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  • 1.
    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.

  • 2.
    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.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    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.

  • 3.
    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.

  • 4.
    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, ISSN 2044-6055, 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.

  • 5.
    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.

  • 6.
    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.
    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, ISSN 1664-3224, 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.

  • 7.
    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, ISSN 1932-6203, 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.

  • 8.
    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).

  • 9.
    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.

  • 10.
    Charalampopoulos, Dimitrios
    et al.
    UCL, England.
    Hermann, Julia M.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Maahs, David M.
    Stanford Univ, CA 94305 USA.
    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.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Holl, Reinhard W.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Birkebaek, Niels H.
    Aarhus Univ Hosp, Denmark.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    University College London, London, U.K..
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Foster, Nicole
    Jaeb Ctr Hlth Res, FL USA.
    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.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Univ Copenhagen, Denmark.
    Dahl-Jorgensen, Knut
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Clements, Mark
    Childrens Mercy Hosp, MO 64108 USA; Univ Missouri Kansas City, MO USA; Univ Kansas, KS 66103 USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 6, p. 1180-1187Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

  • 11.
    Dietrich-Zagonel, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Dietrich, Fabricia
    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.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome2018In: American Journal of Sports Medicine, ISSN 0363-5465, E-ISSN 1552-3365, Vol. 46, no 13, p. 3281-3287Article in journal (Refereed)
    Abstract [en]

    Background:

    The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment.

    Hypothesis:

    A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress).

    Study Design:

    Controlled laboratory study.

    Methods:

    Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance.

    Results:

    Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05).

    Conclusion:

    Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing.

    Clinical Relevance:

    The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.

  • 12.
    Dzidic, Majda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. CSIC, Spain; FISABIO, Spain; CIBER ESP, Spain.
    Abrahamsson, Thomas
    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.
    Artacho, A.
    FISABIO, Spain; CIBER ESP, Spain.
    Collado, M. C.
    CSIC, Spain.
    Mira, A.
    FISABIO, Spain; CIBER ESP, Spain.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Oral microbiota maturation during the first 7 years of life in relation to allergy development2018In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 73, no 10, p. 2000-2011Article in journal (Refereed)
    Abstract [en]

    Background Allergic diseases have become a major public health problem in affluent societies. Microbial colonization early in life seems to be critical for instructing regulation on immune system maturation and allergy development in children. Even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development has not yet been reported. Objective Methods We sought to determine the bacterial composition in longitudinally collected saliva samples during childhood in relation to allergy development. Illumina sequencing of the 16S rDNA gene was used to characterize the oral bacterial composition in saliva samples collected at 3, 6, 12, 24 months, and 7 years of age from children developing allergic symptoms and sensitization (n = 47) and children staying healthy (n = 33) up to 7 years of age. Results Conclusion Children developing allergic disease, particularly asthma, had lower diversity of salivary bacteria together with highly divergent bacterial composition at 7 years of age, showing a clearly altered oral microbiota in these individuals, likely as a consequence of an impaired immune system during infancy. Moreover, the relative amounts of several bacterial species, including increased abundance of Gemella haemolysans in children developing allergies and Lactobacillus gasseri and L. crispatus in healthy children, were distinctive during early infancy, likely influencing early immune maturation. Early changes in oral microbial composition seem to influence immune maturation and allergy development. Future experiments should test the probiotic potential of L. gasseri and L. crispatus isolates.

  • 13.
    Dzidic, Majda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. CSISP FISABIO, Spain; Inst Agrochem and Food Technol IATA CSIC, Spain.
    Collado, Maria C.
    Inst Agrochem and Food Technol IATA CSIC, Spain.
    Abrahamsson, Thomas
    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.
    Artacho, Alejandro
    CSISP FISABIO, Spain.
    Stensson, Malin
    Jonkoping Univ, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mira, Alex
    CSISP FISABIO, Spain.
    Oral microbiome development during childhood: an ecological succession influenced by postnatal factors and associated with tooth decay2018In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 12, no 9, p. 2292-2306Article in journal (Refereed)
    Abstract [en]

    Information on how the oral microbiome develops during early childhood and how external factors influence this ecological process is scarce. We used high-throughput sequencing to characterize bacterial composition in saliva samples collected at 3, 6, 12, 24 months and 7 years of age in 90 longitudinally followed children, for whom clinical, dietary and health data were collected. Bacterial composition patterns changed through time, starting with "early colonizers", including Streptococcus and Veillonella; other bacterial genera such as Neisseria settled after 1 or 2 years of age. Dental caries development was associated with diverging microbial composition through time. Streptococcus cristatus appeared to be associated with increased risk of developing tooth decay and its role as potential biomarker of the disease should be studied with species-specific probes. Infants born by C-section had initially skewed bacterial content compared with vaginally delivered infants, but this was recovered with age. Shorter breastfeeding habits and antibiotic treatment during the first 2 years of age were associated with a distinct bacterial composition at later age. The findings presented describe oral microbiota development as an ecological succession where altered colonization pattern during the first year of life may have long-term consequences for childs oral and systemic health.

  • 14.
    Enander, Rebecka
    et al.
    SkaS Hosp Grp, Sweden.
    Adolfsson, Peter
    Hosp Halland, Sweden; Univ Gothenburg, Sweden.
    Bergdahl, Torun
    SkaS Hosp Grp, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, 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.
    Hanas, Ragnar
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 6, p. 1079-1085Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to see if IV insulin therapy at diagnosis preserves beta‐cell function better than multiple subcutaneous (SC) injections.

    Methods

    Fifty‐four children 9.9 ± 3.5 years (range 2.8‐14.9) without ketoacidosis were included in a 2 years, randomized multicenter study with insulin SC or 48 to 72 hours IV initially. Thirty‐three (61%) were boys, 22 (41%) were pubertal. Forty‐eight subjects completed 12 months follow‐up and 43 completed 24 months. At 1, 6, 12, and 24 months, hemoglobin A1c (HbA1c), C‐peptide and insulin/kg/24 h were measured. At 24 months, a mixed‐meal tolerance test (MMTT) was performed.

