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Addressing Opioid Addiction in Acute Care Settings Addressing Opioid Addiction in Acute Care Settings

Addressing Opioid Addiction in Acute Care Settings - PowerPoint Presentation

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Addressing Opioid Addiction in Acute Care Settings - PPT Presentation

  Michael Lynch MD Assistant Professor of Emergency Medicine and Toxicology University of Pittsburgh Medical Director Pittsburgh Poison Center 2017 US Overdose Deaths gt72000 1 Rapidly rising death rate due to potency fentanyl analogues ID: 755096

opioid naloxone patients overdose naloxone opioid overdose patients treatment 2017 buprenorphine risk 2018 cost distribution drug prescription users withdrawal

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Slide1

Addressing Opioid Addiction in Acute Care Settings

 Michael Lynch, MDAssistant Professor of Emergency Medicine and Toxicology, University of PittsburghMedical Director, Pittsburgh Poison Center Slide2

2017 US Overdose Deaths: >72,0001

Rapidly rising death rate due to potency, fentanyl analoguesU.S. Overdose Deaths-2017

https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates

2018 Drug Enforcement Agency National Drug Threat Assessment; October, 2018.Slide3

Heroin Use Actually Declined

1. Substance Abuse and Mental Health Services Administration. (2018).

Key substance use and mental health indicators in the United States: Results from the 2017 National Survey on Drug Use and Health

(HHS Publication No. SMA 18-5068, NSDUH Series H-53). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from

https://www.samhsa.gov/data/

Despite the rise in opioid overdose fatalities, heroin use declined overall in 2017

1Slide4

PreventionOpioid prescribing stewardship

Alternative and multimodal pain managementEarly identification of potential for use disorder; childhood/adolescence (ACES)Harm ReductionNaloxoneNeedle Exchange, alcohol wipes, group useSafe Consumption Sites?Recovery Treatment EngagementScreening, Brief Intervention, Referral to Treatment (SBIRT)Prevention of withdrawal

Cultural change to

reduce stigma

associated with OUD which may prevent engagement

Reduction of barriersLong-Term TreatmentMedication Assisted Treatment

CounselingSocial, community support; stigma reduction

Strategies to Address the Opioid Epidemic

4Slide5

~79.5% of injection drug users report previous non-medical prescription opioid use1

Not necessarily accurate to state that illicit opioid use started with Rx useUnrecognized behavior and risk factors nearly always present2,3Non-opioid substance usePsychological trauma (ACES)Behavioral health disorderYoung age

Family History/genetics

While opioid prescribing has decreased and prescription opioid related deaths have plateaued, heroin/fentanyl related deaths have increased dramatically

Muhuri

PK et al. Associations of nonmedical pain reliever use and initiation of heroin use in the United States. CBHSQ [Center for Behavioral Health Statistics and Quality] Data Review. August 2013 (

http://www.samhsa.gov/data/sites/default/files/DR006/DR006/nonmedical-pain-reliever-use-2013.htm)

Webster LR. Risk Factors for Opioid-Use Disorder and Overdose. Anesth Analg. 2017 Nov; 125(5): 1741-1748.Kaye AD, et al. Prescription opioid abuse in chronic pain: An updated review of opioid abuse predictors and strategies to curb opioid abuse: Part 1. Pain Physician 2017; 20: S93-S109.

