Factors influencing the duration of untreated illness among patients with anorexia nervosa: A multicenter and multi-informant study.

INTRODUCTION: The duration of untreated illness (DUI), that is, the interval between the onset of anorexia nervosa (AN) symptoms and start of specialized treatments, has a strong influence on the prognosis. OBJECTIVE: To quantify modifiable predictors of the DUI and to derive recommendations for secondary prevention strategies. METHODS: Within a multicenter, multi-informant study, DUI was assessed in interviews with patients undergoing first specialized AN treatment. Modifiable factors were assessed perspectives of AN-patients, their relatives, and primary care practitioners [PCPs]) with the FABIANA-checklist (Facilitators and barriers in anorexia nervosa treatment initiation). The effect of FABIANA-items on the DUI for each perspective was calculated using Cox Regression (control variables: age, eating disorder pathology, health care status, migration background, body mass index [BMI]). RESULTS: We included data from N = 125 female patients with AN (72 adults, 53 adolescents, Mage = 19.2 years, SD = 4.2, MBMI = 15.7 kg/m2 , SD = 1.9), N = 89 relatives (81.8% female, 18.2% male, Mage = 46.0 years, SD = 11.0) and N = 40 PCPs (Mage = 49.7 years, SD = 9.0). Average DUI was 12.0 months. Watching or reading articles about the successful treatment of other individuals with AN (patients' perspective) and regular appointments with a PCP (PCPs' perspective) were related to a shorter DUI (HR = 0.145, p = .046/ HR = 0.395, p = .018). Patients whose relatives rated that PCPs trivialized patients' difficulties had a longer DUI (HR = -0.147, p = .037). PCPs and relatives rated PCPs' competence higher than patients did. DISCUSSION: It is recommended (a) to incorporate treatment success stories in prevention strategies, (b) to inform PCPs about potential benefits of regular appointments during the transition to specialized care, and (c) to train PCPs in dealing with patients' complaints. PUBLIC SIGNIFICANCE: Many individuals with AN seek treatment very late. Our study shows that a promising approach to facilitate earlier AN treatment is to inform patients about successful treatments of affected peers, to foster regular appointments with a PCP and, to motivate these PCPs to take individuals' with AN difficulties seriously. Thus, our study provides important suggestions for interventions that aim to improve early treatment in AN.

The development and psychometric evaluation of FABIANA-checklist: a scale to assess factors influencing treatment initiation in anorexia nervosa.

BACKGROUND: A long duration of untreated illness (DUI) is an unfavorable prognostic factor in anorexia nervosa (AN) and is associated with chronic illness progression. Although previous preventive measures aimed at reducing DUI and thus improving short- and long-term treatment outcomes have been partially successful, a better understanding of the factors involved in the sensitive phase prior to treatment initiation is needed. To date, there is no validated instrument available to assess these factors specifically for patients with AN. The FABIANA-project (Facilitators and barriers in anorexia nervosa treatment initiation) aims at identifying predictors of the DUI in order to target preventive measures better in the future. As part of this project, the FABIANA-checklist was developed, based on a multi-informant perspective and a multimodal bottom-up approach. The present study focusses on the process of item generation, item selection and psychometric validation of the checklist. METHODS: Based upon a previous qualitative study, an initial set of 73 items was generated for the most frequently mentioned facilitators and barriers of treatment initiation in AN. After a process of consensual rating and cognitive pre-testing, the resulting 25-item version of the FABIANA-checklist was provided to a sample of female patients (N = 75), aged ≥ 14 years with AN that underwent their first psychotherapeutic treatment in the last 12 months. After item analysis, dimensionality of the final version of the FABIANA-checklist was tested by Principal Component Analysis (PCA). We evaluated construct validity assuming correlations with related constructs, such as perceived social support (F-SozU), support in the health care system (PACIC-5A), illness perception and coping (BIPQ). RESULTS: We included 54 adult and 21 adolescent patients with AN, aged on average 21.4 years. Average BMI was 15.5 kg/m2, age of onset was 19.2 years and average DUI was 2.25 years. After item analysis, 7 items were excluded. The PCA of the 18-item-FABIANA-checklist yielded six components explaining 62.64% of the total variance. Overall internal consistency was acceptable (Cronbach's α = .76) and construct validity was satisfactory for 14 out of 18 items. Two consistent components emerged: "primary care perceived as supportive and competent" (23.33%) and "emotional and practical support from relatives" (9.98%). With regard to the other components, the heterogeneity of the items led to unsatisfactory internal consistency, single item loading and in part ambiguous interpretability. CONCLUSIONS: The FABIANA-checklist is a valid instrument to assess factors involved in the process of treatment initiation of patients with AN. Psychometrics and dimensionality testing suggests that experienced emotional and practical support from the primary health care system and close relatives are main components. The results indicate that a differentiated assessment at item level is appropriate. In order to quantify the relative importance of the factors and to derive recommendations on early-intervention approaches, the predictive effect of the FABIANA-items on the DUI will be determined in a subsequent study which will further include the perspective of relatives and primary caregivers. Trial registration Clinical Trials.gov Identifier: NCT03713541: https://clinicaltrials.gov/ct2/show/NCT03713541 .

Early treatment contributes to a more favorable illness course and an improved prognosis in patients with anorexia nervosa (AN). The current study presents the development of the FABIANA checklist, which aims to assess factors which influence duration of untreated illness. The FABIANA checklist was developed on the basis of interviews with patients, their relatives and primary care practitioners. It provides data from the first use of the checklist in a German sample of 75 patients with AN. The results of our study suggest that the FABIANA-checklist is a valid instrument to assess factors involved in the process of treatment initiation. Emotional and practical support from the primary health care system and close relatives were the most consistent components. A follow-up study will investigate the relationship between the FABIANA-items and the DUI in order to guide the conception of effective secondary prevention measures.

Induction of heme-binding protein 23/peroxiredoxin I gene expression by okadaic acid in cultured rat hepatocytes.

Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A. In hepatocyte cultures HBP23/Prx I was highly expressed for up to 5 days and, both protein and mRNA levels of HBP23/Prx I were induced by OA. The time kinetics of OA-dependent HBP23/Prx I mRNA upregulation were coordinate to that of heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme-degradation. In contrast to HO-1, however, induction of HBP23/Prx I mRNA by OA was downregulated by dibutyryl-cAMP, and was enhanced by the specific protein kinase A inhibitors KT5720 and H-89. HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays.