Knowledge and attitudes towards eating disorders: A survey of psychiatrists and psychiatry trainees in New South Wales.

OBJECTIVE: To evaluate New South Wales (NSW) psychiatrists' and psychiatry trainees' knowledge and attitudes towards eating disorders (EDs). METHOD: A total of 1781 psychiatrists and trainees in NSW were invited to complete an anonymous questionnaire assessing ED confidence, knowledge and attitudes. RESULTS: A total of 51 doctors responded to the survey, with 38 completing all items. Significant knowledge gaps were revealed. Respondents expressed a desire for more ED training. CONCLUSION: Enhanced ED training in psychiatry education and incorporating the lived experience voice to improve attitudes appear necessary.

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.

Validating and developing a shortened version of the detail and flexibility (DFlex) questionnaire for eating disorders, anxiety and depression.

OBJECTIVE: To validate the original and a shortened version of the Detail and Flexibility (DFlex) Questionnaire. METHOD: Confirmatory factor analyses, internal consistency, and discriminant validity estimates were conducted within individuals with a diagnosis of an eating disorder (ED) (n = 124), an anxiety disorder and/or depression (n = 219), and a community sample (n = 852) (Part 1). Convergent validity of the DFlex through comparisons with the Autism Spectrum Quotient, Wisconsin Card Sorting Task, and Group Embedded Figures Task was undertaken within a combined ED and community sample (N = 68). Test-retest reliability of the DFlex was also examined across 2 years in a community sample (N = 85) (Part 2). RESULTS: The original factor structure of the DFlex was not supported. Hence, a shortened version, the DFlex-Revised, was developed. Good discriminant validity was obtained for the DFlex and DFlex-Revised, however, support for convergent validity was mixed. Finally, the 2-year test-retest reliability for the two DFlex versions was found to be low, suggesting potential malleability in construct over this timeframe. CONCLUSIONS: Further research is needed to validate the DFlex in clinical and non-clinical populations using different neurocognitive tests. Test-retest, using varied time intervals, should also be assessed.

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.

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.

Oxytocin and eating disorders: Knowledge gaps and future directions.

Eating disorders continue to be a major public health issue and important cause of morbidity and premature mortality, particularly for young people. Yet in a concerning dialectic, this occurs in the context of an epidemic of obesity which, with its medical complications, constitutes another vexing public health challenge. While it is not an eating disorder per se obesity is often comorbid with eating disorders. Effective treatment for both eating disorders and obesity has proven to be elusive and in the search for novel therapeutic interventions, the prosocial, anxiolytic, brain plasticity and metabolic effects of oxytocin (OT) have been examined from this perspective. The availability of intranasal oxytocin (IN-OT) has led to a number of interventional treatment studies in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), their atypical and subclinical forms and in medical and psychiatric conditions co-occurring or comorbid with these, obesity with BED would be included here. The aim of this mini review is to collate recent findings on OT as a novel therapeutic intervention in eating disorders and obesity and to identify and address some of the knowledge gaps in the use of IN-OT. The wider clinical perspective utilised here might better address some of the gaps and identify future directions of research. Clearly much remains to be done for OT to fulfil its therapeutic promise in eating disorders. OT might yet be of therapeutic promise and will be appreciated where treatment advances have been hard to come by and prevention challenging for these disorders.

Distinguishing delusional beliefs from overvalued ideas in Anorexia Nervosa: An exploratory pilot study.

