A case series to test the acceptability, feasibility and preliminary efficacy of AVATAR therapy in anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa tend to experience an inner "eating disorder" voice. They struggle to recognise and assert their own identity over the illness's identity and relate to it from a powerless and subordinate position. AVATAR therapy was developed to help patients with psychosis to gain greater power and control over distressing voices. The goal of this study was to test the feasibility, acceptability, safety and preliminary efficacy of an adaptation of AVATAR therapy for anorexia nervosa. METHODS: Twelve adult patients with anorexia nervosa were recruited. Ten completed an assessment session and between five to seven therapy sessions. The assessment session consisted in the creation of an avatar to represent the "eating disorder". This was accomplished by manipulating auditory and visual characteristics through a specialist computer software. During the therapy sessions, patients interacted with the avatar to assert their own desires and will. Patients completed baseline, end of intervention and follow-up (4-week) online questionnaires. A non-concurrent multiple baselines single case experimental design (SCED) was used (A1BA2). Feasibility, acceptability, safety and preliminary efficacy of the intervention were assessed. RESULTS: The therapy met pre-specified criteria relating to (1) Feasibility: sample recruited within three months; retention rate at the end of the treatment phase = 81.9%; therapy completion rate = 90.1%. (2) Safety: no serious adverse events associated with the intervention. (3) Acceptability: mean ratings = 7.5 (SD = 2.61) out of ten, on a 0-10 scale of acceptability (10 = complete satisfaction). With regards to efficacy, participants reported significantly lower levels of distress associated with the eating disorder voice and higher levels of self-compassion at the end of treatment. No other significant changes were observed in frequency of the eating disorder voice, voice's characteristics, such as omnipotence and malevolence, eating disorder symptoms and symptoms of anxiety, depression and stress. Patients' feedback indicated that the therapy had helped with their ability to stand up to the illness, make positive changes around eating, and increase their motivation to recover and self-compassion. CONCLUSION: AVATAR therapy for anorexia nervosa is feasible, acceptable and safe for patients. Larger studies are needed to test clinical efficacy. TRIAL REGISTRATION: The study was pre-registered on the clinicaltrials.gov registry (https://clinicaltrials.gov/ct2/show/NCT04778423).

People with anorexia nervosa often struggle with connecting to their identity beyond the illness. They tend to relate to the eating disorder from a powerless and submissive position. The aim of this study was to test AVATAR therapy for anorexia nervosa. The goal of the intervention was to help patients to assert themselves, their identity, will, power and desires, when confronted with the "voice" of the illness. Twelve patients with anorexia nervosa were recruited and 10 completed one assessment session and five to seven therapy sessions. During the assessment session, patients were guided by the therapist to create a representation of their illness ("the avatar") by manipulating visual and auditory characteristics through a computer software. During treatment, they were supported by the therapist to assert themselves over the illness, responding to the abusive and critical comments of the eating disorder delivered by "the avatar". Patients' qualitative feedback indicated that the therapy was meaningful to them, and that it helped to recognise their own voice as distinct from the illness. The distress perceived in relation to the eating disorder voice decreased over time, and feelings of self-compassion increased at the end of therapy. Findings point towards the acceptability and usefulness of AVATAR therapy for anorexia nervosa. Larger studies are needed expand these results.

A proof-of-concept study for the use of a computerised avatar to embody the eating disorder voice in anorexia nervosa.

PURPOSE: This study assessed (1) the experience of the eating disorder voice in people with anorexia nervosa or in remission, and (2) the feasibility of creating and interacting with a computerised representation (i.e., avatar) of this voice. METHODS: Twenty-one individuals with anorexia nervosa and 18 individuals who were in remission participated in the study. They reported on the characteristics of their eating disorder voice and created a personalised avatar (a visual and auditory representation of the eating disorder voice), using a computerised software. Participants assessed closeness of match between the voice and the avatar, perceived distress and acceptability of re-exposure to the avatar. RESULTS: Patients felt less powerful than their eating disorder voice and unable to disregard the voice's commands. The experience of the voice was associated with negative, as well as some positive emotions, reflecting the prototypical ambivalence towards the illness. Individuals in remission had an opposite pattern of responses. They attributed only negative emotions to the voice, felt more powerful than the voice, and able to disregard its commands. Overall participants reported that there was a good match between the voice and the sound of the avatar. Patients expressed willingness to repeat exposure to the avatar. CONCLUSION: Individuals with anorexia can create personalised digital avatars representing the eating disorder voice and are willing to engage therapeutically with the avatar. The next step is to test the feasibility of repeated exposure to the avatar to address the power and distress associated with the eating disorder voice. LEVEL OF EVIDENCE: Level III.

Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer.