    Results

    HbA1c at diagnosis was 10.7%, (93 mmol/mol) for IV, 10.7%, (94 mmol/mol) for SC. During the first 2 full days of insulin therapy, mean plasma glucose was 8.2 mmol/L for IV, 9.5 for SC (P = .025). Mean insulin dose was 1.5 U/kg/d for IV vs 1.0 for SC (P = .001). Sixteen (7 in IV, 9 in SC group) started with insulin pumps during the follow‐up. At 24 months, we saw no significant differences: HbA1c (7.5%, 58 mmol/mol, for IV, 7.2%, 55 mmol/mol, for SC; ns), insulin doses (0.79 vs 0.88 U/kg/d; ns), fasting C‐peptide (0.08 vs 0.12 nmol/L; ns), maximal MMTT response (0.19 vs 0.25 nmol/L; ns) and AUC (18.26 vs 23.9 nmol/L*min; ns). Peak C‐peptide >0.2 nmol/L in the combined IV and SC groups correlated significantly with HbA1c and C‐peptide at onset in a multiple regression.

    Conclusion

    Residual beta cell function at 2 years seems to be independent from initial insulin regimens but related to HbA1c and C‐peptide at onset.

  • 15.
    Fernlund, Eva
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund University, Sweden.
    Gyllenhammar, T.
    Lund University, Sweden.
    Jablonowski, R.
    Lund University, Sweden.
    Carlsson, M.
    Lund University, Sweden.
    Larsson, A.
    Uppsala University, Sweden.
    Arnlov, J.
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Liuba, P.
    Lund University, Sweden.
    Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 4, p. 853-863Article in journal (Refereed)
    Abstract [en]

    Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p amp;lt; 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e (p amp;lt; 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p amp;lt; 0.05) versus controls. Endostatin and mitral E/e correlated inversely to myocardial perfusion (p aeamp;lt;currencyamp;gt; 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.

  • 16.
    Fernlund, Eva
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Lund University, Sweden.
    Wålinder Österberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Center for Business support and Development.
    Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 6, p. 1262-1268Article in journal (Refereed)
    Abstract [en]

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G amp;gt; A(p.Arg173Gln)] and BAG3 [BAG3 c.785C amp;gt; T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

  • 17.
    Forsander, G.
    et al.
    Univ Gothenburg, Sweden.
    Stallknecht, S.
    Incentive, Denmark.
    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.
    Marcus, C.
    Karolinska Inst, Sweden.
    Bogelund, M.
    Incentive, Denmark.
    Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model2018In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 35, no 5, p. 621-629Article in journal (Refereed)
    Abstract [en]

    AimTo test the possibility of using a discrete choice experiment model, on a national level in adolescents with Type 1 diabetes, in order to obtain a better understanding of drivers of and barriers to diabetes self-care. MethodsA survey instrument was constructed and tested on a small group of the target population: adolescents aged 15 to amp;lt;18 years with Type 1 diabetes. All individuals in Sweden belonging to this target group (N=2112) were then identified via the Swedish paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to answer an online questionnaire. A valid response for the discrete choice experiment analyses was achieved from 431 individuals. ResultsThe included respondents were not statistically different from non-participants in terms of age and duration of diabetes, but more young women entered the study and the participants had (on average) a significantly lower HbA(1c) value than the non-participants. Participants regarded as undesirable both non-severe hypoglycaemic events (day and night) and hyperglycaemic events. Avoiding weight gain and even achieving weight loss were the most important aspects among female respondents, who were willing to trade off a substantial level of glycaemic control [13 mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment improvements were desired. ConclusionsThe responses may provide useful indications of the aspects that the respondents would prioritize given a real-life dilemma. For treatment effects, stratification along gender lines was important, whereas the treatment administration aspects were stratified according to treatment type because these aspects are closely related.

  • 18.
    Forsgren, Lars
    et al.
    Umeå universitet, Umeå, Sweden.
    Sundelin, Heléne
    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.
    Sveinsson, Olafur
    Neurologiska kliniken, Stockholm, Sweden.
    Epilepsins orsaker, förekomst och prognos [Epilepsy: incidens, prevalens and causes]2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article, review/survey (Refereed)
    Abstract [en]

    Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.

  • 19.
    Gawel, Danuta
    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.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    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.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    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. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. 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.
    Benson, Mikael
    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.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

    Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

    Methods

    The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs.

    Results

    We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model.

    Conclusions

    Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.

  • 20.
    Gunnarsson, Rebeqa
    et al.
    Lund Univ, Sweden.
    Dilorenzo, Sebastian
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Lundin-Strom, Kristina B.
    Lund Univ, Sweden.
    Olsson, Linda
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Biloglav, Andrea
    Lund Univ, Sweden.
    Lilljebjorn, Henrik
    Lund Univ, Sweden.
    Rissler, Marianne
    Lund Univ, Sweden.
    Wahlberg, Per
    Uppsala Univ, Sweden.
    Lundmark, Anders
    Uppsala Univ, Sweden.
    Castor, Anders
    Skane Univ Hosp, Sweden.
    Behrendtz, Mikael
    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, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Fioretos, Thoas
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Paulsson, Kajsa
    Lund Univ, Sweden.
    Isaksson, Anders
    Uppsala Univ, Sweden.
    Johansson, Bertil
    Lund Univ, Sweden; Dept Clin Genet and Pathol, Sweden.
    Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia2018In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 10, p. 2117-2125Article in journal (Refereed)
    Abstract [en]

    High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.

  • 21.
    Hanberger, Lena
    et al.
    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.
    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.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Inst Diabet Res, Germany.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    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; Jonkoping Univ, Sweden.
    Hofer, Sabine
    Med Univ Innsbruck, Austria.
    Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 506-511Article in journal (Refereed)
    Abstract [en]

    Objectives: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared. Methods: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed. Results: Patients in Sweden had fewer clinical visits per year (P amp;lt; .05), lower insulin dose per kg (P amp;lt; .001), and lower proportion of fast acting insulin compared with Germany and Austria (P amp;lt; .001). The proportion of pump users was higher in Sweden (P amp;lt; .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P amp;lt; .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P amp;lt; .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys. Conclusions: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.

