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Background Individual, family and service level characteristics and outcomes are described for adult and adolescent patients receiving specialist inpatient or day patient treatment for anorexia nervosa (AN). Potential predictors of treatment outcome are explored. Method Admission and discharge data were collected from patients admitted at 14 UK hospital treatment units for AN over a period of three years (adult units N = 12; adolescent N = 2) (patients N = 177). Results One hundred and seventy-seven patients with a severe and enduring illness with wide functional impairment took part in the study. Following inpatient care, physical improvement was moderate/good with a large increase in BMI, although most patients continued to have a clinical level of eating disorder symptoms at discharge. The potentially modifiable predictors of outcome included confidence to change, social functioning and carer expressed emotion and control. Conclusions Overall, the response to inpatient treatment was modest particularly in the group with a severe enduring form of illness. Adolescents had a better response. Although inpatient treatment produces an improvement in physical health there was less improvement in other eating disorder and mood symptoms. As predicted by the carer interpersonal maintenance model, carer behaviour contributed to the response to inpatient care as did social functioning and confidence to change. [ABSTRACT FROM AUTHOR]

Objective: A restricted region of proinsulin located in the B chain and adjacent region of C-peptide has been shown to contain numerous candidate epitopes recognized by CD8(+) T-cells. Our objective is to characterize HLA class I-restricted epitopes located within the preproinsulin leader sequence.Research Design and Methods: Seven 8- to 11-mer preproinsulin peptides carrying anchoring residues for HLA-A1, -A2, -A24, and -B8 were selected from databases. HLA-A2-restricted peptides were tested for immunogenicity in transgenic mice expressing a chimeric HLA-A*0201/beta2-microglobulin molecule. The peptides were studied for binding to purified HLA class I molecules, selected for carrying COOH-terminal residues generated by proteasome digestion in vitro and tested for recognition by human lymphocytes using an ex vivo interferon-gamma (IFN-gamma) ELISpot assay.Results: Five HLA-A2-restricted peptides were immunogenic in transgenic mice. Murine T-cell clones specific for these peptides were cytotoxic against cells transfected with the preproinsulin gene. They were recognized by peripheral blood mononuclear cells (PBMCs) from 17 of 21 HLA-A2 type 1 diabetic patients. PBMCs from 25 of 38 HLA-A1, -A2, -A24, or -B8 patients produced IFN-gamma in response to six preproinsulin peptides covering residues 2-25 within the preproinsulin region. In most patients, the response was against several class I-restricted peptides. T-cells recognizing preproinsulin peptide were characterized as CD8(+) T-cells by staining with peptide/HLA-A2 tetramers.Conclusions: We defined class I-restricted epitopes located within the leader sequence of human preproinsulin through in vivo (transgenic mice) and ex vivo (diabetic patients) assays, illustrating the possible role of preproinsulin-specific CD8(+) T-cells in human type 1 diabetes. [ABSTRACT FROM AUTHOR]

Tumor cells can have different morphologic or metabolic phenotypes and display genetic instability. Thus they could also vary in their ability to present epitopes to the immune system. We have analyzed the presentation of H-2 Kb- and Db-restricted cytotoxic T lymphocyte (CTL) epitopes of a tumor-associated antigen by three cell lines derived from hepatocarcinomas developed in vivo by mice transgenic for SV40 T targeted to the liver. SV40 T is the obvious tumor-specific antigen and epitopes derived from this antigen were therefore studied. The study included four already known epitopes that can be presented by SV40-transformed kidney cells and two new CTL epitopes that were identified in the present work. CTL lines specific for each epitope were obtained from C57BL/6 mice and were used to map the presentation of SV40 T peptides by the hepatocarcinoma cells. These tumor cells were derived from the same tissue, induced by the same agent and all naturally presented peptide p232-240 from p53. Despite these common features, they all had different patterns of spontaneous presentation of SV40 T CTL epitopes. The mechanisms underlying this disparity are discussed, together with the possible consequences for establishing immunotherapeutic strategies. [ABSTRACT FROM PUBLISHER]