Relationship Between Prescription Opioid Use and HeroinSlide6

Rates of opioid prescribing peaked in 2010-20121

Rx per 100 persons rose from 72.4 in 2006 to 81.2 in 2010; then fell to 70.6 in 2015MME per capita fell from 782 in 2010 to 640 in 2015 (18% reduction)

Opioid PrescribingSlide7

Risk of ongoing 1 year prescription opioid use after first prescriptionAny provider: ~6%

1ED provider: <1.5%2Prescription opioid misuse and addiction is a small subset of that groupFactors associated with long term Rx opioid use (at 1 and 3 years)1First prescription exceeds 10 days (increased risk begins after 3rd day)Filling a subsequent prescription (risk doubles with 2

nd

prescription or first refill)

Cumulative dose >700 MME

Initially prescribed a long-acting opioidInitially prescribed tramadol

Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006–2015. MMWR Morb

Mortal Wkly Rep 2017;66:265–269.Barnett MS, et al. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017; 376: 663-673

Risk of Long Term Opioid Use after First PrescriptionSlide8

Risk Mitigation Strategies (Harm Reduction)Monitor, assess, and treat for adverse effects (e.g. constipation, dry mouth, nausea, etc.)

Counsel regarding risk of driving, operating heavy machinery, etc. when initially prescribing or upon escalation of dosesAvoid prescribing opioids to patients receiving benzodiazepines or other sedativesNaloxoneSlide9

Overdose Risk with High Dose Chronic Opioid Therapy

Relative risk of overdose when compared to patients on <20MME/day150-100 MME/day: 1.9-4.6>100 MME/day: 2-8.9Consider concurrent naloxone prescription for patients on >50-100 MME/day2

Bohnert

ASB, Logan JE,

Ganoczy

D, Dowell D. A detailed exploration into the association of prescribed opioid dosage and prescription opioid overdose deaths among patients with chronic pain. Med Care 2016.

Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016;65(No. RR-1):1–49. DOI:

http://dx.doi.org/10.15585/mmwr.rr6501e1Slide10

Naloxone (NARCAN®)μ-opioid receptor antagonist

No observed effect in individuals without acute opioid toxicity or chronic opioid dependenceRapid onsetShort duration of actionAdverse effects are rare(<1%)1

Available routes of administration: intravenous, intranasal, intramuscular, subcutaneous, endotracheal

Clark AK et al. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med. 2014 May-Jun; 8(3): 153-63.

Understanding Naloxone. Harm Reduction Coalition. http://harmreduction.org/issues/overdose-prevention/overview/overdose-basics/understanding-naloxone/. Accessed December 3, 2015. Slide11

CDC Naloxone RecommendationsConsider provision of naloxone to patients

1:who have survived an overdoserequesting or having just completed detox/rehabilitationwith history of OUD being released from prisondemonstrating behavior concerning for an opioid use disorderconcurrently prescribed benzos and opioidson high doses of chronic opioids (>50-100 MME/day)with obstructive sleep apnea on opioid therapyFamily members should be encouraged to obtain naloxone

Dowell D,

Haegerich

TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR

Recomm

Rep 2016;65(No. RR-1):1–49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1Slide12

Effect of Naloxone on Mortality and Cost

Statistically significant reduction in fatalities in communities where the program was implemented1Adjusted rate ratio of 0.73 (0.57-0.91) with 1-100 enrollments per 100,000 populationAdjusted rate ratio of 0.54 (0.39-0.76) with >100 enrollments per 100,000 population

Incremental Cost-Effectiveness Ratio (ICER) indicated

significant decrease in overall societal cost and increase in quality life years

2

$438-2,429 per Quality-Adjusted Life Years (QALY)

gained, depending upon calculation of future costs for active heroin users$50,000-100,000/QALY is typically considered a cost-effective intervention in the U.S.3

1. Walley AY et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013 Jan 30; 346:f174.2. Coffin PO, Sullivan SD. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Ann Intern Med 2013;158:1–9.3. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl

J Med. 2014 Aug 28;371(9): 796-7.Slide13

Layperson Utilization of NaloxoneFrom 1996-6/2014, 152,283 naloxone kits provided to laypersons

26,463 overdose reversals reportedOne reversal for every 6 kits distributedWheeler E et al. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons-United States, 2014. MMWR Morb Mortal Wkly

Rep. 2015 Jun 19; 64(23):631-5Slide14

Summary of Take Home Naloxone Rationale

Naloxone saves lives1Patients are less likely to fill a prescription or go to pharmacy2Nasal naloxone is safe and easy to use3Recommended by the World Health Organization4

, CDC

5

, SAMHSA

6, and the Surgeon General7

Walley AY et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013 Jan 30; 346:f174.