  • 22.
    Heyne, David
    et al.
    Leiden Univ, Netherlands.
    Gren Landell, Malin
    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.
    Melvin, Glenn
    Monash Univ, Australia.
    Gentle-Genitty, Carolyn
    Indiana Univ, IN 47405 USA.
    Differentiation Between School Attendance Problems: Why and How?2019In: Cognitive and Behavioral Practice, ISSN 1077-7229, E-ISSN 1878-187X, Vol. 26, no 1, p. 8-34Article in journal (Refereed)
    Abstract [en]

    School attendance problems (SAPs) are heterogeneous with respect to etiology and presentation. The long history of conceptualizing SAPs has led to a vast array of terms and definitions as well as different perspectives on the most helpful approach to classification. For educators, practitioners, researchers, and policymakers, this presents a challenge in understanding, assessing, and intervening with SAPs. This paper outlines evolution in the conceptualization of SAPs, focusing on two contemporary approaches to differentiating between them. One approach draws on the longstanding differentiation between SAP types labeled school refusal, truancy, and school withdrawal. A fourth type of SAP, labeled school exclusion, is also considered. The other approach focuses on the function of absenteeism, measured via the School Refusal Assessment Scale (SRAS). Anecdotal and scientific support for the SAP typology is presented, along with the benefits and shortcomings of the SRAS approach to differentiation. The paper offers suggestions for how to differentiate between SAPs and introduces the SNACK, a brief screening measure that permits differentiation by SAP type.

  • 23.
    Ivars, Katrin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, 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.
    Nelson, Nina
    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, Department of Paediatrics in Linköping. Department of Quality and Patient Safety, Karolinska University Hospital, Stockholm, Sweden.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Department of Neurology, Faculty of Medicine and Health, University of Örebro, Örebro, Sweden.
    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.
    Development of salivary cortisol circadian rhythm in preterm infants2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0182685Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life.

    METHODS: This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire.

    RESULTS: A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02).

    CONCLUSIONS: Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

  • 24.
    Kindgren, Erik
    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. Vastervik Hosp, Sweden; Skaraborg Hosp, Sweden.
    Guerrero Bosagna, Carlos
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    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.
    Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study2019In: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 17, article id 33Article in journal (Refereed)
    Abstract [en]

    BackgroundThe etiology of Juvenile Idiopathic Arthritis (JIA) is poorly understood. The purpose of this study was to examine the possible influence of early nutrition on later development of JIA.MethodsIn a population-based prospective birth cohort of 15,740 children we collected nutritional data, including fish consumption, and biological samples during pregnancy, at birth and at different ages. 16years after study inclusion we identified 42 children with JIA, of whom 11 were positive for Antinuclear Antibodies (ANA). Heavy metals were analysed in cord blood of all 42 JIA patients and 40 age and sex-matched controls. A multivariable logistic regression model, adjusted for relevant factors, was used as well as Mann-Whitney U-test.ResultsFish consumption more than once a week during pregnancy as well as during the childs first year of life was associated with an increased risk of JIA (aOR 4.5 (1.95-10.4); pamp;lt;0.001 and aOR 5.1 (2.1-12.4) pamp;lt;0.001) and of ANA-positivity (aOR 2.2 (1.4-3.6); p=0.002 and pamp;lt;0.001). Concentrations of Al, Cd, Hg and Li in cord blood were significantly higher in the JIA-group than in controls. The ANA-positive, all of whom had consumed fish amp;gt;once/week their first year, had significantly higher concentrations of Al (pamp;lt;0.001), Cd (p=0.003), and Li (pamp;lt;0.001) in cord blood than controls. Frequency of fish consumption correlated with concentrations of Cd (p=0.003), Li (p=0.015) and Hg (p=0.011).ConclusionsModerate exposure to heavy metals, associated with fish consumption, during pregnancy and early childhood may cause effects on the immune system of the offspring, resulting in ANA positivity and JIA.

  • 25.
    Klingberg, Sofia
    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. Department of Public Health and Community Medicine, Section for Epidemiology and Social Medicine (EPSO), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Brekke, Hilde K.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
    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.
    Introduction of fish and other foods during infancy and risk of asthma in the All Babies In Southeast Sweden cohort study2019In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 178, no 3, p. 395-402Article in journal (Refereed)
    Abstract [en]

    The etiology of asthma includes lifestyle factors. Breastfeeding and introduction of complementary foods have been suggested to affect asthma risk, but the scientific foundation is not solid. Children from the birth cohort All Babies In Southeast Sweden study were included (n=9727). Breastfeeding duration and timing of introduction of infant formula and food were collected prospectively during the first year. Through linkage to the Swedish Patient Register, 948 children were identified with any asthma until age 15-17years, of which 450 cases were atopic. Breastfeeding duration was not associated to risk of asthma. Introduction of infant formula earlier than at 14weeks of age was associated with higher risk of non-atopic asthma. Introduction of fish before 43weeks of age, as compared to later, was associated with a lower risk of asthma, irrespective of atopic classification. Reverse causation was accounted for but did not explain the results.Conclusion: Introduction of infant formula and timing of introduction of fish seem to impact the long-term risk of doctor-diagnosed asthma. Emphasis on the growing body of evidence that early introduction of allergens offers protection against atopic disease should be considered in future recommendations.

