Practical guidelines for eating disorder risk mitigation in patients undergoing obesity treatment for the pediatric provider.

PURPOSE OF REVIEW: Pediatric obesity is a growing concern globally. Patients with a history of overweight/obesity often experience stigmatization, especially in the healthcare setting, and are at increased risk of developing psychological comorbidities including eating disorders. This review appraises the most recent studies evaluating eating disorder risk in youth undergoing treatment for obesity, identifies gaps in the literature, and offers practical guidelines to pediatric providers regarding the management of this population. RECENT FINDINGS: Recent studies suggest that structured weight management programs may decrease the risk of and/or improve symptoms of certain eating disorders such as binge eating disorder and bulimia nervosa. There is a paucity of research on some components of obesity management such as obesity pharmacotherapeutics and eating disorder risk. SUMMARY: Children and adolescents with obesity are a psychologically vulnerable population with increased risk for the development of eating disorders. Further study is needed to evaluate general risk in the setting of specialized and primary care obesity interventions and develop appropriate screening and mitigation tools. Some evidence-based strategies can aid pediatric providers in both weight management and eating disorder prevention and risk assessment.

Differentiating anorexia nervosa and atypical anorexia nervosa with absolute weight cut-offs results in a skewed distribution for premorbid weight among youth.

OBJECTIVE: Anorexia nervosa (AN) and atypical AN are conceptualized as distinct illnesses, despite similar characteristics and sequelae. Whereas DSM-5 differentiates youth with AN and atypical AN by the presence of clinical 'underweight' (i.e., 5th BMI percentile for age-and-sex (BMI%)), we hypothesized that using this weight cut-off to discern diagnoses creates a skewed distribution for premorbid weight. METHOD: Participants included hospitalized youth with AN (n = 165, 43.1%) and atypical AN (n = 218, 56.9%). Frequency analyses and chi-square tests assessed the distribution of premorbid BMI z-scores (BMIz) for diagnosis. Non-parametric Spearman correlations and Stepwise Linear regressions examined relationships between premorbid BMIz, admission BMIz, and weight loss in kg. RESULTS: Premorbid BMIz distributions differed significantly for diagnosis (p < .001), with an underrepresentation of 'overweight/obesity' (i.e., BMI% ≥ 85th) in AN. Despite commensurate weight loss in AN and atypical AN, patients with premorbid 'overweight/obesity' were 8.31 times more likely to have atypical AN than patients with premorbid BMI% < 85th. Premorbid BMIz explained 57% and 39% of the variance in admission BMIz and weight loss, respectively. DISCUSSION: Findings support a homogenous model of AN and atypical AN, with weight loss predicted by premorbid BMI in both illnesses. Accordingly, premorbid BMI and weight loss (versus presenting BMI) may better denote the presence of an AN-like phenotype across the weight spectrum. Findings also suggest that differentiating diagnoses with BMI% < 5th requires that youth with higher BMIs lose disproportionately more weight for an AN diagnosis. This is problematic given unique treatment barriers experienced in atypical AN. PUBLIC SIGNIFICANCE: Anorexia nervosa (AN) and atypical AN are considered distinct conditions in youth, with differential diagnosis hinging upon a presenting weight status of 'underweight' (i.e., BMI percentile for age-and-sex (BMI%) < 5th). In our study, youth with premorbid 'overweight/obesity' (BMI% ≥ 85th) disproportionately remained above this threshold, despite similar weight loss. Coupled with prior evidence for commensurate characteristics and sequelae in both diagnoses, we propose that DSM-5 differentiation of AN and atypical AN inadvertently reinforces weight stigma and may contribute to treatment disparities in atypical AN.

Emotion coaching skills as an augmentation to family-based therapy for adolescents with anorexia nervosa: A pilot effectiveness study with families with high expressed emotion.

