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  • 1.
    Ahlbeck, Lars
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.
    Ahlberg, Emelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Björkander, Janne
    Acad Hlth & Care, Sweden.
    Aldén, Caroline
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Papapavlou, Georgia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Palmberg, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström Kronander, Ulla
    Region Östergötland, Medicine Center, Allergy Center.
    Retsas, Pavlos
    Region Östergötland, Medicine Center, Allergy Center.
    Nordenfelt, Patrik
    Cty Hosp Ryhov, Sweden.
    Togö, Totte
    Region Östergötland, Medicine Center, Allergy Center.
    Johansen, Pål
    Univ Zurich, Switzerland.
    Rolander, Bo
    Acad Hlth & Care, Sweden.
    Duchén, Karel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen2022In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, no 6, p. 747-759Article in journal (Refereed)
    Abstract [en]

    Introduction

    There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

    Methods

    Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

    Results

    The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

    Conclusions

    Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

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  • 2.
    Ahmadi, Shilan Seyed
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Uddevalla Cent Hosp, Sweden.
    Pivodic, Aldina
    Stat Konsultgrp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Wedel, Hans
    Univ Gothenburg, Sweden.
    Rathsman, Björn
    Sachs Children & Youth Hosp, Sweden.
    Nyström, Thomas
    Karolinska Inst, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lind, Marcus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
    Risk factors for nephropathy in persons with type 1 diabetes: a population-based study2022In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, p. 761-772Article in journal (Refereed)
    Abstract [en]

    Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure >= 140/80 mmHg was associated with increased risk of albuminuria (p <= 0.0001), as were triglycerides >= 1.0 mmol/L (p = 0.039), total cholesterol >= 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI >= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.

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  • 3.
    Al-Motlaq, Mohammad
    et al.
    Hashemite Univ, Jordan.
    Neill, Sarah
    Univ Plymouth, England.
    Foster, Mandie Jane
    Edith Cowan Univ, Australia; Perth Childrens Hosp, Australia.
    Coyne, Imelda
    Trinity Coll Dublin, Ireland; Trinity Coll Dublin, Ireland.
    Houghton, Davina
    Edith Cowan Univ, Australia.
    Angelhoff, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Rising-Holmstrom, Malin
    Mid Sweden Univ, Sweden.
    Majamanda, Maureen
    Univ Malawi, Malawi; Consortium Adv Training Africa CARTA, Kenya.
    Position statement of the international network for child and family centered care: Child and family centred care during the COVID19 pandemic2021In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 61, p. 140-143Article in journal (Refereed)
    Abstract [en]

    It is the position of the International Network for Child and Family Centered Care (INCFCC) that COVID-19 restrictions pose tremendous challenges for the health care team in their efforts to provide child and family centered care (CFCC). COVID-19 restrictions impact on the familys right to be presernt with their ill child and to contribute to the caring process. A limited number of articles have discussed challenges about the successful delivery of CFCC during the COVID-19 pandemic. Based on current literature, the INCFCC stresses the need for continuous facilitation implementation of child and family centred care as, it is essential for childrens physical and psychological wellbeing. Furthermore we believe that the families presence and participation holds more benefits than risks to the health of children, their families, and the health care team. (C) 2021 Elsevier Inc. All rights reserved.

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  • 4.
    Andersson, Nadine G.
    et al.
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Rathe, Mathias
    Odense Univ Hosp, Denmark.
    Molle, Ingolf
    Univ Hosp Aarhus, Denmark.
    Jarvis, Kirsten Brunswig
    Oslo Univ Hosp, Norway.
    Hoffmann, Marianne
    Univ Hosp Copenhagen, Denmark.
    Huurre, Anu
    Turku Univ Hosp, Finland; Turku Univ, Finland.
    Joelsson, Joel
    Karolinska Univ Hosp, Sweden.
    Albertsen, Birgitte Klug
    Aarhus Univ Hosp, Denmark; Aarhus Univ, Denmark.
    Lohi, Olli
    Tampere Univ, Finland; Tampere Univ Hosp, Finland.
    Långström, Satu
    Univ Helsinki, Finland; Univ Helsinki, Finland.
    Overgaard, Ulrik
    Univ Hosp Copenhagen, Denmark.
    Trakymiene, Sonata Saulyte
    Vilnius Univ, Lithuania.
    Vepsäläinen, Kaisa
    Kuopio Univ Hosp, Finland.
    Vogt, Hartmut
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Biomedical and Clinical Sciences.
    Ranta, Susanna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    A survey on thromboprophylaxis and coagulation assessment in children and young adults with acute lymphoblastic leukaemia (ALL) in the Nordic and Baltic countries: Different practices of assessment and management2022In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 199, no 1, p. 117-121Article in journal (Refereed)
    Abstract [en]

    Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low-molecular-weight heparin, no paediatric centre did. Almost all providers performed baseline coagulation studies, but only 59% continued the assessment. Fibrinogen replacement was conducted in 59%, and antithrombin replacement in 28% of the centres. The survey highlights the need for guidelines in the management of coagulopathy during ALL therapy.

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  • 5. Order onlineBuy this publication >>
    Andersson White, Pär
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Social Inequalities in Child Health: Type 1 Diabetes, Obesity, Cardiovascular Risk Factors and the Role of Self-control2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The Swedish Commission on Health Inequality defined health inequality as systematic differences in health between groups in society with different social positions. All avoidable socioeconomic health inequalities are unfair, and as stated by WHO's Commission on the Social Determinants of Health, we have a moral obligation to try to reduce them. "Putting these inequities right is a matter of social justice. Reducing health inequities is, for the Commission on Social Determinants of Health, an ethical imperative." This ethical imperative is especially apparent regarding the health of children and adolescents. Children’s right to the highest attainable standard of health is also enshrined in Article 24 of the Convention on the Rights of the Child. To reach the goal of a reduction of health inequalities, research is necessary to describe the social gradients of health. Research is also needed to better understand why these gradients occur. A better understanding and knowledge about health inequalities can lead to policies that reduce these inequalities and ensure children’s right to health.

    This thesis investigates social inequality in child health using data from a Swedish population-based prospective birth cohort, the All Babies in Southeast Sweden (ABIS) cohort. Social inequality in obesity in the ABIS cohort is also compared with other birth cohorts participating in the Elucidating Pathways to Child Health Inequality (EPOCH) collaboration which includes cohorts from six high-income countries; Sweden, the Netherlands, Canada (one national and one cohort from Quebec), UK, Australia, and USA.

    In Paper 1 we show that health inequalities in overweight and obesity are detectable already at two years of age and that these inequalities increase during childhood. In adolescents, low socioeconomic status increases the risk of becoming overweight and the risk of components of the metabolic syndrome, including high blood pressure and dyslipidemia (low high-density cholesterol).

    The level of inequality in obesity in the Swedish ABIS cohort was lower than in the other participating countries in the EPOCH collaboration (Paper 2). Inequality was lower in absolute and relative terms when SES was measured by household income. Inequality was also lower in absolute, but not relative, terms when SES was measured by maternal education. This finding indicates that some of the policies implemented in Sweden may attenuate social inequalities in obesity in children. Examples of such policies with evidence for reducing social inequality in obesity implemented in Sweden include universal preschools and free school meals.

    This thesis also investigates health inequalities in autoimmune disease (Paper 3). In this study, we found that low socioeconomic status increased the risk of Type 1 Diabetes but not the other autoimmune diseases investigated. Path analysis indicated that part of the increased risk in children with low SES of Type 1 Diabetes might be mediated by a higher body mass index and an elevated risk of serious life events.

    In the final paper, this thesis tests the hypothesis that differences in maternal and child self-control mediate social inequalities in obesity. Two measures of self-control were used; for mothers, the self-control variable was based on behaviors related to self-control (smoking during pregnancy, smoking during the child’s first year of life, breastfeeding duration, and participating in the ABIS study with biological samples). For the children, the self-control variable was based on questionnaire data on the impulsivity subscale of the Strengths and Difficulties Questionnaire (SDQ). The results showed that the two measures of self-control mediated 87.5 % of the increased risk of obesity at age 19 years in children with low maternal education and 93 % of the risk if maternal BMI was also included in the selfcontrol variable.

    In the discussion part of this thesis, the conclusions that can be deduced from understanding the mechanisms of social inequality in child health are discussed. A theory with a central role of self-control for health inequality predicts that social inequality will increase without interventions. In an environment with rising numbers of stimuli of the human reward system, stimuli that also have negative long-term consequences (socalled Limbic traps), child and adolescent health, in general, will decrease. Because of the mechanisms related to SES and self-control, children with low SES will be disproportionally affected. The result of this development will be increasing levels of social inequalities in child health.

    The discussion also includes implications for policies that may improve health and reduce inequalities. These policies should reduce the exposure of children and adolescents to harmful behaviors/limbic traps. Examples of policies that have this effect include universal preschools for all children, free healthy meals in preschools and schools, increased after-school activities for all children, and longer school days for adolescents with increased hours for physical activity, music, and art. Mobile phones and social media restrictions in schools and policies to reduce use at home should also be implemented. Finally, policies should be implemented to reduce residential and school segregation in the community.