  • 26.
    Knip, Mikael
    et al.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Akerblom, Hans K.
    University of Helsinki, Finland.
    Al Taji, Eva
    Charles University of Prague, Czech Republic.
    Becker, Dorothy
    University of Pittsburgh, PA USA.
    Bruining, Jan
    Sophia Childrens University Hospital, Netherlands.
    Castano, Luis
    University of Basque Country, Spain.
    Danne, Thomas
    Kinder-und Jugendkrankenhaus–Auf der Bult, Hannover, Germany.
    de Beaufort, Carine
    Centre Hospital Luxembourg, Luxembourg.
    Dosch, Hans-Michael
    University of Toronto, Canada.
    Dupre, John
    University of Western Ontario, Canada.
    Fraser, William D.
    University of Sherbrooke, Canada.
    Howard, Neville
    Childrens Hospital Westmead, Australia.
    Ilonen, Jorma
    University of Turku, Finland; Turku University Hospital, Finland.
    Konrad, Daniel
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany; University of Childrens Hospital Zurich, Switzerland.
    Kordonouri, Olga
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany.
    Krischer, Jeffrey P.
    University of S Florida, FL USA.
    Lawson, Margaret L.
    Childrens Hospital Eastern Ontario, Canada.
    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.
    Madacsy, Laszlo
    Semmelweis University, Hungary.
    Mahon, Jeffrey L.
    University of Western Ontario, Canada.
    Ormisson, Anne
    Tartu University, Estonia.
    Palmer, Jerry P.
    University of Washington, WA USA.
    Pozzilli, Paolo
    University of Campus Biomed Rome, Italy.
    Savilahti, Erkki
    University of Helsinki, Finland.
    Serrano-Rios, Manuel
    CIBERDEM, Spain.
    Songini, Marco
    St Michelle Hospital, Italy.
    Taback, Shayne
    University of Manitoba, Canada.
    Vaarala, Outi
    University of Helsinki, Finland; AstraZeneca, Sweden.
    White, Neil H.
    Washington University, MO USA.
    Virtanen, Suvi M.
    National Institute Health and Welf, Finland.
    Wasikowa, Renata
    Medical Academic Wroclaw, Poland.
    Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial2018In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 319, no 1, p. 38-48Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.

  • 27.
    Kurien, M.
    et al.
    Univ Sheffield, England.
    Ludvigsson, J. F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden.
    Sanders, D. S.
    Univ Sheffield, England.
    Zylberberg, H. M.
    Columbia Univ Coll Phys and Surg, NY 10032 USA.
    Green, P. H.
    Columbia Univ Coll Phys and Surg, NY 10032 USA.
    Sundelin, Heléne
    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.
    Lebwohl, B.
    Karolinska Inst, Sweden; Columbia Univ Coll Phys and Surg, NY 10032 USA.
    Persistent mucosal damage and risk of epilepsy in people with celiac disease2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 3, p. 592-+Article in journal (Refereed)
    Abstract [en]

    Background and purposeCeliac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy. The objective of this study was to determine whether persistent VA on follow-up biopsy affected long-term epilepsy risk and epilepsy-related hospital emergency admissions. MethodsThis was a nationwide cohort study. We identified all people in Sweden with histological evidence of CD who underwent a follow-up small intestinal biopsy (1969-2008). We compared those with persistent VA with those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant International Classification of Diseases codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures. ResultsVillous atrophy was present in 43% of 7590 people with CD who had a follow-up biopsy. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio, 0.61; 95% confidence interval, 0.38-0.98). On stratified analysis, this effect was primarily amongst males (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80). Among the 58 patients with CD with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (hazard ratio, 0.37; 95% confidence interval, 0.09-1.09). ConclusionsIn a population-based study of individuals with CD, persisting VA on follow-up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. The mechanism as to why persistent VA confers this benefit requires further exploration.

  • 28.
    Larsson, Anna
    et al.
    Lund Univ, Sweden.
    Ottosson, Peter
    Lund Univ, Sweden.
    Törnqvist, Caroline
    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.
    Olhager, Elisabeth
    Lund Univ, Sweden.
    Body composition and growth in full-term small for gestational age and large for gestational age Swedish infants assessed with air displacement plethysmography at birth and at 3-4 months of age2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0207978Article in journal (Refereed)
    Abstract [en]

    Background Being born small for gestational age (SGA) or large for gestational age (LGA) has short and long term metabolic consequences. There is a growing interest in the extent to which body composition, both in the short and the long term, differs in infants born at the extremes of these birth weights. Methods Body composition in 25 SGA and 25 LGA infants were assessed during the first days of life and at 3-4 months of age using air displacement plethysmography. Results SGA infants had significantly lower body fat (%) at birth compared to LGA infants. SGA infants increased their body weight and length at a significantly higher rate between birth and 3-4 months than LGA infants. Fat mass (g) in SGA infants increased 23 times between birth and 3-4 months of age compared to 2.8 times for LGA infants. At 3-4 months of age LGA infants reached a threshold in body fat (%) while SGA infants were still gaining body fat (%). Conclusion Several significant differences have been identified between SGA and LGA infants, indicating that the effects of intrauterine life continues to play an important role in body composition and growth during the first 3-4 months of life.

  • 29.
    Larsson, Christina R.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
    Januszewski, Andrzej S.
    NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia; Department of Diabetes and Endocrinology, St Vincent’s Hospital Melbourne and University of Melbourne, Melbourne, Victoria, Australia.
    McGrath, Rachel T.
    Department of Diabetes, Endocrinology and Metabolism, Northern Clinical School, The University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia.
    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.
    Keech, Anthony C.
    NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
    MacIsaac, Richard J.
    Department of Diabetes and Endocrinology, St Vincent’s Hospital Melbourne and University of Melbourne, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
    Ward, Glenn M.
    Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
    ONeal, David N.
    NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia; Department of Diabetes and Endocrinology, St Vincent’s Hospital Melbourne and University of Melbourne, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
    Fulcher, Gregory R.
    Department of Diabetes, Endocrinology and Metabolism, Northern Clinical School, The University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia.
    Jenkins, Alicia J.
    NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia; Department of Diabetes and Endocrinology, St Vincent’s Hospital Melbourne and University of Melbourne, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
    Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with type 1 diabetes is common2018In: Internal medicine journal (Print), ISSN 1444-0903, E-ISSN 1445-5994, Vol. 48, no 9, p. 1080-1086Article in journal (Refereed)
    Abstract [en]

    Background

    In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education.

    Aim

    To develop and utilise a survey to evaluate patient self‐management of overnight glycaemia in adults with T1D.

    Methods

    Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self‐management and glycaemic control, including responses to hypothetical pre‐bed blood glucose (BG) levels (4–20 mmol/L). Statistical analyses included t‐tests, Chi square tests and ANOVA with significance considered at P < 0.05.

    Results

    There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006.

    Conclusions

    Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self‐management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.

