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1.
  • Jolstedt, Maral, et al. (författare)
  • Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders : a single-centre, single-blind, randomised controlled trial
  • 2018
  • Ingår i: Lancet child and adolescent health. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 2352-4642 .- 2352-4650. ; 2:11, s. 792-801
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Paediatric anxiety disorders are associated with substantial disability and long-term adverse consequences, but only a small proportion of affected children have access to evidence-based treatment. Internet-delivered cognitive behavioural therapy (ICBT) could help increase accessibility but needs further rigorous assessment. We aimed to assess the efficacy and cost-effectiveness of ICBT in the treatment of paediatric anxiety disorders. Methods: We did a single-blind randomised controlled trial in a clinical research unit within the Child and Adolescent Mental Health Services in Stockholm (Sweden). Eligible participants were children aged 8-12 years with a diagnosis of a principal anxiety disorder (seperation anxiety disorder, generalised anxiety disorder, specific phobia, social anxiety disorder, or panic disorder) of at least moderate severity. We randomly allocated participants (1:1) to ICBT or internet-delivered child-directed play, an active comparator aimed to improve parent child relationships and increase a child's self-esteem without directly targeting anxiety. Block sizes for the randomisation varied between four and six and were generated using a computer random-number generator, and the allocation was concealed from the researchers by opaque sealed envelopes. Both treatment programmes comprised 12 modules presented over 12 weeks with weekly asynchronous online therapist support, and consisted of texts, films, illustrations, and exercises. The primary outcome was severity rating of the principal anxiety disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4 corresponds to meeting the criteria for the principal diagnosis), assessed by clinicians masked to treatment allocation. All participants were included in the primary analysis (intention-to-treat). This trial is registered at ClinicalTrials.gov, number NCTO 2350257. Findings: Between March 11, 2015, and Oct 21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or internet-delivered child-directed play (n=65). The clinician-assessed severity rating of the principal anxiety disorder improved significantly after the 12-weeks treatment period for participants in both ICBT (within-group effect size 1.22, 95% CI 0 78-1.65) and the active control (0.72, 0.44-1.00) groups. However, greater improvement was seen with ICBT than with the active control (estimated mean difference 0.79, 95% CI 0.42-1.16, p=0.002; between-group effect size 0.77, 95% CI 0.40-1.15). 29 (48%) participants in the ICBT group no longer had their principal diagnosis, compared to nine (15%) in the active control group (odds ratio 5.41, 95% CI 2.26 to 12.90, p<0.0001); the number needed to treat for ICBT to gain one additional participant in remission was three (95% CI 2.85 to 3.15). ICBT resulted in an average societal-cost saving of 493 05 (95% CI 477.17 to 508.92) per participant. No severe adverse events were reported. Interpretation ICBT is an efficacious and cost-effective treatment for paediatric anxiety disorders that should be considered for implementation in routine clinical care.
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2.
  • Melén, Erik, et al. (författare)
  • Allergies to food and airborne allergens in children and adolescents : role of epigenetics in a changing environment
  • 2022
  • Ingår i: The Lancet Child & Adolescent Health. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 2352-4642. ; 6:11, s. 810-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic diseases today affect millions of children and adolescents worldwide. In this review, we focus on allergies to food and airborne allergens, and provide examples of prevalence trends during a time when climate change is of increasing concern. Profound environmental changes have affected natural systems in terms of biodiversity loss, air pollution levels and climate change. We discuss potential links between these changes and allergic diseases in children, as well as clinical implications. Several exposures of relevance for allergic disease also correlate with epigenetic changes such as DNA-methylation levels. We propose that epigenetics may offer a promising tool by which exposures and hazards related to a changing environment may be captured. Epigenetics may also provide promising biomarkers and help elucidation of mechanisms related to allergic disease initiation and progress. Key messages: • Allergic diseases affect millions of children and adolescents worldwide; between 5 and 30% of adolescents report rhino-conjunctivitis symptoms and up to 10 % report food allergy. • Links between climate change and allergic diseases are of increasing concern, and these include: extended and altered pollen seasons, spread of allergens to new areas along with changing and warmer climate, air pollution exposures changes, increasing exposure to heat events, and altered biodiversity. • These new climate change aspects of allergic diseases have clinical implications for prevention, diagnostics and treatment. • Epigenetic changes, exemplified by DNA methylation, are associated both with environmental exposures and allergic diseases, although causality needs to be explored further. • There is potential in the use of epigenetic signatures and omics profiles to detect and monitor aspects of environmental exposures of relevance for health and disease in children and adolescents.
