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  • 1.
    Alaedini, Armin
    et al.
    Department of Medicine and Celiac Disease Center and Institute of Human Nutrition, Columbia University Medical Center, New York NY, USA .
    Lebwohl, Benjamin
    Department of Medicine and 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 and 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; Örebro University Hospital, Department of Pediatrics, Örebro, Sweden; School of Medicine, University of Nottingham, Division of Epidemiology and Public Health, Nottingham, United Kingdom.
    Borrelia infection and risk of celiac disease2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, 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, Hucknall Road, Nottingham, United Kingdom.
    West, J.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Hucknall Road, Nottingham, United Kingdom.
    Sultan, A. Abdul
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Hucknall Road, Nottingham, United Kingdom.
    Dhalwani, N. N.
    Division of Epidemiology and Public Health, School of Medicine, Nottingham City Hospital, University of Nottingham, Hucknall Road, 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, Hucknall Road, 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, 1833-1841 p.Article 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, 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.
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden..
    Sundstrom, Anders
    Karolinska Inst, Dept Clin Epidemiol Unit, Dept Med, SE-17176 Stockholm, Sweden..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Clin Epidemiol Unit, Dept Med, SE-17176 Stockholm, Sweden.
    Blomqvist, Paul
    Karolinska Inst, Dept Clin Epidemiol Unit, Dept Med, SE-17176 Stockholm, Sweden..
    Kampe, Olle
    Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Bensing, Sophie
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, SE-75185 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, 2009-2018 p.Article 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. Bonamy, Anna-Karin E
    et al.
    Holmström, Gerd
    Stephansson, Olof
    Ludvigsson, Jonas F
    Örebro University Hospital.
    Cnattingius, Sven
    Preterm birth and later retinal detachment: a population-based cohort study of more than 3 million children and young adults.2013In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 120, no 11, 2278-85 p., S0161-6420(13)00320-5Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Ophthalmologic complications after preterm birth are common. Small studies show an association between retinopathy of prematurity and later retinal detachment. There are no population-based studies of preterm birth and risk of retinal detachment, which was the objective of the current investigation.

    DESIGN: Nationwide Swedish cohort study based on population registries.

    PARTICIPANTS: Of 3 423 697 subjects born in Sweden, 1 271 725 were born between 1973 and 1986 (i.e., before the national screening program for retinopathy of prematurity started), and 2 151 972 were born between 1987 and 2008. The participants were followed up from 1 year of age until 2009.

    METHODS: Unadjusted and adjusted hazard ratios (HRs) for retinal detachment were calculated using Cox proportional hazards regression.

    MAIN OUTCOME MEASURES: Incident retinal detachment, as defined by a diagnosis in the Swedish Patient Register (both inpatient and hospital-based outpatient data).

    RESULTS: During follow-up (median follow-up, 17.4 years), 1749 subjects were diagnosed with retinal detachment. Among the 188 852 subjects born prematurely (i.e., at <37 weeks of gestation), there were 124 cases of retinal detachment, of which 42 occurred in the 20 470 subjects born before 32 weeks of gestation. Compared with subjects born at term (37-41 weeks), the adjusted HR for retinal detachment after extremely preterm birth (<28 weeks of gestation) was 19.2 (95% confidence interval [CI], 10.3-35.8) for births between 1973 and 1986 and 8.95 (95% CI, 3.98-20.1) for births between 1987 and 2008. The corresponding HRs in subjects born very prematurely (28-31 weeks) were 4.32 (95% CI, 2.70-6.90) and 2.80 (95% CI, 1.38-5.69), respectively. Moderately preterm birth (32-36 weeks) was not associated with an increased risk of retinal detachment.

    CONCLUSIONS: Birth before 32 weeks of gestation is associated with a substantially increased relative risk of retinal detachment. These findings may have implications for ophthalmologic follow-up of children and adults born very prematurely.

  • 6.
    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, 765-773 p.Article 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.

  • 7.
    Brooke, Hannah Louise
    et al.
    Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Talbäck, 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. 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, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
    Druid, Henrik
    Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
    Feychting, Maria
    Unit of Epidemiology, Institute of Environmental MedicineKarolinska InstitutetStockholmSweden.
    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, 765-773 p.Article 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.

  • 8.
    Busch, K.
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden; Dept Pediat.
    Ekstrom-Smedby, K.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden..
    Ekbom, A.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden..
    Askling, J.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, SE-17176 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, 57-68 p.Article 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.

