Short-term outcomes of the study of refeeding to optimize inpatient gains for patients with atypical anorexia nervosa.

OBJECTIVE: The StRONG trial demonstrated the safety and efficacy of higher calorie refeeding (HCR) in hospitalized adolescents and young adults with malnutrition secondary to restrictive eating disorders. Here we compare refeeding outcomes in patients with atypical anorexia nervosa (atypical AN) versus anorexia nervosa (AN) and examine the impact of caloric dose. METHOD: Patients were enrolled upon admission and randomized to meal-based HCR, beginning 2000 kcal/day and advancing 200 kcal/day, or lower calorie refeeding (LCR), beginning 1400 kcal/day and advancing 200 kcal every other day. Atypical AN was defined as %median BMI (mBMI) > 85. Independent t-tests compared groups; multivariable linear and logistic regressions examined caloric dose (kcal/kg body weight). RESULTS: Among n = 111, mean ± SD age was 16.5 ± 2.5 yrs; 43% had atypical AN. Compared to AN, atypical AN had slower heart rate restoration (8.7 ± 4.0 days vs. 6.5 ± 3.9 days, p = .008, Cohen's d = -.56), less weight gain (3.1 ± 5.9%mBMI vs. 5.4 ± 2.9%mBMI, p < .001, Cohen's d = .51) and greater hypomagnesemia (29% vs. 11%, p = .03, OR = 3.29). These suboptimal outcomes were predicted by insufficient caloric dose (32.4 ± 6.9 kcal/kg in atypical AN vs. 43.4 ± 9.8 kcal/kg in AN, p < .001, Cohen's d = 1.27). For every 10 kcal/kg increase, heart rate was restored 1.7 days (1.0, 2.5) faster (p < .001), weight gain was 1.6%mBMI (.8, 2.4) greater (p < .001), and hypomagnesemia odds were 70% (12, 128) lower (p = .02). DISCUSSION: Although HCR is more efficacious than LCR for refeeding in AN, it contributes to underfeeding in atypical AN by providing an insufficient caloric dose relative to the greater body weight in this diagnostic group. PUBLIC SIGNIFICANCE: The StRONG trial previously demonstrated the efficacy and safety of higher calorie refeeding in patients with malnutrition due to restrictive eating disorders. Here we show that higher calorie refeeding contributes to underfeeding in patients with atypical anorexia nervosa, including poor weight gain and longer time to restore medical stability. These findings indicate these patients need more calories to support nutritional rehabilitation in hospital.

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.

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.

Editorial: What Do Alterations in Plasma Lipidome Tell Us About Refeeding in Anorexia Nervosa?

Tam et al.1 take a rigorous look at the changes in plasma lipids that occur during the early part of the refeeding process in female patients, primarily adolescent girls and young women, with anorexia nervosa (AN). Their detailed analyses are timely, as investigators seek to develop refeeding protocols that are safe and effective, while reducing duration of illness, cost of treatment, and time in higher levels of care for patients with AN,2-4 a physically and mentally disabling disease that has the highest mortality rate of any mental illness. The article by Tam and colleagues is important in what it examines. However, it is also important to note what it does not examine, so that other investigators may be inspired to explore and illuminate other aspects of the refeeding process and associated long-term outcomes.

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.

Effect of Hospitalization on Percent Median Body Mass Index at One Year, in Underweight Youth With Restrictive Eating Disorders.

PURPOSE: Data from low-weight patients with restrictive eating disorders (EDs) treated in outpatient adolescent medicine-based ED treatment programs were analyzed to determine whether there was an association between hospitalization and gain to at least 90% median body mass index (mBMI) at 1-year follow-up. METHODS: Data were retrospectively collected for 322 low-weight (<85% mBMI at intake) patients aged 9-21 years, who presented with restrictive EDs to 14 adolescent medicine-based ED programs in 2010. Positive outcome was defined as being at least 90% mBMI (%mBMI = patient's body mass index/mBMI for age × 100) at 1-year follow-up. Association between treatment at a higher level of care and gain to at least 90% mBMI was analyzed for 140 patients who were <85% mBMI at the time of presentation, had not been previously hospitalized, and had 1-year follow-up data available. RESULTS: For patients presenting at <85% mBMI, those who were hospitalized in the year following intake had 4.0 (95% confidence interval: 1.6-10.1) times the odds of gain to at least 90% mBMI, compared with patients who were not hospitalized, when controlling for baseline %mBMI. CONCLUSION: In this national cohort of patients with restrictive EDs presenting to adolescent medicine-based ED programs at <85% mBMI, those who were hospitalized had greater odds of being at least 90% mBMI at 1-year follow-up.

