for diabetic foot ulcers – Burning, tingling, ”pins & needles”, numbness or “dead” feeling – Repeated unrecognized stress, pressure, friction & shearing. – Lack sensation to feel foreign objects, heat changes, discomfort or pain.

Risk Factors for Ulceration Autonomic Neuropathy • Impairs skin integrity, sweat regulation & blood flow. • Leads to: – thick, dry cracked skin, fissures – callus build‐up at pressure points

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Risk Factors for Ulceration Motor Neuropathy • Loss of muscle tone in the foot • Foot deformities: – Hammer toes – Claw toes • Metatarsal heads become prominent • Changes in pressure distribution & gait pattern

Risk Factors for Ulceration

Under diagnosis of neuropathy • Fundamental problem in primary care. • Impedes early identification, management & prevention of squeals .

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• Occur in presence of: peripheral sensory neuropathy, autonomic neuropathy and trauma.

• Presentation: painless, unilateral oedema, erythema, with or without foot deformity, bounding pedal pulses. Post tib dysfunction in later stages.

Photo used with permission from Dr.Axel Rohrmann, Podiatrist.

CHARCOT FOOT Diabetic Neuropathic Osteoarthropathy • Occur in presence of peripheral sensory neuropathy, autonomic neuropathy & trauma. • Presentation: painless, unilateral edema, erythema, with or without foot deformity, bounding pedal pulses. Post tibial dysfunction in later stages. • Note: – Acute charcot can mimic cellulitis & DVT – Radiological findings can be normal at first – Strict immobilization of foot for management – Patient education, protective footwear to prevent ulcerations

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Risk Factors for Ulceration Calluses • Presence of callus in an insensitive foot is highly predictive of subsequent foot ulceration. • Breakdown of underlying tissues • Regular debridement • Pressure relief : insoles / moulded orthotics • Footwear Calluses increase pressure on underlying tissue by 30%

Photo used with permission from Axel Rohrmann, Podiatrist.

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Risk Factors for Ulceration

Limited Joint Mobility – Hallux rigidus – Hallux limitus – Hammer toes – Claw toes Limited joint mobility can cause increased ground reaction forces under weight‐bearing joints. This can lead to ulceration.

Photo used with permission from Dr. Axel Rohrmann, Podiatrist.

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Risk Factors for Ulceration

Previous Ulceration & Amputation •Skin texture •Scar tissue reduced tensile strength. • Pressure points

Prevalence of Ulcers

• Up to 25 percent of those with diabetes will experience an ulcer or wound at some point.

• Amputation rates can be reduced by 45 to 85 percent with a comprehensive foot care program.

• Without proper treatment, ulcers can quickly escalate into amputation.

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Early Detection is Key

• A simple foot exam can reveal the first signs and symptoms of diabetes, and identify more serious complications that could potentially lead to lower‐limb amputations.

Multi‐Specialty Care

• Primary Care/Internal Medicine • Endocrinology • Podiatry • Opthamology • Vascular Surgery • Nutritionist

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Podiatry Savings

• Limbs • Cost • Quality of life

DIABETIC FOOT HEALTH

• Up to 25%of those with DIABETES will develop a FOOT ULCER • COST OF DIABETES IN THE US $245B • Estimated annual U.S. burden of diabetic foot ulcers is at least $15 BILLION

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INVESTMENT IN CARE

• $1 invested in care by a podiatrist results in $27 to $51 of savings for the health‐care system, • $1 invested in care by a podiatrist results in $9 to $13 of savings, among Medicare eligible patients.

How to Examine?!

• The three minute diabetic foot exam

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Three Minute Exam

• What to ask – H/O previous ulcer or amputation? – Vascular intervention (stents, angioplasty, bypass) – Wounds >3wks to heal? Unexplained foot blisters? – Smoking/nicotine useage

– Do you have a Foot doctor??

Three Minute Exam What to check for • Dermatological – Dystropic toenails? Ingrown? – Corns/calluses/fissured heels? – Between the toes? – Skin color changes • Neurological – Light touch sensation – Semmes weinstein 5.07/10g monofilament

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Three Minute Exam What to check for • Vascular – Hair growth? – Temperature gradient proximal to distal – Foot pulses – CFT

• Muscularskeletal – Hammertoes (reducible vs not) – Equinus – Midfoot arthritis

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Three Minute Exam What to tell the patient • Check feet nightly (mirror or family member) • Dry feet throughly • Report any new changes to feet • NO barefoot walking • Replace shoes Yearly and inserts every 4 months • QUIT SMOKING

• The 5 most dangerous words to a diabetic – “Maybe this will go away”

Mapping a Treatment and Follow‐up Plan

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For More…

• Visit www.apma.org to “Find a Podiatrist”

• Visit www.apma.org/diabetes for more diabetes information

• Visit www.Foothealthfacts.org for common foot and ankle pathology

Questions?

Hormone Therapy Past, Present, Futureh

Terry Mark Gibbs, D.O.

Learning Objectives:

Recognize guidelines for hormone therapy use. Evaluate starting hormone therapy.

11/9/2016

HORMONE THERAPY: PAST, PRESENT, FUTURE

Terry Gibbs DO,NCMP Sandusky 2016

HISTORY OF ESTROGEN

 Early 1900’s- Women drink solutions of animal ovaries to treat menopause symptoms

 Mid 1930’s -Drug companies produce estrogen injections and pills from animal placentas and fetal fluid to relieve symptoms of menopause

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HISTORY OF ESTROGEN CONT.

 1941-1942-Ayerest produces Premarin estrogen produced from urine of pregnant mares

 1951- Sex researcher William Masters re-commends hormone therapy to rejuvenate mental and physical function

HISTORY OF ESTROGEN CONT.

 1953- Mayo Clinic Scientists postulate that estrogen is cardio- protective (Autopsies show women with ovaries removed suffered more advance atherosclerosis than women with ovaries)

 1950s- concerned by animal studies suggesting estrogen is carcinogenic, physicians only prescribed estrogen primarily for short-term relief

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HISTORY OF ESTROGEN CONT.

 1966- Gynecologist, Robert Wilson writes Feminine Forever, promotes estrogen use through a drug company sponsored foundation.

HISTORY OF ESTROGEN CONT.

 1975- Studies show a link between estrogen and endometrial cancer

 1979- Ten year study finds estrogen taken within 3 years of menopause onset reverses bone loss

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HISTORY OF ESTROGEN CONT.

 1984- FDA and NIH sanction estrogen as the most effective drug to prevent osteoporosis  1985- Nurses Health Study, concludes estrogen users have lower risk of heart disease  1985- but… the Framingham Study finds the opposite

HISTORY OF ESTROGEN CONT.

 1991- More than twenty small studies estimate that HT halves heart disease in menopausal women.

 1992- The American College of Physicians recommends HT to all women to prevent cardiovascular disease and osteoporosis

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HISTORY OF ESTROGEN CONT.

 1994- First randomized controlled clinical trial (RCT) of combined HT, shows better cholesterol scores for women taking HT

 1998- Four-Year Heart and Estrogen/ Progesterone Replacement Study finds HT does not reduce heart attacks in women whom already have heart disease

HISTORY OF ESTROGEN CONT.

 2002- Estrogen/Progesterone arm of the 27,000 subject Women’s Health Initiative Study (WHI) is halted three years early when it substantiates increased risk of breast cancer, heart attacks, strokes and blood clots

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HISTORY OF ESTROGEN CONT.

 2004- Estrogen, (Premarin) arm of the WHI study is ended a year ahead of schedule because estrogen alone offered no cardio-protective benefit but increased the risk of blood clots and stroke

WOMEN’S HEALTH INITIATIVE (WHI), AGES 50-79 HORMONE PROGRAM DESIGN

Women who had YES Conjugated equine no uterus at N= 10,739 estrogen (CEE) 0.625 mg/d start of study Placebo

Hysterectomy CEE 0.625 mg/d + medroxyprogesterone Women who had acetate (MPA) 2.5 mg/d a uterus at NO start of study N= 16,608 Placebo

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WHI Estrogen+Progestin Trial Findings, July 2002 ( N=16,608; mean age 63 yrs; mean follow-up 5.2 yrs)

Risks Benefits

Coronary Heart Disease  29%  Hip Fracture 34%  Stroke 41%  Colorectal Cancer 34% Pulmonary Embolism 113%  Breast Cancer 26% 

Threshold Level STOPPED Early, Clear Harm Dementia 105% (age 65+) Stopped 3.3 years early

Adapted from: Writing Group for the Women’s Health Initiative. JAMA 2002;288:321.

WHI Estrogen-Alone and Health Outcomes (N=10,739; mean age 63.6 yrs; mean follow-up 6.8 yrs)

Risks Null Benefits CHD (0.91) Pulm Emb (1.34) Breast Cancer (0.77) Colorectal Cancer (1.08) Total Mortality (1.04) Stroke 39%  Global Index (1.01) Hip Fracture 39% 

STOPPED Early Threshold Level

Dementia 49% (age 65+) Stopped 1 year early

Source: JAMA 2004; 291:1701.

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Key Differences Between the WHI and Observational Studies of Hormone Therapy (HT)

Observational WHI Studies

Age at HT initiation (mean) 63 yrs 52 yrs

Time since menopause (mean) >12 yrs 1-3 yrs

Vasomotor symptoms Generally – Generally +

BMI (kg/m2, mean) 28-30 24-25

Estrogen+Progestin Therapy and Risk of CHD in WHI: Results According to Age and Time Since Menopause

Time since Age RR Menopause Onset RR 50-59 1.27 <10 yrs 0.89 60-69 1.05 10-19 yrs 1.22 70-79 1.44 >20 yrs 1.71* P, interaction 0.4 P, interaction 0.036†

* P-value <0.05 † meta-regression analysis (0.33 as continuous variable)

Source: Manson JE, et al. NEJM 2003.

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Women’s Health Initiative Estrogen-Alone Trial: Detailed CHD Results According to Age at Randomization

RR (95% CI) by Age Group at Baseline

Outcome 50-59 60-69 70-79 MI or CHD Death 0.63 0.94 1.11 (N=418) (0.36-1.08) (0.71-1.24) (0.82-1.52) CABG or PCI 0.55 0.99 1.04 (N=529) (0.35-0.86) (0.78-1.27) (0.78-1.39) Composite MI/CABG/PCI 0.66 1.02 1.08 (N=728) (0.44-0.97) (0.83-1.25) (0.85-1.38)

CEE = conjugated equine estrogens. MI = myocardial infarction. CABG = coronary artery bypass grafting. PCI = percutaneous coronary intervention

Source: J Hsia, R Langer, J Manson, et al. Arch Intern Med 2006.

Absolute Excess Risks (cases per 10,000 pys) by Age in the Combined Trials (E+P and E-Alone) of the WHI

Outcome Age (years)

50-59 60-69 70-79 CHD -2 -1 +18* Stroke +2 +14* +15* Total mortality -10* -4 +14 Global index† -4 +12 +44*

* P <0.05 † Global index is a composite outcome of CHD, stroke, pul embolism, breast ca, colorectal ca, endometrial ca, hip fracture and mortality

Source: Rossouw JE, Prentice RL, Manson JE, et al. JAMA 2007.

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Timing of Hormone Therapy Initiation in Relation to Stage of Atherosclerosis: Observational Studies vs Clinical Trials

Premenopausal Years Postmenopausal Years

Years Since Menopause Onset 5101520

Observational Studies Clinical Trials (1° and 2° Prevention)

Progression of Cardiovascular Disease Fatty streaksFatty plaques Atherosclerotic plaques Plaques grow and may rupture

Favorable Lipid and Prothrombotic and Endothelial Effects of Proinflammatory Effects of Estrogen Predominate Estrogen Predominate (plaque rupture, thrombo-occlusion) Favorable Influence Adverse Influence of Initiating of Initiating From: J Manson, et al. Menopause 2006. Exogenous Estrogens Exogenous Estrogens

Relative Risk of Breast Cancer with E+P and E-Alone in the WHI, Stratified by Age Group

Relative Risk by Age Group at Baseline

50-59 60-69 70-79

E+P 1.20 1.22 1.34 E-Alone 0.72 0.72 0.94

Source: Chlebowski R, et al. JAMA 2003. WHI Investigators. JAMA 2004.

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The statement was published in the journals of The North American Menopause Society (Menopause), the American Society for Reproductive Medicine (Fertility and Sterility), and The Endocrine Society (Journal of Clinical Endocrinology and Metabolism)

ENDORSING ORGANIZATIONS  Academy of Women’s Health  American Academy of Physician Assistants  American Academy of Family Physicians  American Association of Clinical Endocrinologists  American Medical Women’s Association  Asociación Mexicana para el Estudio del Climaterio  Association of Reproductive Health Professionals  National Association of Nurse Practitioners in Women’s Health  National Osteoporosis Foundation  Society for the Study of Reproduction  Society of Obstetricians & Gynaecologists of Canada  SIGMA Canadian Menopause Society

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DURATION OF USE

 With EPT, increased risk of breast cancer incidence and mortality with 3-5 years of use  With ET, no increase of breast cancer with early postmenopausal use; decrease found after hiatus in estrogen exposure  With ET, potential CAD and CHD benefits with early use  Initial increase in CHD risk when EPT is initiated further from menopause(cont’d)

NAMS position statement. Menopause 2012.

DURATION OF USE (CONT’D)

 Extending EPT use is acceptable for:

Women who request it and are well aware of potential risks and benefits

Prevention of further osteoporosis- related fracture and bone loss when alternate therapies are not appropriate or cause unacceptable adverse effects

NAMS position statement. Menopause 2012.

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DISCONTINUATION

 After 3 years of EPT discontinuation: . Rate of cardiovascular events, fractures, and colon cancer same as placebo group . Increase in rate of all cancers and mortality from breast cancer  After 3 years of ET discontinuation:

. No increase in CHD, DVT, stroke, hip fracture, colorectal cancer, or total mortality

. Decrease in breast cancer persisted

(cont’d)

DISCONTINUATION (CONT’D)

 HRs for all-cause mortality neutral for both

 50% chance of vasomotor symptoms recurring when HT discontinued

 Symptom recurrence similar whether tapered or abruptly discontinued

 Decision to continue HT should be individualized

NAMS position statement. Menopause 2012.

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 Hormone therapy still has a role in treating moderate-to-severe menopausal symptoms but shouldn’t be used for chronic disease prevention. Risk stratification (based on time since menopause and underlying risk factors) can be helpful in identifying appropriate candidates for hormone therapy.

SUMMARY

15 Colorectal Cancer: Hitting Your Screening Target

Constance P. Cashen, D.O., FACOS, FACS

Learning Objectives:

Discuss current statistics about colorectal cancer in the US. Recognize what the American Cancer Society’s “80% by 2018 Colorectal Cancer Screening Campaign” is about. Identify what screening tests will meet the CMS screening guidelines.

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Colorectal cancer: Hitting your Screening Target! CONSTANCE CASHEN D.O. FACOS FACS NOVEMBER 11, 2016

Objectives:

 1. Understand the current statistics about colorectal cancer in the United States.  2. Know what the American Cancer Society’s “80% by 2018 Colorectal Screening Campaign” is about.

 3. Know what screening tests will meet quality performance guidelines.

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CRC Stats

*A COMMON and LETHAL CANCER:

• 2nd most common ca in women, 3rd in men • Lifetime incidence in the US is 4.5%

** The SECOND MOST COMMON CAUSE OF CANCER DEATH in the US

***1 in 3 people diagnosed with CRC will die***

Screening can decrease deaths by finding cancer early

 Early diagnosis can save lives:  Localized disease (confined to colon wall) means 5 yr treatment survival is 90%  Regional disease (lymph nodes positive) means 5 yr treatment survival is 68%  Distant metastases at diagnosis means 5 yr treatment survival is sadly only 10%

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But better yet - Screening can actually prevent CRC in the 1st place

 The Polyp – Cancer connection  Focal hyper-proliferation of colorectal epithelial cells forms adenomas also called adenomatous polyps

 Over 7 – 10 yrs adenomatous polyps can progress to cancer  But although 50 – 65% of polyps will be adenomas, the good news is that less than 5% of them will advance to malignancy  In addition to the common pedunculated adenomatous polyp we all know there is also a more flat “sessile serrated adenoma” which occurs more often in the proximal colon and carries similar potential for cancer

 Both types when removed will prevent CRC

Screening impact

 Since the mid-1980’s the incidence of CRC has steeply dropped from 80/100,000 men and 55/100,000 women to 45/100,000 men and 35/100,000 women  This is attributed largely to colonoscopic polypectomy

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Screening methods – are thought of as falling into 2 categories

Structural tests that find both polyps and cancer Colonoscopy, Flexible sigmoidoscopy, DCBE, CT Colonography

Stool tests that primarily detect cancer Fecal Occult Blood Testing(FOBT), Fecal Immunochemical Test (FIT), Stool DNA test (Cologuard)

Though Colonoscopy is the gold standard, the rest have value

 Flexible sigmoidoscopy  Examines the rectum, sigmoid and descending colon

 Less bowel prep  Deep sedation usually not used so some may have discomfort  Risk of perforation <1 / 20,000

 If adenoma is found then colonoscopy is required  A large study in the UK showed that compared to no screening there was a 23% decrease in incidence and a 31% decrease in mortality from CRC with FS (followed by c-scope if polyp found and obviously detected polyps were removed)

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What’s the risk of not evaluating the rest of the colon?

 2 large studies done in 2000 showed 30/2000 people screened (a single company) and 80/3122 VA patients screened who had negative flex sigs were later found to have advanced proximal neoplasia when they developed symptoms  Based on these studies apprx 1.5 – 2.5% of patients screened with flexible sigmoidoscopy will have a proximal cancer or premalignant polyp that progresses to cancer that will be missed

Hence Colonoscopy is the most commonly used screening test in the US

 The entire colon is examined and any polyps or lesions can be biopsied or removed  However it does require a good bowel prep which can be inconvenient and uncomfortable, and requires sedation so a workday for the pt and a chaperone is lost

 Overall complications are 2.8 in 1000 scopes  Perforation is 1/1000 scopes overall with more occurring in the elderly and those with diverticulosis – 1/500 Medicare pts  Post polypectomy bleeding is .2%

 $2500-3000 cost

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Colonoscopy

 Anesthesia risks – either conscious sedation (ie Versed and fentanyl) or MAC (monitored anesthesia care typically using propafol) include cardiac arrhythmias, hypotension, and O2 desaturation in 5.4 of 1000 scopes (.5%)  Missing polyps can occur based on size:

 2% miss for polyps> 10mm  13% miss for polyps 5-10 mm  26% miss for polyps <5mm

 The golden rule of colonoscopy is that you should spend a minimum of 6 minutes withdrawing the scope to see the colon thoroughly

Surveillance Interval if polyp(s) found

 No polyp 10 yrs  Small hyperplastic polyps 10 yrs

 1-2 small <10mm tubular adenoma polyps 5-10 yrs  3-10 small aden polyps, tubular adenoma>10mm 3yrs  Villous adenoma or high grade dysplasia 3yrs

 Sessile serrated polyp <10mm & no dysplasia 5yrs  SSP >10mm or dysplasia or traditional type 3yrs  Serrated polyposis syndrome 1yr

 The doc performing the colonoscopy should indicate when the next c-scope is due in the colonoscopy report.

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Imaging alternatives if patient declines a scope for screening

 DCBE – Double Contrast Barium Enema (barium and air)  Still requires a bowel prep though no sedation required

 Like flex sigmoidoscopy, if a polyp is found (unless<6mm), then colonoscopy will be needed (which means another prep)  Sensitivity for CRC is 85 – 97%. Frequency – every 5 yrs

 CT Colonography – Multiple CT images are used to reconstruct 2D and 3D images of the colon, no sedation required

 Sensitivity for polyps>5mm is good at 90-94%, specificity 80-95%  Requires bowel prep and oral contrast and any polyps>5mm require colonoscopy. Frequency – every 5 yrs

Alternatives to tests requiring bowel prep– Stool analysis tests

 FOBT – Fecal Occult Blood Test

 FIT – Fecal Immunochemical Test

 Fecal DNA Test - Cologuard

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FOBT

 Oldest screening test, several versions – works by detecting blood in stool using the pseudoperoxidase activity of heme in hemoglobin  Recommend use Hemoccult SENSA

 Advantages: cheap, long track record, no bowel prep  Sensitivity= 80-85% Specificity= 88% (for older Hemoccult tests, the specificity is higher-98%, but the sensitivity is only 40%)  Disadvantages: need to sample 3 stools (not random rectal exam in office), variability in interpretation (“is it really blue?”), need to avoid ASA/NSAIDs x 1wk and red meat & High Vit C 3 days (some research shows only Vit C an issue due false neg results)

 Any + needs C-scope follow up

Fecal immunochemical test- FIT

 Works by detecting human globin not the heme component of blood and since any globin from the UGI is digested, only bleeding from the colon will be detected  Advantages: no drug or diet restrictions, only 1 sample, automated interpretation vs a visual judgement

 Sensitivity: 80% (for ca, ½ for polyps), specificity=90-95%  Disadvantages: need to mail it on time, more expensive ($30 vs 10)  + result mandates C-scope

 This is the most common strategy used by large companies

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Fecal DNA test

 Detects DNA (KRAS) mutations and methylation biomarkers as well as an immunochemical test for blood (similar to FIT)  Advantages: requires only 1 stool, no prep or restrictions, only needs to be done every 3 yrs vs annual for FOBT/FIT, covered by Medicare

 Sensitivity=92% Specificity=87%  Disadvantages: need to collect an entire stool, cost ($600 in 2014)  + test mandates C-scope but some question what it means if scope is negative (does a neg scope mean next screen in 10yrs?)

Other tests that may become options for screening

 Blood-based markers  Look for DNA specific for CRC (ie Septin 9 study)

 At best have a sensitivity=75% and specificity=85%  The higher the stage of CRC, the better the s/s so for Stage I CRC the s/s was only about 65/65% - not a good option for early detection or finding polyps

 Colon capsule endoscopy – approved by the FDA but not in use yet  About the size of a vitamin pill, 2 cams, takes 10 hrs of pics, 35/sec  Sensitivity=85% for polyps, Specificity=65-95% (lesion size)  Requires more bowel prep than colonoscopy

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Current Screening Guidelines

 USPSTF 2016:  Emphasizes the need for ANY screening strategy (vs none) for all average risk adults age 50 – 75 (Grade A evidence) and to screen selectively for age 75 – 85 (Grade C evidence of benefit)

 Did not recommend one strategy over another since data demonstrating superior risk/benefit ratio of any specific strategy is lacking  The guideline supports the following: Colonoscopy q10, annual FIT + Flex sigmoidoscopy q10, CT colonography q5, Flex sig alone q5, Fecal DNA q3, FOBT or FIT q1

So what should I recommend to patients?

 Start with the 2008 American Cancer Society guidelines (same as US Multi-Society Task Force on CRC and Am Coll of Radiology)  They distinguish “tests that find cancers and polyps” from “tests that find mostly cancers”

 Start at age 50 unless in a higher risk group* then start at age 40  * a Fhx of CRC/polyps in any 1st degree relative <60y/o or two 1st relatives >60  Since there is no “best test”, offer pts multiple screening options and let them choose – however most common practice shows……

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Tests that find cancer and polyps

 Flexible sigmoidoscopy  Every 5 yrs  Colonoscopy  Every 10 yrs

 DCBE  Every 5 yrs

 CT Colonography  Every 5 yrs

Tests that mainly find cancer

 Fecal Occult Blood Testing  Every year  Fecal Immunochemical  Every year

Test (FIT)  Every 3 yrs  Stool DNA test

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Higher risk groups rec colonoscopy

 With a positive family history - recommend colonoscopy as the best screening strategy and start per the ACS guidelines and then follow the recommended interval indicated by the physician performing the study  If a patient is at higher risk because of a personal hx of polyps, CRC, or IBD, strongly recommend that they have colonoscopy and then follow as above

 If they have multiple family members with cancer including CRC, suspect a genetic syndrome and strongly recommend colonoscopy as the preferred screening method

Remember to Document

 Ideally document that your patient has been informed of the importance of screening and that there are options  Maintain good follow up on screening intervals

 Document if your patient declines to be screened (though the quality parameter police don’t care about this!)  Nonetheless, encourage patients to get screened – by any method – and tell them about the American Cancer Society’s initiative: “80% by 2018” CRC screening goal which will save thousands of Americans from death due to CRC (>140 organizations have joined with the ACS to promote this since 2014)

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“80% by 2018” – 5 things the PCP can do – rec’s from the ACS

 1. Understand the power of the physician recommendation. Surveys show that 90% of pts who were recommended by their physician to get screened, did vs 17% who reported never getting a provider rec

 2. Measure the CRC screening rate in your office/clinic (tools at cancer.org/colonmd)

 3. Use evidence-based practices like EHR alert systems and staff alerts to identify those needing screening.  4. Understand screening options and actively promote Colonoscopy, FOBT and FIT (with f/u c-scope if FOBT/FIT positive).

 5. Make sure that patients and staff know that most insurance companies are required to cover CRC screening.

And finally remember: YOU CAN MAKE THE DIFFERENCE!

13 Ohio’s Opioid Guidelines, Laws and Rules: Protecting the Patient and the Prescriber

Cleanne Cass, D.O.

Learning Objectives:

Define the difference between guidelines, rules and laws and how each impacts opioid prescribing practices. Describe the origin of Ohio’s opioid epidemic and the prescriber’s role in combating it. Describe the opioid guidelines, rules and laws currently in place that affect the practice of medicine in Ohio.

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Ohio’s Opioid Guidelines, Laws and Rules: Protecting the Patient and the Prescriber

Northwest Ohio Osteopathic Association 16th Annual Primary Care Update Sandusky, Ohio November 11, 2016

Today’s Discussion

• Understand the differences between guidelines, rules and laws and how each impacts prescribing practices

• Describe the origins of the opioid epidemic and the prescriber’s role in combating it

• Describe opioid guidelines, laws and rules currently in place in Ohio and how to utilize them for successful pain management in your practice

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Conundrum for Physicians: “Twin Serpents in the Caduceus” To assure that we relieve the pain of our …...never allow our patients, medications to fall but…… into the hands of those they may harm

The Physician’s Dilemma:

“Twin serpents in the Caduceus” •Undertreated Pain and related costs: ‐ Nationally 100 million Americans with chronic pain at a cost of >635 billion dollars IOM Report on Pain ‐ 2011 •Opioid Abuse and related costs ‐ Nationally > 6 million Americans abusing opioids at a cost of 70 billion per year

Money Magazine August, 2009 4

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Institute of Medicine Report – June, 2011:

• Treating pain is a moral imperative • Increase research/ education on pain

• Biopsychosocial model of pain management improves outcomes

• Transformation in our cultural view of pain is needed 5

Chronic Pain –the new 4 letter word

• Cancer pain: validated ‐ relief is an expectation

• Chronic nonmalignant Pain – societal disapproval, treatment hard to find

• Patients with chronic pain and their prescribers are marginalized and even criminalized!!

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Chronic Pain

• Chronic pain ‐ the price tag for a lifetime of active living?

• Chronic pain ‐ the price of being an athlete?

• Chronic pain can be the result of the activities we love : jogging, boating, skiing

• 80 % of patients presenting for care report pain as a reason for seeking medical care

• Undertreated and improperly treated acute pain can transition to chronic pain : complex regional pain syndromes

• Undertreated pain in the elderly is a risk factor for alcohol abuse, deconditioning, and institutionalization

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Who has Chronic Pain?

• Patients with chronic degenerative conditions: COPD, HF, CKD • Patients with musculoskeletal disorders‐ osteoporosis, osteoarthritis, chronic inflammatory conditions • Traumatic injury survivors • Patients with neuoromuscular disorders: MS, Huntington’s chorea, ALS, post Stroke patients • Occupational injury and overuse syndromes • Chronic visceral syndromes: Crohn’s disease, chronic pancreatitis, et al.

Clinical Imperatives

To believe the pain of our real patients : All patients presenting with pain deserve adequate evaluation and treatment based on careful consideration of the risks and benefits Scott Fishman, Responsible Opioid Prescribing 2nd edition , 2014, p37

• To become better pain managers and treat pain in manner that is safe and effective for the patient • To understand and implement Ohio’s regulatory oversight in order to protect our prescriptive rights

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Origins of the opioid epidemic

Aggressive Changes in Marketing of Clinical Pain Opioids Management

Direct‐to‐ Growing Use of Customer Prescriptive Marketing Opioids

Diversion *Internet Self‐Medicating Epidemic *Pill Mills Habits of Baby *Deception/Scams Boomers *Theft *Friends and family

Origins of the Opioid Epidemic in Ohio

• Pockets of socioeconomic deprivation ‐ concentrated in southeastern Ohio

• Genetic predisposition to opioid addiction follows same incidence as predisposition to alchohol addiction : one out of every ten opioid naïve patients given an opioid is at risk of addiction‐ high incidence of oxycodone addiction in southeast Ohio among family groups – genetic predisposition??