OBJECTIVE: To examine the feasibility and acceptability of augmenting family-based treatment (FBT) for adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) with a parent emotion coaching intervention (EC) focused on reducing parent expressed emotion. METHOD: In this pilot effectiveness trial, families of adolescents with AN/AAN exhibiting high expressed emotion received standard FBT with either (1) EC group or (2) support group (an attention control condition focused on psychoeducation). RESULTS: Forty-one adolescents with AN or AAN were recruited (88% female, Mage = 14.9 ± 1.6 years, 95% White: Non-Hispanic, 1% White: Hispanic, 1% Bi-racial: Asian). Most study adolescents were diagnosed with AN (59%) while 41% were diagnosed with AAN. Participating parents were predominantly mothers (95%). Recruitment and retention rates were moderately high (76% and 71%, respectively). High acceptability and feasibility ratings were obtained from parents and interventionists with 100% reporting the EC intervention was "beneficial"-"very beneficial." The FBT + EC group demonstrated higher parental warmth scores at post-treatment compared to the control group (standardized effect size difference, d = 1.58), which was maintained at 3-month follow-up. Finally, at post-treatment, the FBT + EC group demonstrated higher rates of full remission from AN/AAN (40%) compared to FBT + support (27%), and were nine times more likely to be weight restored by 3-month follow-up. DISCUSSION: Augmenting FBT with emotion coaching for parents with high expressed emotion is acceptable, feasible, and demonstrates preliminary effectiveness. PUBLIC SIGNIFICANCE: Family based treatment for AN/AAN is the recommended treatment for youth but families with high criticism/low warmth are less likely to respond to this treatment. Adding a parent emotion coaching group (EC) where parents learn to talk to their adolescents about tough emotions is feasible and well-liked by families.

Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

Associations between presenting weight and premorbid weight and the medical sequelae in hospitalized youth with anorexia nervosa or atypical anorexia nervosa.

PURPOSE: To identify unique treatment considerations for youth with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) and premorbid overweight or obesity, we examined unique relationships between premorbid and presenting weight status and medical sequelae in youth with AN/AAN requiring medical hospitalization. DESIGN AND METHODS: We performed a retrospective study of 150 youth aged mean [SD] of 14.1[2.3] years, hospitalized for AN/AAN. Independent t-tests and Fischer's exact tests assessed differences in demographic and clinical characteristics by premorbid weight status. Logistic regressions assessed associations between premorbid and presenting weight status and vital sign or laboratory abnormalities. RESULTS: Compared to youth with premorbid 'normal' weights, youth with premorbid overweight/obesity demonstrated greater percent (p = .042) and faster rate (p < .001) of weight loss and had 10.9 times the odds of having anemia (p = .025). Youth with AN (<5th percentile for body mass index [BMI]) were more likely to experience hypoglycemia (p < .018) than youth with AAN (≥5th percentile BMI). Greater percent of weight loss significantly predicted bradycardia (p < .001) and hypoglycemia (p = .002), independent of premorbid or presenting weight status. CONCLUSION: Acute medical management of AN/AAN should be commensurate for hospitalized patients, regardless of premorbid weight status. However, those with more significant weight loss and those presenting as underweight may warrant particular monitoring for complications such as bradycardia and hypoglycemia. PRACTICE IMPLICATIONS: In youth with AN/AAN, high percent of weight loss warrants closer monitoring for medical complications during hospitalization. Those with premorbid overweight/obesity may need additional monitoring for anemia, as there may be additional contributors to anemia aside from malnutrition.

Implementing Programs to Initiate Buprenorphine for Opioid Use Disorder Treatment in High-Need, Low-Resource Emergency Departments: A Nonrandomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that implementation facilitation would enable us to rapidly and effectively implement emergency department (ED)-initiated buprenorphine programs in rural and urban settings with high-need, limited resources and dissimilar staffing structures. METHODS: This multicenter implementation study employed implementation facilitation using a participatory action research approach to develop, introduce, and refine site-specific clinical protocols for ED-initiated buprenorphine and referral in 3 EDs not previously initiating buprenorphine. We assessed feasibility, acceptability, and effectiveness by triangulating mixed-methods formative evaluation data (focus groups/interviews and pre/post surveys involving staff, patients, and stakeholders), patients' medical records, and 30-day outcomes from a purposive sample of 40 buprenorphine-receiving patient-participants who met research eligibility criteria (English-speaking, medically stable, locator information, nonprisoners). We estimated the primary implementation outcome (proportion receiving ED-initiated buprenorphine among candidates) and the main secondary outcome (30-day treatment engagement) using Bayesian methods. RESULTS: Within 3 months of initiating the implementation facilitation activities, each site implemented buprenorphine programs. During the 6-month programmatic evaluation, there were 134 ED-buprenorphine candidates among 2,522 encounters involving opioid use. A total of 52 (41.6%) practitioners initiated buprenorphine administration to 112 (85.1%; 95% confidence interval [CI] 79.7% to 90.4%) unique patients. Among 40 enrolled patient-participants, 49.0% (35.6% to 62.5%) were engaged in addiction treatment 30 days later (confirmed); 26 (68.4%) reported attending one or more treatment visits; there was a 4-fold decrease in self-reported overdose events (odds ratio [OR] 4.03; 95% CI 1.27 to 12.75). The ED clinician readiness increased by a median of 5.02 (95% CI: 3.56 to 6.47) from 1.92/10 to 6.95/10 (n(pre)=80, n(post)=83). CONCLUSIONS: The implementation facilitation enabled us to effectively implement ED-based buprenorphine programs across heterogeneous ED settings rapidly, which was associated with promising implementation and exploratory patient-level outcomes.