BACKGROUND: Characterised by the belief that more weight needs to be lost-despite emaciation, failing organs, medical instability and prospect of death-Anorexia Nervosa (AN) is a condition in which irrational, and highly-skewed, beliefs can be of delusional intensity. However, the nexus between delusion and rational awareness and how this is related to body image acceptance and perception has yet to be examined in AN. The current study aims to investigate the relationship between body dissatisfaction and beliefs of delusional intensity in an adult AN inpatient sample. METHODS: Twenty-one adults (n(women) = 20; n(men) = 1), with a mean age of 27 years old (SD = 10), presenting for inpatient treatment for AN (ranging in severity from mild to severe; M(Body Mass Index) = 17 kg/m2; M(Length of Stay) = 22 days) participated in the study. Participants' dominant beliefs (related to AN) and level of insight (delusional; overvalued idea; or fair insight) were measured using either the Brown Assessment of Beliefs Scale (BABS) or the Nepean Beliefs Scale (NBS). The degree of body dissatisfaction was determined by examining the discrepancy between "perceived" and "ideal" body perception. To determine subjective and objective beliefs both the Contour Drawing Rating Scale (subjective) and computerised Body Image Assessment Software (objective) were used. RESULTS: Almost one quarter (23.7%; n = 5) of participants appeared to have beliefs of delusional intensity related to their body shape (M = 27.4; SD = 23.03). Although a positive linear trend was indicated, there were no significant differences in body dissatisfaction scores between level-of-insight. Individuals whose belief was categorised as delusional were more likely to hold a negative affective body image state based on their ratings on the body image state survey when compared to the group who had good/fair insight (95% CI [0.53, 18.19]; p = 0.03). CONCLUSIONS: The current exploratory pilot study concurs with others in the published literature that demonstrate that approximately 25 percent of participants with AN may have delusional ideas. The implications for treatment in similar samples warrant attention. Future research should also seek to understand the clinical significance of this delusional categorisation, the benefits of its utility in this population, and its relation to the severity of AN or stage of illness.

Anorexia Nervosa (AN) is notable for the individual's conviction that they need to lose weight­even when they are dangerously underweight- or to prevent weight gain. However, how these beliefs relate to the emotional experience of the body, in the presence of AN need to be explored further. This study begins to examine this relationship. Twenty-one adults (95% women; average age 27 years) receiving in-patient treatment for AN were asked a series of questions related to beliefs about their body. To allow a comparison between the level-of-insight and body shape dissatisfaction, participants were also asked to rate how satisfied or dissatisfied they were about their body shape. Almost 25% of the sample had beliefs of delusional intensity about their body shape. Further, it was also found that people with AN who had stronger beliefs of delusional intensity were more likely to be dissatisfied with their body shape. This pilot study appears to support previous research that suggests that some individuals with AN have stronger beliefs of delusional intensity. The findings from the current study should be extended with future research looking at the impact of beliefs on illness and treatment.

Neural Response to Low Energy and High Energy Foods in Bulimia Nervosa and Binge Eating Disorder: A Functional MRI Study.

Objective: Bulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating (BE) episodes. Overlap exists between ED diagnostic groups, with BE episodes presenting one clinical feature that occurs transdiagnostically. Neuroimaging of the responses of those with BN and BED to disorder-specific stimuli, such as food, is not extensively investigated. Furthermore, to our knowledge, there have been no previous published studies examining the neural response of individuals currently experiencing binge eating, to low energy foods. Our objective was to examine the neural responses to both low energy and high energy food images in three emotive categories (disgust; fear; and happy) in BN and BED participants. Methods: Nineteen females with BN (n = 14) or BED (n = 5), comprising the binge eating group (BEG; N = 19), and 19 age-matched healthy control (HC)'s completed thorough clinical assessment prior to functional MRI (fMRI). Neural response to low energy and high energy foods and non-food images was compared between groups using whole-brain exploratory analyses, from which six regions of interest (ROI) were then selected: frontal, occipital, temporal, and parietal lobes; insula and cingulate. Results: In response to low energy food images, the BEG demonstrated differential neural responses to all three low energy foods categories (disgust; fear; and happy) compared to HCs. Correlational analyses found a significant association between frequency of binge episodes and diminished temporal lobe and greater occipital lobe response. In response to high energy food images, compared to HC's, the BEG demonstrated significantly decreased neural activity in response to all high energy food images. The HC's had significantly greater neural activity in the limbic system, occipital lobe, temporal lobe, frontal lobe, and limbic system in response to high energy food images. Conclusion: Results in the low energy food condition indicate that binge frequency may be related to increased aberrant neural responding. Furthermore, differences were found between groups in all ROI's except the insula. The neural response seen in the BEG to disgust food images may indicate disengagement with this particular stimuli. In the high energy food condition, results demonstrate that neural activity in BN and BED patients may decrease in response to high energy foods, suggesting disengagement with foods that may be more consistent with those consumed during a binge eating episode.

