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  • 1.
    Alaedini, Armin
    et al.
    Institute of Human Nutrition, Columbia University Medical Center, New York NY, USA; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA .
    Lebwohl, Benjamin
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Wormser, Gary P.
    Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla NY, United States.
    Green, Peter H.
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York NY, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom.
    Borrelia infection and risk of celiac disease2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, article id 169Article in journal (Refereed)
    Abstract [en]

    Background: Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

    Methods: Biopsy reports from all of Sweden's pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.

    Results: Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06-2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40-2.35), with the risk of disease being highest in the first year of follow-up.

    Conclusions: Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

  • 2.
    Ban, L.
    et al.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, United Kingdom.
    West, J.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, United Kingdom.
    Sultan, A. Abdul
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, United Kingdom.
    Dhalwani, N. N.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, United Kingdom.
    Ludvigsson, Jonas F.
    Örebro University Hospital.
    Tata, L. J.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, United Kingdom.
    Limited risks of major congenital anomalies in children of mothers with coeliac disease: a population-based cohort study2015In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 122, no 13, p. 1833-1841Article in journal (Refereed)
    Abstract [en]

    Objective: To examine major congenital anomaly (CA) risks in children of mothers with coeliac disease (CD) compared with mothers without CD.

    Design: Population-based cohort study.

    Setting: Linked maternal-child medical records from a large primary care database from the UK.

    Population: A total of 562332 live singletons of mothers with and without CD in 1990-2013.

    Methods: We calculated the absolute major CA risks in children whose mothers had CD, and whether this was diagnosed or undiagnosed before childbirth. Logistic regression with a generalised estimating equation was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) for CAs associated with CD.

    Main outcome measures: Fourteen system-specific major CA groups classified according to the European Surveillance of Congenital Anomalies and neural tube defects (NTDs).

    Results: Major CA risk in 1880 children of mothers with CD was 293 per 10000 liveborn singletons, similar to the risk in those without CD (282; aOR 0.98, 95% CI 0.74-1.30). The risk was slightly higher in 971 children, whose mothers were undiagnosed (350; aOR 1.14, 95% CI 0.79-1.64), than in 909 children whose mothers were diagnosed (231; aOR 0.80, 95% CI 0.52-1.24). There was a three-fold increase in nervous system anomalies in the children of mothers with undiagnosed CD (aOR 2.98, 95%CI 1.06-8.33, based on five exposed cases and one had an NTD), and these women were all diagnosed with CD at least 4years after their children were born.

    Conclusions: There was no statistically significant increase in risk of major CAs in children of mothers with coeliac disease overall, compared with the general population.

  • 3.
    Ban, Lu
    et al.
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom; Division of Rheumatology, Orthopaedics and Dermatology, Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom.
    Sprigg, Nikola
    Stroke, Division of Neuroscience, University of Nottingham, Nottingham, United Kingdom.
    Abdul Sultan, Alyshah
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom; Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, United Kingdom.
    Nelson-Piercy, Catherine
    Women's Health Academic Centre, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
    Bath, Philip M
    Women's Health Academic Centre, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Stephansson, Olof
    Department of Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Tata, Laila J
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom.
    Incidence of First Stroke in Pregnant and Nonpregnant Women of Childbearing Age: A Population-Based Cohort Study From England2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 4, article id e004601Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pregnant women may have an increased risk of stroke compared with nonpregnant women of similar age, but the magnitude and the timing of such risk are unclear. We examined the risk of a first stroke event in women of childbearing age and compared the risk during pregnancy and in the early postpartum period with the background risk outside these periods.

    METHODS AND RESULTS: We conducted an open cohort study of 2 046 048 women aged 15 to 49 years between April 1, 1997, and March 31, 2014, using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records in England. Risk of first stroke was assessed by calculating the incidence rate of stroke in antepartum, peripartum (2 days before until 1 day after delivery), and early (first 6 weeks) and late (second 6 weeks) postpartum periods compared with nonpregnant time using a Poisson regression model with adjustment for maternal age, socioeconomic group, and calendar time. A total of 2511 women had a first stroke. The incidence rate of stroke was 25.0 per 100 000 person-years (95% CI 24.0-26.0) in nonpregnant time. The rate was lower antepartum (10.7 per 100 000 person-years, 95% CI 7.6-15.1) but 9-fold higher peripartum (161.1 per 100 000 person-years, 95% CI 80.6-322.1) and 3-fold higher early postpartum (47.1 per 100 000 person-years, 95% CI 31.3-70.9). Rates of ischemic and hemorrhagic stroke both increased peripartum and early postpartum.

    CONCLUSIONS: Although the absolute risk of first stroke is low in women of childbearing age, healthcare professionals should be aware of a considerable increase in relative risk during the peripartum and early postpartum periods.

  • 4.
    Bjornsdottir, Sigridur
    et al.
    Dept Mol Med & Surg, Karolinska Inst, Stockholm, Sweden.
    Sundstrom, Anders
    Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Swede.
    Blomqvist, Paul
    Dept Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden.
    Kampe, Olle
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Bensing, Sophie
    Dept Mol Med & Surg, Karolinska Inst, Stockholm, Sweden; Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Drug Prescription Patterns in Patients With Addison's Disease: A Swedish Population-Based Cohort Study2013In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 5, p. 2009-2018Article in journal (Refereed)
    Abstract [en]

    Context: There are no published data on drug prescription in patients with Addison's disease ( AD). Objective: Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. Design and Setting: We conducted a population-based cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. Main Outcome Measure: We determined the ratio of observed to expected number of patients treated with prescribed drugs. Results: Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Conclusion: Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.

  • 5.
    Brooke, Hannah Louise
    et al.
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Talback, Mats
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hörnblad, Jesper
    National Board of Health and Welfare, Stockholm, Sweden.
    Johansson, Lars Age
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Druid, Henrik
    Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Feychting, Maria
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ljung, Rickard
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    The Swedish cause of death register2017In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 32, no 9, p. 765-773Article in journal (Refereed)
    Abstract [en]

    Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.

  • 6.
    Burke, Kristin E.
    et al.
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
    Ananthakrishnan, Ashwin N.
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
    Lochhead, Paul
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
    Olen, Ola
    Pediatric Gastroenterology and Nutrition Unit, Sachs' Children's Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Richter, James M.
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
    Chan, Andrew T.
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Khalili, Hamed
    Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Karolinska Clinical Epidemiology Unit, Karolinska Institutet, Solna, Sweden.
    Smoking is Associated with an Increased Risk of Microscopic Colitis: Results From Two Large Prospective Cohort Studies of US Women2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 5, p. 559-567Article in journal (Refereed)
    Abstract [en]

    Introduction: Long-term data on the influence of smoking on risk of microscopic colitis are limited. We therefore sought to examine and characterize the association between smoking and risk of incident microscopic colitis in two large prospective cohorts of women.

    Methods: We conducted a prospective study of 231,015 women enrolled in the Nurses' Health Study (NHS) and NHSII. Information regarding smoking, other lifestyle factors, and medications were collected biennially from 1976 to 2012 in NHS and 1989 to 2013 in NHSII. Incident cases of microscopic colitis were confirmed through physician medical record review. We used Cox proportional hazards modeling to examine the association between smoking and risk of microscopic colitis.

    Results: We documented 166 incident cases of microscopic colitis over 6,122,779 person-years of follow up. Compared to non-smokers, the multivariable-adjusted hazard ratio (HR) for microscopic colitis was 2.52 (95% CI 1.59 - 4.00) amongst current smokers and 1.54 (95% CI 1.09 - 2.17) amongst past smokers. The risk increased with higher pack-years of smoking (Ptrend = 0.001) and diminished following smoking cessation (Ptrend = 0.017). Current smoking appeared to be more strongly associated with risk of collagenous colitis (3.68; 95% CI 1.94 - 6.97) than lymphocytic colitis (HR 1.71; 95% CI 0.83 - 3.53).

    Conclusion: In two large prospective cohort studies, we observed an association between current smoking and risk of microscopic colitis. Risk of microscopic colitis appeared to increase with higher pack-years and diminish following smoking cessation. Future studies focused on characterizing the biologic mechanisms underlying these associations are warranted.

  • 7.
    Busch, K.
    et al.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    Ekstrom-Smedby, K.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Ekbom, A.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Askling, J.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; Dept Rheumatol, Karolinska Univ Hosp, Stockholm, Sweden.
    Neovius, M.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Nationwide prevalence of inflammatory bowel disease in Sweden: a population-based register study2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 39, no 1, p. 57-68Article in journal (Refereed)
    Abstract [en]

    Background: Regional studies on inflammatory bowel disease (IBD) suggest an increasing prevalence over time, but no nationwide estimate has been published so far.