Clinical characteristics of medically hospitalized youth with anorexia nervosa/atypical anorexia nervosa and premorbid overweight/obesity.

Youth with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) and premorbid overweight/obesity are particularly vulnerable to diagnostic delays, yet research about this patient subset is lacking. This study aimed to compare mental health and demographic characteristics of patients with AN/AAN and premorbid overweight/obesity to patients with premorbid normal weight. Retrospective chart review identified 253 patients (aged 10-22) hospitalized for medical complications of AN/AAN between 2013 and 2020, including 29.6% (n = 75) with and 70.4% (n = 178) without premorbid overweight/obesity. Analyses revealed that patients with AN/AAN and premorbid overweight/obesity were more often cisgender male (24% vs. 8.4%), diagnosed with AAN (62.7% vs. 32%), and had lost a greater percent of body weight (29% vs. 16.4%) than premorbid normal weight counterparts. No significant differences were found for illness duration (10.1 months vs 9.3 months), psychiatric comorbidities (42.7% vs. 32.2%) or psychotropic medication use (25.3% vs. 19.2%), past mental health treatment (44.6% vs. 37.5%), or family history of eating disorders (22.7% vs. 20.8%). Our findings suggest that when relying on historical records, patients hospitalized for medical complications of AN/AAN have similar characteristics across the weight spectrum.

Predictors of caregiver burden before starting family-based treatment for adolescent anorexia nervosa and associations with weight gain during treatment.

PURPOSE: Caregivers play a pivotal role in the success of family-based treatment (FBT) for anorexia nervosa (AN). Caregiver burden is frequently demonstrated in eating disorders (EDs) and may impact FBT outcomes. This study examined factors associated with caregiver burden before starting FBT and whether pre-treatment caregiver burden was associated with weight gain during FBT. METHODS: Participants included 114 adolescents with AN or atypical AN (mean age = 15.6 years, SD = 1.4) and a primary caregiver (87.6% mothers) who received FBT in the United States. Before starting treatment, participants completed self-report measures of caregiver burden (via the Eating Disorder Symptom Impact Scale), caregiver anxiety, caregiver depression, and ED symptoms. Clinical characteristics and percentage of target goal weight (%TGW) at FBT session 1 and 3 and 6 months after starting treatment were obtained via retrospective chart review. Hierarchical regressions examined predictors of caregiver burden before FBT initiation. Associations between pre-treatment caregiver burden and %TGW gain at 3 and 6 months after starting FBT were assessed with hierarchical regressions. RESULTS: Caregiver anxiety (p < 0.001), family history of EDs (p = 0.028), adolescent mental health treatment history (p = 0.024), and ED symptoms (p = 0.042) predicted caregiver burden before starting FBT. Pre-treatment caregiver burden was not associated with %TGW gain at 3 or 6 months. Males demonstrated less %TGW gain than females at 3 months (p = 0.010) and 6 months (p = 0.012). CONCLUSION: Proactively evaluating caregiver burden before starting FBT is suggested. Providing recommendations and/or referrals for identified caregiver vulnerabilities could indirectly impact FBT progress. Males in FBT could require longer courses of treatment and extra vigilance to this demographic is suggested. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Caregiver and adolescent intuitive eating behavior: associations with weight change during family-based treatment for anorexia nervosa.