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Origins of the Opioid Epidemic

• “It is unclear how much abuse, diversion and addiction is the result of well meaning but under‐educated or under‐informed physicians.” Scott Fishman, Responsible Opioid Prescribing 2nd Edition, 2014, p 39

The Opioid Epidemic

• The number of deaths nationwide attributable to prescription opioid analgesics quadrupled between 1999 and 2007

• Opioid overdose is the the second leading cause of accidental death in America , exceeded only by vehicular death; in 17 states opioid overdose is the leading cause of accidental death

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Ohio and U.S. Unintentional Drug Overdose Death Rates per 100,000 Population 1999‐2006 U.S. /1999‐2008 Ohio

Number of Deaths from Motor Vehicle Traffic, Suicide and Unintentional Drug Poisonings by Year in Ohio 1999 – 2008

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Unintentional Drug/Medication Poisoning Death Rates per 100,000 by County 2004 – 2008

Response to the Epidemic: Guidelines for Pain Management ‐ State and Federal

• Developed by consensus agreement of panels of appointed experts and stakeholders • Reviewed, adapted and approved by provider organizations: OOA, OSMA, OAFP, OBP, etc • Are only guidelines – not rules or laws: “shoulds” and not “shalls” • Usually considered to constitute standard of care and therefore can be important in litigation • Insurers may use to determine payment

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Laws

• Bills are sponsored by legislators and introduced into the senate or house of representatives • Generally referred to committee in both houses require public hearings and if passed must be signed by the governor • When enacted they become the law of the land • A provision of the bill will direct an agency such as ODH or OSMB to develop the rules of the law

Rules • Laws direct an agency or bureau to develop rules – laws are a skeleton and the rules are the muscle • The agency or bureau may convene a panel of experts or use its own standing boards to develop rules • Public hearings and comments may provide opinion • Once developed and approved the rules become part of the Ohio Revised Code

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Federal Guidelines

• National Pain Strategy– 2011, developed by the Institute of Medicine and National Institutes of Health ‐ validated the need to address pain in America

• CDC Guidelines for Managing Chronic Pain – 2011 – national response to the opioid epidemic, endorsed findings in the strategy and recommended treatment, education, research

• CDC Guidelines for Managing Chronic Pain, March, 2016‐sharp departure from earlier guidelines‐ not felt to be evidenced based and widely criticized by the American Academy of Pain Management and others www.cdc.gov

With the exception of the DEA, the federal government leaves regulation of opioid prescribing to the states and national guidelines are meant to be educational and guideposts

Numerous other guidelines: Federation of State Medical Boards, American Pain Society, etc

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Ohio’s Automated Rx Reporting System – Prescription Monitoring System

Ohio Revised Code – 4729.75‐4729.84 Effective January 1, 2006, expanded regulations HB 93, HB 341 ( effective April 1, 2015)

• Tool for prescribers, pharmacists to identify and prevent abuse and addiction

• Tool for law enforcement to deter diversion

• Pharmacists must enter data electronically daily

• Reported drugs: schedule CII, CIII, CIV ,V, Carisoprodol (Soma)& Tramadol ( Ultram) effective December 1, 2016 ‐ Gabapentin 23

Ohio’s Automated Rx Reporting System – Prescription Monitoring System

• HB 93 Mandated that all licensing boards must establish rules governing the use of OARxRS by their licensees – OSMB, OSBP, etc

• HB 341 Mandated that all prescribers must attest that they are registered with OARxRS in order to get their licenses renewed

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OARxRS

In 2011 : Ohio Population approximately 11million Scripts in OARRS:46.9 million #of patients in OARRS: 5.7 million

Time to get report: 98% within 23 seconds 5% 5mins ‐3hrs reports available 24/7 Lag time of 1‐3 days from dispensing of medication until report available

Provided Courtesy of the National Association of Boards of Pharmacy®.

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OARxRS

Who can access OARRS?

• Pharmacist – own customer only

• Physician – current patient only

• Physician’s non licensed designees (HB93)

• Individual – own report

• Licensing boards – own licensee

• Law enforcement ‐ only as part of a certified active investigation of suspected diversion, abuse or drug trafficking

OARxRS

• The report is privileged health information (HIPPA), not a public record, not evidence

• You may not share the information with other professionals unless they use same chart

• You may show the patient the data but not give it out

• You must keep report in non reproducible part of chart

• You may not use OARRS to screen employees or potential employees

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OARxRS –How often must you access?

• Before prescribing/dispensing the 1st dose of an opioid to a patient

• Every 90 days that you continue to prescribe/dispense opioids for that patient • Access the data from states adjoining the counties in which you practice

• Every time there is a “RED FLAG” event Red Flag events??

Document in the chart every time you access OARxRS

OARxRS

When must you enter data: • If you dispense a reported drug from your office • Do not need to report injections • Do not need to report if the patient is exempted ( hospice patients and cancer related pain)

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OARxRS

Exemptions‐ when do you not have to access OARxRS • Scripts for less than 7 days supply • Patients who are on hospice • Patients in nursing homes, residential care facilities, hospitalized patients • Cancer pain or pain related to cancer • Before prescribing Gabapentin products

Signing up for OARxRS

Google OARxRS Home page – “Register” ‐ registration takes about 15 minutes

More information – Questions??

614‐466‐4131 option 1 oarrsadmin@ohiopmp./gov

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Ohio’s Chronic Pain Law‐ 1998 ( originally the Intractable Pain Law)

• Provides a definition of “chronic pain”

• Requires that the State Medical Board adopt rules establishing standards to be followed by physicians in the diagnosis and treatment of chronic pain‐ complete text of the rules can be found at : http://med.ohio.gov/rules/4731‐21.htm

• Allows a physician to treat chronic pain with appropriate amounts or combinations of drugs

• Mandates consultation prior to making a diagnosis of intractable pain • Outlines required medical documentation

OSMB rules regarding documentation

• History and physical examination • The diagnosis of chronic pain, including signs, symptoms, and causes • The plan of treatment, the patient's response to treatment, and any modification to plan of treatment • The patient’s name and address, the amounts and dosage forms of the drugs, the dates, on which drugs were prescribed, furnished, or administered • A copy of the report made by the physician or the physician to whom referral for evaluation was made under this division.

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Chronic Pain Law/ OSMB Rules

ORC 4731.052 (D) Addresses fear of regulatory scrutiny:

“A physician who treats chronic pain by managing it with dangerous drugs is not subject to disciplinary action by the board under section 4731.22 of the Revised Code solely because the physician treated the intractable pain with dangerous drugs. The physician is subject to disciplinary action only if the dangerous drugs are not prescribed, furnished, or administered in accordance with this section and the rules adopted under it.”

Ohio’s Opioid Laws

Ohio’s 130th General Assembly, 2013‐2014 there were 17or more opioid bills introduced – most died in committee!

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Sub HB 341 ‐ Chronic Pain: Definition of “12 weeks” defines criteria for checking OARxRS

Sub. HB 341: Requires that a prescriber before prescribing or personally furnishing an opioid analgesic or benzodiazepine request patient information from OARRS, and if the treatment continues for more than 90 days requires the prescriber to access information in OARRS at intervals not > 90 days Effective April 15, 2015

HB 170 ‐ Naloxone

• HB 170 Allows certain licensed professionals to prescribe, administer, dispense or furnish naloxone to patients at risk of overdose or to friends or family of those at risk

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Ohio’s Opioid Laws

• Sub HB 314 Minor Prescriptions‐ requires prescribers to obtain written consent before prescribing a controlled substance to a minor – Effective September 17, 2014 ‐ certain exceptions apply including safety concerns for the youth if parents are aware of the opioid prescription

Ohio’s Opioid Prescribing Guidelines

• Developed by the Governor’s Cabinet Opioid Action Team – 2012‐2015 (GCOAT) • Census project of over 30 stakeholders • Commissioned by Governor Kasich, October, 2011 • “A seat at the table” –the Ohio Osteopathic Association ‐ Jon Wills, Executive Director

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“If you’re not at the table, you’re! on the menu”

‐

Ohio Emergency and Acute Care Facility Prescribing Guidelines: OOCS (opioids and other controlled substances) Prior to deciding whether to treat with an OOCS, ED clinician: _ must access OARRS – Check a photo ID or photograph patient – may perform a drug screen • ED should consider contacting the patient’s regular physician s

• Request a Palliative Care or pain consult, or subspecialty service

• Perform case management on patients repeatedly seen in ED

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Ohio Emergency and Acute Care Facility Prescribing Guidelines:

• Request medical and prescription records

• Require that the patient sign a pain agreement outlining expectations of the ED department regarding pain management

• Use EMR to communicate with other providers about patient

• Limit the Rx of OOCS to a 3 day supply

Ohio Emergency and Acute Care Facility Prescribing Guidelines:

• Discharge instructions with information on addiction risk, dangers of misuse, appropriate storage/disposal of unused meds • Facilities should maintain a list of clinics that provide primary care services and pain management

• ED and other facilities should display signage of these prescribing guidelines and statement of facility position on prescribing of opioids and other controlled substances

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Guidelines for Prescribing Opioids for the Treatment of Chronic, Non-Terminal Pain 80 mg of a Morphine Equivalent Daily Dose (MED) “Trigger Point” Protocol

• Pertains to patients receiving opioids equal to or greater than 80mg MED daily for > 90 days

• Considered to be a “Press Pause “ point to reconsider the patient’s treatment plan and whether as a prescriber you are fully compliant with the accepted and prevailing standards of care

80MED Daily Dose

This is the equivalent of about: 16 Vicodin per day PO 10 oxycodone IR ( Percocet) per day Oxycontin 30 mg 2day PO Fentanyl Patch 37mc/hr topical patches Methadone ??? 15mg /day??

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The Guidelines Tool kit

1. Re‐establish Informed consent, provide the patient with written information on the adverse effects of long‐term opioid therapy

2. Review the patient’s functional status and documentation, including the “4A’s” of chronic pain treatment‐ activities of daily living,

3. Review the patient’s progress toward treatment objectives

4. Check the OARRS report again

4 “A”s of Chronic Pain Treatment

1. Activities of Daily Living ‐ Oswestry low back pain questionaire 2. Analgesia 3. Adverse affects 4. Abberant behaviors : SBIRT, CAGE‐AID, Opioid Risk Tool

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Press Pause at 80MED daily dose

• Consider updating the patients pain treatment agreement : consider more frequent office visits, different treatment options, use of one pharmacy, a drug screen, consequences of non compliance with the terms of the agreement‐ be sure patient is being carefully monitored

• Consider a specialty consult

• Document the performance of a “press pause “ review at the 80MED trigger point

80 MED Daily Dose

Review the patients problem list and med sheet: • COPD?, Heart disease? renal insufficiency?? • Other sedating/ hypnotic drugs – almost all opioid prescription overdoses involve multiple substances!!! • Risky life style behaviors – alcohol use, recreational drugs, marijuana, OTC meds

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Ohio’s Guidelines for Management of Acute Pain Outside the ED‐ January, 2016

1 Assessment of the pain to identify its etiology, determine whether the pain is of somatic, visceral or neuropathic origin based on the patients description of the pain, your examination and diagnostic work up

Acute Pain Guidelines

2.Develop a Plan: • Measureable goals for the reduction of the pain • Use of both non‐pharmacologic and pharmacologic therapies with a clear therapeutic path • Mutually understood expectations for the degree and duration of the pain during therapy • Goal: return to function at baseline rather than complete resolution of pain

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Treatment of Acute Pain

3. Utilize non –Pharmacologic Treatment: ice heat, bracing, splints, directed exercise, massage therapy, acupuncture, Osteopathic neuromuscular care

3. Non –opioid pharmacologic treatment: Acetomeminophen, NSAIDS, Corticosteriods Gabapentin, tricyclics, SNRIs muscle relaxants, others

Opioids for Acute Pain‐ how and when

• Appropriate risk screening – consider a opioid risk tool • Prescribe the least potent opioid to effectively control the pain • Prescribe the minimal quantity/ no refills • Consider checking OARxRS prior to prescribing‐ required if prescribing for 7 or >days • Avoid long acting opioids • Caution: if patient is on other sedating drugs: benzos, sleepers, or if patient is known to use alcohol or recreational drugs

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Opioids for Acute Pain

• Pre plan a wean off of opioids as the pain resolves • Discuss proper storage and safety of opioids in the home • Discuss importance of proper disposal of unused medications • Remind patient that sharing is unsafe and unlawful!!

Acute pain –What to do if pain persists

If pain persists > 14 days: • Reevaluate etiology • Reevaluate the treatment modalities • Determine reason for continued pain • Other diagnostic and management strategies such as a specialty consultation

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Landmarks for Navigating the Waters in a Murky Sea • Know your patient – treat your real patients with real pain • If you don’t trust the patient ‐ don’t treat • Utilize a biopsychosocial model of pain management‐ almost all pain will either come with or develop emotional connections –get on top of this early • Treat the patient and not the pain

Emotional distress and Pain

• Emotional distress always results when an acute pain is severe enough to become chronic

• The development of emotional distress associated with acute pain may be a risk factor for the development of chronic pain Waldman – pp207‐209

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Pain and emotional distress: Operant Conditioning

• Individuals behave in certain ways according to reinforcement patterns • For chronic pain patients maladaptive pain behaviors are often being reinforced negatively and positively while well behaviors are being ignored and extinguished • Operant conditioning has been shown to be effective for increasing activity levels, exercise and tolerance

Navigating the Waters

• Use return to function as the goal – not a reduction in a pain number! • Set realistic, achievable goals • With new onset pain – keep the patient moving right from the start! • Utilize neuropathic pain adjuvants whenever treating chronic pain and early in the coarse of treating acute pain as well

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Navigating the Waters

• Utilize OARxRS – it’s a great tool • Know the OSMB rules and follow them

“Treating Pain is a moral imperative” IOM 2011

At the end of the day

“Physicians need training and experience in pain management if issues of access and under treatment are going to be addressed”

National Pain Care Policy Act of 2009 Incorporated into the Obama Healthcare Reform Bill

The real issue for prescribers in Ohio’s Pain Epidemic is not whether or not to treat pain but how!

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At the end of the day

“Slowly I learn about the importance of powerlessness. I experience it in my own life, and I live with it in my work. The secret is not to be afraid of it, not to run away. Patients know that we are not God… All they only ask is that we do not desert them.” Cassidy, S. Sharing the Darkness. London: Darton, Longman and Todd, 1988

Thank you! Questions?

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References: The Chronic Pain Association

The American Chronic Pain Association has offered support and information for people with chronic pain since 1980. Its mission is to facilitate peer support and education for individuals with chronic pain and their families so that these individuals may live more fully in spite of their pain, and to raise awareness among the healthcare community, policymakers and the public at large about issues associated with living with chronic pain. Learn more about the American Chronic Pain Association at www.theACPA.org.

References

• AAFP Monograph: Balancing Clinical and Risk Management Considerations for Chronic Pain Patients on Opioid Therapy, October, 2008

• Office of National Drug Control Policy Action Plan epidemic: Responding to America’s Prescription Drug Abuse Crisis, 2011

• Veteran’s Affairs/Department of Defense; Clinical Practice Guidelines Summary Management of Opioid Therapy for Chronic Pain, 2010

• Fishman, Scott M Responsible Opioid Prescribing2nd edition, 2014 Waterford Life Sciences, Washington, DC www.fsmb.org/books

• med.ohio.gov/rules4731‐21htm • Twillman, B From Policy to Practice: “How the CDC Guidelines Play Out in Primary Care “ presented at AAPM Annual Meeting, Sept 21‐25, 2016, San Antonio Texas

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References

• AAFP Monograph: Balancing Clinical and Risk Management Considerations for Chronic Pain Patients on Opioid Therapy, October, 2008 • APS‐ AAPM Clinical Guidelines for Opioid Use in Chronic Non Cancer Pain 2009 • Fishman, Scott M. Responsible Opioid Prescribing, 2nd edition, Waterford Life Sciences, 2012 pp 1‐129 • Institute of Medicine: Relieving Pain in America, a Blueprint for transforming prevention, care, education and research. Report Brief, June 2011 • Office of National Drug Control Policy Action Plan epidemic: Responding to America’s Prescription Drug Abuse Crisis, 2011

References

• Reform. 8. Available at: http://www.maydaypainreport.org/docs/A%20Call%20to%20Revolutionize %20Chronic%20Pain%20Care%20in%20America.pdf • Shega , JW. et al. The association between noncancer pain, cognitive impairment and functional disability J. Gerontology Series A, 65 A (8) 880‐886 • The Mayday Fund. (2010). A Call to Revolutionize Chronic Pain Care in America: An Opportunity in Health Care • Veteran’s Affairs/Department of Defense; Clinical Practice Guidelines Summary Management of Opioid Therapy for Chronic Pain, 2010 • Waldman, Steve, Pain Management, Vol 1, Saunders, Philadelphia, 2007 212‐ 221 • Waldman, Steve, Pain Management, Vol 2, Saunders, Philadelphia 2007 pp 965‐ 971, 1003‐1009

34 Sample E-newsletter and Blast Email

Headlines/Subjects:

1—How Can OARRS Help You?

2—Help Improve Patient Care Using OARRS

3—Reduce Prescription Abuse Using OARRS

4—Prescribe Safely Using OARRS

How can Ohio’s Automated Rx Reporting System (OARRS) help you? It can help you improve patient care, reduce prescription abuse, and prescribe safely.

Are you registered for OARRS? If you are not using OARRS, you need to start today (link words “start today” to http://www.ohiopmp.gov/portal/registration/default.aspc)!

OARRS can help you:

 Provide better patient care  Identify patients with potential drug seeking behaviors  Ensure that the patient’s drug therapy is appropriate  Comply with “press pause” clinical guidelines at 80 morphine equivalent dose (MED)  Demonstrate the effectiveness of clinical guidelines making adoption of prescribing rules unnecessary.

The Time is Now! On September 1 all of the state regulatory boards adopted clinical prescribing guidelines (link to PDF – note: if you don’t have PDF you can download it here: http://www.ohioafp.org/wp- content/uploads/Guidelines-for-Prescribing-Opioids-for-the-Treatment-of-Chronic-Non-Terminal- Pain.pdf) that became the standard of care in Ohio. Over the next 15 months, OARRS data will be used to assess the impact of these guidelines.

Using the recently adopted 80 MED guidelines in coordination with OARRS reports is a best practice that offers insight into a patient’s use of controlled substances while also alerting prescribers to possible medication conflicts as well as signs of abuse, addiction or diversion. OARRS reports have recently been enhanced to include a dosage calculator to assist prescribers in determining whether patients are at, near or over the daily 80 MED.

Read more about OARRS (link to OAARS page on your website) and Ohio’s opioid prescribing information (link to http://www.opioid.prescribing.gov).

Watch for more updates in (name and link to your e-newsletter).

State Medical Board of Ohio 30 E. Broad Street, 3rd Floor, Columbus, OH 43215-6127 (614) 466-3934 med.ohio.gov

Guidelines for Prescribing Opioids for the Treatment of Chronic, Non-Terminal Pain 80 mg of a Morphine Equivalent Daily Dose (MED) “Trigger Point”

May 9, 2013

These guidelines address the use of opioids for the treatment of chronic, non-terminal pain. "Chronic pain" means pain that has persisted after reasonable medical efforts have been made to relieve the pain or cure its cause and that has continued, either continuously or episodically, for longer than three continuous months. The guidelines are intended to help health care providers review and assess their approach in the prescribing of opioids. The guidelines are points of reference intended to supplement and not replace the individual prescriber’s clinical judgment. The 80 mg MED is the maximum daily dose at which point the prescriber’s actions are triggered; however, this 80 mg MED trigger point is not an endorsement by any regulatory body or medical professional to utilize that dose or greater.

Recent analysis by the Centers for Disease Control medication for a nontherapeutic use or distribute it and Prevention (CDC) shows that “patients with to other persons, and the potential existence of an mental health and substance use disorders are at illicit market for the medication. increased risk for nonmedical use and overdose from prescription painkillers as well as being Providers must be vigilant to the wide range of prescribed high doses of these drugs.” Drug potential adverse effects associated with long-term overdose deaths increased for the 11th consecutive opioid therapy and misuse of extended-release year in 2010. Nearly 60% of the deaths involved formulations. That vigilance and detailed attention pharmaceuticals, and opioids were involved in has to be present from the outset of prescribing and nearly 75%. Researchers also found that drugs continue for the duration of treatment. Providers prescribed for mental health conditions were should avoid starting a patient on long-term opioid involved in over half. These findings appear therapy when treating chronic pain. Providers should consistent with research previously published in also avoid prescribing benzodiazepines with opioids the Annals of Internal Medicine that concluded as it may increase opioid toxicity, add to sleep apnea that “patients receiving higher doses of prescribed risk, and increase risk of overdose deaths and other opioids are at an increased risk for overdose, which potential adverse effects. underscores the need for close supervision of Providers can further minimize the potential for these patients” (Dunn, et al., 2010). prescription drug abuse/misuse and help reduce the Health care providers are not obligated to use number of unintentional overdose deaths associated opioids when a favorable risk-benefit balance with pain medications by recognizing times to “press cannot be documented. Providers should first pause” in response to certain “trigger points.” This consider non-pharmacologic and non-opioid pause allows providers to reassess their compliance therapies. Providers should exercise the same with accepted and prevailing standards of care. The caution with tramadol as with opioids and must 80 mg Morphine Equivalent Daily Dose (MED) take into account the medication’s potential for “trigger point” is one such time. abuse, the possibility the patient will obtain the

To protect and enhance the health and safety of the public through effective medical regulation

State Medical Board of Ohio Guidelines for Prescribing Opioids – 80 MED “Trigger Point” 2

Providers treating chronic, non-terminal pain The 80 MED “trigger point” is an opportunity to patients who have received opioids equal to or review the plan of treatment, the patient's response greater than 80 mg MED for longer than three to treatment, and any modification to the plan of continuous months should strongly consider doing treatment that is necessary to achieve a favorable the following to optimize therapy and help ensure risk-benefit balance for the patient’s care. If opioid patient safety: therapy is continued, further reassessment will be guided by clinical judgment and decision-making  Reestablish informed consent, including consistent with accepted and prevailing standards of providing the patient with written information care. The “trigger point” also provides an on the potential adverse effects of long-term opportunity to further assess addiction risk or opioid therapy. mental health concerns, possibly using Screening, Brief Intervention, and Referral to Treatment (SBIRT)  Review the patient’s functional status and tools, including referral to an addiction medicine documentation, including the 4A’s of chronic specialist when appropriate. pain treatment: For providers treating acute exacerbation of chronic, o Activities of daily living; non-terminal pain, clinical judgment may not trigger o Adverse effects; the need for using the full array of reassessment o Analgesia; and tools. o Aberrant behavior.

Providers treating patients with acute care  Review the patient’s progress toward conditions in the emergency department or urgent treatment objectives for the duration of care center should refer to the Ohio Emergency and treatment. Acute Care Facility Opioids and Other Controlled

Substances Prescribing Guidelines at  Utilize OARRS as an additional check on patient compliance. http://www.healthyohioprogram.org/ed/guidelines.

 Consider a patient pain treatment agreement that may include: more frequent office visits, different treatment options, drug screens, use of one pharmacy, use of one provider for the prescription of pain medications, and consequences for non-compliance with terms of the agreement.

 Reconsider having the patient evaluated by one or more other providers who specialize in the treatment of the area, system, or organ of the body perceived as the source of the pain. Approved by Medical Board: May 9, 2013

Released January 2016

Ohio Guideline for the Management of Acute Pain Outside of Emergency Departments Preface: This guideline provides a general approach to the outpatient management of acute pain. It is not intended to take the place of clinician judgement, which should always be utilized to provide the most appropriate care to meet the unique needs of each patient. This guideline is the result of the work from the Governor’s Cabinet Opiate Action Team (GCOAT) and the workgroup on Opioids and Other Controlled Substances (OOCS). Introduction A specific diagnosis should be made, when appropriate, to facilitate In 2014, 2,482 individuals in Ohio died from an unintentional opioid- the use of an evidence-based approach to treatment. related overdose – more than a four-fold increase in 10 years1. Unintentional opioid overdose has become one of the leading causes Develop a Plan of injury-related death in Ohio over the past decade. To respond to Upon determining the symptoms fit the definition of acute pain, both this challenge, public health and health care leaders have committed the provider and patient should discuss the risks/benefits of both to helping healthcare providers better serve their patients with pain, pharmacologic and non-pharmacologic therapy. The provider should while reducing the potential for overdose and death. As part of the educate and develop a treatment plan together with the patient that Governor’s Cabinet Opiate Action Team (GCOAT), the workgroup on includes3: Opioids and Other Controlled Substances (OOCS) was charged with • Measureable goals for the reduction of pain developing guidelines for the safe, appropriate and effective • Use of both non-pharmacologic and pharmacologic prescribing of self-administered medications for pain. The two therapies, with a clear path for progression of treatment previously released guidelines are: • Mutually understood expectations for the degree and the • Ohio Emergency and Acute Care Facility Opioids and Other duration of the pain during therapy Controlled Substances Prescribing Guidelines [Released 2012; • Goal: Improvement of function to baseline or pre-injury Revised 2014] • Guidelines for Prescribing Opioids for the Treatment of Chronic, status as opposed to complete resolution of pain Non-Terminal Pain 80mg of a Morphine Equivalent Dose (MED) “Trigger Point” [Released 2013] Treatment of Acute Pain

While these guidelines provide a pathway for the management of Purpose acute pain, not every patient will need each option and care should This third guideline is focused on the management of acute pain and be individualized. the prescribing of self-administered medications for acute pain, delineating a standardized process that includes key checkpoints Non-Pharmacologic Treatment for the clinician to pause and take additional factors into Non-pharmacologic therapies should be considered as first-line consideration. therapy for acute pain unless the natural history of the cause of pain or clinical judgment warrants a different approach. These Definition of Acute Pain therapies often reduce pain with fewer side effects and can be For this guideline, acute pain is defined as pain that normally fades used in combination with non-opioid medications to increase with healing, is related to tissue damage and significantly alters a likelihood of success. Examples may include, but are not limited patient’s typical function. Acute pain is expected to resolve within to: days to weeks; pain present at 12 weeks is considered chronic and • Ice, heat, positioning, bracing, wrapping, splints, stretching should be treated accordingly. This guideline may not apply to acute and directed exercise often available through physical pain resulting from exacerbations of underlying chronic conditions. therapy

• Assessment and Diagnosis of Patient Presenting with Pain Massage therapy, tactile stimulation, For assessing patients presenting with acute pain, in addition to a acupuncture/acupressure, chiropractic adjustment, proper medical history and physical exam, initial considerations manipulation, and osteopathic neuromuscular care should include: • Biofeedback and hypnotherapy • Location, intensity and severity of the pain and associated symptoms Non-Opioid Pharmacologic Treatment Non-opioid medications should be used with non-pharmacologic • Quality of pain e.g. somatic (sharp or stabbing), visceral therapy. When initiating pharmacologic therapy, patients should (ache or pressure) and neuropathic pain (burning, tingling be informed on proper use of medication, importance of or radiating)2 maintaining other therapies and expectation for duration and • Psychological factors, including personal and/or family degree of symptom improvement. Treatment options, by the history of substance use disorder quality of pain, are listed below.

Somatic Pain prescription. (Note: An OARRS report is required for most • Acetaminophen prescriptions of seven days or more.) • Non-steroidal anti-inflammatory drugs (NSAIDS) • Avoid long-acting opioids (e.g. methadone, oxycodone ER, • Corticosteroids fentanyl). Alternatives include the following: gabapentin/pregabalin, • Use caution with prescribing opioids with patients on skeletal muscle relaxants, serotonin-norepinephrine reuptake medications causing central nervous system depression inhibitors, selective serotonin reuptake inhibitors and tricyclic (e.g. benzodiazepines and sedative hypnotics) or patients antidepressants. known to use alcohol, as combinations can increase the risk of respiratory depression and death. Visceral Pain • Discuss with the patient a planned wean off opioid therapy, • Acetaminophen concomitant with reduction or resolution of pain. • Non-steroidal anti-inflammatory drugs (NSAIDS) • Discuss proper secure storage and disposal of unused • Corticosteroids medication to reduce risks to the patient and others. Alternatives include the following: dicyclomine, skeletal muscle • Remind the patient that it is both unsafe and unlawful to relaxants, serotonin-norepinephrine reuptake inhibitors, topical give away or sell opioid medication, including unused or anesthetics and tricyclic antidepressants. leftover medication.

Neuropathic Pain Pain Reevaluation • Gabapentin/pregabalin Key Checkpoint: Reevaluation of patients who receive opioid • Serotonin and norepinephrine reuptake inhibitors therapy for acute pain will be considered if opioid therapy will continue beyond 14 days. This reevaluation may be through an • Tricyclic antidepressants office visit or phone call based on the discretion of the provider. Alternatives include the following: other antiepileptics, baclofen,

bupropion, low-concentration capsaicin, selective serotonin For patients with persisting pain, providers should reevaluate the reuptake inhibitors and topical lidocaine. initial diagnosis and consider the following:

Opioid Pharmacologic Treatment • Pain characteristics (consider using a standardized tool In general, reserve opioids for acute pain resulting from severe [e.g. Oswestry Disability Index]) injuries or medical conditions, surgical procedures, or when • Treatment methods used alternatives (non-opioid options) are ineffective or contraindicated. • Reason(s) for continued pain Short-term opioid therapy may be preferred as a first line therapy • Additional management options, including consultation with in specific circumstances such as the immediate post-operative a specialist period. In most cases, opioids should be used as adjuncts to additional therapies, rather than alone.4 It is critical that Additional Checkpoint: healthcare providers communicate with one another about a For patients with pain unresolved after 6 weeks, providers should patient’s care if the patient may be receiving opiate prescriptions repeat an assessment and determine whether treatment should be from more than one provider to ensure optimum and appropriate adjusted. Referral to guidelines on chronic pain management may be pain management. The following are recommendations for the helpful at this point, although chronic pain is defined as pain general use of opioids to manage acute pain: persisting for longer than 12 weeks. • Appropriate risk screening should be completed (e.g. age, pregnancy, high-risk psychosocial environment, personal References: 1. ODH, Office of Vital Statistics, Analysis by Injury Prevention Program. or family history of substance use disorder). 2013. • Provide the patient with the least potent opioid to effectively 2. Institute for Clinical Systems Improvement. Assessment and management manage pain. A morphine equivalence chart should be of acute pain. Bloomington (MN): Institute for Clinical Systems used if needed. Improvement; 2008 Mar. 58p. 3. Massachusetts Medical Society Opioid Therapy and Physician • Prescribe the minimum quantity needed with no refills Communication Guidelines. May 21, 2015. based on each individual patient, rather than a default 4. Washington State Agency Medical Directors Group. Interagency Guideline number of pills. on Prescribing Opiates for Pain Washington State Guidance. June 2015.

