A phase II randomised controlled trial of intranasal oxytocin in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is an eating disorder (ED) with high mortality rates and limited response to existing treatments, prompting the need to identify effective agents and adjuncts. There is evidence for an emerging role for the neuropeptide oxytocin (OT) in the pathophysiology of AN, with studies showing a perturbed oxytocinergic system in patients with AN. Preliminary evidence has demonstrated that intranasal OT (IN-OT) can produce anxiolytic effects in AN, as well as reducing concern about eating, and dysfunctional attentional biases related to the disorder. IN-OT is a non-invasive treatment option for AN that requires investigation as an adjunct to nutritional rehabilitation. METHODS: This multi-site study (Trial Registration:ACTRN1261000897460) sought to replicate and extend a previous randomised placebo-controlled pilot trial of repeated dose IN-OT in patients with AN hospitalised for nutritional rehabilitation. Patients with AN (N=61) received daily IN-OT (18 IU twice per day) or placebo for four weeks, whilst undergoing inpatient hospital treatment. Outcome measures included ED psychopathology (primary) as measured by the Eating Disorder Examination (EDE) and Body Mass Index (BMI; secondary). Participants were assessed pre- and post-treatment, and at six months following the intervention. The effects of the first and last doses of IN-OT on responses (anxiety ratings and salivary cortisol) to a high-energy snack were also examined. RESULTS: Sixty-one female inpatients (Mage=24.36,SD=7.87) with an average BMI of 16.24 (range: 11.43-18.55), were recruited into the study. No significant differences were found between placebo and OT groups at any of the time points on the outcomes of interest, but significant improvements in almost all psychological parameters in both groups were evident over time. IN-OT did not significantly reduce anxiety nor salivary cortisol in response to a high-calorie snack. CONCLUSION: This is the largest randomised placebo-controlled trial of repeated dose intranasal OT in people with AN, during refeeding. The therapeutically promising findings of the pilot study were not replicated. Limitations and reasons for the non-replication included relatively large variance, baseline psychopathology scores being higher in this patient group, potential ceiling effects in BMI and ED psychopathology as well as differing comorbidities.

Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5+ stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1+ stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease. These PDS3 phenotypic traits are evident across numerous bulk and single-cell datasets, and demark a series of subtle biological states that are currently under-represented in pre-clinical models and are not identified using existing subtyping classifiers.

Educating primary care physicians about eating disorders: Pilot data from a microlearning programme.

BACKGROUND: Over two-thirds of people present to their primary care physician (or general practitioner; GP) as a first point of contact for mental health concerns. However, eating disorders (EDs) are often not identified in a primary care setting. A significant barrier to early detection and intervention is lack of primary care physician training in EDs; compounded by the significant time commitments required for training by already time-poor general practitioners. The aim of the current study was to pilot and evaluate a microlearning programme that can be delivered to general practitioners with high workloads to help support patients with, or at risk of, developing an ED. METHODS: Fifty-one Australian general practitioners aged between 25-to-60 years old were recruited. Participants completed a baseline questionnaire to ascertain their experience working in general practice and with EDs. Participants then completed an online programme consisting of a series of 10 case studies (vignettes) delivered over a 6-10 week period related to various facets of ED care. Following conclusion of the programme, participants were asked to complete an evaluative questionnaire related to the content of the programme; perceived knowledge, confidence, willingness-to-treat, skill change; and their overall experience of microlearning. RESULTS: All 51 GPs completed the programme and reached completion criteria for all vignettes, 40 of whom completed the programme evaluation. Participants indicated improved skill, confidence, willingness-to-treat, and knowledge following the completion of the pilot programme. Almost all (97.5%; n = 39) found microlearning to be an effective method to learn about EDs; with 87.5% (n = 35) of participants reporting they felt able to apply what was learnt in practice. Qualitative feedback highlighted the benefit of microlearning's flexibility to train general practitioners to work with complex health presentations, specifically EDs. CONCLUSIONS: Findings from the current study lend support to the use of microlearning in medical health professional training; notably around complex mental health concerns. Microlearning appears to be an acceptable and effective training method for GPs to learn about EDs. Given the significant time demands on GPs and the resulting challenges in designing appropriate training for this part of the workforce, this training method has promise. The pre-existing interest in EDs in the current study sample was high; future studies should sample more broadly to ensure that microlearning can be applied at scale.

