Course and outcome in individuals with atypical anorexia nervosa: Findings from the Study of Refeeding to Optimize iNpatient Gains (StRONG).

OBJECTIVE: We previously reported that participants with atypical anorexia nervosa (atypical AN) had higher historical and admission weights, greater eating disorder psychopathology, but similar rates of amenorrhea and weight suppression at baseline as compared to anorexia nervosa (AN); here, we compare 1-year outcomes. METHOD: Weight, % median body mass index (%mBMI), Eating Disorder Examination Questionnaire (EDE-Q) scores, resumption of menses, and rehospitalizations were examined at 3, 6, and 12 months post-discharge. Analyses (N = 111) compared changes in %mBMI, weight suppression, and EDE-Q scores over time between atypical AN and AN. RESULTS: Among the participants (48 atypical AN, 63 AN), both groups gained weight but those with atypical AN had lower gains than those with AN in %mBMI (p = .02) and greater weight suppression (p = .002) over time. EDE-Q scores improved over time, independent of weight suppression, with no significant difference between atypical AN and AN. Groups did not differ by rates of resumption of menses (80% atypical AN, 76.9% AN) or rehospitalization (29.2% atypical AN, 37.9% AN). Greater weight suppression predicted longer time to restore menses and more days of rehospitalization. DISCUSSION: Individuals with atypical AN regained a smaller proportion of body mass and were more weight suppressed over time. Change in eating disorder cognitions, resumption of menses, and rehospitalization rates at 1-year follow-up did not differ between groups. There was no significant difference in weight suppression between groups for those who were psychologically improved at 12 months. Findings highlight limitations in our understanding of weight recovery in atypical AN. New metrics for recovery are urgently needed. PUBLIC SIGNIFICANCE: Little is known about outcome in atypical anorexia nervosa (atypical AN). We examined recovery metrics in young people with atypical AN and anorexia nervosa (AN) 1 year after medical hospitalization. Individuals with atypical AN showed slower weight gain and remained further from their pre-illness weight. There were no differences in the rates of psychological recovery, resumption of menses, or rehospitalization. New metrics are needed to assess recovery in atypical AN.

Cross-sectional assessment of body composition and detection of malnutrition risk in participants with low body mass index and eating disorders using 3D optical surface scans.

BACKGROUND: New recommendations for the assessment of malnutrition and sarcopenia include body composition, specifically reduced muscle mass. Three-dimensional optical imaging (3DO) is a validated, accessible, and affordable alternative to dual X-ray absorptiometry (DXA). OBJECTIVE: Identify strengths and weaknesses of 3DO for identification of malnutrition in participants with low body mass index (BMI) and eating disorders. DESIGN: Participants were enrolled in the cross-sectional Shape Up! Adults and Kids studies of body shape, metabolic risk, and functional assessment and had BMI of <20 kg/m2 in adults or <85% of median BMI (mBMI) in children and adolescents. A subset was referred for eating disorders evaluation. Anthropometrics, scans, strength testing, and questionnaires were completed in clinical research centers. Lin's Concordance Correlation Coefficient (CCC) assessed agreement between 3DO and DXA; multivariate linear regression analysis examined associations between weight history and body composition. RESULTS: Among 95 participants, mean ± SD BMI was 18.3 ± 1.4 kg/m2 in adult women (N = 56), 19.0 ± 0.6 in men (N = 14), and 84.2% ± 4.1% mBMI in children (N = 25). Concordance was excellent for fat-free mass (FFM, CCC = 0.97) and strong for appendicular lean mass (ALM, CCC = 0.86) and fat mass (FM, CCC = 0.87). By DXA, 80% of adults met the low FFM index criterion for malnutrition, and 44% met low ALM for sarcopenia; 52% of children and adolescents were <-2 z-score for FM. 3DO identified 95% of these cases. In the subset, greater weight loss predicted lower FFM, FM, and ALM by both methods; a greater percentage of weight regained predicted a higher percentage of body fat. CONCLUSIONS: 3DO can accurately estimate body composition in participants with low BMI and identify criteria for malnutrition and sarcopenia. In a subset, 3DO detected changes in body composition expected with weight loss and regain secondary to eating disorders. These findings support the utility of 3DO for body composition assessment in patients with low BMI, including those with eating disorders. This trial was registered at clinicaltrials.gov as NCT03637855.

