The Prescription Opioid Epidemic and Neonatal Abstinence Syndrome

Transcription

1 The Prescription Opioid Epidemic and Neonatal Abstinence Syndrome Stephen W. Patrick, MD, MPH, MS Ayers Children s Medical Center 2016 General Pediatric Conference September 17, 2016

2 History History Trends in Opioid Use Substance Exposure in Pregnancy NAS Federal and State Policy

3 Happel TJ. Morphinism in its relation to the sexual functions and appetite and its effects on the offspring of the users of the drug. Tr M Soc Tennessee. 1892;

4 Happel TJ. Morphinism in its relation to the sexual functions and appetite and its effects on the offspring of the users of the drug. Tr M Soc Tennessee. 1892;

5 Happel TJ. Morphinism in its relation to the sexual functions and appetite and its effects on the offspring of the users of the drug. Tr M Soc Tennessee. 1892;

6 Happel TJ. Morphinism in its relation to the sexual functions and appetite and its effects on the offspring of the users of the drug. Tr M Soc Tennessee. 1892;

7 Happel TJ. Morphinism in its relation to the sexual functions and appetite and its effects on the offspring of the users of the drug. Tr M Soc Tennessee. 1892;

8 Frakt, Austin. "Painkiller Abuse, a Cyclical Challenge." The New York Times 22 Dec

9 Ø1827 Morphine marketed by Merck Ø Pain relief Ø Treatment of opium addiction Ø Treatment of alcoholism Frakt, Austin. "Painkiller Abuse, a Cyclical Challenge." The New York Times 22 Dec Additional Source: Hendree Jones, PhD

10 Ø1874 Diacetylmorphine discovered Ø 1898 Bayer pharmaceutical marketed under name Heroin Ø The marketing campaign Ø"safe, non-addictive" substitute for morphine Ø 1906 American Medical Association approved Heroin for general use and recommended that it be used in place of morphine. Frakt, Austin. "Painkiller Abuse, a Cyclical Challenge." The New York Times 22 Dec Additional Source: Hendree Jones, PhD

11 NEJM 1980 Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. Jan ;302(2):123.

12 NEJM 1980 Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. Jan ;302(2):123.

13 1996 American Pain Society Pain as the 5th Vital Sign Campaign Federation of State Medical Boards published "Model Guidelines for the Use of Controlled Substances for the Treatment of Pain. The New York Times reports tripling of young adults (18-25) abusing opioid pain relievers. DEA and FDA create task force to crack down on internet sales of opioids. Maker of OxyContin, Purdue Pharma, plead guilty to criminal charges that they misled regulators, doctors and patients about the drug s risk of addiction and its potential to be abused. Results in a $600M settlement Rapid expansion of opioid use in the US Frakt, Austin. "Painkiller Abuse, a Cyclical Challenge." The New York Times 22 Dec

14 Trends in Opioid Use History Trends in Opioid Use Substance Exposure in Pregnancy NAS Federal and State Policy

15 Opioid Pain Reliever Sales Centers for Disease Control and Prevention

16 Opioid Pain Reliever Deaths Centers for Disease Control and Prevention

17 Tennessee #2 in US

18 Opioid Prescription Rates by County TN, 2007 Source: Michael Warren, MD, MPH Tennessee DOH Data source: Tennessee Department of Health; Controlled Substance Monitoring Database.

19 Opioid Prescription Rates by County TN, 2008 Source: Michael Warren, MD, MPH Tennessee DOH Data source: Tennessee Department of Health; Controlled Substance Monitoring Database.

20 Opioid Prescription Rates by County TN, 2009 Source: Michael Warren, MD, MPH Tennessee DOH Data source: Tennessee Department of Health; Controlled Substance Monitoring Database.

21 Opioid Prescription Rates by County TN, 2010 Source: Michael Warren, MD, MPH Tennessee DOH Data source: Tennessee Department of Health; Controlled Substance Monitoring Database.

22 Opioid Prescription Rates by County TN, 2011 Source: Michael Warren, MD, MPH Tennessee DOH Data source: Tennessee Department of Health; Controlled Substance Monitoring Database.

23 Opioid Pain Relievers Prescriptions grew 4-fold over last decade Now account for more overdose deaths than cocaine and heroin combined More deaths than car accidents In 2012, enough OPR were prescribed to give every adult in the US one prescription Source: Centers for Disease Control and Prevention

24 Substance Exposure in Pregnancy History Trends in Opioid Use Substance Exposure in Pregnancy NAS Federal and State Policy

25 Ailes EC, Dawson AL, Lind JN, et al. Opioid prescription claims among women of reproductive age - United States, MMWR Morb Mortal Wkly Rep. Jan ;64(2):37-41.

26 What about Other Drugs? Illicit drug use in pregnancy (averaged across ) 18.3% - pregnant girls 15 to 17 years old 9.0% - pregnant women 18 to 25 years old 5.9% years (less than non-pregnant 10.7%) Legal drugs in pregnancy 17.6% smoke cigarettes 9.4% use alcohol Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services Administration;2013.

27 What about Other Drugs? 440,000 infants exposed to illicit drugs and alcohol per year Only 5% detected at birth Young N, et al. Substance-Exposed Infants: State Responses to the Problem. Rockville, MD: Substance Abuse and Mental Health Services Administration;2009.

28 NAS History Trends in Opioid Use Substance Exposure in Pregnancy NAS Federal and State Policy

29 What is NAS? A withdrawal syndrome experienced by drug exposed newborns after birth Generally follows opioid exposure, though other drugs have been implicated Alcohol, benzodiazepines (valium, etc.), barbiturates (phenobarbital, etc.) 40-80% of heroin and methadone exposed newborns develop NAS ~5% of those exposed to opioid pain relievers

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31 Clinical Features of NAS GI Poor feeding/vomiting/loose stools Leading to dehydration and poor weight gain CNS Tremors/hypertonia Irritability/decreased sleep Exaggerated reflexes (e.g. moro) Seizures Autonomic activation Tachypnea Yawning Dilated pupils

32 Making the Diagnosis Not every exposed newborn has withdrawal Exposure: history, maternal drug screens (urine), infant drug screens (urine, umbilical cord, meconium) Diagnosis made based on scoring system of newborn signs of withdrawal

33 Zimmermann-Baer U. Finnegan neonatal abstinence scoring system: normal values for first 3 days and weeks 5-6 in non-addicted infants. Addiction (Abingdon, England). 2010;105(3):

34 NAS Scoring Issues Scoring Tools Have not undergone rigorous instrument development Significant inter-rater reliability challenges Scoring Cut-point Threshold Scoring Context Never tested in preterm infants Tested on pure opiate-exposed population Currently poly-substance exposure is the norm Finnegan paper = average LOS was 6 days... Source: Madge Buss-Frank

35 NAS Treatment Goal of treatment to control withdrawal, minimizing complications (e.g. seizure) Non-pharmacologic intervention (e.g. environmental controls, etc) Involves using opioids (morphine, methadone) and slowing decreasing dose

36 More Opioids = More NAS?

37 Incidence of NAS in the US, NAS per 1000 Hospital Births Year Patrick SW, et. al. Neonatal Abstinence Syndrome and Associated Healthcare Expenditures United States, JAMA May 9;307(18): Patrick SW, Davis MM, Lehman CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. Apr

38 NAS by US Geographic Division, 2012 vu.edu/nas Patrick SW, Davis MM, Lehman CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. Apr

39 NAS in 28 US States, 2013 Incidence rates per 1000 hospital births > < 1 No data Ko JY, Patrick SW, Tong VT, Patel R, Lind JN, Barfield WD. Incidence of Neonatal Abstinence Syndrome - 28 States, MMWR Morb Mortal Wkly Rep. 2016;65(31):

40 Mean LOS and Hospital Charges for NAS, Mean LOS (day) Mean Charges* (2012 US$) *p<0.001 Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. 2015;35(8):

41 Mean LOS and Hospital Charges for NAS, Mean LOS (day) Mean Charges* (2012 US$) $75,700 $80,500 $87,700 $93,400 *p<0.001 Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. 2015;35(8):

42 Proportion of NICU Days, By NICU (N=299) Tolia VN, Patrick SW, Bennett MM, et al. Increasing Incidence of the Neonatal Abstinence Syndrome in U.S. Neonatal ICUs. N Engl J Med. 2015;372(22):

43 Total Hospital Charges for NAS, Medicaid* $560M $870M $900M $1.2B Private Payer* Self Pay* Other Payer* Total Charges* *p<0.001 Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. 2015;35(8):

44 Total Hospital Charges for NAS, Medicaid* $560M $870M $900M $1.2B Private Payer* $130M $170M $210M $200M Self Pay* $20M $40M $30M $40M Other Payer* $14M $30M $30M $30M Total Charges* $730M $1.1B $1.2B $1.5B *p<0.001 Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to J Perinatol. 2015;35(8):

45 Prescription Opioid Epidemic and Infant Outcomes Patrick SW, Dudley J, Martin PR, et al. Prescription opioid epidemic and infant outcomes. Pediatrics. 2015;135(5):

