OBJECTIVE:To explore congruence between child self-reported and caregiver-proxy-reported health-related quality of life (HRQOL) over time in juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE), and to identify factors associated with the level of congruence. METHODS:Data were from an observational, longitudinal cohort study conducted to validate the Patient-Reported Outcomes Measurement Information System (PROMIS) measures. HRQOL was assessed at baseline, 6, and 12 months. Four hundred fifty-one children (8-17 years) diagnosed with JIA or cSLE and their caregivers completed the PROMIS Pediatric and Parent Proxy measures, respectively. A 1-way random-effects model was used to estimate the intraclass correlation coefficient (ICC) for congruence between child and caregiver reports, and multivariable mixed-effect models were used to identify associated demographic and clinical factors. RESULTS:The study cohort (87.1% JIA) had a mean age of 13.8 years and were 71.4% female. Across all HRQOL domains, child self-reported and caregiver-proxy-reported mobility, physical activity, fatigue, pain interference, depressive symptoms, and psychological stress had moderate associations (ICC 0.50-0.68), whereas child self-reported and caregiver-proxy-reported family relationships and anxiety were weakly associated (ICC 0.34-0.42). Older children had higher congruence with their caregivers on symptom domains (0.25 to 0.75 points) than younger children; female children had higher congruence with their caregivers on psychological symptoms (-2.20 to -1.98 points) than male children. CONCLUSION:Caregivers provide complementary information on the physical aspects of HRQOL, with a tendency to estimate worse symptoms and decreased functioning. Child self-report remains the gold standard for understanding HRQOL in pediatric populations with rheumatic diseases.

PURPOSE:To evaluate the association between teen substance use and neutral or conflicting messages from parents. METHODS:Secondary analysis using multivariable generalized linear mixed-effect logit models examining associations between middle and high school students self-reported past-year alcohol/cannabis use and parental attitudes. RESULTS:Of 4,802 participants (mean age 13.6 years, 48.9% female, 63.8% White, 86.9% non-Hispanic) most reported parental disapproval of teen alcohol (78.3%) and cannabis (80.5%) use. Participants who reported neutral or conflicting parental attitudes were more likely to report past-year alcohol (adjusted odds ratio: 3.35, 95% confidence interval: 2.81-4.00, p < .0001) or cannabis (adjusted odds ratio: 4.23, 95% confidence interval: 3.37-5.31, p < .0001) use. There was no difference in the odds of past-year substance use between those who reported parental "approval" of teen alcohol/cannabis use versus "disagree/have differing perspectives" or "neutral/don't care". DISCUSSION:Neutral or conflicting parental attitudes toward teen substance use appear to have similar impact on teen behavior as frank approval.

PURPOSE:Alcohol and cannabis are psychotropic substances most used by adolescents. Psychological, behavioral, social, and cognitive factors linked to substance use in adolescents with chronic pain (ACP) are unclear. We examined these factors among four groups: those reporting Only Alcohol Use (AU), Only Cannabis Use (CU), Co-use of Alcohol and Cannabis (CAM), and No Substance Use (No-SU). METHODS:From September 2021 to May 2024, we surveyed 243 patients from a pediatric pain clinic in the Northeastern U.S. Kruskal Wallis, Mann-Whitney U, and Monte Carlo Chi-Square tests assessed group differences. RESULTS:Among 243 (Mage = 16.9, SD = 1.42 years, 68% female), 12.3% reported AU, 5.3% CU, 19.8% CAM, and 62.6% No-SU in their lifetime. Groups differed by age, functional disability, depressive symptoms, and behavior avoidance in drive and fun-seeking domains (ps < 0.05). CAM group was older (p < 0.001), more depressed (p = 0.003), stressed (p = 0.03), and had more school-related anxious anticipation (p = 0.03) than No-SU, reporting more drinking and drunkenness (ps < 0.05) than AU. CU group reported greater pain interference (p = 0.04) and functional disability (p = 0.01) than AU, with 100% using for symptom relief and 85.6% for pain. Increased drunkenness past-year was positively associated with stricter curfew times and increased parental supervision in the CAM group (p < 0.006). DISCUSSION:CAM group reported more stress, depression, and alcohol consumption, complicating pain management. CU is frequently used for pain relief and is associated with greater functional disability. Interventions targeting substance use and mental, physical, and social wellbeing in ACP are limited, underscoring the need for multidisciplinary strategies addressing pain and substance use in parallel.

OBJECTIVE:Youth with chronic medical conditions (YCMC) are at increased risk of experiencing alcohol-related health consequences compared to healthy peers. Targeting influential parent beliefs and behaviors may help address YCMC alcohol use. METHOD:This study evaluated YCMC and parent surveys (n = 251) collected during a randomized controlled trial at an urban academic pediatric hospital evaluating "Take Good Care," a psychoeducational intervention targeting YCMC alcohol use. Baseline and follow-up YCMC surveys assessed alcohol use, tolerance of alcohol-related risks, and knowledge of alcohol's health effects. Baseline parent surveys evaluated parent beliefs related to YCMC alcohol use and parenting behaviors. Linear and logistic regression models assessed relationships between parent factors and follow-up YCMC outcomes after adjustment for youth age, baseline measures, parent education, and intervention receipt. RESULTS:Among YCMC, a pattern of persistently high vs persistently low or decreasing tolerance of alcohol-related risks at follow up was associated with parent beliefs that youth use is "inevitable," "OK with supervision," or "harmless." CONCLUSIONS:Parent alcohol-related beliefs are associated with YCMC response to an intervention to address alcohol use. A parent-focused intervention alongside TGC may provide opportunities to address parent beliefs and reinforce effects on youth risk perception and alcohol use.

This cohort study explores trends in urine cotinine concentrations between 2023 and 2025 among adolescents who vaped nicotine and were receiving substance use disorder treatment.

Objective: Young adults (YA) with type 1 diabetes struggle with glycemic control and diabetes distress. As social media (SM) is highly used by YA, we explored how YA with diabetes use SM, identifying associations with demographics and diabetes measures. Research Design and Methods: We developed and emailed a survey to YA seen in clinic, aged 18–25 years with diabetes ≥1 year, querying SM, demographic, and diabetes characteristics, as well as diabetes distress (Problem Areas in Diabetes [PAID]). We divided the sample into lower (<3 h/day) and higher (3+ h/day) SM use and compared characteristics using t-tests and Chi-square. Results: Of 1176 YA approached, 385 (33%) provided evaluable responses. Mean age was 22 years; 61% were female and 86% non-Hispanic white (NHW); 83% used a pump and 96% used a continuous glucose monitor. Mean HbA1c was 7.4% ± 1.3% (56.3 ± 14.2 mmol/mol). Almost all (98%) used SM; Instagram (56%) and TikTok (24%) were most popular. The lower (65%) and higher (35%) SM use groups differed by age (23 vs. 22.3 years, P = 0.02), race/ethnicity (90 vs 78.5% NHW, P = 0.002), HbA1c (7.3% vs. 7.6% [55.2 vs. 59.6], P = 0.007), and PAID score (24.5 vs. 29.7, P = 0.02), respectively. Diabetes content represented <12% of overall SM engagement, while 27.4% of sample reported SM as their primary source of diabetes technology knowledge. Conclusions: YA with higher SM use were younger, had higher HbA1c, reported more diabetes distress, and were less likely to be NHW. Engagement with diabetes SM was relatively low, representing a potential opportunity to disseminate education and support to YA with diabetes.

Purpose: Safety flag (SF) protocols are increasingly used in adolescent substance use research to protect of minor participants. This report examines the relationship between different thresholds for reporting participant substance use and study attrition. Methods: Data were analyzed from 2 concurrent adolescent studies that used an identical SF protocol with the exception of the threshold for heavy episodic drinking (HED). The first study recruited participants from a primary care adolescent medical clinic and the threshold for clinical intervention for past 3-month heavy episodic drinking was 10+ drinks on a single occasion. The second study recruited youth with chronic medical conditions from subspecialty pediatric clinics and used a lower threshold of 3+ to 5+ drinks on a single occasion. Generalized estimating equations were used to assess associations between SF type and subsequent attrition. Results: The baseline analytic sample size was 921 (10+ threshold = 487, 3+ to 5+ threshold = 434). No significant relationship between SF type and attrition was observed in either cohort. Conclusion: Positive SFs were not associated with significant differences in participant attrition. These results suggest that researchers can use different SF thresholds to accommodate adolescent populations with varying levels of risk without compromising study goals.

