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Higher-Calorie Refeeding in Anorexia Nervosa: 1-Year Outcomes From a Randomized Controlled Trial.
Golden, NH, Cheng, J, Kapphahn, CJ, Buckelew, SM, Machen, VI, Kreiter, A, Accurso, EC, Adams, SH, Le Grange, D, Moscicki, AB, et al
Pediatrics. 2021;(4)
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Abstract
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.
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Short-term Outcomes of the Study of Refeeding to Optimize Inpatient Gains for Patients With Anorexia Nervosa: A Multicenter Randomized Clinical Trial.
Garber, AK, Cheng, J, Accurso, EC, Adams, SH, Buckelew, SM, Kapphahn, CJ, Kreiter, A, Le Grange, D, Machen, VI, Moscicki, AB, et al
JAMA pediatrics. 2021;(1):19-27
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Abstract
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.
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Intranasal oxytocin in the treatment of anorexia nervosa: Randomized controlled trial during re-feeding.
Russell, J, Maguire, S, Hunt, GE, Kesby, A, Suraev, A, Stuart, J, Booth, J, McGregor, IS
Psychoneuroendocrinology. 2018;:83-92
Abstract
BACKGROUND Nutritional rehabilitation in anorexia nervosa (AN) is impeded by fear of food, eating and change leading to treatment resistance. Oxytocin (OT) exerts prosocial effects and modulates trust, fear, anxiety and neuroplasticity. The current placebo-controlled RCT examined the effects of intranasal oxytocin (IN-OT) in AN. The aim was to ascertain whether repeated doses of IN-OT enhance treatment outcomes in AN. METHODS AN patients self-administered 36 IU IN-OT or placebo daily for 4-6 weeks during hospital treatment. The outcome measures were change in the Eating Disorders Examination (EDE) scale, weight gain, cognitive rigidity, social anxiety, obsessive and autistic symptoms. The effects of the first and last doses of IN-OT were assessed relative to placebo before and after a high-energy afternoon snack, to determine potential dampening of cortisol and anxiety levels by OT. RESULTS Weight gain was similar in both groups. The EDE eating concern subscale score was significantly lower after IN-OT treatment as was cognitive rigidity. There were no significant differences in social anxiety or any of the other outcomes at follow-up. After four weeks IN-OT, salivary cortisol levels were significantly lowered in anticipation of an afternoon snack compared to placebo. Morning plasma OT levels did not change after chronic IN-OT or with weight restoration. CONCLUSION IN-OT might enhance nutritional rehabilitation in AN by reducing eating concern and cognitive rigidity. Lower salivary cortisol levels in response to IN-OT suggest diminished neuroendocrine stress responsiveness to food and eating. Such effects require replication with inclusion of more sensitive subjective measures.
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Refeeding Low Weight Hospitalized Adolescents With Anorexia Nervosa: A Multicenter Randomized Controlled Trial.
O'Connor, G, Nicholls, D, Hudson, L, Singhal, A
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2016;(5):681-9
Abstract
BACKGROUND Refeeding patients with anorexia nervosa (AN) is associated with high morbidity and mortality. A lack of evidence from interventional studies has hindered refeeding practice and led to worldwide disparities in management recommendations. In the first randomized controlled trial in this area, we tested the hypothesis that refeeding adolescents with AN with a higher energy intake than what many guidelines recommend improved anthropometric outcomes without adversely affecting cardiac and biochemical markers associated with refeeding. MATERIALS AND METHODS Participants aged 10-16 years with a body mass index (BMI) <78% of the median (mBMI) for age and sex were recruited from 6 UK hospitals and randomly allocated to start refeeding at 1200 kcal/d (n = 18, intervention) or 500 kcal/d (n = 18, control). RESULTS Compared with controls, adolescents randomized to high energy intake had greater weight gain (mean difference between groups after 10 days of refeeding, -1.2% mBMI; 95% confidence interval, -2.4% to 0.0%; P = .05), but randomized groups did not differ statistically in QTc interval and other outcomes. The nadir in postrefeeding phosphate concentration was significantly related to percentage mBMI at the start of refeeding (baseline; P = .04) and baseline white blood cell count (P = .005) but not to baseline energy intake (P = .08). CONCLUSIONS Refeeding adolescents with AN with a higher energy intake was associated with greater weight gain but without an increase in complications associated with refeeding when compared with a more cautious refeeding protocol-thus challenging current refeeding recommendations.
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Muscle function and body composition profile in adolescents with restrictive anorexia nervosa: does resistance training help?
