Pediatric acute hospitalization for Anorexia Nervosa: an economic evaluation

Pediatric acute hospitalization for Anorexia Nervosa: an economic evaluation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pediatric acute hospitalization for Anorexia Nervosa: an economic evaluation MariaRosaria Marchili, Elena Bozzola, Stefano Guolo, Silvio Marchesani, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3675318/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Feb, 2024 Read the published version in Italian Journal of Pediatrics → Version 1 posted 4 You are reading this latest preprint version Abstract Background: anorexia nervosa (AN) is a psychiatric disorders which may potentially led to a high risk of health medical complications, suicide and self-harming behaviour. Since Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN. The main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at IRCCS Bambino Gesù Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay. Methods: for the purpose of the study, we included children aged less than 18 years, admitted to IRCCS Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of AN. Medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Basing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022). Results: a total of 260 patients has been included in the study with a median age of 15 years (range 6-18 years). The total health care cost of AN hospitalized patients was of EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930-45,739) and a median daily cost of EUR 593 (range EUR 557-930). Median cost was higher in case of comorbidities, guarded patients, enteral feeding. A prolonged hospitalization has been documented in subgroup A with a higher economic burden. Conclusions: the economic burden of eating disorders is of note. Adequate sanitary policies as well as health economic analyses are required to gain insight into the cost-effectiveness of AN management. Trial registration: 2526-OPBG-2021 Anorexia Nervosa hospitalization hospitalization acute cost children Covid-19 Background Anorexia nervosa (AN) may be defined as a psychiatric disorder that ravages both mind and body, characterized by restriction of food intake leading to starvation, malnutrition and risk of dying for health complications, suicide or self-harming attitudes. In minors, a precise cutoff regarding low body mass index (BMI) to define AN has not been established, since many factors should be considered, including age, sex, BMI before the start of symptoms and the rapidity of weight loss. Intense fear of weight gain is a central feature as well as an obsessive focus on weight and body image, combined with a willing of complete control over everything that is eaten, including the preparation of food. ( 1 ) The major cause for the medical complications in AN is the imbalance between energy intake and requirements, leading to a hypometabolic state. Medical complications are related to weight loss and malnutrition and may include cardiovascular abnormalities, hypotension, hypokalemia, osteoporosis, reduced growth velocity and neurocognitive alterations. Detailed medical, psychiatric, nutritional assessment as well as physical examination and laboratory testing are required to identify complications and comorbidities. In life-threatening cases, an acute phase hospitalization is immediately required to prevent further deterioration of clinical conditions or to contain suicide risk. Psychosocial, psychotherapeutic and pharmacological treatments associated to nutritional rehabilitation. Since Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN, mostly among adolescents, likely correlated to stress, isolation and depression. By the way, an Italian multicentric study revealed that, despite a 48.2% decline of admissions at Emergency Departments, there was a significant increase (83.1%) inpatient admissions for neuropsychiatric problems, including suicidal ideation (+ 147%), depression (+ 115%), eating disorder (+ 78.4%). During the pandemic period, a 39.5% increase in neuropsychiatric disorders (NPD) hospitalizations was observed as well, suggesting that Covid-19 pandemic had a major impact on children's health, mainly on their NPD development. ( 2 ) The main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at Bambino Gesù Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay. Methods For the purpose of the study, we included children aged less than 18 years, admitted to IRCCS Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of AN. The period study ranged from 1st March 2019till 31st October 2022. AN has been defined according to literature and to the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, fifth edition. ( 3 ). Patients were excluded if they did not meet the inclusion criteria. As for the enrolled patients, medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Procedure codes were used, in order to precisely calculate the cost of any single exam and therapy. For any patient, the HAP has been calculated. The final value includes cost of hospital accommodation and management at the General Pediatric Disease Unit. To this cost, the price of procedures (imaging, laboratory exams, medical and paramedical evaluations) and medical treatments was added. The cost data were calculated using an Excel database reporting the cost for each patient correlated to laboratory and imaging exams, specialist evaluations (for example, nutritionist or psychiatric consultant), therapy, and hospital accommodation. Basing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022). In order to compare and correlate data, a statistical analysis was performed. The comparison study among subgroups was performed using the Student t-test (two-sided) for parametric distribution or Mann-Whitney test for nonparametric distribution. Moreover, Chi-squared test or Fisher’s exact test (when appropriate) were performed to compare proportions or categorical outcomes. The regression analysis was studied using Spearman test. Data with statistical significance had a p-value less than 0.05. Statistical analysis was performed using the GraphPad Prism software, version 5 for Machintosh (GraphPad Software, Inc). Results The present study investigated the economic burden of hospitalized patients affected by AN between 1st May 2020 till 1st May 2022 at Bambino Gesù Children Hospital, in addition to evaluating pre-Covid-19 and post- Covid19 (subgroups A and B) influence on AN prevalence and costs. A total of 260 patients has been included in the study (17 males vs 243 females), median age 15 years (range 6–18 years). Other neuropsychological comorbidities, including suicide attempt, psychotic or anxious disorders, have been found in a percentage of 24.2% (n = 63) with a total of 4.2% of guarded patients (n = 11). A percentage of 43.1% (n = 112) required enteral feeding (EF); a median duration of 3 days has been detected between the admission and EF onset (range 0–23 days). General data are summarized in Table 1 and Table 2 . Table 1 General characteristics of the study cohort. Subgroup A: from March 2019 to March 2020. Subgroup B: from March 2020 to October 2022. Parameters Value Number of patients 260 Median age in years (range) 15 (6–18) Number of males/females (%) 17/243 (6.5/93.5) Median length of hospitalization in days (range) 19 (1–65) Number of patients hospitalized in subgroup A (%) 36 (13.8) Number of patients hospitalized in subgroup B (%) 224 (86.2) Number of guarded patients (%) 11 (4.2) Number of patients who required enteral feeding (%) 112 (43.1) Median days between admission and the start of enteral feeding (range) 3 (0–23) Number of patients who presented comorbidities (%) 63 (24.2) Number of patients with mood disorder (%) 39 (15) Number of patients with anxious spectrum disorder (%) 14 (5.4) Number of patients with obsessive compulsive disorder (%) 8 (3.1) Number of patients with other comorbidities (%) 16 (6.1) Total health care cost for hospitalizations in EUR 3,352,333 Median cost for each hospitalization in EUR (range) 11,124 (930-45739) Median daily cost in EUR (range) 593 (557–930) Table 2 therapies and exams performed during hospitalizations. CBC: complete blood count. Chem: chemistry panel. EKG: electrocardiogram. MRI: magnetic resonance image. Therapies Parameters Value Number who underwent fluid therapy (%) 252 (96.9) Number who underwent supplements therapy (%) 233 (89.6) Number who underwent therapy with aripiprazole (%) 209 (80.4) Number who underwent therapy with sertraline (%) 136 (52.3) Number who underwent therapy with fluoxetine (%) 27 (10.4) Number who underwent therapy with olanzapine (%) 16 (6.1) Number who underwent therapy with alprazolam (%) 14 (5.4) Number who underwent therapy with risperidone (%) 4 (1.5) Blood exams Parameters Value Number of patients who underwent CBC and Chem analysis (%) 256 (98.5) Median number of CBC and Chem exams performed during hospitalizations (range) 3 (0–15) Number of patients who underwent vitamin dosages (%) 221 (85) Number of patients who underwent screening for celiac disease (%) 208 (80) Number of patients who underwent hormonal dosages (%) 170 (65.4) Number of patients who underwent urine exams (%) 124 (47.7) Number of patients for whom at least 1 blood gas analysis was performed (%) 22 (8.5) Other exams Parameters Value Number of patients for whom at least 1 EKG was performed (%) 241 (92.7) Number of patients who underwent abdomen ultrasound (%) 202 (77.7) Number of patients who cerebral MRI (%) 99 (38.1) Number of patients who underwent echocardiogram (%) 71 (27.3) Number of patients who underwent Holter EKG (%) 19 (7.3) Number of patients who underwent peripheral vessels doppler ultrasound (%) 16 (6.1) The total health care cost of AN hospitalized patients was EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930 − 45,739) and a median daily cost of EUR 593 (range EUR 557–930). Considering patients age (cut-off of 14 years), no statistically significant differences have been detected as for length of hospitalization (LOS) and economic related burden. Median LOS was statistically significant higher in patients with comorbidities than patients without comorbidities (23 days, range 3–65 days vs 17 days, range 1–55 days; p-value 0.006). Similarly, median cost of AN patient with comorbidities was significantly greater than AN patient without comorbidities (EUR 13,485, range EUR 1814-37,959 vs EUR 10,323, range EUR 930 − 45,739; p-value 0.005). Guarded patients had a higher prevalence of comorbidities compared to not guarded ones (91% vs 23.3%; p-value 0.00001). Those patients required more frequently EF (81.8% vs 41.4%; p-value 0.008) with a longer median LOS compared to not-guarded patients (41 days, range 25–55 days vs 18 days, range 1–65 days) with a higher median medical expenditure (EUR 33,015, range 15,776 − 45,739 vs EUR 10,703, range 930 − 37,673; p-value 0.00001). Median LOS of patients treated with EF was significantly higher compared to median LOS of patients without EF (28 days, range 9–65 days vs 14 days, range 1–47 days; p-value 0.00001) with a greater median hospitalization total cost (EUR 16,391, range EUR 5306-45,739 vs EUR 8580, range EUR 930 − 43,143; p-value 0.00001). The comparisons between these specific subgroups are shown in Table 3 . Table 3 comparison between gender, age, comorbidities, needing of guarding, needing of enteral feeding subgroups. *Results with statistical significance. Gender Value Females Males p-value Median age in years (range) 15 (6–18) 14 (8–17) 0.045* Median length of hospitalization in days (range) 19 (1–65) 15 (5–47) 0.098 Median cost of hospitalization in EUR (range) 11,373 (930 − 45,739) 8703 (3072-43,143) 0.97 Number of patients with comorbidities (%) 58 (23.8) 5 (29.4) 0.61 Number of guarded patients (%) 10 (4.3) 1 (6.2) 0.53 Number of patients who required enteral feeding (%) 107 (44) 3 (21.4) 0.041* Age Value < 14 years ≥ 14 years p-value Median length of hospitalization in days (range) 19 (4–57) 19 (1–65) 0.726 Median cost of hospitalization in EUR (range) 11,509 (2584-36,136) 10,900 (930 − 45,739) 0.098 Median days between admission and the start of enteral feeding (range) 4 (0–14) 3 (0–23) 0.529 Comorbidities Value With comorbidities Without comorbidities p-value Median age in years (range) 15 (8–18) 15 (6–18) 0.342 Median length of hospitalization in days (range) 23 (3–65) 17 (1–55) 0.006* Median cost of hospitalization in EUR (range) 13,485 (1814-37,959) 10,323 (930 − 45,739) 0.005* Median days between admission and the start of enteral feeding (range) 3 (0–23) 4 (1–9) 0.741 Number of guarded patients (%) 10 (91) 53 (23.3) 0.00001* Number of patients who required enteral feeding (%) 35 (23.8) 28 (24.7) 0.765 Guarded patients Value Guarded patients Non-guarded patients p-value Median age in years (range) 15 (6–18) 15 (12–17) 0.896 Median length of hospitalization in days (range) 41 (25–55) 18 (1–65) 0.00001* Median cost of hospitalization in EUR (range) 33,015 (15,776 − 45,739) 10,703 (930 − 37,673) 0.00001* Median days between admission and the start of enteral feeding (range) 3 (0–23) 4 (1–9) 0.912 Number of patients who required enteral feeding (%) 9 (81.8) 103 (41.4) 0.008* Enteral feeding Value EF patients Non-EF patients p-value Median age in years (range) 15 (6–18) 15 (9–18) 0.726 Median length of hospitalization in days (range) 14 (1–47) 28 (9–65) 0.00001* Median cost of hospitalization in EUR (range) 16,391 (5306-45,739) 8580 (930 − 43,143) 0.00001* Concerning differences between subgroup A and B, a greater median LOS has been documented in subgroup A (29 days, range 5–65 days vs 28 days, range 1–57 days; p-value 0.0008) with a higher economic burden considering hospitalization median cost (EUR 16,758, range EUR 3072-45,739 vs EUR 10,695, range EUR 930 − 37,959; p-value 0.0016). A statistically significant difference has been found considering median timing between the AN patient’s admission and EF onset comparing pre and post-Covid19 pandemic (8 days, range 1–14 days vs 3 days, range 0–23 days; p-value 0.0026). Conversely, no statistically significant differences have been described between the two subgroups comparing sex, comorbidities, EF needing (Table 4 ). Table 4 main differences between patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020, Subgroup A), and patients hospitalized after Covid-19 onset (from March 2020 to October 2022, Subgroup B). *Results with statistical significance. Value Subgroup A Subgroup B p-value Number of male patients (%) 5 (13.9) 12 (5.4) 0.0681 Number of female patients (%) 31 (86.1) 212 (94.6) 0.0681 Median age in years (range) 14 (9–17) 15 (6–18) 0.014* Median length of hospitalization in days (range) 29 (5–65) 18 (1–57) 0.0008* Median days between admission and the start of enteral feeding (range) 8 (1–14) 3 (0–23) 0.0026* Median cost of hospitalization in EUR (range) 16,758 (3072-45,739) 10,695 (930 − 37,959) 0.0016* Number of patients with comorbidities (%) 11 (30.5) 52 (30.2) 0.911 Number of guarded patients (%) 7 (19.4) 4 (1.8) 0.0001* Number of patients who required enteral feeding (%) 12 (33.3) 100 (44.6) 0.21 Moreover, a significant positive correlation has been detected between admission, latency of EF onset and total hospitalization costs (Rs 0.2, p-value 0.047). Discussion The main finding of our study is the high acute hospitalization cost (AHC) associated with AN in pediatric patients. Three key factors, namely comorbidities, EF and guarding, correlated to a prolonged LOS and to a higher AHC. Hospitalization is required mainly in malnourished cases. Indications for hospitalization include starvation with profound hypotension or dehydration, severe electrolyte abnormalities, arrhythmias or severe bradycardia, suicide risk. ( 1 ) One of the most significant medical complications, which often leads to hospitalization, is vital sign instability, including bradycardia and orthostatic hypotension, caused by the underlying malnutrition and increased vagal tone. Electrolyte imbalances as well may occur in patients who engage in purging behaviors or in excessive water drinking. For children and pre-adolescents, the goal is to correct undernutrition, to return to the individual’s growth curve for proper growth and pubertal development. Evidence exists that substantial weight gain is best achieved in inpatient settings, requiring a multi-specialist approach. ( 4 ) Most cases may require a prolonged LOS due to the latency of initial EF strategies approach. ( 5 ) At first, nutritional therapy includes supervised meals and additional liquid supplements to prevent dehydration. Nevertheless, in severely emaciated patients at high medical risk, NE, under professional and supportive supervision, should be considered. In case of failure of the above nutritional strategies, parenteral nutrition is even indicated. The risk of a refeeding syndrome, which can lead to delirium, stupor, seizures, coma and death, especially during the early stages, should be kept in mind. So, a monitored program of nutrition, a strict control of parameters and periodic blood examination should be scheduled in order to prevent this fatal complication, especially in those with a severe malnutrition status. The indication for close psychiatric monitoring of safety concerns, including suicidal thoughts, is also to be stressed. AN is often associated to comorbid disorders, mainly depression and anxiety disorders, which should always be screened for as they can further complicate treatment. Of note, depression and anxiety symptoms should be linked to AN. It may be challenging teasing apart primary depressive and anxiety disorders from depressive and anxiety symptoms caused by malnutrition. In fact, there is a consistent overlap in symptoms and signs. ( 6 ) Suicidal ideation and self-injurious behavior may complicate depression, anxiety and AN, requiring dedicated surveillance. ( 7 ) In our study, the average HAC for patient is EUR 11,124. The high economic burden is in line with literature, which, analyzing cost-effectiveness intervention report high economic cost over short and long period analysis. ( 8 , 9 ) Finally, during the Covid-19 pandemic period, there was a raise in the number of admissions to the emergency departments of patients with AN, having a more severe general status, psychiatric comorbidities and dehydration. ( 10 ) At the same time, an increase of AN adolescent’s hospitalization rate has been observed. These findings should raise awareness of the mental difficulties experienced by children and adolescents during the Covid-19 pandemic. Our result are in line with the systematic revision of literature which reported on average a 48% increase in eating disorder admissions during the pandemic compared to previous timepoints. ( 11 ) In fact, after pandemic onset, the increased stress caused by the Covid-19 circulation and the collective sense of lack of personal control likely contributed to increase neuropsychological disorders in adolescents. ( 2 , 12 , 13 ) Nevertheless, in our study, the LOS of AN adolescents was reduced compared to pre-pandemic period. A possible explanation is the rapid start of EF during Covid-19 pandemic (8 days, range 1–14 days) which accelerated the discharge of patients. During the current pandemic, moreover, face-to-face clinical assessments, psychological and psychopathological treatments were reduced to minimize unnecessary physical contact and hence potential exposure to the virus. ( 14 ) So, both medical staff and families’ supporting discharge as soon as possible, which might have led to increased motivation to adhere to the AN treatment protocol and reduce psychopathological and psychological assessment, influenced the shorter duration of hospitalization. No statistically significant differences have been described between pre and post pandemic among patients comparing sex, comorbidities, EF needing in our study. Our results are in contrast with Girardi M et al who found out more intravenous fluids, oral dietetic supplements and enteral nutrition by nasogastric tube in post Covid-19 period than before the onset of pandemic. Moreover, the same group presented higher prevalence of psychiatric comorbidities and required most frequently treatments with psychotropic drugs. ( 15 ) Nevertheless, our result is in line with Goldberg et al who reported a 35% reduction in median hospitalization duration even if there was a significant increase in the number of adolescents hospitalized with AN. ( 16 ) Different findings regarding ED studies may correlate to the variability of restrictive public health measures and to the effects on the population. Conclusion The economic burden of eating disorders is of note, although the available evidence probably under-estimates the costs. In fact, indirect costs, such as parents working missed days, have not been included in the cost-analysis study. As a conclusion, adequate sanitary policies as well as health economic analyses to gain insight into the cost-effectiveness of AN treatment are required. Abbreviations AN: Anorexia nervosa BMI: body mass index Covid-19: Coronavirus disease of 2019 NPD: neuropsychiatric disorders HAP: hospitalization in the acute phase EF: enteral feeding LOS: length of hospitalization CBC: complete blood count. Chem: chemistry panel. EKG: electrocardiogram. MRI: magnetic resonance image. AHC: acute hospitalization cost Declarations Acknowledgements: not applicable. Authors’ contributions: MM and EB coordinated the study; EB and AV conceived the study, SG and SM participated in its design; GS, CM and SV collected data, MM and IT carried out the literature research MR helped to draft the manuscript. All the authors read and approved the final manuscript. Funding: This work was supported also by the Italian Ministry of Health with “current Research funds”. Competing interest: EB is Associate Editor for IJP Availability of data and materials: dataset is available at Marchili’s study room and data will be made available on reasonable request. Ethics approval and consent to participate: The study was approved by ethics committee of the Bambino Gesù Children’s Hospital of Rome (approval number: 2526-OPBG-2021). Informed written consents were obtained by patients’parents. All methods of this study were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication: not applicable. References Mitchell JE, Peterson CB. Anorexia Nervosa. N Engl J Med. 2020;382(14):1343–51. Bozzola E, Ferrara P, Spina G, Villani A, Roversi M, Raponi M, Corsello G, Staiano A. Italian Pediatric COVID-19 Board. The pandemic within the pandemic: the surge of neuropsychological disorders in Italian children during the COVID-19 era. Ital J Pediatr. 2022;48(1):126. Diagnostic. and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association,: DSM V; 2013. Hartmann A, Weber S, Herpertz S, Zeeck A. German Treatment Guideline Group for Anorexia Nervosa. Psychological treatment for anorexia nervosa: a meta-analysis of standardized mean change. Psychother Psychosom. 2011;80(4):216–26. Marchili MR, Diamanti A, Zanna V, Spina G, Mascolo C, Roversi M, Guarnieri B, Mirra G, Testa G, Raucci U, Reale A, Villani A. Early Naso Gastric Feeding and Outcomes of Anorexia Nervosa Patients Nutrients. 2023;15(3):490. Moskowitz L, Weiselberg E. Anorexia Nervosa/Atypical Anorexia Nervosa. Curr Probl Pediatr Adolesc Health Care. 2017;47(4):70–84. Kostro K, Lerman JB, Attia E. The current status of suicide and self-injury in eating disorders: a narrative review. J Eat Disord. 2014;2:19. Svendsen VG, Lokkerbol J, Danner UN, Jansingh A, Evers SM, Wijnen BF. Design and testing of a health economic Markov model for treatment of anorexia nervosa. Expert Rev Pharmacoecon Outcomes Res. 2022;22(8):1243–51. Byford S, Barrett B, Roberts C, Clark A, Edwards V, Smethurst N, Gowers SG. Economic evaluation of a randomised controlled trial for anorexia nervosa in adolescents. Br J Psychiatry. 2007;191:436–40. Spina G, Roversi M, Marchili MR, Raucci U, Fini F, Mirra G, Testa G, Guarnieri B, Clemente A, Diamanti A, Zanna V, Castiglioni MC, Vicari S, Reale A, Villani A. Psychiatric comorbidities and dehydration are more common in children admitted to the emergency department for eating disorders in the COVID-19 era. Eat Weight Disord. 2022;27(7):2473–80. Devoe J, Han D, Anderson A, Katzman A, Patten DK, Soumbasis SB, Flanagan A, Paslakis J, Vyver G, Marcoux E, Dimitropoulos G. The impact of the COVID-19 pandemic on eating disorders: A systematic review. Int J Eat Disord. 2023;56(1):5–25. Haripersad YV, Kannegiesser-Bailey M, Morton K, Skeldon S, Shipton N, Edwards K, Newton R, Newell A, Stevenson PG, Martin AC. Outbreak of anorexia nervosa admissions during the COVID-19 pandemic. Arch Dis Child. 2021;106(3):e15. Herpertz-Dahlmann B, Dempfle A, Eckardt S. The youngest are hit hardest: The influence of the COVID-19 pandemic on the hospitalization rate for children, adolescents, and young adults with anorexia nervosa in a large German representative sample. Eur Psychiatry. 2022;65(1):e84. Walsh O. McNicholas F.Assessment and management of anorexia nervosa during COVID-19. Ir J Psychol Med. 2020;37(3):187–91. Girardi M, Assalone C, Maines E, Genovese A, Naselli A, Nai Fovino L, Soffiati M, Franceschi R. Disease Characteristics and Psychiatric Comorbidities in Adolescents with Anorexia Nervosa Hospitalized During COVID-19 Pandemic. Front Biosci (Schol Ed). 2022;14(4):28. Goldberg L, Ziv A, Vardi Y, Hadas S, Zuabi T, Yeshareem L, Gur T, Steinling S, Scheuerman O, Levinsky Y. The effect of COVID-19 pandemic on hospitalizations and disease characteristics of adolescents with anorexia nervosa. Eur J Pediatr. 2022;181(4):1767–71. Cite Share Download PDF Status: Published Journal Publication published 27 Feb, 2024 Read the published version in Italian Journal of Pediatrics → Version 1 posted Reviewers agreed at journal 02 Jan, 2024 Reviewers invited by journal 28 Dec, 2023 Editor assigned by journal 29 Nov, 2023 First submitted to journal 28 Nov, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3675318","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264128671,"identity":"d6323960-4d12-4c62-b8ff-c9819b5e922e","order_by":0,"name":"MariaRosaria Marchili","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"MariaRosaria","middleName":"","lastName":"Marchili","suffix":""},{"id":264128672,"identity":"329d04b2-e0ee-443a-b6b0-1010cd246e9b","order_by":1,"name":"Elena Bozzola","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACdjB5AEQwHmCoYGAwIKiFGaEFSJ6BaUkgVgtjGxFa+JmZjz34wXBHTr7/8IEDP+fZ5JnzL2B78PEHbi2SzWzphj0Mz4wZG44lHOzdllZsOeMBu+EMPLYYHOYxk+BhOJzYzNhjcIB32+HEDTcOsEnz4NFif5j/m+QfoJY2Zh6Dg3/nQLX8wWcLMw/QTKCWHjYeg8O8DUAt5xvYpPF5X+Iwm5m0jMEzYwketoTDMsdAfmFsk+xJw62Fv735meSbCnCIHXz4pgYUYoePSfywwa0F6jwEM4FBIrGBkHpUkMDAf4A0HaNgFIyCUTDsAQDBh1LFeQoB1AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-2586-019X","institution":"Bambino Gesu Children Hospital","correspondingAuthor":true,"prefix":"","firstName":"Elena","middleName":"","lastName":"Bozzola","suffix":""},{"id":264128673,"identity":"9972edda-3447-44b6-96cd-ba767d4503e3","order_by":2,"name":"Stefano Guolo","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Guolo","suffix":""},{"id":264128674,"identity":"a09869de-99e6-4105-b5a0-6fcf630e7b2b","order_by":3,"name":"Silvio Marchesani","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Silvio","middleName":"","lastName":"Marchesani","suffix":""},{"id":264128675,"identity":"6b26c927-768b-4a02-9f56-cca7daced38a","order_by":4,"name":"Giulia Spina","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Spina","suffix":""},{"id":264128676,"identity":"d741c139-e5a9-4d11-ad79-2c91ec551f26","order_by":5,"name":"Cristina Mascolo","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Mascolo","suffix":""},{"id":264128677,"identity":"7e5ca01a-dc1c-4d35-a95d-40ba3b46e681","order_by":6,"name":"Stefano Vicari","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Vicari","suffix":""},{"id":264128678,"identity":"e91d0a24-31ac-4f85-a512-a77cbb3f5038","order_by":7,"name":"Isabella Tarissi De Jacobis","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Isabella","middleName":"Tarissi","lastName":"De Jacobis","suffix":""},{"id":264128679,"identity":"65a26c08-c5b5-426b-bade-85fbbd2b2162","order_by":8,"name":"Massimiliano Raponi","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Massimiliano","middleName":"","lastName":"Raponi","suffix":""},{"id":264128680,"identity":"8059a516-94cd-42e3-984f-db5d84e8cbdf","order_by":9,"name":"Alberto Villani","email":"","orcid":"","institution":"Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Villani","suffix":""}],"badges":[],"createdAt":"2023-11-28 08:15:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3675318/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3675318/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13052-024-01605-0","type":"published","date":"2024-02-27T15:00:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51958445,"identity":"2787ae99-6de9-42d8-9aee-3a919556132e","added_by":"auto","created_at":"2024-03-04 15:16:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":266227,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3675318/v1/fc6356fe-687a-482c-9ba6-f0bb82022eaa.pdf"}],"financialInterests":"","formattedTitle":"Pediatric acute hospitalization for Anorexia Nervosa: an economic evaluation","fulltext":[{"header":"Background","content":"\u003cp\u003eAnorexia nervosa (AN) may be defined as a psychiatric disorder that ravages both mind and body, characterized by restriction of food intake leading to starvation, malnutrition and risk of dying for health complications, suicide or self-harming attitudes. In minors, a precise cutoff regarding low body mass index (BMI) to define AN has not been established, since many factors should be considered, including age, sex, BMI before the start of symptoms and the rapidity of weight loss. Intense fear of weight gain is a central feature as well as an obsessive focus on weight and body image, combined with a willing of complete control over everything that is eaten, including the preparation of food. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The major cause for the medical complications in AN is the imbalance between energy intake and requirements, leading to a hypometabolic state. Medical complications are related to weight loss and malnutrition and may include cardiovascular abnormalities, hypotension, hypokalemia, osteoporosis, reduced growth velocity and neurocognitive alterations. Detailed medical, psychiatric, nutritional assessment as well as physical examination and laboratory testing are required to identify complications and comorbidities. In life-threatening cases, an acute phase hospitalization is immediately required to prevent further deterioration of clinical conditions or to contain suicide risk. Psychosocial, psychotherapeutic and pharmacological treatments associated to nutritional rehabilitation.\u003c/p\u003e \u003cp\u003eSince Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN, mostly among adolescents, likely correlated to stress, isolation and depression. By the way, an Italian multicentric study revealed that, despite a 48.2% decline of admissions at Emergency Departments, there was a significant increase (83.1%) inpatient admissions for neuropsychiatric problems, including suicidal ideation (+\u0026thinsp;147%), depression (+\u0026thinsp;115%), eating disorder (+\u0026thinsp;78.4%). During the pandemic period, a 39.5% increase in neuropsychiatric disorders (NPD) hospitalizations was observed as well, suggesting that Covid-19 pandemic had a major impact on children's health, mainly on their NPD development. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at Bambino Ges\u0026ugrave; Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eFor the purpose of the study, we included children aged less than 18 years, admitted to IRCCS Bambino Ges\u0026ugrave; Children Hospital, Rome, Italy, with a diagnosis of AN. The period study ranged from 1st March 2019till 31st October 2022. AN has been defined according to literature and to the diagnostic criteria in the \u003cem\u003eDiagnostic and Statistical Manual of Mental Disorders\u003c/em\u003e of the American Psychiatric Association, fifth edition. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients were excluded if they did not meet the inclusion criteria. As for the enrolled patients, medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Procedure codes were used, in order to precisely calculate the cost of any single exam and therapy. For any patient, the HAP has been calculated. The final value includes cost of hospital accommodation and management at the General Pediatric Disease Unit. To this cost, the price of procedures (imaging, laboratory exams, medical and paramedical evaluations) and medical treatments was added. The cost data were calculated using an Excel database reporting the cost for each patient correlated to laboratory and imaging exams, specialist evaluations (for example, nutritionist or psychiatric consultant), therapy, and hospital accommodation.\u003c/p\u003e \u003cp\u003eBasing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022).\u003c/p\u003e \u003cp\u003eIn order to compare and correlate data, a statistical analysis was performed. The comparison study among subgroups was performed using the Student t-test (two-sided) for parametric distribution or Mann-Whitney test for nonparametric distribution. Moreover, Chi-squared test or Fisher\u0026rsquo;s exact test (when appropriate) were performed to compare proportions or categorical outcomes. The regression analysis was studied using Spearman test. Data with statistical significance had a p-value less than 0.05. Statistical analysis was performed using the GraphPad Prism software, version 5 for Machintosh (GraphPad Software, Inc).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe present study investigated the economic burden of hospitalized patients affected by AN between 1st May 2020 till 1st May 2022 at Bambino Ges\u0026ugrave; Children Hospital, in addition to evaluating pre-Covid-19 and post- Covid19 (subgroups A and B) influence on AN prevalence and costs. A total of 260 patients has been included in the study (17 males vs 243 females), median age 15 years (range 6\u0026ndash;18 years). Other neuropsychological comorbidities, including suicide attempt, psychotic or anxious disorders, have been found in a percentage of 24.2% (n\u0026thinsp;=\u0026thinsp;63) with a total of 4.2% of guarded patients (n\u0026thinsp;=\u0026thinsp;11). A percentage of 43.1% (n\u0026thinsp;=\u0026thinsp;112) required enteral feeding (EF); a median duration of 3 days has been detected between the admission and EF onset (range 0\u0026ndash;23 days). General data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral characteristics of the study cohort. Subgroup A: from March 2019 to March 2020. Subgroup B: from March 2020 to October 2022.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of males/females (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/243 (6.5/93.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (1\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients hospitalized in subgroup A (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (13.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients hospitalized in subgroup B (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e224 (86.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of guarded patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (4.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who required enteral feeding (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112 (43.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian days between admission and the start of enteral feeding (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who presented comorbidities (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (24.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with mood disorder (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with anxious spectrum disorder (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with obsessive compulsive disorder (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with other comorbidities (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal health care cost for hospitalizations in EUR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,352,333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost for each hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11,124 (930-45739)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian daily cost in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e593 (557\u0026ndash;930)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003etherapies and exams performed during hospitalizations. CBC: complete blood count. Chem: chemistry panel. EKG: electrocardiogram. MRI: magnetic resonance image.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTherapies\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eParameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent fluid therapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e252 (96.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent supplements therapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233 (89.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with aripiprazole (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e209 (80.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with sertraline (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136 (52.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with fluoxetine (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (10.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with olanzapine (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with alprazolam (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber who underwent therapy with risperidone (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood exams\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eParameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent CBC and Chem analysis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e256 (98.5)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian number of CBC and Chem exams performed during hospitalizations (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent vitamin dosages (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e221 (85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent screening for celiac disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e208 (80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent hormonal dosages (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170 (65.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent urine exams (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (47.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients for whom at least 1 blood gas analysis was performed (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther exams\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eParameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients for whom at least 1 EKG was performed (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e241 (92.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent abdomen ultrasound (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202 (77.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who cerebral MRI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (38.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent echocardiogram (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (27.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent Holter EKG (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who underwent peripheral vessels doppler ultrasound (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe total health care cost of AN hospitalized patients was EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930\u0026thinsp;\u0026minus;\u0026thinsp;45,739) and a median daily cost of EUR 593 (range EUR 557\u0026ndash;930).\u003c/p\u003e \u003cp\u003eConsidering patients age (cut-off of 14 years), no statistically significant differences have been detected as for length of hospitalization (LOS) and economic related burden.\u003c/p\u003e \u003cp\u003eMedian LOS was statistically significant higher in patients with comorbidities than patients without comorbidities (23 days, range 3\u0026ndash;65 days vs 17 days, range 1\u0026ndash;55 days; p-value 0.006). Similarly, median cost of AN patient with comorbidities was significantly greater than AN patient without comorbidities (EUR 13,485, range EUR 1814-37,959 vs EUR 10,323, range EUR 930\u0026thinsp;\u0026minus;\u0026thinsp;45,739; p-value 0.005).\u003c/p\u003e \u003cp\u003eGuarded patients had a higher prevalence of comorbidities compared to not guarded ones (91% vs 23.3%; p-value 0.00001). Those patients required more frequently EF (81.8% vs 41.4%; p-value 0.008) with a longer median LOS compared to not-guarded patients (41 days, range 25\u0026ndash;55 days vs 18 days, range 1\u0026ndash;65 days) with a higher median medical expenditure (EUR 33,015, range 15,776\u0026thinsp;\u0026minus;\u0026thinsp;45,739 vs EUR 10,703, range 930\u0026thinsp;\u0026minus;\u0026thinsp;37,673; p-value 0.00001).\u003c/p\u003e \u003cp\u003eMedian LOS of patients treated with EF was significantly higher compared to median LOS of patients without EF (28 days, range 9\u0026ndash;65 days vs 14 days, range 1\u0026ndash;47 days; p-value 0.00001) with a greater median hospitalization total cost (EUR 16,391, range EUR 5306-45,739 vs EUR 8580, range EUR 930\u0026thinsp;\u0026minus;\u0026thinsp;43,143; p-value 0.00001).\u003c/p\u003e \u003cp\u003eThe comparisons between these specific subgroups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ecomparison between gender, age, comorbidities, needing of guarding, needing of enteral feeding subgroups. *Results with statistical significance.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eFemales\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eMales\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (8\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.045*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (1\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (5\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11,373 (930\u0026thinsp;\u0026minus;\u0026thinsp;45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8703 (3072-43,143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with comorbidities (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of guarded patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who required enteral feeding (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.041*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;14 years\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;14 years\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (4\u0026ndash;57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (1\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11,509 (2584-36,136)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10,900 (930\u0026thinsp;\u0026minus;\u0026thinsp;45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian days between admission and the start of enteral feeding (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eWith comorbidities\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eWithout comorbidities\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (8\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (3\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (1\u0026ndash;55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.006*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13,485 (1814-37,959)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10,323 (930\u0026thinsp;\u0026minus;\u0026thinsp;45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.005*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian days between admission and the start of enteral feeding (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.741\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of guarded patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who required enteral feeding (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGuarded patients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eGuarded patients\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNon-guarded patients\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (12\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (25\u0026ndash;55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (1\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33,015 (15,776\u0026thinsp;\u0026minus;\u0026thinsp;45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10,703 (930\u0026thinsp;\u0026minus;\u0026thinsp;37,673)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian days between admission and the start of enteral feeding (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.912\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who required enteral feeding (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.008*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEnteral feeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eEF patients\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNon-EF patients\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (9\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (1\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (9\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16,391 (5306-45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8580 (930\u0026thinsp;\u0026minus;\u0026thinsp;43,143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eConcerning differences between subgroup A and B, a greater median LOS has been documented in subgroup A (29 days, range 5\u0026ndash;65 days vs 28 days, range 1\u0026ndash;57 days; p-value 0.0008) with a higher economic burden considering hospitalization median cost (EUR 16,758, range EUR 3072-45,739 vs EUR 10,695, range EUR 930\u0026thinsp;\u0026minus;\u0026thinsp;37,959; p-value 0.0016). A statistically significant difference has been found considering median timing between the AN patient\u0026rsquo;s admission and EF onset comparing pre and post-Covid19 pandemic (8 days, range 1\u0026ndash;14 days vs 3 days, range 0\u0026ndash;23 days; p-value 0.0026). Conversely, no statistically significant differences have been described between the two subgroups comparing sex, comorbidities, EF needing (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003emain differences between patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020, Subgroup A), and patients hospitalized after Covid-19 onset (from March 2020 to October 2022, Subgroup B). *Results with statistical significance.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubgroup A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSubgroup B\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of male patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of female patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (86.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e212 (94.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (9\u0026ndash;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (6\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.014*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian length of hospitalization in days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (5\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (1\u0026ndash;57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0008*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian days between admission and the start of enteral feeding (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (1\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0026*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian cost of hospitalization in EUR (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16,758 (3072-45,739)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10,695 (930\u0026thinsp;\u0026minus;\u0026thinsp;37,959)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0016*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with comorbidities (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (30.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.911\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of guarded patients (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients who required enteral feeding (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMoreover, a significant positive correlation has been detected between admission, latency of EF onset and total hospitalization costs (Rs 0.2, p-value 0.047).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main finding of our study is the high acute hospitalization cost (AHC) associated with AN in pediatric patients. Three key factors, namely comorbidities, EF and guarding, correlated to a prolonged LOS and to a higher AHC.\u003c/p\u003e \u003cp\u003eHospitalization is required mainly in malnourished cases. Indications for hospitalization include starvation with profound hypotension or dehydration, severe electrolyte abnormalities, arrhythmias or severe bradycardia, suicide risk. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) One of the most significant medical complications, which often leads to hospitalization, is vital sign instability, including bradycardia and orthostatic hypotension, caused by the underlying malnutrition and increased vagal tone. Electrolyte imbalances as well may occur in patients who engage in purging behaviors or in excessive water drinking. For children and pre-adolescents, the goal is to correct undernutrition, to return to the individual\u0026rsquo;s growth curve for proper growth and pubertal development. Evidence exists that substantial weight gain is best achieved in inpatient settings, requiring a multi-specialist approach. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Most cases may require a prolonged LOS due to the latency of initial EF strategies approach. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) At first, nutritional therapy includes supervised meals and additional liquid supplements to prevent dehydration. Nevertheless, in severely emaciated patients at high medical risk, NE, under professional and supportive supervision, should be considered. In case of failure of the above nutritional strategies, parenteral nutrition is even indicated. The risk of a refeeding syndrome, which can lead to delirium, stupor, seizures, coma and death, especially during the early stages, should be kept in mind. So, a monitored program of nutrition, a strict control of parameters and periodic blood examination should be scheduled in order to prevent this fatal complication, especially in those with a severe malnutrition status.\u003c/p\u003e \u003cp\u003eThe indication for close psychiatric monitoring of safety concerns, including suicidal thoughts, is also to be stressed. AN is often associated to comorbid disorders, mainly depression and anxiety disorders, which should always be screened for as they can further complicate treatment. Of note, depression and anxiety symptoms should be linked to AN. It may be challenging teasing apart primary depressive and anxiety disorders from depressive and anxiety symptoms caused by malnutrition. In fact, there is a consistent overlap in symptoms and signs. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Suicidal ideation and self-injurious behavior may complicate depression, anxiety and AN, requiring dedicated surveillance. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our study, the average HAC for patient is EUR 11,124. The high economic burden is in line with literature, which, analyzing cost-effectiveness intervention report high economic cost over short and long period analysis. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eFinally, during the Covid-19 pandemic period, there was a raise in the number of admissions to the emergency departments of patients with AN, having a more severe general status, psychiatric comorbidities and dehydration. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAt the same time, an increase of AN adolescent\u0026rsquo;s hospitalization rate has been observed. These findings should raise awareness of the mental difficulties experienced by children and adolescents during the Covid-19 pandemic. Our result are in line with the systematic revision of literature which reported on average a 48% increase in eating disorder admissions during the pandemic compared to previous timepoints. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) In fact, after pandemic onset, the increased stress caused by the Covid-19 circulation and the collective sense of lack of personal control likely contributed to increase neuropsychological disorders in adolescents. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eNevertheless, in our study, the LOS of AN adolescents was reduced compared to pre-pandemic period. A possible explanation is the rapid start of EF during Covid-19 pandemic (8 days, range 1\u0026ndash;14 days) which accelerated the discharge of patients. During the current pandemic, moreover, face-to-face clinical assessments, psychological and psychopathological treatments were reduced to minimize unnecessary physical contact and hence potential exposure to the virus. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) So, both medical staff and families\u0026rsquo; supporting discharge as soon as possible, which might have led to increased motivation to adhere to the AN treatment protocol and reduce psychopathological and psychological assessment, influenced the shorter duration of hospitalization.\u003c/p\u003e \u003cp\u003eNo statistically significant differences have been described between pre and post pandemic among patients comparing sex, comorbidities, EF needing in our study. Our results are in contrast with Girardi M et al who found out more intravenous fluids, oral dietetic supplements and enteral nutrition by nasogastric tube in post Covid-19 period than before the onset of pandemic. Moreover, the same group presented higher prevalence of psychiatric comorbidities and required most frequently treatments with psychotropic drugs. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Nevertheless, our result is in line with Goldberg et al who reported a 35% reduction in median hospitalization duration even if there was a significant increase in the number of adolescents hospitalized with AN. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Different findings regarding ED studies may correlate to the variability of restrictive public health measures and to the effects on the population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe economic burden of eating disorders is of note, although the available evidence probably under-estimates the costs. In fact, indirect costs, such as parents working missed days, have not been included in the cost-analysis study. As a conclusion, adequate sanitary policies as well as health economic analyses to gain insight into the cost-effectiveness of AN treatment are required.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAN: Anorexia nervosa\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI: body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCovid-19: Coronavirus disease of 2019\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNPD: neuropsychiatric disorders\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHAP: hospitalization in the acute phase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEF: enteral feeding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLOS: length of hospitalization\u003c/p\u003e\n\u003cp\u003eCBC: complete blood count.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChem: chemistry panel.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEKG: electrocardiogram.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance image.\u003c/p\u003e\n\u003cp\u003eAHC: acute hospitalization cost\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements: not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions: MM and EB coordinated the study; EB and AV conceived the study, SG and SM participated in its design; GS, CM and SV collected data, MM and IT carried out the literature research MR helped to draft the manuscript. All the authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding:\u0026nbsp;This work was supported also by the Italian Ministry of Health with \u0026ldquo;current Research funds\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003eCompeting interest: EB is Associate Editor for IJP\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: dataset is available at Marchili\u0026rsquo;s study room and data will be made available on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate:\u0026nbsp;The study was approved by ethics committee of the Bambino Ges\u0026ugrave; Children\u0026rsquo;s Hospital of Rome (approval number: 2526-OPBG-2021). Informed written consents were obtained by patients\u0026rsquo;parents. All methods of this study were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eConsent for publication: not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMitchell JE, Peterson CB. Anorexia Nervosa. N Engl J Med. 2020;382(14):1343\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBozzola E, Ferrara P, Spina G, Villani A, Roversi M, Raponi M, Corsello G, Staiano A. Italian Pediatric COVID-19 Board. The pandemic within the pandemic: the surge of neuropsychological disorders in Italian children during the COVID-19 era. Ital J Pediatr. 2022;48(1):126.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiagnostic. and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association,: DSM V; 2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHartmann A, Weber S, Herpertz S, Zeeck A. German Treatment Guideline Group for Anorexia Nervosa. Psychological treatment for anorexia nervosa: a meta-analysis of standardized mean change. Psychother Psychosom. 2011;80(4):216\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchili MR, Diamanti A, Zanna V, Spina G, Mascolo C, Roversi M, Guarnieri B, Mirra G, Testa G, Raucci U, Reale A, Villani A. Early Naso Gastric Feeding and Outcomes of Anorexia Nervosa Patients Nutrients. 2023;15(3):490.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoskowitz L, Weiselberg E. Anorexia Nervosa/Atypical Anorexia Nervosa. Curr Probl Pediatr Adolesc Health Care. 2017;47(4):70\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKostro K, Lerman JB, Attia E. The current status of suicide and self-injury in eating disorders: a narrative review. J Eat Disord. 2014;2:19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSvendsen VG, Lokkerbol J, Danner UN, Jansingh A, Evers SM, Wijnen BF. Design and testing of a health economic Markov model for treatment of anorexia nervosa. Expert Rev Pharmacoecon Outcomes Res. 2022;22(8):1243\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eByford S, Barrett B, Roberts C, Clark A, Edwards V, Smethurst N, Gowers SG. Economic evaluation of a randomised controlled trial for anorexia nervosa in adolescents. Br J Psychiatry. 2007;191:436\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpina G, Roversi M, Marchili MR, Raucci U, Fini F, Mirra G, Testa G, Guarnieri B, Clemente A, Diamanti A, Zanna V, Castiglioni MC, Vicari S, Reale A, Villani A. Psychiatric comorbidities and dehydration are more common in children admitted to the emergency department for eating disorders in the COVID-19 era. Eat Weight Disord. 2022;27(7):2473\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevoe J, Han D, Anderson A, Katzman A, Patten DK, Soumbasis SB, Flanagan A, Paslakis J, Vyver G, Marcoux E, Dimitropoulos G. The impact of the COVID-19 pandemic on eating disorders: A systematic review. Int J Eat Disord. 2023;56(1):5\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaripersad YV, Kannegiesser-Bailey M, Morton K, Skeldon S, Shipton N, Edwards K, Newton R, Newell A, Stevenson PG, Martin AC. Outbreak of anorexia nervosa admissions during the COVID-19 pandemic. Arch Dis Child. 2021;106(3):e15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHerpertz-Dahlmann B, Dempfle A, Eckardt S. The youngest are hit hardest: The influence of the COVID-19 pandemic on the hospitalization rate for children, adolescents, and young adults with anorexia nervosa in a large German representative sample. Eur Psychiatry. 2022;65(1):e84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalsh O. McNicholas F.Assessment and management of anorexia nervosa during COVID-19. Ir J Psychol Med. 2020;37(3):187\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGirardi M, Assalone C, Maines E, Genovese A, Naselli A, Nai Fovino L, Soffiati M, Franceschi R. Disease Characteristics and Psychiatric Comorbidities in Adolescents with Anorexia Nervosa Hospitalized During COVID-19 Pandemic. Front Biosci (Schol Ed). 2022;14(4):28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldberg L, Ziv A, Vardi Y, Hadas S, Zuabi T, Yeshareem L, Gur T, Steinling S, Scheuerman O, Levinsky Y. The effect of COVID-19 pandemic on hospitalizations and disease characteristics of adolescents with anorexia nervosa. Eur J Pediatr. 2022;181(4):1767\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anorexia Nervosa, hospitalization, hospitalization acute cost, children, Covid-19","lastPublishedDoi":"10.21203/rs.3.rs-3675318/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3675318/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eanorexia nervosa (AN) is a psychiatric disorders which may potentially led to a high risk of health medical complications, suicide and self-harming behaviour. Since Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN. The main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at IRCCS Bambino Gesù Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003efor the purpose of the study, we included children aged less than 18 years, admitted to IRCCS Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of AN. Medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Basing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003ea total of 260 patients has been included in the study with a median age of 15 years (range 6-18 years). The total health care cost of AN hospitalized patients was of EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930-45,739) and a median daily cost of EUR 593 (range EUR 557-930). Median cost was higher in case of comorbidities, guarded patients, enteral feeding. A prolonged hospitalization has been documented in subgroup A with a higher economic burden.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003ethe economic burden of eating disorders is of note. Adequate sanitary policies as well as health economic analyses are required to gain insight into the cost-effectiveness of AN management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003e2526-OPBG-2021\u003c/p\u003e","manuscriptTitle":"Pediatric acute hospitalization for Anorexia Nervosa: an economic evaluation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-01 20:10:24","doi":"10.21203/rs.3.rs-3675318/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-01-02T09:34:32+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-12-28T13:57:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-11-29T17:06:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2023-11-28T15:16:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"88dd3ffe-5caf-4b46-a848-c83ddf1da3b0","owner":[],"postedDate":"January 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-04T15:10:37+00:00","versionOfRecord":{"articleIdentity":"rs-3675318","link":"https://doi.org/10.1186/s13052-024-01605-0","journal":{"identity":"italian-journal-of-pediatrics","isVorOnly":false,"title":"Italian Journal of Pediatrics"},"publishedOn":"2024-02-27 15:00:53","publishedOnDateReadable":"February 27th, 2024"},"versionCreatedAt":"2024-01-01 20:10:24","video":"","vorDoi":"10.1186/s13052-024-01605-0","vorDoiUrl":"https://doi.org/10.1186/s13052-024-01605-0","workflowStages":[]},"version":"v1","identity":"rs-3675318","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3675318","identity":"rs-3675318","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}