PURPOSE: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies. EXPERIMENTAL DESIGN: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy. RESULTS: Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience a pCR (23% vs. 40%; P = 0.07), had shorter event-free survival (29.4 vs. 32.2 months, P = 0.15), metastasis-free survival (30.3 vs. 32.4 months, P = 0.22); and overall survival (32.6 vs. 34.3 months, P = 0.21). This heterogeneity is mirrored in the molecular profiling. Mutations in PI3KCA (23% vs. 9%, P = 0.07) and its pathway (41% vs. 18%, P = 0.02) were frequently observed and enriched in MpBCs. The gene expression profiles of each histologically defined subtype were distinguishable and characterized by distinctive gene signatures. Among nonmetaplastic (non-Mp) TNBCs, 10% possessed a metaplastic-like gene expression signature and had pCR rates and survival outcomes similar to MpBC. CONCLUSIONS: Further investigations will determine if metaplastic-like tumors should be treated more similarly to MpBC in the clinic. The 23% pCR rate in this study suggests that patients with MpBC should be considered for NAT. To improve this rate, a pathway analysis predicted enrichment of histone deacetylase (HDAC) and RTK/MAPK pathways in MpBC, which may serve as new targetable vulnerabilities.

Breast cancer risk reduction--is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BACKGROUND: Breast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reduction. This study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP). METHODS: A 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity). At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women's, coaches, and radiographers' experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effect. RESULTS: A pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58 ± 5.6 years, mean BMI was 29.2 ± 7.0 kg/m(2) and many (44%) reported a family history of breast cancer. The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95% CI -3.24 kg to -0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others. CONCLUSIONS: Recruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects. TRIAL REGISTRATION: The trial was registered with Current Controlled Trials (ISRCTN56223933).

Centralization of services and reduction of adverse events in pancreatic cancer surgery.

BACKGROUND: The perioperative period is critical in the outcome for patients with pancreatic cancer. The aim of the present analysis was to examine adverse events in patients dying under surgical care in relation to changes in the organization of pancreatic cancer surgery. METHODS: From 1996 to 2005, 1,033 patients with pancreatic cancer, mean age of 71 years (range 21-97 years) died under surgical care. The incidence, mortality, and number of operations for pancreatic cancer remained stable across the time period, but the proportion of patients undergoing surgery in the five specialist cancer centers increased from 50 to 80 % (p < 0.001). Prior to death 260 (25 %) patients underwent operation and 96 (9 %) had endoscopic retrograde cholangiopancreatography (ERCP). There was a significant rise in ERCP (p = 0.03) and a decrease in non-resectional operations (p = 0.001). RESULTS: Since 1996, 52 (15 %) patients in whom 90 adverse events were recorded died following surgical intervention: 28 adverse events related to the perioperative period with 15 due to direct procedure complications such as bleeding or anastomotic leak; 13 were attributed to decision making around the choice or timing of the procedure. The postoperative mortality after curative pancreatic resection reduced from 3.5 to 1.8 %. Identified adverse events fell significantly in patients who died relating to the operative period (median of 3 per annum [1994-2000] to 1 per annum [2001-2005]) (p = 0.014) and medical care (3-0) (p = 0.003). CONCLUSIONS: Continuous peer review audit has demonstrated a reduction in the number of adverse events in patients dying with pancreatic cancer under surgical care as increased numbers of patients treated in specialist cancer centers.

The role of peri-operative cell salvage in instrumented anterior correction of thoracolumbar scoliosis: a case-controlled study.

Anterior scoliosis surgery is associated with potentially high blood loss, usually requiring allogenic transfusion either intra- or post-operatively. Blood loss in this type of surgery has been shown to correlate with surgical and anaesthetic techniques. In our centre the development of specific anaesthetic techniques as well as the routine use of cell salvage has dramatically reduced the rates of allogenic blood transfusion. Specific indications for the use of the cell saver in anterior scoliosis surgery have not been well defined. Previous studies have commented on the benefit from re-infusion of salvaged autologous blood for orthopaedic patients in general, whilst others have shown a negligible advantage specifically in anterior thoraco-lumbar fusion surgery. We carried out a retrospective study of 137 consecutive patients, all of whom underwent instrumented anterior scoliosis correction between March 1999 and September 2004. A study group consisting of 104 patients in whom a cell saver was used was compared with a control group consisting of 33 patients who underwent anterior instrumentation without cell saver. There was no significant difference in the mean ages, extent of surgery and male to female ratio between groups. In the control group 39.4% of patients required allogenic blood transfusion, versus 6.7% in the study group; the difference is statistically significant (p < 0.0001). A significant difference was also noted in post-operative haemoglobin values. The mean post-operative haemoglobin was 9.6 g/dl in the control group, versus 10.2 g/dl in the study group (p = 0.007). Our experience confirms that re-infusion of salvaged autologous blood in anterior scoliosis surgery has a role in the minimisation of postoperative anaemia and allogenic transfusion requirements in this type of surgery.

Dual growing rod technique followed for three to eleven years until final fusion: the effect of frequency of lengthening.

