An overview of genetic services delivery for hereditary breast cancer.

Breast cancer is the most common cancer diagnosed in women worldwide, with approximately 5-10% of cases attributed to high penetrance hereditary breast cancer (HBC) genes. The tremendous advances in precision oncology have broadened indications for germline genetic testing to guide both systemic and surgical treatment, with increasing demand for cancer genetic services. The HBC continuum of care includes (1) identification, access, and uptake of genetic counseling and testing; (2) the delivery of genetic counseling and testing services; and (3) initiation of guideline-adherent follow-up care and family communication of results. Challenges to delivering care on the HBC care continuum include factors such as access to services, cost, discrimination and bias, and lack of education and awareness, which can be mitigated through implementing a multi-level approach. This includes strategies such as increasing awareness and utilization of genetic counseling and testing, developing new methods to meet the growing demand for genetic services, and improving the uptake of follow-up care by increasing patient and provider awareness of the management recommendations.

Framework for Implementing and Tracking a Molecular Tumor Board at a National Cancer Institute-Designated Comprehensive Cancer Center.

BACKGROUND: Over the past few years, tumor next-generation sequencing (NGS) panels have evolved in complexity and have changed from selected gene panels with a handful of genes to larger panels with hundreds of genes, sometimes in combination with paired germline filtering and/or testing. With this move toward increasingly large NGS panels, we have rapidly outgrown the available literature supporting the utility of treatments targeting many reported gene alterations, making it challenging for oncology providers to interpret NGS results and make a therapy recommendation for their patients. METHODS: To support the oncologists at Vanderbilt-Ingram Cancer Center (VICC) in interpreting NGS reports for patient care, we initiated two molecular tumor boards (MTBs)-a VICC-specific institutional board for our patients and a global community MTB open to the larger oncology patient population. Core attendees include oncologists, hematologist, molecular pathologists, cancer geneticists, and cancer genetic counselors. Recommendations generated from MTB were documented in a formal report that was uploaded to our electronic health record system. RESULTS: As of December 2020, we have discussed over 170 patient cases from 77 unique oncology providers from VICC and its affiliate sites, and a total of 58 international patient cases by 25 unique providers from six different countries across the globe. Breast cancer and lung cancer were the most presented diagnoses. CONCLUSION: In this article, we share our learning from the MTB experience and document best practices at our institution. We aim to lay a framework that allows other institutions to recreate MTBs. IMPLICATIONS FOR PRACTICE: With the rapid pace of molecularly driven therapies entering the oncology care spectrum, there is a need to create resources that support timely and accurate interpretation of next-generation sequencing reports to guide treatment decision for patients. Molecular tumor boards (MTB) have been created as a response to this knowledge gap. This report shares implementation strategies and best practices from the Vanderbilt experience of creating an institutional MTB and a virtual global MTB for the larger oncology community. This report describe a reproducible framework that can be adopted to initiate MTBs at other institutions.

The emotional face of anorexia nervosa: The neural correlates of emotional processing.

Social-emotional processing difficulties have been reported in Anorexia Nervosa (AN), yet the neural correlates remain unclear. Previous neuroimaging work is sparse and has not used functional connectivity paradigms to more fully explore the neural correlates of emotional difficulties. Fifty-seven acutely unwell AN (AAN) women, 60 weight-recovered AN (WR) women and 69 healthy control (HC) women categorised the gender of a series of emotional faces while undergoing Functional Magnetic Resonance Imaging. The mean age of the AAN group was 19.40 (2.83), WR 18.37 (3.59) and HC 19.37 (3.36). A whole brain and psychophysical interaction connectivity approach was used. Parameter estimates from significant clusters were extracted and correlated with clinical symptoms. Whilst no group level differences in whole brain activation were demonstrated, significant group level functional connectivity differences emerged. WR participants showed increased connectivity between the bilateral occipital face area and the cingulate, precentral gyri, superior, middle, medial and inferior frontal gyri compared to AAN and HC when viewing happy valenced faces. Eating disorder symptoms and parameter estimates were positively correlated. Our findings characterise the neural basis of social-emotional processing in a large sample of individuals with AN.

The neural correlates of a central coherence task in young women with anorexia nervosa.