  • 30.
    Lentini, Antonio
    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.
    Lagerwall, Cathrine
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Mjoseng, Heidi K.
    Univ Edinburgh, Scotland.
    Douvlataniotis, Dimitrios Karolos
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Vogt, Hartmut
    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.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Meehan, Richard R.
    Univ Edinburgh, Scotland.
    Benson, Mikael
    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, Heart and Medicine Center, Allergy Center.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    A reassessment of DNA-immunoprecipitation-based genomic profiling2018In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 15, no 7, p. 499-+Article in journal (Refereed)
    Abstract [en]

    DNA immunoprecipitation followed by sequencing (DIP-seq) is a common enrichment method for profiling DNA modifications in mammalian genomes. However, the results of independent DIP-seq studies often show considerable variation between profiles of the same genome and between profiles obtained by alternative methods. Here we show that these differences are primarily due to the intrinsic affinity of IgG for short unmodified DNA repeats. This pervasive experimental error accounts for 50-99% of regions identified as enriched for DNA modifications in DIP-seq data. Correction of this error profoundly altered DNA-modification profiles for numerous cell types, including mouse embryonic stem cells, and subsequently revealed novel associations among DNA modifications, chromatin modifications and biological processes. We conclude that both matched input and IgG controls are essential in order for the results of DIP-based assays to be interpreted correctly, and that complementary, non-antibody-based techniques should be used to validate DIP-based findings to avoid further misinterpretation of genome-wide profiling data.

  • 31.
    Lindell, Nina
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Carlsson, Annelie
    Lund University, Sweden.
    Josefsson, Ann
    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, Department of Gynaecology and Obstetrics in Linköping.
    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.
    Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide, prospective, population-based case-control study2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 1, p. 130-137Article in journal (Refereed)
    Abstract [en]

    Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes. Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children. Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p amp;lt; 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p amp;lt; 0.001) in age at onset in relation to the mothers BMI. Among children in the oldest age group (15-19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0-4 years) the pattern was reversed. Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.

  • 32.
    Long, Anna E.
    et al.
    Univ Bristol, England.
    Wilson, Isabel V.
    Univ Bristol, England.
    Becker, Dorothy J.
    Univ Pittsburgh, PA 15260 USA.
    Libman, Ingrid M.
    Univ Pittsburgh, PA 15260 USA.
    Arena, Vincent C.
    Univ Pittsburgh, PA 15260 USA.
    Wong, F. Susan
    Cardiff Univ, Wales.
    Steck, Andrea K.
    Univ Colorado, CO USA.
    Rewers, Marian J.
    Univ Colorado, CO USA.
    Yu, Liping
    Univ Colorado, CO USA.
    Achenbach, Peter
    Tech Univ Munich, Germany; Tech Univ Munich, Germany.
    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.
    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.
    Williams, Alistair J. K.
    Univ Bristol, England.
    Gillespie, Kathleen M.
    Univ Bristol, England.
    Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 6, p. 1484-1490Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of slow progressors (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. Methods Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Barts Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed amp;lt; 5 years old from BOX) using the chi(2) test. Results In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. Conclusion No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

  • 33.
    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.
    Nej – barn med typ 1-diabetes lever inte i ständig livsfara2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Other academic)
  • 34.
    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.
    Vi måste bli bättre på att diagnostisera typ 1-diabetes [Diagnostics of type 1 diabetes must be improved]2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Other academic)
    Abstract [sv]

    Incidence of type 1 diabetes in children and adolescents continues to increase but diagnosis is often delayed and keto-acidosis too common. More information is needed. General auto-antibody screening can be discussed.

  • 35.
    Ludvigsson, Johnny
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lefebvre, Pierre
    Univ Liege, Belgium.
    Nerup, Jorn
    Gentofte Univ Copenhagen, Denmark.
    It is time to restore Rules for Authorship of scientific publications2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 586-586Article in journal (Other academic)
    Abstract [en]

    n/a

  • 36.
    Ludvigsson, Johnny
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    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.
    Letter: Intralymphatic Injection of Autoantigen in Type 1 Diabetes in NEW ENGLAND JOURNAL OF MEDICINE, vol 376, issue 7, pp 697-6992017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, no 7, p. 697-699Article in journal (Other academic)
    Abstract [en]

    n/a

  • 37.
    Lundgren, Oskar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of 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.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regional Board, Research and Development Unit.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institutet, Solna, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Inverted items and validity: A psychobiological evaluation of two measures of psychological resources and one depression scale2018In: Health psychology open, ISSN 2055-1029, Vol. 5, no 1, article id 2055102918755045Article in journal (Refereed)
    Abstract [en]

    Psychological resources and risk factors influence risk of coronary heart disease. We evaluated whether inverted items in the Self-esteem, Mastery, and Center for Epidemiological Studies Depression scales compromise validity in the context of coronary heart disease. In a population-based sample, validity was investigated by calculating correlations with other scales (n = 1004) and interleukin-6 (n = 374), and by analyzing the relationship with 8-year coronary heart disease risk (n = 1000). Negative items did not affect the validity of the resource scales. In contrast, positive items from Center for Epidemiological Studies Depression showed no significant relationships with biological variables. However, they had no major impact on the validity of the original scale.

  • 38.
    Lundgren, Oskar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of 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.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regional Board, Research and Development Unit.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    A journey through chaos and calmness: experiences of mindfulness training in patients with depressive symptoms after a recent coronary event - a qualitative diary content analysis.2018In: BMC Psychology, E-ISSN 2050-7283, Vol. 6, no 1, article id 46Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychological distress with symptoms of depression and anxiety is common and unrecognized in patients with coronary artery disease (CAD). Efforts have been made to treat psychological distress in CAD with both conventional methods, such as antidepressant drugs and psychotherapy, and non-conventional methods, such as stress management courses. However, studies focusing on the experiences of mindfulness training in this population are still scarce. Therefore, the aim of this study was to explore immediate experiences of mindfulness practice among CAD patients with depressive symptoms.

    METHODS: A qualitative content analysis of diary entries, written immediately after practice sessions and continuously during an 8-week long Mindfulness Based Stress Reduction course (MBSR), was applied.