    List of papers
    1. Inequalities in cardiovascular risks among Swedish adolescents (ABIS): a prospective cohort study
    Open this publication in new window or tab >>Inequalities in cardiovascular risks among Swedish adolescents (ABIS): a prospective cohort study
    2020 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 10, no 2, article id e030613Article in journal (Refereed) Published
    Abstract [en]

    Objectives To investigate if socioeconomic status (SES) is predictive of cardiovascular risk factors among Swedish adolescents. Identify the most important SES variable for the development of each cardiovascular risk factor. Investigate at what age SES inequality in overweight and obesity occurs. Design Longitudinal follow-up of a prospective birth cohort. Setting All Babies in Southeast Sweden (ABIS) study includes data from children born between October 1997 and October 1999 in five counties of south east Sweden. Participants A regional ABIS-study subsample from three major cities of the region n=298 adolescents aged 16-18 years, and prospective data from the whole ABIS cohort for overweight and obesity status at the ages 2, 5, 8 and 12 years (n=2998-7925). Outcome measures Blood pressure above the hypertension limit, overweight/obesity according to the International Obesity Task Force definition, low high-density lipoproteins (HDL) or borderline-high low-density lipoproteins according to National Cholesterol Education Program expert panel on cholesterol levels in children. Results For three out of four cardiovascular risk outcomes (elevated blood pressure, low HDL and overweight/obesity), there were increased risk in one or more of the low SES groups (p<0.05). The best predictor was parental occupational class (Swedish socioeconomic classification index) for elevated blood pressure (area under the receiver operating characteristic (ROC) curve 0.623), maternal educational level for overweight (area under the ROC curve 0.641) and blue-collar city of residence for low HDL (area under the ROC curve 0.641). SES-related differences in overweight/obesity were found at age 2, 5 and 12 and for obesity at age 2, 5, 8 and 12 years (all p<0.05). Conclusions Even in a welfare state like Sweden, SES inequalities in cardiovascular risks are evident already in childhood and adolescence. Intervention programmes to reduce cardiovascular risk based on social inequality should start early in life.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2020
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:liu:diva-165977 (URN)10.1136/bmjopen-2019-030613 (DOI)000527786700022 ()32086351 (PubMedID)
    Note

    Funding Agencies|Swedish Research CouncilSwedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation (Barndiabetesfonden); JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); Swedish Council for Working Life and Social ResearchSwedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte) [FAS2004-1775]; Ostgota Brandstodsbolag; Research and PhD studies Committee (FUN), Linkoping University, Sweden (LiU-)

    Available from: 2020-06-04 Created: 2020-06-04 Last updated: 2023-12-22
    2. Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries
    Open this publication in new window or tab >>Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries
    Show others...
    2022 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 46, p. 1703-1711Article in journal (Refereed) Published
    Abstract [en]

    Background/objectives This study analysed the relationship between early childhood socioeconomic status (SES) measured by maternal education and household income and the subsequent development of childhood overweight and obesity. Subjects/methods Data from seven population-representative prospective child cohorts in six high-income countries: United Kingdom, Australia, the Netherlands, Canada (one national cohort and one from the province of Quebec), USA, Sweden. Children were included at birth or within the first 2 years of life. Pooled estimates relate to a total of N = 26,565 included children. Overweight and obesity were defined using International Obesity Task Force (IOTF) cut-offs and measured in late childhood (8-11 years). Risk ratios (RRs) and pooled risk estimates were adjusted for potential confounders (maternal age, ethnicity, child sex). Slope Indexes of Inequality (SII) were estimated to quantify absolute inequality for maternal education and household income. Results Prevalence ranged from 15.0% overweight and 2.4% obese in the Swedish cohort to 37.6% overweight and 15.8% obese in the US cohort. Overall, across cohorts, social gradients were observed for risk of obesity for both low maternal education (pooled RR: 2.99, 95% CI: 2.07, 4.31) and low household income (pooled RR: 2.69, 95% CI: 1.68, 4.30); between-cohort heterogeneity ranged from negligible to moderate (p: 0.300 to < 0.001). The association between RRs of obesity by income was lowest in Sweden than in other cohorts. Conclusions There was a social gradient by maternal education on the risk of childhood obesity in all included cohorts. The SES associations measured by income were more heterogeneous and differed between Sweden versus the other national cohorts; these findings may be attributable to policy differences, including preschool policies, maternity leave, a ban on advertising to children, and universal free school meals.

    Place, publisher, year, edition, pages
    Springer Nature, 2022
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:liu:diva-187410 (URN)10.1038/s41366-022-01171-7 (DOI)000823341900001 ()35821522 (PubMedID)
    Note

    Funding Agencies|Canadian Institutes of Health Research [OCO-79897, MOP-89886, MSH-95353, ROG-110537]; Linkoping University

    Available from: 2022-08-22 Created: 2022-08-22 Last updated: 2023-12-22Bibliographically approved
    3. Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events
    Open this publication in new window or tab >>Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events
    2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1Article in journal (Refereed) Published
    Abstract [en]

    The objective of this paper was to investigate if socioeconomic status (SES), measured by maternal education and household income, influenced the risk of developing autoimmune disease (Type 1 Diabetes, Celiac disease, Juvenile Idiopathic Arthritis, Crohns disease, Ulcerative colitis, and autoimmune thyroid disease), or age at diagnosis, and to analyse pathways between SES and autoimmune disease. We used data from the All Babies in Southeast Sweden (ABIS) study, a population-based prospective birth cohort, which included children born 1997-1999. Diagnoses of autoimmune disease was collected from the Swedish National Patient Register Dec 2020. In 16,365 individuals, low maternal education, but not household income, was associated with increased risk of Type 1 Diabetes; middle education RR 1.54, 95% CI 1.06, 2.23; P 0.02, low education RR 1.81, 95% CI 1.04, 3.18; P 0.04. Maternal education and household income was not associated with any other autoimmune disease and did not influence the age at diagnosis. Part of the increased risk of Type 1 Diabetes by lower maternal education was mediated by the indirect pathway of higher BMI and higher risk of Serious Life Events (SLE) at 5 years of age. The risk of developing Type 1 Diabetes associated to low maternal education might be reduced by decreasing BMI and SLE during childhood.

    Place, publisher, year, edition, pages
    NATURE PORTFOLIO, 2023
    National Category
    General Practice
    Identifiers
    urn:nbn:se:liu:diva-195339 (URN)10.1038/s41598-023-32869-x (DOI)000985906700031 ()37061552 (PubMedID)
    Note

    Funding Agencies|Linkoeping University; County Council of Ostergot-land, Forskningsradet i Sydoestra Sverige, Vetenskapsradet [K2005-72X-11242-11A]; Knut och Alice Wallenbergs Stiftelse [K 98-99D-12813-01A]; Forskningsradet foer Arbetsliv och Socialvetenskap [FAS20041775]; Barndiabetesfonden; Juvenile Diabetes Research Foundation International; Ostgota Brandstodsbolag

    Available from: 2023-06-21 Created: 2023-06-21 Last updated: 2023-12-22
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  • 6.
    Andersson White, Pär
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Abu Awad, Yara
    Concordia Univ, Canada.
    Gauvin, Lise
    Ctr Hosp Univ Montreal, Canada; Univ Montreal, Canada.
    Spencer, Nicholas James
    Univ Warwick, England.
    McGrath, Jennifer J.
    Concordia Univ, Canada.
    Clifford, Susan A.
    Murdoch Childrens Res Inst, Australia; Univ Melbourne, Australia.
    Nikiema, Beatrice
    Univ Montreal, Canada; Cree Board Hlth & Social Serv James Bay, Canada.
    Yang-Huang, Junwen
    Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    Goldhaber-Fiebert, Jeremy D.
    Stanford Univ, CA 94305 USA.
    Markham, Wolfgang
    Univ Warwick, England.
    Mensah, Fiona K.
    Murdoch Childrens Res Inst, Australia; Univ Melbourne, Australia.
    van Grieken, Amy
    Erasmus MC, Netherlands.
    Raat, Hein
    Erasmus MC, Netherlands.
    Jaddoe, V. W. V.
    Erasmus MC, Netherlands; Erasmus MC, Netherlands; Erasmus MC, Netherlands.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries2022In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 46, p. 1703-1711Article in journal (Refereed)
    Abstract [en]

    Background/objectives This study analysed the relationship between early childhood socioeconomic status (SES) measured by maternal education and household income and the subsequent development of childhood overweight and obesity. Subjects/methods Data from seven population-representative prospective child cohorts in six high-income countries: United Kingdom, Australia, the Netherlands, Canada (one national cohort and one from the province of Quebec), USA, Sweden. Children were included at birth or within the first 2 years of life. Pooled estimates relate to a total of N = 26,565 included children. Overweight and obesity were defined using International Obesity Task Force (IOTF) cut-offs and measured in late childhood (8-11 years). Risk ratios (RRs) and pooled risk estimates were adjusted for potential confounders (maternal age, ethnicity, child sex). Slope Indexes of Inequality (SII) were estimated to quantify absolute inequality for maternal education and household income. Results Prevalence ranged from 15.0% overweight and 2.4% obese in the Swedish cohort to 37.6% overweight and 15.8% obese in the US cohort. Overall, across cohorts, social gradients were observed for risk of obesity for both low maternal education (pooled RR: 2.99, 95% CI: 2.07, 4.31) and low household income (pooled RR: 2.69, 95% CI: 1.68, 4.30); between-cohort heterogeneity ranged from negligible to moderate (p: 0.300 to < 0.001). The association between RRs of obesity by income was lowest in Sweden than in other cohorts. Conclusions There was a social gradient by maternal education on the risk of childhood obesity in all included cohorts. The SES associations measured by income were more heterogeneous and differed between Sweden versus the other national cohorts; these findings may be attributable to policy differences, including preschool policies, maternity leave, a ban on advertising to children, and universal free school meals.