  • 9.
    Busch, Katharina
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden..
    da Silva, Simone A.
    Univ Sao Paulo, Dept Prevent Med, Sao Paulo, Brazil..
    Holton, Michelle
    Lorimer Enterprises Inc, Red Deer, AB, Canada..
    Rabacow, Fabiana M.
    Univ Sao Paulo, Dept Prevent Med, Sao Paulo, Brazil..
    Khalili, Named
    Massachusetts Gen Hosp, Digest Healthcare Ctr, Boston, MA 02114 USA..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Pediat; Karolinska Inst, Dept Med Epidemiol & Biostat, 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, 1362-1377 p.Article, 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.

  • 10.
    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, 87-93.e1 p., 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.

  • 11.
    Canova, Cristina
    et al.
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, I-35131 Padua, Italy..
    Pitter, Gisella
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, I-35131 Padua, Italy..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.; Dept Pediat.
    Romor, Pierantonio
    Informat Sistema Enti Locali INSIEL SpA, Friuli Venezia Giulia Reg Hlth Informat Syst, Udine, Italy..
    Zanier, Loris
    Hlth Directorate Friuli Venezia Giulia Reg, Epidemiol Serv, Udine, Italy..
    Zanotti, Renzo
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, I-35131 Padua, Italy..
    Simonato, Lorenzo
    Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, I-35131 Padua, Italy..
    Coeliac disease and asthma association in children: the role of antibiotic consumption2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 46, no 1, 115-122 p.Article in journal (Refereed)
    Abstract [en]

    The relationship between coeliac disease and asthma has been scarcely investigated. Infant antibiotic exposure has been linked to both diseases. We evaluated the association between childhood coeliac disease and asthma and the role of antibiotics in the first year of life. We followed a cohort of children born in 1995-2011 in the Friuli-Venezia Giulia region (Italy). Prescriptions for antibiotics in the first year of life and subsequent treated asthma were retrieved from drug prescription records; coeliac disease incident cases were identified from pathology reports, hospital discharges and exemption from prescription charges for clinical tests.We estimated incidence rate ratios (IRRs) using multivariate Poisson regression models. Among the 143 144 children, we identified 717 coeliac children and 34 969 asthmatics. Children with asthma were at increased risk of coeliac disease (IRR 1.46, 95% CI 1.25-1.67). Restricting the analysis to asthma that occurred before the diagnosis of coeliac disease, the excess risk disappeared, except for coeliac disease diagnosed after 5 years of age (IRR 1.37, 95% CI 1.09-1.71). Antibiotics were not a confounding factor in these associations. Childhood treated asthma and coeliac disease are significantly associated. This association is not confounded by antibiotic exposure in the first year of life and may be explained by other shared risk factors.

  • 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, 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, 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, 1996-2000 p.Article 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, 2634-2642 p.Article 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.
    Karolinska Institutet, Department Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Larsson, Henrik
    Karolinska Institutet, Department Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Lichtenstein, Paul
    Karolinska Institutet, Department Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Institutet, Department Medical Epidemiology and Biostatistics, Stockholm, Sweden; Karolinska University Hospital, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
    Serlachius, Eva
    Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, 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; School of Medicine, University of Nottingham, Division of Epidemiology and Public Health, Nottingham, United Kingdom; Columbia University College of Physicians and Surgeons, Department of Medicine, New York, NY, 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, 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.
    Ciacci, Carolina
    et al.
    Univ Salerno, Dept Med & Surg, Gastroenterol, I-84081 Baronissi, SA, Italy..
    Ciclitira, Paul
    Kings Coll London, Div Diabet & Nutr Sci, Dept Gastroenterol, London WC2R 2LS, England.;St Thomas Hosp, Rayne Inst, London SE1 7EH, England..
    Hadjivassiliou, Marios
    Sheffield Teaching Hosp NHS Trust, Acad Dept Neurosci, Sheffield, S Yorkshire, England.;Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England..
    Kaukinen, Katri
    Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.;Tampere Univ Hosp, Dept Internal Med, Tampere, Finland.;Seinajoki Cent Hosp, Dept Internal Med, Seinajoki, Finland..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden.; Dept Pediat.
    McGough, Norma
    Coeliac UK, High Wycombe, Bucks, England..
    Sanders, David S.
    Royal Hallamshire Hosp, Gastroenterol & Liver Unit, Sheffield S10 2JF, S Yorkshire, England.;Univ Sheffield, Sheffield, S Yorkshire, England..
    Woodward, Jeremy
    Addenbrookes Hosp, Cambridge Intestinal Unit, Cambridge, England..
    Leonard, Jonathan N.
    Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Dermatol, London, England..
    Swift, Gillian L.
    Univ Hosp Llandough, Dept Gastroenterol, Cardiff, S Glam, Wales..
    The gluten-free diet and its current application in coeliac disease and dermatitis herpetiformis2015In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 3, no 2, 121-135 p.Article, review/survey (Refereed)
    Abstract [en]