Characteristics, correlates of burden and support service use of a help-seeking carers of loved ones with an eating disorder.

OBJECTIVE: Carers, vital in the care of individuals with an eating disorder (ED), experience substantial caregiving burden and unmet needs. This study aims to identify factors which contribute to the burden experienced by carers of a loved one with an ED and their support service usage. METHOD: Carers (N = 245) completed an online questionnaire assessing demographic, carer-specific, individual and ED factors. Multivariate relationships with caregiving burden were examined using forwards elimination to produce a parsimonious model of carer burden. RESULTS: The final model, consisting of caregiving factors (e.g., relationship type, skills), carer mental health) and loved one wellbeing (i.e., purging symptoms, depression/self-harm/suicidality) explained a large proportion (62%) of the variance in carers' burden. Carer mental health, caregiving skills and relationship type (e.g., parent, spouse, sibling) were key predictors of carers' burden. Nearly a third of carers had not used any carer support services, yet most carers expressed an interest in such services. CONCLUSION: Caregiving burden is determined by experiences and skills of the carer as well as the person they are caring for. Carer support services should continue to address the general wellbeing of carers and caregiver skills. Research into the barriers to carer support uptake is needed.

Skills-based online self-help program for carers of people with an eating disorder (SupportED): A case series evaluation.

OBJECTIVE: To investigate the acceptability, feasibility, and preliminary effectiveness of "SupportED," a novel, online, self-paced skills-based program for carers/support people of those with lived and/or living experience of an eating disorder (ED). METHOD: Carers of a loved one with an ED were invited to undertake a five-module skills-based (one core module, four optional modules) online program at their own pace. Modules cover general information about EDs, communication, practical skills, treatment engagement, and recovery. Participants completed demographics and were assessed using EDSIS, CASK, and DASS-21 for caregiver burden, skills, and distress, respectively, at program completion and 3-month follow-up. Feedback on the program and modules was also collected. RESULTS: Most carers (65%; 82/126) completed the core module of the program, which is on par with other online learning programs. Nearly half of program completers responded to the 3-month follow-up (n = 39). On average, carers rated the program as relevant and useful and found the information validating and easy to understand, albeit a few carers found the program time-consuming and technically challenging. Intent-to-treat (ITT) linear mixed models demonstrated the preliminary effectiveness of the program for improving carer burden and skills, although the change in carer distress was non-significant. CONCLUSIONS: Results of this case series evaluation suggest SupportED is an acceptable and feasible program for carers and may improve burden and support skill development. Although the online, self-paced format was highly rated, small improvements to improve acceptability were suggested. Reasons for a lack of impact on carer distress are discussed. PUBLIC SIGNIFICANCE: This article describes a case series evaluation of "SupportED," an online skills-based support program for families, carers, and supporters of people with lived experience of an eating disorder. This is the first online carer support program that is designed to be inclusive of all carer types (e.g., partners, siblings) for all eating disorder presentations. Findings suggest the program's suitability and helpfulness for reducing carers' load and bolstering skills and knowledge.

My Diet Study: protocol for a two-part observational, longitudinal, psycho-biological study of dieting in Australian youth.

Introduction: Self-directed dieting (i.e., unsupervised) is very common among adolescents and young adults but has had almost no direct research. This paper describes the protocol for the My Diet Study, a two-arm observational investigation of the natural progression of dieting among young people over a period of 6-months. The study aims to examine the links between self-directed dieting, general physiological and psychological metrics of wellbeing (e.g., depressive symptoms) and biomarkers of gut-brain axis functions (e.g., microbiome and hormones) that are predicted to influence diet adherence through appetite, mood and metabolism regulation. Methods: Young people aged 16-25, intending to start a diet will be invited to participate in this observational study. For Part 1 (psychological arm), participants will be asked to complete a set of questionnaires and diaries at the beginning of every month for 6 months, to assess overall mental (e.g., psychological distress, disordered eating) and physical (e.g., weight) health, perceived diet success, food intake and gastrointestinal movements. For Part 2 (biological arm), a subsample of 50 participants will be asked to provide feces, blood and saliva for bio-sampling each month for the first 3-months of their participation in Part 1. Discussion: The My Diet Study will be the first longitudinal, observational study of dieting in young people combining in-depth psychological and biological data. It is anticipated that the findings will yield psychological & biological information about the impacts and effectiveness of self-directed dieting in young people, inform a framework for advice on safety in dieting among young people and help to establish the potential for biomarkers for risk management and improvement of diet-based lifestyle interventions.