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  • 7.
    Andersson White, Pär
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of this paper was to investigate if socioeconomic status (SES), measured by maternal education and household income, influenced the risk of developing autoimmune disease (Type 1 Diabetes, Celiac disease, Juvenile Idiopathic Arthritis, Crohns disease, Ulcerative colitis, and autoimmune thyroid disease), or age at diagnosis, and to analyse pathways between SES and autoimmune disease. We used data from the All Babies in Southeast Sweden (ABIS) study, a population-based prospective birth cohort, which included children born 1997-1999. Diagnoses of autoimmune disease was collected from the Swedish National Patient Register Dec 2020. In 16,365 individuals, low maternal education, but not household income, was associated with increased risk of Type 1 Diabetes; middle education RR 1.54, 95% CI 1.06, 2.23; P 0.02, low education RR 1.81, 95% CI 1.04, 3.18; P 0.04. Maternal education and household income was not associated with any other autoimmune disease and did not influence the age at diagnosis. Part of the increased risk of Type 1 Diabetes by lower maternal education was mediated by the indirect pathway of higher BMI and higher risk of Serious Life Events (SLE) at 5 years of age. The risk of developing Type 1 Diabetes associated to low maternal education might be reduced by decreasing BMI and SLE during childhood.

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  • 8.
    Andersson White, Pär
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Inequalities in cardiovascular risks among Swedish adolescents (ABIS): a prospective cohort study2020In: BMJ Open, E-ISSN 2044-6055, Vol. 10, no 2, article id e030613Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate if socioeconomic status (SES) is predictive of cardiovascular risk factors among Swedish adolescents. Identify the most important SES variable for the development of each cardiovascular risk factor. Investigate at what age SES inequality in overweight and obesity occurs. Design Longitudinal follow-up of a prospective birth cohort. Setting All Babies in Southeast Sweden (ABIS) study includes data from children born between October 1997 and October 1999 in five counties of south east Sweden. Participants A regional ABIS-study subsample from three major cities of the region n=298 adolescents aged 16-18 years, and prospective data from the whole ABIS cohort for overweight and obesity status at the ages 2, 5, 8 and 12 years (n=2998-7925). Outcome measures Blood pressure above the hypertension limit, overweight/obesity according to the International Obesity Task Force definition, low high-density lipoproteins (HDL) or borderline-high low-density lipoproteins according to National Cholesterol Education Program expert panel on cholesterol levels in children. Results For three out of four cardiovascular risk outcomes (elevated blood pressure, low HDL and overweight/obesity), there were increased risk in one or more of the low SES groups (p<0.05). The best predictor was parental occupational class (Swedish socioeconomic classification index) for elevated blood pressure (area under the receiver operating characteristic (ROC) curve 0.623), maternal educational level for overweight (area under the ROC curve 0.641) and blue-collar city of residence for low HDL (area under the ROC curve 0.641). SES-related differences in overweight/obesity were found at age 2, 5 and 12 and for obesity at age 2, 5, 8 and 12 years (all p<0.05). Conclusions Even in a welfare state like Sweden, SES inequalities in cardiovascular risks are evident already in childhood and adolescence. Intervention programmes to reduce cardiovascular risk based on social inequality should start early in life.

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  • 9.
    Anderzen, Johan
    et al.
    Department of Paediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Hermann, Julia M.
    Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany, German Center for Diabetes Research (DZD), München‐Neuherberg, Germany.
    Samuelsson, Ulf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Charalampopoulos, Dimitrios
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Svensson, Jannet
    Paediatric Department, CPH‐Direct, Herlev University Hospital, Herlev, Denmark.
    Skrivarhaug, Torild
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Froehlich-Reiterer, Elke
    Department of Paediatrics, Medical University of Graz, Graz, Austria.
    Maahs, David M.
    Division of Pediatric Endocrinology and Stanford Diabetes Research Center, Stanford, California, USA.
    Åkesson, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Kapellen, Thomas
    University Children's Hospital Leipzig, Leipzig, Germany.
    Fritsch, Maria
    Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
    Birkebaek, Niels H.
    Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
    Drivvoll, Ann K.
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Miller, Kellee
    Jaeb Center for Health Research, Tampa, Florida, USA.
    Stephenson, Terence
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Hofer, Sabine E.
    Department of Paediatrics, Medical University of Innsbruck, Innsbruck, Austria.
    Fredheim, Siri
    Paediatric Department, CPH‐Direct, Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Foster, Nicole
    Jaeb Center for Health Research, Tampa, Florida, USA.
    Amin, Rakesh
    Great Ormond Street Institute of Child Health, University College London, London, UK.
    Hilgard, Doerte
    Pediatric Practice, Witten, Germany.
    Rami-Merhar, Birgit
    Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
    Dahl-Jorgensen, Knut
    Division of Paediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Clements, Mark
    Children's Mercy Hospital, Kansas City, Missouri, USA University of Missouri, Kansas City, Missouri, USA University of Kansas Medical Center, Kansas City, Kansas, USA.
    Hanas, Ragnar
    Department of Paediatrics, NU Hospital Group, Uddevalla, Sweden and the Sahlgrenska Academy, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Holl, Reinhard W.
    Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany German Center for Diabetes Research (DZD), München‐Neuherberg, Germany.
    Warner, Justin T.
    Department of Paediatric Endocrinology and Diabetes, Children's Hospital for Wales, Cardiff, UK.
    International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study2020In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 21, no 4, p. 621-627Article in journal (Refereed)
    Abstract [en]

    Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.

  • 10.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Askenteg, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wikner, Ulrica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    "To Cope with Everyday Life, I Need to Sleep" - A Phenomenographic Study Exploring Sleep Loss in Parents of Children with Atopic Dermatitis.2018In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 43, p. E59-E65Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The whole family is affected when a child has atopic dermatitis (AD), and parents experience sleep disruption related to the child's condition leading to physical and mental exhaustion, mood swings, loss of concentration and lower job performance. This study aimed to explore and describe perceptions of sleep in parents of children <2 years old with AD, consequences of parental sleep loss, and what strategies the parents used to manage sleep loss and to improve sleep.

    DESIGN AND METHODS: This qualitative interview study had an inductive and descriptive design. Twelve parents (eleven mothers and one father) participated in the study. Data analysis was performed using a phenomenographic approach.

    RESULTS: Three categories of description were found: Acceptance and normalization of parental sleep loss; Changed routines and behavior to compensate for sleep loss; and Support is needed to gain sleep and manage daily life.

    CONCLUSIONS: Sleep loss due to the child's AD affected the parents' emotional state, mood, well-being, cognitive function, ability to concentrate and take initiative, and sensitivity to stress and sound negatively. The parents managed their sleep loss mainly by changing their behavior and creating new routines, by taking me-time and through support from partners.

    PRACTICE IMPLICATIONS: Pediatric nurses should acknowledge sleep loss in parents of small children with AD in time to prevent negative consequences, which affect the well-being of the entire family. Advice on how to improve sleep should be given early to increase the parents' understanding, make them feel safer and strengthen them in their parenthood.

  • 11.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Edéll-Gustafsson, Ulla
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science.
    Morelius, Evalotte
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    The cortisol response in parents staying with a sick child at hospital2019In: Nursing Open, E-ISSN 2054-1058, Vol. 6, no 2, p. 620-625Article in journal (Refereed)
    Abstract [en]

    Aim

    To study the cortisol response in parents staying with their child in paediatric wards, to compare the parents’ cortisol levels between the paediatric ward and at home 4 weeks after discharge and to compare the parents’ cortisol levels with data of an adult reference population, reported by Wust et al., as there are few studies investigating parental cortisol.

    Design

    This study has a descriptive and prospective comparative design.

    Method

    Thirty‐one parents participated. Saliva samples were collected in the paediatric ward and 4 weeks later at home.

    Results

    The parents had lower morning awakening cortisol levels in the paediatric ward than at home after discharge. There were no statistically significant differences in postawakening cortisol or cortisol awakening response (CAR). The child's age, diagnosis or previously diagnosed chronic condition did not affect the parents’ cortisol levels. The morning and postawakening cortisol levels were lower than those of the reference population.

    Conclusion

    The hospital stay with a sick child affects parents’ cortisol levels. Parental stress needs more attention to find interventions to prevent the risk of stress‐related complications that subsequently can affect the care of the child.