STUDY DESIGN: Retrospective case review of children completing dual growing rod treatment at our institutions. Patients had a minimum of 2 years follow-up. OBJECTIVE: To identify the factors influencing dual growing rod treatment outcome followed to final fusion. SUMMARY OF BACKGROUND DATA: Published reports on dual growing rod technique results for early onset scoliosis demonstrate it to be safe and effective in curve correction and maintenance as well as in allowing spinal growth. METHODS: Between 1990 and 2003, 13 patients with no previous surgery and noncongenital curves underwent final fusion. All had preoperative curve progression over 10 degrees after unsuccessful nonoperative treatment. There were 10 females and 3 males. Average age was 6.6 +/- 2.9 years at initial surgery. There were 3 idiopathic, 1 nonspine congenital anomaly, and 9 syndromic patients. Analysis included age at initial surgery and final fusion, number and frequency of lengthenings, and complications. Radiographic evaluation included changes in Cobb angle, T1-S1 length, and instrumentation length over the treatment period. RESULTS: Cobb angle improved from 81.0 +/- 23 degrees to 35.8 +/- 15 degrees postinitial and 27.7 +/- 17 degrees after final fusion. Average number of lengthenings was 5.2 +/- 3 at an interval of 9.4 +/- 5 months. T1-S1 length increased from 24.4 +/- 3.4 to 29.3 +/- 3.6 cm postinitial and 35.0 +/- 3.7 cm postfinal fusion. Average growth was 1.46 +/- 0.66 cm/year. Those lengthened at

Breast cancer (non-metastatic).

INTRODUCTION: Breast cancer affects at least 1 in 10 women in the UK, but most present with primary operable disease, which has an 80% 5-year survival rate overall. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions after breast-conserving surgery for ductal carcinoma in situ? What are the effects of treatments for primary operable breast cancer? What are the effects of interventions in locally advanced breast cancer (stage IIIB)? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 79 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding chemotherapy (cyclophosphamide/methotrexate/ fluorouracil and/or anthracycline and/or taxane-based regimens), or hormonal treatment to radiotherapy; adjuvant treatments (aromatase inhibitors, adjuvant anthracycline regimens, tamoxifen); axillary clearance; axillary dissection plus sentinel node dissection; axillary radiotherapy; axillary sampling; combined chemotherapy plus tamoxifen; chemotherapy plus monoclonal antibody (trastuzumab); extensive surgery; high-dose chemotherapy; hormonal treatment; less extensive mastectomy; less than whole breast radiotherapy plus breast conserving surgery; multimodal treatment; ovarian ablation; primary chemotherapy; prolonged adjuvant combination chemotherapy; radiotherapy (after breast-conserving surgery, after mastectomy, plus tamoxifen after breast-conserving surgery, to the internal mammary chain, and to the ipsilateral supraclavicular fossa, and total nodal radiotherapy); sentinel node biopsy; and standard chemotherapy regimens.

Dual growing rod technique for the treatment of progressive early-onset scoliosis: a multicenter study.

STUDY DESIGN: A retrospective case review of children treated with dual growing rod technique at our institutions. Patients included had no previous surgery and a minimum of 2 years follow-up from initial surgery. OBJECTIVES: To determine the safety and effectiveness of the previously described dual growing rod technique in achieving and maintaining scoliosis correction while allowing spinal growth. SUMMARY OF BACKGROUND DATA: Historically, the growing rod techniques have used a single rod and the reported results have been variable. There has been no published study exclusively on the results of dual growing rod technique for early-onset scoliosis. METHODS: From 1993 to 2001, 23 patients underwent dual growing rod procedures using pediatric Isola instrumentation and tandem connectors. Diagnoses included infantile and juvenile idiopathic scoliosis, congenital, neuromuscular, and other etiologies. All had curve progression over 10 degrees following unsuccessful bracing or casting. Of 189 total procedures within the treatment period, 151 were lengthenings with an average of 6.6 lengthenings per patient. Analysis included age at initial surgery and final fusion (if applicable), number and frequency of lengthenings, and complications. Radiographic evaluation included measured changes in scoliosis Cobb angle, kyphosis, lordosis, frontal and sagittal balance, length of T1-S1 and instrumentation over the treatment period, and space available for lung ratio. RESULTS: The mean scoliosis improved from 82 degrees (range, 50 degrees-130 degrees) to 38 degrees (range, 13 degrees-66 degrees) after initial surgery and was 36 degrees (range, 4 degrees-53 degrees) at the last follow-up or post-final fusion. T1-S1 length increased from 23.01 (range, 13.80-31.20) to 28.00 cm (range, 19.50-35.50) after initial surgery and to 32.65 cm (range, 25.60-41.00) at last follow-up or post-final fusion with an average T1-S1 length increase of 1.21 cm per year (range, 0.13-2.59). Seven patients reached final fusion. The space available for lung ratio in patients with thoracic curves improved from 0.87 (range, 0.7-1.1) to 1.0 (range, 0.79-1.23, P = 0.01). During the treatment period, complications occurred in 11 of the 23 patients (48%), and they had a total of 13 complications. Four of these patients (17%) had unplanned procedures. Following final fusion, 2 patients required extensions of their fusions because of curve progression and lumbosacral pain. CONCLUSION: The dual growing rod technique is safe and effective. It maintains correction obtained at initial surgery while allowing spinal growth to continue. It provides adequate stability, increases the duration of treatment period, and has an acceptable rate of complication compared with previous reports using the single rod technique.