Predictability of buprenorphine-naloxone treatment retention: A multi-site analysis combining electronic health records and machine learning.

BACKGROUND AND AIMS: Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors. DESIGN: This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data. SETTING AND CASES: Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively. MEASUREMENTS: Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts. FINDINGS: Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence. CONCLUSIONS: US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts.

Intergenerational effects of maternal PTSD: Roles of parenting stress and child sex.

OBJECTIVES: Parental posttraumatic stress disorder (PTSD) increases children's risk for emotional and behavioral problems. We examined parenting stress and parenting behavior quality as mediators of the relation between maternal PTSD and problematic child behaviors in a sample at high risk for trauma exposure. We also examined whether child sex moderated this association. METHOD: Participants were 141 African American mother-child dyads (children aged 8-12). Mothers reported PTSD severity, parenting stress, and child behavior (externalizing, internalizing, and emotional self-control). Parenting behavior quality (accounting for factors including parental warmth and engagement) was assessed from an observational parent-child interaction task. RESULTS: Parenting stress, but not observed parenting behavior quality, mediated the relation between maternal PTSD severity and child behaviors. Child sex moderated this association, such that the effect was stronger for girls. CONCLUSIONS: Maternal PTSD may be associated with negative child behavior outcomes, and this relation appears to be mediated by increased parenting stress. Stress-reducing interventions for parents with PTSD could improve child outcomes, especially for girls. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Maternal influences on binge eating behaviors in children.

Binge eating in childhood has been linked to adverse future health outcomes. Parental factors, such as parents' emotion regulation and executive functioning, are likely to influence children's self-regulatory behaviors, including eating. Executive functioning describes a range of higher-order cognitive functions such as planning, abstraction, inhibitory control and working memory, which involves the ability to learn, update and manipulate new information while managing distractions. No studies have examined associations between maternal emotion regulation and executive functioning and the child's maladaptive eating patterns, which was the goal of the present study. Forty-eight mother and child pairs completed self-report clinical measures of emotion dysregulation and attentional control, and mothers completed a brief neuropsychological battery, which included executive functioning measures. Child's disordered eating was measured with the Child Binge Eating Disorder Scale. Linear regression results indicated that mother's performance on a working memory task and child's emotion dysregulation was significantly associated with child's binge eating symptoms (R 2 = 0.34). These data, which reveal that maternal executive functioning is associated with self-regulatory behaviors in children, indicate a possible mechanism through which maladaptive eating behaviors may emerge early in development. This relationship merits further exploration in larger-scale prospective intergenerational studies.

Trauma exposure, PTSD, and parenting in a community sample of low-income, predominantly African American mothers and children.

OBJECTIVES: Trauma and posttraumatic stress disorder (PTSD) are associated with problematic parenting and incidence of trauma and PTSD in children of affected parents. In communities impacted by frequent trauma, parenting may be particularly important to children's PTSD risk. The authors examined relationships among maternal and child trauma and mental health, as well as problematic parenting. METHOD: The authors recruited 112 mother-child dyads (50 girls, 62 boys; ages 8-12 years old) from a community sample of low-income, primarily African American families. They examined rates of trauma exposure and PTSD symptoms in mothers and children, the association of maternal trauma and PTSD with self-reported child abuse potential and parenting stress (i.e., parental distress, dysfunctional parent-child interactions, and perceived child difficulty), and the impact of maternal trauma, PTSD, and parenting on child trauma and PTSD. RESULTS: Rates of trauma and PTSD symptoms were relatively high for mothers and children and included community and family violence. Maternal trauma and PTSD predicted child abuse potential, but only maternal PTSD predicted parental distress. Neither maternal trauma nor PTSD predicted parent-reported dysfunctional parent-child interactions or child difficulty. Maternal child abuse potential and child self-reported trauma, but not maternal trauma or PTSD, significantly predicted child self-reported PTSD. Parenting stress was not associated with child PTSD. CONCLUSIONS: Trauma and PTSD in parents may impact parental distress and child abuse potential, potentially increasing children's risk for not only the experience of child abuse, but also PTSD. Child and family interventions should consider child and parental trauma and PTSD as important factors to address. (PsycINFO Database Record

Exposure to Violence Accelerates Epigenetic Aging in Children.

Epigenetic processes, including DNA methylation, change reliably with age across the lifespan, such that DNA methylation can be used as an "epigenetic clock". This epigenetic clock can be used to predict age and age acceleration, which occurs when methylation-based prediction of age exceeds chronological age and has been associated with increased mortality. In the current study we examined epigenetic age acceleration using saliva samples collected from children between ages 6-13 (N = 101). Children's exposure to neighborhood violence and heart rate during a stressful task were assessed. Age acceleration was associated with children's direct experience of violence (p = 0.004) and with decreased heart rate (p = 0.002). Children who were predicted to be older than their chronological age had twice as much violence exposure as other children and their heart rate was similar to that of adults. The results remained significant after controlling for demographic variables, such as sex, income and education. This is the first study to show the effects of direct violence exposure on epigenetic aging in children using salivary DNA. Although longitudinal studies are needed to determine whether accelerated epigenetic aging leads to adverse health outcomes later in life, these data point to DNA methylation during childhood as a putative biological mechanism.

Maternal buffering of fear-potentiated startle in children and adolescents with trauma exposure.

Parental availability influences fear expression and learning across species, but the effect of maternal buffering on fear learning in humans is unknown. Here we investigated the effect of maternal availability during fear conditioning in a group of children (ages 8-10) and adolescents (ages 11-13) from a low-income population with a range of trauma exposure. Acoustic startle response data were collected to measure fear-potentiated startle (FPS) in 104 participants. A total of 62 participants were tested with the mother available and 42 when the mother was not in the testing room. We observed that maternal availability during fear conditioning interacted with age to affect FPS discrimination between CS+ and CS-. In line with previous findings suggesting an absence of maternal buffering in adolescents, fear discrimination was affected by maternal availability only in children. Second, we observed that the effect of maternal buffering on FPS discrimination in children was not influenced by maternally reported warmth. In conclusion, we demonstrated that maternal availability improved discrimination in children, regardless of the quality of the relationship. Adolescents discriminated irrespective of maternal status, suggesting that childhood may be a sensitive period for environmental influences on key processes such as learning of danger and safety signals.

Maternal Child Sexual Abuse Is Associated With Lower Maternal Warmth Toward Daughters but Not Sons.

Mothers with a history of child sexual abuse report less warmth toward their children, but whether this association differs by child gender is unknown. We examined the association of maternal child sexual abuse and warmth across child gender, accounting for depression, post-traumatic stress disorder, and child physical abuse. We verbally administered self-report measures to a cross-sectional sample of 154 mothers with a child between 8 and 12 years old. Eighty-five mothers based warmth responses on a son, and 69 on a daughter. We conducted a hierarchical multiple regression, including child gender, maternal child sexual abuse, child physical abuse, depression, post-traumatic stress disorder, and 4 two-way interaction terms with child gender. Maternal depression predicted decreased warmth, regardless of child gender, and maternal child sexual abuse predicted decreased warmth, but only toward daughters. Given previous research suggesting that maternal warmth predicts child well-being, the current finding may represent an important avenue of intergenerational transmission of risk in girls.