Switching From Originator to Biosimilar Human Growth Hormone Using Dialogue Teamwork: Single-Center Experience From Sweden

INTRODUCTION: A new treatment plan was implemented at Skåne University Hospital, on economic grounds, for children requiring recombinant human growth hormone (rhGH) treatment. This involved switching patients from treatment with originator rhGHs to treatment with a biosimilar rhGH, somatropin (Omnitrope(®)), using a Dialogue Teamwork approach. The feasibility of using this approach to implement the switch of treatment was assessed, as well as the impact of the switch on treatment efficacy and cost of therapy. METHODS: As part of the Dialogue Teamwork approach, patients/parents received several opportunities for dialogue and sources of information, including discussions with the Head of Department, the responsible physician and a specialized endocrinology nurse. Height and height standard deviation score (HSDS) data were plotted for each individual patient (N = 98). A modeling approach was also used, to predict growth after switching to biosimilar rhGH; the predictions were then compared to the actual observed height after the switch. Costs to the clinic of rhGH therapy were calculated between May–August 2009 and May–August 2012. RESULTS: Of the 102 patients offered the switch, 98 accepted. Height and HSDS data indicated there was no negative impact on growth velocity after the switch to biosimilar rhGH. Modeling demonstrated that observed growth following the switch was consistent with predicted growth based on data before patients were switched. There were no reports of serious or unexpected adverse drug reactions following the switch to biosimilar rhGH. Following the switch, the cost to the clinic of rhGH treatment decreased from approximately 6 million SEK (May–August 2009) to approximately 4 million SEK (May–August 2012). This corresponds to an annual saving of 6 million SEK (€650,000). CONCLUSION: Patients were successfully switched from originator to biosimilar rhGH (somatropin), with no negative impact on growth, and no serious or unexpected adverse drug reactions. The switch from originator to biosimilar rhGH is associated with substantial cost savings

High prevalence of neurodevelopmental problems in adolescents eligible for bariatric surgery for severe obesity.

AIM: To assess the prevalence of neurodevelopmental problems in adolescents with severe obesity and their associations with binge eating and depression. METHODS: Data were collected at inclusion in a randomised study of bariatric surgery in 48 adolescents (73% girls; mean age 15.7 ± 1.0 years; mean body mass index 42.6 ± 5.2 kg/m2 ). Parents completed questionnaires assessing their adolescents' symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder and reported earlier diagnoses. Patients answered self-report questionnaires on binge eating and depressive symptoms. RESULTS: The parents of 26/48 adolescents (54%) reported scores above cut-off for symptoms of the targeted disorders in their adolescents, but only 15% reported a diagnosis, 32% of adolescents reported binge eating, and 20% reported symptoms of clinical depression. No significant associations were found between neurodevelopmental problems and binge eating or depressive symptoms. Only a third of the adolescents reported no problems in either area. CONCLUSION: Two thirds of adolescents seeking surgical weight loss presented with substantial mental health problems (reported by themselves or their parents). This illustrates the importance of a multi-professional approach and the need to screen for and treat mental health disorders in adolescents with obesity

A randomized controlled trial comparing intensive non-surgical treatment with bariatric surgery in adolescents aged 13-16 years (AMOS2): Rationale, study design, and patient recruitment.

BACKGROUND: Previous non-randomized studies show similar outcomes in adolescents and adults after bariatric surgery. We describe the study protocol, recruitment, and selected baseline data of patients in a randomized multi-center study, the Adolescent Morbid Obesity Surgery 2 (AMOS2). METHODS: Three clinics in Sweden collaborated in designing the study and recruitment of patients from August 1, 2014 to June 30, 2017. Patients were selected among adolescents 13-16 years of age attending third-level obesity care for at least one year. Patients were randomized 1:1 to bariatric surgery (predominantly Roux-en-Y gastric bypass) or intensive non-surgical treatment starting with an eight-week low-calorie-diet. RESULTS: Fifty adolescents (37 girls) were randomized, 25 (19 girls) to bariatric surgery. Mean age was 15.7 years (range 13.3-16.9), weight 122.6 kg (range 95-183.3), Body Mass Index (BMI) 42.6 kg/m2 (range 35.7-54.9) and BMI-SDS 3.45 (range 2.9-4.1). One patient had type 2 diabetes mellitus, and 12/45 (27%) had elevated liver enzymes. There were no significant differences between the groups. For the 39 eligible patients who were offered but declined inclusion, BMI was not different from included patients. However, patients who declined were younger, 15.2 years (p = 0.021). A sex difference was also noted with more of eligible girls, 37/53 (69.8%), than boys, 13/36 (36.1%), wanting to participate in the study (p = 0.002). CONCLUSIONS: This clinical trial, randomizing adolescents with severe obesity to bariatric surgery or intensive non-surgical treatment, aims at informing about whether it is beneficial to undergo bariatric surgery in early adolescence. It will also enlighten the outcome of comprehensive non-surgical treatment. The study was registered at www.clinicalTrials.gov number NCT02378259

Mental health in adolescents undergoing bariatric surgery : Psychological outcomes four months and two years after gastric bypass