• Consider checking Ohio Automated Rx Reporting System (OARRS) for all patients who will receive an opiate

The Five Common Disorders of the Hand Seen by PCP’s

C. Jeff Kesler, M.D., FACS

Learning Objectives:

Identify the signs and symptoms of nerve compression syndrome. Perform the physical exam for the five common hand disorders. List necessary diagnostics for nerve compression syndrome. Define treatments for the five common hand disorders.

11/1/2016

FRIDAY, NOVEMBER 11, 2016 NWOOA ELEVENTH ANNUAL PRIMARY CARE UPDATE SANDUSKY, OHIO

DR. C. JEFF KESLER, MD FACS THE FIVE COMMON DISORDERS OF THE HAND SEEN BY PRIMARY CARE PROVIDERS

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INTRODUCTIO N DR. C. JEFF KESLER,M D FACS

INTRODUCTION

▸ COSMETIC RECONSTRUCTIVE SURGEON ▸ ARROWHEAD PLASTIC SURGEONS INC. ▸ UNDERGRADUATE EDUCATION AT YOUNGSTOWN STATE UNIVERSITY, YOUNGSTOWN, OHIO ▸ POST GRADUATE EDUCATION AT MEDICAL COLLEGE OF OHIO IN TOLEDO , OHIO ▸ POST GRADUATE TRAINING IN GENERAL SUGERY AT SWEDISH HOSPITAL MEDICAL CENTER IN SEATTLE, WASHINGTON ▸ BOARD CERTIFIED GENERAL SURGEON ▸ POST GRADUATE RESIDENT IN PLASTIC RECONSTRUCTIVE SURGERY AT MEDICAL COLLEGE OF OHIO IN TOLEDO, OHIO ▸ TRAINED UNDER DRS JOHN KELLEHER AND MICHEAL YANIK ▸ BOARD CERTIFIED PLASTIC RECONSTRUCTIVE SURGEON

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FELLOWSHIP TRAINING

▸ PLASTIC, COSMETIC AND RECONSTRUCTIVE SURGERY

▸ HAND SURGERY

▸ HEAD AND NECK SURGERY

PRACTICING IN TOLEDO, OHIO SINCE 1995 WITH ARROWHEAD PLASTIC SURGEONS INC.

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MY TEAM DAWN BURGE, PATIENT CARE COORDINATOR

MY TEAM MONIQUE NAVARRE , RN

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THE FIVE COMMON DISORDERS OF THE HAND SEEN IN THE PRIMARY CARE 1. NERVE COMPRESSION SYNDROMES SETTING(CARPAL, CUBITAL SYNDROME)

2. TRIGGER FINGER

3. DUPUYTREN’S CONTRACTURE

4. DEQUERVAIN’S SYNDROME

5. GANGLION CYST

OBJECTIVES

1. TO IDENTIFY THE SIGNS AND SYMPTOMS OF NERVE COMPRESSION SYNDROMES, TRIGGER FINGER, DUPUYTRENS CONTRACTURE, DEQUERVAINS SYNDROME AND GANGLION CYST.

2. TO PERFORM THE PHYSICAL EXAM FOR THE 5 COMMON HAND DISORDERS.

3. TO LIST NECESSARY DIAGNOSTICS FOR NERVE COMPRESSION SYNDROMES.

4. TO DEFINE TREATMENTS FOR THE 5 COMMON HAND DISORDERS.

5. TO DETERMINE WHEN IT IS NECESSARY TO REFER THE PATIENT TO THE HAND/ PLASTIC SURGEONS FOR SURGICAL EVALUATION AND TREATMENT.

6. TO DESCRIBE THE NORMAL POST-OPERATIVE COURSE FOR PATIENTS WHO HAVE THESE SURGERIES.

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NERVE COMPRESSION SYNDROMES CARPAL TUNNEL SYNDROME

CARPAL TUNNEL SYNDROMEICD-10 - G56.0 1. SIGNS AND SYMPTOMS EPIDEMIOLOGY 2. CAUSES REPETITIVE MOTION ASSOCIATED CONDITIONS 3. DIAGNOSIS PHYSICAL EXAM ‣ PHALEN’S MANEUVER ‣ TINELS SIGN ‣ DURKAN TEST,CARPAL COMPRESSION TEST ‣ HAND ELEVATION TEST 4. TESTING EMG MRI

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CARPAL TUNNEL SYNDROME 5. PATHOPHYSIOLOGY

6. PREVENTION

7. TREATMENTS

SPLINTS

CORTICOSTEROIDS

SURGERY

OCCUPATIONAL HAND THERAPY

8. PROGNOSIS

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NERVE COMPRESSION SYNDROMES CUBITAL TUNNEL SYNDROME

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CUBITAL TUNNEL SYNDROME

ICD-10 G56.2

1. SIGNS AND SYMPTOMS

2. CAUSES

3. DIAGNOSIS

MOTOR

SENSORY

MIXED

4. PREVENTION

CUBITAL TUNNEL SYNDROME CONTINUED…

5. TREATMENT

CONSERVATIVE

SURGICAL

6. POST- OPERATIVE COURSE

7. PROGNOSIS

8. CUBITAL TUNNEL SYNDROME VERSUS GUYON’S CANAL SYNDROME

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TRIGGER FINGER

ICD-10 M65.3

1. SIGNS AND SYMPTOMS

2. CAUSES

3. TREATMENT

CORTICOSTEROID INJECTIONS

SURGERY

4. POST-OPERATIVE COURSE

5. PROGNOSIS

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DUPUYT REN’S CONTRA CTURE

DUPUYTREN’S CONTRACTURE

ICD-10 M72.0

1. DEFINITION

2. SIGNS AND SYMPTOMS

3. ANATOMY

4. RISK FACTORS

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DUPUTRYEN’S CONTRACTURE CONTINUED…5. TREATMENTS RADIATION THERAPY

SURGICAL

AMPUTATION

INJECTIONS

6. PROGNOSIS

7. POST OPERATIVE CARE

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XIAFLEX INJECTION

DE QUERVAI N’S SYNDRO ME

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DE QUERVAIN SYNDROME ICD-10 M65.4

1. SOCIETY AND CULTURE

2. SIGNS AND SYMPTOMS

3. PATHOPHYSIOLOGY

4. DIAGNOSIS

5. TREATMENT

CONSERVATIVE TREATMENT

SURGERY

OCCUPATIONAL HAND THERAPY

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FINKELSTEIN TEST

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GANGLIO N CYST

GANGLION CYST

ICD-10 M67.4

1. SIGNS AND SYMPTOMS

SITES

SIZE

2. CAUSES

3. DIAGNOSIS

RADIOLOGY

ULTRASOUND

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GANGLION CYST CONTINUED… 4. TREATMENT

DO NOT HIT THE CYST WITH THE BIBLE!!

ASPIRATION

CORTICOSTEROID INJECTION

SURGERY

5. PROGNOSIS

RECURRENCE

SCAR FORMATION

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QUESTI ONS? ASK ME ANYTHING!

CONTACT INFORMATION

DR. C. JEFF KESLER, MD FACS 1360 ARROWHEAD ROAD MAUMEE, OHIO 43537 DAWN BURGE, PATIENT CARE COORDINATOR (419) 887-4507 M-TH MONIQUE A. NAVARRE, RN (419) 887-4526 M-TH

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IT HAS BEEN MY PLEASURE PRESENTING AT THIS WONDERFUL CONFERENCE THANK YOU FOR HAVING ME!

29 See Spot Change: Identification and Management in Primary Care

Erin Hennessey, DNP, APRN, FNP-C

Learning Objectives:

Discuss malignant skin lesions commonly seen in primary care. Identify common treatments and surgical procedures utilized for management. Review criteria for referral to plastic surgery.

11/1/2016

See spot change: Lesion identification and management in primary care ERIN HENNESSEY DNP, APRN, FNP-C

Learning objectives

 Discuss malignant skin lesions commonly seen in primary care.  Identify common treatments and surgical procedures utilized for management.  Review criteria for referral to plastic surgery.

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Commonly seen malignant skin lesions in primary care.

 1) Basal cell carcinoma  2) Squamous cell carcinoma

 3) Melanoma

Non Melanoma and Melanoma Skin Cancer

 History and Physical  With evaluating lesions that may be non healing or present for an extended period of time, it is helpful to obtain the following:  - Ethnicity and skin color (fair, olive, African American)  - Lifetime sun exposure (frequent vs. intermittent)  - History of sunburn as a child or adult  - Tanning bed use  - Smoking or chewing tobacco use  - Occupational exposure  - Immunosuppression or organ transplantation (renal transplant patients have a 253 fold increase in the risk for squamous cell carcinoma)  - History of radiation treatment for cancer or previous PUVA or UVA treatment for psoriasis

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Basal Cell Carcinoma

 Basal cell carcinoma is the most common invasive malignant cutaneous neoplasm. It is traditionally diagnosed by clinical identification and shave or scoop biopsy.  The most common presenting complaint is a bleeding or scabbing sore that heals and recurs.

 Although it will not metastasize, if left untreated it will advance by direct extension and destroy normal tissue causing significant damage.

Location, Epidemiology and Pathogenesis

 85% appear on the head and neck, 25 – 30% occur on the nose which is the most common site for basal cell carcinoma.  20% of tumors occur on sites that are typically sun protected such as the genitals and breasts.  The average lifetime risk for Caucasians to develop BCC is 30%  Individuals with fair skin, blonde or red hair, light eye color, poor tanning ability and sun damaged skin are at the highest risk. Male to female ratio is 2:1 with the exception being women under the age of 40. The closer one lives to the equator, the greater their risk is for developing BCC.  UVB plays a greater role in BCC development than UVA  Arise from basal keratinocytes of the epidermis and adnexal structures (e.g., hair follicles and eccrine sweat ducts)

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Basal Cell carcinoma

Basal cell Nodular Basal Call carcinoma Carcinoma BCC Inferior lateral canthus Left cheek / side burn area Note the rolled borders

BCC

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Squamous Cell Carcinoma

 20% of all non melanoma skin cancers in the US are SCC (80% are BCC). They arise from the epithelium and common in the middle aged and elderly populations. Lifetime risk of 18 – 20% and rising.  Risk factors include exposure to sunlight during childhood, sunburns, ionizing radiation, light skin, hazel, blue or green eyes, blond or red hair, outdoor occupations, freckling, living in the south, previous psoriasis therapy (oral psoralen and UVA radiation), and exposure to arsenic via medication or drinking water.  UVB plays a major role in SCC. UVB damages DNA by inducing the formation of pyrimidine dimers and induces mutation of p53 tumor suppressor genes. These mutations are found in SCC lesions. Cell mediated immunity and immune function may be modulated by UVB as well. HPV virus 6 and 11 are found in genital tumors and HPV 16 in periungual tumors. Diagnosis is made by shave or scoop biopsy.

Location, Epidemiology and Pathogenesis

 Most commonly found in sun exposed areas – scalp, backs of the hands and the pinna – BCC is rarely found on these sites.  They may appear as flat, scaly lesions that indurate. Central crusting and ulceration is common. They can develop a thick , warty appearance on top. It is very common to see SCC of the mouth or lip in smokers or those who use chewing tobacco.  Two major groups (based on malignant potential) A) Those arising in areas of radiation or thermal injury, chronic draining sinuses, and in chronic ulcers are typically aggressive and have a high frequency of metastasis. B) Those originating from actinically damaged skin are less aggressive and less likely to metastasize.  Patients who have undergone solid organ transplantation or who are immunosuppressed need to be monitored closely for SCC. They can be very aggressive in these patients.

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Management of Basal cell and Squamous Cell carcinoma

 Mohs procedure – micrographic surgery excellent in areas where conservation of tissue is salient (e.g., inner or outer canthus of the eye, nasal ala, vermillion border of the lip, fingers and ears. Benefits – excellent cure rate (up to 99%) Drawbacks - time consuming and expensive. There is a risk that the Moh’s surgeon will be unable to close the wound that day and the patient will have to find a plastic surgeon to close.  PDT – is FDA-approved for the treatment of superficial or nodular BCC.. A light- sensitizing agent, topical 5-aminolevulinic acid (5-ALA), is applied to the lesion in the physician’s office. Subsequently, the medicated area is activated by a strong blue light; theoretically, this will selectively destroy BCCs while causing minimal damage to surrounding normal tissue Benefits - cure rates ranging from 70 to 90 percent Draw backs - . Some redness, pain, and swelling can result. Patients must strictly avoid sunlight for at least 48 hours, or UV exposure may further activate the medication, causing severe sunburn. Very time consuming.  Electrodesiccation and curettage - The technique may not be as useful for aggressive BCCs, those in high-risk sites, or sites that would be left with cosmetically undesirable results. Typically, a round, whitish scar is left at the surgery site.

Treatment of BCC and SCC (cont’d)

 Surgical excision - gold standard treatment in our office. If the lesion is on the face, chest, shoulders, neck or lower extremities, referral to plastic surgery is warranted due to the possible need for skin grafting in these areas as well as an optimum aesthetic outcome for patients. Benefits - histologic margin control and rapid healing, and minimal pain Excellent cure rate with frozen section ( approx 99% in our office). Drawbacks – requires a surgical procedure with anesthesia.  BCC only:  Erivedge (vismodegib) – oral capsule used to treat adults with multiple BCCs, recurrent BCC or is not a candidate for surgery or radiation. Pregnancy category X. Females are required to use two forms of birth control for 7-8 months following treatment and Males may not donate semen or impregnate their partner for 3 months due to the birth defect risks associated. Benefit – no surgical procedure needed. Drawbacks – side effects and challenging to use in women of child bearing age.

6 11/1/2016

Actinic Keratosis

 Clinically, these can be felt most times before they are seen. They begin as slightly rough textured skin and gradually an adherent yellow scale forms as the skin inferior becomes more erythematous. They can be biopsied, but most diagnoses are made based on clinical acumen.  Often these progress to thickened or hypertrophic lesions and often times to squamous cell carcinoma.  The extent of the disease may vary from a single lesion to diffuse lesions that most often present on the the forehead, balding scalp, temples and sideburn areas.  Induration, erythema, pain, inflammation, ulceration and oozing are suggestive of progression to malignancy.  Histologically is squamous cell carcinoma in situ confined to the epidermis. It is very difficult to say where a lesion stops being an actinic keratosis and begins to be SCC in situ because they are biologically the same. They are on a continuum of disease

Actinic Keratosis

7 11/1/2016

Management – single lesions of Actinic Keratosis

 Cryotherapy – liquid nitrogen is applied to the area causing separation of the dermis and epidermis. Benefits – highly specific and in light skinned people is usually non scarring. Drawbacks –in darker skinned folks, may cause hyperpigmentation.

 CO2 laser resurfacing, dermabrasion and chemical peels. Benefits – fast and may also soften lines and aesthetically improve the appearance of skin. Drawbacks – not covered by insurance and has a lower cure rate than topical therapies.

 Electrodessication and Curettage

 Surgical excision

Management of multiple or diffuse actinic keratoses

 Field Directed therapy –– total sun avoidance is recommended.  5-fluorouracil – topically applied chemotherapy agent Benefits – good insurance coverage, can be done at home, does not harm healthy skin, can be used over a larger surface area. Drawbacks – intense inflammation, erythema and crusting, at possible risk for secondary infection, poor compliance.  Imiquimod – topical immune response modifier cream. Applied 3x per week for 16 weeks or 3x per week for 4 weeks, 4 weeks of drug holiday, then a second 3x per week for 4 weeks. Can be reduced to 2x per week if there local skin reaction. Benefits – reduction of 86.6% of Aks with 3.75% formulation. Drawbacks – tricky prescription pattern for the patient to follow and possible issues with compliance.  Picato (ingenol mebutate) – plant based (Euphorbia puplus) from Australia – once daily for 2-3 days. Creates the same inflammatory response as other topical chemotherapy agents with clearance in 2 weeks. Benefits –compliance (2-3 days!) Drawbacks – side effects and no long term studies available yet.

8 11/1/2016

Management of multiple or diffuse actinic keratoses (con’t)

 PDT – photo dynamic therapy – topical chemotherapy provides much better histologic response  Diclofenac (Solaraze) – BID for 60 – 90 days – great placebo control studies in transplant patients out of Germany: a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. At 24 months 55% of the patients had recurrent AKs but there were 0 SCC within the group.

Malignant Melanoma

 Malignant melanoma is a cancerous neoplasm of pigment forming cells, melanocytes, and nevus cells.  Clinically it’s hallmarks are: irregularly shaped and pigmented patches, papules or plaques.  Melanoma can arise from a preexisting lesion or de novo. There is no difference in the survival rate, but melanoma arising from a pre-existing lesion is more commonly found on the trunk, in younger individuals, and is more likely to be superficial spreading  The earlier melanoma is diagnosed the better the changes of complete surgical eradication.  Down and dirty - New research shows that having more than 11 nevi on one arm can indicate a increased risk for melanoma and patients can be appropriately advised to follow up with yearly skin exams

9 11/1/2016

Melanoma

 Cutaneous melanoma types: Superficial spreading melanoma Nodular melanoma Acral lentiginous melanoma Lentigo maligna melanoma

Epidemiology and Pathogenesis

 Melanoma is the fifth most common cancer in men and the sixth most common cancer in women.  1 in 50 Americans will develop melanoma in their lifetime For historical perspective, in 1935, the risk was 1 in 1500. The majority of melanoma in the US is diagnosed in the 15 – 50 year old age group.

 Patient with acute, episodic exposures to sunlight have a greater chance of developing melanoma than those with continuous exposure in either adulthood, adolescence or via occupational exposure.

10 11/1/2016

ABCDEs of identifying characteristics.

 A– asymmetry  B – Border irregularity

 C – Color variegation  D – Diameter > 6mm or approximately the size of a pencil eraser  E – Evolution or change

 Lesions can be red, white, blue, have notched borders or a papule or nodule within it.  Ugly duckling rule – 10% of melanoma do not follow the traditional rules. When a patient presents with any pigmented lesion that appear different from other nevi, it should be biopsied.

Malignant Melanoma

11 11/1/2016

Melanoma of the Lip

Superficial spreading melanoma

 70% of ALL cutaneous melanoma  Location: Most commonly found on the trunks of men and the extremities of women (questionable correlation with intermittent sun exposure)

 Asymmetrical presentation with variation in color and border irregularities are common  Papular or nodular component to the lesion may suggest a deeper invasion  Can arise from preexisting moles

12 11/1/2016

Nodular melanoma

 Nodular melanoma comprises 9-20% or invasive melanoma  Occurs most often in the fifth or sixth decade and more often in men than women 2:1

 It does not conform to the usual pattern – is it occasionally flesh colored and resembles a flesh colored nevi or basal cell carcinoma. It is most frequently misdiagnosed as a blood blister, hemangioma, nevus, seborrheic keratosis or dermatofibroma.  They have rapid growth patterns and tend to ulcerate.

Lentigo Maligna Melanoma

 4 – 15% of melanomas  Located on the head, neck, arms and sun damaged skin

 Slow growing: 5 – 20 years  Most commonly presents in the sixth or seventh decade  Clinically appears as a brown to black or blue to black nodule

13 11/1/2016

Acral lentiginous melanoma

 2 – 7% found in Caucasians  30 – 75% of melanomas in African American, Asian and Hispanic

 Located on the palms or soles as well as within the proximal nail fold

Squamous Cell carcinoma

Squamous cell Squamous cell invasive carcinoma carcinoma Squamous cell carcinoma In situ Of the lower right lip

14 11/1/2016

Management of melanoma

 A punch biopsy is performed and lesions are micro staged by a pathologist. If there is extension to the border, a wider excision is indicated. Breslow thickness, ulceration status, mitotic rate, peripheral and deep margin status, anatomic level of invasion and tumor infiltrating lymphocytes are all factored into the staging process.  Surgical margins for invasive melanoma should be at least 1 – 2 cm clinically measured around the primary tumor.

 The decision to perform sentinel node biopsy is based on clinical staging. Pathologic stage 0 – IA do not routinely need node biopsy.

In the pipeline

Sunscreen – Scientists out of Yale have developed a method for encapsulating padimate O creating a bio adhesive nano particle that adheres to the stratum corneum and does not absorb into the skin. It is water resistant, but comes off with towel friction.

Field treatment for actinic keratosis - Low-dose 5-FU/SA is an effective and well-tolerated treatment option licensed for the lesion-directed treatment of mild-to-moderate hyperkeratotic AK lesions and currently under investigation for field-directed treatment.

Europe has developed guidelines for the treatment of actinic keratosis recently and I expect the US to adopt similar guidelines in the next couple years.

15 11/1/2016

Take home points

 If you suspect a non melanoma skin cancer on evaluation, shave or scoop biopsy is appropriate. For a suspected melanoma or pigmented nevus biopsy, punch is recommended to obtain Breslow thickness which better predicts prognosis.  Encourage all patients to utilize chemical free sunscreen. Benefits of wearing chemical containing sunscreen outweigh the risk of damage from UVA and UVB rays in the absence of a better option. SPF 30 – 50 is recommended. Any SPF below 12 will prevent burn, but provide no protection against UVA / UVB radiation.  Follow up for patients who have AKs or have had BCC or SCC treated should be evaluated once yearly with a full body skin exam. Patient’s with a history of melanoma should be evaluated with a full body skin exam every 3 months for the first year then every 6 months or yearly there after.  Patient’s who have greater than 11 nevi on one arm on physical exam should be advised to obtain once yearly skin checks.

References  Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009 Apr;145(4):427-434. doi: 10.1001/archdermatol.2008.609.  Claas Ulrich, Antje Johannsen, Joachim Röwert-Huber, Martina Ulrich, Wolfram Sterry, Eggert Stockfleth Skin Cancer Centre Charité, Department of Dermatology, Charité Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany  Deng, Y., Ediriwickrema, A., Yang, F., Lewis, J., Girardi, M., & Saltzman, W. M. (2015). A Sunblock Based On Bioadhesive Nanoparticles. Nature Materials,14(12), 1278–1285. http://doi.org/10.1038/nmat4422  Habif, T. P. (2004). Clinical dermatology: A color guide to diagnosis and therapy. Edinburgh: Mosby.  Lin, W. M., Luo, S., Muzikansky, A., Lobo, A. C., Tanabe, K. K., Sober, A. J., & ... Duncan, L. M. (2015). Outcome of patients with de novo versus nevus-associated melanoma. Journal Of The American Academy Of Dermatology, 72(1), 54-58. doi:10.1016/j.jaad.2014.09.028  Marks, J. G., Miller, J. J., Lookingbill, D. P., & Lookingbill, D. P. (2006). Lookingbill and Marks' principles of dermatology. Philadelphia, PA: Saunders Elsevier.  Ribero, S., Zugna, D., Osella-Abate, S., Glass, D., Nathan, P., Spector, T. and Bataille, V. (2016), Prediction of high naevus count in a healthy U.K. population to estimate melanoma risk. Br J Dermatol, 174: 312–318. doi:10.1111/bjd.14216  Werner RN, Jacobs A, Rosumeck S, Erdmann R, Sporbeck B, Nast A. Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum. J Eur Acad Dermatol Venereol. 2015;29(11):e1-66.  http://cms.sagepub.com/content/early/2016/07/19/1203475416659259

16 Plastic Surgery Overview for the PCP

A. Thomas Dalagiannis, M.D. FACS

Learning Objectives:

Discuss what the sub-specialty of plastic surgery encompasses. Discuss the basics of burn care and when to refer. Recognize which procedures may be self-pay vs insurance coverage. Common Pediatric Sightings

Tracy A. Karolyi, D.O., FACOP

Learning Objectives:

Distinguish between various pediatric skin conditions. Distinguish between viral and bacterial skin condition. Identify visually common pediatric dermatologic conditions

10/31/2016

Tracy Karolyi, D.O., F.A.C.O.P.

1 10/31/2016

 Aka: Exanthema subitum, sixth disease.  Caused by human HSV-6 or 7.  Usually between ages 6mo-2yrs.  Sudden high fever for few days, followed by rash.  Rash begins on trunk and spreads peripherally.  Common etiology for febrile seizures.  Treatment is supportive.

2 10/31/2016

 First Line Treatment: Penicillin  Second Line Treatment: Macrolides or Cephalosporins  Other symptoms: abdominal pain, swollen glands headache rashes – scarletina Why do we treat? * Peritonsillar abscess * Rheumatic heart disease * Glomerulonephritis

Can an infant get strep???

 Testing should generally not be performed in children younger than 3 years in whom GAS rarely causes pharyngitis and rheumatic fever is uncommon.  In children and adolescents, negative RADT tests should be backed up by a throat culture; positive RADTs do not require a back-up culture. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86– 102

3 10/31/2016

4 10/31/2016

 Types: morbilliform exanthematous urticarial serum sickness Treatment: Stop offending agent Antihistamine for pruritus Steroids for severe reactions

 Penicillin is most widely stated drug allergy by patients (5-10% report)  Although, 85-90% of those who report a PCN allergy either aren’t allergic or allergy has resolved.  PCN IgE antibodies decrease over time, therefore more recent reactions are more likely to be true  50% will lose sensitivity by 5 years  80% will lose sensitivity by 10 years  2% cross reaction with Cephalasporin

5 10/31/2016

6 10/31/2016

 Chronic and recurrent.  Most commonly develops between infancy and age 12.  Neurodermatitis: itch-scratch-rash-itch cycle  Can be localized or generalized  Treatment consists of antihistamines, hydration, topical anti-inflammatory agents (corticosteroids).

7 10/31/2016

 Enterovirus family  Either Coxackie A or B with 24 serotypes  Coxackievirus A16 most common  3-7 day incubation period  Seen more in summer and fall  May have only rash or may have constitutional symptoms of fever, headache, malaise  Treatment is supportive

8 10/31/2016

9 10/31/2016

 Newer strain seen summer of 2012 in US  Previously only seen in Africa and Asia  More widespread, maculopapular rash or vessicles and scabbing  Carries higher risk for serious illness  Rash mimics HSV eruption  Nailbed disruption of fingers and toes.  Significant skin peeling may occur.

10 10/31/2016

 Etiology unknown  Longterm – weeks to months  Usually asymptomatic  Firm, dermal papules in annular arrangement  Usually isolated lesions  May be pruritic  Commonly misdiagnosed as tinea corporis  No treatment generally, however, can put high potency steroid creams topically or intradermally for cosmetic reasons

11 10/31/2016

12 10/31/2016

 Benign and self-limiting  Occurs in up to 50% of newborn infants  Lesions begin 24-48 hrs. after birth  Can come and go for up to 2 weeks

 Smear from pustule reveals: eosinophils

13 10/31/2016

14 10/31/2016

 Likely caused by infectious agent.  “herald patch” presents first and commonly mistaken as an eczema patch or tinea.  May or may not be pruritic.  Spontaneous remission in 6-12 weeks or less.  Treatment is to control pruritus.  More severe cases may respond to UV light.

15 10/31/2016

 Rapidly developing, bright red nodule  Recurrently bleeds when touched  Caused by proliferation of capillaries.  Seen on fingers, lips, mouth, trunk, face.  Common at prior sites of trauma.  Doesn’t spontaneously disappear, must be removed.  Depending on location- derm or plastics.

16 10/31/2016

17 10/31/2016

 Etiology: infectious, drug induced, idiopathic.  Rash can be widespread.  May be pruritic.  If develops mucous membrane involvement then becomes EM Major aka: Stevens Johnson Syndrome.

 Hadn’t had antibiotics for 12 days.  No other constitutional symptoms.  Had developed a nagging cough and was more fatigued.

 Labs ??

18 10/31/2016

 CBC-D, EBV, Mycoplasma ordered  IgG and IgM Mycoplasma both positive

 Treatment: Remember: Did not finish Amox so strep not effectively treated. Also need to treat the mycoplasma. Zithromax 6/kg daily for 5 days.

19 10/31/2016

 Unknown eitiology.  Self-limiting.  1-2 mm, vesiculopustules or ruptured pustules which disappear in 24-48 hours. Leaves a collarette of scale.  Wright stain shows neutrophils.  Differential DX: *toxicum *staph *HSV

20 10/31/2016

 Infection of eyelid or skin surrounding the eye.  Most common under age of 6yr.  Occurs most usually after a scratch or bug bite in the periorbital region.  Most common bacteria implicated: - Staph aureus - Strep pyogenes -H. flu Aggressive treatment to prevent…..

21 10/31/2016

 Rapid swelling of the dermis, subcutaneous tissue or mucosa  Swelling can be itchy and painful  Treatment if localized is antihistamines and cool compresses.

Secondary to a wasp sting to bottom lip

22 10/31/2016

 HISTORY ??

23 10/31/2016

 Caused by minor hemorrhaged capillaries.  Most commonly caused by physical trauma, ie: coughing, vomiting, crying.  This young lady was in marching band and rash began after a marching competition. Remembers her feet being extremely wet and cold.  If petechiae more widespread and associated with systemic symptoms then need to consider vasculitic or infectious processes.

24 10/31/2016

 Psuedocysts  Painless swelling of connective tissue due to ruptured salivary glands, usually secondary to local trauma.  Most commonly located on surface of lower lip, buccal mucosa, ventral surface of tongue or floor of mouth.  Usually are <1 cm in diameter, smooth walled, and bluish or translucent  May resolve spontaneously, if remains chronic then surgical resection necessary

25 10/31/2016

 Hairless, well circumscribed, skin colored or yellowish plaque on scalp.  Due to overgrowth of sebaceous glands.  Small percentage can give rise to secondary neoplasms: basal cell or sebaceous carcinoma  Derm referral as teen for close observation and decision to excise.

26 10/31/2016

 History ??

 Patient was seen 2 weeks prior in Urgent Care and diagnosed with Group A Strep  Treated appropriately with Amoxicillin

27 10/31/2016

 Erythematous, tender nodules on pretibial surface.  Hypersensitivity reaction in the subcutaneous fat tissues.  30-50% of cases unknown etiology.  May be secondary to infectious processes ie. Mycoplasma, Group A strep, Hepatitis C, EBV.  May be result of medications ie. OCP’s, sulfas  Self-limiting resolving in 3-8 wks.  Treatment is supportive and focuses on underlying cause.  Bedrest, elevation of legs, NSAIDS.

28 10/31/2016

 Aka- pityriasis versicolor.  Multiple, oval, scaly lesions.  Hypo or Hyperpigmented.  Usually located on upper back, neck, proximal extremities. Rarely on face.  Caused by fungus: Malassezia globosa or furfur.  Can definitively diagnose by KOH prep or lesions may fluoresce under woods lamp.  Treatment: selenium sulfide shampoos (RX strength), ketoconazole, Ciclopirox (Loprox)

 Vitiligo – won’t have the fine scale and there is complete de-pigmentation.

 Pityriasis Alba- lesions predominantly occur on the face and less commonly on the trunk and upper extremities. Will also have a fine scale.

29 10/31/2016

 Major clinical manifestations:

^ palpable, purpuric rash ^ arthralgias or arthritis ^abdominal pain: colicky ~ 50% GI bleed ~ 20-30% ^renal disease: some form of renal involvement in ~20-50%

30 10/31/2016

 routine blood tests (ex CBC-D, serum chemistries, and urinalysis) are nonspecific.  Renal involvement often becomes detectable after other manifestations of HSP, so urinary screening should be continued beyond the acute presentation.  Most typically will find proteinuria or hematuria.  Abdominal US if severe abdominal pain

31 10/31/2016

 A form of impetigo in which the vesicles enlarge to form bullae with clear yellow fluid.  After bullae rupture, a thin brown crust forms.  Due to a staph aureus that produces an exfoliative toxin A.  Treatment should target s.aureus

32 10/31/2016

TREATMENT: 1. Empiric oral antibiotic therapy with activity against MRSA is particularly important 2. Clindamycin and TMP-SMX are antibiotics of choice. (comparable treatment) 3. Parenteral antibiotic therapy — warranted if ^Extensive soft tissue involvement ^Signs of systemic toxicity ^Rapid progression of clinical manifestations ^ Persistence or progression of symptoms after 48 to 72 hours of oral therapy ^Immunocompromise

33 10/31/2016

 Parvovirus B19  Widespread clinical findings depending on age of patient.  25% children asymptomatic, 50% will have non-specific flu like symptoms/fever, 25% will have rash and arthralgias.  Incubation period of 1-3 wks.  Facial rash followed by lace like extremity or body rash several days later.  Treatment: supportive

34 Angioedema

Todd Rambasek, M.D., FAAAAI

Learning Objectives:

Differentiate among the various causes of urticarial and angioedema. Develop the skills to decide which patients need allergy testing. Recognize the signs of hereditary angioedema.

10/14/2016

Angioedema TODD RAMBASEK M.D. FAAAAI

Angioedema

 Swelling due to vascular leak caused by vasoactive mediators  Histamine induced  Bradykinin Induced

 Histaminergic is identified by response to high dose antihistamine treatment.  Bradykinin induced diagnosed by lack of response to antihistamines.

1 10/14/2016

Edema

Orolabial Angioedema

2 10/14/2016

Angioedema - subtypes

 Histaminergic  Idiopathic histaminergic angioedema  Allergic angioedema (foods – medications – latex – insect)  Physical urticaria/angioedema (cold – vibratory – pressure)  Bradykinin mediated  ACE Inhibitor induced  Idiopathic non-histaminergic angioedema  Hereditary angioedema types 1 & 2  Acquired C1-esterase inhibitor deficiency

12 y.o. girl presents with recurrent lip swelling and abdominal pain that does not respond to antihistamines. She has a paternal uncle who died of laryngeal asphyxiation and her C4 level is 4 (14-40 mg/dl). What test will confirm her diagnosis?

A. CH50 B. Skin testing for food allergens. C. SPEP D. Flow cytometry E. C1 inhibitor level

3 10/14/2016

Hereditary Angioedema

 Autosomal dominant disease caused by deficiency of C1-esterase inhibitor (type 1) or poor function of C1-esterase inhibitor (type 2)  Recurrent non-pruritic angioedema without hives.  May have prodromal erythema marginatum which can mimic hives.  50% of patients present by age 10.

4 10/14/2016

Hereditary Angioedema

Erythema Marginatum

Patienthelp.org

5 10/14/2016

Hereditary Angioedema

 Attacks may be triggered by minor trauma, medical procedures, estrogen, or ACE I or be spontaneous.  May involve face, throat, hands, feet, abdomen, genitals.  Unnecessary surgery is a common historical feature.  GI attacks may cause bowel obstruction.

Hereditary Angioedema

 50% of patients may experience laryngeal attacks at some point.  Historical data suggests that 30% of patients died from asphyxiation.  Any patient may have a laryngeal attack anytime.

6 10/14/2016

HAE – Laboratory Diagnosis

 C4 complement level is low during attacks and asymptomatic periods.  Sensitivity of C4 test is 95% and so may be used for screening.  C1 inhibitor antigenic level will be low in HAE I  C1 inhibitor functional level will be low in HAE I and HAE II

HAE – Acute attacks

 Epinephrine, antihistamines, are steroids and not effective in treating acute attacks  bradykinin mediated.  FFP may help – or worsen.  C1 inhibitor replacement therapy  Kallikrein inhibitor (ecallantide)  Bradykinin receptor antagonist – (icatibant)

7 10/14/2016

8 10/14/2016

HAE – Short Term Prophylaxis

 Needs to be given prior to medical procedure especially dental (not routine cleaning).  C1 INH several hours before procedure  Attenuated androgens 7 days before until 2 days afterword.  Emergency therapy on hand.

HAE – Long Term Prophylaxis

 Patients who experience repeated attacks should be placed on long term prophylaxis.  Daily C1 inhibitor – requires IV access every 3 days.  Danazol – effective and well tolerated but may have virilizing effects.  Tranexemic acid – generally less effective and may have thrombotic side effects.

9 10/14/2016

Acquired C1 inhibitor Deficiency

 Patients present exactly like HAE but at an older age.  Very rare.  The cause is usually B cell lymphoma.  Previously divided into 2 types (I – autoantibody & II Lymphoma related) but these are now thought to be greatly overlapping.  C4 –low –C1 INH low –C1q low.

HAE with normal C1 Inhibitor

 By 2000 – 10 families described with 36 women – no men – with recurrent angioedema including airway compromise and normal C1 INH.  Was initially termed HAE III.  Subsequently other kindreds found with male probands.  Some of these patients found to have a mutation in Factor 12 (XII HAE). Some however do not (U-HAE).  Often have a pharmacologic response to bradykinin inhibiting drugs.

10 10/14/2016

55 y.o. man on an ACE I for 6 yrs has severe tongue and lip swelling without hives and is drooling. There is no response to antihistamines or steroids. Which is true?

A. He is likely to respond to epinephrine. B. He is likely to tolerate an ARB. C. Asphyxiation is rare with ACE angioedema. D. ACE I is not the cause as he has been on it for 6 years. E. There is no drug treatment for ACE I angioedema.

ACE Inhibitor Angioedema

 Angiotensin converting enzyme is involved in the breakdown of bradykinin.  Angioedema occurs in 0.5% of patients on ACE I but is more common in African Americans, women, and smokers. Diabetics are relatively protected.  Latency of onset can vary from several hours to several years.

11 10/14/2016

ACE Inhibitor Angioedema

 Usually localizes to the face and lips – deaths have been reported.  GI angioedema may also occur and lead to obstructive symptoms.  May recur up to 6 weeks after stopping the drug.  Bradykinin mediated

ACE Inhibitor Angioedema

12 10/14/2016

ACE Inhibitor Angioedema - Treatment

 27 patients with ACE I induced angioedema randomized to icatibant 30 mg SC or prednisolone and clemastine.  Median time to resolution of symptoms was:  Icatibant – 8 hours  Prednisolone/clemastine – 27 hours

 $ 11,328.94 per dose

NEJM 2015 Jan

ACE Inhibitor Angioedema – ARB’s

 98% of patients with ACE I angioedema will tolerate an ARB.  However because ARB’s are reported to cause angioedema the risk benefit ratio should be carefully weighed before giving these medications.

13 10/14/2016

26 y.o. woman presents with 20 episodes of swelling of the lips, hands, and feet for 6 months. Occasionally associated hives. Not aware of a food or medication trigger. Family history negative. Mostly better with cetirizine. Which is correct?

A. Order C4 level to rule out hereditary angioedema. B. Skin testing for common food allergens. C. Reassure and treat with cetirizine 20 mg B.I.D. D. C1 inhibitor level to rule our hereditary angioedema. E. Cetirizine 20 mg B.I.D. and epinephrine pen.

Idiopathic (histaminergic) Angioedema

 Common condition that may mimic hereditary angioedema or ACE I.  Differentiated by:  Lack of family history  No ACE use  Less severe episodes  Response to antihistamines  Presence of hives (not always present)

14 10/14/2016

Idiopathic (histaminergic) Angioedema

How do we know it’s not occult allergy?. Autologous serum skin test Isolation studies Anti-FcER1 auto-antibody Associated with Hashimoto’s thyroiditis. No associated wheeze, hypotenstion, GI symptoms History negative

Idiopathic (histaminergic) Angioedema

 Take a careful history. Foods  Sex Medications  NSAIDS Latex  ACE I Stings  Antibiotic creams/ointments Suppositories  Heat/Cold

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Idiopathic (histaminergic) Angioedema

Typical regimen 1. Cetirizine 20 mg B.I.D. (or loratidine) 2. Ranitidine 150 mg B.I.D. (or famotidine) 3. Montelukast 10 mg qd 4. Hydroxyzine 100 mg qhs

34 y.o. man has shrimp at 6:00 p.m., goes to bed at 10:00 pm and wakes at 7:00 am with swelling of the lips but no other symptoms of allergic reaction. We can tell him that 99% of food allergy reactions occur within:

A. 2 hours B. 3 hours C.4 hours D. 6 hours E. 8 hours

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IgE Mediated Food Allergy

 99% occur within 2 hours  95-97% involve:  Peanut/tree nut  Egg  Milk  Soy  Seafood

IgE Mediated Food Allergy

 90% of food reactions involve something on the skin (hives, flush, and angioedema)  Do not result in chronic abdominal symptoms  To differentiate from idiopathic angioedema – food allergy will have:  Wheeze or chest tightness  Low BP  Consistent food trigger within 2 hours  Rapid resolution in 4-6 hours

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Bradykinin Mediated Angioedema

Presentation Diagnosis Treatment

• NO hives • C4 and C1 inh • C1 inh • Face, hands, throat, Low replacement HAE GI • Family History • Kallikrein • After minor trauma inhibitor • Bradykinin

• Older age • C1 inh, C4, and Antagonist Acquired C1 • B Cell Lymphoma C1q all low (icatibant) Esterase typical cause Deficiency

• Stop medication • Face/Lips/tongue • Clinical • May occur up to 6 • 98% tolerate ARB Ace Inhibitor • Consider icatibant wks after stopping Janean Wedeking DO

Histamine Mediated Angioedema

Presentation Diagnosis Treatment

• Wheeze, Low BP, chest • Allergy Testing based • Avoidance tightness on clinical history • Epinephrine Pen • < 2 hours (99%) Allergic IgE • Skin manifestations (90%) • Peanut, egg, milk, soy, seafood (95- 97%)

• Mimics HAE, less severe • Compatible history • High dose H1 and H2 • +/- hives • Normal C4 + montelukast Idiopathic • Responds to antihistamines

Janean Wedeking DO

18 10/14/2016

A Challenging Case – Slide 1

 T.F. is a 26 y.o. woman with a history of systemic lupus erythematosis who presented to the CCF ED on June 15th, 2003 with the chief complaint of throat swelling and difficulty breathing.  Earlier that day, while undergoing hemodialysis and after taking tylenol she had complained of pain and tingling in her hands and then later on that day began feeling swelling in her throat. This then progressed to difficulty swallowing. When she arrived in the ED she was having SOB and her speech was ‘garbled’.

A Challenging Case – Slide 2

 In the ED she was given diphenhydramine, solumedrol, pepcid, and clindamycin. She was then taken to the OR emergently where she was intubated under direct fiberoptic visualization. Fiberoptic exam by an otolaryngologist showed ‘mostly supraglottic swelling with a diffuse boggy epiglottis.’

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A Challenging Case – Slide 3

 T.F. has had a few episodes of facial swelling in the past. One of them was shortly after she was given piperacillin and was attributed to PCN allergy. She does not recall ever having hives with these events which in general have been few and far between. She has never had an episode this severe.

A Challenging Case – Slide 4

 Patient was intubated and admitted to MICU where exam notes a thick tongue, 2/6 systolic murmur and Quinton dialysis catheter. History of SLE w/ ESRD, HIT, endocarditis, anti-phospholipid antibody syndrome, depression, mitral regurgitation, DVT with IVC filter placement, multple line infections, mitral regurgitation, cellulitis, pericardial effusion, strongyloidiasis.

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A Challenging Case – Slide 5

 Patient born in Brazil, adopted to Cleveland and no known family history of angioedema. Labs show a C4 level of 4 (16-64). Because of low C4 level patient was placed on FFP around the clock and danazol and had improvement and was extubated and sent to medical floor. Working diagnosis at this point is C1 inhibitor deficiency.

A Challenging Case – Slide 6

 However 24 hours after going to medical floor patient has recurrent angioedema of face, neck, and tongue and is reintubated. C1 inhibitor antigenic and functional level return as normal. Diagnosis is now unclear.  Follow up phone discussion showed persistent symptoms in spite of use of danazol. Patient’s mother noted that patient had symptoms of persistent facial swelling for as long as one month.

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Given this extensive medical history – the best test to clarify the diagnosis at this point would be:

A. C1-Q auto-antibody level B. Food allergy testing C.Lip biopsy of the facial swelling D. SPEP E. CT of chest - neck

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SVC Syndrome

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SVC Syndrome

 Facial and head swelling which results from compression of the SVC – most often from bronchogenic carcinoma.  Symptoms include shortness of breath, headache, facial swelling, and venous distention of the neck.  May have a positive Pemberton’s sign (facial swelling and cyanosis with raising the arms.)  SVC stenting may relieve the symptoms as was the case for this patient.

24 NOTES ______SATURDAY, NOVEMBER 12, 2016 9.0 credits

7:30 a.m.-7:55a.m. Registration/Breakfast - West Pathway

Moderator: Nicholas G. Espinoza, D.O.

8:00 a.m.-9:00 a.m. Issues in Pain Management Ajith K. Pai, M.D., FACA, DABA

9:00 a.m.-10:00 a.m. Workplace Issues Associated with Legalized Medical Marijuana Sarah E. Pawlicki, Esq., SPHR, SHRM-SCP

10:00 a.m.-10:30 a.m. Break /View Exhibits - West Pathway

10:30 a.m.-11:30 a.m. Prescribing Naloxone and Management of Chronic Non-Cancer Pain Gregory Kramp, PharmD, RPh

11:30 a.m.-12:30 p.m. Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioids James E. Preston D.O., FAODME

12:30 p.m.-12:45 p.m. Lunch Buffet (lunch and Learn)

Moderator: Jennifer Pfleghaar, D.O.

12:45 p.m.-1:45 p.m. Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioids James E. Preston D.O., FAODME

1:45 p.m.-3:45 p.m. Osteopathic Manipulation in a Busy Practice Robert J. Cromley, D.O.

3:45 p.m.-4:00 p.m. Break/View Exhibits – West Pathway

4:00 p.m.-6:00 p.m. Drugs in America 2016 Robert M. Stutman & Judge Jodi Debbrecht Switalski

Issues in Pain Management

Ajith K. Pai, M.D., FACA, DABA

Learning Objectives:

Review management of chronic pain patients Discuss opiate epidemic: Why/what physicians can do. Recognize new Ohio State rules, guidelines and policies regarding Opiate prescriptions. Define opiate withdrawal treatment options

Workplace Issues Associated with Legalized Medical Marijuana

Sarah E. Pawlicki, Esq., SPHR, SHRM-SCP

Learning Objective:

Discuss Ohio’s Amended HB 523 legalizing medical marijuana and its impact on Ohio’s workforce and comparing it to the other states with legalized marijuana. Discuss the practical implications of medical marijuana in the workplace. Navigate the impact of medical marijuana on drug free workplace policies. 10/31/2016

Workplace Issues Associated with Legalized Medical Marijuana

Presented by Sarah E. Pawlicki, Esq., SPHR, SHRM‐SCP

Legalized Marijuana

WWW.EASTMANSMITH.COM

1 10/31/2016

Ohio’s Support of Legalized Medical Marijuana • What percentage of Ohioans support legalization of Medical Marijuana? – March, 2016 Quinnipiac Poll – March, 2015 Quinnipiac Poll – February, 2014 Quinnipiac Poll

WWW.EASTMANSMITH.COM

Federal Law and Marijuana

• Marijuana continues to be classified as a Schedule I drug under the Federal Controlled Substances Act – August 11, 2016 DEA declines petition to reclassify • No currently accepted medical use • Lack of accepted safety for use under medical supervision • High potential for abuse

WWW.EASTMANSMITH.COM

2 10/31/2016

Amended H.B. 523 – September 8, 2016

• Legalizes medical marijuana • Establishes the Medical Marijuana Control Commission • Physicians may recommend and must keep a log of the recommendations and why MJ was recommended over other drugs • No home growing • Minors must have consent of parent or guardian

WWW.EASTMANSMITH.COM

Amended H.B. 523

• Employers are allowed to refuse to hire, discharge, or discipline because of an employee’s use, possession, or distribution of medical MJ • Drug free workplace policies enforceable • Just cause for discharge for unemployment purposes

WWW.EASTMANSMITH.COM

3 10/31/2016

Qualifying Medical Conditions

• Acquired immune deficiency • Hepatitis C; syndrome; • Inflammatory bowel disease; • Alzheimer's disease; • Multiple sclerosis; • Amyotrophic lateral sclerosis; • Parkinson's disease; • Cancer; • Positive status for HIV; • Chronic traumatic • Post‐traumatic stress disorder; encephalopathy; • Sickle cell anemia; • Crohn's disease; • Spinal cord disease or injury; • Epilepsy or another seizure • disorder; Tourette's syndrome; • • Fibromyalgia; Traumatic brain injury; • • Glaucoma; Ulcerative colitis

WWW.EASTMANSMITH.COM

Qualifying Medical Conditions

• Pain that is either of the following: – Chronic and severe; – Intractable. • Any other disease or condition added by the state medical board under section 4731.302 of the Revised Code.

WWW.EASTMANSMITH.COM

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Medical Marijuana Control Program

• Dept. of Commerce and State Board of Pharmacy must establish: – Licensure of medical marijuana cultivators, processors, and retails dispensaries – Registration of patients and caregivers – Licensure of labs that test medical marijuana • State Medical Board – Issue certificates to physicians seeking to recommend • Rules must be adopted within 1 year and the program fully operational in 2 years

WWW.EASTMANSMITH.COM

Medical Marijuana Advisory Committee

• Curtis L. Passafume, Jr., R.Ph. (Chair), • Martin McCarthy, Jr., representing practicing pharmacist and member of caregivers. the State of Ohio Board of Pharmacy. • Dr. Jerry W. Mitchell, Jr., practicing • Stephanie M. Abel, Pharm.D., physician. practicing pharmacist. • Nancy Walsh Mosca, CNP, practicing • James “Ted” Bibart, representing nurse. patients. • Marcie Seidel, representing persons • Tony E. Coder, Jr., representing involved in mental health treatment. persons involved in the treatment of • Dr. Amol Soin, practicing physician drug and alcohol addiction. and member of the State Medical • Michael G. Hirsch, representing Board of Ohio. agriculture. • Michael E. Stanek, representing • Sheriff John Lenhart, representing employers. local law enforcement. • Gary L. Wenk, engages in academic • Jason Kaseman, representing labor. research.

WWW.EASTMANSMITH.COM

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Permissible forms and methods

• Oils; • Tinctures; • Plant material; • Edibles; • Patches; • Any other form approved by the state board of pharmacy under section 3796.061 of the Revised Code.

WWW.EASTMANSMITH.COM

But… No smoking!

• With respect to the methods of using medical marijuana, all of the following apply: (1) The smoking or combustion of medical marijuana is prohibited. (2) The vaporization of medical marijuana is permitted; (3) The state board of pharmacy may approve additional methods of using medical marijuana, other than smoking or combustion, under section 3796.061 of the Revised Code.

• Any form or method that is considered attractive to children, as specified in rules adopted by the board, is prohibited

WWW.EASTMANSMITH.COM

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Affirmative Defense

• How much? Not more than a 90‐day supply • To establish a physician must have written a recommendation certifying: – A bona‐fide physician‐patient relationship exists – Patient diagnosed with a qualifying medical condition – Physician requested an OARRS report – Physician informs the patient that the benefits outweigh the risks • Also gives defense to parent/guardian or caregiver

WWW.EASTMANSMITH.COM

But… No driving

• This section does not authorize a registered patient to operate a vehicle, streetcar, trackless trolley, watercraft, or aircraft while under the influence of medical marijuana.

WWW.EASTMANSMITH.COM

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Medical Marijuana at Work

• Casias v. Wal‐Mart (6th Cir. 2012) Michigan Medical Marihuana Act did not prohibit employer from terminating employee for testing positive for marijuana despite the employee having a registered marijuana card because it did not regulate private employers.

WWW.EASTMANSMITH.COM

Medical Marijuana at Work

• Coats v. DISH Network (CO Supreme Court, June 15, 2015) CO law does not prohibit employers from terminating employees for positive test even where there is no impairment and employee is lawfully using medical marijuana because marijuana use is not “lawful” under federal law.

WWW.EASTMANSMITH.COM

8 10/31/2016

Medical Marijuana at Work

• Braska v. Challenge Manufacturing (MI Court of Appeals, 2014) Employee discharged for positive drug screen entitled to unemployment benefits if the employee has a medical marijuana card and was compliant with MI law.

WWW.EASTMANSMITH.COM

Change in the wind…

• State of CT v. CT Employees Union Independent

WWW.EASTMANSMITH.COM

9 10/31/2016

Legal Issues Associated with Drug Testing

• Drug testing ≠ medical test under ADA

• ADA does not require marijuana use as a “reasonable accommodation”

WWW.EASTMANSMITH.COM

MJ and Workers’ Compensation Claims • Positive post‐accident drug screen ≠ denied workers’ compensation claim • R.C. 4123.54 and the “rebuttable presumption” • Voluntary abandonment for violation of written work rule

WWW.EASTMANSMITH.COM

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Questions?

Sarah E. Pawlicki, Esq., SPHR, SHRM-SCP 419-247-1701 [email protected]

www.eastmansmith.com 419-241-6000

11 Prescribing Naloxone and Management of Chronic Non Cancer Pain

Gregory Kramp, PharmD, RPh

Learning Objective:

Identify patients who would benefit from naloxone. Recognize legal and clinical issues in prescribing naloxone. Describe overdose and its management. Describe evidence based treatment of chronic non-cancer pain. Describe evidence based treatment of addiction. 10/31/2016

Prescribing Naloxone & Management of Chronic Non‐ Cancer Pain

By Greg Kramp, PharmD., RPh. 11/12/2016

Statement of Disclosure

• I have no relevant financial relationships. • I work for a retail pharmacy chain that just began dispensing naloxone through a protocol.

1 10/31/2016

Objectives

At the completion of this program, participants should be able to: • Identify who would benefit from naloxone. • Recognize legal and clinical issues in prescribing naloxone. • Describe an overdose and its management. • Describe treatment of chronic non‐cancer pain. • Describe treatment of addiction.

http://www.cdc.gov/drugoverdose/data/statedeaths.html

24 Overdose Rate 18

Increase from 18 % ‘13 to ‘14 13% 4th National Rank 18th

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Epidemiology

• 50 million in the USA have chronic pain2 • 2015: 3.8 million live with opioid abuse / dependence. 329K are addicted to heroin3 – 12.8% Misuse Rx opioids4 • 18,893 deaths due to rx opioid overdose4 – 2,482 in Ohio ‘ 14

Rudd, R. Increases in Drug and Opioid Overdose Deaths —United States, 2000– 2014. MMWR. January 1, 2016 / 64(50);1378‐82. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm

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Economic Impact

• Pain is a $560 ‐ 635 billion problem5,6 • Non‐medical use of rx opioids $72 billion problem7 – $15.9 B are costs related to overdoses

Clinical Risk Factors of Opioid‐Induced Respiratory Depression and Opioid Overdose8 • Hx of substance abuse • Start/stop of 3A4 • Hx of mental illness inhibitors • Use of long acting • COPD or asthma opioids • Sleep apnea • Switching to another • Reduced kidney or liver opioid fxn • Morphine equivalent • Skin ulcers > 20mg/day • Pancreatitis • Use of BZDs or alcohol • Traumatic injury

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Vital Signs: Overdoses of Prescription Opioid Pain Relievers --- United States, 1999--2008 November 4, 2011 / 60(43);1487-1492. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm#tab1

National Overdose Deaths:

30,000 http://www.drugabuse.gov/related‐topics/trends‐ statistics/overdose‐death‐rates

25,000

20,000

15,000

10,000

5,000

0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Prescription Drugs Opioid Pain Relievers Illicit Drugs Heroin

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Anatomy and Physiology

• Normal rate: 12 –20 breaths/min9 • Controlled by Hypoxic reflex10 – Medulla • μ and δ opioid receptors inhibit 11 – Baroreceptors in the aortic and carotid arteries • μ opioid receptors inhibit11 – ↑ respiratory rate and depth

• pH, O2, CO2

Etiology11

• Taking prescribed medication with alcohol or other sedative • Worsening lung function, kidney, liver fxn • Start / stop of 3A4 inhibitor: fluconazole • Adulterated heroin (fentanyl) • Abuse / misuse

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Pathophysiology12

• RR < 10 / min • Opioids bind to the mu receptor

– ↓response to CO2 – ↓ O2 levels – ↓depth of respiraon – ↓ pharyngeal tone  ↑ upper airway resistance • ↑Heart rate and cardiac output • Similar morphine equilvent dosing similar respiratory depression10 • Tolerance to respiratory depression slower than analgesia

Signs and Symptoms13

• Pinpoint pupils • Low shallow breathing • Unable to wake person with sternal chest rub • Stupor 15 • Diminished oxygen saturation SpO2< 92%

13) Washington Manual. 32nd Edition. 2007 14) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739053/

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Diagnosis13

• Hx: ingestion of multiple meds is common – Seek to identify drugs ingested • Clinical presentation: Check vitals signs, pupillary rxns, neurologic rxns. • Lab studies: ABGs, electrolytes, acid‐base gaps, baseline liver and kidney fxn, pregnancy test, EKG • No need to get opioid levels

Differential Diagnosis 14

• Alcoholic Wernicke‐Korsakoff’s syndrome – 100mg thiamine IVP • Hypoglycemia – 50% dextrose in NS 50mL IV – Oral glucose paste • Carbon Monoxide – Oxygen • Benzodiazepine overdose – Flumazenil • May cause seizures

8 10/31/2016

Treatment 14

• Goal: respiration depression w/o withdrawal • ABCs • IV access • Gastric Lavage – activated charcoal if with in 1 hour of ingestion – Emesis contraindicated • NAC for acetaminophen if needed • Whole bowel irrigation – body packers or fentanyl patch • Naloxone 2mg to 10 mg – High doses for diphenoxylate, buprenorphine, pentazocine

Naloxone

• Competitive μ opioid receptor antagonist • Onset: with in 2 minutes 16 • Duration: 20 ‐ 90 minutes 15 • Dosage 17: Titrate dose to arousal – then 2/3rds of this dose / hour

15) Edward W. Boyer, Management of Opioid Analgesic Overdose Engl J Med. 2012 Jul 12; 367(2): 146–155. doi: 10.1056/NEJMra1202561 16) Evzio PI Rev. April 2012 17) Goldfrank L, Weisman R, Errick J, Lo M. A dosing nomogram for continuous infusion of intravenous naloxone. Annals of Emergency Medicine. 1986;15:566‐570.

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Edward W. Boyer, Management of Opioid Analgesic Overdose Engl J Med. 2012 Jul 12; 367(2): 146–155. doi: 10.1056/NEJMra1202561

Special Populations

• Pregnancy category B – crosses placenta • Nursing mothers: unknown if present in milk • Neonates and Pediatrics: usually require higher doses • Geriatric: unknown / no changes seen • Limited Effect with partial or mixed agonist / antagonists

16) Evzio PI Rev. April 2012

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Side Effects14: Narcan and OD • Hyper / Hypotension • Arrhythmia • Irritability • Renal failure • Anxiety • Rhabdomyolysis • Restlessness • Compartment • Nausea / vomiting Syndrome • Cardiac arrhythmia • Pulmonary edema

Treatment

Product Sig NDC Billing Qty How Supplied

Use one auto‐ injector upon signs of opioid Evizo® 0.4 2 injections + 1 overdose. Call 60842‐0030‐01 0.8 mL* mg/0.4 ml trainer 911. May repeat ×1 after 3 minutes.