    RESULTS: Twelve respondents participated in the study. The main category: a journey through chaos and calmness captured the participants' concurrent experiences of challenges and rewards over time. This journey appears to reflect a progressive development culminating in the harvesting of the fruits of practice at the end of the mindfulness training. Descriptions of various challenging facets of mindfulness practice - both physical and psychological - commonly occurred during the whole course, although distressing experiences were more predominant during the first half. Furthermore, the diary entries showed a wide variety of ways of dealing with these struggles, including both constructive and less constructive strategies of facing difficult experiences. As the weeks passed, participants more frequently described an enhanced ability to concentrate, relax and deal with distractions. They also developed their capacity to observe the content of their mind and described how the practice began to yield rewards in the form of well-being and a sense of mastery.

    CONCLUSIONS: Introducing MBSR in the aftermath of a cardiac event, when depressive symptoms are present, is a complex and delicate challenge in clinical practice. More nuanced information about what to expect as well as the addition of motivational support and skillful guidance during the course should be given in accordance with the participants' experiences and needs.

    TRIAL REGISTRATION: The trial was retrospectively registered in clinicaltrials.gov (registration number: NCT03340948 ).

  • 39.
    Lundin-Ström, Kristina B.
    et al.
    Lund Univ, Sweden.
    Biloglav, Andrea
    Lund Univ, Sweden.
    Lilljebjorn, Henrik
    Lund Univ, Sweden.
    Rissler, Marianne
    Lund Univ, Sweden.
    Fioretos, Thoas
    Lund Univ, Sweden; Department of Clinical Genetics and Pathology, Division of Laboratory Medicine, Lund, Sweden.
    Hansson, Markus
    Lund Univ, Sweden.
    Behrendtz, Mikael
    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.
    Castor, Anders
    Skane Univ Hosp, Sweden.
    Olsson, Linda
    Department of Clinical Genetics and Pathology, Division of Laboratory Medicine, Lund, Sweden.
    Johansson, Bertil
    Lund Univ, Sweden; Department of Clinical Genetics and Pathology, Division of Laboratory Medicine, Lund, Sweden.
    Whole-exome sequencing exploration of acquired uniparental disomies in B-cell precursor acute lymphoblastic leukemia2018In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 9, p. 2058-2062Article in journal (Refereed)
    Abstract [en]

    n/a

  • 40.
    Mattsson, Sven
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Persson, D.
    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.
    Glad Mattsson, Gunilla
    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.
    Lindström, S.
    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.
    Night-time diuresis pattern in children with and without primary monosymptomatic nocturnal enuresis2019In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 15, no 3, p. 229.e1-229.e8Article in journal (Refereed)
    Abstract [en]

    Introduction

    Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor overactivity and high arousal thresholds as alternatives. An earlier finding of night-time polyuria in 12% of healthy non-enuretic schoolchildren underscores that excessive night-time diuresis per se is unlikely the major cause of PMNE.

    Objective

    The objective of this study was to compare the night-time diuresis pattern in children with and without PMNE and to evaluate the role of night-time polyuria in provoking enuretic episodes in children with PMNE.

    Study design

    Night-time diuresis pattern was recorded in 27 children with PMNE, aged 6–15 years, and 29 non-enuretic children, aged 6–13 years. Using a portable ultrasound recorder, the bladder volume was estimated at 15-min intervals for at least three nights with the child sleeping in its own bed at home. The volume of enuretic episodes was controlled using preweighed diapers. All voids were registered by time and volume. Diuresis during night time was estimated from the slope of regression lines fitted to ultrasound recording points. Mean night-time diuresis was calculated from total urine production during the night and time interval from the last void before bedtime to the first morning void.

    Results

    Night-time bladder filling pattern was recorded from 189 nights, giving 149 interpretable patterns for analysis (77 children with PMNE and 72 dry children). The night-time diuresis pattern was similar for children with or without PMNE, showing large variability between different nights of the same child. Most nights displayed a smooth bladder filling at constant low rate, whereas other nights showed an early phase with high diuresis followed by a longer period of low diuresis with no difference between the two groups.

    Discussion

    Night-time diuresis has been non-invasively monitored in children while asleep in their own beds at home. The pattern of night-time diuresis varies considerably between different nights of the same child, with no obvious differences in any diuresis parameters between children with or without PMNE.

    Conclusion

    Non-enuretic children have similar diuresis pattern and maximal night-time diuresis values as children with PMNE, making it unlikely that PMNE is caused by night-time polyuria per se (Summary figure). Delayed maturation of sleep mechanisms such as decreased arousability or sleep inhibition of the micturition reflex is more likely to be the main etiology for enuresis.

  • 41.
    Mörelius, Evalotte
    et al.
    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.
    Ivars, Katrin
    Linköping University, Department of Clinical and Experimental Medicine, 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.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Nelson Follin, Nina
    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, Department of Paediatrics in Linköping. Karolinska University Hospital, Sweden.
    Salivary cortisol circadian rhythm in infants at psychosocial risk showed more variations than previous studies of healthy full-term infants2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 12, p. 2060-2061Article in journal (Refereed)
    Abstract [en]

    n/a

  • 42.
    Nordwall, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, 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. Vrinnevi Hosp, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    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.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Impact of Age of Onset, Puberty, and Glycemic Control Followed From Diagnosis on Incidence of Retinopathy in Type 1 Diabetes: The VISS Study2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 4, p. 609-616Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To evaluate sex, age at diabetes onset, puberty, and HbA1c, with subjects followed from diabetes diagnosis and during different time periods, as risk factors for developing diabetic simplex and proliferative retinopathy.

    RESEARCH DESIGN AND METHODS In a population-based observational study, HbA1c for 451 patients diagnosed with diabetes before 35 years of age during 1983–1987 in southeast Sweden was followed for up to 18–24 years from diagnosis. Long-term mean weighted HbA1c(wHbA1c) was calculated. Retinopathy was evaluated by fundus photography and analyzed in relation to wHbA1c levels.

    RESULTS Lower wHbA1c, diabetes onset ≤5 years of age, and diabetes onset before puberty, but not sex, were associated with longer time to appearance of simplex retinopathy. Proliferative retinopathy was associated only with wHbA1c. The time to first appearance of any retinopathy decreased with increasing wHbA1c. Lower wHbA1c after ≤5 years’ diabetes duration was associated with later onset of simplex retinopathy but not proliferative retinopathy. With time, most patients developed simplex retinopathy, except for those of the category wHbA1c≤50 mmol/mol (6.7%), for which 20 of 36 patients were without any retinopathy at the end of the follow-up in contrast to none of 49 with wHbA1c >80 mmol/mol (9.5%).