Objective: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure., Method: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis., Results: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38)., Conclusions: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies., (© 2023 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Anorexia nervosa (AN) is a serious and disabling mental disorder with a high disease burden. In a proportion of cases, intensive hospital-based treatments, i.e. inpatient or day patient treatment, are required, with day patient treatment often being used as a 'step-down' treatment after a period of inpatient treatment. Demand for such treatment approaches has seen a sharp rise. Despite this, the relative merits of these approaches for patients, their families, and the NHS and wider society are relatively unknown. This paper describes the rationale for, and protocol of, a two-arm multi-centre open-label parallel group non-inferiority randomised controlled trial, evaluating the effectiveness and cost-effectiveness of these two intensive treatments for adults with severe AN: inpatient treatment as usual and a stepped care day patient approach (the combination of day patient treatment with the option of initial inpatient treatment for medical stabilisation). The main aim of this trial is to establish whether, in adults with severe AN, a stepped care day patient approach is non-inferior to inpatient treatment as usual in relation to improving body mass index (BMI) at 12 months post-randomisation., Methods: 386 patients with a Diagnostic and Statistical Manual 5th edition diagnosis of severe AN or related disorder, with a BMI of ≤16 kg/m 2 and in need of intensive treatment will be randomly allocated to either inpatient treatment as usual or a stepped care day patient approach. Patients in both groups will receive treatment until they reach a healthy weight or get as close to this point as possible. Assessments will be conducted at baseline (prior to randomisation), and at 6 and 12 months post-randomisation, with additional monthly symptom monitoring. The primary outcome will be BMI at the 12-month post-randomisation assessment. Other outcomes will include psychosocial adjustment; treatment motivation, expectations and experiences; cost-effectiveness; and carer burden., Discussion: The results of this study will provide a rigorous evaluation of two intensive treatment approaches which will inform future national and international treatment guidelines and service provision., Trial Registration: ISRCTN ISRCTN10166784 . Registered 28 February 2020. ISRCTN is a primary registry of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) network and includes all items from the WHO Trial Registration Data Set., (© 2022. The Author(s).)

Background: First Episode Rapid Early Intervention for Eating Disorders (FREED) is a service model and care pathway for emerging adults aged 16 to 25-years with a recent onset eating disorder (ED) of <3 years. A previous single-site study suggests that FREED significantly improves clinical outcomes compared to treatment-as-usual (TAU). The present study (FREED-Up) assessed the scalability of FREED. A multi-centre quasi-experimental pre-post design was used, comparing patient outcomes before and after implementation of FREED in participating services., Methods: FREED patients (n = 278) were consecutive, prospectively ascertained referrals to four specialist ED services in England, assessed at four time points over 12 months on ED symptoms, mood, service utilization and cost. FREED patients were compared to a TAU cohort (n = 224) of similar patients, identified retrospectively from electronic patient records in participating services. All were emerging adults aged 16-25 experiencing a first episode ED of <3 years duration., Results: Overall, FREED patients made significant and rapid clinical improvements over time. 53.2% of FREED patients with anorexia nervosa reached a healthy weight at the 12-month timepoint, compared to only 17.9% of TAU patients (X 2 [1, N = 107] = 10.46, p < .001). Significantly fewer FREED patients required intensive (i.e., in-patient or day-patient) treatment (6.6%) compared to TAU patients (12.4%) across the follow-up period (X 2 [1, N = 40] = 4.36, p = .037). This contributed to a trend in cost savings in FREED compared to TAU (-£4472, p = .06, CI -£9168, £233)., Discussion: FREED is robust and scalable and is associated with substantial improvements in clinical outcomes, reduction in inpatient or day-patient admissions, and cost-savings., (© 2021 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: The First Episode Rapid Early Intervention for Eating Disorders (FREED) service model is associated with significant reductions in wait times and improved clinical outcomes for emerging adults with recent-onset eating disorders. An understanding of how FREED is implemented is a necessary precondition to enable an attribution of these findings to key components of the model, namely the wait-time targets and care package., Aims: This study evaluated fidelity to the FREED service model during the multicentre FREED-Up study., Method: Participants were 259 emerging adults (aged 16-25 years) with an eating disorder of <3 years duration, offered treatment through the FREED care pathway. Patient journey records documented patient care from screening to end of treatment. Adherence to wait-time targets (engagement call within 48 h, assessment within 2 weeks, treatment within 4 weeks) and care package, and differences in adherence across diagnosis and treatment group were examined., Results: There were significant increases (16-40%) in adherence to the wait-time targets following the introduction of FREED, irrespective of diagnosis. Receiving FREED under optimal conditions also increased adherence to the targets. Care package use differed by component and diagnosis. The most used care package activities were psychoeducation and dietary change. Attention to transitions was less well used., Conclusions: This study provides an indication of adherence levels to key components of the FREED model. These adherence rates can tentatively be considered as clinically meaningful thresholds. Results highlight aspects of the model and its implementation that warrant future examination.