OBJECTIVE: Heightened detail-processing and low levels of central coherence are common in individuals with anorexia nervosa (AN) and predict poorer prognosis. However, it is unclear whether these processing styles predate the disorder or, rather, emerge during later stages of AN. The current study aimed to address this question by investigating central coherence, and the neural correlates of central coherence, in a sample of young women with AN with shorter duration of illness than previous studies recruiting adult samples. METHODS: We recruited 186 participants, including: 73 young women with AN, 45 young women weight-recovered from AN, and 68 age-matched controls. Participants completed the Embedded Figures Task during an fMRI scan. RESULTS: There were no significant differences between the participant groups in performance accuracy or reaction time. There were no other between-groups differences in neural response to the Embedded Figures Task. CONCLUSIONS: These findings contrast with evidence from older adults demonstrating differences in the neural underpinning of central coherence amongst participants with AN versus control participants. The current study adds to an increasing literature base demonstrating the resilience of neuropsychological traits and associated brain systems in the early stages of AN.

Assessing the impact of First Episode Rapid Early Intervention for Eating Disorders on duration of untreated eating disorder: A multi-centre quasi-experimental study.

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.

A pilot evaluation of a novel First Episode and Rapid Early Intervention service for Eating Disorders (FREED).

This pilot study assesses the impact of FREED (First Episode Rapid Early Intervention for Eating Disorders [ED]), a novel transdiagnostic service for emerging adults with recent ED onset, on clinical outcomes. Data were collected from 56 patients and 19 carers for 12 months following enrolment. FREED patients showed significant improvements in ED and other symptoms across time. Carers also showed psychological improvements. For FREED anorexia nervosa (AN) patients, body mass index (BMI) at initial clinical assessment was similar to that of comparable patients (audit cohort) seen in our service before (16.4 vs 16.1 kg/m2 ). By start of treatment, because of their shorter wait, FREED-AN had gained weight whereas audit patients had lost (16.7 vs 15.8 kg/m2 ). This difference continued throughout treatment, and at 12 months, nearly 60% FREED-AN patients returned to a BMI of 18.5 or greater. FREED shows promise as a service model for emerging adults with EDs.

How resistant is 'treatment-resistant' obsessive-compulsive disorder in youth?

OBJECTIVES: Obsessive-compulsive disorder (OCD) is often perceived as being difficult to treat. This study aimed to test the hypothesis that treatment non-response in routine clinical practice is often due to failures in the delivery of treatment, and that most patients who are apparently treatment-resistant will respond to treatment if adequately delivered. DESIGN: Retrospective cohort data analysis. METHODS: Forty-three young people with severe, treatment-resistant OCD (defined as Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS] scores ≥ 30 and non-response to previous cognitive behaviour therapy [CBT] and selective serotonin reuptake inhibitors) were referred to a specialist clinic and completed a course of manualized CBT, with (N = 21) or without (N = 22) optimization of medication. A sub-sample (N = 15) completed a semi-structured interview to determine characteristics of their previous CBT; quality was assessed according to pre-determined criteria. RESULTS: Specialist treatment was associated with significant reductions in OCD symptoms at post-treatment with gains maintained at 3-month follow-up. At the 3-month follow-up, 58% of patients showed a meaningful clinical response (≥ 35% drop on the CY-BOCS) and 22% were in remission (≤ 12 on the CY-BOCS). Patients whose medication was optimized tended (non-significantly) to have better responses. The quality of previous CBT was assessed in a sub-group of participants and rated as inadequate in 95.5% of cases. The most common inadequacy was insufficient focus on exposure techniques. CONCLUSIONS: These findings provide support for the notion that treatment non-response in routine practice may be due to technical treatment failures and highlight the need to disseminate good quality evidence-based treatment among this population. Research is also needed to understand factors that impede outcome to further improve response and remission rates. PRACTITIONER POINTS: Among young people with OCD, failure to respond to treatment in routine clinical practice may often reflect the nature of the treatment received. Exposure techniques may often be overlooked in CBT for OCD, potentially resulting in poor therapeutic response. Most young people with severe and apparent treatment-resistant OCD respond to outpatient CBT incorporating E/RP. Further research is needed to establish effective methods for disseminating good quality CBT for OCD.

Exploring emotion recognition in adults and adolescents with anorexia nervosa using a body motion paradigm.