Drainoni ML, Koppelman EA, Feldman JA, Walley AY, Mitchell PM, Ellison J, Berstein E. Why is it so hard to implement change? A qualitative examination of barriers and facilitators to distribution of naloxone for overdose prevention in a safety net environment.

Mueller SR, Walley AY, Calcaterra SL, 

Glanz JM

Binswanger IA

. A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice.

Subst

Abus

.

 2015;36(2):240-53.

World Health Organization. Community management of opioid overdose. Geneva, Switzerland: World Health Organization; 2014

Wheeler E, Jones TS, 

Gilbert MK

Davidson PJ

Centers for Disease Control and Prevention (CDC)

. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014.

MMWR

Morb

Mortal

Wkly

Rep.

 2015 Jun 19;64(23):631-5.

https://www.samhsa.gov/medication-assisted-treatment/treatment/naloxone

https://www.surgeongeneral.gov/priorities/opioid-overdose-prevention/naloxone-advisory.htmlSlide15

Surgeon General RecommendationSlide16

Popular misconceptions

Best Evidence

Opioid users will not want naloxone

The majority of opioid users would accept take-home naloxone from the ED

1

If opioid users wanted naloxone they can get it on their own because of the standing order

Significant stigma remains regarding asking for naloxone, in addition to barriers in cost and lack of availability in all pharmacies

2,3,4,5

Opioid users will be willing to use more potent opioids and/or higher doses if they have naloxone

Multiple studies indicate that opioid users do not have more confidence when using due to naloxone availability, and habitual users do not want naloxone reversal at any time

6,7

Opioid users will no longer come to the Emergency Department after an overdose

Referral rates to EDs remain the same with or without bystander naloxone administration

6,8,9

Providing naloxone enables substance users to continue using

 

Providing naloxone enables people to survive and receive treatment

6,7,8,10

Someone who overdoses couldn’t use their own naloxone

Almost all bystander naloxone administered in Allegheny County has been by other opioid users

11

Naloxone will not last as long as the overdose drug and can be a liability risk

The vast majority of overdoses that require naloxone do not require repeat dosing, and naloxone administration prevents death

12

Naloxone distribution and administration doesn’t seem to really be making a difference in this problem

Bystander naloxone and Take-Home-Naloxone programs have repeatedly demonstrated mortality reductions

9,10

Naloxone distribution/administration adds to healthcare and taxpayer expenses

Analysis of community distribution of naloxone has shown significant decrease in overall societal cost and increase in quality life years

13Slide17

Narcan Myths (References)

Kestler, A et al. Factors Associated With Participation in an Emergency Department–Based Take-Home Naloxone Program for At-Risk Opioid Users. Ann Emerg Med. Volume 69, Issue 3, 340 - 346Bakhireva LN et al. Barriers and Facilitators to Dispensing of Intranasal Naloxone by Pharmacists.

Subst

Abus

. 2017 Oct 18:0. Cressman, AM et al. Availability of naloxone in Canadian

pharmacies:a population-based survey. CMAJ Open. 2017 Nov 8;5(4):E779-E784 Green, TC et al. Perpetuating stigma or reducing risk? Perspectives from naloxone consumers and pharmacists on pharmacy-based naloxone in 2 states. J Am Pharm Assoc (2003). 2017 Mar - Apr;57(2S):S19-S27.

Heindel, GA et al. Rising cost of antidotes in the U.S.: cost comparison from 2010 to 2015. Clin Toxicol (Phila). 2017 Jun;55(5):360-363.

Clark AK et al. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med. 2014 May-Jun; 8(3): 153-63.Heavey, SC et al. 'I have it just in case' - Naloxone access and changes in opioid use

behaviours

.