PURPOSE: Intuitive eating (IE) is an adaptive eating construct for which little research exists in eating disorder (ED) samples. IE is negatively correlated with disordered eating behaviors in healthy adolescents and adults, and similar associations have been found in adults with EDs. This study aims to examine IE in a treatment seeking sample of adolescents and their caregivers to understand the role of IE in weight gain during FBT. METHODS: Descriptive statistics and bivariate correlations were calculated in a sample of 47 pairs of adolescent patients and their caregivers who initiated outpatient FBT at a large academic medical center. Analyses examined associations between caregiver and adolescent IE on the Intuitive Eating Scale (IES), change in percent expected body weight (%EBW) by session 4 and end of treatment (EOT), clinical impairment, and ED pathology. RESULTS: Significant correlations were found between aspects of adolescent IE, ED symptoms, and clinical impairment. Caregiver IES scores (Reliance on Hunger and Satiety Cues, Body-Food Choice Congruence, IES Total) were negatively related to adolescent ED symptoms (EDE-Q Weight Concerns, EDE-Q Shape Concerns, EDE-Q Global) at baseline. Caregiver IE (Eating for Physical Rather than Emotional Reasons) was positively associated with adolescent weight gain at FBT session 4 and EOT, even when statistically adjusting for gender and initial level of care. CONCLUSION: Study results were consistent with past research indicating adolescent IE is negatively associated with ED behaviors, cognitions, and impairment. This study is the first to provide evidence that caregiver IE is positively associated with adolescent weight gain in FBT and is the first to provide evidence that caregiver IE is negatively related to adolescent ED symptoms. Future research should examine adolescent and caregiver IE throughout FBT to understand the role of IE in treatment response. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

Early Life Trauma and Social Processing in HIV: The Role of Neuroendocrine Factors and Inflammation.

OBJECTIVE: Early life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association. METHODS: We used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations. RESULTS: Of 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized ß [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05). CONCLUSIONS: Our pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally.

Global sensitivity analysis of randomized trials with nonmonotone missing binary outcomes: Application to studies of substance use disorders.

In this paper, we present a method for conducting global sensitivity analysis of randomized trials in which binary outcomes are scheduled to be collected on participants at prespecified points in time after randomization and these outcomes may be missing in a nonmonotone fashion. We introduce a class of missing data assumptions, indexed by sensitivity parameters, which are anchored around the missing not at random assumption introduced by Robins (Statistics in Medicine, 1997). For each assumption in the class, we establish that the joint distribution of the outcomes is identifiable from the distribution of the observed data. Our estimation procedure uses the plug-in principle, where the distribution of the observed data is estimated using random forests. We establish n$\sqrt {n}$ asymptotic properties for our estimation procedure. We illustrate our methodology in the context of a randomized trial designed to evaluate a new approach to reducing substance use, assessed by testing urine samples twice weekly, among patients entering outpatient addiction treatment. We evaluate the finite sample properties of our method in a realistic simulation study. Our methods have been implemented in an R package entitled slabm.

Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems.

BACKGROUND: Pragmatic primary care trials aim to test interventions in "real world" health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial. METHODS: This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16-90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization ("baseline"). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD). RESULTS: Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics' patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: - 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42). CONCLUSIONS: trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.

Eating disorder severity and psychological morbidity in adolescents with anorexia nervosa or atypical anorexia nervosa and premorbid overweight/obesity.

PURPOSE: A significant proportion of adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) experience premorbid overweight/obesity, yet distinct characteristics among this subset of patients remain unclear. This study examined eating disorder (ED) symptom severity, psychological morbidity, and weight stigma in patients with premorbid overweight/obesity as compared to patients with premorbid normal weights. METHODS: Participants included adolescents with AN or AAN (aged 12-18) who received multidisciplinary treatment at a pediatric medical center in the United States. ED symptoms, anxiety, and depression were compared among patients with premorbid overweight/obesity (n = 43) and premorbid normal weights (n = 63). Associations between weight stigma, ED severity, and psychological morbidity were also examined. RESULTS: Patients with premorbid overweight/obesity reported greater ED severity (p = 0.04), anxiety (p < 0.003), depression (p = 0.02), and a higher frequency of weight-based teasing by peers (p = 0.003) and parent weight talk about their own weights (p < 0.001). Weight-based teasing was positively associated with ED symptoms, anxiety, and depression for all patients, regardless of premorbid weight status. CONCLUSIONS: Adolescents with AN or AAN and a history of overweight/obesity may present with greater ED symptom severity and psychological morbidity than patients with normal weight histories. Distinct prevention and treatment interventions for adolescents with AN or AAN and premorbid overweight/obesity may be warranted. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Insufficient Assessment and Treatment of Vitamin D in the Medical Management of Adolescents with Anorexia Nervosa.