The mind-in-mind study: A pilot randomised controlled trial that compared modified mentalisation based treatment with supportive clinical management for patients with eating disorders without borderline personality disorder.

OBJECTIVE: Mentalisation-based treatment (MBT) aims to improve reflective functioning. There is a growing evidence base outlining positive clinical outcomes for the use of MBT in eating disorder patients with co-morbid borderline personality disorder (BPD). The use of MBT has not been studied for eating disorder patients without BPD. This pilot study is an exploratory randomised controlled trial in which outcomes from MBT are compared with standard clinical management in a cohort of patients diagnosed with an eating disorder but not BPD. The main objectives were two-fold-to explore the use of MBT as a therapeutic modality and to test the acceptability and feasibility of the protocol design. METHOD: Thirty-two participants were randomised to receive either MBT or standard treatment during an inpatient eating disorders program. All patients enrolled in the study were diagnosed with an eating disorder but did not meet DSM-5 criteria for BPD. On admission patients were categorised as very underweight (BMI 15.0-16.4 kg/m2 ), underweight (BMI 16.5-18.4 kg/m2 ) or healthy weight range (BMI ≥ 18.5-24.9 kg/m2 ). Upon discharge participants were further categorised as weight restored (BMI ≥ 18.5 kg/m2 ) or non-weight restored (BMI < 18.5 kg/m2 ). The primary outcome was the subscale score on the Reflective Functioning Questionnaire (RFQ-8). Secondary outcomes were subscale scores on the Eating Disorder Examination Questionnaire and the Depression, Anxiety and Stress Scale (DASS)-21. Participants were assessed at baseline and on discharge. Statistical significance was determined using repeated measurements analysis of variance (ANOVA). RESULTS: Both groups experienced improvements in eating disorder symptoms and measures of psychological well-being. Participants within the MBT group exhibited greater improvements in reflective capacity as defined by the RFQ-8 however these benefits appeared to be limited to patients who achieved weight restoration at discharge. The eligibility criteria-which excluded comorbid BPD-led to challenges in recruitment which limited the power of the study analysis. As participants with a range of different eating disorder diagnoses were included this led to complexities in estimating the treatment effect within a defined cohort. CONCLUSIONS: Although the small sample size must be noted as a limitation-the finding that weight restoration appears to be associated with improvements in reflective capacity in MBT would be worth exploring in a subsequent larger study. Modification of eligibility criteria and recruitment from a defined cohort may increase the efficiency of a future study.

A standard enteral formula versus an iso-caloric lower carbohydrate/high fat enteral formula in the hospital management of adolescent and young adults admitted with anorexia nervosa: a randomised controlled trial.