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  • 12.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mörelius, Evalotte
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Sleep quality and mood in mothers and fathers accommodated in the family-centred paediatric ward2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 3-4, p. e544-e550Article in journal (Refereed)
    Abstract [en]

    Aims and objectives

    To describe sleep quality and mood in parents accommodated with their sick child in a family‐centred paediatric ward. Secondary aims were to compare mothers’ and fathers’ sleep quality and mood in the paediatric ward and to compare the parents’ sleep quality and mood between the paediatric ward and in a daily‐life home setting after discharge.

    Background

    Frequent interruptions, ward noise and anxiety affect parents’ sleep quality and mood negatively when accommodated with their sick child in paediatric wards. Poor sleep quality and negative mood decrease the parents’ ability to sustain attention and focus, and to care for their sick child.

    Methods

    This was a prospective and descriptive study. Eighty‐two parents (61 mothers and 21 fathers) with children (median age 6.25 years) admitted to six paediatric wards participated in the study. Uppsala Sleep Inventory, a sleep diary and the Mood Adjective Checklist were used to measure sleep quality and mood.

    Results

    The parents had a good sleep quality in the paediatric ward even though they had more nocturnal awakenings compared to home. Moreover, they were less alert, less interested and had reduced concentration, and were more tired, dull and passive in the hospital than at home after discharge. Vital sign checks, noises made by the staff and medical treatment were given reasons influencing sleep. Poor sleep quality correlated with negative mood.

    Conclusion

    Parents’ sleep quality in family‐centred paediatric care is good. However, the habitual sleep efficacy before admittance to the hospital is lower than expected and needs to be further investigated.

    Relevance to Clinical Practice

    The healthcare professionals should acknowledge parents’ sleep and mood when they are accommodated with their sick child. Further should care at night be scheduled and sleep promoted for the parents to maintain health and well‐being in the family.

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  • 13.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Faresjö, Tomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sundell, Anna Lena
    Inst Postgrad Dent Educ, Sweden; Jonkoping Univ, Sweden.
    Measuring hair cortisol concentration, insomnia symptoms and quality of life in preschool children with severe early childhood caries - a case-control pilot study2023In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 81, no 7, p. 508-516Article in journal (Refereed)
    Abstract [en]

    ObjectiveThis study aimed to 1) investigate the relationships between hair cortisol concentration (HCC), insomnia symptoms, Health-Related Quality of Life (HRQoL) and Oral Health-Related Quality of Life (OHRQoL) in preschool children with severe early childhood caries, 2) compare HCC, insomnia symptoms, HRQoL and OHRQoL in preschool children with severe early childhood caries with these factors in children without clinical signs of dental caries, and 3) explore correlations between caries scores and HCC, insomnia symptoms, HRQoL and OHRQoL.Material and MethodsA case-control pilot study, including 12 children with severe early childhood caries and 28 controls, aged 3-5 years. Dental examination was performed and hair samples for cortisol were taken. Parents filled out questionnaires about their childs insomnia symptoms, HRQoL and OHRQoL. Interpreters were used in families with language difficulties.ResultsThe key findings in this pilot study were tendencies that children with severe early childhood caries had more insomnia symptoms, and poorer OHRQoL than the controls. Caries scores was correlated with insomnia symptoms and OHRQoL.ConclusionsDentists should include questions about the childs sleep when they see the child, as insomnia related to dental caries may lead to several physical, mental, and social problems.

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  • 14.
    Angelhoff, Charlotte
    et al.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Grundström, Hanna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Norrköping. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Department of Biomedical and Clinical Sciences.
    Supporting girls with painful menstruation - A qualitative study with school nurses in Sweden2023In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 68, p. e109-e115Article in journal (Refereed)
    Abstract [en]

    Background: Painful menstruation is common among girls. To optimize school nurses' work more knowledgeabout their experiences of supporting these girls is needed. The aim of this study was to describe school nurses'experiences of supporting girls with menstrual pain.Methods: Interviews were conducted with 15 school nurses in Sweden and analyzed using thematic analysis.Results: Three themes emerged: Taking menstrual pain seriously, Being a disseminator of knowledge, andExternal conditions for conducting professional work as a school nurse.Conclusion: School nurses felt competent in supporting girls with menstrual pain. However, they lacked struc-tural, written guidelines and routines for how to treat, support, follow-up and refer girls with menstrual pain.Practice implications: School education about menstruation and sexual health needs to be strengthened. Cooper-ation with other healthcare facilities and networks with other school nurses should be increased. Specific guide-lines on how to support girls with menstrual pain should be implemented.

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  • 15.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Ersta Skondal Bracke Univ Coll, Sweden.
    Johansson, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Sundell, Anna Lena
    Inst Postgrad Dent Educ, Sweden; Jonkoping Univ, Sweden.
    Correction: Swedish translation and validation of the Pediatric Insomnia Severity Index (vol 20, 253, 2020)2020In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, BMC PEDIATRICS, Vol. 20, no 1, article id 333Article in journal (Other academic)
    Abstract [en]

    An amendment to this paper has been published and can be accessed via the original article.

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  • 16.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Ersta Skondal Bracke Univ Coll, Sweden.
    Johansson, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Sundell, Anna Lena Lena
    Inst Postgrad Dent Educ, Sweden; Jonkoping Univ, Sweden.
    Swedish translation and validation of the Pediatric Insomnia Severity Index2020In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, BMC PEDIATRICS, Vol. 20, no 1, article id 253Article in journal (Refereed)
    Abstract [en]

    Background

    To increase health and well-being in young children, it is important to acknowledge and promote the child’s sleep behaviour. However, there is a lack of brief, validated sleep screening instruments for children. The aims of the study were to (1) present a Swedish translation of the PISI, (2) examine the factor structure of the Swedish version of PISI, and test the reliability and validity of the PISI factor structure in a sample of healthy children in Sweden.

    Methods

    The English version of the PISI was translated into Swedish, translated back into English, and agreed upon before use. Parents of healthy 3- to 10-year-old children filled out the Swedish version of the PISI and the generic health-related quality of life instrument KIDSCREEN-27 two times. Exploratory and confirmatory factor analyses for baseline and test-retest, structural equation modelling, and correlations between the PISI and KIDSCREEN-27 were performed.

    Results

    In total, 160 parents filled out baseline questionnaires (test), whereof 100 parents (63%) filled out the follow-up questionnaires (retest). Confirmative factor analysis of the PISI found two correlated factors: sleep onset problems (SOP) and sleep maintenance problems (SMP). The PISI had substantial construct and test-retest reliability. The PISI factors were related to all KIDSCREEN-27 dimensions.

    Conclusions

    The Swedish version of the PISI is applicable for screening sleep problems and is a useful aid in dialogues with families about sleep.

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  • 17.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Sjolie, Hege
    Oslo Metropolitan Univ, Norway.
    Mörelius, Evalotte
    School of Nursing and Midwifery, Edith Cowan University, Joondalup, WA, Australia; Perth Children’s Hospital, Nedlands, WA, Australia.
    Loyland, Borghild
    Oslo Metropolitan Univ, Norway.
    Like Walking in a Fog: Parents' perceptions of sleep and consequences of sleep loss when staying overnight with their child in hospital2020In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 29, no 2, article id e12945Article in journal (Refereed)
    Abstract [en]

    Disruption of parental sleep in hospital, with frequent awakenings and poor sleep quality, limits the parents resources to meet the childs needs and maintain parental wellbeing. The aim of the study was to explore and describe how parents perceive their sleep when staying overnight with their sick child in hospital. A further aim was to explore and describe parents perception of what circumstances influence their sleep in the hospital. Twenty-two parents who were accommodated with their sick child (0-17 years) in paediatric wards in Norway and Sweden participated. Interviews were conducted during the hospital stay to elicit their perspectives. Phenomenography was used to analyse data. Two descriptive categories were found: (a) "Perceptions of sleep", with two sub-categories: "Sleep in the paediatric ward" and "Consequences of sleep loss"; and (b) "Circumstances influencing sleep in the paediatric ward" with three sub-categories: "The importance of the family", "Information and routines at the paediatric ward", and "Accommodation facilities". Parents sleep and needs must be acknowledged in paediatric wards. An individual plan of care for the upcoming night could be a valuable tool for both the parents and nurses. The childs medical needs must be met with respect to the parents willingness to take part in the childs care during the night, and the need for rest and sleep for both parent and child.