    Aim: To estimate the IBD prevalence in 2010 in Sweden overall, by disease, and in specific patient segments.

    Methods: Patients were identified according to international classification codes for ulcerative colitis and Crohn's disease in in-patient care (1987-2010), day surgery and nonprimary out-patient care (1997-2010) in the nationwide Swedish Patient Register.

    Results: Requiring two or more diagnoses of IBD in nonprimary care, a total of 61344 individuals with physician-diagnosed IBD were alive in Sweden in 2010 (mean age 50years; 51% men), corresponding to a prevalence of 0.65% (95% CI, 0.65-0.66). The prevalence increased with age, and peaked in women at ages 50-59years and in men at ages 60-69years. Adding the requirement of IBD as main (vs. main or contributory) diagnosis code, or diagnosis from an internal medicine/gastroenterology/surgery department did not change the prevalence estimate. Prevalence of actively treated disease (defined as two or more IBD-related visits, of which one occurred in 2010, plus at least one dispensed prescription of IBD-related drugs in 2010) was 0.27% (95% CI, 0.27-0.28).

    Conclusions: The Swedish nationwide register-based IBD prevalence was higher compared with previous Swedish and international estimates. While prevalence estimates were robust across different case definitions, once two or more visits were required, only about one-third of prevalent patients were drawing resources from specialised care in 2010.

  • 8.
    Busch, Katharina
    et al.
    Dept Med Solna, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    da Silva, Simone A.
    Dept Prevent Med, Univ Sao Paulo, Sao Paulo, Brazil.
    Holton, Michelle
    Lorimer Enterprises Inc, Red Deer AB, Canada.
    Rabacow, Fabiana M.
    Dept Prevent Med, Univ Sao Paulo, Sao Paulo, Brazil.
    Khalili, Named
    Digest Healthcare Ctr, Massachusetts Gen Hosp, Boston, USA.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Pediat, Örebro University Hospital, Örebro, Sweden; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Sick leave and disability pension in inflammatory bowel disease: A systematic review2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 11, p. 1362-1377Article, review/survey (Refereed)
    Abstract [en]

    Background & aims: Inflammatory bowel disease has considerable effects on work-related outcomes and leads to high societal costs due to sick leave and disability pension. The aims of this study were to systematically review evidence on work-related outcomes that are relevant to productivity losses and to evaluate whether medical or surgical interventions have a positive impact on patients work ability.

    Methods: A systematic literature search in PubMed was conducted in June 2013. Abstracts were screened by two independent reviewers, and full-text articles describing the frequency of work-related outcomes were retrieved. Two independent reviewers extracted data according to the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses. Findings were organized by study design (non-interventional/interventional). Non-interventional studies were structured according to whether they presented data in comparison to control groups or not and interventional studies were summarized according to type of intervention.

    Results: This review included 30 non-interventional (15 with comparison groups and 15 without comparison group) and 17 interventional studies (9 surgical and 8 medical). The majority of the studies reported a high burden of work:related outcomes among inflammatory bowel disease patients regardless of the methodology used. While biologic agents showed positive effect on work absenteeism and presenteeism in randomized clinical trials, the impact of surgical interventions needs further evaluation.

    Conclusions: Inflammatory bowel disease patients experience a high burden in work-related outcomes. Additional data on productivity losses and the long-term impact of interventions is needed to help inform decision-makers about treatment options and their benefits in reducing productivity losses in inflammatory bowel disease patients. (C) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 9.
    Butwicka, Agnieszka
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden .
    Frisén, Louise
    Child and Adolescent Psychiatry Research Center, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Celiac disease is associated with childhood psychiatric disorders: A Population-Based Study2017In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 184, p. 87-93.e1, article id S0022-3476(17)30153-1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands.

    STUDY DESIGN: This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression.

    RESULTS: Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders.

    CONCLUSIONS: Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.

  • 10.
    Butwicka, Agnieszka
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
    Sariaslan, Amir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Myrelid, Pär E.
    Division of Surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University, Linköping, Sweden; Department of Surgery, County Council of Östergötland, Linköping, Sweden.
    Olén, Ola
    Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Frisen, Louise
    Child and Adolescent Psychiatry Research Center, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.
    No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2018-316326Article in journal (Refereed)
  • 11.
    Canova, Cristina
    et al.
    Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
    Pitter, Gisella
    Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
    Zanier, Loris
    Epidemiological Service, Health Directorate, Friuli Venezia-Giulia Region, Udine, Italy.
    Simonato, Lorenzo
    Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
    Michaelsson, Karl
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Risk of Fractures in Youths with Celiac Disease: A Population-Based Study2018In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 198, p. 117-120Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the risk of any fracture requiring hospital care in a cohort of individuals with celiac disease diagnosed in childhood/adolescence compared with reference individuals matched by age and sex.

    Study design: Our study cohort consisted of 213 635 people born and residing in Friuli-Venezia Giulia Region, Italy, in 1989-2011. We selected, through pathology reports, hospital discharge records, or co-payment exemptions, 1233 individuals with celiac disease (aged 0-17 years at diagnosis) and compared them with 6167 reference individuals matched by sex and year of birth. Fractures were identified through hospital discharge records. We calculated hazard ratios (HRs) for any fracture after celiac disease diagnosis (or index date for reference individuals) with Cox regression and ORs for any fracture before celiac disease diagnosis with conditional logistic regression.

    Results: During the follow-up period (maximum 23 years), 22 individuals with celiac disease (9394 person-years) and 128 reference individuals (47 308 person-years) experienced a fracture. giving an overall HR of 0.87 (95% CI 0.55-1.37). The risk was not modified by sex, age at diagnosis, or calendar period of diagnosis. We obtained similar HRs when excluding fractures occurring after the age of 18 years and adjusting for maternal education or vitamin D supplementation. The odds of previous fracture also did not differ between subjects with celiac disease and reference individuals (22 and 96 cases, respectively: OR 1.15: 95% CI 0.72-1.84).

    Conclusions: We did not find any evidence of an increased risk of fractures during childhood and youth among patients with celiac disease.

  • 12.
    Canova, Cristina
    et al.
    Department of Molecular Medicine, University of Padua, Padua, Italy.
    Pitter, Gisella
    Department of Molecular Medicine, University of Padua, Padua, Italy; School of Specialization in Hygiene and Preventive Medicine, University of Padua, Padua, Italy.
    Zanier, Loris
    Epidemiological Service, Udine, Italy.
    Zanotti, Renzo
    Department of Molecular Medicine, University of Padua, Padua, Italy.
    Simonato, Lorenzo
    Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York NY, USA.
    Inflammatory Bowel Diseases in Children and Young Adults with Celiac Disease: A Multigroup Matched Comparison2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 11, p. 1996-2000Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Celiac disease (CD) has been linked to inflammatory bowel disease (IBD) but previous reports have been inconsistent and may have been affected by surveillance bias.

    METHODS: Matched birth cohort study in Friuli-Venezia Giulia Region, Italy. We identified 1294 individuals with CD aged 0 to 23 years at diagnosis using pathology reports, hospital discharge records, or copayment exemptions. Each CD individual was matched with up to 5 general population reference individuals from the regional Medical Birth Register in Friuli-Venezia Giulia (n = 5681). As secondary comparison groups, we used individuals undergoing small intestinal biopsy but not having villous atrophy (either Marsh 0-1-2 or exclusively Marsh 0). Individuals with IBD were identified through hospital discharge records or copayment exemptions. Conditional logistic regression was used to estimate odds ratios (ORs) for having IBD among CD individuals (before or after CD diagnosis) compared with their matched references.

    RESULTS: Overall 35 individuals with IBD were identified (29 with CD and 6 general population controls). This corresponded to an increased risk of IBD in CD (OR = 24.17; 95% CI, 10.03-58.21). However, compared with individuals with Marsh 0-1-2 the OR decreased to 1.41 (95% CI, 0.91-2.18) and restricting our comparison group to individuals with Marsh 0, the OR was 1.28 (95% CI, 0.61-2.70).

    CONCLUSIONS: In conclusion, this article found a highly increased risk of IBD in individuals with CD when comparing with the general population. Bias is the likely explanation for the very high risk increase for IBD in CD because the excess risk was substantially lower when we used individuals with a small intestinal biopsy without villous atrophy as our reference.