OBJECTIVE: There is consistent evidence of difficulties in social cognition in adults with anorexia nervosa (AN), but less is known about adolescents. The aim of this study was to investigate the ability to recognise emotion expressed in body movement in adults and adolescents with AN. METHOD: One hundred and ninety-three females participated in the study (AN = 97: 61 adults and 36 adolescents). The performance of participants with AN on a body emotion recognition task was compared to age-matched healthy controls (HC = 96). RESULTS: AN participants were significantly worse than HC recognising sadness, with adolescent AN participants showing worse performance overall. There were no difficulties in the recognition of other emotions. DISCUSSION: The results partially support previous studies and the literature on facial emotion recognition, showing poorer recognition of sadness in AN. The results also suggest that difficulties in emotion recognition through body movements may be more subtle than other socio-emotional difficulties observed in AN.

Set shifting in children and adolescents with anorexia nervosa: an exploratory systematic review and meta-analysis.

OBJECTIVE: Set shifting inefficiencies in adults with anorexia nervosa (AN) are established, however the neurocognitive profile of children and adolescents with AN is less clear. This study aimed to provide a review of the literature. METHOD: Electronic databases were used to search for manuscripts. RESULTS: Meta-analysis was performed on seven studies using two neuropsychological tests (Trail Making Task, TMT; Wisconsin Card Sorting Task, WCST). The mean difference in outcome between AN and healthy control (HC) groups was standardized by calculating Cohen's d. Meta-analysis of TMT studies showed a nonsignificant negative, pooled standardized mean difference of -0.005 (95% C.I. -0.416 to 0.406, z = 0.02, p = .98). WCST studies revealed a nonsignificant pooled effect size of d = 0.196 (95% C.I. -0.091-0.483, z = 1.34, p = .18). Studies which did not allow for a calculation of effect size typically showed a nonsignificant, worse performance by the AN groups. DISCUSSION: The inefficiencies in set shifting that are apparent in the adult AN literature do not appear to be as pronounced in children. This may suggest that set shifting difficulties in adult AN are the result of starvation or indicative of longer duration of illness. Larger studies are needed to confirm these impressions.

Exploring the role of insomnia in the relation between PTSD and pain in veterans with polytrauma injuries.

BACKGROUND: Soldiers returning from Operation Enduring Freedom/Operation Iraqi Freedom experience polytrauma injuries including traumatic brain injury. Traumatic brain injury is often complicated by symptoms of insomnia, posttraumatic stress disorder (PTSD), and pain that can impact treatment and rehabilitation. METHODS: The medical records of 137 veterans seen at a Veterans Affairs Medical Center Polytrauma clinic who sustained traumatic brain injury in combat were reviewed for this study. Demographic variables include age, sex, ethnicity, military branch, and service connection. Outcome measures include PTSD, pain, and insomnia. RESULTS: Analyses revealed a high prevalence of PTSD, insomnia, and pain co-occurring in 51.8% of veterans. Increased PTSD symptomatology was significantly correlated with reports of more pain severity (r = 0.53), pain interference (r = 0.61), and insomnia (r = 0.67). Further analyses, controlling for service connection, indicated that insomnia partially mediated the relation between PTSD and both pain severity and interference. CONCLUSIONS: These results highlight the overlap and complexity of presenting complaints in veterans and help identify the role of sleep disturbances in complicating diagnosis and treatment of veterans. As sleep problems reduce pain tolerance and exacerbate other symptoms, such as cognitive deficits and irritability, failure to address sleep disturbances may compromise rehabilitation efforts, suggesting the importance of a multidisciplinary team approach to assessing and treating these veterans.

Is poor global processing a transdiagnostic feature of Body Dysmorphic Disorder and Anorexia Nervosa? A meta-analysis.

Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are characterised by body image disturbance. It has been suggested that poor global integration in visual processing may underlie distorted body image, but empirical studies have yielded mixed results. The current study involved two meta-analyses aimed at examining the extent to which poor global processing is evident in BDD and AN. Studies were identified through a systematic literature search up to October 2020. The BDD search yielded 16 studies and the AN search yielded 18 studies. Random-effect models demonstrated a small pooled effect size for BDD (g = -0.44, 95 % CI -0.70, -0.17, p < 0.001) and a moderate pooled effect size for AN (g = -0.63, 95 % CI -0.77, -0.49, p <  .001), with no evidence of significant publication bias for either. The results provide evidence that poor global processing is a transdiagnostic feature of both BDD and AN, although effects may be more pronounced in AN. Our findings highlight the possibility that interventions aimed at promoting global visual processing could prove beneficial in disorders characterised by distorted body image.

Assessing implementation fidelity in the First Episode Rapid Early Intervention for Eating Disorders service model.

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.

Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

People with anorexia nervosa (AN) commonly exhibit social difficulties, which may be related to problems with understanding the perspectives of others, commonly known as Theory of Mind (ToM) processing. However, there is a dearth of literature investigating the neural basis of these differences in ToM and at what age they emerge. This study aimed to test for differences in the neural correlates of ToM processes in young women with AN, and young women weight-restored (WR) from AN, as compared to healthy control participants (HC). Based on previous findings in AN, we hypothesized that young women with current or prior AN, as compared to HCs, would exhibit a reduced neural response in the medial prefrontal cortex (mPFC), the inferior frontal gyrus, and the temporo-parietal junction (TPJ) whilst completing a ToM task. We recruited 73 young women with AN, 45 WR young women, and 70 young women without a history of AN to take part in the current study. Whilst undergoing a functional magnetic resonance imaging (fMRI) scan, participants completed the Frith-Happé task, which is a commonly used measure of ToM with demonstrated reliability and validity in adult populations. In this task, participants viewed the movements of triangles, which depicted either action movements, simple interactions, or complex social interactions. Viewing trials with more complex social interactions in the Frith-Happé task was associated with increased brain activation in regions including the right TPJ, the bilateral mPFC, the cerebellum, and the dorsolateral prefrontal cortex. There were no group differences in neural activation in response to the ToM contrast. Overall, these results suggest that the neural basis of spontaneous mentalizing is preserved in most young women with AN.

Corrigendum: Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

[This corrects the article DOI: 10.3389/fpsyg.2020.568073.].

Cost-effectiveness analysis of telephone cognitive-behaviour therapy for adolescents with obsessive-compulsive disorder.

BACKGROUND: Telephone cognitive-behaviour therapy (TCBT) may be a cost-effective method for improving access to evidence-based treatment for obsessive-compulsive disorder (OCD) in young people.AimsEconomic evaluation of TCBT compared with face-to-face CBT for OCD in young people. METHOD: Randomised non-inferiority trial comparing TCBT with face-to-face CBT for 72 young people (aged 11 to 18) with a diagnosis of OCD. Cost-effectiveness at 12-month follow-up was explored in terms of the primary clinical outcome (Children's Yale-Brown Obsessive-Compulsive Scale, CY-BOCS) and quality-adjusted life-years (QALYs) (trial registration: ISRCTN27070832). RESULTS: Total health and social care costs were higher for face-to-face CBT (mean total cost £2965, s.d. = £1548) than TCBT (mean total cost £2475, s.d. = £1024) but this difference was non-significant (P = 0.118). There were no significant between-group differences in QALYs or the CY-BOCS and there was strong evidence to support the clinical non-inferiority of TCBT. Cost-effectiveness analysis suggests a 74% probability that face-to-face CBT is cost-effective compared with TCBT in terms of QALYs, but the result was less clear in terms of CY-BOCS, with TCBT being the preferred option at low levels of willingness to pay and the probability of either intervention being cost-effective at higher levels of willingness to pay being around 50%. CONCLUSIONS: Although cost-effectiveness of TCBT was sensitive to the outcome measure used, TCBT should be considered a clinically non-inferior alternative when access to standard clinic-based CBT is limited, or when patient preference is expressed.Declaration of interestD.M.-C. reports research grants from the Swedish Research Council (Vetenskapsrådet), the Swedish Research Council for Health, working life and welfare (Forte), the US National Institute of Mental Health (NIMH), the UK National Institute of Health Research (NIHR), as well as royalties from Wolters Kluwer Health and Elsevier, all unrelated to the submitted work.

Computerised analysis of facial emotion expression in eating disorders.

BACKGROUND: Problems with social-emotional processing are known to be an important contributor to the development and maintenance of eating disorders (EDs). Diminished facial communication of emotion has been frequently reported in individuals with anorexia nervosa (AN). Less is known about facial expressivity in bulimia nervosa (BN) and in people who have recovered from AN (RecAN). This study aimed to pilot the use of computerised facial expression analysis software to investigate emotion expression across the ED spectrum and recovery in a large sample of participants. METHOD: 297 participants with AN, BN, RecAN, and healthy controls were recruited. Participants watched film clips designed to elicit happy or sad emotions, and facial expressions were then analysed using FaceReader. RESULTS: The finding mirrored those from previous work showing that healthy control and RecAN participants expressed significantly more positive emotions during the positive clip compared to the AN group. There were no differences in emotion expression during the sad film clip. DISCUSSION: These findings support the use of computerised methods to analyse emotion expression in EDs. The findings also demonstrate that reduced positive emotion expression is likely to be associated with the acute stage of AN illness, with individuals with BN showing an intermediate profile.