    CONCLUSIONS Onset at ≤5 years of age and lower wHbA1c the first 5 years after diagnosis are associated with longer duration before development of simplex retinopathy. There is a strong positive association between long-term mean HbA1c measured from diagnosis and up to 20 years and appearance of both simplex and proliferative retinopathy.

  • 43.
    Norman, Mikael
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Umea Univ Hosp, Sweden.
    Hallberg, Boubou
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Abrahamsson, Thomas
    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.
    Bjorklund, Lars J.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Domellof, Magnus
    Umea Univ, Sweden.
    Farooqi, Aijaz
    Umea Univ, Sweden; Umea Univ, Sweden.
    Foyn Bruun, Cathrine
    Umea Univ, Sweden.
    Gadsboll, Christian
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Hellstrom-Westas, Lena
    Uppsala Univ, Sweden.
    Ingemansson, Fredrik
    Ryhov Cty Hosp, Sweden.
    Kallen, Karin
    Lund Univ, Sweden.
    Ley, David
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Marsal, Karel
    Lund Univ, Sweden.
    Normann, Erik
    Uppsala Univ, Sweden.
    Serenius, Fredrik
    Uppsala Univ, Sweden.
    Stephansson, Olof
    Karolinska Inst, Sweden.
    Stigson, Lennart
    Gothenburg Univ, Sweden.
    Um-Bergstrom, Petra
    Karolinska Inst, Sweden; Soder Sjukhuset, Sweden.
    Hakansson, Stellan
    Umea Univ, Sweden.
    Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-20162019In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 12, p. 1188-1199Article in journal (Refereed)
    Abstract [en]

    Importance  Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown.

    Objective  To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016.

    Design, Setting and Participants  All births at 22-26 weeks’ gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016.

    Exposures  Delivery at 22-26 weeks’ gestational age.

    Main Outcomes and Measures  The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia).

    Results  During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks’ gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks’ gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, −7% [95% CI, −11% to −2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks’ gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, −6% [95% CI, −11% to −1.7%], P = .008).

    Conclusions and Relevance  Among live births at 22-26 weeks’ gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

  • 44.
    Norman, Mikael
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Vasterbotten Cty Council, Sweden.
    Kallen, Karin
    Vasterbotten Cty Council, Sweden; Lund Univ, Sweden.
    Wahlstrom, Erik
    Natl Board Hlth and Welf, Sweden.
    Hakansson, Stellan
    Vasterbotten Cty Council, Sweden; Umea Univ, Sweden.
    Skiold, Beatrice
    Swedish Neonatal Soc, Sweden; Karolinska Inst, Sweden.
    Naver, Lars
    Karolinska Inst, Sweden.
    Domellof, Magnus
    Umea Univ, Sweden.
    Abrahamsson, Thomas
    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.
    Stigson, Lennart
    Gothenburg Univ, Sweden.
    Blomqvist, Ylva Thernstrom
    Uppsala Univ, Sweden.
    Nyholm, Annika
    Umea Univ, Sweden.
    Ingemansson, Fredrik
    Jonkoping Acad, Sweden.
    Holmstrom, Gerd
    Uppsala Univ, Sweden.
    Bjorklund, Lars
    Lund Univ, Sweden.
    Wikstrom, Anna-Karin
    Uppsala Univ, Sweden.
    Wallin-Gyokeres, Annica
    Parent Representat, Sweden.
    The Swedish Neonatal Quality Register - contents, completeness and validity2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 8, p. 1411-1418Article in journal (Refereed)
    Abstract [en]

    Aim To describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers. Methods SNQ collects data for infants admitted to neonatal units during the first four postnatal weeks. Completeness and registers agreement were determined cross-linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years. Results In total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24-34, completeness of SNQ was 98-99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near-term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re-admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic-ischaemic encephalopathy) were often missing in the population registers. Conclusion SNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.

  • 45.
    Oberg, Daniel
    et al.
    Vastervik Hosp, Sweden.
    Salemyr, Jenny
    Karolinska Inst, Sweden; Univ Hosp, Sweden.
    Ortqvist, Eva
    Karolinska Inst, Sweden; Univ Hosp, Sweden.
    Juul, Anders
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Bang, Peter
    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.
    A longitudinal study of serum insulin-like growth factor-I levels over 6 years in a large cohort of children and adolescents with type 1 diabetes mellitus: A marker reflecting diabetic retinopathy2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 5, p. 972-978Article in journal (Refereed)
    Abstract [en]

    Objective

    To evaluate longitudinal serum insulin‐like growth factor‐I (IGF‐I) in a large cohort of children and adolescents with type 1 diabetes in relation to hemoglobin A1c (HbA1c), age, diabetes duration, and body mass index (BMI), its association to height and retinopathy, and in comparison with healthy subject references.

    Methods

    A total of 2683 serum IGF‐I values were obtained from 806 children and adolescents with T1DM, from annual blood samples for up to 6 consecutive years.

    Results

    In a multiple regression analysis IGF‐I values were negatively correlated to HbA1c and diabetes duration, and positively correlated to BMI (P < .001, P < .001, and P < .001, respectively, adjusted r2 = 0.102). Children and adolescents with T1DM had lower mean IGF‐I levels and reference interval limits compared to healthy subjects. In boys, mean (SD) IGF‐I SD score (SDS) levels were −1.04 (±1.3) calculated from the healthy reference. IGF‐I peaked at 15 years of age, similarly to healthy controls, but with markedly lower levels in late puberty. Girls were more affected at later stages of puberty but with a slightly less depressed overall mean IGF‐I SDS of −0.69 (±1.2). In a subgroup of 746 subjects with fundus photography, a negative correlation was seen between individual mean IGF‐I SDS and preproliferative retinopathy (P = .004, adjusted r2 = 0.021). In another subgroup of 84 adolescents, no correlation was seen between individual mean IGF‐I SDS and target height SDS or distance to target height SDS.

