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Background: Despite their use in clinical practice, there is little evidence to support the use of therapist written goodbye letters as therapeutic tools. However, preliminary evidence suggests that goodbye letters may have benefits in the treatment of anorexia nervosa (AN)., Aims: This study aimed to examine whether therapist written goodbye letters were associated with improvements in body mass index (BMI) and eating disorder symptomology in patients with AN after treatment., Method: Participants were adults with AN (n = 41) who received The Maudsley Model of Anorexia Treatment for Adults (MANTRA) in a clinical trial evaluating two AN out-patient treatments. As part of MANTRA, therapists wrote goodbye letters to patients. A rating scheme was developed to rate letters for structure and quality. Linear regression analyses were used to examine associations between goodbye letter scores and outcomes after treatment., Results: Higher quality letters and letters that adopted a more affirming stance were associated with greater improvements in BMI at 12 months. Neither the overall quality nor the style of goodbye letters were associated with improvements in BMI at 24 months or reductions in eating disorder symptomology at either 12 or 24 months., Conclusions: The results highlight the potential importance of paying attention to the overall quality of therapist written goodbye letters in the treatment of AN, and adopting an affirming stance.

Background: There has been no randomised controlled trial (RCT) of fluid bolus therapy in paediatric sepsis in the developed world despite evidence that excess fluid may be associated with harm., Objectives: To determine the feasibility of the Fluids in Shock (FiSh) trial - a RCT comparing restricted fluid bolus (10 ml/kg) with current practice (20 ml/kg) in children with septic shock in the UK., Design: (1) Qualitative feasibility study exploring parents' views about the pilot RCT. (2) Pilot RCT over a 9-month period, including integrated parental and staff perspectives study., Setting: (1) Recruitment took place across four NHS hospitals in England and on social media. (2) Recruitment took place across 13 NHS hospitals in England., Participants: (1) Parents of children admitted to a UK hospital with presumed septic shock in the previous 3 years. (2) Children presenting to an emergency department with clinical suspicion of infection and shock after 20 ml/kg of fluid. Exclusion criteria were receipt of > 20 ml/kg of fluid, conditions requiring fluid restriction and the patient not for full active treatment (i.e. palliative care plan in place). Site staff and parents of children in the pilot were recruited to the perspectives study., Interventions: (1) None. (2) Children were randomly allocated (1 : 1) to 10- or 20-ml/kg fluid boluses every 15 minutes for 4 hours if in shock., Main Outcome Measures: (1) Acceptability of FiSh trial, proposed consent model and potential outcome measures. (2) Outcomes were based on progression criteria, including recruitment and retention rates, protocol adherence and separation between the groups, and collection and distribution of potential outcome measures., Results: (1) Twenty-one parents were interviewed. All would have consented for the pilot study. (2) Seventy-five children were randomised, 40 to the 10-ml/kg fluid bolus group and 35 to the 20-ml/kg fluid bolus group. Two children were withdrawn. Although the anticipated recruitment rate was achieved, there was variability across the sites. Fifty-nine per cent of children in the 10-ml/kg fluid bolus group and 74% in the 20-ml/kg fluid bolus group required only a single trial bolus before shock resolved. The volume of fluid (in ml/kg) was 35% lower in the first hour and 44% lower over the 4-hour period in the 10-ml/kg fluid bolus group. Fluid boluses were delivered per protocol (volume and timing) for 79% of participants in the 10-ml/kg fluid bolus group and for 55% in the 20-ml/kg fluid bolus group, mainly as a result of delivery not being completed within 15 minutes. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) transfers, and days alive and PICU free did not differ significantly between the groups. Two adverse events were reported in each group. A questionnaire was completed by 45 parents, 20 families and seven staff were interviewed and 20 staff participated in focus groups. Although a minority of site staff lacked equipoise in favour of more restricted boluses, all supported the trial., Conclusions: Even though a successful feasibility and pilot RCT were conducted, participants were not as unwell as expected. A larger trial is not feasible in its current design in the UK., Future Work: Further observational work is required to determine the epidemiology of severe childhood infection in the UK in the postvaccine era., Trial Registration: Current Controlled Trials ISRCTN15244462., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 51. See the NIHR Journals Library website for further project information., Competing Interests: Mark J Peters reports membership of the National Institute for Health Research (NIHR) Health Technology Assessment General Board since June 2018. Kathryn M Rowan is a member of the NIHR Health Services and Delivery Research Board.

Objective: The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial., Design: Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years., Participants: Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child's hospital admission (range: 1-41)., Results: All parents said they would have provided consent for the use of their child's data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child's death, but supported a personalised postal 'opt-out' approach to consent., Conclusions: Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents' views informed the development of the pilot trial protocol and site staff training., Trial Registration Number: ISRCTN15244462-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blink modulation (SEM) task. In a balanced amino acid state, AN REC showed an increased appetitive response (decreased startle potentiation) to illness-compatible cues (underweight and active female body pictures (relative to neutral and non-active cues, respectively)). The HC had an aversive response (increased startle potentiation) to the same illness-compatible stimuli (relative to neutral cues). Importantly, these effects, which may be taken to resemble symptoms observed in the acute stage of illness and healthy behaviour respectively, were not present when DA was depleted. Thus, AN REC implicitly appraised underweight and exercise cues as more rewarding than did HC and the process may, in part, be DA-dependent. It is proposed that the positive motivational salience attributed to cues of emaciation and physical activity is, in part, mediated by dopaminergic reward processes and this contributes to illness pathology. These observations are consistent with the proposal that, in AN, aberrant reward-based learning contributes to the development of habituation of AN-compatible behaviours., Competing Interests: The authors have declared that no competing interests exist.

Objective: Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms., Method: Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models., Results: Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003)., Discussion: Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882)., (© 2016 Wiley Periodicals, Inc.)

This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

This focussed narrative review examines neurobiological and psychophysiological evidence supporting a role for altered reward processes in the development and maintenance of anorexia nervosa (AN). In AN, there does not appear to be a generalised inability to experience reward. Rather, data suggest that a reluctance to gain weight leads to an aversive appraisal of food- and taste-related stimuli. As a result, cues compatible with this aberrant mode of thinking become rewarding for the individual. Evidence also suggests that attribution of motivational salience to such cues promotes anorectic behaviours. These findings are consistent with models in which interactions between cognition and reward are important in eliciting the anorectic "habit". A model is proposed which is consistent with elements of other theoretical frameworks, but differs in that its emphasis is towards neural overlaps between AN and addiction. It is consistent with AN being a reward-based learned behaviour in which aberrant cognitions related to eating and shape alter functioning of central reward systems. It proposes that the primary neural problem responsible for the development, maintenance, and treatment resistance is centred in the striatal reward system. This helps shift the emphasis of aetiological models towards reward processing, particularly in the context of illness-compatible cues. Furthermore, it suggests that continuing to explore the utility and valued nature of AN in the patient's life would be a useful inclusion in treatment and prevention models., (Copyright © 2015. Published by Elsevier Ltd.)