  • 13.
    Carr, Hanna
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Cnattingius, Sven
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bonamy, Anna-Karin Edstedt
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Women ’ s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Preterm Birth and Risk of Heart Failure Up to Early Adulthood2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 21, p. 2634-2642Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In small clinical studies, preterm birth was associated with altered cardiac structure and increased cardiovascular mortality in the young.

    OBJECTIVES: The goal of this study was to determine the association between preterm birth and risk of incident heart failure (HF) in children and young adults.

    METHODS: This register-based cohort study included 2,665,542 individuals born in Sweden from 1987 to 2012 who were followed up from 1 year of age to December 31, 2013. The main study outcome was diagnosis of HF in the National Patient Register or the Cause of Death Register. The association between preterm birth and risk of incident HF was analyzed by using a Poisson regression model. Estimates were adjusted for maternal and pregnancy characteristics, socioeconomic status, and maternal and paternal cardiovascular disease.

    RESULTS: During 34.8 million person-years of follow-up (median 13.1 years), there were 501 cases of HF. After exclusion of 52,512 individuals with malformations (n = 196 cases), 305 cases of HF remained (0.88 per 100,000 person-years). Gestational age was inversely associated with the risk of HF. Compared with individuals born at term (>= 37 weeks' gestation), adjusted incidence relative risks for HF were 17.0 (95% confidence interval [CI]: 7.96 to 36.3) after extremely preterm birth (<28 weeks) and 3.58 (95% CI: 1.57 to 8.14) after very preterm birth (28 to 31 weeks). There was no risk increase after moderately preterm birth (32 to 36 weeks) (relative risk: 1.36; 95% CI: 0.87 to 2.13).

    CONCLUSIONS: There was a strong association between preterm birth before 32 weeks of gestation and HF in childhood and young adulthood. Although the absolute risk of HF is low in young age, our findings indicate that preterm birth may be a previously unknown risk factor for HF. (J Am Coll Cardiol 2017;69:2634-42) (C) 2017 by the American College of Cardiology Foundation.

  • 14.
    Cederlöf, Martin
    et al.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Serlachius, Eva
    Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Karolinska Institutet, Department Medical Epidemiology and Biostatistics, Stockholm, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings2016In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 16, article id 207Article in journal (Refereed)
    Abstract [en]

    Background: To assess the risk of psychiatric disorders in Ehlers-Danlos syndrome (EDS) and hypermobility syndrome.

    Methods: Nationwide population-based matched cohort study. EDS, hypermobility syndrome and psychiatric disorders were identified through Swedish national registries. Individuals with EDS (n = 1,771) were matched with comparison individuals (n = 17,710). Further, siblings to individuals with EDS who did not have an EDS diagnosis themselves were compared with matched comparison siblings. Using conditional logistic regression, risk of autism spectrum disorder (ASD), bipolar disorder, attention deficit hyperactivity disorder (ADHD), depression, attempted suicide, suicide and schizophrenia were estimated. The same analyses were conducted in individuals with hypermobility syndrome (n = 10,019) and their siblings.

    Results: EDS was associated with ASD: risk ratio (RR) 7.4, 95 % confidence interval (95 % CI) 5.2-10.7; bipolar disorder: RR 2.7, CI 1.5-4.7; ADHD: RR 5.6, CI 4.2-7.4; depression: RR 3.4, 95 % CI 2.9-4.1; and attempted suicide: RR 2.1, 95 % CI 1.7-2.7, but not with suicide or schizophrenia. EDS siblings were at increased risk of ADHD: RR 2.1, 95 % CI 1.4-3.3; depression: RR 1.5, 95 % CI 1.1-1.8; and suicide attempt: RR 1.8, 95 % CI 1.4-2.3. Similar results were observed for individuals with hypermobility syndrome and their siblings.

    Conclusions: Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders.

  • 15.
    Dixit, Rohit
    et al.
    Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, Columbia Univ, New York NY, USA..
    Lebwohl, Benjamin
    Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, Columbia Univ, New York NY, USA.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Lewis, Suzanne K.
    Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, Columbia Univ, New York NY, USA.
    Rizkalla-Reilly, Norelle
    Dept Pediat, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, Columbia Univ, New York NY, 10027 USA.
    Green, Peter H. R.
    Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, Columbia Univ, New York NY. USA; NewYork Presbyterian Hosp, New York NY, USA.
    Celiac Disease Is Diagnosed Less Frequently in Young Adult Males2014In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 59, no 7, p. 1509-1512Article in journal (Refereed)
    Abstract [en]

    The female predominance in celiac disease is difficult to explain because population-based screening studies reveal similar rates for celiac disease-specific autoantibodies in males and females. The aim of this study was to explore the role of age and gender in the presentation of celiac disease. The frequency of presentation according to age, gender and mode of presentation was determined by analysis of a prospectively maintained database of children and adults seen at a tertiary medical center. Of 1,682 patients (68 % female) aged 3 months to 86 years who were diagnosed with celiac disease, age at diagnosis in females peaked at 40-45 years, whereas the age at diagnosis for males had two peaks: 10-15 and 35-40 years. A significantly lower percentage of males in early adulthood were diagnosed compared with males in all other age groups (P < 0.0001). The young and elderly had a more even gender distribution. Based on our analysis, males are diagnosed with celiac disease less frequently than females, especially in early adulthood. There should be more emphasis on the diagnosis of celiac disease among young adult males.

  • 16.
    Dornbusch, Hans Juergen
    et al.
    Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
    Hadjipanayis, Adamos
    Department of Paediatrics, Larnaca General Hospital, Derynia, Cyprus; Medical School, European University of Cyprus, Nicosia, Cyprus .
    Del Torso, Stefano
    Dipartimento della Sanità Pubblica, Padova, Italy.
    Mercier, Jean-Christophe
    Service de Pédiatrie-Urgences, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris & Université Paris Diderot, Paris, France .
    Wyder, Corinne
    Paediatric Primary Care Center Kurwerk, Burgdorf, Switzerland.
    Schrier, Lenneke
    Juliana Children’s Hospital, The Hague, Netherlands.
    Ross-Russell, Robert
    Department of Paediatric Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
    Stiris, Tom
    Department of Neonatology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway .
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    We strongly support childhood immunisation-statement from the European Academy of Paediatrics (EAP)2017In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 176, no 5, p. 679-680Article in journal (Refereed)
    Abstract [en]

    The eradication of smallpox and the elimination of several other infectious diseases from much of the world has provided convincing evidence that vaccines are among the most effective interventions for promoting health. The current scepticism about immunisation among members of the new US administration carries a risk of decreasing immunisation rates also in Europe. While only a small minority of the population are strongly anti-vaccine, their public activities have significantly influenced an uncertainty among the general population about both the safety of and the necessity for vaccination. Therefore, the EAP calls for greater publically available, scientifically supported information on vaccination, particularly targeted at health care providers, for the further development of electronically based immunisation information systems (IIS). We further call on all European countries to work together both in legislative and public health arenas in order to increase vaccination coverage among the paediatric population. In the interest of children and their parents, the EAP expresses its strong support for childhood immunisation and recommended vaccination schedules. We are prepared to work with governments and media and share the extensive evidence demonstrating the effectiveness and safety of vaccines.

  • 17.
    Eberhardson, M.
    et al.
    Danderyd's Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Söderling, J. K.
    Karolinska Institutet, Stockholm, Sweden.
    Neovius, M.
    Karolinska Institutet, Stockholm, Sweden.
    Cars, T.
    Public Healthcare Service, Stockholm, Sweden; Uppsala University, Uppsala, Sweden.
    Myrelid, P.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Institutet, Stockholm, Sweden.
    Askling, J.
    Karolinska Institutet, Stockholm, Sweden.
    Ekbom, A.
    Karolinska Institutet, Stockholm, Sweden.
    Olén, O.
    Karolinska Institutet, Stockholm, Sweden; Sachs' Children's Hospital, Stockholm, Sweden.
    Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 6, p. 589-598Article in journal (Refereed)
    Abstract [en]

    Background: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohn's disease, but few studies have examined their effect beyond the first year of treatment.

    Aim: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naive TNFi-treated Crohn's disease patients and whether patients on TNFi >= 12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months.

    Methods: We identified all individuals in Sweden with Crohn's disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up.

    Results: We identified 1856 Crohn's disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohn's disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival < 12 months and >= 12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified.

    Conclusions: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.

