Adverse Childhood Experiences ACEs What are they and

Adverse Childhood Experiences (ACEs) What are they and what can we do?

Objectives • Describe the physical and mental health consequences of ACEs. • Discuss the use of the ACE survey in the medical home and how this may assist physicians to better engage and care for their patients. • Discuss the impact of resilience on mitigating the negative health consequences of ACEs. • Describe how trauma-informed care can benefit patients. 2

Outline • Define ACEs • The landmark 1998 study and follow-up studies • Population prevalence • ACE survey tool • Adult health and mental health consequences • Child health consequences • Trauma-informed care • Resilience studies and tools 3

Definition of ACEs • “Adverse childhood experiences (ACEs) are potentially traumatic events that can have negative, lasting effects on health and wellbeing. These experiences range from physical, emotional, or sexual abuse to parental divorce or the incarceration of a parent or guardian. ” Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to the many leading causes of death in adults: The Adverse Childhood Experiences. Am J Prev Med. 1998; 14(4): 245 -258. 4

The first ACEs study • First comprehensive retrospective study of early childhood exposure to potential adverse experiences and subsequent health outcomes. • Kaiser patients whose medical records were available for review were surveyed. • Surveys were sent to almost 13, 500 Kaiser members and close to 10, 000 responded. • Responses were grouped into 7 categories of exposure: • Abuse (3)…. Psychological abuse Physical abuse Sexual abuse • Household (4)… Substance abuse in a parent Mental illness in a parent Intimate partner violence (IPV) toward the mother Criminal behavior/incarceration Felitti VJ, Anda RF, Nordenberg D, et al. Am J Prev Med. 1998; 14(4): 245 -258. 5

The ACEs study continued • 10 significant health risk factors: • Morbid obesity - Physical inactivity - Depressed mood – Suicide attempts • Smoking - Alcoholism – Any drug abuse – Parenteral (IV) drug abuse • High lifetime number of sexual partners (>50) – History of a sexually transmitted infection (STI) • 8 specific conditions in the respondents: • • Ischemic heart disease (myocardial infarction or nitroglycerin use) Any cancer Stroke Chronic bronchitis Chronic obstructive pulmonary disease (COPD) Diabetes Hepatitis/Jaundice Skeletal fractures Felitti VJ, Anda RF, Nordenberg D, et al. Am J Prev Med. 1998; 14(4): 245 -258. 6

ACEs study results • Patients scored on a 0 -7 scale on the ACE survey – one for each category of exposure • More than half had at least 1 exposure and a quarter had 2 or more exposures • Compared to individuals with scores of 0, individuals with a score of 4 or more had: • 4 fold to 12 fold increase chances for alcoholism, drug abuse, depression, and suicide attempts • 2 fold to 4 fold increased in smoking, poor self-rated health, >50 sexual partners, and STI • 1. 4 fold to 1. 6 fold increase in physical inactivity and severe obesity Felitti VJ, Anda RF, Nordenberg D, et al. Am J Prev Med. 1998; 14(4): 245 -258. 7

Childhood Experiences vs Liver Disease Childhood Experiences vs Adult Alcoholism 12 % Hepatitis/jaundice % Alcoholism 20 15 10 6 4 2 0 0 1 2 3 4+ Childhood Experiences vs Chronic Depression 60 50 40 30 Women 20 Men 10 0 0 1 2 3 4+ 0 Prescription rate per 100 person years 0 % Depression 8 1 2 3 4+ Childhood Experiences vs Antidepressant Prescription 120 100 80 60 40 20 0 0 1 2 3 4 5+ Felitti V and Anda R. The Impact of Early Life Trauma on Health and Disease. The Hidden Epidemic, edited by Lanius RA, 8 Vermetten E, Pain C. Cambridge University Press, 2010

Childhood Experiences vs Suicide Attempts Childhood Experiences vs Later Being Raped 35 30 15 % Reporting rape % Attempting suicide 20 10 5 20 15 10 5 0 0 1 2 3 0 4+ 0 Childhood Experiences vs Perpetrating IPV 1 2 3 4+ Childhood Experiences vs Teen Sexual Behaviors 14 50 12 40 10 8 Women 6 Men 4 2 0 0 1 2 3 4 5+ % % Perpetrating domestic violence 25 0 30 1 20 2 10 3 0 4+ Intercourse by Teen Pregnancy Teen Paternity 15 Felitti V and Anda R. The Impact of Early Life Trauma on Health and Disease. The Hidden Epidemic, edited by Lanius RA, 9 Vermetten E, Pain C. Cambridge University Press, 2010

Childhood Experiences vs COPD % with COPD 18 16 14 12 10 8 6 4 2 0 0 1 2 3 5 -Apr 6+ 20 18 16 14 12 10 8 6 4 2 0 0 1 2 3 4+ Childhood Experiences vs Impaired Work/Life Performance Prevalence of impaired performance % Smoking Childhood Experiences vs Smoking as an Adult 25 20 0 15 1 10 2 5 3 0 4+ Absenteeism Serious Financial Problems Serious Prob Performing Job Felitti V and Anda R. The Impact of Early Life Trauma on Health and Disease. The Hidden Epidemic, edited by Lanius RA, 10 Vermetten E, Pain C. Cambridge University Press, 2010

New Zealand study • 30 year prospective New Zealand study of 1, 000 people born between 1972 and 1973 • Incidence of early childhood trauma and later health consequences • Similar adverse health effects as the Felitti study: • 40% of children had one or more adverse experience • Children who were physically or sexually abused or experienced maternal neglect were almost 3 times more likely to report a major depression by their early 30 s and almost twice as likely to carry an elevated risk for heart disease Danese A, Moffitt TE, Harrington H-L et al. Archives of Pediatric and Adolescent Medicine 2009; 163(12): 1135 -1143. 11

How common are ACEs? % of study respondents reporting # of ACEs Types of ACEs reported Substance use disorder Physical abuse Four or more 12% Parental separation Sexual abuse Three 9% Zero 37% Mental illness Emotional neglect Two 16% Intimate Partner Violence Parental incarceration One 26% Based on the Behavioral Risk Factor Surveillance System https: //www. cdc. gov/violenceprevention/acestudy/ACE_graphics. html Emotional abuse Physical neglect 0 5 10 15 20 25 Prevalence % 12 30

Did a parent, step-parent or other adult in the household often or very often… Swear at you, insult you, put you down, or humiliate you? or Act in a way that made you afraid that you might be physically hurt? YES or NO Did a parent, step-parent or other adult in the household often or very often… Push, grab, slap, or throw something at you? or Ever hit you so hard that you had marks or where injured? YES or NO Did an adult or person at least 5 years older than you ever… Touch or fondle you or have you touch their body in a sexual way? or Attempt or actually have oral, anal or vaginal intercourse with you? YES or NO Did you often or very often feel that… No one in your family loved you or thought you were important or special? or Your family didn’t look out for each other, feel close to each other, or support each other? YES or NO Did you often or very often feel that… You didn’t have enough to eat, had to wear dirty clothes, and had no one to protect you? or Your parents were too drunk or high to take care of you or take you to the doctor if you needed it? YES or NO Were your parents ever separated or divorced? YES or NO Was your parent, step-parent or another adult who was helping to raise you: Often or very often pushed, grabbed, slapped, or had something thrown at them? or Sometimes, often, or very often kicked, bitten, hit with a fist, or hit with something hard? or Ever repeatedly hit over at least a few minutes or threatened with a gun or knife? YES or NO Did you live with anyone who was a problem drinker or alcoholic, or who used street drugs? YES or NO Was a household member depressed or mentally ill, or did a household member attempt suicide? YES or NO Did a household member go to prison? YES or NO Did you often, very often or sometimes feel that you were treated badly or unfairly because of your race or ethnicity? YES or NO Did you see or hear someone being beaten up, stabbed, or shot in real life multiple times? YES or NO Did you feel unsafe in your neighborhood some, most, or all of the time? YES or NO Were you bullied by a peer or classmate all of the time or most of the time? YES or NO Were you ever in foster care? YES or NO The Philadelphia ACE Survey is used with permission from the Health Federation of Philadelphia and Philadelphia ACE Research and Data Committee. http: //healthfederation. org/ACEs Note: The Philadelphia ACE Survey responses were collected using a scale rather than simply yes or no answers. We have simplified this for our purposes to yes or no responses.