Bariatric surgery is tried out as a new treatment option for adolescents with severe obesity. Little is known about outcomes in mental health in adolescents who undergo weight loss surgery.The 3 studies in this thesis assess mental health in adolescents before, and after 4 months, 1 year and 2 years after undergoing gastric bypass. The studies are part of the Swedish national AMOS study and all adolescents in the studies are from the AMOS cohort. AMOS included adolescents 13–18 years with a BMI ≥ 40 or ≥ 35 with comorbidity who had been under regular childhood obesity treatment for at least one year before undergoing surgery. Exclusion criteria were few but included psychotic disease and alcohol/drug dependence. Two out of 3 adolescents in AMOS are girls; mean age at surgery was 16.8 years and mean BMI 45.6.In study I, mental health was evaluated in 37 adolescents from baseline to 4 months after surgery. Compared to age and gender-matched population norms, the adolescents presenting for bariatric surgery reported impaired mental health. Four months after surgery significant improvements were seen for anxiety, depressive symptoms and self-concept. No significant change was seen for anger or disruptive behavior. The adolescents reported on average a mental health comparable to norms 4 months after surgery. However, not all adolescents had a positive mental health outcome and 16 % reported clinically significant impaired mental health on two or more variables. No baseline differences could be seen between the impaired adolescents and the improved or unchanged adolescents. In study II mental health was assessed in 88 adolescents at baseline and 1 and 2 years after surgery. Two years after surgery significant reduction was seen in symptoms of anxiety, depression, anger, and disruptive behavior. Also obesity-related problems were reduced. Improvements were seen for self-concept, self-esteem and mood. Improvements took place mainly during the first year after surgery and the second year was characterized by stabilization. Two years after surgery, the adolescents reported on average symptoms of anxiety, depression, anger, and disruptive behavior comparable to norms. Also self-concept was at a normative level. However, the adolescents reported mood lower than age-matched peers and mood was also low when it was compared to middle-aged adults undergoing surgery. A marked group, 19 %, reported depressive symptoms in the clinical range and 13 % reported severe depressive symptoms.In study III adolescents (20 %) who reported poor mental health (PMH) 2 years after surgery were compared to adolescents who reported average/good mental health 2 years after surgery. Anxiety, depression and mental health at baseline could significantly predict PMH 2 years after surgery. However, several aspects of mental health were assessed at baseline and no other variable could predict mental health after surgery. Significant differences were seen between the groups at the follow-up 1 year after surgery; however few mental health variables had a significantly different trend between the groups over the first year. Suicidal ideation was reported by 14 % of the adolescents 2 years after surgery. Weight outcome was comparable between the two groups at all assessment points and physical health was equally improved in both groups 2 year after surgery. The studies in the present thesis show a general improvement in several aspects of mental health in adolescents, such as reduced symptoms of anxiety and depression, reduced externalizing symptoms, improved self-concept and reduced problems related to weight and body shape over 2 years after gastric bypass. However, not all adolescents have a positive psychosocial outcome and 4 months after surgery 16 % report impaired mental health. Depressive symptoms in the clinical range are reported by 1 out of 5, 2 years after surgery and 14 % report suicidal ideation. These figures are much higher than expected from the adult surgery literature. The studies in the present thesis indicate that adolescent bariatric surgery candidates are a vulnerable group and that repeated monitoring and psychological interventions are important before and after bariatric surgery

Three decades of increase in health anxiety : Systematic review and meta-analysis of birth cohort changes in university student samples from 1985 to 2017

Health anxiety can be defined as a multifaceted trait that is primarily characterised by a fear of, or preoccupation with, serious illness. Whereas low levels of health anxiety can be helpful, clinically significant levels are associated with personal suffering and substantial societal costs. As general anxiety is probably on the rise, and the Internet has increased access to health-related information, it is commonly speculated that health anxiety has increased over the past decades. We tested this hypothesis based on a systematic review and meta-analysis of birth cohort mean health anxiety in Western university student samples from 1985 to 2017. Sixty-eight studies with 22 413 student participants were included. The primary analysis indicated that the mean score on the Illness Attitudes Scales had increased by 4.61 points (95 % CI: 1.02, 8.20) from 1985 to 2017. The percentage of general population Internet users in the study year of data collection was not predictive of student mean health anxiety. In conclusion, this study corroborates the hypothesis of an increase in health anxiety, at least in the student population, over the past decades. However, this increase could not be linked to the introduction of the Internet

Long-term outcomes following adolescent metabolic and bariatric surgery

Severe obesity in adolescence negatively impacts upon health and wellbeing. Lifestyle modifications do not usually achieve a sufficient degree or durability of weight loss to mitigate the risk of medical complications. In recent years, metabolic and bariatric surgery (MBS), already a well-established treatment for adults with severe obesity, has emerged as an option in adolescents. Controlled studies in this age group have demonstrated substantial and sustained weight loss, improvements in associated health parameters, and a safety profile surpassing that observed in adult patients. This review aims to present published data on the results of MBS in adolescents with a focus on long-term outcomes. Indications for bariatric surgery and aspects of timing in the young persons life are also presented, along with safety considerations and factors influencing patient selection for surgery. We conclude, predominantly from short- to medium-term outcomes data, that MBS is a safe and valuable therapeutic option for adolescents with severe obesity. Considering the poor health and social wellbeing prognosis in this group, MBS appears to be underutilized. The need for continued research, multiprofessional specialist provision, coherent contemporary clinical guidelines, and routine long-term follow-up in adolescents undergoing MBS is highlighted