  • 18.
    Elfstrom, Peter
    et al.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Granath, Fredrik
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Smedby, Karin Ekstrom
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences. Department of Primary Care and Public Health, Charing Cross Hospital, Imperial College, London, United Kingdom.
    Askling, Johan
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ekbom, Anders
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease2011In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 103, no 5, p. 436-444Article in journal (Refereed)
    Abstract [en]

    Background Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown. Methods We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28 989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13 140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227 911 age-and sex-matched reference individuals. Results Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100 000 person-years, 83.4 per 100 000 person-years, and 28.0 per 100 000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas. Conclusion The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.

  • 19.
    Elfström, P.
    et al.
    Department of Neonatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Sundström, J.
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 40, no 10, p. 1123-1132Article, review/survey (Refereed)
    Abstract [en]

    Background: In the past decade, a number of population-based studies have examined the prevalence of coeliac disease in individuals with type 1 diabetes but prevalences have differed considerably.

    Aim: To examine the prevalence of coeliac disease in individuals with type 1 diabetes.

    Methods: A systematic review of English-language articles published in PubMed Medline between 2000 and May 2014. Search terms included celiac disease' or coeliac disease' and diabetes mellitus'. Studies were selected with at least 100 individuals with type 1 diabetes being screened for coeliac disease where the coeliac diagnosis was later confirmed through small intestinal biopsy. Data synthesis used random-effects inverse variance-weighted models, and metaregression was used to examine heterogeneity in subgroups.

    Results: A pooled analysis, based on 26,605 patients with type 1 diabetes, found a prevalence of biopsy-confirmed coeliac disease of 6.0% (95% CI=5.0-6.9%). Heterogeneity was large (I-2=93.2%). The prevalence was lower in adults with type 1 diabetes (2.7%), and in mixed populations with both children and adults with type 1 diabetes (4.7%) than in children (6.2%) with type 1 diabetes (P<0.001). Additional subgroup analyses could not explain the large variation in coeliac disease prevalence between studies.

    Conclusion: More than one in twenty patients with type 1 diabetes have biopsy-verified coeliac disease. This prevalence is high enough to motivate screening for coeliac disease among patients with type 1 diabetes.

  • 20.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Granath, Fredrik
    Ekström Smedby, Karin
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Askling, Johan
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3Manuscript (Other academic)
    Abstract [en]

    Background: Celiac disease (CD) is associated with an increased risk of lymphoma, but it is unknown if borderline mucosal damage and latent CD are risk factors for lymphoma.Methods: We examined the risk of hematopoietic cancer in a nationwide population–based cohort of 28,800 individuals with biopsy-verified CD (villous atrophy, Marsh 3), 12,663 individuals with small intestinal inflammation (Marsh 1+2), and 3,551 with latent CD (positive antiendomysial, tissue transglutaminase or antigliadin test but normal mucosa on biopsy). The study participants were identified through all pathology departments (n=28) in Sweden and were biopsied in 1969-2006 (median: 1998). Cox regression estimated the hazard ratio (HR) for hematopoietic malignancies.Results: While biopsy-verified CD and intestinal inflammation were both statistically significantly associated with lymphoma (CD: HR = 3.18; 95% CI = 2.63-3.83; inflammation: 1.66; 1.28-2.17), latent CD was not (1.04; 0.44-2.43). CD was associated with both non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) (4.81; 3.81-6.07 and 4.39; 2.59-7.45 respectively). Risk estimates for NHL and HL were lower in inflammation (1.65; 1.15-2.38 and 1.48; 0.60-3.62 respectively) and latent CD (1.79; 0.74-4.34 and 1.08; 0.13-9.00 respectively). No increased risk of lymphoma was seen in children with a small intestinal biopsy. This study found no association between leukemia and small intestinal pathology.Conclusion: CD is associated with an increased risk of lymphoma. This risk increase was also seen in individuals with small intestinal inflammation. Latent CD is not associated with lymphoma of any kind, and positive CD serology alone cannot be used to predict future risk of lymphoma.

  • 21.
    Elfström, Peter
    et al.
    Department of Neonatology, Astrid Lindgren Children's Hospital-Danderyd, Karolinska University Hospital, Stockholm, Sweden.
    Granath, Fredrik
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ye, Weimin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Low Risk of Gastrointestinal Cancer Among Patients With Celiac Disease, Inflammation, or Latent Celiac Disease2012In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 10, no 1, p. 30-36Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Celiac disease has been associated with gastrointestinal (GI) cancers in small studies; risks have not been estimated from large populations or based on histopathology analyses.

    METHODS: We examined the risk of GI cancers by using data from cohorts of patients with celiac disease (villous atrophy, Marsh score of 3; n = 28,882) or inflammation (Marsh score of 1-2; n = 12,860); biopsy samples were evaluated at 28 pathology centers. A third cohort included 3705 individuals with latent celiac disease (normal mucosa, but positive serology results). Data were compared with those from an age-and sex-matched population.

    RESULTS: Of patients with celiac disease, 372 developed incident GI cancers; 347 patients with inflammation and 38 with latent celiac disease developed GI cancers. In the first year after diagnosis and initial biopsy, celiac disease was associated with 5.95-fold increase in risk of incident GI cancer (95% confidence interval [ CI], 4.64-7.64); the hazard ratio [HR] for inflammation was 9.13 (95% CI, 7.19-11.6) and for latent celiac disease was 8.10 (95% CI, 4.69-14.0). After the first year, patients were at no significant increase in risk for GI cancers; the HR for celiac disease was 1.07 (95% CI, 0.93-1.23), for inflammation it was 1.16 (95% CI, 0.98-1.37), and for latent celiac disease it was 0.96 (95% CI, 0.56-1.66). The absolute risk for any GI cancer in patients with celiac disease was 101/100,000 person-years, with an excess risk of 2/100,000 person-years.

    CONCLUSIONS: Although celiac disease, inflammation, and latent disease all increase risk for GI cancers in the first year after diagnosis, there is no increase in risk thereafter.

  • 22.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Kämpe, Olle
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Risk of Thyroid Disease in Individuals with Celiac Disease2008In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, no 10, p. 3915-3921Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up ofmorethan 1 yr and withnothyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR)_4.4;95% confidence interval (CI) _ 3.4 –5.6; P _ 0.001], thyroiditis (HR _ 3.6; 95% CI _1.9–6.7; P _ 0.001) and hyperthyroidism (HR_2.9;95%CI_2.0–4.2; P_0.001). The highest risk estimates were found in children (hypothyroidism, HR _ 6.0 and 95% CI _ 3.4 –10.6; thyroiditis, HR _ 4.7 and 95% CI _ 2.1–10.5; hyperthyroidism, HR _ 4.8 and 95% CI _ 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI_2.7– 4.4; P_0.001), 3.3 for thyroiditis(95%CI_1.5–7.7; P_0.001), and 3.1 for hyperthyroidism (95% CI _ 2.0–4.8; P _ 0.001).Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.

  • 23.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Bert
    Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Elfström, Peter
    Department of Neonatology, Astrid Lindgren Children's Hospital Danderyd, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Sweden; the Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 3, article id e001594Article in journal (Refereed)
    Abstract [en]

    Background: Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology.

    Methods and Results: From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052).

    Conclusion: This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD.

  • 24.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmland County, Sweden.
    Carlsson, R.
    PCI unit, Department of Cardiology, Central Hospital, Karlstad, Sweden.
    Holmqvist, M.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Sweden.
    James, S.
    Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Pediatrics.
    The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 9, p. 905-914Article in journal (Refereed)
    Abstract [en]

    Background: Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors.

    Aim: To characterise IHD according to CD status.

    Methods: Data on duodenal or jejunal biopsies were collected in 20062008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals.

    Results: We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P<0.001) and cholesterol values (P<0.001) and were less likely to be active smokers (OR=0.74; 95% CI=0.560.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR=0.80; 95% CI=0.660.97; three-vessel disease: OR=0.73; 95% CI=0.570.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P=0.766).

    Conclusion: Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.