History of Overweight/Obesity as Predictor of Care Received at 1-year Follow-Up in Adolescents With Anorexia Nervosa or Atypical Anorexia Nervosa.

PURPOSE: Previous research has indicated that patients with anorexia nervosa (AN) or atypical AN with premorbid history of overweight/obesity have greater weight loss and longer illness duration than patients with no such history. However, little is known about the association of premorbid overweight/obesity and receiving inpatient medical care during treatment for an eating disorder. METHODS: Using logistic regression, we sought to determine if history of overweight/obesity was associated with receiving inpatient medical care in a sample of 522 patients (mean age 15.5 years, 88% female) with AN/atypical AN. RESULTS: Binary results demonstrated greater percent weight loss (27.4% vs. 16.2%) and higher percent median body mass index (%mBMI, 99.8% vs. 85.2%) at presentation in those with a history of overweight/obesity (p < .001) but no difference in duration of illness (p = .09). In models adjusted for demographics and percent weight loss, history of overweight/obesity was associated with lower odds of receiving inpatient medical care (odds ratio .60 [95% confidence interval: .45-.80]) at 1-year follow-up. However, these associations were no longer significant after adjusting for %mBMI. Mediation results suggest that %mBMI fully mediates the relationship between history of overweight/obesity and inpatient medical care, in that those with a history of overweight/obesity are less likely to receive care due to presenting at a higher weight. CONCLUSIONS: Our findings suggest that, despite greater degree of weight loss and no difference in duration of illness, participants with a history of overweight/obesity are less likely to receive inpatient medical care.

Use of Psychopharmacologic Medications in Adolescents With Restrictive Eating Disorders: Analysis of Data From the National Eating Disorder Quality Improvement Collaborative.

PURPOSE: Psychopharmacologic medications are often prescribed to patients with restrictive eating disorders (EDs), and little is known about the frequency of use in adolescents. We examined the use of psychopharmacologic medications in adolescents referred for treatment of restrictive ED, potential factors associated with their use, and reported psychiatric comorbidities. METHODS: Retrospective data from the initial and 1-year visits were collected for patients referred for evaluation of restrictive ED at 12 adolescent-based ED programs during 2010 (Group 1), including diagnosis, demographic information, body mass index, prior treatment modalities, and psychopharmacologic medications. Additional data regarding patients' comorbid psychiatric conditions and classes of psychopharmacologic medications were obtained from six sites (Group 2). RESULTS: Overall, 635 patients met inclusion criteria and 359 had 1-year follow-up (Group 1). At intake, 20.4% of Group 1 was taking psychopharmacologic medication and 58.7% at 1 year (p ≤ .0001). White, non-Hispanic race (p = .020), and prior higher level of care (p < .0001) were positively associated with medication use at 1 year. Among Group 2 (n = 256), serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors use was most common, and 62.6% had a reported psychiatric comorbidity. Presence of any psychiatric comorbidity was highly associated with medication use; odds ratio, 10.0 (5.6, 18.0). CONCLUSIONS: Adolescents with restrictive ED treated at referral centers have high rates of reported psychopharmacologic medication use and psychiatric comorbidity. As more than half of this referral population were reported to be taking medication, continued investigation is warranted to ensure the desired outcomes of the medications are being met.

Predictors of outcome at 1 year in adolescents with DSM-5 restrictive eating disorders: report of the national eating disorders quality improvement collaborative.

PURPOSE: The National Eating Disorders Quality Improvement Collaborative evaluated data of patients with restrictive eating disorders to analyze demographics of diagnostic categories and predictors of weight restoration at 1 year. METHODS: Fourteen Adolescent Medicine eating disorder programs participated in a retrospective review of 700 adolescents aged 9-21 years with three visits, with DSM-5 categories of restrictive eating disorders including anorexia nervosa (AN), atypical AN, and avoidant/restrictive food intake disorder (ARFID). Data including demographics, weight and height at intake and follow-up, treatment before intake, and treatment during the year of follow-up were analyzed. RESULTS: At intake, 53.6% met criteria for AN, 33.9% for atypical AN, and 12.4% for ARFID. Adolescents with ARFID were more likely to be male, younger, and had a longer duration of illness before presentation. All sites had a positive change in mean percentage median body mass index (%MBMI) for their population at 1-year follow-up. Controlling for age, gender, duration of illness, diagnosis, and prior higher level of care, only %MBMI at intake was a significant predictor of weight recovery. In the model, there was a 12.7% change in %MBMI (interquartile range, 6.5-19.3). Type of treatment was not predictive, and there were no significant differences between programs in terms of weight restoration. CONCLUSIONS: The National Eating Disorders Quality Improvement Collaborative provides a description of the patient population presenting to a national cross-section of 14 Adolescent Medicine eating disorder programs and categorized by DSM-5. Treatment modalities need to be further evaluated to assess for more global aspects of recovery.

Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome.

PURPOSE: To determine the effect of higher caloric intake on weight gain, length of stay (LOS), and incidence of hypophosphatemia, hypomagnesemia, and hypokalemia in adolescents hospitalized with anorexia nervosa. METHODS: Electronic medical records of all subjects 10-21 years of age with anorexia nervosa, first admitted to a tertiary children's hospital from Jan 2007 to Dec 2011, were retrospectively reviewed. Demographic factors, anthropometric measures, incidence of hypophosphatemia (≤3.0 mg/dL), hypomagnesemia (≤1.7 mg/dL), and hypokalemia (≤3.5 mEq/L), and daily change in percent median body mass index (BMI) (%mBMI) from baseline were recorded. Subjects started on higher-calorie diets (≥1,400 kcal/d) were compared with those started on lower-calorie diets (<1,400 kcal/d). RESULTS: A total of 310 subjects met eligibility criteria (age, 16.1 ± 2.3 years; 88.4% female, 78.5 ± 8.3 %mBMI), including 88 in the lower-calorie group (1,163 ± 107 kcal/d; range, 720-1,320 kcal/d) and 222 in the higher-calorie group (1,557 ± 265 kcal/d; range, 1,400-2,800 kcal/d). Neither group had initial weight loss. The %mBMI increased significantly (p < .001) from baseline by day 1 in the higher-calorie group and day 2 in the lower-calorie group. Compared with the lower-calorie group, the higher-calorie group had reduced LOS (13.0 ± 7.3 days versus 16.6 ± 9.0 days; p < .0001), but the groups did not differ in rate of change in %mBMI (p = .50) or rates of hypophosphatemia (p = .49), hypomagnesemia (p = 1.0), or hypokalemia (p = .35). Hypophosphatemia was associated with %mBMI on admission (p = .004) but not caloric intake (p = .14). CONCLUSIONS: A higher caloric diet on admission is associated with reduced LOS, but not increased rate of weight gain or rates of hypophosphatemia, hypomagnesemia, or hypokalemia. Refeeding hypophosphatemia depends on the degree of malnutrition but not prescribed caloric intake, within the range studied.

An eleven site national quality improvement evaluation of adolescent medicine-based eating disorder programs: predictors of weight outcomes at one year and risk adjustment analyses.

PURPOSE: This quality improvement project collected and analyzed short-term weight gain data for patients with restrictive eating disorders (EDs) treated in outpatient adolescent medicine-based ED programs nationally. METHODS: Data on presentation and treatment of low-weight ED patients aged 9-21 years presenting in 2006 were retrospectively collected from 11 independent ED programs at intake and at 1-year follow-up. Low-weight was defined as < 90% median body weight (MBW) which is specific to age. Treatment components at each program were analyzed. Risk adjustment was performed for weight gain at 1 year for each site, accounting for clinical variables identified as significant in bivariate analyses. RESULTS: The sites contained 6-51 patients per site (total N = 267); the mean age was 14.1-17.1 years; duration of illness before intake was 5.7-18.6 months; % MBW at intake was 77.5-83.0; and % MBW at follow-up was 88.8-93.8. In general, 40%-63% of low weight ED subjects reached ≥90% MBW at 1-year follow-up. At intake, patients with higher % MBW (p = .0002) and shorter duration of illness (p = .01) were more likely to be ≥90% MBW at follow-up. Risk-adjusted odds ratios controlled for % MBW and duration of illness were .8 (.5, 1.4)-1.3 (.3, 3.8), with no significant differences among sites. CONCLUSION: A total of 11 ED programs successfully compared quality improvement data. Shorter duration of illness before intake and higher % MBW predicted improved weight outcomes at 1 year. After adjusting for risk factors, program outcomes did not differ significantly. All adolescent medicine-based ED programs were effective in assisting patients to gain weight.