46 NAS Risk Prescription opioids include Short-acting (e.g. hydrocodone) Long-acting (e.g. oxymorphone ER) Maintenance (e.g. methadone, buprenorphine) Factors associated with developing NAS unclear Dose (only evaluated for maintenance drugs) Tobacco Selective Serotonin Reuptake Inhibitor

47 Characteristics of Mothers Maternal race African American Caucasian Other Psychiatric Diagnoses Depression Anxiety Other Exposures Tobacco SSRI (at delivery) No Opioid % N = 80,675 Any Opioid Use % N = 31,354 p-value

48 Characteristics of Mothers No Opioid Any Opioid Use % N = 80,675 % N = 31,354 p-value Maternal race <0.001 African American 32.2% 26.7% Caucasian 65.8% 72.4% Other 1.6% 0.6% Psychiatric Diagnoses Depression 2.7% 5.3% <0.001 Anxiety 1.6% 4.3% <0.001 Other Exposures Tobacco 25.8% 41.8% <0.001 SSRI (at delivery) 1.9% 4.3% <0.001

49 Characteristics of Mothers No Opioid Any Opioid Use % N = 80,675 % N = 31,354 p-value Maternal race <0.001 African American 32.2% 26.7% Caucasian 65.8% 72.4% Other 1.6% 0.6% Psychiatric Diagnoses Depression 2.7% 5.3% <0.001 Anxiety 1.6% 4.3% <0.001 Other Exposures Tobacco 25.8% 41.8% <0.001 SSRI (at delivery) 1.9% 4.3% <0.001

50 Characteristics of Mothers No Opioid Any Opioid Use % N = 80,675 % N = 31,354 p-value Maternal race <0.001 African American 32.2% 26.7% Caucasian 65.8% 72.4% Other 1.6% 0.6% Psychiatric Diagnoses Depression 2.7% 5.3% <0.001 Anxiety 1.6% 4.3% <0.001 Other Exposures Tobacco 25.8% 41.8% <0.001 SSRI (at delivery) 1.9% 4.3% <0.001

51 Characteristics of Mothers No Opioid Any Opioid Use % N = 80,675 % N = 31,354 p-value Maternal race <0.001 African American 32.2% 26.7% Caucasian 65.8% 72.4% Other 1.6% 0.6% Psychiatric Diagnoses Depression 2.7% 5.3% <0.001 Anxiety 1.6% 4.3% <0.001 Other Exposures Tobacco 25.8% 41.8% <0.001 SSRI (at delivery) 1.9% 4.3% <0.001

52 50% 45% Oxycodone HCl 10mg q6h x 5 weeks Buprenorphine HCl 24mg q24h x 25 weeks 40% 35% 30% 25% 20% 15% 10% 5% 0% No SSRI, No Smoking SSRI, No Smoking No SSRI, Smoking 1 pack SSRI and Smoking 1 pack *Results shown after adjustment for maternal age, education, race, infant gender, birthweight, year of birth, interaction drug type and cumulative opioid exposure (0.0002), interaction of number of cigarettes smoked per day and cumulative opioid exposure (p<0.001), drug type and number of cigarettes smoked per day.

53 Implications Medicaid insures ~80% of infants with NAS States well-positioned to minimize unnecessary opioid use in pregnancy The AAP recommends observation of opioid exposed infants for 4-7 days Low-risk discharged sooner? High-risk closer observation?

54 NAS Care Improvement

55 NAS Treatment No clear optimal treatment Opioid (e.g. morphine or methadone) for opioid withdrawal American Academy of Pediatrics 2012 Policy statement Every hospital should have a protocol Adhering to protocols improves outcomes Data suggests this is not occurring Hall ES, Wexelblatt SL, Crowley M, et al. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014;134(2):e

56 NAS Quality Collaborative Vermont Oxford Network >1000 NICUs around the world engaged in quality improvement In 2012, 199 centers enrolled in a NAS focused improvement collaborative Toolkit focused on understanding process Interactive webinar Digital communication Real time center-specific feedback

57 Hospital Policies 6 Number of Hospital Policies (mean) Feb-13 Aug-13 Feb-14 Aug-14 Patrick SW, Schumacher RE, Horbar JD, Buus-Frank M, et. al., Improving Care for Infants with Neonatal Abstinence Syndrome: A Multicenter Prospective Collaborative. Pediatrics May;137(5).

58 Infant Outcomes February 2013 August 2013 February 2014 August 2014 Median (IQR) Median (IQR) Median (IQR) Median (IQR) p-value Length of treatment (days) 16 (10, 27) 15 (10, 23) 15 (10, 24) 15 (10, 24) Length of hospital stay (days) N=3,458 Patrick SW, Schumacher RE, Horbar JD, Buus-Frank M, et. al., Improving Care for Infants with Neonatal Abstinence Syndrome: A Multicenter Prospective Collaborative. Pediatrics May;137(5).

59 Infant Outcomes February 2013 August 2013 February 2014 August 2014 Median (IQR) Median (IQR) Median (IQR) Median (IQR) p-value Length of treatment (days) 16 (10, 27) 15 (10, 23) 15 (10, 24) 15 (10, 24) Length of hospital stay (days) 21 (14, 33) 20 (14, 28) 20 (14, 29) 19 (15, 28) <0.001 N=3,458 Patrick SW, Schumacher RE, Horbar JD, Buus-Frank M, et. al., Improving Care for Infants with Neonatal Abstinence Syndrome: A Multicenter Prospective Collaborative. Pediatrics May;137(5).

60 Collaborative Summary Decreased LOT, LOS Proportion of infants discharged home on pharmacotherapy decreased In adjusted analyses, scoring standardization associated with lowest LOT/LOS Centers focusing on keeping mom/baby together Estimated savings of 2 day shorter hospital stay: $170M

61 Federal and State Policy History Trends in Opioid Use Substance Exposure in Pregnancy NAS Federal and State Policy

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63 White House Plan Education Parents, youth, and patients Requiring prescribers to receive education on the appropriate and safe use, and proper storage and disposal of prescription drugs Monitoring Every state with a Prescription Drug Monitoring Program Work towards interstate interoperability

64 White House Plan Proper Medication Disposal Develop convenient and environmentally responsible prescription drug disposal programs to help decrease the supply of unused prescription drugs in the home. Enforcement Provide law enforcement with the tools necessary to eliminate improper prescribing practices and stop pill mills.

65 NAS Policy

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67 GAO: Highlights NIH Funding from $21.6 million 14 federal programs provide direct services Need coordination, suggest one HHS contact there is a risk that federal efforts may be duplicated, overlapping, or fragmented

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69 Protecting Our Infants Act, 2015 Requests that HHS: Review and improve coordination in HHS Develop a strategy to address gaps in research and federal programs Study and develop recommendations for preventing and treating prenatal opioid use and NAS Improve data and public health response by supporting states and tribes Signed by President Obama in November 2015 HHS: U.S. Department of Health and Human Services Public Law No:

70 Comprehensive Addiction and Recovery Act of 2016 Highlights: Broad approach to prevention, expansion of treatment inclusive of pregnant women and children National All Schedules Prescription Electronic Reporting (NASPER) Reauthorization Improving Treatment for Pregnant and Postpartum Women GAO report on NAS Infant Plan of Safe Care Signed by President Obama in July 2016; however, to date, not fully funded GAO: Government Accountability Office Public Law No:

71 Tennessee: Criminal Justice vs. Public Health Safe Harbor Act of 2013 ensure that family-oriented drug abuse or drug dependence treatment is available Treatment by 20 th week -> No prosecution, no child removal just for history of drug misuse Public Chapter 820 A woman can be charged with a misdemeanor if she illegally uses narcotics during pregnancy and if the baby is harmed as a result (ex. Neonatal Abstinence Syndrome)

72 Opioid misuse is not new Conclusions Recent rise of opioid use and NAS left the health system unprepared Public health approaches are needed Care for NAS needs standardization Better identification Site of care More efficient care

73 Vanderbilt Bill Cooper, MD, MPH Kathy Hartmann, MD, PhD Frank Harrell, MD E. Wes Ely, MD, MPH Jeff Reese, MD John Benjamin, MD, MPH Hendrik Weitkamp, MD Bill Walsh, MD Susan Guttentag, MD Ann Stark, MD Melinda Buntin, PhD Carrie Fry, M.Ed. Faouzi Maalouf, MD Katie Charles, MS4 Shannon Stratton, RN Stacey Copeland Michelle DeRanieri, MSN Judy Dudley, BA Terri Scott, MS Pennie Bell, MSN Heidi Holstein-Edwards Angie Tune Chris Lehmann, MD Acknowledgements Cincinnati Children s Hospital Heather Kaplan, MD, MSCE Kathy Auger, MD, MSc Johns Hopkins Lauren Jansson, MD Children s Hospital of Philadelphia Scott Lorch, MD, MSCE Tennessee Department of Health Michael Warren, MD, MPH Tim Jones, MD John Dreyzehner, MD, MPH Vermont Oxford Network Madge Buus-Frank, MS, APRN-BC, Jeffrey Horbar, MD Roger Soll, MD Erika Edwards, PhD University of Michigan Matthew M. Davis, MD, MAPP Gary L. Freed, MD, MPH Robert E. Schumacher, MD James Burke, MD, MS Pediatrix Veeral Tolia, MD Reese Clark, MD

74 Acknowledgements Funders: Robert Wood Johnson Foundation Clinical Scholars Program Tennessee Department of Health/HRSA National Institutes of Health - 5KL2TR National Institute on Drug Abuse - 1K23DA National Institute on Drug Abuse Loan Repayment Program

75 Thank you!

76 Morbidity and Mortality Weekly Report Implementation of a Statewide Surveillance System for Neonatal Abstinence Syndrome Tennessee, 2013 Michael D. Warren, MD 1, Angela M. Miller, PhD 1, Julie Traylor, MPH 1, Audrey Bauer, DVM 1, Stephen W. Patrick, MD 2 (Author affiliations at end of text) First state to begin public reporting Able to target prevention efforts Several other states following suit Kentucky, Ohio, Massachusetts, Indiana

77 Neonatal Abstinence Syndrome, Tennessee, 2013 Warren MD, Miller AM, Traylor J, Bauer A, Patrick SW. Implementation of a statewide surveillance system for neonatal abstinence syndrome - Tennessee, MMWR Morb Mortal Wkly Rep. Feb ;64(5):

78 Do PDMPs Work? Patrick SW, Fry CE, Jones TF, Buntin MB. Prescription Drug Monitoring Programs and Opioid-Related Overdose Deaths. In press, Health Affairs.

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80 PDMPs PDMPs vary in structure Number of schedules monitored Mandatory registration Mandatory use Frequency of update Little data evaluating their effectiveness

81 PDMPs Effective? Sample: 34 US States that implemented a PDMP between 1999 to 2013 Unit of observation: state, year Predictor of interest: PDMP Implementation/structure Covariates: education, unemployment, legislative enactment, time trend Outcome: Opioid-related overdose deaths per 100,000 population Analysis: interrupted time series, state fixed effects

82 Implementation PDMPs 1999

83 Implementation of PDMPs 2013

84 Prescription Opioid-Related Death Rate 1999

85 Prescription Opioid-Related Death Rate 2013

86 Results Variable PDMP Implementation Number of Drug Schedules Monitored Adjusted Mortality Rate (per 100,000) a (95% CI) (-1.68, -0.55) Adjusted Mortality Rate (per 100,000) a, b (95% CI) Four + -- Frequency Data is Updated in PDMP Weekly or greater -- Mandatory Use or Registration a Adjusted for time trend, PDMP legislative enactment, educational attainment, unemployment rate, interaction of PDMP implementaiton*time and state fixed-effects b West Virginia excluded --

87 Results Variable PDMP Implementation Adjusted Mortality Rate (per 100,000) a (95% CI) (-1.68, -0.55) Adjusted Mortality Rate (per 100,000) a, b (95% CI) -- Number of Drug Schedules Monitored Four + -- Frequency Data is Updated in PDMP (-1.02, -0.08) Weekly or greater -- Mandatory Use or Registration a Adjusted for time trend, PDMP legislative enactment, educational attainment, unemployment rate, interaction of PDMP implementaiton*time and state fixed-effects b West Virginia excluded --

88 Results Variable PDMP Implementation Adjusted Mortality Rate (per 100,000) a (95% CI) (-1.68, -0.55) Adjusted Mortality Rate (per 100,000) a, b (95% CI) -- Number of Drug Schedules Monitored Four + -- Frequency Data is Updated in PDMP Weekly or greater -- Mandatory Use or Registration (-1.02, -0.08) (-1.25, -0.38) a Adjusted for time trend, PDMP legislative enactment, educational attainment, unemployment rate, interaction of PDMP implementaiton*time and state fixed-effects b West Virginia excluded --

89 Results Variable PDMP Implementation Adjusted Mortality Rate (per 100,000) a (95% CI) (-1.68, -0.55) Adjusted Mortality Rate (per 100,000) a, b (95% CI) -- Number of Drug Schedules Monitored Four + -- Frequency Data is Updated in PDMP Weekly or greater -- Mandatory Use or Registration (-1.02, -0.08) (-1.25, -0.38) 0.30 (-0.27, 0.87) a Adjusted for time trend, PDMP legislative enactment, educational attainment, unemployment rate, interaction of PDMP implementaiton*time and state fixed-effects b West Virginia excluded

90 Implications PDMPs implementation was associated with a decrease in overdose death even when accounting for potential confounders One death prevented every 2 hours in the US after PDMP implementation More schedules monitored and more frequent updates associated with decreases Next steps, other outcomes? NAS?