Background: Duration of untreated eating disorder (DUED), that is, the time between illness onset and start of first evidence-based treatment, is a key outcome for early intervention. Internationally, reported DUED ranges from 2.5 to 6 years for different eating disorders (EDs). To shorten DUED, we developed FREED (First Episode Rapid Early Intervention for EDs), a service model and care pathway for emerging adults with EDs. Here, we assess the impact of FREED on DUED in a multi-centre study using a quasi-experimental design., Methods: Two hundred and seventy-eight patients aged 16-25, with first episode illness of less than 3 years duration, were recruited from specialist ED services and offered treatment via FREED. These were compared to 224 patients, of similar age and illness duration, seen previously in participating services (treatment as usual [TAU]) on DUED, waiting times and treatment uptake., Results: FREED patients had significantly shorter DUED and waiting times than TAU patients. On average, DUED was reduced by ∼4 months when systemic delays were minimal. Furthermore, 97.8% of FREED patients took up treatment, versus 75.4% of TAU., Discussion: Findings indicate that FREED significantly improves access to treatment for emerging adults with first episode ED. FREED may reduce distress, prevent deterioration and facilitate recovery., (© 2020 Eating Disorders Association and John Wiley & Sons Ltd.)

Rationale: Psychotherapies for eating disorders (EDs) are routinely assessed using standardised patient-reported outcome measures (PROMs). PROMs have been criticised for their lack of patient centeredness and clinical utility. The Psychological Outcome Profiles (PSYCHLOPS) is an individualised PROM that allows patients to specify their own outcomes., Aims: (1) To validate the use of the PSYCHLOPS in ED treatment, and (2) to identify patient concerns beyond those measured by common ED PROMs., Methods: Two hundred and seventy-eight emerging adult patients, presenting with a first-episode ED (aged 16-25, illness duration <3 years) completed the PSYCHLOPS and two standardised ED PROMs (the EatingDisorder Examination Questionnaire [EDE-Q] and the Clinical Impairment Assessment Questionnaire [CIA]) at four time points across 12 months. Psychometrics of the PSYCHLOPS were assessed quantitatively against the EDE-Q and CIA. Content analysis assessed unique patient concerns identified by PSYCHLOPS., Results: The PSYCHLOPS had adequate to good psychometric properties. A total of 53.3% of participants reported a concern not addressed by the EDE-Q or the CIA, the most common being depression/anxiety, academic problems, treatment concerns and disturbed sleep., Discussion: PROMs can be complemented by the PSYCHLOPS to identify problems specific to an individual's context. As ED patients are typically ambivalent about change, understanding their concerns is vital in building motivation for change., (© 2021 Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Eating disorders (EDs) typically start during adolescence or emerging adulthood, periods of intense biopsychosocial development. FREED (First Episode Rapid Early Intervention for EDs) is a service model and care pathway providing rapid access to developmentally-informed care for emerging adults with EDs. FREED is associated with reduced duration of untreated eating disorder and improved clinical outcomes, but patients' experiences of treatment have yet to be assessed., Objective: This study aimed to assess emerging adults' experiences of receiving treatment through FREED., Method: This study triangulated qualitative data on participants' experiences of FREED treatment from questionnaires and semi-structured interviews. Participants were 106 emerging adults (aged 16-25; illness duration < 3 yrs) (questionnaire only = 92; interview only = 6; both = 8). Data were analysed thematically., Results: Most participants reported psychological and behavioural changes over the course of treatment (e.g. reduction in symptoms; increased acceptance and understanding of difficulties). Participants identified five beneficial characteristics of FREED treatment: i) rapid access to treatment; ii) knowledgeable and concerned clinicians; iii) focusing on life beyond the eating disorder; iv) building a support network; v) becoming your own therapist., Conclusion: This study provides further supports for the implementation of early intervention and developmentally-informed care for EDs. Future service model development should include efforts to increase early help-seeking.

Aims and methodThis service evaluation was conducted to find out: (1) if mixed gender accommodation in eating disorder units is perceived to be helpful or unhelpful for recovery, and (2) if men were being discriminated against by the implementation of the 2010 Department of Health (DoH) guidelines on the elimination of mixed gender wards. All 32 in-patient units accredited on the Quality Network for Eating Disorders were contacted via a survey. RESULTS: We received 38 responses from professionals from 26 units and 53 responses from patients (46 female, 7 male) from 7 units. Four units had closed admissions to male patients due to DoH guidelines.Clinical implicationsWe found that it is possible to provide admission for men with eating disorders, while respecting the single gender accommodation rules, and that doing so is likely to be helpful for both genders and prevents discrimination against men.Declaration of interestNone.