    Background: A gluten-free diet (GFD) is currently the only available therapy for coeliac disease (CD). Objectives: We aim to review the literature on the GFD, the gluten content in naturally gluten-free (GF) and commercially available GF food, standards and legislation concerning the gluten content of foods, and the vitamins and mineral content of a GFD. Methods: We carried out a PubMed search for the following terms: Gluten, GFD and food, education, vitamins, minerals, calcium, Codex wheat starch and oats. Relevant papers were reviewed and for each topic a consensus among the authors was obtained. Conclusion: Patients with CD should avoid gluten and maintain a balanced diet to ensure an adequate intake of nutrients, vitamins, fibre and calcium. A GFD improves symptoms in most patients with CD. The practicalities of this however, are difficult, as (i) many processed foods are contaminated with gluten, (ii) staple GF foods are not widely available, and (iii) the GF substitutes are often expensive. Furthermore, (iv) the restrictions of the diet may adversely affect social interactions and quality of life. The inclusion of oats and wheat starch in the diet remains controversial.

  • 16.
    Dixit, Rohit
    et al.
    Columbia Univ, Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, New York, NY USA..
    Lebwohl, Benjamin
    Columbia Univ, Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, 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.
    Lewis, Suzanne K.
    Columbia Univ, Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, New York, NY USA..
    Rizkalla-Reilly, Norelle
    Columbia Univ, Dept Pediat, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, New York, NY 10027 USA..
    Green, Peter H. R.
    Columbia Univ, Dept Med, Celiac Dis Ctr, Columbia Univ Coll Phys & Surg, New York, NY USA.;NewYork Presbyterian Hosp, New York, NY 10032 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, 1509-1512 p.Article 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.

  • 17.
    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, 679-680 p.Article 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.

  • 18.
    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, 589-598 p.Article 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.

  • 19. Elfstrom, Peter
    et al.
    Granath, Fredrik
    Smedby, Karin Ekstrom
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Askling, Johan
    Ekbom, Anders
    Ludvigsson, Jonas F.
    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, 436-444 p.Article 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.

  • 20.
    Elfström, P.
    et al.
    Department of Neonatology, Astrid Lindgren Children's Hospital-Danderyd, 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.
    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, 1123-1132 p.Article, 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.

  • 21.
    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.

  • 22.
    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, 30-36 p.Article 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.

  • 23.
    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, 3915-3921 p.Article 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.

  • 24.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Medicine.
    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, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Sweden; the Clinical Epidemiology Unit, Department of Medicine Solna, 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, 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.

  • 25.
    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 and Karolinska Institutet, Sweden.
    James, S.
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, J. 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, 905-914 p.Article 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.

  • 26.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carlsson, R.
    James, S.
    Ludvigsson, J. 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, 1118-1118 p.Article in journal (Refereed)
  • 27.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Vårdcentralen 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
    epartment 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 and Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics.
    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, 83-90 p.Article 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.

  • 28.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Primary Care Res Unit, Värmlands Nysäter, Värmland County, 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 Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics.
    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, 359-364 p.Article 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.

  • 29.
    Emilsson, Louise
    et al.
    Vardcentralen Varmlands Nysater, Primary Care Res Unit, Varmland County, Sweden.;Univ Oslo, Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, Oslo, Norway..
    Lebwohl, Benjamin
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY 10032 USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Sundstrom, Johan
    Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Uppsala, Sweden..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.; Dept Pediat.
    Cardiovascular disease in patients with coeliac disease: A systematic review and meta-analysis2015In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 47, no 10, 847-852 p.Article in journal (Refereed)
    Abstract [en]

    Background: Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. Methods: Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English-language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I-2 statistic. Results: Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95% CI 1.03-1.28). In a meta-analysis, we observed an increased risk of stroke (OR 1.11; 95% CI 1.02-1.20). The risks of myocardial infarction (OR 1.12; 95% CI 0.83-1.40) and cardiovascular death (OR 1.12; 95% CI 0.96-1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. Conclusion: Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited.