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3.
  • Bruze, Gustaf, et al. (författare)
  • Mental health from 5 years before to 10 years after bariatric surgery in adolescents with severe obesity: a Swedish nationwide cohort study with matched population controls
  • 2024
  • Ingår i: LANCET CHILD & ADOLESCENT HEALTH. - : ELSEVIER SCI LTD. - 2352-4642 .- 2352-4650. ; 8:2, s. 135-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The long-term effects of bariatric surgery on the mental health of adolescents with severe obesity remain uncertain. We aimed to describe the prevalence of psychiatric health-care visits and filled prescription psychiatric drugs among adolescents with severe obesity undergoing bariatric surgery in the 5 years preceding surgery and throughout the first 10 years after surgery, and to draw comparisons with matched adolescents in the general population. Methods: Adolescents with severe obesity and who underwent bariatric surgery were identified through the Scandinavian Obesity Surgery Registry. We included adolescents who had bariatric surgery between 2007 and 2017 and were younger than 21 years at time of surgery. Each adolescent patient was matched with ten adolescents from the general population by age, sex, and county of residence. Specialist psychiatric care and filled psychiatric prescriptions were retrieved from nationwide data registers. Findings: 1554 adolescents (<21 years) with severe obesity underwent bariatric surgery between 2007 and 2017, 1169 (75%) of whom were female. At time of surgery, the mean age was 19.0 years [SD 1.0], and the mean BMI was 43.7 kg/m(2) (SD 5.5). 15 540 adolescents from the general population were matched with adolescents in the surgery group. 5 years before the matched index date, 95 (6.2%) of 1535 surgery patients and 370 (2.5%) of 14 643 matched adolescents had a psychiatric health-care visit (prevalence difference 3.7%; 95% CI 2.4-4.9), whereas 127 (9.8%) of 1295 surgery patients and 445 (3.6%) of 12 211 matched adolescents filled a psychiatric drug prescription (prevalence difference 6.2%; 95% CI 4.5-7.8). The year before the matched index date, 208 (13.4%) of 1551 surgery patients and 844 (5.5%) of 15 308 matched adolescents had a psychiatric health-care visit (prevalence difference 7.9%; 95% CI 6.2-9.6), whereas 319 (20.6%) of 1551 surgery patients and 1306 (8.5%) of 15 308 matched adolescents filled a psychiatric drug prescription (prevalence difference 12.0%; 10.0-14.1). The prevalence difference in psychiatric health-care visits peaked 9 years after the matched index date (12.0%; 95% CI 9.0-14.9), when 119 (17.6%) of 675 surgery patients and 377 (5.7%) of 6669 matched adolescents had a psychiatric health-care visit. The prevalence difference in filled psychiatric drug prescription was highest 10 years after the matched index date (20.4%; 15.9-24.9), when 171 (36.5%) of 469 surgery patients and 739 (16.0%) of 4607 matched adolescents filled a psychiatric drug prescription. The year before the matched index date, 19 (1.2%) of 1551 surgery patients and 155 (1.0%) of 15304 matched adolescents had a health-care visit associated with a substance use disorder diagnosis (mean difference 0.2%, 95% CI -0.4 to 0.8). 10 years after the matched index date, the prevalence difference had increased to 4.3% (95% CI 2.3-6.4), when 24 (5.1%) of 467 surgery patients and 37 (0.8%) of 4582 matched adolescents had a health-care visit associated with a substance use disorder diagnosis. Interpretation: Psychiatric diagnoses and psychiatric drug prescriptions were more common among adolescents with severe obesity who would later undergo bariatric surgery than among matched adolescents from the general population. Both groups showed an increase in prevalence in psychiatric diagnoses and psychiatric drug prescriptions leading up to the time of surgery, but the rate of increase in the prevalence was higher among adolescents with severe obesity than among matched adolescents. With the exception of health-care visits for substance use disorders, these prevalence trajectories continued in the 10 years of follow-up. Realistic expectations regarding mental health outcomes should be set preoperatively. Funding: Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare.