Background: Considerable progress has been made in recent years in developing effective treatments for child and adolescent anorexia nervosa, with a general consensus in the field that eating disorders focussed family therapy (often referred to as Maudsley Family Therapy or Family Based Treatment) currently offers the most promising outcomes. Nevertheless, a significant number do not respond well and additional treatment developments are needed to improve outcomes. Multifamily therapy is a promising treatment that has attracted considerable interest and we report the results of the first randomised controlled trial of multifamily therapy for adolescent anorexia nervosa., Methods: The study was a pragmatic multicentre randomised controlled superiority trial comparing two outpatient eating disorder focussed family interventions - multifamily therapy (MFT-AN) and single family therapy (FT-AN). A total of 169 adolescents with a DSM-IV diagnosis of anorexia nervosa or eating disorder not otherwise specified (restricting type) were randomised to the two treatments using computer generated blocks of random sizes to ensure balanced numbers in the trial arms. Independent assessors, blind to the allocation, completed evaluations at baseline, 3 months, 12 months (end of treatment) and 18 months., Results: Both treatment groups showed clinically significant improvements with just under 60% achieving a good or intermediate outcome (on the Morgan-Russell scales) at the end of treatment in the FT-AN group and more than 75% in the MFT-AN group - a statistically significant benefit in favour of the multifamily intervention (OR = 2.55 95%; CI 1.17, 5.52; p = 0.019). At follow-up (18 months post baseline) there was relatively little change compared to end of treatment although the difference in primary outcome between the treatments was no longer statistically significant. Clinically significant gains in weight were accompanied by improvements in mood and eating disorder psychopathology. Approximately half the patients in FT-AN and nearly 60% of those in MFT-AN had started menstruating., Conclusions: This study confirms previous research findings demonstrating the effectiveness of eating disorder focused family therapy and highlights the additional benefits of bringing together groups of families that maximises the use of family resources and mutual support leading to improved outcomes., Trial Registration: Current Controlled Trials ISRCTN11275465 ; Registered 29 January 2007 (retrospectively registered).

Background: The underlying core of personality is insufficiently assessed by any single instrument. This has led to the development of instruments adapted for written records in the assessment of personality disorder., Aims: To test the construct validity and inter-rater reliability of a new personality assessment method., Method: This study (four parts) assessed the construct validity of the Schedule for Personality Assessment from Notes and Documents (SPAN-DOC), a dimensional assessment from clinical records. We examined inter-rater reliability using case vignettes (Part 1) and convergent validity in three ways: by comparison with NEO Five-Factor Inventory in 130 Korean patients (Part 2), with agreed ICD-11 personality severity levels in two populations (Part 3) and determining its use in assessing the personality status in 90 British patients with eating disorders (Part 4)., Results: Internal consistency (alpha = .90) and inter-rater reliability (intraclass correlation coefficient ≥ .88) were satisfactory. Each factor in the five-factor model of personality was correlated with conceptually valid SPAN-DOC variables. The SPAN-DOC domain traits in those with eating disorders were categorized into 3 clusters: self-aggrandisement, emotionally unstable, and anxious/dependent., Conclusions: This study provides preliminary support for the usefulness of SPAN-DOC in the assessment of personality disorder. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objectives: To investigate physical activity (PA) and drive for exercise in anorexia nervosa (AN) in relation to eating disorder (ED) pathology and anxiety., Method: Female participants were recruited into four groups: AN outpatients (n = 37), AN inpatients (n = 18), an anxiety group (n = 34), and healthy controls (HCs; n = 30). PA was measured by actigraphy and self-report together with drive/reasons for exercise, ED pathology, anxiety, depression, stress, BMI, and body composition., Results: ED psychopathology, general psychopathology, and physiological measures were consistent with diagnosis. All groups showed a wide range in activity, especially on self-report. No significant group differences were observed in objective PA levels, yet AN groups reported 57-92% higher total activity than HCs. Outpatients reported more walking and moderate exercise than HCs, and inpatients reported more walking but less moderate and vigorous activity than all other groups. AN groups had significantly higher drive to exercise and valued "improving tone" as important and health and enjoyment as less important reasons to exercise., Discussion: Self-perceived activity rather than objective data may partly explain the increased activity reported in AN. Drive to exercise in AN appears to be more related to ED pathology than to anxiety., (© 2014 Wiley Periodicals, Inc.)

Objective: Caring for someone diagnosed with an eating disorder (ED) is associated with a high level of burden and psychological distress which can inadvertently contribute to the maintenance of the illness. The Eating Disorders Symptom Impact Scale (EDSIS) and Accommodation and Enabling Scale for Eating Disorders (AESED) are self-report scales to assess elements of caregiving theorised to contribute to the maintenance of an ED. Further validation and confirmation of the factor structures for these scales are necessary for rigorous evaluation of complex interventions which target these modifiable elements of caregiving. Method: EDSIS and AESED data from 268 carers of people with anorexia nervosa (AN), recruited from consecutive admissions to 15 UK inpatient or day patient hospital units, were subjected to confirmatory factor analysis to test model fit by applying the existing factor structures: (a) four-factor structure for the EDSIS and (b) five-factor structure for the AESED. Results: Confirmatory factor analytic results support the existing four-factor and five-factor structures for the EDSIS and the AESED, respectively. Discussion: The present findings provide further validation of the EDSIS and the AESED as tools to assess modifiable elements of caregiving for someone with an ED.