  • 30.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, 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.
    Review of 103 Swedish healthcare quality registries2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 1, 94-136 p.Article 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.

  • 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, University of Nottingham, Nottingham City Hospital, Nottingham NG5 1PB, UK; Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, Nottingham NG7 2UH, UK.
    Melander, Olle
    Department of Clinical Sciences, Lund University, Malmo¨ , Sweden.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, 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, 2430-7 p.Article 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.
    Emilsson, Louise
    et al.
    Vardctr Varmlands Nysater, Primary Care Res Unit, S-66195 Varmlands Nysater, Varmland County, Sweden.;Univ Oslo, Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, N-0316 Oslo, Norway..
    Sultan, Alyshah Abdul
    Univ Nottingham, City Hosp, Div Epidemiol & Publ Hlth, Clinical Sci Bldg,Hucknall Rd, Nottingham NG5 1PB, England.;Nottingham Univ Hosp NHS Trust, Biomed Res Unit, Nottingham Digest Dis Ctr, Natl Inst Hlth Res, Nottingham, England.;Univ Nottingham, Nottingham NG7 2RD, England..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.; Dept Pediat.
    No increased mortality in 109,000 first-degree relatives of celiac individuals2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 4, 376-380 p.Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have shown an excess mortality in individuals with celiac disease (CD). However, it is unknown if also first-degree relatives (FDRs) to celiac patients are at increased risk of death. Aim: We aimed to assess mortality in FDRs to celiac patients. Methods: Individuals with CD were identified through biopsy reports (equal to Marsh grade III). Each celiac individual was matched on sex, age, county and calendar year with up to five control individuals. Through Swedish healthcare registries we identified all FDRs (father, mother, sibling, offspring) of CD individuals and controls. Through Cox regression we calculated hazard ratios (HRs) for mortality (all-cause death, circulatory, cancer and other). Results: We identified 109,309 FDRs of celiac individuals and 549,098 FDRs of controls. Overall mortality was increased in FDRs to celiac individuals (HR = 1.02, 95%CI = 1.00-1.04, p = 0.03). This corresponded to an excess risk of 5.9 deaths per 100,000 person-years of follow-up. When limiting follow-up to time since celiac diagnosis in the index individual, we found no increased risk of death (HR = 1.01; 95%CI = 0.98-1.03). Conclusion: FDRs to individuals with CD are at increased risk of death. This excess risk is however minimal and unlikely to be of any clinical importance to the individual. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  • 33.
    Emilsson, Louise
    et al.
    Vardctr Varmlands Nysater, Primary Care Res Unit, S-66195 Varmlands Nysater, Varmland County, Sweden.;Univ Oslo, Inst Hlth & Soc, Dept Hlth Management & Hlth Econ, Oslo, Norway..
    Wijmenga, Cisca
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Murray, Joseph A.
    Mayo Clin, Dept Internal Med, Div Gastroenterol & Hepatol, Rochester, MN USA..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.; Dept Pediat.
    Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease2015In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 13, no 7, 1271-1277.e2 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. METHODS: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. RESULTS: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P =.11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. CONCLUSIONS: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.

  • 34.
    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, 722-729 p.Article 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.

  • 35.
    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, 1369-1370 p.Article in journal (Refereed)
    Abstract [en]

    No abstract is available for this article.

  • 36.
    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.
    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 Universit, 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, Örebro University Hospital, 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, 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 Sweden2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012Article 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.

  • 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 and 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, 443-450 p.Article 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.
    Humes, David J.
    et al.
    Univ Nottingham, City Hosp, Sch Med, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England.;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Nordenskjold, Agneta
    Karolinska Inst, Unit Paediat Surg, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden..
    Walker, Alex J.
    Univ Nottingham, City Hosp, Sch Med, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England..
    West, Joe
    Univ Nottingham, City Hosp, Sch Med, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.; Dept Paediat.
    Risk of venous thromboembolism in children after general surgery2015In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 50, no 11, 1870-1873 p.Article in journal (Refereed)
    Abstract [en]