A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition.

Introduction: There is an emerging need for plant-based, vegan options for patients requiring nutritional support. Methods: Twenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed. Results: Patients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition ('MUST' score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p > 0.06) with no serious adverse events related. Discussion: This study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition.

Psychotherapies for eating disorders: findings from a rapid review.

BACKGROUND: Psychotherapy is considered central to the effective treatment of eating disorders-focusing on behavioural, psychological, and social factors that contribute to the illness. Research indicates psychotherapeutic interventions out-perform placebo, waitlist, and/or other treatments; but, outcomes vary with room for major improvement. Thus, this review aims to (1) establish and consolidate knowledge on efficacious eating disorder psychotherapies; (2) highlight select emerging psychotherapeutic interventions; and (3) identify knowledge gaps to better inform future treatment research and development. METHODS: The current review forms part of a series of Rapid Reviews published in a special issue in the Journal of Eating Disorders to inform the development of the Australian-government-funded National Eating Disorder Research and Translation Strategy 2021-2031. Three databases were searched for studies published between 2009 and 2023, published in English, and comprising high-level evidence studies (meta-analyses, systematic reviews, moderately sized randomised controlled studies, moderately sized controlled-cohort studies, and population studies). Data pertaining to psychotherapies for eating disorders were synthesised and outlined in the current paper. RESULTS: 281 studies met inclusion criteria. Behavioural therapies were most commonly studied, with cognitive-behavioural and family-based therapies being the most researched; and thus, having the largest evidence-base for treating anorexia nervosa, bulimia nervosa, and binge eating disorder. Other therapies, such as interpersonal and dialectical behaviour therapies also demonstrated positive treatment outcomes. Emerging evidence supports specific use of Acceptance and Commitment; Integrative Cognitive Affective; Exposure; Mindfulness; and Emotionally-Focused therapies; however further research is needed to determine their efficacy. Similarly, growing support for self-help, group, and computer/internet-based therapeutic modalities was noted. Psychotherapies for avoidant/restrictive food intake disorder; other, and unspecified feeding and eating disorders were lacking evidence. CONCLUSIONS: Currently, clinical practice is largely supported by research indicating that behavioural and cognitive-behavioural psychotherapies are most effective for the treatment of eating disorders. However, the efficacy of psychotherapeutic interventions varies across studies, highlighting the need for investment and expansion of research into enhanced variants and novel psychotherapies to improve illness outcomes. There is also a pressing need for investigation into the whole range of eating disorder presentations and populations, to determine the most effective interventions.

Evaluating the efficacy of treatment options for eating disorders (EDs) is important and necessary to inform both treatment guidelines and clinical practice. However, treatment outcomes in studies, and in clinical practice, can vary widely. Therefore, this review aimed to pool evidence related to a wide range of psychological treatments to help better understand what gaps in treatment need to be addressed. Using a rapid review method, three academic databases were searched, and 281 articles were identified and analysed. Results indicated that cognitive-behavioural approaches had the most evidence for well-defined EDs (such as anorexia nervosa, bulimia nervosa, and binge eating disorder). However, little research was found on other types of EDs. There was emerging evidence that provided support for self-help, group, and computer/internet-based therapies. Overall, the findings highlighted that more research is required on novel eating disorder treatments beyond what is currently available and being used as 'gold standard'.

A randomised controlled trial of clinician supported vs self-help delivery of online cognitive behaviour therapy for Bulimia Nervosa.

