Obesity treatment in adolescents and adults in the era of personalized medicine.

In this multi-professional review, we will provide the in-depth knowledge required to work in the expanding field of obesity treatment. The prevalence of obesity has doubled in adults and quadrupled in children over the last three decades. The most common treatment offered has been lifestyle treatment, which has a modest or little long-term effect. Recently, several new treatment options-leading to improved weight loss-have become available. However, long-term care is not only about weight loss but also aims to improve health and wellbeing overall. In the era of personalized medicine, we have an obligation to tailor the treatment in close dialogue with our patients. The main focus of this review is new pharmacological treatments and modern metabolic surgery, with practical guidance on what to consider when selecting and guiding the patients and what to include in the follow-up care. Furthermore, we discuss common clinical challenges, such as patients with concurrent eating disorder or mental health problems, and treatment in the older adults. We also provide recommendations on how to deal with obesity in a non-stigmatizing way to diminish weight stigma during treatment. Finally, we present six microcases-obesity treatment for persons with neuropsychiatric disorders and/or intellectual disability; obesity treatment in the nonresponsive patient who has "tried everything"; and hypoglycemia, abdominal pain, and weight regain after metabolic surgery-to highlight common problems in weight-loss treatment and provide personalized treatment suggestions.

Family meals on prescription as treatment for childhood obesity-a randomized controlled trial.

The aim with the present study was to evaluate the effects and tolerability of Family Meals on Prescription, a 3-month intensive dietary intervention with a participatory approach on body mass index (BMI) and metabolic health in children living with obesity. In this prospective randomized controlled trial, children aged 5-15 years were included from the Pediatric Obesity outpatient Clinics in Halland, Sweden. Participants were randomly assigned to receive lifestyle treatment with or without Family Meals on Prescription (FMP) consisting of a subsidized prepacked grocery bag including recipes and provisions for five Family Meals per week for 3 months. The primary endpoint was changed in BMIz after 3, 12 and 18-24 months and secondary endpoints included to assess tolerability of FMP and effects on metabolic biomarker and frequency of shared meals. Eighty-nine children (51.7% female) entered the study, 54 patients in the intervention group and 35 in the control group. There were no significant differences between the groups concerning gender, age or level of obesity at baseline. The Family Meal on Prescription intervention combined with lifestyle treatment led to a significantly greater reduction in BMIz than lifestyle treatment alone after the 3-month long intervention (- 0.17 vs + 0.01, p < 0.01); however, this difference was not sustained throughout the study period, and in fact, the control group had a greater reduction in BMIz after 18-24 months.A subsidized prepacked grocery bag may be a novel, well-tolerated and effective tool in the treatment of childhood obesity. The fact that the BMIz reduction shown at the end of the intervention did not persist over time emphasized the need of long-term treatment. Registered at clinicaltrals.gov 27 Nov 2020, retrospectively registered: clinicaltrials.gov number 19002468. https://clinicaltrials.gov/study/NCT05225350 What is Known: • Swedish data shows that lifestyle treatment alone is not sufficient for many families undergoing treatment for childhood obesity. • Regular family meals and mealtime routines have been shown to be important for nutritional health and dietary patterns in children and adolescents. What is New: • This intervention with a participatory approach involving prepacked family meals was well tolerated and led to a significant reduction in BMIz during the intervention. • That fact that these results were not sustained over time indicates a need to evaluate longer interventions, and that childhood obesity is a chronic and complex disease which requires long-time treatments.

Family screening for neurodevelopmental problems and its associations with child cognitive function enable tailored treatment for childhood obesity.

AIM: To identify neurodevelopmental disorders in children with obesity, and investigate associations to cognitive functions as well as parents' self-reported neurodevelopmental problems. METHODS: Eighty children were included at two outpatient obesity clinics in Sweden 2018-2019. Of these, 50 children without previously diagnosed neurodevelopmental disorders were screened, and so were their parents. Children who screened positive for neurodevelopmental problems were referred to a specialised psychiatry unit for further diagnosis. Test results of cognitive functioning were compared with the norm and between study groups by neurodevelopmental diagnoses. RESULTS: Of the screened families, 17/50 children were diagnosed by the psychiatric unit with attention deficit-hyperactivity disorder (ADHD) and 15/82 parents screened positive for neurodevelopmental problems. Having a mother who screened positive for neurodevelopmental problems was associated with child ADHD (p < 0.05). The children's full-scale intelligence quotient (92.86 ± 12.01, p < 0.001) and working memory index (90.62 ± 12.17, p < 0.001) were lower than the norm. Working memory index was lower in children with ADHD compared to without ADHD: 84.76 ± 9.58 versus 94.09 ± 12.29 (p ≤ 0.01). Executive constraints were associated with verbal deviances. CONCLUSION: Increased awareness is needed about the overlap between neurodevelopmental problems and obesity in obesity clinics.