    Background/purpose: The purpose of the study was to determine absolute and relative rates of venous thromboembolism (VTE) following general surgical procedures in children compared to the general population. Methods: We analyzed data from all patients under the age of 18 years in the Clinical Practice Research Datalink, linked to Hospital Episode Statistics from England (2001-2011) undergoing a general surgical procedure and population controls. Crude rates of VTE and adjusted hazard ratios were calculated using Cox regression. Results: We identified 15,637 children who had a surgical procedure with 161,594 controls. Six children undergoing surgery had a VTE diagnosed in the year after compared to five children in the population cohort. The overall rate of VTE following surgery was 0.4 per 1000 person years (pyrs) (95% confidence interval [CI] 0.15-0.88) compared to 0.04 per 1000 pyrs (95% CI 0.02-0.09) in the population cohort. This represented a 9 fold increase in risk compared to the population cohort (adjusted hazard ratio [HR] 8.80; 95% CI 2.59-29.94). Conclusions: Children are at increased risk for VTE following general surgical procedures compared to the general population however the absolute risk is small and given this the benefits of thromboprophylaxis need to be balanced against the risk of complications following its use.

  • 39. 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, 139-143 p.Article 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.

  • 40. 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, 42- p.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. 

  • 41. 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, 1321-1325 p.Article 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.

  • 42.
    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.
    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, 216-221 p.Article 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.

  • 43.
    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, Orebro University Hospital, Orebro, 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, 1614-1620 p.Article 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.

  • 44.
    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.
    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, Värmland, 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, S-17177 Stockholm, Sweden.;Columbia Univ, Dept Med, Celiac Dis Ctr, New York, NY USA.;Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.;Univ Nottingham, City Hosp, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England..
    Birth weight, sex, and celiac disease: a nationwide twin study2017In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, 567-577 p.Article 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.

  • 45.
    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.
    Wijmenga, Cisca
    Department of Genetics, University of Groningen, University Medical Center, 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, University of Nottingham, City Hospital, 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, 1793-1798 p.Article 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.

  • 46.
    Kurien, Matthew
    et al.
    Royal Hallamshire Hosp, Gastroenterol & Liver Unit, Sheffield S10 2JF, S Yorkshire, England.;Univ Sheffield, Sheffield, S Yorkshire, 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.
    Royal Hallamshire Hosp, Gastroenterol & Liver Unit, Sheffield S10 2JF, S Yorkshire, England.;Univ Sheffield, Sheffield, S Yorkshire, 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, 1003-1004 p.Article in journal (Refereed)
  • 47.
    Kurien, Matthew
    et al.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK; Academic Unit of Gastroenterology, University of Sheffield, Sheffield, UK.
    Mollazadegan, Kaziwe
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sanders, David S.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK; Academic Unit of Gastroenterology, University of Sheffield, Sheffield, UK.
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital.
    A nationwide population-based study on the risk of coma, ketoacidosis and hypoglycemia in patients with celiac disease and type 1 diabetes2015In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 52, no 6, 1167-1174 p.Article in journal (Refereed)
    Abstract [en]

    Celiac disease (CD) may influence metabolic control in type 1 diabetes (T1D). This work examines whether CD in T1D influences hospital admissions due to coma, ketoacidosis and hypoglycemia.

    In population-based cohort study, individuals with CD were identified using biopsy data (1969-2008) from Sweden's 28 pathology departments. T1D was defined as a recorded diagnosis of T1D at age a parts per thousand currency sign30 years in the Swedish National Patient Register between 1964 and 2009. In total, 906 individuals had both T1D and CD and were matched for sex, age and calendar period with 4303 reference individuals. Through stratified Cox regression analysis, we modeled CD as a time-dependent covariate and estimated the risk of future coma, ketoacidosis and hypoglycemia, defined by relevant international classification of disease codes among T1D patients with and without CD.

    During follow-up, patients with both T1D and CD had 49 hospital admissions with diabetic coma, 91 episodes of ketoacidosis and 25 hypoglycemic events. Among patients with T1D, CD did not influence the risk of coma (adjusted HR 0.97; 95 % CI 0.72-1.32), ketoacidosis (adjusted HR 1.08; 95 % CI 0.86-1.34), or hypoglycemia (adjusted HR 1.34; 95 % CI 0.87-2.05). The absolute risk of coma was 621/100,000 person-years in T1D and CD (637 in controls). Corresponding figures for ketoacidosis were 1175/100,000 person-years in T1D and CD (1092 in controls) and for hypoglycemia 316/100,000 person-years (236 in controls). HRs for metabolic emergencies in T1D were similar in the first 5 years after T1D diagnosis as thereafter.

    Having a diagnosis of CD is unlikely to influence the risk of coma, ketoacidosis and hypoglycemia in T1D patients.