A fentanyl vaccine would serve as a passive model of overdose prevention and a harm reduction strategy that could save the lives of those at risk of fentanyl overdose. Implementation of this innovation has the potential to be impeded by concerns for safety, efficacy, and risk of unintended harms, as well as resistance to change from clinical, programmatic, and public sectors. The Human Papillomavirus (HPV) vaccine also faced barriers to its implementation, with a lower acceptance rate than other standard vaccines. Concerted efforts to increase uptake of the HPV vaccine have been successful and contributed to the significant declines in HPV infections and associated precancers documented since its introduction. This report summarizes parallels between factors that negatively affected the acceptability of the HPV vaccine which may similarly impact acceptability of a fentanyl vaccine and summarizes potential strategies to mitigate barriers in the potential future implementation of a fentanyl vaccine.

OBJECTIVE:Children and adolescents living with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE) frequently experience mental health comorbidities. This study evaluated sex differences in symptoms of depression, anxiety, and psychological stress in JIA and cSLE. METHODS:This multicenter, prospective cohort study recruited children and adolescents from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric self-report measures of Depressive Symptoms and Anxiety were collected at 3 timepoints over 12 months, and Psychological Stress was collected at baseline. Differences by sex were tested using chi-square and Wilcoxon rank-sum tests. Linear mixed effect models (LMMs) were created for each PROMIS measure to evaluate differences by sex. The prespecified α was 0.05. RESULTS:Among 393 children/adolescents with JIA and 58 children/adolescents with cSLE, Depressive Symptoms, Anxiety, and Psychological Stress scores were higher (indicating poorer mental health symptoms) for girls than boys. At baseline, approximately 1 in 3 girls with JIA and 1 in 2 girls with cSLE had moderate-to-severe Depressive Symptoms and Psychological Stress, compared to approximately 1 in 6 boys with JIA or cSLE. LMMs showed significantly higher scores (indicating poorer symptoms) for girls than boys, generally exceeding the minimally important difference threshold. CONCLUSION:Girls self-reported worse symptoms of depression, anxiety, and psychological stress compared to boys. Significant sex differences persisted after adjusting for rheumatic disease activity, time, and other pertinent variables. Mental health screening, management, and interventions may need to be tailored by sex.

INTRODUCTION:Adolescents accounted for 5% of fatal overdoses in the United States in 2023 (Centers for Disease Control and Prevention, 2024), yet existing research on the risk factors for non-medical opioid use (not prescribed, more frequent, or in a greater quantity than intended) among adolescent patients remains limited. Surgical procedures serve as a first exposure to opioids for many adolescents and may lead to an increased likelihood of non-medical opioid use or future opioid use disorder (OUD). Although the prevalence of OUD in adolescents ages 12-17 is low-1.2% (Center for Behavioral Health Statistics S, 2024)-- identifying risk of opioid use disorder (ROUD) in adolescence could present an opportunity to intervene and support vulnerable individuals. Preventive interventions for adolescents undergoing surgical procedures could interrupt the trajectory from non-medical use to OUD, minimizing negative health effects and reducing the risk for fatal overdose. METHODS:Using a biopsychosocial model of the development of OUD, the Adolescent outcomes of Post-operative opioid EXposure (APEX) study gathers medical record and survey data from adolescent-parent dyads to better understand the relationship between pain, pain management, prescription opioid use and recovery from surgical procedures. RESULTS:In this paper, we describe objectives and design of the APEX study, which aims to develop and validate systematic tools that are designed to detect ROUD in adolescent surgical patients in the 12 months following surgery. CONCLUSIONS:Results of this study could provide insight into predictors of ROUD, which may inform prescribing practices in the future, help update protocols for managing pain in young people and guide future research efforts.

OBJECTIVES:Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide. METHODS:21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets. The Core cSLE Dataset was designed to include data essential to meaningful clinical research across many settings. The Expanded cSLE Dataset was designed for centres able to consistently collect data to address broader research questions. Final data items for the Core and Expanded datasets were determined by consensus defined as >80% agreement) using an adapted nominal group technique and voting. RESULTS:The resulting Core cSLE Dataset contains 46 items, including demographics, clinical features, laboratory results, medications and significant adverse events. The Expanded cSLE Dataset adds 26 additional items and includes patient-reported outcomes. Consensus was also achieved regarding the frequency and time points for data collection: baseline, quarterly follow-up visits, annually and flare visits. CONCLUSION:Standardised Core and Expanded cSLE Datasets for registry-based international cSLE research were defined through the consensus of global experts and patient/caregiver representatives, endorsed by CARRA and PReS. These datasets incorporate disease-specific and patient-specific features, optimised for diverse settings to facilitate international collaborative research for children and adolescents with SLE worldwide.

Opioid overdose deaths are an evolving public health emergency in the United States. Recent advancements in drug conjugate vaccine design and adjuvantation technologies have re-ignited interest in the potential clinical utility of opioid vaccination. Here we present the concept of fentanyl vaccination as a complementary strategy for opioid overdose prevention with a focus on vaccine safety, efficacy, and considerations for vaccine development and testing in early phase human clinical trials.

OBJECTIVE:Adolescents and young adults with chronic diseases face unique challenges during the college years and may consume alcohol and other substances to cope with stressors. This study aimed to assess the patterns of substance use and to determine psychosocial correlates of these behaviors among college youth with type 1 diabetes (T1D). METHODS:College youth with T1D were recruited via social media and direct outreach into a web-based study. Participants answered validated questions about substance use, and they completed validated screeners of depressive and anxiety symptoms (PHQ-2 and GAD-2), illness acceptance (ICQ), interpersonal support (ISEL), and grit (Grit scale). Descriptive statistics, bivariate analyses, and multivariable regression evaluated substance use behaviors as a function of psychosocial factors while adjusting for age and sex. RESULTS:Alcohol (84.06%) and marijuana (41.30%) were the most common substances reported. In bivariate analyses, depressive symptoms were positively associated (p = .01) and illness acceptance was inversely associated (p = .02) with marijuana use. Higher grit scores were inversely associated with marijuana use (p < .001) and prescription drug misuse (p = .04). The significant associations between marijuana use and depressive symptoms (adjusted odds ratio [AOR] 1.31, 95% confidence interval [CI] 1.04-1.66), illness acceptance (AOR 0.96, 95% CI 0.91-0.99), and grit (AOR 0.32, 95% CI 0.17-0.60) persisted after adjustment for age and sex. CONCLUSIONS:Substance use is prevalent among college youth with T1D. While psychosocial factors such as depressive symptoms may confer an increased risk, illness acceptance and grit may be protective-especially against marijuana use. Providers should address both positive and negative psychosocial factors to mitigate substance use in this population.

ObjectiveThe current cross-sectional study retrospectively investigated associations between COVID-19-related factors and subsequent substance use in adolescents with chronic pain.MethodsA total of 243 adolescents with diagnosed pain disorders were retrospectively surveyed from September 2021 to May 2024. Descriptive statistics summarized past-month and past-year substance use; COVID-19 exposures, impact, and distress; mental health; and pain-related indicators. Logistic regressions estimated the odds of substance use based on COVID-19 exposures, impact, and distress, controlling for demographics, mental health, and pain.ResultsOf the 243 adolescents (Mage = 16.9, SD = 1.42 years; 68.44% female), 39.9% reported past-year substance use, and 28.4% reported past-month substance use. All participants reported COVID-19 exposures (M = 9.68, SD = 3.53), impact (M = 34.00, SD = 10.11), and distress (M = 5.25, SD = 2.19). No differences in Exposures or Distress emerged between youth with vs. without substance use (p’s > 0.05). Youth with past-month (U = 2,522, p < 0.001) and past-year (U = 3,998, p < 0.001) substance use reported more Impact, compared with those without use. COVID-19 social impact predicted odds of past-year (OR = 1.25, 95% CI = 1.13–1.38) and past-month (OR = 1.27, 95% CI = 1.14–1.42) substance use, controlling for gender, anxiety, depression, stress, pain intensity, pain interference, and functional disability.DiscussionThe social impact of COVID-19 uniquely predicted subsequent substance use, over and above mental and physical health symptoms in adolescents with chronic pain. Incorporating socially focused interventions into multidisciplinary pain treatment and prevention efforts may better support the health and wellness of youth with chronic pain.