Prevalence of overweight and obesity from 5 to 19 years of age in Gothenburg, Sweden.

AIM: The aim of this study was to present prevalence data for overweight and obesity across school age in a large, recent, population-based cohort of children in Gothenburg, Sweden. METHODS: We included 66,807 children (48.5% girls) aged 5-18.9 years who had their height and weight measured in school health care 2015-2018. The BMI values were categorised according to the age-dependent cut-offs for overweight and obesity from the International Obesity Task Force (IOTF). RESULTS: Overall, the prevalence of overweight and obesity for girls and boys was 18.1% and 18.0%, respectively. We observed increasing proportions of overweight (girls 11.5-17.1% and boys 8.4-17.4%) and obesity (girls 3.0-4.2% and boys 2.7-6.1%) with increasing age (p < 0.001 for trend in both sexes). Moreover, girls had higher prevalence of overweight during ages 5.0 to 8.9 years compared with boys (p < 0.001), while boys had higher prevalence of obesity 15.0-18.9 years compared with girls (p < 0.001). CONCLUSION: In conclusion, we demonstrate increasing prevalence of overweight and obesity across the entire school age range, as well as differences in prevalences between boys and girls, in a population-based sample of 67,000 children in Gothenburg city, Sweden. Continuous monitoring of schoolchildren, together with effective preventive measures, is crucial to curb the obesity epidemic and its consequences.

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.

Neurodevelopmental disorders in children seeking obesity treatment- associations with intellectual ability and psychiatric conditions.

Background: Neurodevelopmental disorders (NDD), psychiatric comorbidity and cognitive deficits are commonly seen in children with obesity; however, little is known about the overlap between these conditions. This study aimed to examine the undiagnosed and diagnosed frequency of NDDs and explore its association with psychiatric conditions and general intellectual ability (IQ) in children presenting for obesity treatment. Methods: In this observational study at two outpatient obesity clinics during 2018-2019, 80 children (8-17 years) were consecutively recruited, and screened for NDD unless already diagnosed with an NDD. A psychiatric unit evaluated children who screened positive for NDD. Diagnoses and clinical background factors were collected from medical records. IQ was assessed with the Weschler Intelligence Scales and internalizing symptoms were assessed using the Beck Youth Inventories. Associations between background factors, IQ and internalizing symptoms were explored in relation to having an NDD or not. Results: We found that 47/80 children had at least one NDD. Children with a diagnosed NDD before study start (n = 30) had significantly more comorbidities than children diagnosed after the study screening (n = 17) (P = .01). Greater cognitive impairment was seen in children with NDD compared with children without an NDD (P = .01). Also, 33/73 participants self-reported substantial internalizing symptoms. At follow-up, 21/79 participants, in addition to NDD, had been diagnosed with another psychiatric disorder. Ten of these were children that had been diagnosed with an NDD before study start. Conclusion: The overlap between NDD, cognitive deficits and psychiatric conditions in children with obesity is an important consideration for clinical practice. Screening for these conditions may be necessary when providing targeted interventions.

Systematic Development of National Guidelines for Obesity Care: The Swedish Approach.

INTRODUCTION: With the rapid development of treatment modalities for obesity management, there is an increasing demand for guidance to facilitate the prioritization of interventions. In 2020, the Swedish National Board of Health and Welfare started the process of producing the first national guidelines for obesity care directed to decision makers who allocate resources to the best knowledge-based care. The main aim of this paper was to describe the systematic development of these guidelines, designed to guarantee uniformly high standards of care throughout the whole country. METHODS: The standardized procedures of the National Board of Health and Welfare were applied to construct guidelines in a systematic and transparent way, including priority setting of recommendations and quality indicators to evaluate the progress of implementation. The process involved independent expert committees including professionals and patient representatives, and the guidelines were reviewed through an open public consultation. RESULTS: National guidelines were issued in 2023, encompassing a broad scope, from identification and diagnosis to multiple treatment modalities, embedded in a life-course perspective from pregnancy to the elderly, as well as highlighting the need for improved knowledge and competence of health care providers. CONCLUSIONS: National guidelines for improved standard care and evidence-based and efficient use of health care resources for obesity treatment can be developed in a systematic way with professionals and patient representatives.