Int

J Drug Policy. 2017 Nov 17;51:27-35.

Piper TM et al. Evaluation of a naloxone distribution and administration program in New York City.

Subst

Use

Misue

. 2008; 43(7):858-70.

Walley AY et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ. 2013 Jan 30; 346:f174.

Wheeler E et al. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons-United States, 2014. MMWR

Morb

Mortal

Wkly

Rep. 2015 Jun 19; 64(23):631-5

Prevention Point Pittsburgh: Naloxone Cumulative Data – July 2005 – June 2015

Willman MW et al. Do heroin overdose patients require observation after receiving naloxone?

Clin

Toxicol

(

Phila

). 2017 Feb;55(2):81-87.

Coffin PO, et al. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Ann Intern Med 2013;158:1–9.Slide18

Starting 12/19/2017

17 UPMC EDs able to provide naloxone to high risk patients at no costProcess akin to other ED take home meds Patient education and training $75/kit public interest pricing (compared to $125 retail price)UPMC sponsored community benefitEMR alert prompts providers

UPMC ED Naloxone DistributionSlide19

What’s in the kit

2 pack of Narcan nasal sprayno assembly requiredResource describing:Opioid overdose recognitionOpioid overdose responseNaloxone administrationAddiction and dependence

Follow up resourcesSlide20

Narcan® Nasal SpraySlide21

580 kits distributed in 9.5 months

16 different hospital EDs throughout western PA participated7 in month 116 by month 7Assuming 1 reversal for every 6 kits distributed (Wheeler et al):~97 lives saved (*estimated; definitive data is not available)~$448 per life ($43,500 spent on naloxone by the system)

UPMC ED Naloxone Distribution Data, 12/19/2017-9/30/2018Slide22

Triggered by chief complaint key words or OUD diagnosis in the last two yearsExample Chief Complaint triggers:

“Opioid”“Overdose or OD”“Drug”“Detox” “Withdrawal” “Naloxone”Specific opioids, e.g. “fentanyl”, “heroin”, “oxycodone”Appears at the time of discharge to remind providers to supply naloxone

EMR PromptSlide23

Program development Multidisciplinary group including: Internal Medicine, Toxicology, Palliative Care, Nursing, Pharmacy, Social Work, Case Management

ProcessHigh risk hospitalized patients identifiedNaloxone e-prescribed to on-site outpatient pharmacyNarcan nasal spray kit (including educational resource) delivered to the patient prior to dischargePatient survey administered PaymentInsurance billedPatient responsible for co-pay (waived for Medicaid patients)Uninsured or unable to afford co-pay

$75 cost of kit covered by $5,000 grant from UPMC Community Medicine, Inc.

UPMC Presbyterian/Montefiore Naloxone “Meds to Beds”Slide24

PUH/MUH Naloxone Kit Inpatient Distribution

24Slide25

May 10, 2017-July 17, 2018 (14 months)

Distribution/Costs:

Distributed 205 kits

to at-risk PUH/MUH inpatients prior to discharge

43 patients were uninsured

Average cost of kit to pilot fund =

$15.73

Survey Results (n=95):

High risk population was identified

54% had previously received naloxone

61% had previously overdosed or knew someone who had

59% had used naloxone or knew someone who had

Positive impact on current and future patient care

82% indicated that they would not have or would have been very unlikely to have sought out a kit if not for this program

74% indicated that this program positively impacted their patient experience

Inpatient Naloxone Pilot - Data

25Slide26

OUD Treatment Medications

Buprenorphine (Suboxone™)MethadoneNaltrexone (Vivitrol™)Adherence to methadone or buprenorphine is associated with:Reduction in nonmedical opioid use2Reduced incidence of HIV and Hepatitis C1,3,4Mortality reduction of up to 50%

4

Reduction in crime and improved social functioning

4

Correction of neurobiological dysfunction that leads to relapse1

42% overall annual reduction in healthcare costs5Opioid Use Disorder Pharmacotherapy

Bart G. Maintenance Medication for Opiate Addiction: The Foundation of Recovery.

J Addict Dis.

2012 July; 31(3): 207-225.

Weiss, R.D.; Potter, J.S.; Griffin, M.L. et al. Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study. 

Drug and Alcohol Dependence

 150:112-119, 2015

Tsui

JI et al. Opioid agonist therapy is associated with lower incidence of hepatitis C virus infection in young adult persons who inject drugs.

JAMA Intern Med.

2014 December; 174(12): 1974-1981.

Schuckit

MA. Treatment of Opioid-Use Disorders.

N

Engl

J Med.

2016 July 28; 375: 357-368

Tkacz

J,

Volpicelli

J, Un H,

Ruetsch

C. Relationship between buprenorphine adherence and health service utilization and costs among opioid dependent patients. J

Subst

Abuse Treat. 2014 Apr; 46(4): 456-62Slide27

Emergency management of acute withdrawal with long-acting opioid agonists (e.g. buprenorphine or methadone) is legal

Specifically, Title 21, Chapter II Part 1306 (§1306.07) section b of the Code of Federal Regulations, the “Three Day Rule”, states: “Nothing in this section shall prohibit a physician who is not specifically registered to conduct a narcotic treatment program from administering (but not prescribing) narcotic drugs to a person for the purpose of relieving acute withdrawal symptoms when necessary while arrangements are being made for referral for treatment. Not more than one day's medication may be administered to the person or for the person's use at one time. Such emergency treatment may be carried out for not more than three days and may not be renewed or extended.”

ED Management of Acute WithdrawalSlide28

Buprenorphine1

Superior to clonidine in reducing withdrawal symptomsEasy and safe to administerImproves addiction treatment engagement/completionMethadone2Single 10mg IM methadone dose significantly improved subjective and observed opioid withdrawal scores

Love JS, Perrone J, Nelson LS. Should buprenorphine be administered to patients with opioid withdrawal in the emergency department? Ann

Emerg

Med. 2017 Nov 3.

Su MK, Lopez JH,

Crossa A, Hoffman RS. Low dose intramuscular methadone for acute mild to moderate opioid withdrawal syndrome. Am J Emerg Med. 2018 Mar 2.

ED Management of Acute WithdrawalSlide29

ED initiation of buprenorphine therapy associated with:

Improved treatment engagementTwice as many patients treated with buprenorphine were engaged in treatment at 30 days compared to referral without medicationReduced illicit drug useD’Onofrio G, O’Connor PG, Pantalon

MV,

Chawarski

MC, Busch SH, Owens PH, Bernstein SL,

Fiellin DA. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015 Apr 28; 313(16): 1636-44.

D’Onofrio G, Chawarski MD, O’Connor PG, Pantalon MV, Busch SH, Owens PH, Hawk K, Berstein SL, Fiellin

DA. Emergency department-initiated buprenorphine for opioid dependence with continuation in primary care: Outcomes during and after intervention. J Gen Intern Med. 2017 Jun; 32(6): 660-666.

ED Buprenorphine for OUDSlide30

Dosing:Typical initial dosing is 4-8mg

Maintenance dosing is usually 8-16mg/day (Daily or divided BID)“Ceiling Effect” at ~24-32mg/dayCan be prescribed by any provider with a DEA X-waiverBuprenorphine without naloxone is only recommended for pregnant patients or those with naloxone allergiesAdverse Effects:

Primarily induction of precipitated withdrawal in dependent patients not yet suffering withdrawal symptoms

BuprenorphineSlide31

Coordinated effort among:Emergency Medicine/Toxicology

PharmacyCommunity Centers of Excellence and other treatment providersHospital AdministrationProcess:Patients presenting in opioid withdrawal are identifiedA single dose of 8-2mg of buprenorphine-naloxone is providedThe patient is observed for adequate resolution of symptoms and to ensure no adverse effectA single repeat dose can be provided if needed