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  • 18.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Ersta Skondal Bracke Univ Coll, Sweden.
    Sveen, Josefin
    Ersta Skondal Bracke Univ Coll, Sweden; Uppsala Univ, Sweden.
    Alvariza, Anette
    Ersta Skondal Bracke Univ Coll, Sweden; Dalen Hosp, Sweden.
    Weber-Falk, Megan
    Ersta Skondal Bracke Univ Coll, Sweden.
    Kreicbergs, Ulrika
    Ersta Skondal Bracke Univ Coll, Sweden; Karolinska Inst, Sweden.
    Communication, self-esteem and prolonged grief in parent-adolescent dyads, 1 - 4 years following the death of a parent to cancer2021In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 50, article id 101883Article in journal (Refereed)
    Abstract [en]

    Purpose: Talking and grieving together may be advantageous for maintaining belief in a meaningful future and can help bereaved adolescents and their parents to cope better with the situation. The aim of this study was to explore communication, self-esteem and prolonged grief in adolescent-parent dyads, following the death of a parent to cancer. Method: This study has a descriptive and comparative design. Twenty family dyads consisting of parentally bereaved adolescents (12 & ndash;19 years) and their widowed parents completed the Parent and Adolescent Communication Scale, Rosenberg Self-Esteem Scale and Prolonged Grief-13, 1 & ndash;4 years following the death of a parent. Results: Twelve family dyads reported normal-high parent-adolescent communication, 11 dyads rated normal high self-esteem. Two adolescents and three parents scored above the cut-off for possible prolonged grief disorder (&gt;= 35), none of these were in the same dyads. There was a difference (p &lt; .05) between boys (mean 40.0) and girls (mean 41.9) with regard to open family communication, as assessed by parents. Girls reported lower self-esteem (mean 26.0) than boys (mean 34.1, p &lt; .01). Conclusions: This study provides insights from parentally bereaved families which indicate that despite experiencing the often-traumatic life event of losing a parent or partner, most participants reported normal parent adolescent communication, normal self-esteem and few symptoms of prolonged grief. The potential usefulness of identifying families who may need professional support in family communication following the death of a parent is discussed.

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  • 19.
    Angelhoff, Charlotte
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Faculty of Medicine and Health Sciences.
    Thernström Blomqvist, Ylva
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Sahlén Helmer, Charlotte
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Clinical and Experimental Medicine.
    Olsson, Emma
    Department of Pediatrics and Centre for Health Care Sciences, Örebro University, Örebro, Sweden.
    Shorey, Shefaly
    Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
    Frostell, Anneli
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Mörelius, Evalotte
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Effect of skin-to-skin contact on parents sleep quality, mood, parent-infant interaction and cortisol concentrations in neonatal care units: study protocol of a randomised controlled trial2018In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 7, article id e021606Article in journal (Refereed)
    Abstract [en]

    Introduction Separation after preterm birth is a major stressor for infants and parents. Skin-to-skin contact (SSC) is a method of care suitable to use in the neonatal intensive care unit (NICU) to minimise separation between parents and infants. Less separation leads to increased possibilities for parent-infant interaction, provided that the parents’ sleep quality is satisfactory. We aimed to evaluate the effect of continuous SSC on sleep quality and mood in parents of preterm infants born <33 weeks of gestation as well as the quality of parent-infant interaction and salivary cortisol concentrations at the time of discharge.

    Methods and analysis A randomised intervention study with two arms—intervention versus standard care. Data will be collected from 50 families. Eligible families will be randomly allocated to intervention or standard care when transferred from the intensive care room to the family-room in the NICU. The intervention consists of continuous SSC for four consecutive days and nights in the family-room. Data will be collected every day during the intervention and again at the time of discharge from the hospital. Outcome measures comprise activity tracker (Actigraph); validated self-rated questionnaires concerning sleep, mood and bonding; observed scorings of parental sensitivity and emotional availability and salivary cortisol. Data will be analysed with pairwise, repeated measures, Mann Whitney U-test will be used to compare groups and analysis of variance will be used to adjust for different hospitals and parents’ gender.

    Ethics and dissemination The study is approved by the Regional Research Ethics Board at an appropriate university (2016/89–31). The results will be published in scientific journals. We will also use conferences and social media to disseminate our findings.

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  • 20.
    Arnqvist, Hans
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Westerlund, Malin C.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nordwall, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Impact of HbA(1c) Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study2022In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, no 11, p. 2675-2682Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) &gt;9.5% (&gt;80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) &lt;7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.

  • 21.
    Aydemir, Ozkan
    et al.
    Univ Massachusetts, MA USA.
    Noble, Janelle A.
    Childrens Hosp Oakland, CA 94609 USA.
    Bailey, Jeffrey A.
    Univ Massachusetts, MA USA.
    Lernmark, Ake
    Lund Univ, Sweden.
    Marsh, Patrick
    Univ Massachusetts, MA USA.
    Svard, Agnes Andersson
    Lund Univ, Sweden.
    Bearoff, Frank
    Drexel Univ, PA 19104 USA.
    Blankenhorn, Elizabeth P.
    Drexel Univ, PA 19104 USA.
    Mordes, John P.
    Univ Massachusetts, MA 01655 USA.
    Persson, Martina
    Karolinska Univ Hosp, Sweden.
    Larsson, Helena Elding
    Lund Univ, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ivarsson, Sten-Anders
    Lund Univ, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Carlsson, Annelie
    Lund Univ, Sweden.
    Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes2019In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, no 7, p. 1523-1527Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as "expression quantitative trait loci," modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals.

  • 22.
    Bach Jensen, Georg
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Ahlsson, Fredrik
    Uppsala Univ, Sweden.
    Domellöf, Magnus
    Umeå Univ, Sweden.
    Elfvin, Anders
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Naver, Lars
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Abrahamsson, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial the N-forte trial2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 11, article id e053400Article in journal (Refereed)
    Abstract [en]

    Introduction The mortality rate of extremely low gestational age (ELGA) (born &lt;gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants receiving human milk have lower incidence of sepsis and NEC than those fed a bovine milk-based preterm formula. Despite this, fully human milk fed ELGA infants most often have a significant intake of cows milk protein from bovine-based protein fortifier. The aim of this study is to evaluate whether the supplementation of human milk-based, as compared with bovine-based, nutrient fortifier reduces the prevalence of NEC, sepsis and mortality in ELGA infants exclusively fed with human milk. Methods and analysis A randomised-controlled multicentre trial comparing the effect of a human breast milk-based fortifier with a standard bovine protein-based fortifier in 222-322 ELGA infants fed human breast milk (mothers own milk and/or donor milk). The infants will be randomised to either fortifier before reaching 100 mU kg/day in oral feeds. The intervention, stratified by centre, will continue until the target postmenstrual week 34+0. The primary outcome is a composite of NEC, sepsis or death. Infants are characterised with comprehensive clinical and nutritional data collected prospectively from birth until hospital discharge. Stool, urine, blood and breast milk samples are collected for analyses in order to study underlying mechanisms. A follow-up focusing on neurological development and growth will be performed at 2 and 5.5 years of age. Health economic analyses will be made. Ethics and dissemination The study is conducted according to ICH/GCP guidelines and is approved by the regional ethical review board in Linkoping Sweden (Dnr 2018/193-31, Dnr 2018/384-32). Results will be presented at scientific meetings and published in peer-reviewed publications.

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  • 23.
    Badam, Tejaswi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering. Skovde Univ, Sweden.
    Hellberg, Sandra
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lechner-Scott, Jeannette
    Univ Newcastle, Australia; Hunter Med Res Inst, Australia; John Hunter Hosp, Australia.
    Lea, Rodney A.
    Univ Newcastle, Australia; Hunter Med Res Inst, Australia; Queensland Univ Technol, Australia.
    Tost, Jorg
    CEA Inst Biol Francois Jacob, France.
    Mariette, Xavier
    Univ Paris Saclay, France.
    Svensson-Arvelund, Judit
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Berg, Göran
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases2022In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 17, no 9, p. 1040-1055Article in journal (Refereed)
    Abstract [en]

    Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.

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  • 24.
    Bang, Peter
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Polak, Michel
    Hop Univ Necker Enfants Malad, France; France Univ Paris Cite, France.
    Bossowski, Artur
    Med Univ Bialystok, Poland.
    Maghnie, Mohamad
    IRCCS Ist Giannina Gaslini, Italy; Univ Genoa, Italy.
    Argente, Jesus
    Univ Nino Jesus, Spain; Univ Autonoma Madrid, Spain; Inst Salud Carlos III, Spain; IMDEA Food Inst, Spain.
    Ramon-Krauel, Marta
    Hosp St Joan De Deu, Spain; Inst Salud Carlos III, Spain.
    Sert, Caroline
    Ipsen Pharma, France.
    Perrot, Valerie
    Ipsen Pharma, France.
    Mazain, Sarah
    Ipsen Pharma, France.
    Woelfle, Joachim
    Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany.
    Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry2024In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 109, no 1, p. 46-56Article in journal (Refereed)
    Abstract [en]

    Context The European Increlex & REG; Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD).Objective This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1.Methods Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor.Results In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced & GE; 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01.Conclusion Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.

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  • 25.
    Bang, Peter
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Polak, Michel
    Univ Paris, France.
    Perrot, Valerie
    Ipsen Pharma, France.
    Sert, Caroline
    Ipsen Pharma, France.
    Shaikh, Haris
    Ipsen Pharm, Wales.
    Woelfle, Joachim
    Friedrich Alexander Univ Erlangen Nurnberg, Germany.
    Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex(R) Growth Forum Database Registry2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 812568Article in journal (Refereed)
    Abstract [en]

    BackgroundPuberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex(R) Growth Forum Database (Eu-IGFD) Registry (NCT00903110). MethodsThe Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019. ResultsThis analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1. ConclusionChildren and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.