  • 25.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carlsson, R.
    James, S.
    Ludvigsson, Jonas F.
    Örebro University Hospital.
    Letter: coeliac disease and ischaemic heart disease - a true additional risk factor? Authors' reply2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 11, p. 1118-1118Article in journal (Refereed)
  • 26.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmlands Nysäter, Sweden.
    Carlsson, Roland
    PCI unit, Department of Cardiology, Central Hospital, Karlstad, Sweden .
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.
    Hambraeus, Kristina
    Department of Cardiology and Clinical Research Centre, Falun Hospital, Falun, Sweden .
    Ludvigsson, Jonas F.
    Örebro University Hospital. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Follow-up of ischaemic heart disease in patients with coeliac disease2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    Patients with coeliac disease and myocardial infarction have a more favourable atherosclerotic risk factor profile than controls with myocardial infarction (MI). Therefore, MI prognosis and treatment may differ according to coeliac status. This paper reports on the study of Swedish MI patients with and without coeliac disease (equal to villous atrophy; Marsh histopathology stage 3) based on duodenal or jejunal biopsy data. We used the Swedish Quality Register (SWEDEHEART) to identify individuals with a record of MI from 2005 to 2008 and to obtain data on medication, coronary interventions, and clinical and laboratory parameters at 6–10 weeks and one year after first MI. One-year mortality and coronary interventions were assessed for 430 coeliac patients and 1988 controls. For other outcome variables, we compared 42 coeliac patients with MI and 201 general population controls with MI. Odds ratios (ORs) were calculated by logistic regression. The results showed that compared with controls with MI, coeliac individuals with MI had significantly higher one-year all-cause mortality (OR = 1.43; 95% confidence interval (CI) = 1.04–1.95) but less often underwent a percutaneous coronary intervention (OR = 0.77; 95% CI = 0.61–0.96). Coeliac patients were more often prescribed warfarin but less often aspirin and statins. The readmission rate due to cardiac events in coeliac patients was 15.2% vs. 12.6% in controls (p-value  = 0.69). Other clinical and laboratory parameters were similar. We conclude that the follow up of MI does not seem to differ between coeliac patients and controls, and is unlikely to explain the excess mortality from cardiovascular disease noted in Swedish patients with CD.

  • 27.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Res Unit, Värmlands Nysäter, Värmland County Council, Sweden.
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ischaemic heart disease in first-degree relatives to coeliac patients2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 4, p. 359-364Article in journal (Refereed)
    Abstract [en]

    Objective: Coeliac disease (CD) has been linked to an increased risk of ischaemic heart disease (IHD). We examined the risk of IHD in first-degree relatives and spouses to coeliac patients to ascertain the genetic contribution to IHD excess risk.

    Study design and setting: Coeliac disease was defined as having a biopsy-verified villous atrophy (Marsh grade 3) in 1969-2008 (n=29096). Coeliac patients were matched to 144522 controls. Through Swedish registers, we identified all first-degree relatives and spouses to coeliac patients and their controls, in total 87622 unique coeliac relatives and 432655 unique control relatives. Our main outcome measure was IHD defined according to relevant international classification of disease codes in the Swedish Inpatient Registry or in the Cause of Death Registry. Hazard ratios (HR) and confidence intervals (CI) were estimated through Cox regression adjusted for sex, age-group and calendar year at study entry of the relative.

    Result: During a median follow-up of 108 years, 2880 coeliac relatives and 13817 control relatives experienced IHD. First-degree relatives of coeliac patients were at increased risk of IHD (HR=105; 95% CI=100-109, P-value=004), while spouses were at no increased risk (HR=099; 95% CI=087-112). The excess risk of IHD in coeliac first-degree relatives aged 40-59years was 70/100000 person-years.

    Conclusion: First-degree relatives to coeliac patients seem to be at an increased risk of IHD but the excess risk is so small that it has little clinical relevance.

  • 28.
    Emilsson, Louise
    et al.
    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Vårdcentralen Värmlands Nysäter & Centre for Clinical Research, County Council of Värmland, Sweden.
    Lebwohl, Benjamin
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, United States.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, United States.
    Murray, Joseph A.
    Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Rochester, MN, United States.
    Mårild, Karl
    Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Barbara Davis Center, University of Colorado, Aurora CO, United States.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, United Kingdom.
    Mucosal healing and the risk of serious infections in patients with celiac disease2018In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 6, no 1, p. 55-62Article in journal (Refereed)
    Abstract [en]

    Background: Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk.

    Methods: We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden's 28 pathology departments undergoing biopsy 1969-2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing).

    Results: Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing (p<0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR=0.99; 95% CI=0.88-1.11) or with any of the specific infections.

    Conclusions: In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.

  • 29.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Värmlands Nysäter. Sweden; Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway.
    Lindahl, B.
    Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, University of Uppsala, Uppsala, Sweden.
    Köster, M.
    National Board of Health and Welfare, Stockholm, Sweden .
    Lambe, M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Regional Cancer Centre, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Review of 103 Swedish healthcare quality registries2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 1, p. 94-136Article in journal (Refereed)
    Abstract [en]

    Background and objectives: In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs.

    Methods: From March to September 2013, we examined the 2012 applications of 103 QRs to the Swedish Association of Local Authorities and Regions (SALAR) and also studied the annual reports from the same QRs. After initial data abstraction, the coordinator of each QR was contacted at least twice between June and October 2013 and asked to confirm the accuracy of the data retrieved from the applications and reports.

    Results: About 60% of the QRs covered 80% of their target population (completeness). Data recorded in Swedish QRs include aspects of disease management (diagnosis, clinical characteristics, treatment and lead times). In addition, some QRs retrieve data on self-reported quality of life (EQ5D, SF-36 and disease-specific measures), lifestyle (smoking) and general health status (World Health Organization performance status, body mass index and blood pressure).

    Conclusion: Detailed clinical data available in Swedish QRs complement information from government-administered registries and provide an important source not only for assessment and development of quality of care but also for research.

  • 30.
    Emilsson, Louise
    et al.
    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, United States; Primary Care Research Unit, Va°rdcentralen Värmlands Nysäter, Värmland County, Sweden.
    Roy, Abhik
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Lebwohl, Benjamin
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Clinical Sciences Building 2, City Hospital, Nottingham, United Kingdom.
    Depression and anxiety in caregivers of patients with celiac disease: Author's reply2018In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 50, no 3, p. 320-321Article in journal (Refereed)
  • 31.
    Emilsson, Louise
    et al.
    Arvika Hospital, Värmland County, Arvika, Sweden.
    Smith, J Gustav
    Department of Cardiology, Lund University, Lund, Sweden; Broad Institute of Harvard and MIT, Cambridge MA, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden.
    West, Joe
    Division of Epidemiology and Public Health, Nottingham City Hospital, University of Nottingham, Nottingham, UK; NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Nottingham, UK.
    Melander, Olle
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 19, p. 2430-7Article in journal (Refereed)
    Abstract [en]

    Aims: Inflammatory markers are established risk factors for atrial fibrillation (AF), but the role of autoimmune diseases is unknown. The aim of the study was to examine the association between coeliac disease (CD) and AF in a large cohort of patients with biopsy-verified CD.

    Metods and results: We identified 28,637 patients with CD through biopsy reports (defined as Marsh 3: villous atrophy) from all pathology departments (n = 28) in Sweden. Biopsies had been performed between 1969 and 2008. Age- and sex-matched reference individuals (n = 141,731) were identified from the Swedish Total Population Register. Data on AF were obtained from the Swedish Hospital Discharge Register, the Hospital Outpatient Register, and the Cause of Death Register. Hazard ratios (HRs) for AF were estimated using Cox regression. In the CD cohort, 941 individuals developed AF (vs. 2918 reference individuals) during a median follow-up of 9 years. The corresponding adjusted HR for AF was 1.34 (95% CI = 1.24-1.44). The absolute risk of AF in CD was 321 of 100,000 person-years, with an excess risk of 81 of 100,000. A prior AF diagnosis was also associated with an increased risk of subsequent CD (odds ratio = 1.45, 95% CI = 1.31-1.62).

    Conclusions Atrial fibrillation is more common both before and after CD diagnosis in patients with CD though the excess risk is small. Potential explanations for the increased risk of AF in CD include chronic inflammation and shared risk factors, but ascertainment bias may also have contributed.

    CLINICAL IMPLICATIONS: Coeliac disease affects 1-2% of the Western population. Our results indicate that patients with coeliac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation. Additional studies are needed to clarify the mechanistic link between atrial fibrillation and autoimmune diseases such as coeliac disease.