Active connection is made to community provider for next business day (warm handoff)

Patients may return to the ED for a dose on days 2 and 3, if necessary

UPMC Mercy ED Buprenorphine ProgramSlide32

ED patients treated with buprenorphine, 11/1/2017-9/30/2018

140 visits 109 individual patients~22% return visitsNo adverse events were observedEngagement50% filled subsequent prescriptions for buprenorphine

UPMC Mercy ED Buprenorphine Program

Month

# Visits

# Patients

November, 2017

8

7

December, 2017

5

5

January, 2018

10

8

February, 2018

9

7

March, 2018

15

11

April, 2018

15

12

May, 2018

12

11

June, 2018

16

11

July, 2018

16

14

August, 2018

17

10

September, 2018

17

13

Totals:

140

109Slide33

Patients admitted to a hospital for medical/surgical illness may be treated with an opioid agonist, e.g. methadone or buprenorphine, to manage co-occurring addiction and withdrawal without specific licensing

Specifically, according to Title 21 of the Code of Federal Regulations (CFR) section 1306.07 C:“…This section is not intended to impose any limitations on a physician or authorized hospital staff to administer or dispense narcotic drugs in a hospital to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction, or to administer or dispense narcotic drugs to persons with intractable pain in which no relief of cure is possible or none has been found after reasonable efforts,”

Hospital Treatment with Long-Acting Opioid AgonistsSlide34

Specialized addiction consult team including initiation of buprenorphine

1:72% engagement in outpatient treatment VS.12% in patients who were simply detoxifiedReduced 30 day illicit drug useBoston Medical Center Experience21% reduction in one year admission rate for patients with substance use disorder

Massachusetts General Hospital Experience

17.5% reduction in 30 day readmission rate

Inpatient Initiation of MAT

1) Liebschutz JM, Crooks D, Herman D et al. Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial.

JAMA Intern Med

2014;174(8):1369-1376Slide35

Substance Use Referral Program (Warm Handoff)

Opioid overdose and naloxone education with medical simulationProviders and lay publicLaw enforcement collaborationSurveillance and public health collaborationMedical trainee educationDrug Takeback coordination and supportPublic educationPediatric opioid safety recommendationsBuprenorphine and methadone management guidelines

Examples of Poison Center Opioid ProgramsSlide36

Exponential growth in overdose deaths.

Hawre Jalal et al. Science 2018;361:eaau1184

Published by AAASSlide37

Overdose death rates remain unacceptably high

Early indicators suggest a bend in the curveOngoing efforts to:Minimize excessive opioid availability (without limiting appropriate pain management)Identify and limit sources of illicit opioidsReduce death and harm associated with drug useReduce stigma associated with SUDImprove access to addiction treatmentPrepare for changes in drug use trends, e.g. cocaine, amphetamines/methamphetamines, synthetic cannabinoids, etc.

Turning the Corner?

https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm

Accessed 10/16/2018Slide38

HOPE!Slide39

Opioid prescribing stewardshipTake home naloxone reduces mortality and is cost-effective

ED Naloxone distribution is effective and feasibleInpatient naloxone “Meds to Beds” Increases likelihood that high risk patients will receive naloxoneIs cost-effective; insurance billingImproves patient satisfactionPoison Center expertise can assist clinicians and patients in real time, reduce healthcare costs, and provide public and provider education

Medication Assisted Treatment (MAT) reduces mortality and relapse rates

MAT is associated with significant healthcare cost savings

ED buprenorphine management

Improves immediate treatment of withdrawal

Increases likelihood of treatment engagementInpatient addiction treatmentImproves patient adherence to therapyReduces subsequent drug useImproves overall quality of careFacilitates follow up MAT engagement

SummarySlide40

Questions?Slide41

Thank you!