    Conclusion

    Poor metabolic control and diabetes duration impact negatively on serum IGF‐I levels. A low individual mean IGF‐I level was associated with progression of retinopathy independently of HbA1c, age, gender, and diabetes duration. Disease, sex and age related IGF‐I SDS may become clinical helpful as a supplement to HbA1c in predicting the long‐term outcome for children and adolescents with T1DM.

  • 46.
    Olsen Faresjö, Åshild
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. 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.
    Pet exposure in the family during pregnancy and risk for type 1 diabetes: The prospective ABIS study2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 7, p. 1206-1210Article in journal (Refereed)
    Abstract [en]

    Background: The autoimmune process later leading to type 1 diabetes (T1D) seems to start very early in life. Different viruses have been suspected to contribute to the development of T1D, some already during pregnancy. As viruses may be hosted by animals and from them transferred to humans we decided to investigate if exposure to pets during pregnancy is related to later development of T1D. Methods: ABIS (All Babies in Southeast Sweden)-is a prospective population-based cohort study of unselected children born in southeast Sweden between Oct first 1997 to Oct first 1999. Parents of 16384 children answered a questionnaire within 3 days after birth including information about exposure to different pets. The ABIS registry has been connected to the National Registry of diagnosis and also the national Registry of Drug prescriptions so we know that 137 children have got T1D, and they were compared with the non-diabetic population. Results: During pregnancy, 45.5% of the mothers had pet animals at home. Most common were cats (25.0%) and dogs (18.7%). Neither exposure to dogs (OR = 1.27, P = 0.23) or cats (OR = 0.81, P = 0.31) were associated to later T1D risks. However, exposure to hamsters increased the T1D risk (OR 4.21, P = 0.0007). In a multiple regression this association remained (P = 0.005) when adjusted for other possible risk factors. Conclusions: Exposure to hamster during pregnancy seems to increase the risk of T1D in the child. One possibility could be infection by virus hosted by the pet.

  • 47.
    Olsson, Linda
    et al.
    Div Lab Med, Sweden.
    Lundin-Ström, Kristina B.
    Lund Univ, Sweden.
    Castor, Anders
    Skåne Univ Hosp, Sweden.
    Behrendtz, Mikael
    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, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Biloglav, Andrea
    Lund Univ, Sweden.
    Noren-Nyström, Ulrika
    Umeå Univ, Sweden.
    Paulsson, Kajsa
    Lund Univ, Sweden.
    Johansson, Bertil
    Div Lab Med, Sweden; Lund Univ, Sweden.
    Improved cytogenetic characterization and risk stratification of pediatric acute lymphoblastic leukemia using single nucleotide polymorphism array analysis: A single center experience of 296 cases2018In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 57, no 11, p. 604-607Article in journal (Refereed)
    Abstract [en]

    Single nucleotide polymorphism array (SNP-A) analyses are increasingly being introduced in routine genetic diagnostics of acute lymphoblastic leukemia (ALL). Despite this, only few studies that have compared the diagnostic value of SNP-A with conventional chromosome banding have been published. We here report such a comparison of 296 ALL cases, the largest series to date. Only genomic imbalances amp;gt;5Mb and microdeletions targeting the BTG1, CDKN2A/B, EBF1, ERG, ETV6, IKZF1, PAX5, and RB1 genes and the pseudoautosomal region 1 (PAR1) were ascertained, in agreement with recent guidelines. Of 36 T-cell ALL cases, the karyotypes of 24 cases (67%) were revised by SNP-A analyses that either revealed additional imbalances amp;gt;5Mb or better characterized the changes found by G-banding. Of 260 B-cell precursor (BCP) ALL cases, SNP-A analyses identified additional copy number alterations, including the above-mentioned microdeletions, or better characterized the imbalances found by G-banding in 236 (91%) cases. Furthermore, the cytogenetic subtype classification of 41/260 (16%) BCP ALL cases was revised based on the SNP-A findings. Of the subtype revisions, 12/41 (29%) had clinical implications as regards risk stratifying cytogenetic groups or genotype-specific minimal residual disease stratification. We conclude that SNP-A analyses dramatically improve the cytogenetic characterization of both T-cell and BCP ALL and also provide important information pertinent to risk stratification of BCP ALL.

  • 48.
    Persson, M.
    et al.
    Karolinska Univ Hosp, Sweden.
    Becker, C.
    Skane Univ Hosp, Sweden.
    Larsson, H. Elding
    Lund Univ, Sweden.
    Lernmark, A.
    Lund Univ, Sweden.
    Forsander, G.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ivarsson, S. A.
    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.
    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.
    Marcus, C.
    Karolinska Inst, Sweden.
    Carlsson, A.
    Lund Univ, Sweden.
    The Better Diabetes Diagnosis (BDD) study - A review of a nationwide prospective cohort study in Sweden2018In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 140, p. 236-244Article, review/survey (Refereed)
    Abstract [en]

    The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects. (C) 2018 Elsevier B.V. All rights reserved.

  • 49.
    Samuelsson, Ulf
    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. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Åkesson, Karin
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Peterson, Anette
    Jonkoping Univ, Sweden; Jonkoping Univ, Sweden.
    Hanas, Ragnar
    Uddevalla Cent Hosp, Sweden; Univ Gothenburg, Sweden.
    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.
    Continued improvement of metabolic control in Swedish pediatric diabetes care2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 1, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams. Methods: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes. Results: The proportion of patients in IQ-1 with a mean HbA1c amp;lt;7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P amp;lt; .001), and from 30.2% to 37.2% (P amp;lt; .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P amp;lt; .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (amp;gt;8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group. Conclusions: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.

  • 50.
    Sandestig, Anna
    et al.
    Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gréen, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Vogt, Hartmut
    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.
    Wahlström, Johan
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Pepler, Alexander
    Department of CeGaT GmbH, Tübingen, Germany.
    Ellnebo, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Biskup, Saskia
    Department of CeGaT GmbH, Tübingen, Germany.
    Stefanova, Margarita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change?: Two Novel Mutations and Literature Review2019In: Molecular Syndromology, ISSN 1661-8769, E-ISSN 1661-8777, Vol. 9, no 5, p. 259-265Article in journal (Refereed)
    Abstract [en]

    The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208Camp;gt;G (p.Pro70Ala) and c.511Camp;gt;T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.

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