Despite significant public health attention and investment, hundreds of thousands of individuals have suffered fatal opioid overdose since the onset of the opioid crisis. Risk of opioid overdose has been exacerbated by the influx of fentanyl, a powerful synthetic opioid, into the drug supply. The National Institutes of Health Helping End Addiction Long-term (HEAL) Initiative is supporting the development of vaccines targeting fentanyl to protect against overdose. If successful, a vaccine would induce anti-fentanyl antibodies to sequester fentanyl (but not other opioids) in the blood, preventing fentanyl from crossing into the brain and reaching the central nervous system where it can cause overdose. Introduction of an overdose preventing strategy that relies on a vaccine to confer passive protection may be impactful. However, vaccines are poorly understood by the public and politicized. Moreover, the overdose ecosystem is complex and extends across numerous social, economic, medical, and cultural systems. As such, optimal use of a vaccine strategy to address overdose may benefit from multidisciplinary consideration of the social, ethical, and systemic factors that influence substance use and overdose that may also impact the acceptability of a fentanyl vaccine and related implementation strategies.In March 2022, Dr. Elissa Weitzman convened a two-day conference at the Harvard Radcliffe Institute for Advanced Study on the Social Complexity of a Fentanyl Vaccine to Prevent Opioid Overdose. In all, 19 professionals from diverse disciplines (medicine, psychology, history, ethics, immunology, vaccinology, communications, policy) attended the conference and led discussions that centered on population health and epidemiology, history of medicine and frameworks for understanding substance use, ethics, decision-making and attitudes, and operational issues to the question of a novel immunotherapy targeting fentanyl overdose. Participants also debated the risks and benefits of vaccine administration in response to fictional clinical case vignettes. A summary of the conference presentations and discussions follows.

Importance:Characterizing cannabis use (CU) rates in pediatric pain is critical as adolescence is a period of increased substance use and risk for negative outcomes. Youths with chronic pain may engage in CU to cope with symptoms. Objective:To examine CU rates, risk perceptions, and motivations for use among treatment-seeking youths with diagnosed pain disorders. Design, Setting, and Participants:Cross-sectional survey study conducted from September 2021 to May 2024 at a pain treatment clinic at a pediatric hospital in the Northeast United States. Participants were 251 adolescents receiving treatment for diagnosed pain conditions. Of 312 approached, 40 did not complete the survey; 17 were excluded. Exposures:Validated self-report measures assessing demographics, pain, and substance use. Main Outcomes and Measures:CU rates, motivations for use, and perceived risks. Results:Of 245 adolescents providing complete data (mean [SD] age 16.9 [1.4] years; 168 [68.6%] female; 1 [0.4%] American Indian, 3 [1.2%] Asian, 3 [1.2%] Black, 19 [7.8%] Hispanic or Latino, and 201 [82.1%] White), 62 (25.3%) endorsed lifetime CU, with a mean (SD) age at first use of 15.3 (1.9) years. Among those endorsing CU, past-year prevalence was 90.2% (56 of 62 participants) and past-month prevalence was 64.5% (40 of 62 participants). The CU group was older (mean difference, 0.9 years; 95% CI, 0.5 to 1.2 years; P < .001), included fewer female participants (difference, -14.0%; 95% CI, -32.6% to -2.9%; P = .03), and reported greater pain interference scores (mean difference, 2.7; 95% CI, 0.8-4.6; P = .01) and depressive symptoms scores (mean difference, 6.2; 95% CI, 2.8-9.5; P < .001) compared with the no CU group. The no CU group perceived cannabis as riskier (odds ratio, 2.37; 95% CI, 1.28-4.39; P = .01). Among youths endorsing CU, 48 of 62 (77.4%) endorsed instrumental use (IU) to alleviate psychological or physical symptoms (primarily pain, sleep, and anxiety), representing an overall IU prevalence of 19.6% (48 of 245 participants). Youths reporting IU were younger (mean difference, -0.7 years; 95% CI, -1.3 to -0.1 years; P = .04) and reported greater functional disability scores (mean difference, -8.4; 95% CI, 2.1 to 12.6; P = .01) compared with the no IU group. Conclusions and Relevance:In this cross-sectional study, approximately 25% of treatment-seeking youths with chronic pain reported CU, with more than 75% using cannabis instrumentally to treat symptoms despite limited evidence supporting cannabis for pain, sleep, or anxiety. Given CU rates in this population, education about the risks of self-medication and the development of alternative coping strategies are needed.

