Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study.

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Comorbid mental disorders during long-term course in a nationwide cohort of patients with anorexia nervosa.

OBJECTIVE: Comorbid mental disorders in anorexia nervosa during long-term course require detailed studies. METHOD: This matched cohort study was based on nationwide Danish register data of all patients born 1961-2008 with a first-time ICD-10 diagnosis of anorexia nervosa (AN) between 1994 and 2018 at age 8-32 and matched controls taken from all individuals without an eating disorder (ED). For nine categories of non-eating mental disorders, time from date of first AN-diagnosis (inclusion date) to time of first diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9,985 patients with AN (93.5% females) and 49,351 matched controls were followed for a median (IQR) of 9.0 (4.4-15.7) years. For patients, there was about 25% and 55% risk of receiving any non-ED disorder during the first 2 years and two decades after inclusion, respectively. A hazard ratio (HR) of seven for any non-ED was found for the first 12 months after inclusion, a ratio that reduced to two at five or more years after inclusion. During the first years, large HRs ranging in 6-9 were found for affective, autism spectrum, personality, and obsessive-compulsive disorders with the latter displaying the highest continuous increased risk. The HR at 12 months after inclusion was highest for any non-ED disorder and affective disorders in patients aged 8-13 at diagnosis. DISCUSSION: Comorbid mental disorders in AN are most frequently diagnosed in the first years after diagnosis of AN and on longer terms imply a double immediate risk.

Explanatory Factors for Disease-Specific Health-Related Quality of Life in Women with Anorexia Nervosa.

A better understanding of explanatory factors for disease-specific health-related quality of life (HRQoL) in anorexia nervosa (AN) could help direct treatment providers to aspects of the most relevance for patient wellbeing and recovery. We aimed to investigate whether factors associated with HRQoL are the same for women with AN and normal-weight controls. The participants in this study were women with AN recruited from specialized eating disorder centers in Denmark and healthy, normal-weight controls invited via online social media. Participants completed online questionnaires on medical history, disease-specific HRQoL (Eating Disorders Quality of Life Scale, EDQLS) and generic HRQoL (SF-36), eating disorder symptomatology, depression, psychological wellbeing, and work and social adjustment. Questionnaires were fully completed by 211 women with AN (median age 21.7 years) and 199 controls (median age 23.9 years). Women with AN had poorer scores on all measures, i.e., worse HRQoL, psychological health, and work/social functioning. Eating disorder symptomatology affected EDQLS score in both groups, but poorer HRQoL in women with AN was also significantly associated with worse scores on bulimia, maturity fears, depression, vitality, and with older age. The factors investigated together explained 79% of the variance in EDQLS score. Management of disordered self-assessment and thought processes may be of particular importance to women with AN. Greater emphasis on these aspects alongside weight gain could enhance patient-clinician alliance and contribute to better treatment outcomes.

Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment.

BACKGROUND: Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services-related studies are lacking. The present study was a descriptive exploration of time-trends in treatment modes of patients with free and equal access to health services. METHODS: The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994-2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered. RESULTS: The cohort of patients with AN with at least 5 years of follow-up amounted to N = 7,505. A clear trend was observed in the per patient five-year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five-year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits. CONCLUSIONS: The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.

Assessment of fracture risk in women with eating disorders: The utility of dual-energy x-ray absorptiometry (DXA)-Clinical cohort study.

OBJECTIVE: Eating disorders (EDs) are associated with decreased bone mineral density (BMD) and increased fracture risk. The association between BMD and fracture risk in EDs is not well elucidated. We aimed to assess BMD in an ED cohort of patients with active disease and patients in remission, and to assess the predictive value of BMD on incidence of fractures. METHOD: We included 344 female patients (median age 19, IQR 16; 24) referred to ED treatment. Later, patients were invited to follow-up including assessment of remission status and a dual-energy x-ray absorptiometry (DXA)-scan. Information on fractures was obtained through the Danish National Registry of Patients. RESULTS: Patients with current anorexia nervosa (AN) had significantly lower BMD compared to controls at lumbar spine (16% lower, p < .0001), femoral neck (18% lower, p < .0001), and total hip (23% lower, p < .0001). Recovered AN patients had higher BMD compared to those with current disease (p < .0001 for all measures), but lower BMD compared to controls at lumbar spine (p < .01) and hip (p < .001). BMD did not differ between BN patients and controls. In patients with active eating disorders not otherwise specified, BMD was lower only at the total hip (p < .005). We found no association between BMD and fracture risk. CONCLUSION: We confirm that AN is associated with low BMD, whereas BN is not. Remission is associated with higher BMD compared to patients with active AN, but a deficit remains. We found no significant association between BMD and fracture risk, challenging the benefit of the widespread use of DXA scans in young women with ED. CLINICAL TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov, number NCT00267228.

Hunger and satiety perception in patients with severe anorexia nervosa.

OBJECTIVES: Appetite is a subjective essential sense. In patients with severe anorexia nervosa (AN), controversy remains whether this sensation is altered. The objectives were to clarify, in patients with severe AN: (1) Whether the appetite changes during partial weight restoration, (2) Whether potential changes in appetite are related to (i) diagnostic subtype of AN, (ii) psychopharmacological treatment, (iii) disease duration, (iv) duration of hospitalization, and (v) baseline body mass index (BMI). METHODS: The study consisted of 39 patients, with a mean age of 23.7 ± 8 and an admission mean BMI of 13.1 ± 2.0 kg/m2. The patients were consecutively admitted to a specialized somatic nutrition unit between 2015 and 2016. They were asked to rate their hunger and satiety on a numeric visual analog scale (VAS), before and after a lunch meal at admission and at discharge in the same standardized environment. The patients could participate more than once if readmitted, resulting in a total of 119 observed meals. Data were analyzed in a regression model for repeated measures. RESULTS: At admission, changes in hunger and satiety perception were weak. After weight gain of 10.4% ± 8.5% within a median of 26 (IQR: 25) days, there was a slight increase in hunger perception, p = 0.049. However, there was no detectable change in satiety perception. There was no noticeable correlation between appetite change and psychopharmacological treatment, diagnostic subtype, BMI, duration of hospitalization, and disease duration. CONCLUSION: Hospitalized patients with severe AN exhibit strikingly weak changes in hunger and satiety perception during standardized and supervised meals. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series analysis.

A Danish translation of the eating disorder quality of life scale (EDQLS).

BACKGROUND: In Denmark, only generic health-related quality of life measures have been developed to assess quality of life in patients with eating disorders. So far, no disease-specific questionnaires have been translated and validated. The objective of this study was to translate the Eating Disorders Quality of Life Scale into Danish and to perform a preliminary validation of the questionnaire in a small sample. METHODS: The translation process was conducted according to recommendations from the World Health Organization, using the WHO-5 Well-Being Index as a reference standard. The validation process included 41 outpatients with eating disorders. Patients were recruited from specialized outpatient clinics in the Capital Region of Denmark and asked to complete the quality of life questionnaire and the WHO-5 Well-Being Index. RESULTS: This study found poor agreement, but high correlation, between the two self-rating scales. CONCLUSION: The translated questionnaire was concluded to be valid. However, a replication study on a larger sample with more male patients and more extensive symptoms is necessary.

Funen Anorexia Nervosa Study - a follow-up study on outcome, mortality, quality of life and body composition.

Eating disorders (EDs) comprise a wide range of symptoms, with severe psychological and physical implications for the patient. EDs include anorexia nervosa (AN), bulimia nervosa (BN) and until 2013 eating disorder not otherwise specified (EDNOS), if criteria for AN or BN were not met. Patients suffering from an ED have poor prognosis, with more than half of AN patients not obtaining complete remission. One-fifth develops a chronic disease. EDs have an increased risk of premature death and patients with EDs report poorer quality of life (QoL) compared to both the general population and other psychiatric/somatic diseases. Patients who, apparently, obtain complete remission will still be affected in QoL when compared to a healthy reference group. Treatment is complicated by high drop-out rates, hence making large retrospective follow-up studies difficult to conduct. The multiple endocrine disturbances as a result of the severe malnourishment in AN often result in amenorrhea and a weight goal for remenorrhea has been ambiguous. This thesis encompasses results from four studies examining the abovementioned challenges and is based on a large retrospective cohort of ED patients referred to a highly specialized ED treatment unit. Study 1: QoL in EDs was reported for a large retrospective Danish cohort. Furthermore, meta-analysis on existing published literature was performed to determine potential differences between the diagnostic groups. QoL in EDs was significantly decreased compared to the general population and no difference between the diagnostic groups was established. Study 2: ED pathology (measured by the Eating Disorder Inventory - 2 (EDI-2)) and outcome (measured by the Morgan Russell Outcome Schedule (MROS)) was reported for a large retrospective Danish cohort. The correlation between the patient-reported measurements (SF-36 & EDI-2) and clinician-assessed characteristics (BMI and remission status) was investigated in a group of ED patients (n=383). A high association between EDI scores and BMI was observed in AN and EDNOS, despite remission status, representing an increase in symptomatology with increasing BMI. This was not present in BN. We found no association between HRQoL and BMI in any of the diagnostic groups. Study 3:  Mortality rates were calculated in a large group of ED patients (n=998) including AN, BN and EDNOS with a long follow-up time. We found a SMR of 2.9 for AN, which was considerably lower than previous published results. We compared the results to data from the same catchment area published prior to the establishment of a multidisciplinary ED center. Patients with EDs had a significantly increased risk of premature death compared to the general population; however the mortality rates had decreased since the formation of the ED unit. Study 4: The association between body composition measures and amenorrhea was studied in a cohort of adult patients with a history of AN (n=113) and predicted probabilities for the resumption of menses was determined. We found a high association between DXA scans and BMI in predicting the resumption of menses. Half of the patients were predicted to resume their menstrual status at BMI 19/fat percentage 23, however at BMI 14/fat percentage 11 still 25% of patients were predicted to resume their menses.

The Role of Body Weight on Bone in Anorexia Nervosa: A HR-pQCT Study.

Anorexia nervosa (AN) is associated with decreased bone mineral density and increased risk of fracture. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), trabecular microarchitecture and estimated failure load in weight-bearing vs. non-weight-bearing bones in AN. We included twenty-five females with AN, and twenty-five female controls matched on age and height. Bone geometry, vBMD and trabecular microarchitecture were assessed using high-resolution peripheral quantitative computed tomography of the distal radius and tibia. At both sites, cortical perimeter and total bone area were similar in patients and controls. Total vBMD was lower in the AN group in the tibia (p < 0.0005) but not in the radius. In the tibia, cortical thickness was approximately 25% lower (p < 0.0005) in the AN group, whereas there was no significant difference in the radius. In terms of trabecular microarchitecture, all indices [bone volume/tissue volume (BV/TV); trabecular thickness (Tb.Th.), trabecular number (Tb.N) and trabecular spacing (Tb.Sp.)] were impaired in AN in the tibia (p values range < 0.01-0.0001). In the radius, BV/TV and Tb.N were lower (p < 0.05 and p < 0.001, respectively); Tb.Sp. was higher (p < 0.001), whereas Tb.Th. did not differ, compared to controls. Estimated failure load was lower in patients in both the radius and the tibia (p < 0.0005 and p < 0.0001, respectively), most pronounced in the tibia. In conclusion, the impairment of cortical thickness and estimated failure load were significantly more pronounced in the weight-bearing tibia, compared to the non-weight-bearing radius, implying a direct effect of low body weight on bone loss in AN.

Body composition and menstrual status in adults with a history of anorexia nervosa-at what fat percentage is the menstrual cycle restored?

OBJECTIVE: To study the association between body composition measures and menstrual status in a large sample of adult patients with a history of anorexia nervosa and to calculate the predicted probability of resumption of menstrual function. Furthermore, to establish whether fat percentage is superior to body mass index in predicting the resumption of menses. METHOD: One hundred and thirteen adult women with a history of anorexia nervosa underwent a dual energy X-ray absorptiometry (DXA) scan and completed questionnaires regarding medication prescription and menstrual function. RESULTS: Fifty percent of patients were expected to resume their menstrual function at a body mass index of 19 kg m-2 or a fat percentage of 23%. Twenty-five percent of patients were expected to resume their menstrual function at body mass index 14 kg m-2 or fat percentage 11%. Fat percentage and body mass index were equally capable of predicting the resumption of menses. DISCUSSION: Fat percentage and body mass index were positive predictors of the resumption of menses, however, body composition measured by dual energy X-ray absorptiometry was not superior to body mass index in predicting menstrual recovery, which is of great clinical relevance as body mass index is easier and cheaper to obtain. Body composition measures only account for one of numerous factors involved in the resumption of menses. Regression models based on our data had a R2 value of 0.14, indicating that only 14% of the variation in menstrual recovery could be explained by the variables included. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:370-377).

Patient- and clinician- reported outcome in eating disorders.

Patient-reported outcome is increasingly applied in health sciences. Patients with eating disorders (EDs) characteristically have a different opinion of their needs to that of the health professionals, which can lead to ambivalence towards treatment and immense compliance difficulties. This cross-sectional study compared data assessed by the clinician to patient-reported measures in patients with a history of EDs. We included data from a cohort of patients with EDs (n=544) referred to a specialized ED unit in Denmark. Patient-reported measures included the Eating Disorder Inventory-2 (EDI-2) and the Short Form 36 (SF-36), and clinical data included remission status and body mass index (BMI). We found a positive association between BMI and EDI-2 scores for anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS), reflecting increasing ED symptomatology with increasing BMI. This association was not observed in bulimia nervosa (BN). We did not find a correlation between SF-36 scores and BMI in any of the diagnostic groups.

Does specialization of treatment influence mortality in eating disorders?--A comparison of two retrospective cohorts.

Eating disorders (EDs) are psychiatric disorders associated with high morbidity and mortality. It is well established that patients with anorexia nervosa (AN) have an increased risk of premature death, whereas mortality data are lacking for the other EDs. This study aimed to establish mortality rates in a sample of ED patients (n=998) with a mean follow-up of 12 years. This was compared to previous data from the same catchment area before a multidisciplinary centre was established. The standardized mortality ratio (SMR) was calculated. To compare the two cohorts, adjusted crude ratios were calculated with the confounding variables: body mass index (BMI), age at referral and diagnosis. In the latest cohort the SMR for AN was 2.89 vs 11.16 in the time before our specialization. SMR for bulimia nervosa (BN) and for eating disorder not otherwise specified (EDNOS) in the latest cohort were 2.37 and 1.14 respectively. When comparing two retrospective cohorts it is not possible to draw a definite conclusion, however the present study supports that integrating a somatic unit in a multidisciplinary centre may have a favourable influence on mortality in AN.

Quality of life in eating disorders: a meta-analysis.

Eating disorders (EDs) comprise a variety of symptoms and have a profound impact on everyday life. They are associated with high morbidity and mortality. The objective of this study was to analyse published data on health-related quality of life (HRQoL) in EDs so as to compare the results to general population norm data and to investigate potential differences between ED diagnostic groups. A systematic review of the current literature was conducted using a keyword-based search in PubMed and PsychInfo. The search covered anorexia nervosa (AN), bulimia nervosa (BN), eating disorders not otherwise specified (EDNOS) and binge eating disorder (BED) and used the Medical Outcomes Study Short Form-36 Health Survey (SF-36) as a measure of HRQoL. Of the 102 citations identified, 85 abstracts were reviewed and seven studies were included in the meta-analysis. AN patients were included in five studies (n=227), BN in four studies (n=216), EDNOS in two studies (n=166) and BED in four studies (n=148). We tested for between-study variation and significant differences between the diagnostic groups. The results confirmed a significantly lower level of HRQoL in all EDs compared to a population mean. It was not possible to establish any differences between the diagnostic groups.