11 10/31/2016

Product Sig NDC Billing Qty How Supplied

Spray one‐half of syringe into each nostril upon signs of Naloxone 2 4ml ( 2 opioid 76329‐3369‐01 2 syringes / box mg/2 ml syringes) overdose. Call 911. May repeat x 1 after 3 minutes

Use as directed Dispense with 2 McKesson ID: 25 atomizer / for naloxone 2 atomizers† atomizers 2580348 box administration

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13 10/31/2016

Product Sig NDC Billing Qty How Supplied

Naloxone 0.4 25 multi‐dose 00409‐1219‐01 10 mL (1 vial) mg/ml 10mL Inject 1 ml IM vials / case upon signs of Naloxone 0.4 opioid mg/ml single overdose. Call 00409‐1215‐01 2 mL (2 vials) dose vial, 2 vials 911. May 10 single‐dose repeat ×1 after vials / box Naloxone 0.4 3 minutes. mg/ml single 67457‐0292‐02 2 mL (2 vials) dose vial, 2 vials

Use as directed BD 3mL 23 g x for naloxone 08290‐3095‐71 2 (2 syringes) 100 / case 1in Syringe administration

Product Sig NDC Billing Qty How Supplied

Use 1 spray in 1 Narcan Nasal 1 box of 2 ready nostril as Spray 4mg / 69547‐0353‐02 2 to use nasal needed may 0.1mL sprays. repeat after

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Laws

• OH: through physician protocol – Someone at risk or caregiver or friend or police officer – One‐stop shop on www.pharmacy.ohio.gov : Protocol, patient handout, guidance document • MI: so far police have it – Working on rx thru protocol law

15 10/31/2016

Narcan by Protocol: What Patients Get

• Verbal and written education required – Call 911 – Overdose: Risk factors, how to prevent, signs / symptoms, how to respond – Info on naloxone: how to use, store, expiration – Where to get a referral for substance abuse tx – Now at: CVS, Drug Mart, Giant Eagle, Kroger, Meijer, Rite Aid, Walgreens • 65% of all retail pharmacies

Identify and talk with our high‐risk patients: 1) Previous opioid intoxication or overdose. 2) History of nonmedical opioid use. 3) Initiation or cessation of methadone or buprenorphine for opioid use disorder treatment. 4) Higher‐dose (>50 mg morphine equivalent/day) opioid prescription. 5) Patients who may have difficulty accessing emergency medical services (distance, remoteness). 6) Voluntary request from a family member, friend, peace officer or other person in a position to assist an individual who there is reason to believe is at risk of experiencing an opioid‐related overdose 7) Receiving any opioid prescription plus:

16 10/31/2016

Receiving any opioid prescription plus:

a. Rotated from one opioid to another because of possible incomplete cross‐tolerance.

b. Smoking, COPD, emphysema, asthma, sleep apnea, respiratory infection or other respiratory illness. c. Renal dysfunction, hepatic disease, cardiac illness or HIV/AIDS. d. Known or suspected concurrent alcohol use. e. Concurrent benzodiazepine or other sedative prescription. f. Concurrent antidepressant prescription.

Naloxone Laws Lay distribution Immunity: Immunity: Immunity: Lay & Prescribing Prescribers Dispensers administrator possession permitted Rx

w/o order

Party

Civil Civil Civil State Criminal Criminal Criminal 3rd Disciplinary Disciplinary Distribution Standing Possession

OH Yes Yes Yes Yes Yes Yes ‐‐ Yes Yes ‐‐ Yes Yes Not MI Yes ‐‐ ‐‐ Yes ‐‐ ‐‐ Yes ‐‐ Yes Yes Yes Yet

OH: HB 170 (2014); HB 4 (2015) MI: MI Comp. Law: 691.1503 & 333.17744b Davis, Corey, JD. Legal Interventions to Reduce Overdose Mortality Naloxone Access & Overdose Good Samaritan Laws. The Network for Public Health Law. https://www.networkforphl.org/_asset/qz5pvn/network‐naloxone‐10‐4.pdf

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Guidelines

• WHO, AMA, VA: Those likely to witness an OD should have access to Narcan. – (Strongly recommended / opinion) • WHO: No preference to dosage form – (Recommendation based on cost / opinion)

Pain Management ‐ CDC

• Non‐opioids are preferred – Exercise, SSRI, SNRI, TCAs, anticonvulsants, CBT • Opioids when benefits out‐weigh risks • Tx Goals and plan to stop if benefits not seen • Initially lowest effective dose of IR opioid • Recheck w/ dose ↑ ≥ 50mg Morphine / day • Avoid BZDs when possible • Recheck every 3 months (urine screen yearly)

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Neuropathic Pain ‐ IASP

1st line: Neurontin (gabapentin), Lyrica (pregabalin), Cymbalta (duloxetine), Effexor (venlafaxine), TCAs (amitriptyline) (desipramine) 2nd line: Lidoderm (lidocaine), Ultram (tramadol), Qutenza (capsaicin 8%) 3rd line: Opioids, Botox (botulinum toxin A)

Lancet Neurol. 2015;14(2):162‐73

Pain Assessment

• PEG: Pain, Enjoyment, General Activity • PHQ‐9: depression scale • ORT, SOAPP(‐R): Opioid Risk Tools – Low Level of evidence • 4 As: Analgesia, Activities of daily living, adverse effects, aberrant drug behavior • Patient education: E.g. https://theacpa.org/

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April 1st 2015 OARRS for Physicians

• Before prescribing opioids or benzodiazepines – Previous 12 months / every 90 days / documented • Exceptions – Hospice or terminally ill – If for 7 days or less – Tx of cancer or condition associated with cancer – Tx in hospital, LTC, nursing patient – Tx of acute pain from pregnancy, surgery, invasive procedure

OARRS for Pharmacists

Outpatient scripts only All controlled substances New drug, directions, strength Every 12 months MD or pt outside of area More than 1 prescriber (not same office) Your judgment: early refill, intoxicated, “Percs”

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Opioid Use Disorder –DSM‐5

• Mild, moderate, or severe • Inability to control or reduce use • Interferes with major obligations or social fxn – DSM5.org

Medication Assisted Treatment (MAT) • Methadone, buprenorphine, naltrexone • Allows addicts to fxn – Prevent relapse, reduce Hep C & HIV transmission www.samhsa.gov

Suboxone Preferred

• If suspect a lower tolerance to opioids (opinion) • If concurrent heavy or unstable use of sedating drugs/medication(uncontrolled intervention) • If elderly (opinion) • If significant respiratory illness (opinion) • Subutex preferred over methadone in pregnancy • Ceiling effect for respiratory depression

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Source: www.hhs.gov/sites/default/files/factshee t‐opioids‐061516.pdf

New Treatments

• Suboxone Docs: 1st year: 30→ 2nd 100→ 3rd 275 patients ‐ CNPs & PAs coming soon • FDA approves Probuphine® – buprenorphine implant • Each implant supplies 8mg/day for 6 months • Max 1 year of tx: once in each upper arm • Vivitrol (Naltrexone) – Every month in the glut for EtOH or opioids – After withdrawals & in counseling www.hhs.gov/sites/default/files/factsheet‐opioids‐061516.pdf ®http://probuphine.com/prescribing‐info www.vivitrol.com

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What Works & Doesn’t

• PDMP –no evidence of deaths prevented • OARRSa – 11.6% decrease in opioid scripts – 71% decrease in MD shopping • Abuse deterrent meds decrease useb – Oxycontin less 42% – Opana less 68% a: http://www.logandaily.com/news/opioid‐doses‐prescriptions‐for‐ohio‐patients‐ continue‐to‐decrease/article_6852f902‐9b7f‐5daf‐a7ac‐182973a8d1f8.html b: http://www.radars.org/portals/1/newsletters/2013q3‐radars‐system‐newsletter.pdf

Works (cont.)

• Methadone – 2.5% taper off successfully – 12 –52 weeks better vs. < 12 weeks • Slower taper is more effective

Source: Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: Results from a population‐based retrospective cohort study. Addiction. 2012 Sep; 107(9): 1621–1629. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376663/

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Heroin

Ohio Substance Abuse Monitoring (OSAM) – A law enforcement professional reflected on the link between increased monitoring of prescription opioids and increased use of heroin:“When we [law enforcement] really made the push on the oxy’s [OxyContin®] and on the pain clinics, it really kinda pushed it [drug abusers] over into the heroin … and you’re seeing it almost as a national trend now

(OSAM) Jan to June ‘15 http://mha.ohio.gov/Portals/0/assets/Research/OSAM‐TRI /June2015‐ExecutiveSummary.pdf • Heroin –easier to get than Rx opioids – Often mixed with fentanyl – 1/10th gram $10 ‐ $40 – ½ gram $40 ‐ $90 – 1 gram $80 ‐ $200 • Dealers sell syringes – $2 ‐ $5 a piece – Indiana saw 188 new cases of HIV/HCV • cost ~ $80 million in medical expenses

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• Typical user is white 18 –40 years old • Some make a living off selling rx opioids – $1‐ $2 /mg • Hancock Probation: 30% of positive urine screens for Suboxone – $10 ‐ $35 per film • For withdrawal – Kratom, Lyrica 75mg $1.50, Gabapentin 300mg $2

Arrowhead Behavioral

Inpatient: $750 / day x 5days = $3750 1) $250 / day x 10 days over 2 weeks = $2500 Or 2) $175 / day x 18 days over 6 weeks = $3150

Then Suboxone classes at $80 / session. Weekly or monthly. Not included: med costs, physician fees

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References

1) Rudd, R. Increases in Drug and Opioid Overdose Deaths —United States, 2000–2014. January 1, 2016 / 64(50);1378‐82. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm?s_cid=mm6450a3_w ( Accessed 9/7/2016) 2) Nahin, R. 2015. Estimates of Pain Prevalence and Severity in Adults: United States, 2012. J Pain. 2015 Aug: 16(8):769‐780. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562413/ (Accessed 9/8/2016) 3) Center for Behavioral Health Statistics and Quality. (2016). Prescription Drug Use and Misues in the United States: Results from the 2015 National Survey on Drug Use and Health (HHS PublicationNo. SMA 16‐4984, NSDUH Series H‐51). Retrieved from http://www.samhsa.gov/data/. Accessed: 9/8/2016 4) Center for Behavioral Health Statistics and Quality. (2016). Key substance use and mental health indicators in the United States: Results from the 2015 National Survey on Drug Use and Health (HHS PublicationNo. SMA 16‐4984, NSDUH Series H‐ 51). Retrieved from http://www.samhsa.gov/data/sites/default/files/NSDUH‐FFR2‐2015/NSDUH‐FFR2‐2015.htm /. Accessed: 9/8/2016 5) Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011. http://books.nap.edu/openbook.php?record_id=13172&page=1. 6) The economic costs of pain in the United States. J Pain. 2012 Aug;13(8):715‐24. doi: 10.1016/j.jpain.2012.03.009. Epub 2012 May 16. http://www.jpain.org/article/S1526‐5900(12)00559‐7/fulltext 7) http://www.cdc.gov/vitalsigns/pdf/2011‐11‐vitalsigns.pdf 8) Fala L, Welz JA. New perspectives in treatment of opioid‐induced respiratory depression. American Health & Drug Benefits. Oct 2015. Vol 8: 6 Supl 3 S51‐63 9) https://my.clevelandclinic.org/health/healthy_living/hic_Pre‐participation_Evaluations/hic_Vital_Signs 10) Goodman & Gillman 11th ed. P 390 11) White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction. 1999;94:961–72. [PubMed] 12) http://www.medscape.com/viewarticle/749755_3 . Risk Factors for Opioid‐Induced Excessive Respiratory Depression Carla R. Jungquist, RN, PhD; Suzanne Karan, MD; Michael L. Perlis, PhDPain Manag Nurs. 2011;12(3):180‐187.

26 Risk Evaluation and Mitigation Strategies (REMS) for Extended-Release and Long-Acting Opioids

James E. Preston, D.O., FAODME

Learning Objective:

Describe the opioid crisis in America and the REMS development as a consortia to improve the physician opioid prescribing safety and appropriateness. List several representative opioids commercially available and their indications. Describe the contraindications to opioids and safe opioid prescribing procedures. List the patient consent and educational requirements for opioid prescriptions. 10/31/2016

Presented by CO*RE Collaboration for Relevant PresentedEducation by CO*RE www.core-rems.org Collaboration for REMS Education www.corerems.org

Collaborative for REMS Education Collaborative for REMS Education

James E. Preston, DO, FAODME

Bio: Senior Medical Director Stein Hospice and Palliative Care Inc. Assistant Dean, Clinical Affairs Ohio University Heritage College of Osteopathic Medicine Program Director Firelands Regional Medical Center Fellowship Hospice and Palliative Medicine

DISCLOSURE: Dr. Preston has nothing to disclose.

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James E. Preston, DO, FAODME

Senior Medical Director Stein Hospice and Palliative Care Inc.

Assistant Dean, Clinical Affairs Ohio University Heritage College of Osteopathic Medicine

Program Director Firelands Regional Medical Center Fellowship in Hospice and Palliative Medicine

DISCLOSURE: Dr. Preston has nothing to disclose.

3 | © CO*RE 2013 Collaborative for REMS Education

Collaborative for REMS Education

On July 9, 2012, the Founded in June, 2010, the Food and Drug Collaborative on REMS Education Administration (FDA) (CO*RE), a multi-disciplinary team of approved a Risk 13 partners has designed a core Evaluation and curriculum based on needs assessment, Mitigation Strategy practice gaps, clinical competencies, (REMS) for extended- and learner self-assessment to meet release (ER) and long- the requirements of the FDA REMS acting (LA) opioid Blueprint. medications.

www.core-rems.org

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Organizations

Our Partners

. American Pain Society (APS) • Healthcare Performance Consulting (HPC) . American Academy of Hospice and • Interstate Postgraduate Medical Palliative Medicine (AAHPM) Association (IPMA) . American Association of Nurse • Nurse Practitioner Healthcare Practitioners (AANP) Foundation (NPHF) . American Academy of Physician • Physicians Institute for Excellence Assistants (AAPA) in Medicine which coordinates 15 state medical societies . American Osteopathic Association (AOA) • Medscape • American College of Emergency . American Society of Addiction Physicians (ACEP) Medicine (ASAM) . California Academy of Family Physicians (CAFP)

Collaborative for REMS Education

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Content Development/Planner/Reviewer Disclosures The following individuals disclose no relevant financial relationships: David Bazzo, MD Professor of Family Medicine, University of California San Diego School of Medicine

Roberto Cardarelli, DO, Professor, Department of Family and Community Medicine, University of Kentucky College of Medicine MPH

Ronald Crossno, MD Senior National Medical Director, Gentiva Health Services, Rockdale, TX Katherine Galluzzi, DO Professor and Chair, Department of Geriatrics, Philadelphia College if Osteopathic Medicine, Philadelphia, PA Carol Havens, MD Family physician and addiction medicine specialist, The Permanente Medical Group, Sacramento, CA Randall Hudspeth PhD, Practice and Regulation Consultant in Advanced Practice Pain Management and Palliative Care APRN‐CNP, FRE, FAANP Edwin A. Salsitz, MD, Beth Israel Medical Center, Division of Chemical Dependency; Assistant Professor, Albert Einstein College of FASM Medicine Barbara St. Marie, PhD, Supervisor, Pain and Palliative Care; Adult and Gerontology Nurse Practitioner, Pain Management, Associate ANP‐BC Faculty, University of Iowa College of Nursing, Iowa City, IA

Cynthia Kear, CHCP, MDiv Senior Vice President, California Academy of Family Physicians, San Francisco, CA Jerri Davis, CHCP Director, Continuing Professional Development, California Academy of Family Physicians

Robin and Neil Heyden Staff, CO*RE Operations Team, Heyden TY, Alameda, CA Julie Bruno, MSW LCSW Director, Education and Training, American Academy of Hospice and Palliative Medicine, Chicago, IL Anne Norman, DNP, Associate Vice President of Education, American Association of Nurse Practitioners APRN, FNP‐BC Marie‐ Michele Leger, MPH, PA‐C Director, Clinical Education, American Academy of Physician Assistants, Alexandria, VA Eric D. Peterson, EdM, Senior Director, Performance Improvement CME, American AcademyCollaborative of Physician Assistants for REMS Education FACEHP

CO*RE Staff Disclosures The following individuals disclose no relevant financial relationships:

Public Health Project Manager, Department of Research and Development, American Osteopathic Stephanie Townsell, MPH Association, Chicago, IL Sharon McGill, MPH Director, Department of Quality and Research, American Osteopathic Association, Chicago, IL

Jennifer Reinard Education Manager, American Pain Society Catherine Underwood, MBA, CAE Chief Executive Officer, American Pain Society, Chicago, IL

Arlene Deverman, CAE, CFRE Vice President, Professional Development, American Society of Addiction Medicine Penny Mills, MBA Executive Vice President and CEO, American Society of Addiction Medicine Chevy Chase, MD

Thomas McKeithen Jr, BS, MBA Partners, Healthcare Performance Consulting Inc., Indianapolis, IN Chris Larrison

Kate Nisbet, BBA, MBA Director of Health Systems Education, Interstate Postgraduate Medical Association Mary Ales, BA Executive Director, Interstate Postgraduate Medical Association, Madison, WI

Pam Jenkins‐Wallace, MS, NP Program Director, NPHF Continuing Education Program Phyllis Zimmer, MN, FNP, FAAN President, Nurse Practitioner Healthcare Foundation, Bellevue, WA

Sara Bennett Project Manager, Physicians’ Institute for Excellence in Medicine Adele Cohen, MS, PCMH CCE Senior Vice President, Physicians’ Institute for Excellence in Medicine, Atlanta, GA

Piyali Chatterjee Director, Medical Education, Medscape, LLC New York ,NY Cyndi Grimes, CCMEP CME/CE Director, Medscape, LLC, New York, NY Sarah Williams, PhD Scientific Director, Medscape, LLC, New York, NY

Cynthia Singh Director, Grants and Foundation Development, American College of Emergency Physicians Lori Foley Director, Strategic Partnerships, American College of Emergency Physicians, Irving, TX

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Acknowledgement Presented by [Insert Partner Name], a member of the Collaborative on REMS Education (CO*RE), 13 interdisciplinary organizations working together to improve pain management and prevent adverse outcomes. This educational activity is supported by an independent educational grant from the ER/LA Opioid Analgesic REMS Program Companies. Please see http://ce.er-la- opioidrems.com/IwgCEUI/rems/pdf/List_of_RPC_Co mpanies.pdf for a listing of the member companies. This activity is intended to be fully compliant with the ER/LA Opioid Analgesic REMS education requirements issued by the US Food & Drug Administration.

9 | © CO*RE 20132015 Collaborative for REMS Education

Products Covered by this REMS Brand Name Products Generic Products • Avinza® morphine sulfate ER capsules • Fentanyl ER transdermal • Belbuca® buprenorphine buccal film systems • Butrans® buprenorphine transdermal system • Methadone hydrochloride • Dolophine® methadone hydrochloride tablets tablets • Duragesic® fentanyl transdermal system • Methadone hydrochloride oral concentrate • Embeda® morphine sulfate/naltrexone ER capsules • Exalgo® hydromorphone hydrochloride ER tablets • Methadone hydrochloride oral solution • Hysingla® ER (hydrocodone bitartrate) ER tablets • Morphine sulfate • Kadian® morphine sulfate ER capsules ER tablets • MorphaBond® morphine sulfate ER tablets • Morphine sulfate • MS Contin® morphine sulfate CR tablets ER capsules • Nucynta® ER tapentadol ER tablets • Oxycodone hydrochloride ® • Opana ER oxymorphone hydrochloride ER tablets ER tablets • OxyContin® oxycodone hydrochloride CR tablets • Targiniq™ oxycodone hydrochloride/naloxone hydrochloride ER tablets • Zohydro® hydrocodone bitartrate ER capsules

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WHY PRESCRIBER EDUCATION IS IMPORTANT

Introduction

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Prescribers of ER/LA Opioids Should Balance:

The benefits The risks of prescribing of serious ER/LA opioids adverse to treat pain outcomes

ER/LA opioid analgesics should be prescribed only by health care professionals who are knowledgeable in the use of potent opioids for the management of pain

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Opioid Misuse/Abuse is a Major Public Health Problem Improper use of any opioid can result in serious AEs including overdose & death This risk can be greater w/ ER/LA opioids

ER opioid dosage units contain more Methadone is a potent opioid with opioid than IR formulations a long, highly variable half-life

In 2012 In 2011 37 million Americans age ≥12 488,004 ED visits involved had used an opioid for nonmedical use of opioids nonmedical use some • Methadone involved in 30% of time in their life prescription opioid deaths

SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Detailed Tables. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD. SAMHSA. (2013). Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD. CDC. CDC Vital Signs. Prescription Painkiller Overdoses. Use and abuse of methadone as a painkiller. 2012. FDA. Questions and Answers: FDA approves a Risk Evaluation and Mitigation Strategy for Extended-Release and Long-Acting Opioid Analgesics. www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm309742.htm. 2012.

13 | © CO*RE 2015 Collaborative for REMS Education

In 2013 43,982 Americans DIED FROM DRUG POISONINGS Nearly 16,235 deaths involved prescription opioids In 2008

NCHS Data Fact Sheet, June 2015 http://www.cdc.gov/nchs/data/factsheets/factsheet_drug_poisoning.pdf CDC. Policy Impact: Prescription Painkiller Overdoses. http://www.cdc.gov/homeandrecreationalsafety/rxbrief/ (Historical content - 2008 data) (accessed on 1/6/15).

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First-Time Use of Specific Drugs Among Persons Age ≥ 12 (2012) 3

2.5 2.4

2 1.9

1.5 1.4

1 0.9 0.7 0.6 0.6 Number in millions Number in 0.5 0.4 0.2 0.2 0.1 0

SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD.

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Learning Objectives

Describe the opioid crisis in America, and the REMS development as a consortia to improve the physician opioid prescribing safety and appropriateness.

List several representative opioids commercially available and their indications

Describe the contra-indications to opioids and safe opioid prescribing procedures.

List the patient consent and education requirements for opioid prescriptions.

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Misuse, abuse, divergence and overdose of ER/LA opioids is a major public health crisis.

YOU and YOUR TEAM can have an immediate and positive impact on this crisis while also caring for your patients appropriately.

17 | © CO*RE 2015 Collaborative for REMS Education

ASSESSING PATIENTS FOR TREATMENT WITH ER/LA OPIOID ANALGESIC THERAPY

Unit 1

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Balance Risks Against Potential Benefits

Conduct thorough H&P Comprehensive benefit- and appropriate testing to-harm evaluation

Benefits Include Risks Include

• • Analgesia Overdose (adequate pain control) • Life-threatening respiratory depression • Improved Function • Abuse by patient or household contacts • Misuse & addiction • Physical dependence & tolerance • Interactions w/ other medications & substances • Risk of neonatal withdrawal syndrome w/ prolonged use during pregnancy • Inadvertent exposure/ingestion by household contacts, especially children

Chou R, et al. J Pain. 2009;10:113-30. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010. FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. Modified 08/2014. www.fda.gov/downloads/ Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 19 | © CO*RE 2015 Collaborative for REMS Education

Adequately DOCUMENT all patient interactions, assessments, test results, & treatment plans

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Clinical Interview: Patient Medical History

Illness relevant to (1) effects or (2) metabolism of opioids

1. Pulmonary disease, constipation, nausea, cognitive impairment 2. Hepatic, renal disease

Illness possibly linked to substance abuse, e.g.:

Hepatitis HIV Tuberculosis Cellulitis

Trauma, Cardiac Pulmonary STIs burns disease disease

Chou R, et al. J Pain. 2009;10:113-30. Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010. 21 | © CO*RE 2015 Collaborative for REMS Education

Clinical Interview: Pain & Treatment History

Description of pain

Onset/ Variations / Location Intensity Quality Duration Patterns / Rhythms What relieves the pain? What relieves the pain? What causes or increases pain?

Effects of pain on physical, emotional, and psychosocial function

Patient’s pain & functional goals

Heapy A, Kerns RD. Psychological and Behavioral Assessment. In: Raj's Practical Management of Pain. 4th ed. 2008;279-95. Zacharoff KL, et al. Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc., 2010. 22 | © CO*RE 2015 Collaborative for REMS Education

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Clinical Interview: Pain & Treatment History, cont’d

Pain Medications

Past use

Current use • Query state PDMP where available to confirm patient report • Contact past providers & obtain prior medical records • Conduct UDT Dosage • For opioids currently prescribed: opioid, dose, regimen, & duration ‒ Important to determine if patient is opioid tolerant General effectiveness

Nonpharmacologic strategies & effectiveness

23 | © CO*RE 2015 Collaborative for REMS Education

Perform Thorough Evaluation & Assessment of Pain

Components of Order diagnostic Seek objective patient evaluation tests (appropriate confirmatory data for pain to complaint)

General: vital signs, Musculoskeletal Exam appearance, posture, • Inspection gait, & pain behaviors • Palpation Cutaneous or • Percussion trophic findings • Auscultation Neurologic exam • Provocative maneuvers

Lalani I, Argoff CE. History and Physical Examination of the Pain Patient. In: Raj's Practical Management of Pain. 4th ed. 2008;177-88. Chou R, et al. J Pain. 2009;10:113-30. 24 | © CO*RE 2015 Collaborative for REMS Education

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Assess Risk of Abuse, Including Substance Use & Psychiatric Hx Obtain a complete Hx of current & past substance use

• Prescription drugs • Illegal substances Social history also relevant • Alcohol & tobacco ‒ Substance abuse Hx does not prohibit treatment w/ ER/LA opioids but may Employment, cultural require additional monitoring & expert background, social consultation/referral network, marital history, • Family Hx of substance abuse & legal history, & other psychiatric disorders behavioral patterns • Hx of sexual abuse

25 | © CO*RE 2015 Collaborative for REMS Education

Risk Assessment, cont’d

Understand & Be knowledgeable use addiction about risk factors Conduct a UDT or abuse for opioid abuse screening tools

• Personal or family • Assess potential • Understand Hx of alcohol or risks associated limitations drug abuse w/ chronic opioid therapy • Younger age • Manage patients • Presence of using ER/LA psychiatric opioids based on conditions risk assessment

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Risk Assessment Tools: Examples Administered Tool # of items By Patients considered for long-term opioid therapy: ORT Opioid Risk Tool 5patient SOAPP® Screener & Opioid Assessment for Patients w/ Pain 24, 14, & 5 patient DIRE Diagnosis, Intractability, Risk, & Efficacy Score 7 clinician Characterize misuse once opioid treatments begins: PMQ Pain Medication Questionnaire 26 patient COMM Current Opioid Misuse Measure 17 patient PDUQ Prescription Drug Use Questionnaire 40 clinician Not specific to pain populations: CAGE-AID Cut Down, Annoyed, Guilty, Eye-Opener Tool, 4 clinician Adjusted to Include Drugs RAFFT Relax, Alone, Friends, Family, Trouble 5patient DAST Drug Abuse Screening Test 28 patient SBIRT Screening, Brief Intervention, & Referral to Treatment Varies clinician

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Opioid Risk Tool (ORT) Mark each box that applies Female Male 1. Family Hx of substance abuse Administer Alcohol 1 3 Illegal drugs 2 3 On initial visit Prescription drugs 4 4

2. Personal Hx of substance abuse Prior to opioid Alcohol 3 3 therapy Illegal drugs 4 4 Prescription drugs 5 5 Scoring (risk)

3. Age between 16 & 45 yrs 1 1 0-3: low 4. Hx of preadolescent sexual abuse 3 0

5. Psychologic disease 4-7: moderate ADD, OCD, bipolar, schizophrenia 2 2 Depression 1 1 ≥8: high Scoring Totals:

Webster LR, Webster RM. Pain Med. 2005;6:432-42. 28 | © CO*RE 2015 Collaborative for REMS Education

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Screener & Opioid Assessment for Patients with Pain (SOAPP)® Identifies patients as at high, moderate, or low risk for misuse of opioids prescribed for chronic pain

How is SOAPP® administered?

Usually self- Prescribers should May be completed administered in have a completed as part of an waiting room, & scored SOAPP® interview w/ a exam room, or while making nurse, physician, prior to an opioid treatment or psychologist office visit decisions

SOAPP® Monitoring Recommendations. https://painedu.org/soapp/SOAPP_Monitoring_Recommendations.pdf The SOAPP® Version 1.0 Tutorial. https://painedu.org/soapp-tutorial_01.asp 29 | © CO*RE 2015 Collaborative for REMS Education

When to Consider a Trial of an Opioid

Potential benefits are likely to outweigh risks

Failed to adequately respond to nonopioid & nondrug interventions Continuous, around-the-clock opioid analgesic is needed for an extended period of time

Pain is chronic and severe

No alternative therapy is likely to pose as favorable a balance of benefits to harms

Chou R, et al. J Pain. 2009;10:113-30. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. 2010.

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When to Consider a Trial of an Opioid, cont’d 60-yr-old w/ chronic disabling OA pain • Nonopioid therapies not effective, IR opioids provided some relief but experienced end-of-dose failure

• No psychiatric/medical comorbidity or personal/family drug abuse Hx ‒ High potential benefits relative to potential risks ‒ Could prescribe opioids to this patient in most settings w/ routine monitoring

30-yr-old w/ fibromyalgia & recent IV drug abuse • High potential risks relative to benefits (opioid therapy not 1st line for fibromyalgia) • Requires intensive structure, monitoring, & management by clinician w/ expertise in both addiction & pain ‒ Not a good candidate for opioid therapy

Chou R, et al. J Pain. 2009;10:113-30. 31 | © CO*RE 2015 Collaborative for REMS Education

When to Consider a Trial of an Opioid, cont’d Selection of patients between these 2 extremes requires:

Careful Structuring of care assessment & to match risk

characterization In patients w/ Hx of substance abuse of patient risk or a psychiatric comorbidity, this may require assistance from experts in managing pain, addiction, or other mental health concerns

In some cases opioids may not be appropriate or should be deferred until the comorbidity has been adequately addressed ‒ Consider referral

Chou R, et al. J Pain. 2009;10:113-30. 32 | © CO*RE 2015 Collaborative for REMS Education

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Referring High-Risk Patients

Prescribers should

Understand when to appropriately refer Also check your state high-risk patients to regulations for pain management or requirements addiction specialists

Chou R, et al. J Pain. 2009;10:113-30. 33 | © CO*RE 2015 Collaborative for REMS Education

Special Considerations: Elderly Patients Does patient have medical problems that increase risk of opioid-related AEs? Respiratory depression more likely in elderly, cachectic, or debilitated patients • Altered PK due to poor fat stores, muscle wasting, or altered clearance • Monitor closely, particularly when − Initiating & titrating ER/LA opioids − Given concomitantly w/ other drugs that depress respiration • Reduce starting dose to 1/3 to 1/2 the usual dosage in debilitated, nonopioid-tolerant patients • Titrate dose cautiously Older adults more likely to develop constipation • Routinely initiate a bowel regimen before it develops Is patient/caregiver likely to manage opioid therapy responsibly?

American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57:1331- 46. Chou R, et al. J Pain. 2009;10:113-30. 34 | © CO*RE 2015 Collaborative for REMS Education

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Special Considerations: Pregnant Women Managing chronic pain in pregnant women is challenging, & affects both mother and fetus

Potential risks of opioid therapy to the newborn include: • Low birth weight • Neonatal death • Premature birth • Prolonged QT syndrome • Hypoxic-ischemic brain injury • Neonatal opioid withdrawal syndrome Given these potential risks, clinicians should: • Counsel women of childbearing potential about risks & benefits of opioid therapy during pregnancy & after delivery • Encourage minimal/no opioid use during pregnancy, unless potential benefits outweigh risks If chronic opioid therapy is used during pregnancy, anticipate & manage risks to the patient and newborns

Chou R, et al. J Pain. 2009;10:113-30. 35 | © CO*RE 2015 Collaborative for REMS Education

Special Considerations: Children (<18 years) Safety & effectiveness of most ER/LA opioids unestablished Pediatric analgesic trials pose challenges Transdermal fentanyl approved in children aged ≥2 yrs Oxycodone ER dosing changes for children ≥ 11 yrs (see Unit 6)

Most opioid studies focus on inpatient safety

Opioids are common sources of drug error

Opioid indications are primarily life-limiting conditions Few children with chronic pain due to non-life-limiting conditions should receive opioids

When prescribing opioids to children: Consult pediatric palliative care team or pediatric pain specialist or refer to a specialized multidisciplinary pain clinic

Berde CB, et al. Pediatrics. 2012;129:354-64. Gregoire MC, et al. Pain Res Manag 2013;18:47-50. Mc Donnell C. Pain Res Manag. 2011;16:93-8. Slater ME, et al. Pain Med. 2010;11:207-14. 36 | © CO*RE 2013 Collaborative for REMS Education

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Challenge: The Friday Afternoon Patient

It is 4 pm on Friday and you are four patients Red Flag: behind schedule. Mr. Kingston asks you to increase his current dosage of hydrocodone, because he says it is not relieving his pain. It Adjusting a would take you two minutes to say yes. prescription without performing Action: Check your local PDMP. Employ appropriate practice management strategies that maximize evaluation or efficiency. screening • Patient-administered screening tools • Office staff to administer and score tools, document results, and communicate to the prescriber

37 | © CO*RE 2015 Collaborative for REMS Education

Challenge: The Delayed Surgery

Ms. Van Buskirk says she needs opioids to Red Flag: manage her pain until she can have surgery. She reports continued delays in getting to surgery. You phone the Patient may be surgeon and discover that no date has stalling to been set and that she has cancelled continue an several appointments. opioid regimen

Action: Set expectations for time limitations. Offer non-medicine and nonopioid options for pain management. Consider referral to addiction specialist.

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Unit 1 Pearls for Practice

Document EVERYTHING Conduct a Comprehensive H&P General and pain-specific Assess Risk of Abuse Compare Risks with Expected Benefits Determine Whether a Therapeutic Trial is Appropriate

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Unit II

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Federal & State Regulations Comply w/ federal & state laws & regulations that govern the use of opioid therapy for pain Federal State

• Code of Federal Regulations, Title • Database of state statutes, 21 Section 1306: rules governing regulations, & policies for the issuance & filling of pain management prescriptions pursuant to section – www.medscape.com/resource/pain/opioid-policies 309 of the Act (21 USC 829) – www.painpolicy.wisc.edu/database-statutes- – www.deadiversion.usdoj.gov/21cfr/cfr/2106cfrt.htm regulations-other-policies-pain-management • United States Code (USC) - Controlled Substances Act, Title 21, Section 829: prescriptions

– www.deadiversion.usdoj.gov/21cfr/21usc/829.htm

41 | © CO*RE 2015 Collaborative for REMS Education

Initiating Treatment Prescribers should regard initial treatment as a therapeutic trial May last from several weeks to several months

Decision to proceed w/ long-term treatment should be intentional & based on careful consideration of outcomes during the trial

Progress toward meeting Presence of opioid- therapeutic goals related AEs

Changes in underlying Changes in psychiatric or pain condition medical comorbidities

Identification of aberrant drug-related behavior, addiction, or diversion

Chou R, et al. J Pain. 2009;10:113-30 42 | © CO*RE 2015 Collaborative for REMS Education

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ER/LA Opioid-Induced Respiratory Depression

Chief hazard of Manifested by Instruct opioid agonists, reduced urge to patients/family including breathe & members to ER/LA opioids decreased call 911* • If not immediately respiration rate • Managed w/ close recognized & treated, • Shallow breathing observation, may lead to supportive measures, respiratory arrest • CO2 retention can & opioid antagonists, & death exacerbate opioid depending on sedating effects • Greatest risk: initiation patient’s clinical of therapy or after status dose increase

Chou R, et al. J Pain. 2009;10:113-30. FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/UCM311290.pdf 43 | © CO*RE 2015 Collaborative for REMS Education

ER/LA Opioid-Induced Respiratory Depression More likely to occur Reduce risk

• In elderly, cachectic, or debilitated • Proper dosing & titration are patients essential – Contraindicated in patients w/ • Do not overestimate dose when respiratory depression or conditions converting dosage from another that increase risk opioid product • If given concomitantly w/ other – Can result in fatal overdose w/ drugs that depress respiration first dose • Instruct patients to swallow tablets/capsules whole – Dose from cut, crushed, dissolved, or chewed tablets/capsules may be fatal, particularly in opioid-naïve individuals

FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 44 | © CO*RE 2015 Collaborative for REMS Education

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Initiating & Titrating: Opioid-Naïve Patients

Monitor patients Individualize dosage by Drug & dose selection closely titration based on is critical for respiratory efficacy, tolerability, depression & presence of AEs

Some ER/LA opioids or Especially within 24-72 h Check ER/LA opioid dosage forms are only of initiating therapy & product PI for minimum recommended for increasing dosage titration intervals opioid-tolerant patients Supplement w/ IR • ANY strength of transdermal fentanyl or hydromorphone ER analgesics (opioids • Certain strengths/doses of & nonopioid) if pain other ER/LA products (check is not controlled drug PI) during titration

The ER/LA Opioid Analgesics Risk Evaluation & Mitigation Strategy. Selected Important Safety Information. Abuse potential & risk of life-threatening respiratory depression. www.er-la-opioidrems.com/IwgUI/rems/pdf/important_safety_information.pdf. 2012. Chou R, et al. J Pain. 2009;10:113-30. FDA. Blueprint for Prescriber Education for ER/LA Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/UCM311290.pdf 45 | © CO*RE 2015 Collaborative for REMS Education

Initiating: Opioid-Tolerant Patients If opioid tolerant – no restrictions on which products can be used Patients considered opioid tolerant are taking at least – 60 mg oral morphine/day – 25 mcg transdermal fentanyl/hr – 30 mg oral oxycodone/day – 8 mg oral hydromorphone/day For 1 Wk – 25 mg oral oxymorphone/day Or Longer – An equianalgesic dose of another opioid Still requires caution when rotating a patient on an IR opioid to a different ER/LA opioid

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Opioid Rotation Definition: Change from an existing opioid regimen to another opioid w/ the goal of improving therapeutic outcomes or to avoid AEs attributed to the existing drug, e.g., myoclonus

Rationale: Differences in pharmacologic or other effects make it likely that a switch will improve outcomes • Effectiveness & AEs of different mu opioids vary among patients • Patients show incomplete cross-tolerance to new opioid – Patient tolerant to 1st opioid can have improved analgesia from 2nd opioid at a dose lower than calculated from an EDT

Fine PG, et al. J Pain Symptom Manage. 2009;38:418-25. Knotkova H, et al. J Pain Symptom Manage. 2009;38:426-39. Pasternak GW. Neuropharmacol. 2004;47(suppl 1):312-23. 47 | © CO*RE 2015 Collaborative for REMS Education

Equianalgesic Doses Opioid rotation requires calculation of an approximate equianalgesic dose

Equianalgesic dose is a construct derived from relative Relative potency estimates opioid potency estimates

• Potency refers to dose required • Ratio of doses necessary to produce a given effect to obtain roughly equivalent effects • Calculate across drugs or routes of administration • Relative analgesic potency is converted into an equianalgesic dose by applying the dose ratio to a standard

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Equianalgesic Dose Tables (EDT)

Many different versions:

Published Online

Online Interactive Smart-phone apps

Vary in terms of: Whether ranges Equianalgesic values are used

Which opioids May or may not include transdermal opioids, rapid-onset are included: fentanyl, ER/LA opioids, or opioid agonist-antagonists

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Example of an EDT for Adults

Equianalgesic Dose Usual Starting Doses Drug SC/IV PO Parenteral PO

5-15 mg q3-4hr 2.5-5 mg SC/IV q3-4hr Morphine 10 mg 30 mg (IR or oral solution) ( 1.25 – 2.5mg) ( 2.5-7.5 mg)

5-10 mg q3-4 Oxycodone NA 20 mg NA ( 2.5 mg)

5 mg q3-4h ( 2.5 mg) Hydrocodone NA 30 mg NA

1-2 mg q3-4hr 0.2-0.6 mg SC/IV q2-3hr Hydromorphone 1.5 mg 7.5 mg ( 0.5-1 mg) ( 0.2mg)

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Limitations of EDTs Single-dose potency studies using a specific route, conducted in patients w/ limited opioid exposure

Did Not Consider

Chronic dosing High opioid doses Other routes

Gender, ethnicity, Comorbidities or advanced age, or Different pain types organ dysfunction concomitant medications

Inter-patient Direction of switch Incomplete cross- variability in from 1 opioid to tolerance among pharmacologic another mu opioids response to opioids

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Utilizing Equianalgesic Doses

Incomplete cross-tolerance & inter-patient variability require use of conservative dosing when converting from one opioid to another Equianalgesic dose a starting point for opioid rotation

Intended as General Guide

Calculated dose of new drug Closely follow patients based on EDT must be during periods of dose reduced, then titrate the adjustments new opioid as needed Follow conversion instructions in individual ER/LA opioid PI, when provided

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Guidelines for Opioid Rotation

Reduce calculated equianalgesic dose by 25%-50%*

Select % reduction based on clinical judgment

Calculate Closer to 50% reduction if Closer to 25% reduction equianalgesic patient is if patient dose of new opioid from • Receiving a relatively • Does not have these EDT high dose of current characteristics opioid regimen • Is switching to • Elderly or a different medically frail administration route of same drug

*75%-90% reduction for methadone

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Guidelines for Opioid Rotation, cont’d If switching to methadone:

• Standard EDTs are less helpful in opioid rotation to methadone • In opioid tolerant patients, methadone doses should not exceed 30-40 mg/day upon rotation. • Consider inpatient monitoring, including serial EKG monitoring • In opioid-naïve patients, methadone should not be given as an initial drug If switching to transdermal: • Fentanyl, calculate dose conversion based on equianalgesic dose ratios included in the PI • Buprenorphine, follow instructions in the PI

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Guidelines for Opioid Rotation, cont’d

Have a strategy to frequently assess analgesia, AEs and withdrawal symptoms

Titrate new opioid dose to optimize outcomes & safety

Dose for breakthrough pain (BTP) using a short-acting, immediate release preparation is 5%-15% of total daily opioid dose, administered at an appropriate interval

If oral transmucosal fentanyl product is used for BTP, begin dosing lowest dose irrespective of baseline opioid dose

NEVER use ER/LA opioids for BTP

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Breakthrough Pain in Chronic Pain Patients Patients on stable ATC opioids may Therapies Consider adding experience BTP

Disease progression • Directed at cause • PRN IR opioid trial based or a new or of BTP or on analysis of benefit unrelated pain precipitating factors versus risk ‒ Risk for aberrant drug-related • Nonspecific behaviors symptomatic therapies ‒ High-risk: only in conjunction w/ to lessen impact frequent monitoring & follow-up of BTP ‒ Low-risk: w/ routine follow-up & monitoring • Nonopioid drug therapies • Nonpharmacologic treatments

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Reasons for Discontinuing ER/LA Opioids

No progress toward Intolerable & Pain level decreases in therapeutic goals Unmanageable AEs stable patients

Nonadherence or Aberrant behaviors suggestive unsafe behavior of addiction &/or diversion

• 1 or 2 episodes of increasing dose • Use of illicit drugs or without prescriber knowledge unprescribed opioids • Sharing medications • Repeatedly obtaining opioids • Unapproved opioid use to treat from multiple outside sources another symptom (e.g., insomnia) • Prescription forgery • Multiple episodes of prescription loss

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Challenge: The Broken Stereotype

Ms. Yeun seems like a “good” patient. She Red Flag: has never abused opioids previously. She has been in the practice a long time, has never been a problem, and in fact, is rather Making enjoyable. She always brings Christmas assumptions cookies for the staff around the holidays. about a patient’s risk Action: Require all patients receiving opioids factors without to follow a treatment plan and adhere to objective defined expectations. Evaluate risk in all evidence patients. Use patient-provider agreements, contracts, or other tools.

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Challenge: The Early Refill

You have prescribed Mr. Arias a long-acting Red Flag: opioid for low back pain and a short-acting PRN opioid for breakthrough pain. Every Patient requests month he requests a refill for both an early refill prescriptions 3-8 days early. Upon every month. questioning, Mr. Arias tells you that he takes both pills whenever he feels he needs them.

Action: Make sure that patients understand each medication’s dosage, time of day, and maximum daily dose. Ask them to repeat these instructions back to you. Avoid clinical terms such as “PRN” that the patient may not understand.

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Unit 2 Pearls for Practice

Treat Initiation of Opioids as a Therapeutic Trial Anticipate ER/LA Opioid-Induced Respiratory Depression It can be immediately life-threatening Be Conservative and Thoughtful In Dosing When initiating, titrating, and rotating opioids First calculate equinalgesic dose, then reduce dose appropriately Discontinue ER/LA opioids slowly and safely

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MANAGING THERAPY WITH ER/LA OPIOID ANALGESICS Unit III

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Informed Consent

Before initiating a trial of opioid analgesic therapy, confirm patient understanding of informed consent to establish:

Analgesic & functional goals of treatment The potential for & how to manage: • Common opioid-related AEs Expectations (e.g., constipation, nausea, sedation) • Other serious risks (e.g., abuse, addiction, respiratory depression, overdose) Potential risks • AEs after long-term or high-dose opioid therapy (e.g., hyperalgesia, endocrinologic or Alternatives to opioids sexual dysfunction)

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Patient-Prescriber Agreement (PPA) Document signed by both patient & prescriber at time an opioid is prescribed

Clarify treatment plan & goals of treatment w/ patient, patient’s family, & other clinicians involved in patient’s care

Assist in patient education

Inform patients about the risks & benefits

Document patient & prescriber responsibilities

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Consider a PPA Reinforce expectations for appropriate & safe opioid use

• Obtain opioids from a • Commitments to return for single prescriber follow-up visits • Fill opioid prescriptions at a • Comply w/ appropriate designated pharmacy monitoring • Safeguard opioids – E.g., random UDT & pill counts – Do not store in medicine • Frequency of prescriptions cabinet • Enumerate behaviors that – Keep locked (e.g., use a may lead to opioid medication safe) discontinuation – Do not share or sell medication • An exit strategy • Instructions for disposal when no longer needed

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Monitor Patients During Opioid Therapy

Therapeutic risks & Periodically assess benefits do not Identify patients continued need for remain static opioid analgesic

Affected by change in • Who are benefiting from Re-evaluate underlying underlying pain opioid therapy medical condition condition, coexisting • Who might benefit more if clinical presentation disease, or w/ restructuring of changes psychologic/ social treatment or receiving circumstances additional services (e.g., addiction treatment) • Whose benefits from treatment are outweighed by risks

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Monitor Patients During Opioid Therapy, cont’d

Patients requiring more Periodically evaluate: frequent monitoring include:

• Pain control • High-risk patients – Document pain intensity, pattern, • Patients taking high opioid doses & effects • Functional outcomes – Document level of functioning – Assess progress toward achieving therapeutic goals • Health-related QOL • AE frequency & intensity • Adherence to prescribed therapies

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Anticipate & Treat Common AEs

most common AE; does not Nausea & tend to diminish over Constipation resolve with time vomiting days or weeks

. Initiate a bowel regimen before constipation develops . Increase fluid & fiber intake, stool Oral & rectal antiemetic therapies as needed softeners, & laxatives . Opioid antagonists may help prevent/treat opioid-induced bowel dysfunction

Drowsiness & Pruritus & tend to diminish over tend to wane over time sedation myoclonus days or weeks

Counsel patients about driving, work & home Treatment strategies for either condition safety as well as risks of concomitant exposure largely anecdotal to other drugs & substances w/ sedating effects

Chou R, et al. J Pain. 2009;10:113-30

Monitor Adherence and Aberrant Behavior Routinely monitor patient adherence to treatment plan

• Recognize & document aberrant drug-related behavior – In addition to patient self-report also use: • State PDMPs, where available • UDT – Positive for nonprescribed drugs – Positive for illicit substance – Negative for prescribed opioid • Family member or caregiver interviews • Monitoring tools such as the COMM, PADT, PMQ, or PDUQ • Medication reconciliation (e.g., pill counts)

PADT=Pain Assessment & Documentation Tool

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Address Aberrant Drug-Related Behavior Behavior outside the boundaries of agreed-on treatment plan:

Behaviors that are less Behaviors that are more indicative of aberrancy indicative of aberrancy

Unsanctioned dose escalations or Multiple dose escalations or other other noncompliance w/ therapy noncompliance w/ therapy despite on 1 or 2 occasions warnings

Unapproved use of the drug to Prescription forgery treat another symptom

Openly acquiring similar drugs Obtaining prescription drugs from from other medical sources nonmedical sources

Prescription Drug Monitoring Programs (PDMPs) 49 states have an operational PDMP DC has enacted PDMP legislation, not yet operational 1 state has no legislation Individual state laws determine

• Who has access to PDMP information • Which drug schedules are monitored • Which agency administers the PDMP • Whether prescribers are required to register w/ the PDMP • Whether prescribers are required to access PDMP information in certain circumstances • Whether unsolicited PDMP reports are sent to prescribers

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PDMP Benefits

Record of a patient’s Provide warnings of controlled substance potential misuse/abuse prescriptions

• Some are available • Existing prescriptions not online 24/7 reported by patient • Opportunity to discuss • Multiple w/ patient prescribers/pharmacies • Drugs that increase overdose risk when taken together • Patient pays for drugs of abuse w/ cash Prescribers can check their own prescribing Hx

PDMP Unsolicited Patient Threshold Reports Reports automatically generated on patients who cross certain thresholds when filling prescriptions. Available in some states.

E-mailed to prescribers to Prescribers review records to confirm it is whom prescriptions were your patient & you wrote the prescription(s) attributed attributed to you

If you wrote the prescription(s), patient If inaccurate, contact safety may dictate need to discuss the PDMP patient w/ other prescribers listed on report • Decide who will continue to prescribe for the patient & who might address drug abuse concerns.

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Rationale for Urine Drug Testing (UDT)

Help to identify drug misuse/addiction • Prior to starting opioid treatment Assist in assessing adherence during opioid therapy • As requirement of therapy w/ an opioid • Support decision to refer

UDT frequency is based on clinical judgment

Depending on patient’s display of aberrant behavior Check state regulations for and whether it is sufficient to requirements document adherence to treatment plan

Main Types of UDT Methods

Initial testing w/ IA drug panels: • Classify substance as present or absent according to cutoff • Many do not identify individual drugs within a class • Subject to cross-reactivity • Either lab based or at POC

Identify specific drugs &/or metabolites w/ sophisticated lab-based testing; e.g., GC/MS or LC/MS* • Specifically confirm the presence of a given drug – e.g., morphine is the opiate causing a positive IA* • Identify drugs not included in IA tests * GC/MS=gas chromatography/ mass spectrometry • When results are contested IA=immunoassay LC/MS=liquid chromatography/ mass spectrometry

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Detecting Opioids by UDT

Most common opiate IA GC/MS or LC/MS will drug panels identify specific opioids

• Detect “opiates” morphine & • Confirm presence of codeine, but doesn’t distinguish a drug causing a positive IA • Do not reliably detect • Identify opioids not included in semisynthetic opioids IA drug panels, including – Specific IA panels can be ordered semisynthetic & synthetic for some opioids • Do not detect synthetic opioids • Identify opioids not included in (e.g., methadone, fentanyl) IA drug panels, including semisynthetic & synthetic – Only a specifically directed IA panel will detect synthetics opioids

Interpretation of UDT Results

Demonstrates recent use Positive • Most drugs in urine have detection times of 1-3 d Result • Chronic use of lipid-soluble drugs: test positive for ≥1 wk Does not diagnose • Drug addiction, physical dependence, or impairment Does not provide enough information to determine • Exposure time, dose, or frequency of use

Does not diagnose diversion Negative • More complex than presence or absence of a drug in urine Result May be due to maladaptive drug-taking behavior • Bingeing, running out early • Other factors: eg, cessation of insurance, financial difficulties

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Interpretation of UDT Results, cont’d

Be aware Differences exist between IA test menu panels vary Testing technologies & • Cross-reactivity patterns methodologies evolve – Maintain list of all patient’s prescribed & OTC drugs – Assist to identify false-positive result • Cutoff levels

Time taken to Opioid metabolism may eliminate drugs explain presence • Document time of last use & of apparently quantity of drug(s) taken unprescribed drugs

Examples of Metabolism of Opioids

Codeine Morphine 6-MAM* Heroin

t½=25-30 min t½=3-5 min

Hydrocodone Hydromorphone

Oxycodone Oxymorphone

*6-MAM=6-monoacetylmorphine

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Interpretation of UDT Results

Use UDT results in conjunction w/ other clinical information

Investigate unexpected results

Schedule appointment Discuss w/ the lab w/ patient to discuss unexpected/abnormal results

Chart results, interpretation, & action

Do not ignore the unexpected positive result

May necessitate closer monitoring &/or referral to a specialist

Gourlay DL, et al. Urine Drug Testing in Clinical Practice. The Art & Science of Patient Care. Ed 4. 2010. 79 | © CO*RE 2015 Collaborative for REMS Education

ER/LA Opioid Use in Pregnant Women

No adequate & well-controlled studies

Only use if potential benefit justifies the risk to the fetus

Be aware of the pregnancy status of your patients

If prolonged use is required during pregnancy: • Advise patient of risk of neonatal withdrawal syndrome • Ensure appropriate treatment will be available

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Be Ready to Refer Be familiar w/ referral sources for abuse or addiction that may arise from use of ER/LA opioids

SAMHSA substance SAMHSA mental abuse treatment health treatment facility locator facility locator

http://findtreatment.samhsa.gov/Treatme http://findtreatment.samhsa.gov/MHTreat ntLocator/faces/quickSearch.jspx mentLocator/faces/quickSearch.jspx

Challenge: The Insistent Patient

Red Flag: Mr. Lee’s daily function has improved significantly over the past two years. You suggest titrating his dosage down or trying alternative Patient refuses pain management options. He is extremely to consider resistant and tells you “Nothing else relieves my non-opioid pain.” treatment options

Action: Work with your patient to set treatment goals and expectations. Select and document a therapy plan or use a patient- provider agreement. Evaluate Mr. Lee for potential addiction; consider referral to psychiatry or addiction medicine.

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Unit 3 Pearls for Practice

Anticipate and Treat Common Adverse Effects

Use Informed Consent and Patient Provider Agreements Use UDT and PDMP as Valuable Sources of Data About your Patient However, know their limitations Monitor Patient Adherence, Side Effects, Aberrant Behaviors, and Clinical Outcomes Refer Appropriately if Necessary

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Use Patient Counseling Document to help counsel patients

Download: www.er-la- opioidrems.com/IwgUI/rems/pdf/patient_co unseling_document.pdf

Order hard copies: www.minneapolis.cenveo.com/pcd/SubmitOr ders.aspx

FDA. EXTENDED-RELEASE (ER) AND LONG-ACTING (LA) OPIOID ANALGESICS RISK EVALUATION AND MITIGATION STRATEGY (REMS). Modified 08/2014. www.fda.gov/downloads/ Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf

Counsel Patients About Proper Use

Instruct patients/ Explain caregivers to

• Product-specific information about • Read the ER/LA opioid the prescribed ER/LA opioid Medication Guide • How to take the ER/LA opioid as received from pharmacy prescribed every time an ER/LA opioid is dispensed • Importance of adherence to dosing regimen, handling • At every medical missed doses, & contacting appointment explain all their prescriber if pain cannot medications they take be controlled

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Counsel Patients About Proper Use, cont’d

Counsel patients/caregivers: • On the most common AEs of ER/LA opioids • About the risk of falls, working w/ heavy machinery, & driving • Call the prescriber for advice about managing AEs • Inform the prescriber about AEs

Prescribers should report serious AEs to the FDA: www.fda.gov/downloads/AboutFDA/ReportsManualsForms /Forms/UCM163919.pdf or 1-800-FDA-1088

Warn Patients

Never break, chew, crush or snort an oral ER/LA tablet/capsule, or cut or tear patches prior to use • May lead to rapid release of ER/LA opioid causing overdose & death • When a patient cannot swallow a capsule whole, prescribers should refer to PI to determine if appropriate to sprinkle contents on applesauce or administer via feeding tube

Use of CNS depressants or alcohol w/ ER/LA opioids can cause overdose & death • Use with alcohol may result in rapid release & absorption of a potentially fatal opioid dose • Other depressants include sedative-hypnotics & anxiolytics, illegal drugs

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Warn Patients, cont’d Misuse of ER/LA opioids can lead to death • Take exactly as directed* • Counsel patients/caregivers on risk factors, signs, & symptoms of overdose & TAKE 1 TABLET BY MOUTH opioid-induced respiratory depression, GI EVERY 12 HOURS obstruction, & allergic reactions OXYCONTIN 10 MG • Call 911 or poison control Qty: 60 TABLETS 1-800-222-1222 *Serious side effects, including death, can occur even when used as recommended Do not abruptly stop or reduce the ER/LA opioid use • Discuss how to safely taper the dose when discontinuing

Co-Prescribing Naloxone Naloxone: Available as: • An opioid antagonist • Naloxone kit (w/ syringes, • Reverses acute opioid-induced respiratory depression needles) but will also cause withdrawal and reverse analgesia • EVZIO™ (naloxone • Administered intramuscularly and subcutaneously HCl) auto-injector • Intranasal formulation currently under consideration • NARCAN nasal with the FDA spray What to do: • Encourage patients to create an ‘overdose plan’ • Involve and train family, friends, partners and/or caregivers • Check expiration dates and keep a viable dose on hand • In the event of known or suspected overdose, administer Naloxone and call

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When to Consider Co-Prescribing Naloxone:

Those at a higher risk for opioid overdose including… • Taking opioid high-doses for pain (50 mg/day equiv) • Receiving rotating opioid medication regimes (at risk for incomplete cross tolerance) • On opioid preparations with increased overdose risk • With respiratory disease (COPD, emphysema, asthma) • With renal or hepatic impairment • Concurrent benzodiazepine use

Abuse Deterrent/Tamper Resistant Opioids

• Response to growing nonmedical use problem • An ER/LA opioid with physical barrier to deter extraction • less likely to be crushed, injected, or snorted • Consider these formulations as one part of an overall REMS strategy • There is mixed evidence on the impact of ADF/TR on misuse • Remember overdose is still possible if taken orally in excessive amounts

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Protecting the Community

Caution Patients

• Sharing ER/LA opioids w/ others may cause them to have serious AEs – Including death • Selling or giving away ER/LA opioids is against the law • Store medication safely and securely • Protect ER/LA opioids from theft • Dispose of any ER/LA opioids when no longer needed – Read product-specific disposal information included w/ ER/LA opioid

Source of Most Recent Rx Opioids Among Past-Year Users (2011-2012) 0.2% 1.8% 4.3% 5.1% Free: friend/relative 1 doctor 14.9% Bought/took: friend/relative Other 54.0% Drug dealer/stranger 19.7% >1 doctor Bought on Internet

SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD. Collaborative for REMS Education 94 | © CO*RE 2015

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Educate Parents: Not in My House

Step 1: Monitor

. Note how many pills in each prescription bottle or pill packet . Keep track of refills for all household members . If your teen has been prescribed a drug, coordinate & monitor dosages & refills . Make sure friends & relatives—especially grandparents— are aware of the risks . If your teen visits other households, talk to the families about safeguarding their medications

Rx Opioid Disposal New “Disposal Act” expands ways for patients to dispose of unwanted/expired opioids Decreases amount of opioids introduced into the environment, particularly into water

Collection receptacles Voluntarily maintained by: Call DEA Registration Call Center at • Law enforcement 1-800-882-9539 to find a local collection • Authorized collectors, including: receptacle . Manufacturer . Distributer . Reverse distributer Mail-back packages . Retail or hospital/clinic pharmacy • Including long-term care Obtained from authorized collectors facilities

Local take-back events DEA National • Conducted by Federal, State, tribal, or Prescription Drug local law enforcement Take-Back Day on • Partnering w/ community groups April 30, 2016

DEA. Federal Register. 2014; 79(174):53520-70. Final Rule. Disposal of Controlled Substances. [Docket No. DEA-316] www.deadiversion.usdoj.gov/fed_regs/rules/2014/2014-20926.pdf DEA. Disposal Act: General Public Fact Sheet. www.deadiversion.usdoj.gov/drug_disposal/fact_sheets/disposal_public.pdf Collaborative for REMS Education 96 | © CO*RE 2015

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Other Methods of Opioid Disposal

If collection receptacle, mail-back program, or take-back event unavailable, throw out in household trash • Take drugs out of original containers • Mix w/ undesirable substance, e.g., used coffee grounds or kitty litter – Less appealing to children/pets, & unrecognizable to people who intentionally go through your trash • Place in sealable bag, can, or other container – Prevent leaking or breaking out of garbage bag • Before throwing out a medicine container – Scratch out identifying info on label

Prescription Drug Disposal

FDA lists especially harmful medicines – in some cases fatal w/ just 1 dose – if taken by someone other than the patient • Instruct patients to check medication guide Flush down sink/toilet if no collection receptacle, mail-back program, or take-back event available • As soon as they are no longer needed – So cannot be accidentally taken by children, pets, or others • Includes transdermal adhesive skin patches – Used patch worn for 3d still contains enough opioid to harm/kill a child – Dispose of used patches immediately after removing from skin • Fold patch in half so sticky sides meet, then flush down toilet • Do NOT place used or unneeded patches in household trash

– Exception is Butrans: can seal in Patch-Disposal Unit provided & dispose of in the trash

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Challenge: The Offended Patient

Mrs. Jorgensen has been your patient for Red Flag: eight years and has never caused any problems. When you ask her to under You decide not to urine drug testing, she becomes upset and request routine accuses you of not trusting her. risk assessment for fear of creating conflict

Action: Describe UDT as a routine part of medication monitoring rather than a “drug test”. Create an office policy for performing UDT on all ER/LA opioid patients. Practice by following universal precautions. Use a patient-provider agreement to clarify expectations of treatment.