BACKGROUND: The nutritional rehabilitation of malnourished patients hospitalised with anorexia nervosa is essential. The provision of adequate nutrition must occur, while simultaneously, minimising the risk of refeeding complications, such as electrolyte, metabolic, and organ dysfunction. The aim of this study was to compare the efficacy and safety of an iso-caloric lower carbohydrate/high fat enteral formula (28% carbohydrate, 56% fat) against a standard enteral formula (54% carbohydrate, 29% fat). METHODS: Patients (aged 15-25 years) hospitalised with anorexia nervosa were recruited into this double blinded randomised controlled trial. An interim analysis was completed at midpoint, when 24 participants, mean age 17.5 years (± 1.1), had been randomly allocated to lower carbohydrate/high fat (n = 14) or standard (n = 10) feeds. RESULTS: At baseline, there was no significant difference in degree of malnutrition, medical instability, history of purging or serum phosphate levels between the two treatment arms. A significantly lower rate of hypophosphatemia developed in patients who received the lower carbohydrate/high fat formula compared to standard formula (5/14 vs 9/10, p = 0.013). The serum phosphate level decreased in both feeds, however it decreased to a larger extent in the standard feed compared to the lower carbohydrate/high fat feed (standard feed 1.11 ± 0.13 mmol/L at baseline vs 0.88 ± 0.12 mmol/L at week 1; lower carbohydrate/high fat feed 1.18 ± 0.19 mmol/L at baseline vs 1.06 ± 0.15 mmol/L at week 1). Overall, serum phosphate levels were significantly higher in the lower carbohydrate/high fat feed compared with standard feed treatment arm at Week 1 (1.06 ± 0.15 mmol/L vs 0.88 ± 0.12 mmol/L, p < 0.001). There was no significant difference in weight gain, number of days to reach medical stability, incidence of hypoglycaemia, or hospital length of stay. CONCLUSIONS: The results of this study indicate that enteral nutrition provided to hospitalised malnourished young people with anorexia nervosa using a lower carbohydrate/high fat formula (28% carbohydrate, 56% fat) seems to provide protection from hypophosphatemia in the first week compared to when using a standard enteral formula. Further research may be required to confirm this finding in other malnourished populations. TRIAL REGISTRATION: ANZCTR, ACTRN12617000342314. Registered 3 March 2017, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000342314.

Patients hospitalised with anorexia nervosa require nutrition support as part of their treatment, whilst refeeding complications are prevented. Of particular concern, is the reintroduction of carbohydrate to malnourished patients, which has been proposed to cause a surge in insulin levels and disturbance in electrolytes, particularly a decrease in blood phosphate levels. This double-blinded randomised controlled trial measured the occurrence of low phosphate blood levels and other refeeding complications, in adolescent and young adult patients hospitalised with anorexia nervosa. These patients were provided either a lower carbohydrate/high fat feed (28% carbohydrate, 56% fat) or a standard enteral feed (54% carbohydrate, 29% fat). Fewer patients in the lower carbohydrate/high fat feed group (5/14) than standard feed group (9/10) developed a low phosphate level. There was no significant difference in weight gain, number of days to reach medical stability, occurrence of hypoglycaemia, or hospital length of stay.

Supported online cognitive behavioural therapy for bulimia nervosa: a study protocol of a randomised controlled trial.

BACKGROUND: Despite the availability of effective treatments for bulimia nervosa (BN), a number of barriers to accessibility exist. Examples include access to trained clinicians, the expense of treatment, geographical limitations, and personal limitations such as stigma regarding help seeking. Self-help interventions, delivered via a digital platform, have the potential to overcome treatment gaps by providing patients with standardised, evidence-based treatments that are easily accessible, cost-effective, and require minimal clinician support. Equally, it is important to examine the shortcomings of digital interventions when compared to traditional to face-to-face delivery (e.g., high dropout rates) in order to maximise the therapeutic effectiveness of online, self-help interventions. METHODS: A three-arm, multisite randomised controlled trial will be conducted in Australia examining the effectiveness and cost-effectiveness of a newly developed online self-help intervention, Binge Eating eTherapy (BEeT), in a sample of patients with full or sub-threshold BN. The BEeT program consists of 10, multimedia sessions delivering the core components of cognitive behaviour therapy. Eligible participants will be randomised to one of three groups: independent completion of BEeT as a purely self-help program, completion of BEeT alongside clinician support (in the form of weekly telemedicine sessions), or waitlist control. Assessments will take place at baseline, weekly, post-intervention, and three-month follow up. The primary outcome is frequency of objective binge episodes. Secondary outcomes include frequency of other core eating disorder behavioural symptoms and beliefs, psychological distress, and quality of life. Statistical analyses will examine treatment effectiveness, feasibility, acceptability and cost effectiveness. DISCUSSION: There is limited capacity within the mental health workforce in Australia to meet the demand of people seeking treatment for eating disorders. This imbalance has only worsened following outbreak of the COVID-19 pandemic. Further research is required into innovative digital modes of treatment delivery with the capacity to service mental health needs in an accessible and affordable manner. Self-help programs may also appeal to individuals who are more reluctant to engage in traditional face-to-face treatment formats. This study will provide rigorous evidence on how to diversify treatment options for individuals with BN, ensuring more people with the illness can access evidence-based treatment. The study has been registered with the Australia New Zealand Clinical Trials Registry (ANZCTR Registration Number: ACTRN12619000123145p). Registered 22 January 2019, https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619000123145 .