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  • 26.
    Bang, Peter
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Woelfle, Joachim
    Univ Erlangen Nurnberg, Germany.
    Perrot, Valerie
    Ipsen Pharma, France.
    Sert, Caroline
    Ipsen Pharma, France.
    Polak, Michel
    Univ Paris, France.
    Effectiveness and safety of rhIGF1 therapy n patients with or without Laron syndrome2021In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 184, no 2, p. 267-276Article in journal (Refereed)
    Abstract [en]

    Objective: The European Increlex (R) Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex (R)) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS). Design: Ongoing, open-label, observational registry (NCT00903110). Methods: Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008-2017 (n = 242). The treatment-naive/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain &gt;= 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs). Results: Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years treatment (P &lt; 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P &lt; 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P &lt; 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common. Conclusions: In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.

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  • 27.
    Barcenilla, Hugo
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology. Orebro Univ, Sweden; Orebro Univ, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Casas, Rosaura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+CD8+T Cells in Patients With Recent-Onset Type 1 Diabetes2022In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 797172Article in journal (Refereed)
    Abstract [en]

    Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naive and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD(65) only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

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  • 28.
    Barcenilla, Hugo
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Mass Cytometry Identifies Distinct Subsets of Regulatory T Cells and Natural Killer Cells Associated With High Risk for Type 1 Diabetes2019In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, article id 982Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin producing beta-cells. The time from onset of islet autoimmunity to manifest clinical disease can vary widely in length, and it is fairly uncharacterized both clinically and immunologically. In the current study, peripheral blood mononuclear cells from autoantibody-positive children with high risk for T1D, and from age-matched healthy individuals, were analyzed by mass cytometry using a panel of 32 antibodies. Surface markers were chosen to identify multiple cell types including T, B, NK, monocytes, and DC, and antibodies specific for identification of differentiation, activation and functional markers were also included in the panel. By applying dimensional reduction and computational unsupervised clustering approaches, we delineated in an unbiased fashion 132 phenotypically distinct subsets within the major immune cell populations. We were able to identify an effector memory Treg subset expressing HLA-DR, CCR4, CCR6, CXCR3, and GATA3 that was increased in the high-risk group. In addition, two subsets of NK cells defined by CD16(+) CD8(+) CXCR3(+) and CD16(+) CD8(+) CXCR3(+) CD11c(+) were also higher in the same subjects. High-risk individuals did not show impaired glucose tolerance at the time of sampling, suggesting that the changes observed were not the result of metabolic imbalance, and might be potential biomarkers predictive of T1D.

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  • 29.
    Bensberg, Maike
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Rundquist, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Selimovic, Aida
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Lagerwall, Cathrine
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Vogt, Hartmut
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lentini, Antonio
    Karolinska Inst, Sweden.
    Nestor, Colm
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia2021In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 34, article id e2110758118Article in journal (Refereed)
    Abstract [en]

    Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggres-sive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methyl-ation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improv-ing prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respec-tively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Impor-tantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous ret-roviruses (HERVs), which was further enhanced by the addition of phys-iological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL.

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  • 30.
    Berryman, Meghan A.
    et al.
    Univ Florida, FL 32611 USA.
    Ilonen, Jorma
    Univ Turku, Finland.
    Triplett, Eric W.
    Univ Florida, FL 32611 USA.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut2023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1270488Article, review/survey (Refereed)
    Abstract [en]

    Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator. Graphical representation of central hypothesis.

  • 31.
    Berryman, Meghan A.
    et al.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Milletich, Patricia L.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Petrone, Joseph R.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Roesch, Luiz FW.
    Roesch Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Ilonen, Jorma
    Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
    Triplett, Eric W.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Autoimmune-associated genetics impact probiotic colonization of the infant gut2022In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 133, article id 102943Article in journal (Refereed)
    Abstract [en]

    To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.

  • 32.
    Besser, Rachel E. J.
    et al.
    UCL, England; Oxford Univ Hosp NHS Fdn Trust, England; Churchill Hosp, England.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Hindmarsh, Peter C.
    UCL, England.
    Cole, Tim J.
    UCL, England.
    Exploring C-peptide loss in type 1 diabetes using growth curve analysis2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 7, article id e0199635Article in journal (Refereed)
    Abstract [en]

    Objectives C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods Between 1976 and 2011, 442 T1D patients initially aged amp;lt; 18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9,18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (Superlmposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curves mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results The square root (root) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and root AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p amp;lt; 0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.

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  • 33.
    Bird, Philippa K
    et al.
    Department of Health Sciences, University of York, York, North Yorkshire, UK // Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Pickett, Kate E
    Department of Health Sciences, University of York, York, North Yorkshire, UK.
    Graham, Hilary
    Department of Health Sciences, University of York, York, North Yorkshire, UK.
    Faresjö, Tomas
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Jaddoe, Vincent W V
    Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands // Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
    Ludvigsson, Johnny
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health.
    Raat, Hein
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    Seguin, Louise
    Department of Social and Preventive Medicine, Universite de Montreal, Montreal, Québec, Canada.
    Wijtzes, Anne I
    Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
    McGrath, Jennifer J
    Department of Psychology, Concordia University, Montreal, Québec, Canada.
    Income inequality and social gradients in children's height: a comparison of cohort studies from five high-income countries.2019In: BMJ Paediatrics Open, E-ISSN 2399-9772, Vol. 3, no 1, article id e000568Article in journal (Refereed)
    Abstract [en]

    Background: Health and well-being are better, on average, in countries that are more equal, but less is known about how this benefit is distributed across society. Height is a widely used, objective indicator of child health and predictor of lifelong well-being. We compared the level and slope of social gradients in children's height in high-income countries with different levels of income inequality, in order to investigate whether children growing up in all socioeconomic circumstances are healthier in more equal countries.

    Methods: We conducted a coordinated analysis of data from five cohort studies from countries selected to represent different levels of income inequality (the USA, UK, Australia, the Netherlands and Sweden). We used standardised methods to compare social gradients in children's height at age 4-6 years, by parent education status and household income. We used linear regression models and predicted height for children with the same age, sex and socioeconomic circumstances in each cohort.

    Results: The total analytic sample was 37 063 children aged 4-6 years. Gradients by parent education and household income varied between cohorts and outcomes. After adjusting for differences in age and sex, children in more equal countries (Sweden, the Netherlands) were taller at all levels of parent education and household income than children in less equal countries (USA, UK and Australia), with the greatest between-country differences among children with less educated parents and lowest household incomes.

    Conclusions: The study provides preliminary evidence that children across society do better in more equal countries, with greatest benefit among children from the most disadvantaged socioeconomic groups.

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  • 34.
    Birkebaek, N. H.
    et al.
    Aarhus Univ, Denmark.
    Kahlert, J.
    Aarhus Univ Hosp, Denmark.
    Bjarnason, R.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Drivvoll, A. K.
    Oslo Univ Hosp, Norway.
    Johansen, A.
    Rigshosp, Denmark.
    Konradsdottir, E.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Pundziute-Lycka, A.
    Queen Silvia Childrens Hosp, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Skrivarhaug, T.
    Oslo Univ Hosp, Norway.
    Svensson, J.
    Univ Copenhagen, Denmark.
    Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA(1c) and other predictors of increasing BMISDS2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 7, p. 1198-1205Article in journal (Refereed)
    Abstract [en]

    Background: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Methods: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A(1c) (HbA(1c)), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. Results: Totally, 11025 children (48% females) (30994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA(1c), 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA(1c) and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P amp;lt; .001). Conclusion: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA(1c), long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA(1c).

  • 35.
    Birkebaek, Niels H.
    et al.
    Aarhus Univ Hosp, Denmark.
    Hermann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Charalampopoulos, Dimitrios
    UCL, England.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Svensson, Ann-Marie
    Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    UCL, England.
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev Univ Hosp, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Rigshosp, Denmark.
    Kapellen, Thomas M.
    Univ Childrens Hosp Leipzig, Germany.
    Hilgard, Doerte
    Pediat Diabetol Practice, Germany.
    Dahl-Jorgensen, Knut
    Univ Oslo, Norway; Univ Oslo, Norway.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Fritsch, Maria
    Med Univ Vienna, Austria.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Letter: Center Size and Glycemic Control: An International Study With 504 Centers From Seven Countries in DIABETES CARE, vol 42, issue 3, pp E37-E392019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 3, p. E37-E39Article in journal (Other academic)
    Abstract [en]

    n/a

  • 36.
    Bjoerkman, Anders
    et al.
    Karolinska Inst, Sweden.
    Gisslen, Magnus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Gullberg, Martin
    Univ Umea, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    The Swedish COVID-19 approach: a scientific dialogue on mitigation policies2023In: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, article id 1206732Article in journal (Refereed)
    Abstract [en]

    During the COVID-19 pandemic, Sweden was among the few countries that did not enforce strict lockdown measures but instead relied more on voluntary and sustainable mitigation recommendations. While supported by the majority of Swedes, this approach faced rapid and continuous criticism. Unfortunately, the respectful debate centered around scientific evidence often gave way to mudslinging. However, the available data on excess all-cause mortality rates indicate that Sweden experienced fewer deaths per population unit during the pandemic (2020-2022) than most high-income countries and was comparable to neighboring Nordic countries through the pandemic. An open, objective scientific dialogue is essential for learning and preparing for future outbreaks.

