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 6 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 (b = 20.492 [confidence interval (CI) 20.883 to 20.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (b = 20.005 [CI 20.010 to 0.000]; P = .04) and longer duration (b = 20.011 [CI 20.017 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. WHAT'S KNOWN ON THIS SUBJECT: Lower weight was traditionally equated with more severe illness in anorexia nervosa. The rapid rise in patients with atypical anorexia nervosa who require hospitalization at normal weight has challenged reliance on current weight to guide clinical concern. WHAT THIS STUDY ADDS: Patients with large, rapid, or longduration of weight loss were more severely ill regardless of their current weight. Weight history can help guide clinical concern for pediatricians tasked with assessing restrictive eating disorders in today' s diverse population of adolescents.

IMPORTANCEThe 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 PARTICIPANTSIn 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. RESULTSBecause 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

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.

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.

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.