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4.
  • Järvholm, Kajsa, et al. (författare)
  • 5-year mental health and eating pattern outcomes following bariatric surgery in adolescents : a prospective cohort study
  • 2020
  • Ingår i: The Lancet Child and Adolescent Health. - : Elsevier. - 2352-4642 .- 2352-4650. ; 4:3, s. 210-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13–18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI −7 to 16], p=0·4263) or after intervention (10% [−6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [−10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.
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5.
  • Järvholm, Kajsa, et al. (författare)
  • Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden
  • 2023
  • Ingår i: LANCET CHILD & ADOLESCENT HEALTH. - : ELSEVIER SCI LTD. - 2352-4642 .- 2352-4650. ; 7:4, s. 249-260
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 Malmo). 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 center dot 8 years (SD 0 center dot 9) and mean BMI at baseline was 42 center dot 6 kg/m2 (SD 5 center dot 2). After 2 years, BMI change was -12 center dot 6 kg/m2 (-35 center dot 9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0 center dot 2 kg/m2 (0 center dot 4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12 center dot 4 kg/m2 [95% CI -15 center dot 5 to -9 center dot 3]; p<0 center dot 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 center dot 9 [95% CI -1 center dot 2 to -0 center dot 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. Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved.
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6.
  • Galera, Cédric, et al. (författare)
  • Prospective associations between ADHD symptoms and physical conditions from early childhood to adolescence : a population-based longitudinal study
  • 2023
  • Ingår i: The Lancet. Child & adolescent health. - : Elsevier. - 2352-4642 .- 2352-4650. ; 7:12, s. 863-874
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The co-occurrence between attention-deficit hyperactivity disorder (ADHD) and physical conditions is frequent but often goes unrecognised. Most available evidence on the links between ADHD and physical conditions relies on cross-sectional studies. Understanding temporal sequences of associations is key to inform appropriate treatment and preventive strategies. We aimed to assess possible longitudinal associations between ADHD symptoms and a broad range of physical conditions, adjusting for several confounding factors.METHODS: Participants came from the population-based Quebec Longitudinal Study of Child Development. Participants were selected from the Quebec Birth Registry, recruited between October, 1997, and July, 1998, from the province of Quebec, Canada, and followed up in early childhood (n=2120; age 5 months-5 years), middle childhood (n=1750; age 6-12 years), and adolescence (n=1573; age 13-17 years). Main outcome measures included ADHD symptom severity and physical conditions, which were reported by the person most knowledgeable of the child in early childhood, by teachers in middle childhood, and self-reported in adolescence. Multivariable regression analyses were conducted to study the prospective associations between ADHD symptoms and later physical conditions, and physical conditions and later ADHD symptoms, adjusting for multiple confounders.FINDINGS: We found several prospective associations between ADHD symptoms and physical conditions including asthma, high BMI (≥1 SD above the mean), epilepsy, dental caries, acute infections, injuries, and sleep problems. After adjusting for key confounding factors, several associations remained: ADHD symptoms in early childhood were associated with later high BMI during middle childhood (odds ratio [OR] 1·19 [95% CI 1·05-1·35]) and adolescence (OR 1·14 [1·01-1·29]), and with unintentional injuries during adolescence (OR 1·10 [1·01-1·21]). ADHD symptoms in middle childhood were significantly associated with later dental caries during adolescence (OR 1·10 [1·01-1·20]). Unintentional injuries in early childhood were associated with later ADHD symptoms in middle childhood (standardised mean difference [SMD] 0·15 [0·05-0·24]) and adolescence (SMD 0·13 [0·04-0·23]), and restless legs syndrome symptoms in middle childhood were associated with later ADHD symptoms in adolescence (SMD 0·15 [0·05-0·25]).INTERPRETATION: Our results point to the need to carefully monitor children with ADHD in early or middle childhood for several physical conditions, and to monitor children with particular physical conditions for ADHD symptoms. Our study also calls for policies to promote more integrated health-care systems for children with complex mental and physical needs, bridging the current gap between mental and physical health-care services.