Study protocol for a randomised controlled trial investigating two different refeeding formulations to improve safety and efficacy of hospital management of adolescent and young adults admitted with anorexia nervosa.

INTRODUCTION: Providing effective nutritional rehabilitation to patients hospitalised with anorexia nervosa (AN) is challenging, partly due to conservative recommendations that advocate feeding patients at low energy intakes. An 'underfeeding syndrome' can develop when patients are not provided with adequate nutrition during treatment, whereby malnourished patients fail to restore weight in a timely matter, and even lose weight. Of particular concern, the reintroduction of carbohydrate in a starved patient can increase the risk of developing electrolyte, metabolic and organ dysfunction. The proposed trial assesses the efficacy and safety of a lower carbohydrate enteral formula (28% carbohydrate) against a standard enteral formula (54% carbohydrate), in adolescent and young adult patients (aged 15-25 years), hospitalised with AN. METHODS AND ANALYSIS: The study employs a double-blind randomised controlled trial design. At admission to hospital, malnourished adolescent and young adults with AN will be randomly allocated to commence feeding on a standard enteral feeding formula (1.5 kcal/mL, 54% carbohydrate) or a lower carbohydrate isocaloric enteral feeding formula (1.5 kcal/mL, 28% carbohydrate). Assessments of nutritional intake, weight and biochemistry (phosphate, magnesium, potassium) will be conducted at baseline and during the first 3 weeks of hospital admission. The primary outcome measure will be incidence of hypophosphatemia. Secondary outcomes include weight gain, oedema, other electrolyte distortion, length of hospital admission, admission to the Intensive Care Unit (ICU) and number of days to reach medical stability, using defined parameters. ETHICS AND DISSEMINATION: The protocol was approved by the Western Sydney Local Health District Human Research Ethics Committee and institutional research governance approvals were granted. Written informed consent will be sought prior to study enrolment. Study findings will be widely disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12617000342314); Pre-results.

A relationship-based approach to improving clinical trials: The imCORE research network experience.

The rapid evolution of cancer immunotherapies has increased demand for timely introduction of new therapies and subsequently increased the demand on leading cancer research institutions worldwide. As a leader in cancer therapy research, Roche created the immunotherapy Centers of Research Excellence (imCORE) Network, a worldwide research network designed to more closely connect members in an open environment of shared information, expertise, and decisions. This network is dedicated to increasing the understanding of the underlying science in order to prioritize and accelerate the most promising new treatment options for patients. The network consists of two key pillars, Roche-sponsored clinical trials operational excellence and the imCORE network scientific collaborations. This paper focuses on the Roche-sponsored trial clinical operational excellence aspects of the network. This special contribution introduces the rationale, design, and success factors of sponsored trials within the imCORE Network, including critical components and examples of tangible improvements to clinical trial operations between the company sponsor and the trial sites. Pivotal success factors have included relationship architecture and management, transparent communication channels, open information-sharing, and the development of new processes and tools to overcome historical inefficiencies and challenges of all sizes. The shared dedication of stakeholders to cancer therapy innovation, operational improvement of clinical trials, and a durable, sustainable worldwide research collaborative has made this component of imCORE effective to date. The authors share this experience with the broader research community for the first time, in the same spirit of collective advancement of care for patients with cancer.

Harm minimization in severe and enduring anorexia nervosa.