Challenge: The Daughter’s Party

Red Flag: Your patient’s daughter, Jody, stole her father’s opioids from his bedside Patients do not drawer to take to a “fishbowl party”. safeguard their Her best friend consumed a mix of opioid opioids and alcohol and died of an medications overdose. correctly

Action: Always counsel patients about safe drug storage; warn patients about the serious consequences of theft, misuse, and overdose. Tell your patients that taking another person’s medication, even once, is against the law.

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Unit 4 Pearls for Practice

Establish Informed Consent Counsel Patients about Proper Use Appropriate use of medication Consequences of inappropriate use Educate the Whole Team Patients, families, caregivers Tools and Documents Can Help with Counseling Use them!

GENERAL DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS

Unit V

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General ER/LA Opioid Drug Information Prescribers should be knowledgeable about general characteristics, toxicities, & drug interactions for ER/LA opioid products:

ER/LA opioid Respiratory Constipation analgesic products depression is the most are scheduled is the most common under the Controlled serious long-term Substances Act & opioid AE AE can be misused & abused Can be immediately Should be life-threatening anticipated

For Safer Use: Know Drug Interactions, PK, & PD

Some ER/LA products rapidly CNS depressants can potentiate release opioid (dose dump) when sedation & respiratory depression exposed to alcohol Some drug levels may increase without dose dumping

Use w/ MAOIs may increase respiratory depression Can reduce efficacy of diuretics Certain opioids w/ MAOIs can cause Inducing release of antidiuretic hormone serotonin syndrome

Drugs that inhibit or induce CYP Methadone & buprenorphine can enzymes can increase prolong QTc interval or lower blood levels of some opioids

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Opioid Tolerant Tolerance to sedating & respiratory-depressant effects is critical to safe use of certain ER/LA opioid products, dosage unit strengths, or doses Patients must be opioid tolerant before using • Any strength of transdermal fentanyl or hydromorphone ER • Certain strengths or daily doses of other ER products Opioid-tolerant patients are those taking at least • 60 mg oral morphine/day • 25 mcg transdermal fentanyl/hr • 30 mg oral oxycodone/day FOR 1 WK • 8 mg oral hydromorphone/day OR LONGER • 25 mg oral oxymorphone/day • An equianalgesic dose of another opioid

Key Instructions: ER/LA Opioids

Individually titrate to Times required a dose that provides to reach adequate analgesia steady-state plasma & minimizes concentrations adverse reactions are product-specific

Continually Refer to product re-evaluate to assess information for maintenance of titration interval pain control & emergence of AEs

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Key Instructions: ER/LA Opioids, cont’d When an ER/LA During chronic opioid is no therapy, longer required, especially for If pain increases, gradually titrate non-cancer- attempt to dose downward related pain, identify to prevent signs periodically source, while & symptoms of reassess the adjusting dose withdrawal in continued need physically for opioids dependent patients Do not abruptly discontinue

Common Drug Information for This Class Dosage reduction Limitations Relative potency for hepatic or of usage to oral morphine renal impairment • Reserve for when See individual drug PI • Intended as general guide alternative options (eg, • Follow conversion non-opioids or IR opioids) instructions in individual PI are ineffective, not tolerated, or otherwise • Incomplete cross- inadequate tolerance & inter-patient variability require • Not for use as an conservative dosing when as-needed analgesic converting from 1 • Not for mild pain or pain opioid to another not expected to persist for – Halve calculated an extended duration comparable dose & titrate • Not for acute pain new opioid as needed

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Transdermal Dosage Forms Do not cut, damage, chew, or swallow

Exertion or exposure Prepare skin: clip - Rotate location of to external heat can not shave - hair & application lead to fatal overdose wash area w/ water

Monitor patients w/ fever for Metal foil backings are not signs or symptoms of safe for use in MRIs increased opioid exposure

Drug Interactions Common to this Class Concurrent use w/ other CNS Avoid concurrent use of depressants can increase risk partial agonists* or mixed of respiratory depression, agonist/antagonists† with hypotension, profound full opioid agonist sedation, or coma May reduce analgesic effect &/or Reduce initial dose of one precipitate withdrawal or both agents

Concurrent use w/ May enhance neuromuscular anticholinergic medication blocking action of skeletal increases risk of muscle relaxants & increase urinary retention & respiratory depression severe constipation May lead to paralytic ileus

*Buprenorphine; †Pentazocine, nalbuphine, butorphanol

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Drug Information Common to This Class

Use in opioid- Contraindications tolerant patients

• See individual PI for products • Significant respiratory depression which: • Acute or severe asthma in an – Have strengths or total daily doses unmonitored setting or in only for use in opioid-tolerant absence of resuscitative patients equipment – Are only for use in opioid-tolerant • Known or suspected patients at all strengths paralytic ileus • Hypersensitivity (e.g., anaphylaxis) • See individual PI for additional contraindications

Unit 5 Pearls for Practice

Patients MUST be opioid-tolerant in order to safely take most ER/LA opioid products

Be familiar with drug-drug interactions, pharmacokinetics and pharmacodynamics of ER/LA opioids

Central nervous system depressants (alcohol, sedatives, hypnotics, tranquilizers, tricyclic antidepressants) can have a potentiating effect on the sedation and respiratory depression caused by opioids.

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Challenge: The Patient in the ER

Red Flag: Action: Be familiar with risk factors for respiratory depression and know You are woken when opioids are contra-indicated. by a telephone Anticipate possible risks and develop call at 2 am contingency plans. Teach patients, reporting that family, and caregivers about your patient, Mr. Diallo, is in the respiratory depression and its ER with symptoms. apparent respiratory depression.

SPECIFIC DRUG INFORMATION FOR ER/LA OPIOID ANALGESIC PRODUCTS Unit VI

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Specific Characteristics Know for opioid products you prescribe:

Drug Dosing Formulation Strength substance interval

Use in opioid- Product- Relative Key tolerant specific safety potency to instructions patients concerns morphine

Specific information about Specific drug interactions product conversions, if available

For detailed information, refer to online PI: DailyMed at www.dailymed.nlm.nih.gov Drugs@FDA at www.fda.gov/drugsatfda

Morphine Sulfate ER Capsules (Avinza) Capsules 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, and 120 mg

Dosing interval • Once a day • Initial dose in opioid non-tolerant patients is 30 mg • Titrate in increments of not greater than 30 mg using a minimum of 3-4 d intervals Key instructions • Swallow capsule whole (do not chew, crush, or dissolve) • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing; use immediately • MDD:* 1600 mg (renal toxicity of excipient, fumaric acid) • Alcoholic beverages or medications w/ alcohol may result in rapid Drug release & absorption of potentially fatal dose interactions • P-gp* inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold Opioid-tolerant • 90 mg & 120 mg capsules for use in opioid-tolerant patients only Product- specific safety • None concerns

* MDD=maximum daily dose; P-gp= P-glycoprotein

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Buprenorphine Buccal Film (Belbuca) 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg, and 900 mcg

Dosing • Every 12 h (or once every 24 h for initiation in opioid naïve patients interval & patients taking less than 30 mg oral morphine sulfate eq

• Opioid-naïve pts or pts taking <30 mg oral morphine sulfate eq: Initiate treatment with a 75 mcg buccal film, once daily, or if tolerated, every 12 h - Titrate to 150 mcg every 12 h no earlier than 4 d after initiation - Individual titration to a dose that provides adequate analgesia and minimizes adverse reaction should proceed in increments of 150 mcg every 12 h, no more frequently than every 4 d Key • When converting from another opioid, first taper the current opioid instructions to no more than 30 mg oral morphine sulfate eq/day prior to initiating Belbuca - If prior daily dose before taper was 30 mg to 89 mg oral morphine sulfate eq, initiate with 150 mcg dose every 12 h - If prior daily dose before taper was 90 mg to 160 mg oral morphine sulfate eq, initiate with 300 mcg dose every 12 h - Titration of the dose should proceed in increments of 150 mcg every 12 h, no more frequently than every 4 d

Buprenorphine Buccal Film (Belbuca) cont’d • Maximum dose: 900 mcg every 12 h due to the potential for QTc prolongation • Severe Hepatic Impairment: Reduce the starting and incremental dose by Key half that of patients with normal liver function instructions • Oral Mucositis: Reduce the starting and incremental dose by half that of patients without mucositis • Do not use if the package seal is broken or the film is cut, damaged, or changed in any way • CYP3A4 inhibitors may increase buprenorphine levels • CYP3A4 inducers may decrease buprenorphine levels Specific Drug Interactions • Benzodiazepines may increase respiratory depression • Class IA and III antiarrhythmics, other potentially arrhythmogenic agents, may increase risk for QTc prolongation and torsade de pointes Use in Opioid- • Belbuca 600 mcg, 750 mcg, and 900 mcg are for use following titration Tolerant from lower doses of Belbuca Patients

Product- • QTc prolongation and torsade de pointes Specific Safety Concerns • Hepatotoxicity

Relative Potency: Oral • Equipotency to oral morphine has not been established. 118 | © CO*RE 2015 Collaborative for REMS Education Morphine

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Buprenorphine Transdermal System (Butrans) Transdermal System 5 mcg/hr, 7.5 mcg/hr, 10 mcg/hr, 15 mcg/hr, 20 mcg/hr

Dosing • One transdermal system every 7 d interval • Initial dose in opioid non-tolerant patients on <30 mg morphine equivalents & in mild-moderate hepatic impairment: 5 mcg/h • When converting from 30 mg-80 mg morphine equivalents, first taper to 30 mg morphine equivalent, then initiate w/ 10 mcg/h • Titrate in 5 or 10 mcg/h increments by using no more than 2 patches of the 5 or 10 mcg/h system(s) w/ minimum of 72 h prior between dose adjustments. Total dose from all patches should be ≤20 mcg/h Key • Maximum dose: 20 mcg/h due to risk of QTc prolongation instructions • Application • Apply only to sites indicated in PI • Apply to intact/non-irritated skin • Prep skin by clipping hair; wash site w/ water only • Rotate application site (min 3 wks before reapply to same site) • Do not cut • Avoid exposure to heat • Dispose of patches: fold adhesive side together & flush down toilet

Buprenorphine Transdermal System (Butrans) cont’d

• CYP3A4 inhibitors may increase buprenorphine levels • CYP3A4 inducers may decrease buprenorphine levels Drug interactions • Benzodiazepines may increase respiratory depression • Class IA & III antiarrythmics, other potentially arrhythmogenic agents, may increase risk of QTc prolongation & torsade de pointe

Opioid- • 7.5 mcg/h, 10 mcg/h, 15 mcg/h, & 20 mcg/h for use in opioid- tolerant tolerant patients only

Product- • QTc prolongation & torsade de pointe specific • Hepatotoxicity safety concerns • Application site skin reactions Relative potency: oral • Equipotency to oral morphine not established morphine

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Methadone Hydrochloride Tablets (Dolophine)

Dosing • Every 8 to 12 h interval • Initial dose in opioid non-tolerant patients: 2.5 – 10 mg • Conversion of opioid-tolerant patients using equianalgesic tables can result in overdose & death. Use low doses according to table in full PI • Titrate slowly with dose increases no more frequent than every 3-5 d. Because of high variability in methadone metabolism, some patients Key may require substantially longer periods between dose increases (up to instructions 12 d). • High inter-patient variability in absorption, metabolism, & relative analgesic potency • Opioid detoxification or maintenance treatment only provided in a federally certified opioid (addiction) treatment program (CFR, Title 42, Sec 8) • Pharmacokinetic drug-drug interactions w/ methadone are complex − CYP 450 inducers may decrease methadone levels − CYP 450 inhibitors may increase methadone levels Drug − Anti-retroviral agents have mixed effects on methadone levels interactions • Potentially arrhythmogenic agents may increase risk for QTc prolongation & torsade de pointe • Benzodiazepines may increase respiratory depression

FDA. Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics. 08/2014. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM311290.pdf 121 | © CO*RE 2013 Collaborative for REMS Education

Methadone Hydrochloride Tablets (Dolophine) cont’d

Opioid- • Refer to full PI tolerant

• QTc prolongation & torsade de pointe Product- • Peak respiratory depression occurs later & persists longer than specific analgesic effect safety • concerns Clearance may increase during pregnancy • False-positive UDT possible

Relative potency: • Varies depending on patient’s prior opioid experience oral morphine

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Fentanyl Transdermal System (Duragesic) 12, 25, 37.5*, 50, 62.5*, 75, 87.5*, and 100 mcg/hr (*These strengths are available only in generic form)

Dosing • Every 72 h (3 d) interval • Use product-specific information for dose conversion from prior opioid • Hepatic or renal impairment: use 50% of dose if mild/moderate, avoid use if severe • Application − Apply to intact/non-irritated/non-irradiated skin on a flat surface Key − Prep skin by clipping hair, washing site w/ water only instructions − Rotate site of application − Titrate using a minimum of 72 h intervals between dose adjustments − Do not cut • Avoid exposure to heat • Avoid accidental contact when holding or caring for children • Dispose of used/unused patches: fold adhesive side together & flush down toilet

Fentanyl Transdermal System (Duragesic), cont’d

Specific contraindications: • Patients who are not opioid-tolerant Key instructions • Management of − Acute or intermittent pain, or patients who require opioid analgesia for a short time − Post-operative pain, out-patient, or day surgery − Mild pain • CYP3A4 inhibitors may increase fentanyl exposure • CYP3A4 inducers may decrease fentanyl exposure Drug interactions • Discontinuation of concomitant CYP P450 3A4 inducer may increase fentanyl plasma concentration Opioid-tolerant • All doses indicated for opioid-tolerant patients only • Accidental exposure due to secondary exposure to unwashed/unclothed application site Product-specific • Increased drug exposure w/ increased core body temp or fever safety concerns • Bradycardia • Application site skin reactions Relative potency: • See individual PI for conversion recommendations from prior opioid oral morphine

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Morphine Sulfate ER-Naltrexone (Embeda) Capsules 20 mg/0.8 mg, 30 mg/1.2 mg, 50 mg/2 mg, 60 mg/2.4 mg, 80 mg, 3.2 mg, 100 mg/4 mg

Dosing interval • Once a day or every 12 h

• Initial dose as first opioid: 20 mg/0.8 mg • Titrate using a minimum of 1-2 d intervals • Swallow capsules whole (do not chew, crush, or dissolve) Key instructions • Crushing or chewing will release morphine, possibly resulting in fatal overdose, & naltrexone, possibly resulting in withdrawal symptoms • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately • Alcoholic beverages or medications w/ alcohol may result in rapid release Drug & absorption of potentially fatal dose interactions • P-gp inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold

Opioid-tolerant • 100 mg/4 mg capsule for use in opioid-tolerant patients only

Product-specific • None safety concerns

Hydromorphone Hydrochloride (Exalgo) ER Tablets 8 mg, 12 mg, 16 mg, 32 mg

Dosing interval • Once a day • Use conversion ratios in individual PI • Start patients w/ moderate hepatic impairment on 25% dose prescribed for patient w/ normal function • Renal impairment: start patients w/ moderate on 50% & patients w/ Key instructions severe on 25% dose prescribed for patient w/ normal function • Titrate in increments of 4-8 mg using a minimum of 3-4 d intervals • Swallow tablets whole (do not chew, crush, or dissolve) • Do not use in patients w/ sulfite allergy (contains sodium metabisulfite) Drug interactions • None Opioid-tolerant • All doses are indicated for opioid-tolerant patients only Product-specific • Allergic manifestations to sulfite component adverse reactions

Relative potency: • ~5:1 oral morphine to hydromorphone oral dose ratio, use conversion oral morphine recommendations in individual product information

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Hydrocodone Bitartrate (Hysingla ER) ER Tablets, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120mg

Dosing • Once a day interval

• Opioid-naïve patients: initiate treatment with 20 mg orally once daily. • During titration, adjust the dose in increments of 10 mg to 20 mg every 3 to 5 days until adequate analgesia is achieved. • Swallow tablets whole (do not chew, crush, or dissolve). • Consider use of an alternative analgesic in patients who have difficulty Key swallowing or have underlying gastrointestinal disorders that may predispose instructions them to obstruction. • Take one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. • Use 1/2 of the initial dose and monitor closely for adverse events, such as respiratory depression and sedation, when administering Hysingla ER to patients with severe hepatic impairment or patients with moderate to severe renal impairment.

Hydrocodone Bitartrate (Hysingla ER), cont’d

• CYP3A4 inhibitors may increase hydrocodone exposure. • CYP3A4 inducers may decrease hydrocodone exposure. • Concomitant use of Hysingla ER with strong laxatives (e.g., Lactulose) that Drug interactions rapidly increase GI motility may decrease hydrocodone absorption and result in decreased hydrocodone plasma levels. • The use of MAO inhibitors or tricyclic antidepressants with Hysingla ER may increase the effect of either the antidepressant or Hysingla ER. Opioid-tolerant • A single dose ≥ 80 mg is only for use in opioid tolerant patients. • Use with caution in patients with difficulty swallowing the tablet or underlying gastrointestinal disorders that may predispose patients to obstruction. • Esophageal obstruction, dysphagia, and choking have been reported with Hysingla ER. • In nursing mothers, discontinue nursing or discontinue drug. QTc Product-specific prolongation has been observed with Hysingla ER following daily doses of safety concerns 160 mg. • Avoid use in patients with congenital long QTc syndrome. This observation should be considered in making clinical decisions regarding patient monitoring when prescribing Hysingla ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QTc interval. • In patients who develop QTc prolongation, consider reducing the dose. Relative potency: Collaborative for REMS Education • See individual PI for conversion recommendations from prior opioid oral morphine

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Morphine Sulfate (Kadian) ER Capsules 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 100 mg, 130mg, 150 mg, 200 mg

Dosing interval • Once a day or every 12 h

• PI recommends not using as first opioid • Titrate using minimum of 2-d intervals Key instructions • Swallow capsules whole (do not chew, crush, or dissolve) • May open capsule & sprinkle pellets on applesauce for patients who can reliably swallow without chewing, use immediately

• Alcoholic beverages or medications w/ alcohol may result in rapid release & absorption of potentially fatal dose of morphine Drug interactions • P-gp inhibitors (e.g., quinidine) may increase absorption/exposure of morphine by ~2-fold

• 100 mg, 130 mg, 150 mg, 200 mg capsules for use in opioid-tolerant Opioid-tolerant patients only

Product-specific • None safety concerns

Morphine Sulfate (MorphaBond) ER Tablets 15 mg, 30 mg, 60 mg, 100 mg

Dosing interval • Every 8 h or every 12h

• Product information recommends not using as first opioid Key instructions • Titrate using a minimum of 1 – 2 d intervals • Swallow tablets whole (do not chew, crush, or dissolve)

• P-gp inhibitors (e.g. quinidine) may increase the Specific Drug absorption/exposure of morphine sulfate by about two-fold interactions

• MorphaBond 100 mg tablets are for use in opioid-tolerant Opioid-tolerant patients only

Product-specific • None safety concerns

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Morphine Sulfate (MS Contin) ER Tablets 15 mg, 30 mg, 60 mg, 100 mg, 200mg

Dosing interval • Every 8 h or every 12 h

• Product information recommends not using as first opioid. Key instructions • Titrate using a minimum of 1-2 d intervals • Swallow tablets whole (do not chew, crush, or dissolve)

• P-gp inhibitors (e.g., quinidine) may increase Drug interactions absorption/exposure of morphine by ~2-fold

• 100 mg & 200 mg tablet strengths for use in opioid-tolerant Opioid-tolerant patients only

Product-specific • None safety concerns

Tapentadol (Nucynta ER) ER Tablets 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

Dosing interval • Every 12 h • 50 mg every 12 h is initial dose in opioid non-tolerant patients • Titrate by 50 mg increments using minimum of 3-d intervals • MDD: 500 mg • Swallow tablets whole (do not chew, crush, or dissolve) Key instructions • Take 1 tablet at a time w/ enough water to ensure complete swallowing immediately after placing in mouth • Dose once/d in moderate hepatic impairment (100 mg/d max) • Avoid use in severe hepatic & renal impairment • Alcoholic beverages or medications w/ alcohol may result in rapid Drug interactions release & absorption of a potentially fatal dose of tapentadol • Contraindicated in patients taking MAOIs Opioid-tolerant • No product-specific considerations Product-specific • Risk of serotonin syndrome safety concerns • Angio-edema Relative potency: • Equipotency to oral morphine has not been established oral morphine 132 | © CO*RE 2015 Collaborative for REMS Education

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Oxymorphone Hydrochloride (Opana ER) ER Tablets 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg

• Every 12 h dosing, some may benefit from asymmetric (different Dosing interval dose given in AM than in PM) dosing • Use 5 mg every 12 h as initial dose in opioid non-tolerant patients & patients w/ mild hepatic impairment & renal impairment (creatinine clearance <50 mL/min) & patients >65 yrs • Swallow tablets whole (do not chew, crush, or dissolve) Key instructions • Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth • Titrate in increments of 5-10 mg using a minimum of 3-7 d intervals • Contraindicated in moderate & severe hepatic impairment • Alcoholic beverages or medications w/ alcohol may result in Drug interactions absorption of a potentially fatal dose of oxymorphone Opioid-tolerant • No product-specific considerations • Use with caution in patients who have difficulty swallowing or Product-specific underlying GI disorders that may predispose to obstruction (e.g. small safety concerns gastrointestinal lumen) Relative potency: • Approximately 3:1 oral morphine to oxymorphone oral dose ratio oral morphine 133 | © CO*RE 2015 Collaborative for REMS Education

Oxycodone Hydrochloride (OxyContin) NEW DOSING ER Tablets 10mg, 15mg, 20,mg, 30mg, 40mg, 60mg and 80 mg INFO Dosing interval • Every 12 h • Initial dose in opioid-naïve and non-tolerant patients: 10 mg every 12 h • Titrate using a minimum of 1-2 d intervals • Hepatic impairment: start w/ ⅓-½ usual dosage • Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage Key instructions • Consider other analgesics in patients w/ difficulty swallowing or underlying GI disorders that predispose to obstruction. Swallow tablets whole (do not chew, crush, or dissolve) • Take 1 tablet at a time, w/ enough water to ensure complete swallowing immediately after placing in mouth • CYP3A4 inhibitors may increase oxycodone exposure Drug interactions • CYP3A4 inducers may decrease oxycodone exposure • Single dose >40 mg or total daily dose >80 mg for use in opioid-tolerant patients Opioid-tolerant only

Product-specific • Choking, gagging, regurgitation, tablets stuck in throat, difficulty swallowing tablet safety concerns • Contraindicated in patients w/ GI obstruction

Relative potency: • Approximately 2:1 oral morphine to oxycodone oral dose ratio oral morphine

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Oxycodone Hydrochloride (OxyContin) con’t ER Tablets 10mg, 15mg, 20,mg, 30mg, 40mg, 60mg and 80 mg

For Adults: • Single dose greater than 40 mg or total daily dose greater than 80 mg are for use in adult patients in whom tolerance to an opioid of comparable tolerance has been established. • When a dose increase is clinically indicated, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose. For Pediatric Patients (11 years and older) Key instructions • For use only in opioid tolerant pediatric patients already receiving and tolerating opioids for at least five (5) consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent for at least 2 days immediately preceding dosing with Oxycodon ER. Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage • If needed, pediatric dose may be adjusted in 1 to 2 day intervals. • When a dose increase is clinically indicated, the total daily oxycodone dose usually can be increased by 25% of the current daily dose.

• Opioids are rarely indicated or used to treat pediatric patients with chronic pain. • The recent FDA approval for this oxycodone formulation was NOT IMPORTANT: intended to increase prescribing or use of this drug in pediatric pain

135 | © CO*RE 2015 treatment. Review the product informationCollaborative and adhere for toREMS best Education practices in the literature.

Oxycodone Hydrochloride/Naloxone Hydrochloride (Targiniq ER) ER Tablets 10 mg/5mg, 20 mg/10 mg, 40 mg/20 mg

Dosing interval • Every 12 h • Opioid-naïve patients: initiate treatment w/ 10mg/5mg every 12 h • Titrate using min of 1-2 d intervals • Do not exceed 80 mg/40 mg total daily dose (40 mg/20 mg q12h) • May be taken w/ or without food Key instructions • Swallow whole. Do not chew, crush, split, or dissolve: this will release oxycodone (possible fatal overdose) & naloxone (possible withdrawal) • Hepatic impairment: contraindicated in moderate-severe impairment. In patients w/ mild impairment, start w/ ⅓-½ usual dosage • Renal impairment (creatinine clearance <60 mL/min): start w/ ½ usual dosage Drug • CYP3A4 inhibitors may increase oxycodone exposure interactions • CYP3A4 inducers may decrease oxycodone exposure • Single dose >40 mg/20 mg or total daily dose of 80 mg/40 mg for opioid- Opioid-tolerant tolerant patients only Product-specific • Contraindicated in patients w/ moderate-severe hepatic impairment safety concerns Relative potency: • See individual PI for conversion recommendations from prior opioids 136oral | © CO*RE morphine 2015 Collaborative for REMS Education

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Hydrocodone Bitartrate (Zohydro ER) ER Capsules 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg

Dosing interval • Every 12 h • Initial dose in opioid non-tolerant patient is 10 mg Key instructions • Titrate in increments of 10 mg using a min of 3-7 d intervals • Swallow capsules whole (do not chew, crush, or dissolve) • Alcoholic beverages or medications containing alcohol may result in rapid release & absorption of a potentially fatal dose of Drug interactions hydrocodone • CYP3A4 inhibitors may increase hydrocodone exposure • CYP3A4 inducers may decrease hydrocodone exposure • Single dose >40 mg or total daily dose >80 mg for use in Opioid-tolerant opioid-tolerant patients only Product-specific • None safety concerns Relative potency: • Approximately 1.5:1 oral morphine to hydrocodone oral dose ratio oral morphine

Naloxone (Narcan)

• IM or SQ: onset 2-5 minutes, duration >45 min Dosing interval • IV: onset 1-2 min, duration 45 minutes

• Monitor respiratory rate • Monitor level of consciousness for 3-4 hours after expected peak of blood Key instructions concentrations • Note that reversal of analgesia will occur

Drug • Larger doses required to reverse effects of buprenorphine, butorphanol, interactions nalbuphine, or pentazocine • Assess signs and symptoms of opioid withdrawal, may occur w-i 2 min – 2 hrs Opioid-tolerant • Vomiting, restlessness, abdominal cramps, increased BP, temperature • Severity depends on naloxone dose, opioid involved & degree of dependence • Ventricular arrhythmias, hypertension, hypotension, nausea & vomiting Product-specific • safety concerns As naloxone plasma levels decrease, sedation from opioid overdose may increase

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Summary

Prescription opioid abuse & overdose is a national epidemic. Clinicians must play a role in prevention

Be familiar w/ how to Understand how to initiate therapy, Know how to manage assess patients for modify dose, & ongoing therapy w/ treatment discontinue use of ER/LA opioids w/ ER/LA opioids ER/LA opioids

Know how to counsel Be familiar w/ general patients & caregivers & product-specific about the safe drug information use of ER/LA opioids, concerning including proper ER/LA opioids storage & disposal

IMPORTANT!

Thank you for completing the post-activity assessment for this CO*RE session. Your participation in this assessment allows CO*RE to report de-identified numbers to the FDA. A strong show of engagement will demonstrate that clinicians have voluntarily taken this important education and are committed to patient safety and improved outcomes. THANK YOU!

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Thank you! www.core-rems.org

71 Osteopathic Manipulation for the Busy Practice

Robert J. Cromley, D.O.

Learning Objectives:

Define a fundamental approach to patients to increase the inclusion of OMM in a clinical practice. Describe common clinical scenarios where OMM is underutilized. Present a practical approach to utilizing OMM in a way to increase usefulness in a busy practice. Drugs in America 2016

Robert M. Stutman Jude Jodi Debbrecht Switalski

Learning Objectives:

Describe the paradigm shift in the US involving substance abuse. Describe what actions medical professionals can take to better identify and prevent prescription drug misuse/abuse and diversion. Discuss what physician liabilities exist for a patient’s addiction to or overdose from prescription drugs. Discuss current trends in the use of medication assisted treatments for opioid addition and the argument for and against their use.

NOTES ______SUNDAY, NOVEMBER 13, 2016 5 credits

7:00 a.m. Breakfast Buffet - West Pathway

Moderator: Roger L. Wohlwend, D.O.

7:00 a.m.-9:00 a.m. Breakfast Buffet Served

8:00 a.m.-9:00 a.m. Breast Cancer Update 2016: The Latest in Diagnosis and Treatment Sarath K. Palakodeti, D.O.