Hospital-based higher calorie refeeding and mealtime distress in adolescents and young adults with anorexia nervosa or atypical anorexia nervosa.

OBJECTIVE: The StRONG study demonstrated that higher calorie refeeding (HCR) restored medical stability faster in patients hospitalized with anorexia nervosa (AN) and atypical AN (AAN), with no increased safety events compared with standard-of-care lower calorie refeeding (LCR). However, some clinicians have expressed concern about potential unintended consequences of HCR (e.g., greater mealtime distress). The purpose of this study was to examine patient treatment preference and compare mealtime distress, food refusal, and affective states between treatments. METHOD: Participants (N = 111) in this multisite randomized clinical trial were ages 12-24 years, with AN or AAN, admitted to hospital with medical instability who received assigned study treatment (HCR or LCR). Treatment preference was assessed prior to randomization in the full sample. In a subset of participants (n = 45), linear mixed effect models were used to analyze momentary ratings of mealtime distress (pre, during, and post-meals) and daily affective state during the hospitalization. RESULTS: About half (55%) of participants reported a preference for LCR. Treatment assignment was not associated with food refusal, mealtime distress, or affective states in the subsample. Food refusal increased significantly over the course of refeeding (p = .018). Individuals with greater depression experienced more negative affect (p = .033), with worsening negative affect over time for individuals with higher eating disorder psychopathology (p = .023). DISCUSSION: Despite understandable concerns about potential unintended consequences of HCR, we found no evidence that treatment acceptability for HCR differed from LCR for adolescents and young adults with AN and AAN. PUBLIC SIGNIFICANCE: The efficacy and safety of higher calorie refeeding in hospitalized patients with anorexia nervosa has been demonstrated. However, it is not known whether higher calorie refeeding (HCR) increases meal-time distress. This study demonstrated that HCR was not associated with increased mealtime distress, food refusal, or affective states, as compared with lower calorie refeeding. These data support HCR treatment acceptability for adolescents/young adults with anorexia nervosa and atypical anorexia nervosa.

Assessment of vitamin D among male adolescents and young adults hospitalized with eating disorders.

PURPOSE: Medical complications of eating disorders in males are understudied compared to females, as is the case of vitamin D deficiency. The aim of this study was to assess vitamin D levels among male and female adolescents and young adults hospitalized for medical complications of eating disorders. METHODS: We retrospectively reviewed electronic medical records of patients aged 9-25 years (N = 565) admitted to the University of California, San Francisco Eating Disorders Program for medical instability, between May 2012 and August 2020. Serum vitamin D (25-hydroxy) level was assessed at admission as was history of prior calcium, vitamin D, or multivitamin supplementation. Linear regression was used to assess factors associated with vitamin D levels. RESULTS: A total of 93 males and 472 females met eligibility criteria (age 15.5 ± 2.8, 58.8% anorexia nervosa; admission body mass index 17.6 ± 2.91). Among male participants, 44.1% had 25-hydroxyvitamin D levels < 30 ng/mL, 18.3% had 25-hydroxyvitamin D levels < 20 ng/mL, and 8.6% had 25-hydroxyvitamin D levels < 12 ng/mL. There were no significant differences in 25-hydroxyvitamin D levels in males compared to females, except that a lower proportion (1.9%) of female participants had 25-hydroxyvitamin D levels < 12 ng/mL (p = 0.001). Only 3.2% of males reported calcium or vitamin D-specific supplementation prior to hospital admission, while 8.6% reported taking multivitamins. White race, prior calcium/vitamin D supplementation, and higher calcium levels were associated with higher vitamin D levels on admission. CONCLUSIONS: Nearly half of patients admitted to the hospital for malnutrition secondary to eating disorders presented with low 25-hydroxyvitamin D levels; males were more likely than females to have severe vitamin D deficiency. These findings support vitamin D assessment as part of the routine medical/nutritional evaluation for hospitalized eating disorder patients, with particular attention on male populations.