For many sufferers of anorexia nervosa, the time course is long, and the prospect of disability and family burden great. This is all too often the case, even with early diagnosis and treatment. The term severe and enduring anorexia nervosa has been applied to these survivors. Yet, a majority of patients do eventually recover and, even where this is not the case, adaptive medical stability and function can be maintained despite alarming dilapidation. Managing the years of illness so as to have the best outcome physically and psychologically, even where full weight recovery does not occur, or has not yet occurred, is the topic of this article. Literature pertaining to harm minimization in chronic, severe, enduring, and long-standing anorexia nervosa was selectively reviewed using an Ovid data base and Google Scholar. The authors' own clinical experience over almost four decades in public and private hospital and community settings has also informed much of what has been written. The authors would like to think that it is possible to do better than the familiar injunction (variously attributed to Hippocrates, Galen, and others) of 'primum non nocere'-although this is a good place to start.

Novel Role of T Cells and IL-6 (Interleukin-6) in Angiotensin II-Induced Microvascular Dysfunction.

Hypertension is an established risk factor for subsequent cardiovascular diseases, with Ang II (angiotensin II) playing a major role in mediating thrombotic and inflammatory abnormalities. Although T cells and IL-6 (interleukin-6) play an important role in adaptive immune responses, little is known about their role(s) in the thromboinflammatory responses associated with Ang II. Here we show using intravital microscopy coupled with the light/dye injury model that Rag-1 deficient (Rag-1-/-) and IL-6 deficient (IL-6-/-) mice are afforded protection against Ang II-induced thrombosis. Blocking IL-6 receptors (using CD126 and gp130 antibodies) significantly diminished Ang II-mediated thrombosis and inflammatory cell recruitment in mice. Furthermore, the adoptive transfer of IL-6-/--derived T cells into Rag-1-/- mice failed to accelerate Ang II-induced thrombosis compared with Rag-1-/- mice reconstituted with wild-type-derived T cells, suggesting T cell IL-6 mediates the thrombotic abnormalities associated Ang II hypertension. Interestingly, adoptive transfer of WT T cells into Rag-1-/-/Ang II mice resulted in increased numbers of immature platelets, which constitutes a more active platelet population, that is, prothrombotic and proinflammatory. To translate our in vivo findings, we used clinical samples to demonstrate that IL-6 also predisposes platelets to an interaction with collagen receptors, thereby increasing the propensity for platelets to aggregate and cause thrombosis. In summary, we provide compelling evidence for the involvement of IL-6, IL-6R, and T-cell-dependent IL-6 signaling in Ang II-induced thromboinflammation, which may provide new therapeutic possibilities for drug discovery programs for the management of hypertension.

Beliefs about Binge Eating: Psychometric Properties of the Eating Beliefs Questionnaire (EBQ-18) in Eating Disorder, Obese, and Community Samples.

Binge eating is a core diagnostic feature of bulimia nervosa, binge eating disorder, anorexia nervosa binge/purge type, and is a common feature of "other specified" and "unspecified" feeding and eating disorders. It has been suggested that specific metacognitive beliefs about food, eating, and binge eating may play a key role in the maintenance of binge eating behaviour. The Eating Beliefs Questionnaire (EBQ-18) provides a brief self-report assessment tool measuring three types of metacognitive beliefs: negative, positive, and permissive beliefs about food and eating. This study aimed to build on past research by validating the factor structure and psychometric properties of the EBQ-18 using both a clinical and non-clinical sample. A sample of 688 participants (n = 498 non-clinical participants, n = 161 participants seeking treatment for an eating disorder, and n = 29 participants seeking treatment for obesity) completed a battery of questionnaires, including the EBQ-18 and other measures of eating disorder symptoms and relevant constructs. A subset of 100 non-clinical participants completed the test battery again after an interval of two-weeks, and 38 clinical participants completed the EBQ-18 before and after receiving psychological treatment for their eating disorder. A confirmatory factor analysis (CFA) was conducted and psychometric properties of this measure were assessed. The results of this study provide support for the three-factor model of the EBQ-18. In addition, the EBQ-18 was found to be a valid and reliable measure, with excellent internal consistency, good test-retest reliability in the non-clinical sample, and also demonstrated evidence of sensitivity to treatment in clinical samples with binge eating pathology. Receiver operating characteristic (ROC) curve analyses were used to identify optimal cut-off scores for the EBQ-18. This study provides valuable information about the utility of the EBQ-18 as a measure for use in both clinical and research settings.