Child health outcomes • Impaired immune function in the setting of PTSD and depression • Poorer performance on standardized behavioral and socialization surveys • Brain development Bielas H, Jud A, Lips U, et al. Neuro. Immuno. Modulation 2015; 22: 303 -310. Kerker BD, Zhang J, Nadeem E, et al. Academic Pediatrics 2015; 15(5): 510 -517. Bick J and Nelson CA. Neuropsychopharmacology REVIEWS 2016; 41(1): 177– 196. 14

ACEs and brain development • A review of studies looking at brain development in children experiencing family maltreatment and others enduring psychologic deprivation in institutional settings • Global volumetric changes in the brain can be seen in children experiencing maltreatment • Emotional neglect and physical abuse may be associated with smaller amygdala volumes; PTSD, depression and emotional neglect may be associated with smaller hippocampal volumes • Volumetric changes in the prefrontal cortex and cerebellum have been associated with maltreatment-related PTSD Bick J and Nelson CA. Neuropsychopharmacology REVIEWS 2016; 41(1): 177– 196. 15

Child abuse and neglect • Health care providers, teachers and certain licensed professionals in ALL states are required to report suspected child abuse and/or neglect • Since 1974 states have been mandated to establish a mechanism to investigate these reports, and the Child Abuse Prevention and Treatment Act of 1988 established federal funding for states for prevention, assessment, investigation, prosecution and treatment endeavors • Each state has it’s own child protection service and providers need to know the contact information for their particular state to report possible child endangerment Child Welfare Information Gateway. (2016). Mandatory reporters of child abuse and neglect. Washington, DC: U. S. Department of Health and Human Services, Children's Bureau. The United States Department of Justice. https: //www. justice. gov/elderjustice/elder-justice-statutes-0 (2018). 16 Durborow N, Lizdas KC, O'Flaherty A, Anna Marjavi. Compendium of State Statutes and Policies on Domestic Violence and Health Care. 2010.

Adult outcomes: follow-up studies • Lower levels of parent-child attachment • Type 2 Diabetes • Cardiovascular Disease Risk • Inflammatory Gene Expression • Premature Mortality Murphy A, Steele M, Dube SR, et al. Adverse Childhood Experiences (ACEs) Questionnaire and Adult Attachment Interview (AAI): Implications for parent child relationships. Child Abus Negl. 2014; 38(2): 224 -233. doi: 10. 1016/j. chiabu. 2013. 09. 004 Huang H, Yan P, Shan Z et al. Metabolism 2015; 64(11): 1408 -1418. Su S, Jimenez MP, Roberts CTF and Loucks EB. Current Cardiology Reports 2015; 17: 88. Levine ME, Cole SW, Weir DR and Crimmins EM. Social Science & Medicine 2015; 130: 16 -22. 17 Brown DW, Anda RF, Tiemeier H et al. American Journal of Preventive Medicine 2009; 37(5): 389 -396.

ACEs and type 2 diabetes • A 2015 study examined ACEs and risks for type 2 diabetes in adulthood • Systematic review of existing evidence from 7 published studies • Among the 87, 000 + participants, they found for type 2 diabetes: • • An odds ratio of 1. 30 for exposure to physical abuse An odds ratio of 1. 32 for any ACE exposure An odds ratio of 1. 39 for exposure to sexual abuse An odds ratio of 1. 92 for exposure to neglect Huang H, Yan P, Shan Z et al. Metabolism 2015; 64(11): 1408 -1418. 18

ACEs and cardiovascular disease (CVD) • Another 2015 review looked at ACEs and CVD risk • Systematic review of studies that demonstrated: • A linear trend with # of ACEs for confirmed CVD in almost 24, 000 patients • Early childhood maltreatment was associated with early-onset CVD in women – the review included almost 67, 000 patients • Exposure to 4 or more ACEs in almost 54, 000 patients was associated with higher chances of CVD compared to 0 ACEs • Smoking rates were increased in individuals with higher ACE scores • Childhood abuse, residential mobility, household dysfunction, and parental divorce appeared to be independent risks for smoking regardless of SES measures such as level of educational attainment and/or employment in adulthood Su S, Jimenez MP, Roberts CTF and Loucks EB. Current Cardiology Reports 2015; 17: 88. 19