High dropout rates and poor adherence associated with digital interventions have prompted research into modifications of these treatments to improve engagement and completion rates. This trial aimed to investigate the added benefit of clinician support when paired alongside a ten-session, online cognitive behaviour therapy (CBT) self-help intervention for bulimia nervosa (BN). As part of a three-arm, phase II randomised controlled trial, 114 participants (16 years or over) with full or subthreshold BN were randomly assigned to complete the intervention in a self-help mode (with administrative researcher contact; n = 38), with adjunct clinician support (weekly 30-minute videoconferencing sessions; n = 37), or a no-treatment waitlist control (WLC; n = 39). Baseline to post-treatment (12-weeks) decreases in objective binge episode frequency were significantly greater for clinician-supported participants as compared to WLC, but not for self-help when compared to WLC. However, due to continued improvements for self-help across follow-up (24-weeks), both arms outperformed WLC when analysed as an overall rate of change across three timepoints. Clinician-supported participants outperformed self-help in regards to laxative use and dietary restraint. Our results demonstrate that good clinical outcomes can be achieved with a relatively brief online CBT-based program even in the absence of structured clinical support, indicating a possible overreliance upon clinician support as a primary adherence-facilitating mechanism.

The acceptability, feasibility, and preliminary efficacy of a supported online self-help treatment program for binge-eating disorder.

Introduction: Studies in transdiagnostic eating disorder (ED) samples suggest supported online self-help programs (eTherapies) are effective and may improve access to treatment; however, their evaluation in those with binge-eating disorder (BED) is limited. Given BED's high prevalence and low levels of treatment uptake, further eTherapy evaluation is needed to broaden access to effective, evidence-based treatment options. The aim of this study was to investigate the acceptability, feasibility, and preliminary efficacy of a supported eTherapy for those with BED or subthreshold BED, and to examine symptom change across the duration of therapy. Method: Nineteen women with BED completed a supported, 10-session Cognitive Behavioural Therapy-based eTherapy in an uncontrolled, pre-post, and 3 months follow up intervention study. Key outcomes were assessed by the Eating Disorder Examination Questionnaire (EDE-Q): objective binge episode (OBE) frequency and ED psychopathology. Feasibility was evaluated via program adherence and dropout, whilst acceptability was assessed through participant feedback post-treatment. Weekly symptom change (ED psychopathology) during treatment was assessed by the Eating Disorder Examination - Questionnaire Short (EDE-QS). Results: Generalised estimating equations showed statistically and clinically significant reductions in OBEs and ED psychopathology (large effects) post-treatment, with these decreases maintained at follow up. Across weekly assessment, a marked slowing in the rate of change in ED psychopathology was observed after four sessions of the program. Program feasibility was high (i.e., 84% of content completed), as was program acceptability (i.e., 93% of participants expressed high levels of satisfaction). Discussion: These results support the acceptability, feasibility, and preliminary efficacy of a supported eTherapy program for those with BED and suggest the variability of symptom change across the duration of therapy. Future research should further investigate findings in an adequately powered randomised controlled trial.

International consensus on patient-centred outcomes in eating disorders.

The effectiveness of mental health care can be improved through coordinated and wide-scale outcome measurement. The International Consortium for Health Outcomes Measurement has produced collaborative sets of outcome measures for various mental health conditions, but no universal guideline exists for eating disorders. This Position Paper presents a set of outcomes and measures for eating disorders as determined by 24 international experts from professional and lived experience backgrounds. An adapted Delphi technique was used, and results were assessed through an open review survey. Final recommendations suggest outcomes should be tracked across four domains: eating disorder behaviours and cognitions, physical health, co-occurring mental health conditions, and quality of life and social functioning. Outcomes are collected using three to five patient-reported measures. For children aged between 6 years and 12 years, the measures include the Children's Eating Attitude Test (or, for those with avoidant restrictive food intake disorder, the Eating Disorder in Youth Questionnaire), the KIDSCREEN-10, and the Revised Children's Anxiety and Depression Screener-25. For adolescents aged between 13 years and 17 years, the measures include the Eating Disorder Examination Questionnaire (EDE-Q; or, for avoidant restrictive food intake disorder, the Nine-Item Avoidant Restrictive Food Intake Disorder Screener [NIAS]), the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), the two-item Generalised Anxiety Disorder (GAD-2), the seven-item Generalised Anxiety Disorder (GAD-7), and the KIDSCREEN-10. For adults older than 18 years, measures include the EDE-Q (or, for avoidant restrictive food intake disorder, the NIAS), the PHQ-2, the PHQ-9, the GAD-2, the GAD-7, the Clinical Impairment Assessment, and the 12-item WHO Disability Assessment Schedule 2.0. These questionnaires should be supplemented by information on patient characteristics and circumstances (ie, demographic, historical, and clinical factors). International adoption of these guidelines will allow comparison of research and clinical interventions to determine which settings and interventions work best, and for whom.