Neuroimaging in bulimia nervosa and binge eating disorder: a systematic review.

OBJECTIVE: In recent decades there has been growing interest in the use of neuroimaging techniques to explore the structural and functional brain changes that take place in those with eating disorders. However, to date, the majority of research has focused on patients with anorexia nervosa. This systematic review addresses a gap in the literature by providing an examination of the published literature on the neurobiology of individuals who binge eat; specifically, individuals with bulimia nervosa (BN) and binge eating disorder (BED). METHODS: A systematic review was conducted in accordance with PRISMA guidelines using PubMed, PsycInfo, Medline and Web of Science, and additional hand searches through reference lists. 1,003 papers were identified in the database search. Published studies were included if they were an original research paper written in English; studied humans only; used samples of participants with a diagnosed eating disorder characterised by recurrent binge eating; included a healthy control sample; and reported group comparisons between clinical groups and healthy control groups. RESULTS: Thirty-two papers were included in the systematic review. Significant heterogeneity in the methods used in the included papers coupled with small sample sizes impeded the interpretation of results. Twenty-one papers utilised functional Magnetic Resonance Imaging (fMRI); seven papers utilized Magnetic Resonance Imaging (MRI) with one of these using both MRI and Positron Emission Technology (PET); three studies used Single-Photon Emission Computed Tomography (SPECT) and one study used PET only. A small number of consistent findings emerged in individuals in the acute phase of illness with BN or BED including: volume reduction and increases across a range of areas; hypoactivity in the frontostriatal circuits; and aberrant responses in the insula, amygdala, middle frontal gyrus and occipital cortex to a range of different stimuli or tasks; a link between illness severity in BN and neural changes; diminished attentional capacity and early learning; and in SPECT studies, increased rCBF in relation to disorder-related stimuli. CONCLUSIONS: Studies included in this review are heterogenous, preventing many robust conclusions from being drawn. The precise neurobiology of BN and BED remains unclear and ongoing, large-scale investigations are required. One clear finding is that illness severity, exclusively defined as the frequency of binge eating or bulimic episodes, is related to greater neural changes. The results of this review indicate additional research is required, particularly extending findings of reduced cortical volumes and diminished activity in regions associated with self-regulation (frontostriatal circuits) and further exploring responses to disorder-related stimuli in people with BN and BED.

A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40-/-, and CD40L-/- mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; α5ß1) antagonist, ATN-161. Our results demonstrate that CD40-/-, CD40L-/-, and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40-/- or CD40L-/- mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

Depression and cardiac dysautonomia in eating disorders.

PURPOSE: Individuals with eating disorder (ED) are at an increased risk of cardiac arrhythmias due to cardiac dysautonomia, which may be exacerbated if depression is also present. The aim of the study was to use heart rate analysis as a marker for cardiac dysautonomia in patients with eating disorders and depression as a comorbidity. METHODS: Clinical data, including presence of depression, was obtained from all participants. A three-lead ECG was used to determine interbeat intervals, and these were analyzed using time domain, frequency domain, and nonlinear heart rate variability measures. RESULTS: Thirty ED patients and 44 healthy controls participated in the research. The presence of depression was associated with additional decreased time domain (RMSSD 36.8 ± 26 vs. 22.9 ± 12.3; p < 0.05), frequency domain (HF power 788 ± 1075 vs. 279 ± 261; p < 0.05), and nonlinear domain (DFAα2 0.82 ± 0.1 vs. 0.97 ± 0.1; p < 0.01) which results in the ED group compared to patients with no depression. CONCLUSIONS: The presence of depression in ED patients decreased HRV even further compared to the non-depressed patient group and controls, suggesting that higher vigilance and a holistic treatment approach may be required for these patients to avoid cardiac arrhythmia complications.