Importance In the US, 25% of youths have a chronic medical condition (CMC). Alcohol use is prevalent among youths with a CMC and is associated with treatment nonadherence, simultaneous exposure to contraindicated medications, poor self-care, and elevated rates of progression to heavy and problem use by young adulthood. Preventive interventions targeting these youths are scarce and lack evidence about longer-term risk-stratified effects. Objective To evaluate the 12-month effects of a preventive intervention for alcohol use among youths with a CMC reporting baseline no or low-risk alcohol use vs high-risk alcohol use, testing the hypothesis of no difference. Design, Setting, and Participants This presepecified secondary analysis used data from a 2-group, parallel randomized clinical trial of the Take Good Care (TGC) intervention. Convenience samples of youths (aged 14-18 years) with a CMC, such as type 1 diabetes, juvenile idiopathic arthritis, or inflammatory bowel disease, were randomly assigned to the intervention or treatment as usual (TAU) between May 11, 2017, and November 20, 2018, and were followed up for up to 12 months. High-risk alcohol use was defined as heavy episodic (binge) alcohol use in the past 3 months and alcohol-related blackouts, injuries, vomiting, or emergency department visits in the past 12 months. Data were analyzed from September 21, 2023, to February 3, 2024. Interventions The self-administered, tablet computer-based TGC intervention was developed with patient and expert input, and it delivers disease-tailored psychoeducational content about the effects of alcohol use on overall health, disease processes, and treatment safety and efficacy. Main Outcomes and MeasuresThe main outcome was self-reported frequency of alcohol use (in days) over the past 3 months, measured by a single validated question. Maximum likelihood methods incorporating all available data were used assuming data missing at random. Results The trial included 451 participants (229 female youths [50.8%]), with a mean (SD) age of 16.0 (1.4) years. Of these youths, 410 (90.9%) participated in the 12-month follow-up. At baseline, 52 youths (11.5%) reported high-risk alcohol use. Among participants with high-risk alcohol use, the observed mean (SD) frequency of alcohol use from baseline to the 12-month follow-up decreased in the intervention group (from 6.3 [4.6] to 4.9 [4.3] days) and increased in the TAU group (from 5.5 [4.9] to 9.0 [5.8] days), with an adjusted relative rate ratio of 0.60 (95% CI, 0.38 to 0.94). There were no group differences among youths reporting no or low-risk alcohol use. Conclusions and Relevance In this trial of a brief chronic illness-tailored preventive intervention, medically vulnerable youths with a high risk of alcohol use and harm decreased alcohol use. These findings support the use of a personalized preventive intervention with this group.

We analyze adolescent substance use trends during and after the COVID-19 pandemic in the context of the major disruptions that it created. Adolescent substance use overall declined during the pandemic and subsequently rebounded to pre-pandemic levels. While overall rates of use decreased during periods of lockdown, rates of high intensity use increased. The pandemic created a unique landscape of risks and protective factors that impacted the prevalence of substance use in the adolescent population, and created a cohort that experienced a unique insult during a formative developmental period. Examining the impact of the COVID-19 pandemic and its resolution on this group may provide new insights into substance use risk and protective factors.