PURPOSE: Suboptimal vitamin D levels are implicated in low bone mineral density, a common medical complication of anorexia nervosa. This study aimed to examine the frequency of vitamin D assessment and treatment for adolescents with anorexia nervosa in outpatient medical management. DESIGN AND METHODS: Retrospective chart review was used to examine 179 adolescents (M age = 15.5 years, SD = 2.2), newly diagnosed with anorexia nervosa at a tertiary care medical center in the United States between January 2000 and July 2016. RESULTS: Only 16% of patients (n = 29) received serum vitamin D assessments following diagnosis, of whom 52% had suboptimal vitamin D levels (n = 15). Only three patients with suboptimal vitamin D were advised to begin supplementation. No patients in our sample were encouraged to begin prophylactic vitamin D supplementation. CONCLUSIONS/PRACTICE IMPLICATIONS: Findings from this study highlight the critical need for widespread care team education about vitamin D assessment and treatment in the medical management of adolescents with anorexia nervosa, particularly in light of the potentially serious consequences of bone mineral density.

Modifiable factors associated with mental health symptoms in siblings of adolescents with anorexia nervosa.

PURPOSE: Research demonstrates that anorexia nervosa (AN) takes a significant toll on affected families, yet the well-being of siblings has been largely overlooked. This study examines mental health symptoms in siblings of adolescents with AN and seeks to identify modifiable factors associated with well-being. METHOD: Participants included 34 siblings (aged 11-19) of adolescents with AN and 47 age and sex matched controls. Participants and their caregivers completed assessments of anxiety, depression, internalizing and externalizing problems, and parentification. Siblings of adolescents with AN also completed the Sibling Perception Questionnaire, an assessment of perceptions and attitudes about AN. RESULTS: Analyses indicated that siblings of adolescents with AN reported greater anxiety and parentification than controls. On caregiver reports of participants' internalizing and externalizing symptoms, no significant differences were found across groups. In siblings of adolescents with AN, females were more vulnerable to anxiety, depression, and negative attitudes and perceptions about AN than males. Perceived negative interpersonal interactions, specific to having a brother or sister with AN, were associated with greater anxiety and depression among AN siblings. CONCLUSION: Findings from this pilot study suggest that siblings of adolescents with AN are vulnerable to anxiety and parentification behaviors. Negative interpersonal interactions specific to having a brother or sister with AN may perpetuate risk for poorer well-being. Caregivers may not be attuned to these struggles, highlighting the importance of provider and family education about sibling vulnerabilities. Therapeutic interventions that target siblings of adolescents with AN are also indicated. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Dialectical behavioral therapy skills group as an adjunct to family-based therapy in adolescents with restrictive eating disorders.

Dialectical behavior therapy (DBT) is commonly used in the treatment of eating disorders (ED), yet few studies have examined the utility of DBT skills groups as an adjunct to evidence-based therapy for ED. Thus, we sought to examine the preliminary efficacy of a DBT skills group as an adjunct to Family-Based Treatment (FBT) for adolescent restrictive ED. Our preliminary pilot study included 18 adolescent girls ages 13-18 (M= 15.3, SD = 1.64) with restrictive ED, including Anorexia Nervosa (AN; N = 10), Atypical Anorexia Nervosa (AAN, N = 5), and Other Specific Feeding or Eating Disorder (OSFED; N = 3). All participants were enrolled in a 6-month, weekly DBT skills group and were concurrently receiving family-based treatment (FBT). Participants who completed the intervention experienced large effect sizes for increases in adaptive skills (Cohen's d = .71) and decreases in general dysfunctional coping strategies (Cohen's d = .85); and small to medium effect sizes for decreases in binge eating (Cohen's d = .40) and increases in percent expected body weight (% EBW; Cohen's d = .32). Finally, small effect sizes were evidenced in decreases in Global EDE-Q scores (Cohen's d = .26), EDE-Q restraint (Cohen's d = .29) and CDI scores (Cohen's d = .28). Our study presents promising preliminary data suggesting that adolescents with restrictive EDs receiving FBT could benefit from an adjunctive DBT skills group. Feasibility of and considerations for tailoring a DBT skills group to an outpatient ED treatment program are discussed.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

An intensive family-based treatment guided intervention for medically hospitalized youth with anorexia nervosa: Parental self-efficacy and weight-related outcomes.