Cognitive functioning in adolescents with severe obesity undergoing bariatric surgery or intensive non-surgical treatment in Sweden (AMOS2): a multicentre, open-label, randomised controlled trial.

Background: Severe obesity during childhood is associated with cognitive deficits. Studies in adults have suggested improvements in executive functioning and memory after bariatric surgery. Our aim was to explore changes in cognitive function in adolescents over two years after bariatric surgery or intensive non-surgical treatment. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) is a multicentre, open-label, randomised controlled trial in which adolescents (aged 13-16 years) with severe obesity (defined as body mass index (BMI) ≥35 kg/m2) at three specialised obesity centres in Sweden, were randomly assigned to receive bariatric surgery or intensive non-surgical treatment. Herein we report the results of the prespecified exploratory endpoint of change in cognitive functioning. Inclusion in AMOS2 required Tanner pubertal stage ≥3, previous participation in lifestyle obesity treatment for at least one year, and passed assessment form a paediatrician and a paediatric psychologist. Adolescents with severe intellectual disability or other severe, pervasive developmental disorder were excluded. Participants underwent baseline assessment of general intellectual ability, executive functioning, and memory before randomisation. Tests were administrated by clinical psychologists and repeated at one- and two-year follow-up timepoints. Differences in means between groups during follow-up are provided with confidence intervals. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: Between October 28 2015 and June 7 2017, 46 adolescents (74% girls), with a mean age of 15.8 (±0.92) years and a mean BMI of 42.8 (±5.4) kg/m2, were included and randomised (23 to bariatric surgery and 23 to intensive non-surgical treatment). At baseline 23/46 (50%) of the adolescents had general intellectual functioning classified as borderline or below. For 15/18 (83%) aspects of cognitive functioning, no significant differences in change over two years were identified between groups; Immediate (average difference during follow-up 1.0 [95% CI: -2.6 to 4.6]) and Delayed (0.5 [95% CI: -0.6 to 1.6]) Verbal Recall, Category Fluency (1.1 [95% CI: -1.6 to 3.8]) and Switching (1.5 [95% CI: -0.0 to 2.9]), Number (-6.0 [95% CI: -12.3 to 0.3]) and Letter (0.1 [95% CI: -5.2 to 5.3]) Sequencing, Number-Letter Switching (-10.3 [95% CI: -26.4 to 5.8]), Motor Speed (-8.3 [95% CI: -17.5 to 0.9]), Colour Naming (-1.9 [95% CI: -4.2 to 0.3]), Inhibition (-3.6 [95% CI: -9.6 to 2.5]), Inhibition Switching (-6.7 [95% CI: -15.3 to 1.9]), Mazes (-0.5 [95% CI: -4.9 to 3.9]), Digit Span Forward (0.1 [95% CI: -0.6 to 0.9 ]) and Backward (0.6 [95% CI: -0.4 to 1.6 ]), and Estimated IQ (0.4 [95% CI: -3.9 to 4.8]; all p > 0.05). Three sub-tests assessing fundamental cognitive skills improved more over two years in operated adolescents than in intensive non-surgical treatment; Letter Fluency (average difference during follow-up 3.8 [95% CI: 0.1-7.5]; p = 0.046), Visual Scanning (-6.5 [95% CI: -11.6 to -1.5]; p = 0.011), and Word Reading (-1.9 [95% CI: -3.3 to -0.4]; p = 0.011). Interpretation: In contrast to non-randomised studies in adults, we could not demonstrate an association of bariatric surgery and its accompanying significant weight loss with overall greater improvement in executive functions and memory in adolescents over two years compared with a non-surgical group without weight loss. However, lack of statistical power is a potential limitation. The clinical relevance of greater improvements in basic cognitive skills needs to be explored. Funding: Sweden's innovation agency (VINNOVA), Swedish Research Council, Joanna Cocozza foundation for paediatric research, The Skane University Hospital Psychology Research and Development Grant, Tore Nilsson's Foundation, SUS Foundations and Donations, and Mary von Sydow's Foundation.

Metabolic and Bariatric Surgery in Adolescents: For Whom, When, and How?