  • 37.
    Björklund, Anneli
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Acad Specialist Ctr, Sweden.
    Hals, Ingrid K.
    Trondheim Reg & Univ Hosp, Norway; Norwegian Univ Sci & Technol NTNU, Norway; Nord Trondelag Hosp Trust, Norway.
    Grill, Valdemar
    Trondheim Reg & Univ Hosp, Norway.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Latent Autoimmune Diabetes in Adults: Background, Safety and Feasibility of an Ongoing Pilot Study With Intra-Lymphatic Injections of GAD-Alum and Oral Vitamin D2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 926021Article in journal (Refereed)
    Abstract [en]

    BackgroundLatent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study). Material and MethodsFourteen GADA-positive (&gt;190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within &lt; 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 mu g GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day -30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 ng/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed. ResultsPreliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months). ConclusionsIntra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials.

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  • 38.
    Björnsson, Bergthor
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Borrebaeck, Carl
    Lund Univ, Sweden.
    Elander, Nils
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Gasslander, Thomas
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Gawel, Danuta
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jornsten, Rebecka
    Univ Gothenburg, Sweden; Chalmers Univ Technol, Sweden.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Li, Xinxiu
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Lilja, Sandra
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Karolinska Univ Hosp, Sweden; Dept Lab Med, Sweden.
    Sandström, Per
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Schäfer, Samuel
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Stenmarker, Margaretha
    Futurum Acad Hlth and Care, Sweden; Inst Clin Sci, Sweden.
    Sun, Xiao-Feng
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Sysoev, Oleg
    Linköping University, Department of Computer and Information Science, The Division of Statistics and Machine Learning. Linköping University, Faculty of Arts and Sciences.
    Zhang, Huan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Benson, Mikael
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health.
    Digital twins to personalize medicine2020In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 12, no 1, article id 4Article in journal (Other academic)
    Abstract [en]

    Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.

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  • 39.
    Blixt, Cornelia
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Johansson, Elin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Forsner, Maria
    Umea Univ, Sweden; Karolinska Inst, Sweden.
    Angelhoff, Charlotte
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Compassion fatigue and compassion satisfaction in pediatric and neonatal care nurses during the COVID-19 pandemic in Sweden2023In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 73, p. e646-e651Article in journal (Refereed)
    Abstract [en]

    Purpose: Quality of care and the mental and physical health of nurses are interlinked. The COVID-19 pandemic has imposed an extremely high burden on health care. This study aimed to: 1) describe professional quality of life of registered nurses (RN) working in the pediatric and neonatal care units during the COVID-19 pandemic in Sweden, 2) compare professional quality of life between RNs with and without a Master's degree in specialist nursing pediatric care (MSc), and 3) compare differences in professional quality of life associated with the nursing experience (years). Design and methods: This study adopted a cross-sectional survey design. The PROQoL (R)-5-questionnaire was administered as a web survey to 160 RNs at four pediatric wards and two neonatal units of two hospitals in Sweden. Results: Seventy-one RNs responded to the survey. Overall, they reported a sufficient professional quality of life. RNs with an MSc suffered significantly lower secondary traumatic stress levels. Experienced RNs reported significantly higher compassion satisfaction and lower occupational burnout. Conclusion: Higher education and longer experience are beneficial for nurses' professional quality of life when working in pediatric care units. Practical implications: Results from this study highlights the importance of offering RN education in pediatric care at master level and supporting novice nurses, to prevent negative professional well-being outcomes in pediatric care, because the health of nurses is of utterly importance when crisis such as a pandemic hits the world. The findings also suggest that the conditions for professional quality of life could improve through activities such as self-care, time for reflection, better working hours, competence-adjusted salary, and educational opportunities. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

  • 40.
    Bolk, Jenny
    et al.
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden; Soder Sjukhuset, Sweden.
    Simatou, Eleni
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Söderling, Jonas
    Karolinska Inst, Sweden.
    Thorell, Lisa B.
    Karolinska Inst, Sweden.
    Persson, Martina
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden; Soder Sjukhuset, Sweden.
    Sundelin, Heléne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Karolinska Univ Hosp, Sweden.
    Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder2022In: JAMA Network Open, E-ISSN 2574-3805, Vol. 5, no 4, article id e228884Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. OBJECTIVE To assess the risk of ADHD in children after pediatric ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. EXPOSURES Pediatric ischemic stroke. MAIN OUTCOMES AND MEASURES Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and international Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. RESULTS Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI, 1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). CONCLUSIONS AND RELEVANCE This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD. particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

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  • 41.
    Bruzzaniti, Sara
    et al.
    CNR, Italy.
    Piemonte, Erica
    Univ Naples Federico II, Italy.
    Bruzzese, Dario
    Univ Napoli Federico II, Italy.
    Lepore, Maria Teresa
    CNR, Italy.
    Strollo, Rocky
    Univ Telemat San Raffaele Roma, Italy.
    Izzo, Lavinia
    Univ Naples Federico II, Italy.
    Di Candia, Francesca
    Univ Napoli Federico II, Italy.
    Franzese, Adriana
    Univ Napoli Federico II, Italy.
    Bifulco, Maurizio
    Univ Naples Federico II, Italy.
    Mozzillo, Enza
    Univ Napoli Federico II, Italy.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Matarese, Giuseppe
    CNR, Italy; Univ Naples Federico II, Italy.
    Galgani, Mario
    CNR, Italy; Univ Naples Federico II, Italy.
    Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children2024In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesisType 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb+) children to identify molecules related to type 1 diabetes progression.MethodsWe measured the levels of 14 sICM in the sera of AAb+ children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb+ children were followed up and divided based on their progression to type 1 diabetes (AAbP) or not (AAbNP) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAbP children.ResultsWe found that AAb+ children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb+ children who progressed to type 1 diabetes (AAbP) had higher sICM concentrations than non-progressors (AAbNP). Further, sICM levels decreased in AAbP children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).Conclusions/interpretationThis study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.

  • 42.
    Bruzzaniti, Sara
    et al.
    CNR, Italy; Univ Napoli Federico II, Italy.
    Piemonte, Erica
    Univ Napoli Federico II, Italy.
    Mozzillo, Enza
    Univ Napoli Federico II, Italy.
    Bruzzese, Dario
    Univ Napoli Federico II, Italy.
    Lepore, Maria Teresa
    CNR, Italy.
    Carbone, Fortunata
    CNR, Italy; Fdn Santa Lucia, Italy.
    de Candia, Paola
    Univ Napoli Federico II, Italy.
    Strollo, Rocky
    Univ Campus Biomed Roma, Italy.
    Porcellini, Antonio
    Univ Napoli Federico II, Italy.
    Marigliano, Marco
    Univ Verona, Italy; Azienda Osped Univ Integrata Verona, Italy.
    Maffeis, Claudio
    Univ Verona, Italy; Azienda Osped Univ Integrata Verona, Italy.
    Bifulco, Maurizio
    Univ Napoli Federico II, Italy.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Franzese, Adriana
    Univ Napoli Federico II, Italy.
    Matarese, Giuseppe
    CNR, Italy; Univ Napoli Federico II, Italy.
    Galgani, Mario
    CNR, Italy; Univ Napoli Federico II, Italy.
    High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease2022In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 65, p. 1390-1397Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD(+) children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD(-) children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time.

  • 43.
    Bybrant, Mara Cerqueiro
    et al.
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Grahnquist, Lena
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Hepatology and Nutrition, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Ortqvist, Eva
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Pediatric Diabetes Clinic, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Andersson, Cecilia
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Forsander, Gun
    The Queen Silvia Children’s hospital, Sahlgrenska University hospital and The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Elding Larsson, Helena
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Lernmark, Ake
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institutet, Stockholm, Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Lund, Sweden.
    Ivarsson, Sten A.
    Department of clinical sciences, Lund University, Skåne University hospital, Malmö, Sweden.
    Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study2018In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 51, no 5, p. 221-227Article in journal (Refereed)
    Abstract [en]

    Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

    Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

    Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018).

    Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

  • 44.
    Bybrant, Mara Cerqueiro
    et al.
    Karolinska Inst, Sweden.
    Uden, Elin
    Lund Univ, Sweden.
    Frederiksen, Filippa
    Karolinska Inst, Sweden.
    Gustafsson, Anna L.
    Hallands Hosp, Sweden.
    Arvidsson, Carl-Goran
    Vastmanlands Hosp, Sweden.
    Fureman, Anna-Lena
    Ostersund Hosp, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Larsson, Helena Elding
    Lund Univ, Sweden.
    Ivarsson, Sten A.
    Lund Univ, Sweden.
    Lindgren, Marie
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping. Lund Univ, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Lycka, Auste Pundziute
    Sahlgrens Univ Hosp, Sweden.
    Persson, Martina
    Karolinska Univ Hosp, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Sarnblad, Stefan
    Orebro Univ, Sweden.
    Akesson, Karin
    Ryhov Cty Hosp, Sweden; Jonkoping Univ, Sweden.
    Ortqvist, Eva
    Karolinska Inst, Sweden.
    Carlsson, Annelie
    Lund Univ, Sweden.
    Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes2021In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 22, no 3, p. 417-424Article in journal (Refereed)
    Abstract [en]

    Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were &gt;= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG &gt;= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