Pharmacotherapy, alternative and adjunctive therapies for eating disorders: findings from a rapid review.

BACKGROUND: The current review broadly summarises the evidence base for pharmacotherapies and adjunctive and alternative therapies in the treatment of eating disorders and disordered eating. METHODS: This paper forms part of a Rapid Review series examining the evidence base in the field of eating disorders. This was conducted to inform the Australian National Eating Disorder Research and Translation Strategy 2021-2030. ScienceDirect, PubMed and Ovid/Medline were searched for included studies published between 2009 and 2021 in English. High-level evidence such as meta-analyses, large population studies and randomised control trials were prioritised, and grey literature excluded. Data from included studies relating to pharmacotherapy, and to adjunctive and alternative therapies in eating disorders, were synthesised and disseminated in the current review. RESULTS: A total of 121 studies were identified, relating to pharmacotherapy (n = 90), adjunctive therapies (n = 21) and alternative therapies (n = 22). Some of the identified studies involved combinations of the above (e.g. adjunctive pharmacotherapy). Evidence of efficacy of interventions across all three categories was very limited with few relevant high quality clinical trials. There was a particular scarcity of evidence around effective treatments for anorexia nervosa (AN). With treatment of bulimia nervosa (BN), fluoxetine has exhibited some efficacy leading to regulatory approval in some countries. With binge eating disorder (BED), recent evidence supports the use of lisdexamfetamine. Neurostimulation interventions show some emerging efficacy in the treatment of AN, BN and BED but some, such as deep brain stimulation can be highly invasive. CONCLUSION: Despite widespread use of medications, this Rapid Review has identified a lack of effective medications and adjunctive and alternative therapies in the treatment of EDs. An intensification of high-quality clinical trial activity and drug discovery innovation are required to better assist patients suffering from EDs.

Eating disorders have the highest mortality rates and treatment costs of all mental health conditions. This rapid review summarises the evidence around the use of medications and various alternative therapies in the treatment of eating disorders. The review highlights a lack of effective interventions for the treatment of anorexia nervosa with an urgent need to trial new treatments for this condition. Two medications show some efficacy in treating other eating disorders: the antidepressant drug fluoxetine for the treatment of bulimia nervosa, and the stimulant drug lisdexamfetamine for binge eating disorder. There is some positive evidence emerging from novel therapies that involve brain stimulation technologies. Overall, more high-quality research is needed to discover and develop new medications, and other alternative therapies, to better assist patients with eating disorders.

Eating disorders in weight-related therapy (EDIT): Protocol for a systematic review with individual participant data meta-analysis of eating disorder risk in behavioural weight management.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

A descriptive analysis of scoring patterns on clinically relevant questionnaires in 26 adults with diagnosed muscle dysmorphia.

OBJECTIVE: Few studies have recruited adults with a formal diagnosis of muscle dysmorphia (MD), a psychological illness defined by preoccupation that one lacks muscularity and/or leanness, combined with significant functional impairment. This study presented descriptive statistics for a range of clinically relevant questionnaires in one of the largest samples of adults with confirmed diagnoses of MD. METHOD: We recruited 29 adults who met diagnostic criteria for MD as determined by semi-structured diagnostic interviews and administered a battery of questionnaires assessing MD symptomology, compulsive exercise, and disordered eating. Descriptive statistics were calculated for both total and subscale scores for each questionnaire. Raincloud plots are included to show the distribution of total scores. RESULTS: Of the 29 participants, 26 completed all questionnaires. Mean scores were high across all questionnaires and broadly consistent with results in past studies that also recruited a clinical MD sample. Most participants scored above proposed clinical cut-off scores for questionnaires assessing compulsive exercise and disordered eating. CONCLUSIONS: This study adds to the small body of published questionnaire data in clinical MD samples. We stress that questionnaire scores should not be used alone to infer the presence of MD, but could be considered as a useful adjunct to a comprehensive clinical interview.

Eating disorder outcomes: findings from a rapid review of over a decade of research.

BACKGROUND: Eating disorders (ED), especially Anorexia Nervosa (AN), are internationally reported to have amongst the highest mortality and suicide rates in mental health. With limited evidence for current pharmacological and/or psychological treatments, there is a grave responsibility within health research to better understand outcomes for people with a lived experience of ED, factors and interventions that may reduce the detrimental impact of illness and to optimise recovery. This paper aims to synthesise the literature on outcomes for people with ED, including rates of remission, recovery and relapse, diagnostic crossover, and mortality. METHODS: This paper forms part of a Rapid Review series scoping the evidence for the field of ED, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021-2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/MEDLINE were searched for studies published between 2009 and 2022 in English. High-level evidence such as meta-analyses, large population studies and Randomised Controlled Trials were prioritised through purposive sampling. Data from selected studies relating to outcomes for people with ED were synthesised and are disseminated in the current review. RESULTS: Of the over 1320 studies included in the Rapid Review, the proportion of articles focused on outcomes in ED was relatively small, under 9%. Most evidence was focused on the diagnostic categories of AN, Bulimia Nervosa and Binge Eating Disorder, with limited outcome studies in other ED diagnostic groups. Factors such as age at presentation, gender, quality of life, the presence of co-occurring psychiatric and/or medical conditions, engagement in treatment and access to relapse prevention programs were associated with outcomes across diagnoses, including mortality rates. CONCLUSION: Results are difficult to interpret due to inconsistent study definitions of remission, recovery and relapse, lack of longer-term follow-up and the potential for diagnostic crossover. Overall, there is evidence of low rates of remission and high risk of mortality, despite evidence-based treatments, especially for AN. It is strongly recommended that research in long-term outcomes, and the factors that influence better outcomes, using more consistent variables and methodologies, is prioritised for people with ED.

Eating disorders are complex psychiatric conditions that can seriously impact a person's physical health. Whilst they are consistently associated with high mortality rates and significant psychosocial difficulties, lack of agreement on definitions of recovery, remission and relapse, as well as variations in methodology used to assess for standardised mortality and disability burden, means clear outcomes can be difficult to report. The current review is part of a larger Rapid Review series conducted to inform the development of Australia's National Eating Disorders Research and Translation Strategy 2021­2031. A Rapid Review is designed to comprehensively summarise a body of literature in a short timeframe to guide policymaking and address urgent health concerns. This Rapid Review synthesises the current evidence-base for outcomes for people with eating disorders and identifies gaps in research and treatment to guide decision making and future clinical research. A critical overview of the scientific literature relating to outcomes in Western healthcare systems that may inform health policy and research in an Australian context is provided in this paper. This includes remission, recovery and relapse rates, diagnostic cross-over, the impact of relapse prevention programs, factors associated with outcomes, and findings related to mortality.

Appraisal of the costs, health effects, and cost-effectiveness of screening, prevention, treatment and policy-indicated evidence-based interventions for eating disorders: a systematic review protocol.

BACKGROUND: Having reliable information to make decisions about the allocation of healthcare resources is needed to improve well-being and quality-of-life of individuals with eating disorders (EDs). EDs are a main concern for healthcare administrators globally, particularly due to the severity of health effects, urgent and complex healthcare needs, and relatively high and long-term healthcare costs. A rigorous assessment of up-to-date health economic evidence on interventions for EDs is essential for informing decision-making in this area. To date, health economic reviews on this topic lack a comprehensive assessment of the underlying clinical utility, type and amount of resources used, and methodological quality of included economic evaluations. The current review aims to (1) detail the type of costs (direct and indirect), costing approaches, health effects, and cost-effectiveness of interventions for EDs; (2) assess the nature and quality of available evidence to provide meaningful insights into the health economics associated with EDs. METHODS: All interventions for screening, prevention, treatment, and policy-based approaches for all Diagnostic and Statistics Manual (DSM-IV and DSM-5) listed EDs among children, adolescents, and adults will be included. A range of study designs will be considered, including randomised controlled trials, panel studies, cohort studies, and quasi-experimental trials. Economic evaluations will consider key outcomes, including type of resources used (time and valued in a currency), costs (direct and indirect), costing approach, health effects (clinical and quality-of-life), cost-effectiveness, economic summaries used, and reporting and quality assessments. Fifteen general academic and field-specific (psychology and economics) databases will be searched using subject headings and keywords that consolidate costs, health effects, cost-effectiveness and EDs. Quality of included clinical studies will be assessed using risk-of-bias tools. Reporting and quality of the economic studies will be assessed using the widely accepted Consolidated Health Economic Evaluation Reporting Standards and Quality of Health Economic Studies frameworks, with findings of the review presented in tables and narratively. DISCUSSION: Results emanating from this systematic review are expected to highlight gaps in healthcare interventions/policy-focused approaches, under-estimates of the economic costs and disease-burden, potential under-utilisation of ED-related resources, and a pressing need for more complete health economic evaluations.

Gaining consensus on clinical quality outcomes for eating disorders: Framework for the development of an Australian national minimum dataset.

OBJECTIVES: Eating disorders (EDs) are complex psychiatric illnesses requiring multidisciplinary care across both mental and medical healthcare settings. Currently, no nationally comprehensive, consistent, agreed on or mandated data set or data collection strategy exists for EDs in Australia: thus, little is known about the outcomes of care nor treatment pathways taken by individuals with EDs. InsideOut Institute was contracted by the Australian Government Department of Health to develop a minimum dataset (MDS) for the illness group with consideration given to data capture mechanisms and the scoping of a national registry. DESIGN: A four-step modified Delphi methodology was used, including national consultations followed by three rounds of quantitative feedback by an expert panel. SETTING: Due to social distancing protocols throughout the global SARS-CoV-2 pandemic, the study was conducted online using video conferencing (Zoom and Microsoft Teams) (Step 1), email communication and the REDCap secure web-based survey platform (Steps 2-4). PARTICIPANTS: 14 data management organisations, 5 state and territory government departments of health, 2 Aboriginal and Torres Strait Islander advising organisations and 28 stakeholders representing public and private health sectors across Australia participated in consultations. 123 ED experts (including lived experience) participated in the first quantitative round of the Delphi survey. Retention was high, with 80% of experts continuing to the second round and 73% to the third. MAIN OUTCOME MEASURES: Items and categories endorsed by the expert panel (defined a priori as >85% rating an item or category 'very important' or 'imperative'). RESULTS: High consensus across dataset items and categories led to the stratification of an identified MDS. Medical status and quality of life were rated the most important outcomes to collect in an MDS. Other items meeting high levels of consensus included anxiety disorders, depression and suicidality; type of treatment being received; body mass index and recent weight change. CONCLUSIONS: Understanding presentation to and outcomes from ED treatment is vital to drive improvements in healthcare delivery. A nationally agreed MDS has been defined to facilitate this understanding and support improvements.

Semaphorin 4B is an ADAM17-cleaved adipokine that inhibits adipocyte differentiation and thermogenesis.

OBJECTIVE: The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis. METHODS: We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology. RESULTS: ADAM17adipoq-creΔ/Δ mice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues, that acts to inhibit adipocyte differentiation and dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to repress the expression of genes involved in adipogenesis, thermogenesis, and lipid uptake, storage and catabolism. CONCLUSIONS: Our findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that modulates energy balance in adipocytes by inhibiting adipocyte differentiation, thermogenesis and lipid catabolism.

Identifying Factors Which Influence Eating Disorder Risk during Behavioral Weight Management: A Consensus Study.

This study aimed to understand clinician, researcher and consumer views regarding factors which influence eating disorder (ED) risk during behavioral weight management, including individual risk factors, intervention strategies and delivery features. Eighty-seven participants were recruited internationally through professional and consumer organizations and social media and completed an online survey. Individual characteristics, intervention strategies (5-point scale) and delivery features (important/unimportant/unsure) were rated. Participants were mostly women (n = 81), aged 35-49 y, from Australia or United States, were clinicians and/or reported lived experience of overweight/obesity and/or ED. There was agreement (64% to 99%) that individual characteristics were relevant to ED risk, with history of ED, weight-based teasing/stigma and weight bias internalization having the highest agreement. Intervention strategies most frequently rated as likely to increase ED risk included those with a focus on weight, prescription (structured diets, exercise plans) and monitoring strategies, e.g., calorie counting. Strategies most frequently rated as likely to decrease ED risk included having a health focus, flexibility and inclusion of psychosocial support. Delivery features considered most important were who delivered the intervention (profession, qualifications) and support (frequency, duration). Findings will inform future research to quantitatively assess which of these factors predict eating disorder risk, to inform screening and monitoring protocols.