Recent studies suggest the efficacy of family-based treatment (FBT) among youth with anorexia nervosa (AN) in intensive treatment settings. This study aimed to assess weight outcomes in youth who received an FBT intervention while hospitalized for medical complications of AN. Parental self-efficacy among participating caregivers was also measured. Post-discharge weights of 49 participants were compared with weights of 44 youth who were hospitalized prior to the provision of the FBT intervention. Youth who received the FBT intervention gained significantly more weight than youth in the retrospective treatment as usual group at 3 and 6 months following discharge. FBT youth were 2.84 times more likely than retrospective treatment as usual youth to achieve at least 95% of treatment goal weight at 6 months post-discharge. Finally, parental self-efficacy significantly increased in caregivers who participated in the FBT intervention. Findings provided preliminary support for the provision of FBT to medically hospitalized youth with AN.

Adolescent males with atypical anorexia nervosa and premorbid obesity: three case reports.

PURPOSE: Premorbid obesity is an identified risk factor for eating disorder (ED) development among adolescent males. However, pervasive gender- and weight-related biases about ED inhibit timely diagnosis and treatment among this demographic. This study examined the psychological and medical characteristics of three adolescent males with premorbid obesity who were not diagnosed with atypical anorexia nervosa (AAN) until medical sequelae of malnutrition warranted emergent hospitalization. Factors associated with diagnostic delays among these cases were identified to facilitate increased awareness of this at-risk demographic. METHODS: Retrospective chart review was conducted on three adolescent males (aged 12-17) with AAN and premorbid obesity who were medically hospitalized for 13-24 days (M = 20.3, SD = 9.7). Demographic variables, psychological characteristics, and physical data were extracted. RESULTS: Each case presented at normal or overweight BMI status (M = 22.7 kg/m2, SD = 3.2) following a significant loss of weight ranging from 19 to 42% of total body mass (M = 31.7%, SD = 9.5) over 5-12 months (M = 8.3, SD = 2.9). Plausible factors associated with diagnostic delays included initial weight loss recommendations by a medical provider, with little support or oversight; limited insight that symptoms were problematic; social reinforcement of dieting behaviors; low prevalence of psychiatric comorbidity; parental obesity; and parental history of bariatric surgery. CONCLUSIONS: These cases elucidate the importance of close follow-up of youth with obesity who are encouraged to lose weight. Further education about AAN among males with premorbid obesity is crucial for timely diagnosis and intervention.

Impact of short-term refeeding on appetite and meal experiences in new onset adolescent eating disorders.

Restrictive eating disorders (ED) are increasing and represent a serious risk to the health of adolescent females. Restrictive ED in youth are often treated through aggressive short-term refeeding. Although evidence supports that this intervention is the "gold standard" for improving ED outcomes in youth, little research has specifically probed appetite and meal-related responses to this type of intensive, short-term refeeding in newly diagnosed individuals. Information about appetite and meal-related dysfunction could provide valuable insights regarding treatment-interfering features of ED in both acute inpatient and longer-term outpatient treatment. The purpose of this study was to evaluate the hunger, fullness, olfactory, and gustatory responses of adolescents with newly-diagnosed restrictive ED and to probe how and when these responses are altered by refeeding. Using a quasi-experimental ecologically valid methodology, this study described and compared profiles of hunger, fullness, olfactory, and gustatory responses in adolescent females (n = 15) with newly diagnosed restrictive ED at hospital admission (i.e., severe malnutrition) and after medical refeeding, in comparison to healthy controls (n = 15). Results showed that newly diagnosed (i.e., malnourished) adolescents with ED showed significantly different meal-related experiences than controls. Refeeding improved some of these differences, but not all. Following refeeding, females with ED continued to show lower hunger, greater fullness, and lower pleasantness of smell ratings compared to controls. Unpleasantness of taste ratings maladaptively increased, such that females who were re-fed reported more aversive scents than pre-treatment. Profiles of meal-related responses were also identified and compared between groups. The applicability of these findings are discussed within the context of critical periods of change during refeeding treatment and potentially promising intervention targets that might enhance treatment outcomes for adolescents with newly onset, restrictive ED.