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  • 45.
    Bélteky, Malin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Milletich, Patricia L.
    Univ Florida, FL 32611 USA.
    Ahrens, Angelica P.
    Univ Florida, FL 32611 USA.
    Triplett, Eric W.
    Univ Florida, FL 32611 USA.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Infant gut microbiome composition correlated with type 1 diabetes acquisition in the general population: the ABIS study2023In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis While autoantibodies are traditional markers for type 1 diabetes development, we identified gut microbial biomarkers in 1-year-old infants associated with future type 1 diabetes up to 20 years before diagnosis. Methods Infants enrolled in the longitudinal general population cohort All Babies In Southeast Sweden (ABIS) provided a stool sample at a mean age of 12.5 months. Samples (future type 1 diabetes, n=16; healthy controls, n=268) were subjected to 16S ribosomal RNA (rRNA) sequencing and quantitative PCR. Microbial differences at the taxonomic and core microbiome levels were assessed. PICRUSt was used to predict functional content from the 16S rRNA amplicons. Sixteen infants, with a future diagnosis of type 1 diabetes at a mean age of 13.3 +/- 5.4 years, and one hundred iterations of 32 matched control infants, who remained healthy up to 20 years of age, were analysed. Results Parasutterella and Eubacterium were more abundant in healthy control infants, while Porphyromonas was differentially more abundant in infants with future type 1 diabetes diagnosis. Ruminococcus was a strong determinant in differentiating both control infants and those with future type 1 diabetes using random forest analysis and had differing trends of abundance when comparing control infants and those with future type 1 diabetes. Flavonifractor and UBA1819 were the strongest factors for differentiating control infants, showing higher abundance in control infants compared with those with future type 1 diabetes. Alternatively, Alistipes (more abundant in control infants) and Fusicatenibacter (mixed abundance patterns when comparing case and control infants) were the strongest factors for differentiating future type 1 diabetes. Predicted gene content regarding butyrate production and pyruvate fermentation was differentially observed to be higher in healthy control infants. Conclusions/interpretation This investigation suggests that microbial biomarkers for type 1 diabetes may be present as early as 1 year of age, as reflected in the taxonomic and functional differences of the microbial communities. The possibility of preventing disease onset by altering or promoting a healthy gut microbiome is appealing. Data availability The forward and reverse 16S raw sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject PRJNA875929. Associated sample metadata used for statistical comparison are available in the source data file. R codes used for statistical comparisons and figure generation are available at: https://github.com/PMilletich/T1D_Pipeline.

  • 46.
    Bélteky, Malin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Maternal respiratory infections in early pregnancy increases the risk of type 1 diabetes2020In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 21, no 7, p. 1193-1201Article in journal (Refereed)
    Abstract [en]

    Background/Objective

    Is exposure to maternal infections and use of antibiotics in the prenatal period associated with increased risk of T1D, regardless of genetic risk? Methods Data on infections and use of antibiotics during pregnancy were collected from questionnaires at birth from parents to 16 292 children in the All Babies in Southeast Sweden (ABIS) cohort and validated against national diagnosis registers. As of November 2017, 137 ABIS children had developed T1D, 72 boys and 65 girls (0.8% of the original cohort).

    Results

    More cases were born in spring and summer than fall and winter. However, onset of T1D appeared to be more common in either summer or winter. In univariate analyses, respiratory tract infection in the first trimester (P= .002) and gastroenteritis during pregnancy (P= .04) were associated with later risk of T1D in the offspring. Other types of infection or antibiotic treatment were not associated with an increased risk. In a multiple logistic regression model, a mother with an autoimmune disease (P &lt; .001), father with T1D (P &lt; .001) and respiratory tract infection during the first trimester (P= .005) remained as risk factors for T1D in the offspring. In children with neutral HLA alleles antibiotic treatment may increase the risk of T1D (P= .01, OR 3.46, 95% CI 1.25-9.55).

    Conclusions

    In the general population there seems to be an association between seasonal maternal respiratory tract infection in the first trimester of pregnancy and later risk of T1D in the offspring. HLA may play a role for the effect of exposure to infections and antibiotics.

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  • 47.
    Carlander, Anders
    et al.
    Univ Gothenburg, Sweden.
    Cassel, Sophie
    Univ Gothenburg, Sweden.
    Hook, Malin J-Son
    Generat Pep, Sweden.
    Lundgren, Oskar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Löf, Marie
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Validation and normative data on the Revised Child Anxiety and Depression Scale RCADS-25 in a Swedish national probability sample of children and adolescents aged 4-17 years2024In: International Journal of Methods in Psychiatric Research, ISSN 1049-8931, E-ISSN 1557-0657, Vol. 33, no 1, article id e2007Article in journal (Refereed)
    Abstract [en]

    BackgroundMental health problems among children and adolescents are a growing public health concern. Self-report questionnaires are pivotal for screening and early detection of mental health issues. We evaluate the psychometric properties and provide norm data of the 25-item child and 25-item parent-report versions of the Revised Child Anxiety and Depression Scale (RCADS).MethodsA random probability sample of 29,000 children and adolescents (ages 4-17) from the Swedish population registry was invited. Data collection occurred from September 2021 to January 2022, accompanied by one postal and four SMS reminders.ResultsParticipants (N = 7045, 48.98% girls) demonstrate that the RCADS-25 possesses relatively sound psychometric properties, albeit that the child-report version assessed with children and adolescents aged 8 to 17 years rendered relatively better psychometric properties (e.g., omega = 0.87-0.92, CFI = 0.89) compared with the parent-report version and the children 4 to 7 years old (e.g., omega = 0.72-0.82, CFI = 0.84).ConclusionThe RCADS-25 instruments may be used as an effective instrument for the initial assessment of anxiety and depression in children and adolescents in Sweden.

  • 48.
    Carlsson, Annelie
    et al.
    Lund Univ, Sweden.
    Shepherd, Maggie
    Univ Exeter, England.
    Ellard, Sian
    Univ Exeter, England; Royal Devon and Exeter NHS Fdn Trust, England.
    Weedon, Michael
    Univ Exeter, England.
    Lernmark, Ake
    Lund Univ, Sweden.
    Forsander, Gun
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Colclough, Kevin
    Royal Devon and Exeter NHS Fdn Trust, England.
    Brahimi, Qefsere
    Lund Univ, Sweden.
    Valtonen-Andre, Camilla
    Univ and Reg Labs Reg, Sweden.
    Ivarsson, Sten A.
    Lund Univ, Sweden.
    Elding Larsson, Helena
    Lund Univ, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Ortqvist, Eva
    Karolinska Inst, Sweden.
    Groop, Leif
    Univ Helsinki, Finland.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Hattersley, Andrew T.
    Univ Exeter, England.
    Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study2020In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, no 1, p. 82-89Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.

    RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCKHNF1A, and HNF4A, through either routine clinical or research testing.

    RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.

    CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.

  • 49.
    Casas, Rosaura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Fabricia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Barcenilla, Hugo
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Tavira Iglesias, Beatriz
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Achenbach, Peter
    Helmholtz Zentrum Munchen, Germany; Tech Univ Munich, Germany.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients2020In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, article id 564921Article in journal (Refereed)
    Abstract [en]

    In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 mu g GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD(65)-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC &lt; 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8(+) T cells activation. Patients with poorer clinical response had higher baseline levels of GAD(65-)induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment.

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  • 50.
    Casas, Rosaura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Fabricia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Puente Marin, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Barcenilla, Hugo
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Tavira Iglesias, Beatriz
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Achenbach, Peter
    Tech Univ Munich, Germany.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Intra-lymphatic administration of GAD-alum in type 1 diabetes: long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial)2022In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, p. 687-696Article in journal (Refereed)
    Abstract [en]

    Aim To evaluate the long-term effect of intra-lymphatic administration of GAD-alum and a booster dose 2.5 years after the first intervention (DIAGNODE Extension study) in patients with recent-onset type 1 diabetes. Methods DIAGNODE-1: Samples were collected from 12 patients after 30 months who had received 3 injections of 4 mu g GAD-alum into a lymph node with one-month interval. DIAGNODE Extension study: First in human, a fourth booster dose of autoantigen (GAD-alum) was given to 3 patients at 31.5 months, who were followed for another 12 months. C-peptide was measured during mixed meal tolerance tests (MMTTs). GADA, IA-2A, GADA subclasses, GAD(65)-induced cytokines, PBMCs proliferation and T cells markers were analyzed. Results After 30-month treatment, efficacy was still seen in 8/12 patients (good responders, GR). Partial remission (IDAA1c &lt; 9) had decreased compared to 15 months, but did not differ from baseline, and HbA1c remained stable. GAD(65)-specific immune responses induced by the treatment started to wane after 30 months, and most changes observed at 15 months were undetectable. GADA subclasses IgG2, IgG3 and IgG4 were predominant in the GR along with IgG1. A fourth intra-lymphatic GAD-alum dose to three patients after 31.5 months gave no adverse events. In all three patients, C-peptide seemed to increase the first 6 months, and thereafter, C-peptide, HbA1c, insulin requirement and IDAA1c remained stable. Conclusion The effect of intra-lymphatic injections of GAD-alum had decreased after 30 months. Good responders showed a specific immune response. Administration of a fourth booster dose after 31.5 months was safe, and there was no decline in C-peptide observed during the 12-month follow-up.

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