  • 32.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.
    Marsal, Jan
    Immunology Section, Lund University, Lund, Sweden; Department of Gastroenterology, Skåne University Hospital, Lund, Sweden.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vigren, Lina
    Department of Internal Medicine, Ystad Hospital, Ystad, Sweden.
    Björk, Jan
    Department of Medicine, Center for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet Solna, Stockholm, Sweden.
    Eberhardson, Michael
    Department of Medicine, Center for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet Solna, Stockholm, Sweden.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Söderman, Charlotte
    Department of Internal Medicine, St Göran Hospital, Stockholm, Sweden.
    Myrelid, Pär
    Department of Clinical and Experimental Medicine, Linköping University and Department of Surgery, Linköping University Hospital, Linköping, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sjöberg, Daniel
    Center for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Thörn, Mari
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden.
    Karlén, Per
    Department of Internal Medicine, Danderyd Hospital, Stockholm, Sweden.
    Hertervig, Erik
    Department of Gastroenterology, Skåne University Hospital, Lund, Sweden.
    Strid, Hans
    Department of Internal Medicine, Södra Älvsborgs Sjukhus, Borås, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Almer, Sven
    Department of Medicine, Center for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet Solna, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

    Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index<5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index<3 in ulcerative colitis (UC).

    Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p<.0001 in both groups). Faecal-calprotectin decreased in CD (p<.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).

    Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

  • 33.
    Everhov, A. H.
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Olén, O.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of paediatric gastroenterology and nutrition, Sachs’ Children and Youth Hospital, Stockholm, Sweden.
    Ludvigsson, Jonas F
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Editorial: importance of definition of inflammatory bowel disease and an increased incidence in children2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 10, p. 1369-1370Article in journal (Refereed)
    Abstract [en]

    No abstract is available for this article.

  • 34.
    Everhov, Å. H.
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro.
    Olén, O.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs’ Children and Youth Hospital, Stockholm, Sweden.
    Letter: phenotype and natural history of elderly onset inflammatory bowel disease2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 47, no 10, p. 1420-1421Article in journal (Refereed)
  • 35.
    Everhov, Åsa H.
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Myrelid, Pär
    Division of surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University, Linköping, Sweden; Department of Surgery, County Council of Östergötland, Linköping, Sweden.
    Sachs, Michael C.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nordenvall, Caroline
    Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Digestive Disease, Div. of Coloproctology, Karolinska University Hospital, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Neovius, Martin
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
    Askling, Johan
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Olén, Ola
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of pediatric gastroenterology and nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden.
    Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden2018In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 154, no 3, p. 518-528Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Diagnosis of inflammatory bowel diseases (IBD) is increasing among elderly persons (60 years or older). We performed a nationwide population-based study to estimate incidence and treatment.

    METHODS: We identified all incident IBD cases in Sweden, from 2006 through 2013, using national registers, and up to 10 matched population comparator subjects. We collected data on the patients' health care contacts and estimated incidence rates, health service burden, pharmacologic treatments, extra-intestinal manifestations, and surgeries in relation to age of IBD onset (pediatric, less than 18 years; adults, 18-59 years; elderly, 60 years or older).

    RESULTS: Of 27,834 persons diagnosed with incident IBD, 6443 (23%) had a first diagnosis of IBD at 60 years or older, corresponding to an incidence rate of 35/100,000 person-years (10/100,000 person-years for Crohn's disease, 19 /100,000 person-years for ulcerative colitis, and 5/100,000 person-years for IBD unclassified). During a median follow-up period of 4.2 years (range 0-9 years), elderly patients had less IBD-specific outpatient health care but more IBD-related hospitalizations and overall health care use than adult patients with IBD. Compared to patients with pediatric or adult onset, elderly patients used fewer biologics and immunomodulators, but more systemic corticosteroids. Occurrence of extra-intestinal manifestations was similar in elderly and adult patients, but bowel surgery was more common in the elderly (13% after 5 years vs 10% in adults) (P<.001). The absolute risk of bowel surgery was higher in the elderly than in the general population, but in relative terms, the risk increase was larger in younger age groups.

    CONCLUSIONS: In a nationwide cohort study in Sweden, we associated diagnosis of IBD at age 60 years or older with a lower use of biologics and immunomodulators but higher absolute risk of bowel surgery, compared to diagnosis at a younger age. The large differences in pharmacological treatment of adults and elderly patients are not necessarily due to a milder course of disease and warrant further investigation.

  • 36.
    Humes, D. J.
    et al.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Stockholm, Stockholm, Sweden.
    Abdul-Sultan, A.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK.
    Walker, A. J.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Stockholm, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    West, J.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Nottingham, UK.
    Duration and magnitude of postoperative risk of venous thromboembolism after planned inguinal hernia repair in men: a population-based cohort study2018In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 22, no 3, p. 447-453Article in journal (Refereed)
    Abstract [en]

    Purpose: Little is known regarding the magnitude and timing of the risk of VTE following inguinal hernia surgery. We aimed to determine the absolute and relative rates of venous thromboembolism (VTE) following planned inguinal hernia repair.

    Methods: We analysed male adults with a first inguinal hernia repair with no prior record of VTE from the Clinical Practice Research Datalink, linked to the Hospital Episode Statistics (2001-2011). Crude rates and adjusted hazard ratios (HR) of the first VTE were calculated using Cox regression analysis to compare specific time periods following the surgery compared to the general population.

    Results: We identified 28,782 men who underwent an inguinal hernia repair with 53 (0.18%) having a first VTE in the 90 days following surgery. The overall rate of VTE in the first 90 days following surgery was 7.61 per 1000 person years (pyrs) (95% CI 5.82-9.96). Increasing age, a body mass index > 30 kg/m(2) and an in-patient procedure were associated with an increased risk of VTE, when compared to the general population. The risk of VTE was highest in the 1st month following the surgery with a 2.3- (aHR 2.33; 95% CI 1.09-4.99) and 3.5- (aHR 3.47; 95% CI 2.07-5.83) fold increased risk compared to the general population for both day case and planned in-patient procedures, respectively.

    Conclusions: Reassuringly, the absolute rates of VTE following inguinal hernia repair are low. Patients should be informed that their peak risk of VTE is during the 1st month following the surgery. Further studies on the optimum duration of thromboprophylaxis following surgery are required in high-risk patients undergoing hernia repair.

  • 37.
    Humes, D. J.
    et al.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Biomedical Research Unit, Queens Medical Centre Campus, University of Nottingham Nottingham, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Walker, A. J.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK .
    Hunt, B. J.
    Thrombosis and Haemophilia Centre Guy's Hospital, London, UK; St Thomas' NHS Foundation Trust, London, UK.
    Sultan, A. A.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    West, J.
    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
    Risk of symptomatic venous thromboembolism following emergency appendicectomy in adults2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 4, p. 443-450Article in journal (Refereed)
    Abstract [en]

    Background: Appendicectomy is the commonest intra-abdominal emergency surgical procedure, and little is known regarding the magnitude and timing of the risk of venous thromboembolism (VTE) after surgery. This study aimed to determine absolute and relative rates of symptomatic VTE following emergency appendicectomy.

    Methods: A cohort study was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data of patients who had undergone emergency appendicectomy from 2001 to 2011. Crude rates and adjusted incidence rate ratios (IRRs) for VTE were calculated using Poisson regression, compared with baseline risk in the year before appendicectomy.

    Results: A total of 13 441 patients were identified, of whom 56 (0·4 per cent) had a VTE in the first year after surgery. The absolute rate of VTE was highest during the in-hospital period, with a rate of 91·29 per 1000 person-years, which was greatest in those with a length of stay of 7 days or more (267·12 per 1000 person-years). This risk remained high after discharge, with a 19·1- and 6·6-fold increased risk of VTE in the first and second months respectively after discharge, compared with the year before appendicectomy (adjusted IRR: month 1, 19·09 (95 per cent c.i. 9·56 to 38·12); month 2, 6·56 (2·62 to 16·44)).

    Conclusion: The risk of symptomatic VTE following appendicectomy is relatively high during the in-hospital admission and remains increased after discharge. Trials of extended thromboprophylaxis are warranted in patients at particularly high risk.

  • 38. Huus, Karina
    et al.
    Brekke, Hilde K.
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Ludvigsson, Johnny
    Relationship of food frequencies as reported by parents to overweight and obesity at 5 years2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 1, p. 139-143Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate if food frequencies are related to overweight/obesity in 5-year-old children.

    METHODS: During 1997-1999, 21 700 infants were invited to participate in ABIS (All Babies in Southeast Sweden), a prospective, cohort study. Participants were followed from birth (n = 16 058) to 5 years (n = 7356). Food frequencies reported by parents at 2.5 and 5 years were studied in the relation to overweight/obesity at 5 years using multiple logistic regressions. A p-value < 0.01 was considered statistically significant.