Medical complications of eating disorders in males are understudied compared to females. Little is known about vitamin D levels in male adolescents and young adults with eating disorders. We studied vitamin D levels in male and female adolescents and young adults hospitalized at the University of California, San Francisco between 2012 and 2020. We found that 44% of males had low vitamin D levels. Despite nearly half of males having low vitamin D, few were receiving calcium, vitamin D, or multivitamin supplementation prior to the hospitalization. White race, prior calcium or vitamin D supplementation, and higher calcium levels were associated with higher vitamin D levels. Medical providers should consider assessing for low vitamin D levels among males and females with eating disorders.

Renal Function in Patients Hospitalized With Anorexia Nervosa Undergoing Refeeding: Findings From the Study of Refeeding to Optimize Inpatient Gains.

PURPOSE: Among complications of malnutrition secondary to anorexia nervosa (AN) or atypical anorexia nervosa (AAN), renal impairment remains poorly elucidated. Evaluating renal function in hospitalized pediatric patients with AN and AAN undergoing refeeding will yield important information to guide clinicians in screening and managing renal dysfunction in this population. METHODS: This is a secondary analysis of data from the Study of Refeeding to Optimize Inpatient Gains trial, a multicenter randomized clinical trial comparing higher calorie refeeding versus lower calorie refeeding in 120 adolescents and young adults hospitalized with medical instability secondary to AN or AAN. Baseline disease characteristics were obtained. Vital sign measurements, weight, electrolytes, and fluid status were evaluated daily to ascertain medical stability. Renal function on admission and throughout hospitalization was quantified using daily creatinine measurement and calculation of the estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. Regression analysis and mixed linear models were utilized to evaluate factors associated with eGFR. RESULTS: Of the 111 participants who completed treatment protocol, 33% had a baseline eGFR less than 90, suggesting renal impairment. Patients who experienced more rapid weight loss and more severe bradycardia were more likely to have low admission eGFR. While eGFR improved during refeeding, eGFR change by day based on refeeding treatment assignment did not reach statistical significance (95% confidence interval, -1.61, 0.15]; p = .095). DISCUSSION: Renal impairment is evident on admission in a significant number of adolescents and young adults hospitalized with AN and AAN. We demonstrate that short-term medical refeeding yields improvement in renal function.

Sex differences and associations between zinc deficiency and anemia among hospitalized adolescents and young adults with eating disorders.

PURPOSE: To determine sex differences in and associations between zinc deficiency and anemia among adolescents and young adults hospitalized for medical complications of eating disorders. METHODS: We retrospectively reviewed electronic medical records of 601 patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability, between May 2012 and August 2020. Descriptive statistics, crude, and adjusted logistic regression models were used to assess the association between zinc deficiency (< 55 mcg/dL) and anemia (< 13.6 g/dL in males [M] and < 11.8 g/dL in females [F]). RESULTS: A total of 87 males and 450 females met eligibility criteria (age 15.98 ± 2.81, 59.4% anorexia nervosa; admission body mass index 17.49 ± 2.82). In unadjusted comparisons, plasma zinc in males and females were not statistically different (M 64.88 ± 14.89 mcg/dL vs F 63.81 ± 13.96 mcg/dL, p = 0.517); moreover, there were no differences in the percentage of males and females with zinc deficiency (M 24.14% vs F 24.89%). However, a greater percentage of males than females were anemic (M 50.00% vs F 17.61%, p < 0.001), with similar findings in the subgroup with anorexia nervosa. In logistic regression models stratified by sex and eating disorder diagnosis, zinc deficiency was significantly associated with anemia in males (AOR 3.43, 95% CI 1.16, 10.13), but not females (AOR 1.47, 95% CI 0.86, 2.54). CONCLUSIONS: For the first time, we demonstrate that zinc deficiency is equally severe in males compared to females hospitalized with medical complications from eating disorders, with nearly a quarter of inpatients experiencing zinc deficiency. Anemia is more common in males than females hospitalized with eating disorders. LEVEL OF EVIDENCE: Level V: descriptive cross-sectional study.

Sex differences in refeeding among hospitalized adolescents and young adults with eating disorders.