Inflammation and premature mortality • A study of patients 51 to 95 years old examined levels of expression of three proinflammatory genes and exposure to childhood trauma, childhood low SES, and childhood health as well as adult trauma and low SES in adulthood showed that only childhood trauma was associated with increased inflammatory transcription in adulthood which was further exacerbated by low SES in adulthood. • A follow-up study looked at more than 17, 000 individuals assessing 8 ACE exposure categories (abuse, DV, separation/divorce, mental illness, substance abuse or incarcerated parent) from 1995 -1997 and then reassessed in 2006 for causes of death. • ACE scores of 6 or more were associated with an average death 20 years earlier compared to a score of 0 • These very high risk adults were 1. 7 times more likely to die under the age of 75 and 2. 4 times more likely to die before age 65 compared to their low scoring counterparts Levine ME, Cole SW, Weir DR and Crimmins EM. Social Science & Medicine 2015; 130: 16 -22. Brown DW, Anda RF, Tiemeier H et al. American Journal of Preventive Medicine 2009; 37(5): 389 -396. 20

Environment Nutrition Toxins Drugs Pathogens Toxic stress SNPs Mutations mi. RNA nc. RNA Altered childhood development Cp. G methylation Histone modification Epigenetics Genetics Shonkoff JP et. al. Technical Report. Pediatrics 2012; 129: e 232 -e 246. 21

Evolving framework exploring the impact of toxic stress across the lifespan • Transient exposure to stress with release of stress hormones is welltolerated, but chronic stress can be toxic to the developing brain and organs • Intergenerational perpetuation of adverse exposures may be further exacerbated by poorer educational achievement and poverty • Unhealthy behaviors are a means of coping with stress • This is the “solution” the individual finds to cope when few external or internal resources are available • This, as well as lower access to medical care, can lead to increased risk for chronic disease and early mortality Shonkoff JP et. al. Technical Report. Pediatrics 2012; 129: e 232 -e 246. 22

Defining the problem ACEs: • Can have lasting adverse effects on health and can affect anyone • May disproportionately impact children living in poverty • May be considered social determinants of health and may underlie health disparities in some communities • Result in consequences not simply stemming from health-related behaviors • Are therefore NOT strictly a social dilemma • Are medical problems and, as healthcare providers, we need to take this on and own it • Significantly impact both child and adult health 23

Potential interventions Prevention Key practices Specialized care • Recognizing risk factors in expectant parents • Parenting programs • Policies addressing social determinants (prevention of poverty IPV, teen pregnancy, substance use disorders; pre-school enrichment programs) • Securing medical homes for families • Asking about ACEs • Trauma-informed care • Personalized treatment for chronic illnesses • Promoting resilience • Community resource referrals • Social services referrals • Mental health and substance use • Trauma-focused cognitive behavioral therapy • Group-attachment based interventions for parents with high ACE scores • Home-visiting services Kerker BD, Storfer-Isser A, Szilagi M et al. Academic Pediatrics 2016; 16(2): 154 -160. Balistreri KS. Matern Child Health J 2015; 19: 2492 -2500. 24 Murphy A, Steele H, Bate J et. al. Fam Community Health 2015; 38(3): 268 -279.

Trauma-informed care • An organizational approach to patients, families, and staff: • Seeing trauma’s widespread impact • Knowing about pathways for recovery • Acknowledging signs and symptoms of trauma as it impacts all involved in the healthcare arena • Using knowledge to develop a comprehensive program embedded in office/practice/institutional policies and procedures • Efforts to prevent re-traumatization https: //www. samhsa. gov/nctic/trauma-interventions 25

6 principles of trauma-informed care Safety Trustworthiness and transparency Peer support Collaboration and mutuality Empowerment, voice, and choice Cultural, historical, and gender issues https: //www. samhsa. gov/nctic/trauma-interventions 26

Resilience can mitigate the impact of ACEs • In this study, children were assessed by their teachers whether or not they exhibited the quality of resilience and then assessed for their school performance • Comparisons were then made among children who scored 0, 1 or 2+ points on the ACE survey • Increasing risks for emotional, mental health or behavioral issues were noted with increasing ACE scores across the board • However, for each ACE score (0, 1 or 2+), resilient children demonstrated: • Less absenteeism • More classroom engagement • Less need to repeat a grade Sege R, Bethell C, Linkenback J et al. Balancing Adverse Childhood Experiences (ACEs) with HOPE* New 27 Insights into the Role of Positive Experience on Child and Family Development. 2017.