Severe obesity in adolescence profoundly impacts health and social well-being. Lifestyle modifications are seldom successful in maintaining sufficient weight loss to mitigate the risk of complications. Metabolic and bariatric surgery (MBS) is a standard treatment for adult patients and has emerged as an option for adolescent patients. Several high-quality studies of adolescent MBS show substantial and sustained improvements both in weight and cardiometabolic parameters, as well as a safety profile similar to that seen in adult patients. Patients report improvements in health- and weight-related quality of life. Concerns around adolescent MBS can be attributed to a fear of side effects on growth and puberty, risk of nutritional deficiencies and osteoporosis, alcohol abuse, psychosocial vulnerability, and the ability to consent in the decision process. Guidelines give somewhat different recommendations, but the most comprehensive guidelines from the American Society for Metabolic and Bariatric Surgery recommend MBS for class III obesity or class II obesity with comorbidity. This mini-review aimed to pre-sent published data on MBS in adolescents. We discuss indications for MBS and the optimal timing in the young person's life, the choice of surgical method, and MBS in relation to the new anti-obesity medications. Based on data primarily from the USA and Sweden, we conclude that MBS is a valuable treatment option for adolescents with severe obesity that appears underutilized against the backdrop of the poor prognosis of severe obesity. We argue for continued research, development of guidelines, multi-professional teamwork, long-term follow-up, and centralization of adolescent MBS.

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

BACKGROUND: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. METHODS: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. FINDINGS: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. INTERPRETATION: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. FUNDING: Sweden's Innovation Agency, Swedish Research Council Health.

Adolescents' and professionals' experiences of metabolic and bariatric surgery and requirements for preoperative and postoperative support through mHealth: a qualitative study.

OBJECTIVES: This study aimed to explore adolescents' and professionals' incentives and experiences of metabolic and bariatric surgery (MBS) and to explore perceived needs and requirements for preoperative and postoperative support through an mHealth intervention to improve long-term healthy lifestyle behaviour and health outcomes. DESIGN: An inductive qualitative study using in-depth semistructured interviews. SETTING: Three hospital-based specialist paediatric obesity treatment units in Sweden. PARTICIPANTS: A total of 18 participants (14 women and 4 men). Nine adolescents aged between 17 and 22 years who had undergone or were about to undergo surgery, and nine professionals, including researchers and clinicians working in various professional roles such as physiotherapist, dietician, nurse, psychologist, physician and pedagogue. RESULTS: Both informant groups of participants highlighted that undergoing MBS is a complex process, and hence actions are required on several levels to optimise the positive, long-term effects of surgery. Efficient communication between the healthcare professionals and adolescents was considered crucial and a key success factor. Informants acknowledged the need for additional support that relates to psychosocial well-being and mental health in order to understand, form and accept new behaviours and identity. An mHealth intervention should be seen as complementary to physical appointments, and informants acknowledged that an app could be a way of improving access to healthcare, and a useful tool to allow for individually tailored and easily available support. CONCLUSIONS: The findings address the importance of a personal encounter and a need for additional support that relates to psychosocial well-being, mental health and healthy lifestyle behaviour. These findings should be incorporated into future research concerning mHealth interventions in MBS during adolescence.

Impact of obesity on intensive care outcomes in patients with COVID-19 in Sweden-A cohort study.

BACKGROUND: Previous studies have shown that a high body mass index (BMI) is a risk factor for severe COVID-19. The aim of the present study was to assess whether a high BMI affects the risk of death or prolonged length of stay (LOS) in patients with COVID-19 during intensive care in Sweden. METHODS AND FINDINGS: In this observational, register-based study, we included patients with COVID-19 from the Swedish Intensive Care Registry admitted to intensive care units (ICUs) in Sweden. Outcomes assessed were death during intensive care and ICU LOS ≥14 days. We used logistic regression models to evaluate the association (odds ratio [OR] and 95% confidence interval [CI]) between BMI and the outcomes. Valid weight and height information could be retrieved in 1,649 patients (1,227 (74.4%) males) with COVID-19. We found a significant association between BMI and the risk of the composite outcome death or LOS ≥14 days in survivors (OR per standard deviation [SD] increase 1.30, 95%CI 1.16-1.44, adjusted for sex, age and comorbidities), and this association remained after further adjustment for severity of illness (simplified acute physiology score; SAPS3) at ICU admission (OR 1.30 per SD, 95%CI 1.17-1.45). Individuals with a BMI ≥ 35 kg/m2 had a doubled risk of the composite outcome. A high BMI was also associated with death during intensive care and a prolonged LOS in survivors assessed as separate outcomes. The main limitations were the restriction to the first wave of the pandemic, and the lack of information on socioeconomic status as well as smoking. CONCLUSIONS: In this large cohort of Swedish ICU patients with COVID-19, a high BMI was associated with increasing risk of death and prolonged length of stay in the ICU. Based on our findings, we suggest that individuals with obesity should be more closely monitored when hospitalized for COVID-19.

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.