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8.
  • Wintzell, Viktor, et al. (författare)
  • Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease : a Swedish-Danish nationwide cohort study
  • 2019
  • Ingår i: Lancet Child and Adolescent Health. - : Elsevier. - 2352-4642 .- 2352-4650. ; 3:3, s. 158-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known. We aimed to investigate whether use of azathioprine is associated with the risk of acute pancreatitis in children with inflammatory bowel disease.Methods: We did a nationwide register-based cohort study in Sweden (2006-16) and Denmark (2000-16). All paediatric patients (<18 years of age) with inflammatory bowel disease during the study period were identified through hospital records. Episodes of incident azathioprine use and no use of any thiopurine were matched (1:1) using propensity scores, controlling for sociodemographic characteristics, comorbidities, previous treatment, indicators of disease severity, and health care use. Incident acute pancreatitis (physician-assigned diagnosis with ICD-10 code K85) occurring in the 90 days following treatment initiation were identified through outpatient and inpatient hospital records.Findings: We identified 3574 azathioprine episodes and 18 700 no-use episodes, which resulted in 3374 pairs after propensity score matching; baseline characteristics in the matched cohort were well balanced. Among the matched azathioprine episodes, mean age was 14.3 years (SD 3.1), 1854 (54.9%) were male, 1923 (57.0%) had Crohn's disease, and 1451 (43.0%) had ulcerative colitis or unclassified inflammatory bowel disease. Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49.1 events per 1000 person-years) compared with six events in the no-use group (8.4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5.82 [95% CI 2.47-13.72]; absolute difference 1.0 [95% CI 0.3-2.6] events per 100 patients) during the 90-day risk period.Interpretation: Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies.
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10.
  • Crump, Casey, et al. (författare)
  • Gestational age at birth and mortality from infancy into mid-adulthood : a national cohort study
  • 2019
  • Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 3:6, s. 408-417
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Breakthroughs in the treatment of preterm birth approximately 40 years ago have enabled a generation of preterm survivors to now reach mid-adulthood. Understanding their health sequelae is essential for guiding their long-term care. We did a study to examine preterm birth in relation to mortality into mid-adulthood. Methods: A national cohort study was done of all 4 296 814 singleton livebirths in Sweden between 1973 and 2015, who were followed up for mortality through Dec 31, 2017 (maximum age 45 years). Cox regression was used to examine gestational age at birth in relation to all-cause and cause-specific mortality, and cosibling analyses assessed for potential confounding by shared familial (genetic or environmental)factors. Findings: In 103·5 million person-years of follow-up, 43 916 (1·0%)deaths were reported. Gestational age at birth was inversely associated with mortality from infancy to mid-adulthood. Relative to full-term birth (39–41 weeks), the adjusted hazard ratios for mortality associated with gestational age at birth were: 66·14 (95% CI 63·09–69·34)for extremely preterm (22–27 weeks), 8·67 (8·32–9·03)for very preterm (28–33 weeks), 2·61 (2·52–2·71)for late preterm (34–36 weeks), and 1·34 (1·30–1·37)for early term (37–38 weeks), from birth to age 45 years; and 2·04 (0·92–4·55)for extremely preterm, 1·48 (1·17–1·87)for very preterm, 1·22 (1·07–1·39)for late preterm, and 1·16 (1·08–1·25)for early term, at ages 30–45 years. Preterm birth accounted for more deaths among males than females (additive interaction p<0·001). Multiple underlying causes were identified, including congenital anomalies; respiratory, endocrine, cardiovascular, and neurological diseases; cancer; and external causes. Cosibling analyses suggested that the observed associations were not due to shared genetic or environmental factors in families. Interpretation: Preterm and early term birth should be recognised as chronic conditions that require long-term follow-up for adverse health sequelae in adulthood. Funding: National Heart, Lung, and Blood Institute at the National Institutes of Health.
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