Fernández-del-Valle, M, Larumbe-Zabala, E, Morande-Lavin, G, Perez Ruiz, M
Disability and rehabilitation. 2016;(4):346-53
Abstract
PURPOSE The aim of this study was to analyze the effects of short-term resistance training on the body composition profile and muscle function in a group of Anorexia Nervosa restricting type (AN-R) patients. METHODS The sample consisted of AN-R female adolescents (12.8 ± 0.6 years) allocated into the control and intervention groups (n = 18 each). Body composition and relative strength were assessed at baseline, after 8 weeks and 4 weeks following the intervention. RESULTS Body mass index (BMI) increased throughout the study (p = 0.011). Significant skeletal muscle mass (SMM) gains were found in the intervention group (p = 0.045, d = 0.6) that correlated to the change in BMI (r = 0.51, p < 0.031). Meanwhile, fat mass (FM) gains were significant in the control group (p = 0.047, d = 0.6) and correlated (r > 0.60) with change in BMI in both the groups. Significant relative strength increases (p < 0.001) were found in the intervention group and were sustained over time. CONCLUSIONS SMM gain is linked to an increased relative strength when resistance training is prescribed. Although FM, relative body fat (%BF), BMI and body weight (BW) are used to monitor nutritional progress. Based on our results, we suggest to monitor SMM and relative strength ratios for a better estimation of body composition profile and muscle function recovery. Implications for Rehabilitation Anorexia Nervosa Restricting Type (AN-R) AN-R is a psychiatric disorder that has a major impact on muscle mass content and function. However, little or no attention has been paid to muscle recovery. High intensity resistance training is safe for AN-R after hospitalization and enhances the force generating capacity as well as muscle mass gains. Skeletal muscle mass content and muscular function improvements are partially maintained for a short period of time when the exercise program ceases.
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The Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC): Comparison of the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) with specialist supportive clinical management (SSCM) in outpatients with broadly defined anorexia nervosa: A randomized controlled trial.
Schmidt, U, Magill, N, Renwick, B, Keyes, A, Kenyon, M, Dejong, H, Lose, A, Broadbent, H, Loomes, R, Yasin, H, et al
Journal of consulting and clinical psychology. 2015;(4):796-807
Abstract
OBJECTIVE Anorexia nervosa (AN) in adults has poor outcomes, and treatment evidence is limited. This study evaluated the efficacy and acceptability of a novel, targeted psychological therapy for AN (Maudsley Model of Anorexia Nervosa Treatment for Adults; MANTRA) compared with Specialist Supportive Clinical Management (SSCM). METHOD One hundred forty-two outpatients with broadly defined AN (body mass index [BMI] ≤ 18.5 kg/m²) were randomly allocated to receive 20 to 30 weekly sessions (depending on clinical severity) plus add-ons (4 follow-up sessions, optional sessions with dietician and with carers) of MANTRA (n = 72) or SSCM (n = 70). Assessments were administered blind to treatment condition at baseline, 6 months, and 12 months after randomization. The primary outcome was BMI at 12 months. Secondary outcomes included eating disorders symptomatology, other psychopathology, neuro-cognitive and social cognition, and acceptability. Additional service utilization was also assessed. Outcomes were analyzed using linear mixed models. RESULTS Both treatments resulted in significant improvements in BMI and reductions in eating disorders symptomatology, distress levels, and clinical impairment over time, with no statistically significant difference between groups at either 6 or 12 months. Improvements in neuro-cognitive and social-cognitive measures over time were less consistent. One SSCM patient died. Compared with SSCM, MANTRA patients rated their treatment as significantly more acceptable and credible at 12 months. There was no significant difference between groups in additional service consumption. CONCLUSIONS Both treatments appear to have value as first-line outpatient interventions for patients with broadly defined AN. Longer term outcomes remain to be evaluated.
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Anthropometric changes in adolescents with anorexia nervosa in response to resistance training.
Fernandez-del-Valle, M, Larumbe-Zabala, E, Graell-Berna, M, Perez-Ruiz, M
Eating and weight disorders : EWD. 2015;(3):311-7
Abstract
PURPOSE The follow-up of anthropometric percentiles such as triceps and mid-thigh skinfold thickness (TSF, MTSF), mid-upper arm and mid-thigh circumferences (MUAC, MTC), and arm and mid-thigh muscle areas (AMA, MTMA) after a resistance training might allow for detecting nutritional progress of fat and muscular tissue during the treatment of anorexia nervosa restricting (AN-R) type patients. METHODS A total of 44 AN-R patients were randomized for control (CG 13.0 ± 0.6 years) and intervention (IG 12.7 ± 0.7 years) groups after hospitalization. The intervention group underwent a resistance training program of 8 weeks following the guidelines for healthy adolescents (3 days/week; 70 % of 6 RM). All measurements were obtained prior to starting the program (PRE) and after 8 weeks of training (POST) in both groups. TSF, MTSF, MUAC, and MTC were measured, and AMA and MTMA were calculated. Data were matched with percentile tables for general population. Changes were assessed using statistical tests for categorical data. RESULTS The distribution of percentile categories within the groups did not differ statistically after 8 weeks (p > 0.05). After training, 73 % of the patients were at the same percentile interval of MUAC, 18 % higher and 9 % lower, while 30 % of CG was at lower percentile categories. Further, 54 % of the IG patients remained at the same percentile interval of MTC after training, and 36 % higher, while 20 % were at lower categories in the CG. The AMA increased (32 %) after training or remained at the same interval (59 %) in the IG, while the IG showed greater frequency of percentile decreases (45 %). CONCLUSIONS Anthropometric measurements could be useful for assessing muscle status in AN-R patients during the treatment process. However, exact standard deviation scores should be used instead of percentile categories to increase the sensitivity to changes in TSF, MTSF, MUAC, MTC or AMA.