Group cognitive remediation therapy for younger adolescents with anorexia nervosa: a feasibility study in a Japanese sample.

OBJECTIVE: Cognitive remediation therapy (CRT) aims to increase patients' cognitive flexibility by practicing new ways of thinking as well as facilitating bigger picture thinking, supporting patients with relevant tasks and encouraging an awareness of their own thinking styles. CRT has been applied in the treatment of adult anorexia nervosa (AN), and has been shown to be effective and acceptable. In adolescents, CRT has been piloted on both individual and group format. However, no studies are published in CRT for adolescents with AN in a Japanese sample. The objectives of this study were to assess the feasibility, to estimate effect sizes for the purpose of designing a larger study, and to assess the acceptability of a CRT group for younger adolescents with AN in a Japanese sample. METHODS: Group CRT interventions were carried out with a total of seven adolescents with AN. Neuropsychological and psychological assessments (motivation, self-efficacy and depression) were administered before and after the group intervention. The participants completed worksheets (documents of participants' thinking about their thinking style and the relation of the skills that they learnt through each session to real-life) and questionnaires after the group. RESULTS: There were small effect sizes differences between the part of the pre and post neuropsychological tests and the pre and post ability to change (motivation). There were medium effect sizes differences between the pre and post depressive symptoms and importance to change (motivation). There was a large effect size shown between the pre and post weights. All participants were able to reflect on their own thinking styles, such as having difficulty with changing feelings and the tendency to focus on details in real-life. Adolescents' feedback was positive, and the rate of dropout was low. CONCLUSION: CRT groups could be feasible and acceptable for younger adolescents with AN in a Japanese sample. Trial registration UMIN No. 000020623. Registered 18 January 2016.

Is inefficient cognitive processing in anorexia nervosa a familial trait? A neuropsychological pilot study of mothers of offspring with a diagnosis of anorexia nervosa.

OBJECTIVES: Inefficient set shifting and poor global processing are thought to be possible traits in anorexia nervosa (AN). This study aimed to investigate the neuropsychological processing style of unaffected mothers of offspring with AN (unaffected AN mothers). METHODS: The performance of 21 unaffected AN mothers were compared to 20 mothers of healthy control offspring on neuropsychological measures of set shifting (Wisconsin Card Sorting Test, WCST) and central coherence (Fragmented Pictures Task, FPT, and Rey Osterrieth Complex Figures Task, ROCFT). Associations between neuropsychological performance and clinical measures were examined in the unaffected AN mothers group. RESULTS: There were significant differences in perseverative errors on the WCST (P≤0.01), with the unaffected mothers displaying a more inflexible thinking style compared to the control group. There were also significant differences on the FPT (P ≤ 0.01) and the ROCFT (P ≤ 0.01), whereby unaffected AN mothers showed lower levels of global processing. CONCLUSIONS: The results of this study support the idea of the familial nature of cognitive styles in AN. The implications of these findings are discussed.

Factors Affecting Health Care Utilization in OEF/OIF Veterans: The Impact of PTSD and Pain.

OBJECTIVES: Returning Operation Enduring Freedom and Operation Iraqi Freedom veterans are at a high risk for physical and mental health symptoms including pain (90%) and post-traumatic stress disorder (PTSD) (58%). These often present concurrently and result in many health problems, functional impairments, and overall poor rehabilitation. To address postdeployment health, effective and efficient allocation of health care resources is needed. METHODS: Retrospective study of 144 veterans who completed a second-level screening in the Polytrauma clinic. Veterans completed the PTSD Checklist-Civilian Version. Their pain rating and health care utilization (sum of visits during 12 months, categorized as medical or mental health) was extracted through chart review. RESULTS: The majority of veterans reported significant PTSD (72%) and pain (87%) symptoms; 45% received adequate mental health treatment, defined as ≥8 sessions in 12 months. PTSD and the interaction with pain predicted medical utilization; at high pain levels veterans' PTSD severity predicted utilization. PTSD alone predicted mental health utilization. CONCLUSIONS: The results show the increased influence of PTSD symptoms on medical health care services when pain ratings are high and suggest the need for interdisciplinary pain clinics that are able to address the overlapping symptoms of pain and common mental health conditions. Implication of results for VA planning are discussed.