  • 48.
    Kurien, Matthew
    et al.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, U.K.; Academic Unit of Gastroenterology, University of Sheffield, Sheffield, U.K..
    Mollazadegan, Kaziwe
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sanders, David S.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, U.K.; Academic Unit of Gastroenterology, University of Sheffield, Sheffield, U.K.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Celiac Disease Increases Risk of Thyroid Disease in Patients With Type 1 Diabetes: A Nationwide Cohort Study2016In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, no 3, 371-375 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Both type 1 diabetes (T1D) and celiac disease (CD) have been linked to autoimmune thyroid disease (ATD). We examined if individuals with both T1D and CD were at a higher risk of ATD than those with only T1D.

    Research design and methods: This study was a nationwide population-based cohort study. We defined T1D as having an inpatient or a hospital-based outpatient diagnosis of T1D at age ≤30 years in the Swedish National Patient Register between 1964 and 2009. Data on CD were obtained through small intestinal biopsy reports showing villous atrophy (Marsh histopathology grade III) between 1969 and 2008 at any of the 28 pathology departments in Sweden. ATD included hyperthyreosis and hypothyreosis, defined according to the Swedish National Patient Register. We identified 947 individuals with T1D and biopsy-verified CD. These were matched to 4,584 control subjects with T1D but no CD diagnosis. Cox regression then estimated the risk of ATD.

    Results: Among T1D, CD was a risk factor for later ATD. During follow-up, 90 T1D+CD patients developed ATD (expected n = 54). Adjusting for sex, age, and calendar period, this corresponded to a hazard ratio (HR) of 1.67 (95% CI 1.32-2.11; P < 0.001). This excess risk was highest in those who had CD for 10 years or more (HR 2.22 [95% CI 1.49-3.23]). Risk increases were seen in both males and females. CD was a risk factor for both hypothyreosis (HR 1.66 [95% CI 1.30-2.12]) and hyperthyreosis (HR 1.72 [95% CI 0.95-3.11]).

    Conclusions: Among patients with T1D, CD is a risk factor for the later development of ATD.

  • 49.
    Kurien, Matthew
    et al.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; Academic Unit of Gastroenterology, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Sanders, David S.
    Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; Academic Unit of Gastroenterology, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ciacci, Carolina
    Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
    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; 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.
    Increased rate of abdominal surgery both before and after diagnosis of celiac disease2017In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 49, no 2, 147-151 p.Article in journal (Refereed)
    Abstract [en]

    Background: The detection of celiac disease (CD) is suboptimal.

    Aims: We hypothesized that misdiagnosis is leading to diagnostic delays, and examine this assertion by determining if patients have increased risk of abdominal surgery before CD diagnosis.

    Methods: Through biopsy reports from Sweden's 28 pathology departments we identified all individuals with CD (Marsh stage 3; n=29,096). Using hospital-based data on inpatient and outpatient surgery recorded in the Swedish Patient Register, we compared abdominal surgery (appendectomy, laparotomy, biliary tract surgery, and uterine surgery) with that in 144,522 controls matched for age, sex, county and calendar year. Conditional logistic regression estimated odds ratios (ORs).

    Results: 4064 (14.0%) individuals with CD and 15,760 (10.9%) controls had a record of earlier abdominal surgery (OR=1.36, 95% CI=1.31-1.42). Risk estimates were highest in the first year after surgery (OR=2.00; 95% CI=1.79-2.22). Appendectomy, laparotomy, biliary tract surgery, and uterine surgery were all associated with having a later CD diagnosis. Of note, abdominal surgery was also more common after CD diagnosis (hazard ratio=1.34; 95% CI=1.29-1.39).

    Conclusions: There is an increased risk of abdominal surgery both before and after CD diagnosis. Surgical complications associated with CD may best explain these outcomes. Medical nihilism and lack of CD awareness may be contributing to outcomes.

  • 50.
    Laszkowska, Monika
    et al.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Shiwani, Henna
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Belluz, Julia
    Vox Media, Washington DC, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA; 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, United Kingdom.
    Green, Peter H. R.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Sheehan, Daniel
    Carto, Brooklyn NY, New York, USA.
    Rundle, Andrew
    Department of Epidemiology, Mailman School of Public Health, Columbia University, New York NY, USA.
    Lebwohl, Benjamin
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York NY, USA.
    The Gluten-Free Diet Epidemic: Socioeconomic Factors Predict Google Search Trends More Than Health Related Factors.2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 17, 30928-XArticle in journal (Refereed)
    Abstract [en]

    In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.

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