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The impact of induced positive mood on symptomatic behaviour in eating disorders. An experimental, AB/BA crossover design testing a multimodal presentation during a test-meal.
Cardi, V, Esposito, M, Clarke, A, Schifano, S, Treasure, J
Appetite. 2015;:192-8
Abstract
OBJECTIVE The aim of this study was to test the impact of a multimodal positive mood vodcast including pleasant images, background uplifting music and a script designed to elicit positive mood on eating disorders-related symptoms in participants suffering from an Eating Disorder (ED) and healthy controls (HCs). METHOD Forty-two women with an ED (Anorexia Nervosa [AN]: N = 19; Bulimia Nervosa [BN]: N = 23) and 36 HCs were included in an AB/BA cross-over design which compared the use of a positive mood induction procedure ("positive mood vodcast") with a control condition (i.e. blue static background, neutral music, and script describing objective facts) during a test-meal. Self-report measures and behavioural tasks were completed before and after the test-meal. RESULTS The positive mood vodcast was associated with greater consumption of the test meal in the AN group; reduced vigilance to food stimuli and lower anxiety in the BN sample; and no significant changes in the HC group. DISCUSSION The use of a positive mood vodcast was associated with some beneficial effects in the context of an experimental test-meal in participants with an ED.
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[Locus of control in girls with anorexia readiness syndrome].
Jaros, K, Oszwa, U
Psychiatria polska. 2014;(3):441-51
Abstract
PURPOSE The aim of the research was to indicate whether there are differences between locus of control (LOC) in girls with anorexia readiness syndrome (ARS) and without this syndrome. There was also a question about the relationship between LOC and the tendency to respond in incorrect attitudes towards food, eating and their bodies under stress. METHOD The sample consisted of girls aged 13-18 years randomly selected from five public Polish middle and high schools. Tools: 1) Eating Attitudes Questionnaire (EAQ) by B. Ziółkowska; 2) Locus of Control Questionnaire (LOCQ) by G. Krasowicz, A. Kurzyp-Wojnarska, to assess LOC of the subjects. The criterion group (N=23) was formed by girls who received high score in EAQ (signs of ARS) in the first stage of research (N=189). The control group (N = 23) were girls who received a low score in EAQ (no signs of ARS). RESULTS Subjects with ARS were characterized by more external LOC than girls without any signs of this syndrome (t = -2.898; p < 0.01). The results did not confirm the hypothesis about the relationship between LOC and the tendency to respond by abnormal attitude to eating and own body in difficult situations in both groups. CONCLUSIONS In pathogenesis of ARS where anorexic behaviors can become a way to a regain lost control, LOC may play a role as a mediating variable rather than a direct determinant of this syndrome.
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Inhibition of Pref-1 (preadipocyte factor 1) by oestradiol in adolescent girls with anorexia nervosa is associated with improvement in lumbar bone mineral density.
Faje, AT, Fazeli, PK, Katzman, D, Miller, KK, Breggia, A, Rosen, CJ, Mendes, N, Misra, M, Klibanski, A
Clinical endocrinology. 2013;(3):326-32
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Abstract
OBJECTIVE Adolescents with anorexia nervosa (AN) are amenorrheic and have decreased bone mass accrual and low bone mineral density (BMD). The regulation of mesenchymal stem cell differentiation is an important factor governing bone formation. Preadipocyte factor 1 (Pref-1), an inhibitor of adipocyte and osteoblast differentiation, is elevated in states of oestrogen deficiency. In this study, we aim to (i) investigate effects of transdermal oestradiol on Pref-1 in adolescent girls with AN, and (ii) examine associations of changes in Pref-1 with changes in lumbar BMD and bone turnover markers. DESIGN Adolescent girls with AN and normal-weight controls were studied cross-sectionally. Girls with AN were examined longitudinally in a double-blind study and received transdermal oestradiol (plus cyclic medroxyprogesterone) or placebo for 12 months. PATIENTS Sixty-nine girls (44 with AN, 25 normal-weight controls) 13-18 years were studied at baseline; 22 AN girls were followed prospectively. MEASUREMENTS Pref-1 levels, bone formation and resorption markers, and BMD. RESULTS Pref-1 levels decreased in girls with AN after treatment with transdermal oestradiol compared with placebo (-0·015 ± 0·016 vs 0·060±0·026 ng/ml, P = 0·01), although at baseline, levels did not differ in AN vs controls (0·246 ± 0·015 vs 0·267 ± 0·022 ng/ml). Changes in Pref-1 over 12 months correlated inversely with changes in lumbar BMD (r = -0·48, P = 0·02) and positively with changes in CTX (r = 0·73, P = 0·006). CONCLUSIONS For the first time, we show that Pref-1 is negatively regulated by oestradiol in adolescent girls with AN. Inhibition of Pref-1 may mediate the beneficial effects of transdermal oestradiol replacement on BMD in girls with AN.