Positive childhood experiences can mitigate the impact of ACEs • Study of adults who had ACE scores greater than or equal to 4 • Adults were assessed for depression, poor health, obesity and smoking • Asked about 4 positive childhood experiences a) Family stood by me c) Sense of belonging in HS b) Felt supported by friends d) Enjoyed community traditions • Statistically significant decreased rates of: depression (a-d), poor health (a and b), obesity (a and b), and smoking (c) Jones J, Bethell CD, Linkenbach J and Sege R. Health effects of ACEs mitigated by positive childhood experiences. 28 (Manuscript in preparation)

Childhood resilience survey • Take time to reflect on the following based on your experiences growing up. Someone in my family often stood by me in hard times. YES or NO I had someone in my family to talk with about difficult feelings. YES or NO I often felt supported by friends. YES or NO I often felt a sense of belonging in high school YES or NO I often enjoyed community traditions. YES or NO I often had at least 2 adults, other than my parents, who took an interest in me. YES or NO Sege R, Bethell C, Linkenback J et al. Balancing Adverse Childhood Experiences (ACEs) with HOPE* New Insights into the Role of Positive Experience on Child and Family Development. 2017. Found at: https: //hria. org/wp-content/uploads/2017/05/Balancing-ACEs-with-HOPE. pdf. 29

Devereux adult resilience survey Take time to reflect and complete each item on the survey below. There are no right answers. Once you have finished, reflect on your strengths and then start small and plan for one or two things that you feel are important to improve. Items Relationships 1. I have good friends who support me 2. I have a mentor or someone who shows me the way 3. I provide support to others 4. I am empathetic to others 5. I trust my close friends Internal beliefs 1. My role as a caregiver is important 2. I have personal strengths 3. I am creative 4. I have strong beliefs 5. I am hopeful about my future 6. I am lovable Yes Some- Not yet times Items Yes Sometimes Initiative 1. I communicate effectively with those around me 2. I try many different ways to solve a problem 3. I have a hobby that I engage in 4. I seek out new knowledge 5. I am open to new ideas 6. I laugh often 7. I am able to say no 8. I can ask for help Self-control 1. I express my emotions 2. I set limits for myself 3. I am flexible 4. I can calm myself down Mackrain, M. (2007). Devereux Adult Resilience Survey. In M. Mackrain & N. Bruce. Building Your Bounce: Simple Strategies for a Resilient you (p. 10). Lewisville, NC: Kaplan. Found at: https: //www. centerforresilientchildren. org/ 30 Not yet

The medical home Education and awareness for parents Increased uptake of services that reduce ACE exposures Parenting programs Literacy Job assistance Social services Families Medical home Supportive healthcare environment Personalized care plans Integrated multidisciplinary model --Behavioral health --Social work --Family resource specialist Trauma-informed care training for all staff Referrals Community Partners Balistreri KS. Adverse childhood experiences, the medical home, and child well-being. Matern Child Health J. 2015; 19(11): 2492 -2500 31

Summary • ACEs are potentially traumatic events that can have negative, lasting effects on health and well-being across the lifespan • Providers within the medical home can use knowledge about ACEs to better care for patients who have significant exposures and mitigate the risk for disease • Trauma-informed care focuses on recognizing the impact of trauma and avoiding re-traumatization with a safe, trustworthy, clinical environment that encourages self-efficacy, collaboration, and empowerment • Resilience can mitigate the potential impact of ACEs, and as more evidence accumulates about the power of resilience, additional resources may become available 32

Questions? 33

References • Balistreri KS. Adverse childhood experiences, the medical home, and child well-being. Matern Child Health J 2015; 19: 2492 -2500. • Bick J and Nelson CA. Early adverse experiences and the developing brain. Neuropsychopharmacology REVIEWS 2016; 41(1): 177– 196. • Bielas H, Jud A, Lips U, et al. Preliminary evidence for a compromised T-cell compartment in maltreated children with depression and posttraumatic stress disorder. Neuro. Immuno. Modulation 2015; 22: 303 -310. • Brown DW, Anda RF, Tiemeier H et al. Adverse childhood experiences and the risk of premature mortality. American Journal of Preventive Medicine 2009; 37(5): 389 -396. • Centers for Disease Control and Prevention. Adverse Childhood Experiences Presentation Graphics (2016). Found at: https: //www. cdc. gov/violenceprevention/acestudy/ACE_graphics. html • Cronholm PF, Forke CM, Wade R, et al. Adverse childhood experiences: Expand the concept of adversity. American Journal of Preventive Medicine 2015; 49(3): 354 -361. 34

References • Danese A, Moffitt TE, Harrington H-L et al. Adverse childhood experiences and adult risk factors for age-related disease. Archives of Pediatric and Adolescent Medicine 2009; 163(12): 1135 -1143. • Felitti VJ, Anda RF, Nordenberg D et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. American Journal of Preventive Medicine 1998; 14(4): 245 -258. • Felitti VJ. Reverse alchemy in childhood: Turning gold into lead. Health Alert 2001 8(1). • Felitti VJ and Anda R. The Impact of Early Life Trauma on Health and Disease. The Hidden Epidemic, edited by Lanius RA, Vermetten E, Pain C. Cambridge University Press, 2010. • Felitti VJ. Reverse alchemy in childhood: Turning gold into lead. Health Alert (2001). Found at: http: //akhouse. org/tarr/docs/HCR 21_Position-Paper_Reverse. Alchemy-in-Childhood_V-Felitti. pdf 35

References • Huang H, Yan P, Shan Z et al. Adverse childhood experiences and risk of type 2 diabetes: A systematic review and meta-analysis. Metabolism 2015; 64: 1408 -1418. • Jones J, Bethell CD, Linkenbach J and Sege R. Health effects of ACEs mitigated by positive childhood experiences. (Manuscript in preparation) • Kerker BD, Storfer-Isser A, Szilagi M et al. Do pediatricians ask about adverse childhood experiences in pediatric primary care? Academic Pediatrics 2016; 16(2): 154 -160. • Kerker BD, Zhang J, Nadeem E, et al. Adverse childhood experiences and mental health, chronic medical conditions, and development in young children. Academic Pediatrics 2015; 15(5): 510 -517. • Levine ME, Cole SW, Weir DR and Crimmins EM. Childhood and later life stressors and increased inflammatory gene expression at older ages. Social Science & Medicine 2015; 130: 16 -22. • Mackrain, M. (2007). Devereux Adult Resilience Survey. In M. Mackrain & N. Bruce, Building Your Bounce: Simple Strategies for a Resilient you (p. 10). Lewisville, NC: Kaplan. Found at: https: //www. centerforresilientchildren. org/. Accessed May 16, 2018. • Murphy A, Steele H, Bate J et. al. Group attachment-based intervention – trauma-informed care for families with adverse childhood experiences. Fam Community Health 2015; 38(3): 268 -279. 36

References • Murphy A, Steele M, Dube SR, et al. Adverse Childhood Experiences (ACEs) Questionnaire and Adult Attachment Interview (AAI): Implications for parent child relationships. Child Abus Negl. 2014; 38(2): 224 -233. doi: 10. 1016/j. chiabu. 2013. 09. 004 • Philadelphia ACE Research and Data Committee. The Philadelphia ACE Survey. Found at: http: //healthfederation. org/ACEs. Accessed May 16, 2018. • Sege R, Bethell C, Linkenback J et al. Balancing Adverse childhood experiences (ACEs) with HOPE* New insights into the role of positive experience on child and family development (2017). Found at: https: //hria. org/wp-content/uploads/2017/05/Balancing-ACEs-with-HOPE. pdf. Accessed May 16, 2018. • Shonkoff JP et. al. Technical Report. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 2012; 129: e 232 -e 246. • Su S, Jimenez MP, Roberts CTF and Loucks EB. The role of adverse childhood experiences in cardiovascular disease risk: A review with emphasis on plausible mechanisms. Current Cardiology Reports 2015; 17: 88. • Substance Abuse and Mental Health Services Administration. Trauma-Informed Care Approach and Trauma -Specific Interventions (2018). Found at: https: //www. samhsa. gov/nctic/trauma-interventions • Tough, P. The Poverty Clinic. The New Yrker, March 21, 2011. 37