9:00 a.m.-10:00 a.m. Young , Healthy…and Immortal: Discussing Advance Directives with Patients Who Don’t Think They Need Them Laura T. Phillipps, RN, MSN, CHPN

10:00 a.m.-11:00 a.m. The Basic Principles and History of Hyperbaric Oxygen Therapy George Thomas Magill, M.D.

11:00 a.m.-12:00 p.m. TMS Therapy: A Unique and Proven Approach to Treating Depression Carlos G. Lowell, D.O.

12:00 pm.-1:00 p.m. The Anterior Approach to Hip Replacement Richard M. Miller, D.O., FAOAO

8:00 a.m.-1:00 p.m. ACLS Recertification - Tamarind Room Brent C. DeVries, D.O. & Captain David Degnan, Fire Chief

Breast Cancer Update 2016: The Latest in Diagnosis and Treatment

Sarath K. Palakodeti, D.O.

Learning Objectives: Identify breast lesions and masses, and know appropriate workup for a breast mass. List appropriate patient recommendations based on breast imaging BIRADS guidelines. Recognize the latest in breast cancer diagnosis and treatment. Young, Healthy…and Immortal: Discussing Advance Directives with Patients Who Don’t Think They Need Them

Laura T. Phillipps, RN, MSN, CHPN

Learning Objectives:

Review the evolution of advance directives and advance care planning in our country. Explain Ohio advance directives forms. Discuss the advance care planning process with a healthy adult.

NOTES ______

The Basic Principles and History of Hyperbaric Oxygen Therapy

George Thomas Magill, M.D.

Learning Objectives:

Recognize the basic principles and history of hyperbaric oxygen therapy (HBOT). Define the role of HBOT in wound healing Identify the chronic and acute indications for HBOT.

11/10/2016

Introduction to Hyperbaric Medicine

George Magill, MD Wound Care Solutions Bryan Hospital Bryan, Ohio

CME Disclosure No relevant financial relationships with commercial interests

Purpose of Presentation

History of Hyperbaric Medicine Physiology & Pharmacology Of HBO2 Rationale For HBO2 In Wound Healing HBO Indications

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Monoplace chambers are designed for one patient at a time using 100% Oxygen

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The model we are using is easy to operate, with few moving parts and no computerization.

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We are plumbed for two chambers. One tech can safely operate two chambers at a time.

 1670: Robert Boyle demonstrated that a reduction in ambient pressure could lead to bubble formation in living tissue. This description of a viper in a vacuum was the first recorded description of decompression sickness

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Where Did It All Start ?

Interestingly, The Story Starts With the Brooklyn Bridge

 1873: Andrew Smith first utilized the term "caisson disease" describing 110 cases of decompression sickness as the physician in charge during construction of the Brooklyn Bridge. The project employed 600 compressed air workers. Recompression treatment was not used. The project chief engineer Washington Roebling suffered from caisson disease, and endured the after-effects of the disease for the rest of his life.

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There were many reports of illness associated with compressed air environments prior to the building of the Brooklyn Bridge, But Smith was the first to “put it all together” and write it up.

Caisson Disease

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Launching Size and weight of Brooklyn Caisson: 168 x 102 x 14.5 feet; 3000 tons. Launching Size and weight of New York Caisson: 172 x 102 x 14.5 feet; 3250 tons

 1900: Leonard Hill used a frog model to prove that decompression causes bubbles and that recompression resolves them. Hill advocated linear or uniform decompression profiles. This type of decompression is used today by saturation divers.

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HBOT History

 1930s- Used to speed nitrogen removal from divers

 1950s- HBO first used in treatment of tumors.  Life without Blood

 1960s- Used to treat gas gangrene and CO Poisoning

 1970s- Committee formed to study Hyperbaric Oxygen Therapy as approved treatment for Decompression Sickness, Air Embolism, Carbon Monoxide Poisoning

Beginning of Modern HBO2

 I. Churchill-Davidson, MD (1955) study of radiosensitivity of tumors

Churchill-Davidson I et al. High pressure oxygen and radiotherapy. Lancet 1955; 1: 1091-95.

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Ite Boerema, MD Father of Hyperbaric Oxygen Therapy

 Leven Zonder Bloed (1960)  “Life Without Blood” is possible under hyperbaric conditions  Pig study at 3 ata  Paved way for HBO2 for wounds

Ite Boerema, MD

What is… Hyperbaric Oxygen Therapy?

 Breathing 100% Oxygen while pressurized greater than One Atmosphere (sea level)

 Increased pressure causes Oxygen to dissolve in the plasma

 Substantial increase in tissue Oxygenation

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What does Hyperbaric Oxygen Therapy do?

 Enhances Wound Healing through ROS and RNS which..  Stimulates new blood vessel growth -increases growth factors, mobilizes stem cells that form new blood vessels and… > Decreases inflammation  Arrests certain types of infections

HBO Chamber Differences

Multi-place  Monoplace

 Larger multi-person  One person

 Air Atmosphere  100% oxygen

 100% O2 via hood  Mask for air breaks

 More acute patients can  Stable patient be treated  Patient alone in chamber  In chamber tender

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Growth in Hyperbaric Medicine  More Acceptance in Mainstream Medicine  Published Clinical Trials  Maturity of the Field  Fellowships  Board Certification  Access to Training  UHMS Approved Introductory Courses in HM  Reimbursed by Medicare/ Medicaid & Private Insurance

Clinical Hyperbaric Facilities in USA

1400

1200

1000

800

600

400

200

0 1965 1976 1986 1996 2001 2004 2008 2012

Sources: Univ of Maryland, UHMS, CMS, IATMO

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Approved Non- Emergent Indications

 Diabetic Wounds of Lower Extremity

 Radiation Tissue Damage

 Osteoradionecrosis (ORN)

 Chronic Refractory Osteomyelitis

 Compromised Skin Grafts and Flaps

Approved Indications

 Clostridial Myonecrosis (Gas Gangrene)  Actinomycosis  Air or Gas Embolism  Carbon Monoxide Poisoning  Smoke Inhalation  Decompression Sickness  Severe Anemia  Cyanide Poisoning  Thermal Burns  Crush Injury, Compartment Syndrome & other acute Traumatic Ischemias

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Physiology & Pharmacology of HBO2

Pressure in 0 ATA Space Atmospheres

Absolute 1 ATA SL (ATA)

2 ATA 33 fsw Most HBO Treatments 3 ATA 66 fsw

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Daltonʼs Law Applies

 Total pressure = sum of partial pressures  PB (air) = PO2 + PN2 + Pothers 2.5

1.5 pOthers pN2 1 pO2

0.5

0 1 ata 2 ata As total pressure doubles, pO2 doubles

Hyperbaric Oxygen Therapy is a spin-off of technology for treating DCS

Bubble compression High dose oxygen

2500 1 ata 2000

1500 2 ata pO2 1000

3 ata 500

0 123 ata

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 The atmospheric pressure decrease at 10,000-foot altitude = 523mm Hg ambient air pressure resulting in 87 percent hemoglobin saturation and 61mm Hg arterial oxygen.  At 15,000 feet (429mm Hg) the hemoglobin saturation is 80 percent (we need 87-97 percent for normal functioning), and arterial oxygen is 44mm Hg .

Benefits of HBO2 in Wound Healing

 Hyperoxygenation  Vasoconstriction

 Angiogenesis  Leukocyte Oxidative Killing  Antibacterial Effects

 Attenuates Reperfusion Injury  Mobilizes Stem Cells

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Hyperoxygenation of Tissue

As pressure inside the chamber increases: Alveolar PO2 O2 transport Tissue O2 uptake

Aids healing of hypoxic wounds

Oxygen Gradient

 Between capillary perfused edge and wound space <20 mm Hg O2 Gradient  Capillaries  >40 mm Hg >40 mm Hg  Wound Edge  <20 mm Hg  Important for GF release and angiogenesis

Photo courtesy of TK Hunt, MD

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O2 Electrodes Confirm: Problem Wounds Have Low PO2 Patient 946OP: Amputation of 2 Toes on Left Foot

Air 02 Air 02 Air 02 Air 30

20 Wound 10 at 1 ATA 0 10 20 5 20 5 20 10 Time interval (min) Sheffield PJ, 1985

O2 Electrodes Confirm: HBO2 Elevates Wound PO2 Patient 603EM: Radiation necrosis over sacrum Weekly wound response at 1 ata & 2.4 ata

1 ata 2.4 ata 1 ata

O2 O2 O2 1500

1000 O2 O2 O2 4 wks HBO2 500

PO2 (mm Hg) PO2 (mm 1 wk HBO2 0

0 30 60 90 120 150 180 210 Lapse time (min) Sheffield PJ, 1985

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HBO2 Effect on Plasma O2

Vol % = ml O2 / 100 cc plasma Pressure Vol % in Vol % in (ata) Plasma (air) Plasma (O2) 1.0 0.3 2.1 2.0 0.8 4.4 2.4 1.0 5.2 3.0 1.3 6.8

Effect on Microorganisms: Leukocyte Oxidative Killing  Leukocytes  Improved phagocytosis  Neutrophil-generated high energy oxygen radicals  Protected by superoxide dismutase enzyme system Mandell G, 1974

 Gas Gangrene (Clostridium perfringens)  Alpha toxin ceases when pO2 > 250mmHg

 Bactericidal when pO2 >1500 mmHg Van Unnik AJM, 1965

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Effect on Microorganisms: Antibacterial Effects Count  Converts anaerobic 7 wounds with low pH to aerobic wounds with 6 Control normal pH 5 HBO2  Some antibiotics do not 4 work well in acid pH 3 TM  HBO2 + tobramycin best 2 eradicates Pseudomonis HBO2 + aeruginosa from infected 1 TM bone 0 Mader JT, et al, 1987 21 28 35 42 Days

HBO2 Attenuates Reperfusion Injury

 Direct injury from severe hypoxia Indirect injury from prolonged ischemia - Inappropriate activation of leukocytes - Neutrophils block venules & prevent flow

HBO2 protects tissue from reperfusion injury - Inhibits sequestration of neutrophils in venules - Prevents “no reflow” Zamboni WA, et al, 1989

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HBO2 stimulates stem cell mobilization from bone marrow and more cells are recruited to the skin wounds

 HBO2 mobilizes stem/ progenitor cells by stimulating •NO synthesis  Circulating stem cells doubled after HBO  Nitric oxide synthase activity increased in platelets and remained elevated > 20 hrs  Adult stem cells repair and remodel the tissue in which they are found

Thom SR, et al. Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. Wound Repair Regen, 2011 Mar;19(2): 149-61.

What is the Evidence for HBOT in Diabetic Foot Ulcers?

 10 published, independent, evidence based reviews for HBO in DFUs  7 RCT, 2 CT, 7 retrospective case series all with different end points, patient selection criteria, protocols, endpoints.

 Despite the differences, HBO was consistently shown to be beneficial.  Margolis et al. is one of the few dissenting papers. This retrospective study had many limitations. Included Wagner 1, 2 and 3 Ulcers.

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What is the Evidence for HBOT in Radiation Injuries?

 Used for more than 30 years as therapy for delayed radiation injury.  Stimulates angiogenesis, reduces fibrosis, and mobilizes/increases stem cells in irradiated tissues.

 Radiation induced mandibular necrosis responds well to HBOT when combined with surgical excision of necrotic bone.

Delayed Radiation Injuries

 Robert Marx, DDS has done the most definitive work on the role of HBOT in mandibular necrosis. He established that the majority of the HBO treatments need to happen BEFORE surgical removal of all necrotic bone.  Marx reports a 100% success rate on 268 patients using a well-defined protocol.

 There have been negative reports, usually these did NOT follow Marx’s guidelines and total less than 60 patients.

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Burn Wound Angiogenesis Ketchum et al 1969

 Scald wound on back of rat at 22 days

- HBO2 treated

 Control

Ketchum etal 1969: Angiographic studies of the effects of HBO on burn wound revascularization. Proceedings of 4th Int Cong on Hyperb Med. Baltimore, Williams & Wilkins;388-394.

Patient Selection is Very Important

 Patients Who Patients Who  Patients Who Will Heal Might Heal With Will Not Heal Without HBOT HBOT Even With HBOT

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HBO2 As A Drug

 Absolute Complications & Side Contraindications Effects

 Untreated  Confinement Anxiety pneumothorax  Barotrauma  Selected medications  Ears, sinuses, lungs  Doxorubicin  O2 toxicity (Adriamycin®)  Eyes, brain, lungs  Mafenide Acetate (Sulfamylon®)

Kindwall EP, Whelan HT, 2008

CNS Oxygen Toxicity

 Time / dose relationship  Exposure: 100% O2 at >2.0 ata  Incidence: 1 per 10,000 patient tx

5 4 Risk of Seizure ATA 3 2 Safe Zone 1

1234 Hours

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PtcO2 <40 mmHg Impaired Healing

38 studies 1982 - 2009 Defined PtcO2 < 40 mm Hg (on air) as hypoxia sufficient to impair or prevent healing

 Fife CE et al . Transcutaneous oximetry in clinical practice. Consensus statements from an expert panel based on evidence. UHM 2009; 36(1): 43-53.

What Does Tissue Oximetry Do? TCOM

 Measures tissue PO2

 Approximates capillary PO2  Identifies

 Tissue that is hypoxic

 Tissue that responds to O2  Nutritive oxygen value

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Conducting A TCOM Assessment of Wound Healing Potential

 Question 1: Is wound healing complicated by hypoxia?

 Test 1: Baseline - Air [Air at 1 atm abs]

 > 40 Adequate to heal  31-40 Mild hypoxia  21-30 Moderate hypoxia

 11-20 Severe hypoxia  0-10 Profound hypoxia

 Positive test for healing: PtcO2 > 40 mm Hg

Conducting A TCOM Assessment of Wound Healing Potential  Question 2: Is wound healing complicated by peripheral arterial occlusive disease?

 Test 2: Leg Elevation 30o [Air at 1 atm abs]

 Positive test: Sustained 10% decrease is significant

 Disease is present if PtcO2 remains diminished while leg is elevated

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Conducting A TCOM Assessment of Wound Healing Potential

 Question 3: Does the patientʼs wound site respond to oxygen breathing?

 Test 3: O2 Challenge [O2 at 1 atm abs]

 Positive test for healing w/HBO2: Mean O2 value > 35 mm Hg > 50% rise above air value

Conducting A TCOM Assessment of Wound Healing Potential

 Question 4: Does the patientʼs wound site respond to hyperbaric oxygen?

 Test 4: HBO2 challenge [O2 at 2-2.5 atm abs]  Positive test for healing w/ HBO2: Achieve >200 mm Hg

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Conclusions of the Cohort Study: PtcO2 as a Predictor of Healing Outcome

 Best parameters for predicting healing w/ HBO2: TC-O2 >35 mmHg and TC % Rise >50%

Sheffield PJ et al. Mean PtcO2 values as an outcome predictor in hyperbaric oxygen treatment of hypoxic wounds, UHM 2008; 35(4): 272 abstract.

In-Chamber Oxygen Dose Outcome: 6 Center Study in Diabetic Wounds (n=222)

 Retrospective analysis of 1144 diabetic foot ulcer patient outcomes  Likelihood of benefiting from HBO2 > 90% when in-chamber PtcO2 was >200 mm Hg Fife et al (2002)

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Documentation

 Failed 30 days of standard therapy  No improvement with standard therapy during the previous 30 days.  Wagner 3 with infection  Hemoglobin A 1 C (Controlled blood sugars)  Blood glucose levels before and after treatment  Vascular assessment  Control of infection  Offloading  Optimize nutritional status  Physician supervision  ACLS immediately available

28 TMS Therapy: A Unique and Proven Approach to Treating Depression

Carlos G. Lowell, D.O.

Learning Objectives:

Describe TMS therapy. Discuss when you would consider referring a patient for TMS therapy. Recognize what excludes a patient from being a TMS therapy candidate. Define mechanism of action for TMS-How does it work?

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TMS THERAPY: A UNIQUE AND PROVEN APPROACH TO TREATING DEPRESSION

CARLOS G. LOWELL, D.O.

DES MOINES UNIVERSITY COLLEGE OF OSTEOPATHIC MEDICINE

FIRELANDS REGIONAL MEDICAL CENTER D.O. ROTATING INTERNSHIP

MEDICAL COLLEGE OF WISCONSIN PSYCHIATRIC RESIDENCY

TMS INSTITUTE OF OHIO MEDICAL DIRECTOR

1 10/31/2016

DISCLOSURES:

I HAVE NO CONSULTING CONTRACTS WITH ANY TMS MANUFACTURERS OR PHARMACEUTICAL COMPANIES. NOR DO I HAVE ANY GOVERNMENT GRANTS.

THE BIOLOGY OF DEPRESSION

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Major Depression is a Brain Disease

Major Depressive Disorder

anterior prefrontal cingulate cortex cortex striatum

HIGH hypothalamus In MDD, some areas of the thalamus brain are Neural Activity hypoactive and others are brainstem neurotransmitter hyperactive. amygdala centers LOW hippocampus

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Major Depressive Disorder: Circuits and Neurotransmitters concentration pleasure/ psychomotor fatigue interests (physical) pleasure/interests psychomotor When there is fatiguemonoamine •an Monoamine appropriate (mental) sleep neurotransmitter Regions implicated in MDD are dysfunctionamount of is guilt appetite projections connected to the brainstem linkedmonoamine to MDD suicidality via monoaminergic circuits worthlessness neurotransmitter • Malfunctioningactivity, mood neuronalcircuits leadactivity to throughoutspecific the guilt brainsymptoms functions suicidality normally. worthlessness mood

Monoamine Serotonin (5-HT) Dopamine (DA) Norepinephrine (NE) Neurotransmitters

STAR*D Treatment Algorithm

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Study demonstrates that medication treatment have limited effectiveness

Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry

Study also demonstrates the discontinuing treatment increases with each NEW medication

Systemic Drug Side Effects

 Weight Gain  Fatigue

 Constipation  Headache/ Migraine  Diarrhea  Abnormal  Nausea Ejaculation

 Drowsiness  Impotence

 Insomnia  Sweating

 Decreased  Tremor Libido  Treatment  Nervous Anxiety Discontinuation Side Effects  Increased Appetite  Weakness

 Decreased  Dry Mouth Appetite  Dizziness

Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J 10 Psychiatry; Neuronetics, Inc. (data on file) 10

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Chemical Antidepressants

Antidepressant TherapeuticSide AntidepressantEffects Effects such such as: increased concentration as : blurred vision insomnia agitation dry mouth fatigue insomnia nausea blood pressure GI changes distress

sexual weight gain improved dysfunction mood

reduced feelings of guilt, suicidality,weight and worthlessnessgain

Medication May Not Work for Everyone! STAR*D study sponsored by NIMH using antidepressant medications shows: When patients don’t benefit from antidepressant medication…

… their chances of getting better from additional medication treatments declines

… they are more likely to stop a medication due to unwanted side effects

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TRANSCRANIAL MAGNETIC STIMULATION: MECHANISM OF ACTION

Science Behind TMS Started in 1831 with Michael Faraday

The physical principles of This current in turn depolarizes TMS were discovered in neurons and can generate 1831 by Michael Faraday, various physiological and who observed that a pulse of behavioral effects depending on the targeted brain area. electric current passing through wire coil generates a The conductors in TMS are magnetic field. neurons in the brain, allowing The rate of change of this electrical stimulation in the magnetic field determines brain in a non-invasive fashion. the induction of a secondary current in a nearby conductor.

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TMS Therapy Directly Depolarizes Cortical Neurons

Neuron Pulsed magnetic fields: • induce a local electric current in the cortex which depolarizes neurons Neurons are • eliciting action “electrochemical cells” potentials and respond to either • causing the release of electrical or chemical stimulation chemical neurotransmitters

TMS RELEASES Neurotransmitters in the Brain

Depolarization of neurons in the DLPFC causes local neurotransmitter release

Dorsolateral prefrontalThese effects are cortexassociated with Anteriorimprovements in cingulate cortexdepressive

Kito (2008)symptoms J Neuropsychiatry Clin Neurosci

Depolarization of pyramidal neurons in the DLPFC also causes Activation of deeper brain neurons neurotransmitter release in deeper then exerts secondary effects on brain neurons remaining portions of targeted mood circuits 16

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Targeted Effects on Mood Circuits in Brain

L R

TMS Coil L R

Activation of fronto-cingulate brain circuit following a course of TMS applied to the left dorsolateral prefrontal cortex in patients with Major Depression

Kito (2008) J Neuropsychiatry Clin Neurosci 17

Biological and Behavioral Effects of TMS

Effects Seen After Chronic Exposure: . Specific outcome is dependent upon stimulation parameters . Alteration of monoamine concentrations . Beta-receptor, serotonin-receptor modulation . Evidence of induction of neurogenesis genes (eg, BDNF) . Plasticity-like actions (ie, LTD/LTP-like effects) . Local GABA, glutamate effects . Stimulation of the dorsolateral prefrontal cortex (DLPFC) alters functional activity of the anterior cingulate (AC) and deeper limbic regions

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TMS Increases Neurogenesis in Hippocampal Dentate Gyrus

Ueyama, et al., 2011

TMS Restrains the Activation of HPA Axis During Chronic Stress

Czeh, B., et al., Biol Psychiatry. 2002;52:1057-1065

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NeuroStar TMS Brainsway TMS Device Therapy System

Magstim System Magventur System

TMS Therapy Session . Patient is awake and alert . No anesthesia or sedation needed . No negative effects on thinking and memory . After treatment, patients can drive or return to work . Some patients experience headache or mild to moderate pain or discomfort at or near the treatment area . None of the side effects typical with antidepressant medications

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TMS: Contraindications

. Non-removable metallic objects in or around the head . Conductive, ferromagnetic or other magnetic sensitive metals that are implanted or are non-removable within 30 cm of treatment coil . Implanted electrodes/ stimulators . Deep Brain Stimulator . Aneurysm clips or coils . Cochlear implants . Stents . Bullet or other metal fragments

NeuroStar TMS Therapy System User Manual. Neuronetics, Inc: Malvern, PA. 23

TMS Therapy: A Well-Tolerated Antidepressant (Adverse Events with Incidence > 5%)

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Time Course for Most Common Adverse Events

Janicak PG et al. J Clin Psychiatry. 2008;69(2):222- 232. 25

Potential Serious Adverse Events . Cognition

. Suicide Ideation

. Seizures

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TMS and Cognition

Data on file. Neuronetics, Inc. 27

Emergence of Suicidal Ideation: Multicenter Study

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TMS and Seizures . Seizure is the most serious side effect associated with TMS . Most cases associated with TMS were prior to the publication of the TMS safety guidelines in 1998 . Considering the large number of healthy individuals and patients who have undergone TMS sessions since 1998 and the small number of seizures reported, the risk of TMS to induce seizures could be considered very low.

Wassermann, E. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996. Electroencephalography and Clinical Neurophysiology, 108, 1998 29

SCIENTIFIC EVIDENCE OF EFFICACY FOR TMS THERAPY

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Large-Scale Randomized Controlled Trials (RCT’s)

. Four large-scale studies (sample size > 100) . Two large multicenter industry supported trials that lead to FDA approval for two devices . One NIH-funded study with dosage parameters similar to those in the industry-sponsored study but with sham design enhancements . One European study of the augmentation effects of TMS when used in combination with pharmacotherapy

George et al., Archives of General Psychiatry. 2010(67);507-516 Herwig et al., British Journal Psychiatry. 2007;191, 441-448 Levkovitz et al., World Psychiatry. 2015(14); 64-73 O’Reardon et al., Biological Psychiatry. 2008(62); 1208-1216 31

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis

. Evaluate the efficacy of TMS in patients with treatment- resistant depression (TRD) . Included 18 TRD studies published from Jan 1980 – March 2013 . Those receiving TMS were 3 times more likely to respond and 5 times more likely to obtain remission vs. those who received sham

JBN Gaynes et al., Clin Psychiatry 2014;75(5):477–489 32

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Multisite Naturalistic Observational Study of TMS for MDD: Acute Treatment Outcomes and One-Year Follow-Up

Study Goal: Define real world outcomes associated with TMS Therapy across a broad spectrum of patients and practitioners

42 Sites: Comprised of 307 Patients: Unipolar, non- institutions and private psychotic MDD patients in acute practice phase

Acute Phase Long-term Outcomes Acute Phase Treatment(treatment course course driven by Measured at 3, 6, 9 and 12 months patientdriven clinical by patient response clinical response)

Carpenter, Depression and Anxiety, 2012; Dunner, et al., (2014) J. Clin Psych 33

Patients Who Entered Study Had Significant Morbidity

Carpenter, Depression and Anxiety, 2012 34

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Comparison of End of Acute Treatment Clinical Status: Clinician-and Patient-Assessed Outcomes

Clinician Rating Patient Rating (CGI-Severity of Illness) (PHQ-9 Scale) 80 80 70 70 60 58.0% 60 56.4% 50 50 40 40 30 30 20 20 10 10 % of Patients (N=307) 0 0 Baseline End of Treatment Baseline End of Treatment

LOCF Analysis of intent-to-treat population Markedly ill or worse Moderately ill Mildly ill or better

Carpenter, et al, (2012) Depression and Anxiety 35

Remission is Possible with TMS Therapy: 1 in 2 Patients Respond, 1 in 3 Achieve Remission

Clinician Rating Patient Rating (CGI-Severity of Illness) (PHQ-9 Scale) 70

60 58.0% 56.4%

50 37.1% 40

(N=307) 28.7% 30

Percent ofPercent Patients 20

0 Responders (CGI-S ≤3, PHQ-9 Remitters (CGI-S ≤2, PHQ-9 <10) <5) LOCF Analysis of intent-to-treat population

Carpenter (2012), Depression and Anxiety 36

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Long-Term Phase Results at 12 Months

Clinician Rating Patient Rating (CGI-Severity of Illness) (PHQ-9 Scale) Outcomes measured for one 70 67.7% 60.7% year following end of acute 60 treatment 50 45.1% 44% . Physician directed standard of care . 36.2% of patients received TMS 40 37% reintroduction 30

N=257 . Average number of TMS treatment 20 days = 16 Percent of Patients Percent 10 Long term durability of effect has 0 not been established in a Responders (CGI-S ≤3, PHQ-9 Remitters (CGI-S ≤2, PHQ-9 controlled trial <10) <5)

Dunner, et al., (2014) J. Clin Psych 37

Why are Real World Results Better than Clinical Trial Results?

. Combination Strategies

. Well tolerated with medication Biological . Psychotherapy . Engagement in Life Social Psychological . Intensive Outpatient Program – Factors . Routine . Interaction . Engaging with People who Care

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Maintenance TMS ■ No approved maintenance protocol ■ Do not need full course ■ If treat with re-emergence of depression, TMS is more effective with fewer number of treatments “It is notable that TMS reintroduction was successful in rescuing most patients with threshold deterioration and returning them to their prior level of depressive symptom relief.” Important observation given: • The chronic and relapsing nature of pharmacoresistant major depression • Absence of definitive data suggesting that re-treatment with previously effective medications is capable of doing the same. The results provide support for long-term treatment strategy that incorporates retreatment with TMSforpatientswhoshowedpositiveresponsetoaninitialacutecourse.(p.257)

N.S Phillip et al., Brain Stimulation 2016;9:251-257 39

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WHO MAY BE CANDIDATES FOR TMS THERAPY?

Why Do We Need to Consider Neuromodulation as Treatment Option?

. Depression is a common mental disorder. Globally, more than 350 million people of all ages suffer from depression. . Depression is the leading cause of disability worldwide, and is a major contributor to the burden of disease. . ~50% individuals diagnosed seek help and more than 30% do not receive adequate treatment from medication or psychotherapy

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STAR-D Data Supports Need for Other Treatment Options

**After 6 weeks of acute phase treatment, NeuroStar TMS Therapy achieved statistically significantly superior outcomes as measured by QIDS-SR total scores compared to next choice antidepressant medication treatment, when compared to a propensity score matched sample of patients in the STAR*D Study.

Demitrack, et al., 2013

Who is Right for TMS Therapy? Indicated for: •TMS Therapy is indicated for the treatment of Major Depressive Disorder in adult patients who have failed to receive satisfactory improvement from prior antidepressant medications at or above the minimal effective dose and duration in the current episode Patient Characteristics: •In a recurrent episode •Multiple medication attempts, yet still symptomatic •Considering a complex drug regimen •Experience frequent side effects from medication

Carpenter, et al. (2012), Depression and Anxiety 44

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TMS is Included in Practice Guidelines Following Failure of Initial Treatment

Schlaepfer, et al. World J Biol Psychiatry (2009); Kennedy, et al J Aff Disorders (2009); Institute for Clinical Systems Improvement (2010); American Psychiatric Association (2010) 45

TMS Insurance Coverage

. TMS has coverage in every state for Major Depressive Disorder 248.4 M Covered Lives . Covered by all major private insurance companies

. Covered by Medicare in every state

. Coverage policies vary, but most typically require a failure of 3-6 antidepressant medications from different classes and Psychotherapy

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Conclusion . TMS is focal non-invasive form of brain stimulation based on principles of electromagnetic induction that has been well established for nearly 200 years. . TMS is a safe and effective treatment of moderate to severe MDD and research supporting it’s efficacy in treatment of other mental and neurological disorders. . TMS is well-tolerated and without risks of systemic side effects seen with medications. . TMS needs to be considered as a treatment option.

24 The Anterior Approach to Hip Replacement

Richard M. Miller, D.O., FAOAO

Learning Objectives:

Describe the history of anterior hip replacement. Recognize the difference between the traditional approach vs the anterior approach. Identify the anticipated results of the anterior approach.

NOTES ______

ACLS Re-Certification

Brent C. DeVries, D.O. & Captain David Degnan, Fire Chief

Learning Objectives:

Respond to and initiate early management of peri-arrest conditions that may result in cardiac arrest or complicate resuscitation outcome. Respond to unresponsive victim initiating high-quality CPR skills/appropriate airway management. Respond appropriately to Respiratory Arrest with a Pulse/w/o a Pulse. Respond appropriately to Ventricular Fibrillation/Pulseless VT (AED).

NOTES ______