OBJECTIVE: To determine sex differences in refeeding (i.e., short-term nutritional rehabilitation) outcomes among hospitalized adolescents and young adults with eating disorders. METHODS: We retrospectively reviewed electronic medical records of 601 patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical and nutritional management between May 2012 and August 2020. Descriptive statistics, crude, and adjusted linear regression models were used to assess the association between sex and nutritional outcomes and predictors of length of stay. RESULTS: A total of 588 adolescents and young adults met eligibility criteria (16% male, mean [SD] age 15.96 [2.75], 71.6% anorexia nervosa, admission percent median body mass index [%mBMI] 87.1 ± 14.1). In unadjusted comparisons, there were no significant sex differences in prescribed kilocalories (kcal) per day at admission (2013 vs. 1980, p = .188); however, males had higher estimated energy requirements (EER, kcal) (3,694 vs. 2,925, p < .001). In linear regression models adjusting for potential confounders, male sex was associated with higher prescribed kcals at discharge (B = 835 kcal, p < .001), greater weight change (B = 0.47 kg, p = .021), and longer length of stay (B = 1.94 days, p = .001) than females. Older age, lower admission weight, lower prescribed kcal at admission, higher EER, and lower heart rate at admission were factors associated with longer length of stay in a linear regression model. DISCUSSION: These findings support the development of individualized approaches for males with eating disorders to improve quality of care and health care efficiency among an underserved population.

Higher-Calorie Refeeding in Anorexia Nervosa: 1-Year Outcomes From a Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: We recently reported the short-term results of this trial revealing that higher-calorie refeeding (HCR) restored medical stability earlier, with no increase in safety events and significant savings associated with shorter length of stay, in comparison with lower-calorie refeeding (LCR) in hospitalized adolescents with anorexia nervosa. Here, we report the 1-year outcomes, including rates of clinical remission and rehospitalizations. METHODS: In this multicenter, randomized controlled trial, eligible patients admitted for medical instability to 2 tertiary care eating disorder programs were randomly assigned to HCR (2000 kcals per day, increasing by 200 kcals per day) or LCR (1400 kcals per day, increasing by 200 kcals every other day) within 24 hours of admission and followed-up at 10 days and 1, 3, 6, and 12 months post discharge. Clinical remission at 12 months post discharge was defined as weight restoration (≥95% median BMI) plus psychological recovery. With generalized linear mixed effect models, we examined differences in clinical remission over time. RESULTS: Of 120 enrollees, 111 were included in modified intent-to-treat analyses, 60 received HCR, and 51 received LCR. Clinical remission rates changed over time in both groups, with no evidence of significant group differences (P = .42). Medical rehospitalization rates within 1-year post discharge (32.8% [19 of 58] vs 35.4% [17 of 48], P = .84), number of rehospitalizations (2.4 [SD: 2.2] vs 2.0 [SD: 1.6]; P = .52), and total number of days rehospitalized (6.0 [SD: 14.8] vs 5.1 [SD: 10.3] days; P = .81) did not differ by HCR versus LCR. CONCLUSIONS: The finding that clinical remission and medical rehospitalization did not differ over 1-year, in conjunction with the end-of-treatment outcomes, support the superior efficacy of HCR as compared with LCR.

Short-term Outcomes of the Study of Refeeding to Optimize Inpatient Gains for Patients With Anorexia Nervosa: A Multicenter Randomized Clinical Trial.

Importance: The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome. Objective: To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa. Design, Setting, and Participants: In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach. Interventions: Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day. Main Outcomes and Measures: Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay. Results: Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, -6.1 to -1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, -$28 819 to -$9293) in hospital charges per participant. Conclusions and Relevance: In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT02488109.

Weight Loss and Illness Severity in Adolescents With Atypical Anorexia Nervosa.

BACKGROUND: Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight. METHODS: We examined weight history and illness severity in 12- to 24-year-olds with AN (n = 66) and AAN (n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers. RESULTS: Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (ß = -0.492 [confidence interval (CI) -0.883 to -0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (ß = -0.005 [CI -0.010 to 0.000]; P = .04) and longer duration (ß = -0.011 [CI -0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus. CONCLUSIONS: Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission.