Intensive Treatments in Adolescent Anorexia Nervosa.

Approximately one-fifth to one-third of patients with adolescent anorexia nervosa (AN) need intensive care in the course of their illness. This article provides an update and discussion on different levels of intensive care (inpatient treatment (IP), day patient treatment (DP) and home treatment (HoT)) in different health care systems based on recently published literature. Important issues discussed in this article are new recommendations for the refeeding process and the definition of target weight as well as principles of medical stabilization and psychotherapeutic approaches. The pros and cons of longer or shorter hospitalization times are discussed, and the advantages of stepped care and day patient treatment are described. A new promising intensive treatment method involving the patient, their caregivers and the direct home environment is introduced. Parents and caregivers should be included in treatment research to foster collaborative work with the attending clinicians. There is an urgent need to evaluate the mid- to long-term outcomes of various intensive treatment programs to compare their effectiveness and costs across different health care systems. This could help policy makers and other stakeholders, such as public and private insurances, to enhance the quality of eating disorder care.

Medical Complications of Anorexia Nervosa and Bulimia Nervosa.

Anorexia nervosa and bulimia nervosa are mental illnesses with associated complications affecting all body systems with arguably the highest mortality of all mental health disorders. A comprehensive medical evaluation is an essential first step in the treatment of anorexia nervosa and bulimia nervosa. Weight restoration and cessation of purging behaviors are often essential components in the management of medical complications of these illnesses.

Psychiatric comorbidity as a risk factor for mortality in people with anorexia nervosa.

Anorexia nervosa (AN) is found associated with increased mortality. Frequent comorbidities of AN include substance use disorders (SUD), affective disorders (AD) and personality disorders (PD). We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders in the observation window between January 2007 and March 2016 for 1970 people with AN, using data from the case register of the South London and Maudsley (SLaM) NHS Foundation Trust, an almost monopoly-secondary mental healthcare service provider in southeast London. We retrieved data from its Clinical Records Interactive Search (CRIS) system as data source. Mortality was ascertained through nationwide tracing by the UK Office for National Statistics (ONS) linked to CRIS database on a monthly basis. A total of 43 people with AN died during the observation period. Standardized Mortality Ratio (SMR) with England and Wales population in 2012 as standard population for our study cohort was 5.21 (95% CI 3.77, 7.02). In univariate analyses, the comorbidity of SUD or PD was found to significantly increase the relative risks of mortality (HRs = 3.10, 95% CI 1.21, 7.92; and 2.58, 95% CI 1.23, 5.40, respectively). After adjustment for demographic and socioeconomic covariates as confounders, moderately but not significantly elevated risks were identified for SUD (adjusted HR = 1.39, 95% CI 0.53, 3.65) and PD (adjusted HR = 1.58, 95% CI 0.70, 3.56). These results suggest an elevated mortality in people with AN, which might be, at least partially, explained by the existence of the comorbidities SUD or PD.

QTc Interval and Risk of Cardiac Events in Adults With Anorexia Nervosa: A Long-Term Follow-Up Study.

BACKGROUND: The literature contains several cases of anorexia nervosa (AN) patients with prolonged QTc interval. However, the risk of prolonged QTc interval is controversial and the risk of cardiac events in AN patients has yet to be investigated. METHODS: We estimated the difference in mean QTc interval and relative risk of borderline prolonged QTc (>440 ms) and prolonged QTc (>460 ms) between 430 adult women AN patients and 123 healthy controls using 3 correction formulas. In a follow-up study, we estimated the risk of a primary end point (a composite of ventricular tachycardia, aborted cardiac arrest, and cardiac arrest) in AN patients compared with a population-based cohort derived from the Danish Civil Register. RESULTS: Mean QTc for AN patients was 408 ms (Hodges), 402 ms (Fridericia), and 399 ms (Bazett). Hodges' found a slightly increased mean QTc (6.8 ms, 95% confidence interval, 1.6-12.0; P=0.01) and percentage with QTc >440 ms in AN patients (relative risk, 3.7, 95% confidence interval, 1.4-10.3; P=0.01), not observed with Fridericia's and Bazett's formulas. There was no difference in the risk of QTc >460 ms between AN patients and healthy controls. During a median follow-up of 10.1 years, AN patients had an increased risk of the primary end point compared with the population-based cohort (hazard ratio, 10.4, 95% confidence interval, 2.6-41.6; P=0.001). However, absolute numbers were small with cumulative incidences of 0.5% and 0.07%, respectively, after 10 years. No events occurred in any AN patient with QTc >440 ms. All-cause mortality was also significantly increased in AN patients compared with the population-based cohort (hazard ratio, 11.2, 95% confidence interval, 5.1-24.5; P<0.001). CONCLUSIONS: Overall, there was no difference in mean QTc interval or risk of prolonged QTc between AN patients and healthy controls. However, AN patients had a notably increased all-cause mortality, as well as an increased risk of cardiac events, which was not related to the baseline QTc interval.

Hemostasis at Extremes of Body Weight.

Extremes of body weight are not uncommon in the modern world and include anorexia nervosa (AN) and obesity. Both conditions are associated with increased morbidity and mortality: AN has the highest mortality rate of all mental illnesses and unfortunately obesity has reached epidemic proportions and is a well-recognized risk factor for cardiovascular disease including venous thromboembolism (VTE). This article summarizes the current understanding of hemostatic changes of these extremes of body weight. The hemostatic changes of AN have not been well described. Severe AN is associated with pancytopenia with decreased bone marrow cellularity, which causes a mild thrombocytopenia. Platelet hyperaggregability has been recognized in AN and has been attributed at least in part to increased adrenoceptor density. Obesity and the metabolic syndrome are associated with prothrombotic changes, which have been well characterized and related to complex adipocyte-induced inflammatory changes, including increased levels of plasminogen activator inhibitor type 1, von Willebrand factor, fibrinogen, and other evidence of increased coagulation and platelet activation. Accumulating evidence suggests a significant role for increased tissue factor expression and signaling in this relationship, with increased tissue factor expression present in adipose and possibly systemic tissues, induced by adipose-generated cytokines. Intriguingly, the hemostatic changes do not seem to increase with increasing BMI, although the risk of VTE increases with BMI, suggesting that decreased venous flow due to venous enlargement may play the most important role in increased VTE risk with obesity.

Worse survival after breast cancer in women with anorexia nervosa.

PURPOSE: A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. METHODS: This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. RESULTS: We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. CONCLUSIONS: We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.

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.

Long-term outcome of anorexia nervosa: Results from a large clinical longitudinal study.

OBJECTIVE: Assessment of the long-term outcome of anorexia nervosa (AN) in a very large sample of inpatients (N = 1,693) and identification of predictors for poor outcome. METHOD: Over 25 years (mean 10 years), consecutively admitted inpatients of a specialized hospital were followed. A subsample of 112 patients with 20-year follow-up was defined. Bivariate comparisons and logistic regression analysis identified risk factors of poor outcome. RESULTS: Body mass index (BMI) increased during the follow-up period. Eating behavior as well as general psychopathology improved but did not reach the level of healthy controls. Remission was found in 30% (total sample) and in 40% (20-year follow-up subsample). Crossover from AN to binge-eating disorder or obesity was rare. The predictors of a negative course of illness included lower BMI at admission; a higher score on the Eating Disorder Inventory Maturity Fears subscale at admission; fewer follow-up years; and higher age at admission. The main diagnostic crossover occurred from AN to eating disorder not otherwise specified. Motherhood was related to better outcome. DISCUSSION: Many patients with very severe AN recover from their illness but AN also shows considerable long-term negative consequences. Over long time periods, survivors show improvement but better treatments for severe cases are still needed. Predictors of outcome included symptom severity, chronicity, and length of follow-up but not psychiatric comorbidity.

Anorexia nervosa in males: excess mortality and psychiatric co-morbidity in 609 Swedish in-patients.

BACKGROUND: Anorexia nervosa (AN) is a psychiatric disorder with high mortality. METHOD: A retrospective register study of 609 males who received hospitalized care for AN in Sweden between 1973 and 2010 was performed. The standardized mortality ratios (SMRs) and Cox regression-derived hazard ratios (HRs) were calculated as measures of mortality. The incidence rate ratios (IRRs) were calculated to compare the mortality rates in patients with AN and controls both with and without psychiatric diagnoses. RESULTS: The SMR for all causes of death was 4.1 [95% confidence interval (CI) 3.1-5.3]. For those patients with psychiatric co-morbidities, the SMR for all causes of death was 9.1 (95% CI 6.6-12.2), and for those without psychiatric co-morbidity, the SMR was 1.6 (95% CI 0.9-2.7). For the group of patients with alcohol use disorder, the SMR for natural causes of death was 11.5 (95% CI 5.0-22.7), and that for unnatural causes was 35.5 (95% CI 17.7-63.5). The HRs confirmed the increased mortality for AN patients with psychiatric co-morbidities, even after adjusting for confounders. The IRRs revealed no significant difference in mortality patterns between the AN patients with psychiatric co-morbidity and the controls with psychiatric diagnoses, with the exceptions of alcohol use disorder and neurotic, stress-related and somatoform disorders, which seemed to confer a negative synergistic effect on mortality. CONCLUSION: Mortality in male AN patients was significantly elevated compared with the general population among only the patients with psychiatric co-morbidities. Specifically, the presence of alcohol and other substance use disorders was associated with more profound excess mortality.

Impact of somatic severity on long-term mortality in anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a severe pathology on account of the high levels of associated morbidity and mortality. This study aimed to assess whether time in somatic intensive care unit, justified by a patient's somatic condition in the course of hospital care, has any relationship with patient outcome in terms of mortality in the long term. METHODS: 195 patients were hospitalised for AN between April 1996 and May 2002, 97 were re-assessed 9 years later on average. RESULTS: Out of 195 patients hospitalised for AN between April 1996 and May 2002, 29 had required transfer to intensive care. Mortality at 9 years was 20 times higher in the group having been transferred to intensive care, irrespective of the duration of follow-up. CONCLUSION: The clinical seriousness of the somatic condition during hospitalisation for AN is a risk factor for excess mortality in the medium term.

Sex differences in response to activity-based anorexia model in C57Bl/6 mice.

Anorexia nervosa is a severe eating disorder often associated with physical hyperactivity and is more frequently observed in female sex. Activity-Based Anorexia (ABA) model combines physical activity (PA) and reduced food intake and thus allows a better understanding of the mechanisms underlying anorexia nervosa. We aimed to assess sex differences in response to ABA model in C57Bl/6 mice. Twenty four male and 16 female C57BL/6 mice were studied. ABA mice were placed in individual cages with a continuously recorded activity wheel. ABA mice had a progressive limited food access from 6h/day (day 6) to 3h/day (day 9) until the end of the protocol (day 17). Body weight and food intake were daily measured. We studied physical activity during 24h, during the dark phase (D-PA) and the light phase (L-PA). We also evaluated the feeding anticipatory physical activity (A-PA), the physical activity during food intake period (FI-PA) and the post-prandial physical activity (PP-PA). We observed 16.7% of mortality in males (4 out of 24 mice) during ABA protocol while no female mice died (p=0.09). At day 17, food intake was significantly higher in females than in males (p<0.05) that was associated with a lower body weight loss than in females (p<0.05). Before limited food access, no gender differences in wheel running activity were observed. From day 9, A-PA significantly increased over time in males (p<0.05 vs females) while females exhibited higher FI-PA and PP-PA (p<0.05 vs males). Correlations between wheel running activities and, respectively, food intake and body weight loss showed gender differences, in particularly for L-PA and A-PA. Our results suggest a greater susceptibility of male mice to develop ABA, males and females exhibit different patterns of physical activity after limitation of food access. Underlying mechanisms should be further investigated.

Long-term follow up of hospitalized pediatric anorexia nervosa restricting type.

BACKGROUND: Information on long-term follow up of childhood-onset anorexia nervosa is scarce. This study investigated long-term (>10 years) course, outcome and prognostic factors for hospitalized childhood-onset anorexia nervosa restricting type (ANR). METHODS: Forty-one ANR girls admitted to a single regional center participated. Median age at first admission was 13.3 years (range, 8.6-15.6 years). The longitudinal clinical course was retrospectively determined for a median follow-up period of 17.1 years (range, 10.4-21.1 years). We analyzed physical, psychological, and social variables to predict partial remission (PR) and full remission (FR). RESULTS: The completion rate of follow up >10 years was high at 97%. At final evaluation (n = 38), distribution of prognosis was as follows: FR, n = 27 (71%); PR, n = 6 (16%); and non-remission, n = 5 (13%). The cumulative ratio of PR and FR increased during the first 5-6 years, and gradually reached a plateau at around 10 years. More than 10 years after the onset, one patient eventually achieved FR, and one patient died. Seven patients were rehospitalized and two died due to suicide during the entire follow up. On multivariate analysis, family disorders/problems rating score was a significant predictor of PR and FR. CONCLUSIONS: This study included hospitalized ANR children aged ≤15 years, the youngest cohort ever reported. Long-term prognosis is generally favorable, but the mortality rate was 5%. Careful long-term follow up >10 years is needed to evaluate outcome of childhood-onset ANR, and family therapy is important in high-risk patients with family disorders/problems.

Mortality in Women With Anorexia Nervosa: The Role of Comorbid Psychiatric Disorders.

OBJECTIVE: To investigate mortality in anorexia nervosa (AN) with a psychiatric comorbidity. METHODS: Using Swedish registers, data for 8069 female inpatients with AN were retrospectively collected for 1973-2010. Mortality patterns were assessed using standardized mortality ratios (SMRs), Cox regression-derived hazard ratios, and incidence rate ratios. A control cohort of 76,995 women was used. RESULTS: Patients with AN and a psychiatric comorbidity had higher mortality rates did than those without a comorbidity. The SMRs for patients with AN and a psychiatric comorbidity were 5.4 (95% confidence interval [CI] = 4.6-6.4) and 18.1 (95% CI = 15.2-21.3) for natural and unnatural causes of death, respectively. The SMRs for patients with AN without a comorbidity were 2.8 (95% CI = 2.3-3.5) and 3.1 (95% CI = 2.2-4.1) for natural and unnatural causes of death, respectively. The adjusted hazard ratios for mortality from natural or unnatural causes were 2.0 (95% CI = 1.5-2.7) and 5.7 (95% CI = 3.9-8.2), respectively. Incidence rate ratios comparing patients with AN and controls, both with psychiatric comorbidities, suggest a negative synergistic effect of comorbid AN and psychiatric disorder on mortality, which was greater for unnatural causes of death. CONCLUSIONS: Mortality in patients with AN was greater in the presence of a psychiatric comorbidity, and even more pronounced for unnatural causes of death and suicides. Substance abuse, especially alcohol use disorder, increased mortality from natural causes of death. These findings highlight the need for early detection and treatment of psychiatric comorbidity in AN, to potentially improve long-term outcomes.

Mortality in eating disorders - results of a large prospective clinical longitudinal study.

OBJECTIVE: To report on long-term mortality in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and eating disorder not otherwise specified (ED-NOS), causes of death, and predictors of early death. METHOD: A large sample of consecutively admitted inpatients (N = 5,839) was followed-up on vital status through the German civil registry office. Of these patients 1,639 were treated for AN, 1,930 for BN, 363 for BED, and 1,907 for ED-NOS. Data from the main inpatient hospital treatment were applied to bivariate and multivariate Cox regression analyses on survival time from onset of eating disorder to death or end of observation. Standardized mortality ratios (SMR) were computed matched for age, gender, and person-years. RESULTS: SMR were 5.35 for AN, 1.49 for BN, 1.50 for BED, 2.39 for narrowly defined ED-NOS, and 1.70 for widely defined ED-NOS. Patients with AN died earlier than patients with BN, BED, or ED-NOS who did not differ. A diagnosis of AN, chronicity, later age of onset, not living in a relationship, and an irregular type of discharge from index inpatient treatment were major predictors of a shorter time to death. Suicidality was a univariate predictor of a shorter time to death in BN only. AN patients mostly died from natural causes related to their eating disorder. DISCUSSION: Mortality in AN is excessive and considerably higher than in BN, BED, and ED-NOS.

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.

Follow-up mortality study of compulsorily treated patients with anorexia nervosa.

OBJECTIVE: In a previous study we found that compulsory inpatient treatment was associated with an increase in the number of deaths over the following 5 years when compared to non-compulsory admission. This study aimed to examine the longer term mortality of patients admitted compulsorily. METHOD: The mortality outcome of patients with a compulsory admission (n = 81) and a comparison group (n = 81) of patients admitted to the specialized eating disorder unit at the Maudsley Hospital in the period 1983-95 was traced over two decades through the National Register held by the National Health Service (NHS) Central Register. RESULTS: Approximately 20 years following admission there were 27 deaths in the series. The standardized mortality rate in the compulsory treatment group no longer differed significantly from that of the non-compulsory group. The suicides were not particularly linked with compulsory admission. DISCUSSION: Although the mortality in the 5 years following a compulsory admission is higher than that seen in the non-compulsory patients, this difference is attenuated over time. The overall standardized mortality rate remains elevated.

Re-examining premature mortality in anorexia nervosa: a meta-analysis redux.

Anorexia nervosa (AN) is reported to have the highest premature mortality of any psychiatric disorder, but recent meta-analyses may have inflated estimates. We sought to re-estimate mortality after methodological corrections and to identify predictors of mortality. We included 41 cohorts from 40 peer-reviewed studies published between 1966 and 2010. Methods included double data extraction, log-linear regression with an over-dispersed Poisson model, and all-cause and suicide-specific standardized mortality ratios (SMRs), with 95% Poisson confidence intervals. Participants with AN were 5.2 [3.7-7.5] times more likely to die prematurely from any cause, and 18.1 [11.5-28.7] times more likely to die by suicide than 15-34 year old females in the general population. Our estimates were 10% and 49% lower, respectively, than previously reported SMRs. Risk of premature mortality was highest in studies with older participants, although confounding by treatment was present. Gender, ascertainment, and diagnostic criteria also impacted risk.