    RESULTS: At 2.5 years frequencies of intake of cheese were positively associated with overweight/obesity at 5 years while porridge, fried potatoes/french fries and cream/crème fraiche showed a negative association. When adjusting for known risk factors, porridge and fried potatoes/french fries remained negatively associated with overweight/obesity. At 5 years, chocolate and lemonade were positively associated with overweight/obesity whereas cream/crème fraiche, pastries and candy were negatively associated. Candy remained negatively associated to overweight/obesity after adjustment for potential confounders.

    CONCLUSION: Food frequencies do not offer any simple explanation for overweight/obesity. Porridge at 2.5 years may protect against overweight/obesity at 5 years, while lemonade may contribute to overweight. Our finding that fried potatoes/french fries may protect against overweight/obesity is unexpected and must be interpreted with caution. These findings should be confirmed by prospective studies using objective recordings.

  • 39. Huus, Karina
    et al.
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Enskär, Karin
    Ludvigsson, Johnny
    Exclusive breastfeeding of Swedish children and its possible influence on the development of obesity: a prospective cohort study2008In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 8, p. 42-Article in journal (Refereed)
    Abstract [en]

    Background Overweight and obesity are increasing among children all over the world. Socio-economic factors may influence the development of overweight and obesity in childhood, and it has been proposed that breastfeeding may protect against obesity. The aim of our study was to examine the relationship between exclusive breastfeeding and obesity when potential confounders, such as socioeconomic factors, are considered.

    Methods The data analyzed was from ABIS (All Babies in Southeast Sweden), a prospective cohort study. All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden (n = 21,700) were asked to participate. Parents were asked to answer periodic questionnaires from the time of the child's birth (n = 16,058) until he/she was five years of age (n = 7,356). Cutoffs for overweight and obesity were defined according to Cole et al, age and gender adjusted. Short-term exclusive breastfeeding was defined as < 4 months of exclusive breastfeeding. Multiple logistic regressions were used to identify variables that predict the child's BMI (Body Mass Index) at five years of age.

    Results At five years of age, 12.9% of the children in the study wereoverweight and 4.3% were obese. At the age of three months, 78.4% of the children were being breastfed exclusively. The median exclusive breastfeeding duration was four months. High maternal BMI > 30 (AOR = 1.07; CI = 1.05–1.09; P < 0.001), maternal smoking (AOR = 1.43; CI = 1.05–1.95; P = 0.023) and being a single parent (AOR = 2.10; CI = 1.43–3.09; P < 0.001) were associated with short-term exclusive breastfeeding (less than 4 months). Short-term exclusive breastfeeding was less common if one of the parents had a university degree (Mother: AOR = 0.74; CI = 0.61–0.90; P = 0.003 Father: AOR = 0.73; CI = 0.58–0.92; P = 0.008) or if the father was more than 37 years old (AOR = 0.74; CI = 0.55–0.99; P = 0.045). Short-term exclusive breastfeeding was associated with obesity in five-year-old children (simple logistic regression: OR = 1.44; CI = 1.00–2.07; P = 0.050), but when including other independent factors in the analysis, short-term exclusive breastfeeding did not attain statistical significance.

    Conclusion We cannot exclude the possibility that exclusive breastfeeding influences weight development, but it does not seem to protect against obesity at five years of age. 

  • 40. Huus, Karina
    et al.
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Enskär, Karin
    Ludvigsson, Johnny
    Risk factors in childhood obesity: findings from the All Babies In Southeast Sweden (ABIS) cohort2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 9, p. 1321-1325Article in journal (Refereed)
    Abstract [en]

    Aim: Our objective was to investigate whether overweight at a very young age predicts overweight at 5 years and to identify risk factors for overweight/obesity at 5 years, thereby making it easier for Child Health Services to focus their prevention strategies on risk groups.

    Methods: We analysed data from the ABIS study (All Babies In Southeast Sweden), a prospective cohort study. Parents answered questionnaires between childbirth (n = 16,058) and 5 years (n = 7356).

    Results: High body mass index (BMI; >95th percentile) at 1 year (adjusted odds ratio [AOR]= 6.57; 95% CI = 4.63–9.33; p < 0.001) and age-adjusted BMI > 25 at 2.5 years (AOR = 14.24; 95% CI = 10.52–19.29; p < 0.001) were associated with increased risk of obesity (age-adjusted BMI > 30) at 5 years. Heredity for type 2 diabetes (p = 0.022), high parental BMI and the child's own BMI at birth and at 1 year predicted higher BMI of the child at 5 years (p < 0.001). High parental education was inversely associated with child overweight (p = 0.054 respective p < 0.005).

    Conclusion: Obesity at age 1 and at 2.5 years predicts obesity at 5 years. Obese parents, especially in families with heredity for type 2 diabetes and low education, should be targeted in early obesity prevention strategies by the Child Health Service.

  • 41.
    Jakobsson, Gustav L.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sternegård, Emil
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Olén, Ola
    Department of Pediatric Gastroenterology, Sachs’ Children’s Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm.
    Myrelid, Pär
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Surgery, Linköping University Hospital, Linköping, Sweden.
    Ljung, Rickard
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Strid, Hans
    Department of Internal Medicine, Södra Älvsborgs sjukhus, Borås, Sweden; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 216-221Article in journal (Refereed)
    Abstract [en]

    Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown.

    Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn's disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated.

    Results: For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with ≥2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD.

    Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.

  • 42.
    Jarrick, Simon
    et al.
    Örebro University, School of Medical Sciences. Department of Pediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lundberg, Sigrid
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Welander, Adina
    Boston Consulting Group, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Fored, Michael C.
    Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital, Örebro, Sweden; Karolinska Institutet, Stockholm, Sweden; University of Nottingham, Nottingham, England.
    Clinical validation of immunoglobulin A nephropathy diagnosis in Swedish biopsy registers2017In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 67-73Article in journal (Refereed)
    Abstract [en]

    Aims: The aims of this study were to validate the diagnosis of IgA nephropathy (IgAN) in Swedish biopsy registers against patient charts and to describe the clinical characteristics of patients with a biopsy indicating IgAN.

    Methods: This is a population-based cohort study. Out of 4,069 individuals with a renal biopsy consistent with IgAN (biopsies performed in 1974-2011), this study reviewed patient charts of a random subset of 127 individuals. Clinical and biopsy characteristics at the time of biopsy were evaluated, and positive predictive values (PPV) were calculated with 95% confidence intervals (CI).

    Results: Out of 127 individuals with a renal biopsy consistent with IgAN, 121 had a likely or confirmed clinical diagnosis of IgAN, primary or secondary to Henoch-Schonlein purpura, yielding a PPV of 95% (95% CI =92%-99%). The median age at biopsy was 39 years (range: 4-79 years); seven patients (6%) were <16 years. The male to female ratio was 2.8:1. The most common causes for consultation were macroscopic hematuria (n=37; 29%), screening (n=33; 26%), and purpura (n=14, 11%). In patients with available data, the median creatinine level was 104 mu mol/L (range 26-986 mu mol/L, n=110) and glomerular filtration rate 75 mL/min/1.73m(2) (range 5-173 mL/min/1.73m(2), n=114). Hypertension was noted in 59 (46%) individuals. IgA deposits were reported in 97% of the biopsy records (n= 123), mesangial hypercellularity in 76% (n= 96), C3 deposits in 89% (n=113), and C1q deposits in 12% (n=15). Conclusion: A histologic diagnosis of IgAN has a high PPV for a diagnosis of IgAN confirmed by review of patient charts.

  • 43.
    Kalman, D.
    et al.
    Linköping Univ, Faulty Hlth Sci, Dept Clin & Expt Med, Div Surg, Linköping, Sweden.; Cty Council Östergötland, Dept Surg, Linköping, Sweden.
    Nordenvall, C.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Ctr Digest Dis, Div Coloproctol, Stockholm, Sweden.
    Everhov, A. Hallqvist
    Karolinska Inst, Södersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden; Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England; Columbia Univ Coll Phys & Surg, Dept Med, New York NY USA.
    Sachs, M. C.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Ekbom, A.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Olen, O.
    Karolinska Inst, Södersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden; Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden; Sachs Children & Youth Hosp, Dept Pediat Gastroenterol & Nutr, Stockholm, Sweden.
    Myrelid, P.
    Linköping Univ, Faulty Hlth Sci, Dept Clin & Expt Med, Div Surg, Linköping, Sweden; Cty Council Östergötland, Dept Surg, Linköping, Sweden.
    Need for primary abdominal surgery, but not repeated surgery, has decreased: a nationwide study of temporal trends in Crohn surgery in Sweden 1990-20142018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S11-S12Article in journal (Other academic)
  • 44.
    Kalman, D.
    et al.
    Linköping Univ, Div Surg, Dept Clin & Expt Med, Fac Hlth Sci, Linköping, Sweden; Cty Council Östergötland, Dept Surg, Linköping, Sweden.
    Nordenvall, C.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Div Coloproctol, Ctr Digest Dis, Stockholm, Sweden.
    Everhov, A. Hallqvist
    Karolinska Inst, Södersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden; Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Sachs, M. C.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England; Columbia Univ Coll Phys & Surg, Dept Med, New York NY USA.
    Ekbom, A.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Myrelid, P.
    Linköping Univ, Div Surg, Dept Clin & Expt Med, Fac Hlth Sci, Linköping, Sweden; Cty Council Östergötland, Dept Surg, Linköping, Sweden.
    Olen, O.
    Karolinska Inst, Södersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden; Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden; Sachs Children & Youth Hosp, Dept Pediat Gastroenterol & Nutr, Stockholm, Sweden.
    Need for ileocaecal resections, but not ileo-colic re-resections, has decreased: a nationwide study of temporal trends in Crohn surgery in Sweden 1990-20142018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S60-S61Article in journal (Other academic)
  • 45.
    Khalili, Hamed
    et al.
    Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hakansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Chan, Simon S.
    Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, United Kingdom.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics.
    Olen, Ola
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Pediatric Gastroenterology and Nutrition Unit, Sachs’ Children’s Hospital, Stockholm, Sweden.
    Chan, Andrew T.
    Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Hart, Andrew R.
    Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, United Kingdom.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    No Association Between Consumption of Sweetened Beverages and Later Risk of Crohn's Disease or Ulcerative Colitis2018In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Consumption of sweetened beverages has been associated with inflammation, based on measurements of C-reactive protein and tumor necrosis factor, as well as immune-mediated disorders including rheumatoid arthritis. We investigated associations with Crohn's disease (CD) or ulcerative colitis (UC).

    METHODS: We conducted a prospective cohort study of 83,042 participants (44-83 years old) enrolled in the Cohort of Swedish Men or the Swedish Mammography Study. Dietary and lifestyle data were collected using a validated food frequency questionnaire at baseline in 1997. Diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modeling to calculate hazard ratios (HR) and 95% CIs.

    RESULTS: Through December of 2014, we confirmed 143 incident cases of CD (incidence; rate = 11 cases/100,000 person-years) and 349 incident cases of UC (incidence rate = 28 cases/100,000 person-years) over 1,264,345 person-years of follow up. Consumption of sweetened beverages was not associated with increased risk of CD (Ptrend = 0.34) or UC (Ptrend = 0.40). Compared to participants who reported no consumption of sweetened beverages, the multivariable-adjusted HRs for 1 or more servings per day were 1.02 for CD (95% CI, 0.60-1.73) and 1.14 for UC (95% CI, 0.83-1.57). The association between consumption of sugar-sweetened beverages and risk of CD or UC were not modified by age, sex (cohort), body mass index, or smoking (all Pinteraction ≥ 0.12).

    CONCLUSION: In analyses of data from 2 large prospective cohort studies from Sweden, we observed no evidence for associations between consumption of sweetened beverages and later risk of CD or UC.

  • 46.
    Khalili, Hamed
    et al.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, United States; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Digestive Healthcare Center, Crohn's and Colitis Center, Massachusetts General Hospital, Boston MA, United States.
    Neovius, Martin
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Solna, Sweden; Department of Pediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Division of Digestive and Liver Diseases, Columbia College of Physicians and Surgeons, New York NY, United States.
    Askling, Johan
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA, United States.
    Olen, Ola
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children's Hospital, Department of Pediatric Gastroenterology, Stockholm, Sweden.
    Oral Contraceptive Use and Risk of Ulcerative Colitis Progression: A Nationwide Study2016In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 111, no 11, p. 1614-1620Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Oral contraceptive (OC) use has been consistently linked to increased risk of inflammatory bowel disease. Nonetheless, a specific role of OC in the natural history of ulcerative colitis (UC) is unknown.

    METHODS: We identified 6,104 incident female UC cases aged 16-51 years at diagnosis from the Swedish National Patient Register starting in January of 2003. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005. We followed cases through December of 2014 for primary outcome defined as first UC-related surgery, and the secondary outcomes defined by recipient of the first prescription of oral steroids or anti-tumor necrosis factor (anti-TNF) use. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratio (aHR) and 95% confidence interval (CI).

    RESULTS: Over 31,421 person-years of follow up, we observed 162 cases of UC-related surgery. Compared with nonusers, current and past use of OC were not significantly associated with risk of UC-related surgery (aHR= 0.79; 95% CI, 0.52-1.18; and aHR= 0.74, 95% CI, 0.46-1.18, respectively). The association did not appear to be modified by type of OC use (progestin-only vs. combination of progestin and estrogen), longer duration of use, or higher number of dispensed prescriptions (All P-trend > 0.28). Similarly, longer use or higher cumulative number of OC prescriptions were not associated with increased risk of receiving a steroid prescription (P-trend = 0.68 and 0.63, respectively). In exploratory analyses restricted to Stockholm county, current OC use was not associated with increased risk of receiving anti-TNF therapy (aHR= 0.83, 95% CI, 0.59-1.18).

    CONCLUSIONS: In a large nationwide registry of UC patients, we found no association between OC use and UC progression. Our data offer reassurance regarding the safety of OC assessed by its effect on risk of surgery and steroid or anti-TNF use in women with established UC.

  • 47.
    Kuja-Halkola, Ralf
    et al.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lebwohl, Benjamin
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York NY, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Emilsson, Louise
    Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; Centre for Clinical Research, Vårdcentralen Värmlands Nysäter, County Council of Värmland, Karlstad, Sweden.
    Magnusson, Patrik K.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Columbia Univ, Dept Med, Celiac Dis Ctr, New York NY, USA; Örebro Univ Hosp, Dept Pediat, Örebro, Sweden; City Hosp, Sch Med, Div Epidemiol & Publ Hlth, Univ Nottingham, Nottingham, England.
    Birth weight, sex, and celiac disease: a nationwide twin study2017In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 567-577Article in journal (Refereed)
    Abstract [en]

    Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.

    Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.

    Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD-non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97-1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11-2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.

    Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

  • 48.
    Kuja-Halkola, Ralf
    et al.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lebwohl, Benjamin
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wijmenga, Cisca
    Department of Genetics, University Medical Center, University of Groningen, Groningen, The Netherlands.
    Magnusson, Patrik K. E.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, City Hospital, University of Nottingham, Nottingham, UK.
    Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 11, p. 1793-1798Article in journal (Refereed)
    Abstract [en]

    Background and objective: Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.

    Design: In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.

    Results: We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD.

    Conclusions: CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.

  • 49.
    Kurien, Matthew
    et al.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Sanders, David S.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    A no biopsy strategy for adult patients with suspected coeliac disease: making the world gluten-free2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, no 6, p. 1003-1004Article in journal (Refereed)
  • 50.
    Kurien, Matthew
    et al.
    Academic Unit of Gastroenterology Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sanders, David S.
    Academic Unit of Gastroenterology Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Zylberberg, Haley M.
    Celiac Disease Center Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Green, Peter H.
    Celiac Disease Center Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Sundelin, Heléne E. K.
    Department of Pediatrics, University Hospital, Linköping, Sweden.
    Lebwohl, Benjamin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Celiac Disease Center Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Persistent mucosal damage and the 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-e38Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of CD patients have persistent villous atrophy (VA) on follow-up biopsy. This study's objective was to determine whether persistent VA on follow-up biopsy affects long-term epilepsy risk and epilepsy-related hospital emergency admissions.

    METHODS: 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 to those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant ICD codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures.

    RESULTS: Of 7590 people with CD who had a follow-up biopsy, VA was present in 43%. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38-0.98). On stratified analysis this effect was primarily amongst males (HR 0.35; 95 CI 0.15-0.80). Among the 58 CD patients with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (HR 0.37; 95%CI 0.09-1.09).

    CONCLUSIONS: In a population-based study of CD individuals, persisting VA on follow up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. Mechanisms as to why persistent VA confers this benefit requires further exploration. This article is protected by copyright. All rights reserved.

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