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  • 101.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Kämpe, Olle
    Uppsala Universitet.
    Ekbom, Anders
    Karolinska Institutet.
    Ludvigsson, Jonas F.
    Risk of primary adrenal insufficiency in patients with celiac disease2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 9, p. 3595-3598Article in journal (Refereed)
    Abstract [en]

    Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.

  • 102.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Kämpe, Olle
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Risk of Thyroid Disease in Individuals with Celiac Disease2008In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, no 10, p. 3915-3921Article in journal (Refereed)
    Abstract [en]

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

  • 103.
    Ericson, Anna
    et al.
    Uppsala University, Uppsala, Sweden.
    Ställberg, Björn
    Uppsala University, Uppsala, Sweden.
    Janson, Christer
    Uppsala University, Uppsala, Sweden.
    Sundh, Josefin
    Örebro University, School of Medicine, Örebro University, Sweden. Department Respiratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kampe, Mary
    Uppsala University, Uppsala, Sweden.
    Efraimsson, Eva Osterlund
    Dalarna University, Falun, Sweden.
    Patients' evaluation on asthma severity was related to level of asthma control and quality of life over seven years follow-up2013In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 42, no 57, article id 2744Article in journal (Other academic)
  • 104.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Rundquist, Sara
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, Ida
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK .
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-20102017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 8, p. 748-757Article in journal (Refereed)
    Abstract [en]

    Background: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.

    Aim: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.

    Methods: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Orebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.

    Results: The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).

    Conclusion: The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

  • 105.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Rundquist, Sara
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Zhulina, Yaroslava
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, Ida
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Editorial: do thiopurines and biologics decrease the risk of colectomy? Authors' reply2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 9, p. 897-898Article in journal (Other academic)
  • 106.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences.
    Henriksson, Ida
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brus, Ole
    Örebro University, School of Medical Sciences.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden; University College London, London, United Kingdom.
    Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort studyManuscript (preprint) (Other academic)
  • 107.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Henriksson, Ida
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brus, Ole
    Örebro University, School of Medical Sciences.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population-based cohort study2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 6, p. 638-645Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence and short-term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown.

    AIM: To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD.

    METHODS: A random sample of 342 patients was obtained from the population-based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system.

    RESULTS: In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4-23.7) per 100 person-years and the prevalence was 28.7% (CI: 22.0-36.2), compared with 12.9 (CI: 9.8-16.5) and 16.5% (CI: 11.2-22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02-2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20-3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00-6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10-5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03).

    CONCLUSIONS: Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome.

  • 108.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Rundquist, Sara
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 4, p. 623-632Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.

    DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.

    RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).

    CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

  • 109.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences.
    Rundquist, Sara
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    The impact of thiopurine drugs on the natural history and surgical outcome of ulcerative colitis: A cohort study2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S481-S481Article in journal (Other academic)
  • 110.
    Fadl, Helena
    et al.
    Örebro University Hospital. Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Magnuson, A.
    Östlund, Ingrid
    Örebro University Hospital. Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Hanson, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Schwarcz, Erik
    Örebro University, School of Health Sciences. Department of Internal Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Gestational diabetes mellitus and later cardiovascular disease: a Swedish population based case-control study2014In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 121, no 12, p. 1530-1536Article in journal (Refereed)
    Abstract [en]

    Objective: To identify if gestational diabetes mellitus (GDM) is a clinically useful marker of future cardiovascular disease (CVD) risk and if GDM combined with other risks (smoking, hypertension or body mass) identifies high-risk groups.

    Design: Population-based matched case-control study.

    Setting: National Swedish register data from 1991 to 2008.

    Population: A total of 2639 women with a cardiovascular event and matched controls.

    Methods: Conditional logistic regression examined associations with CVD before and after adjustment for conventional risk factors and confounders. Effect modification for the association of GDM with CVD by body mass index (BMI), smoking and chronic hypertension was assessed by stratification and interaction testing. Adjustment for diabetes post-pregnancy evaluated its mediating role.

    Main outcome measures: Inpatient diagnoses or causes of death identifying ischemic heart disease, ischemic stroke, atherosclerosis or peripheral vascular disease.

    Results: The adjusted odds ratios (and 95% confidence intervals) for the association of CVD with GDM are 1.51 (1.07-2.14), 2.23 (2.01-2.48) for smoking, 1.98 (1.71-2.29) for obesity and 5.10 (3.18-8.18) for chronic hypertension. In stratified analysis the association of CVD with GDM was only seen among women with BMI 25, with an odds ratio of 2.39 (1.39-4.10), but only women with a BMI <30 accounted for this increased risk. Adjustment for post-pregnancy diabetes attenuated it somewhat to 1.99 (1.13-3.52).

    Conclusions: In the absence of other recognised cardiovascular risk factors, such as smoking, obesity or chronic hypertension, GDM is a useful marker of raised CVD risk among women with BMI between 25 and 29.

  • 111.
    Fadl, Helena
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Patil, Snehal
    Örebro University, School of Medical Sciences. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Wikström, Anna-Karin
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Jansson, Stefan P. O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Sengpiel, Verena
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Berntorp, Kerstin
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Ryen, Linda
    Örebro University, School of Health Sciences. Örebro University Hospital. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Ahlsson, Fredrik
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Lindholm, Elisabeth S.
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Strevens, Helena
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Wennerholm, Ulla-Britt
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Persson, Martina
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    de Brun, Maryam
    Örebro University, School of Medical Sciences. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    SIMMONS, DAVID
    Örebro, Sweden; Uppsala, Sweden; Gothenburg, Sweden; Lund, Sweden; Kullavik, Sweden; Stockholm, Sweden; Västerås, Sweden; Campbelltown, Australia.
    Association of GDM Risk Factors with Glucose at Diagnosis and Treatment in Sweden2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no Supplement_1, article id 1039-PArticle in journal (Refereed)
  • 112.
    Fadl, Helena
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Obstetrics and Gynaecology.
    Saeedi, Maryam
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, University Hospital Örebro, Örebro, Sweden.
    Patil, Snehal
    Örebro University, School of Medical Sciences.
    Simmons, David
    Örebro University, School of Medical Sciences. Macarthur Clinical School, Western Sydney University, Campbelltown, Australia.
    Schwarcz, Erik
    Department of Internal Medicine, Schoolof medical health and sciences, Örebro University Hospital, Örebro, Sweden.
    Berntorp, Kerstin
    Department of Endocrinology, Skåne University Hospital, Clinical Research Center Malmö, Lund University, Lund, Sweden.
    Jansson, Stefan P. O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Center.
    Persson, Martina
    Department of Paediatrics, Sachsska Children’s and Youth hospital and Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden.
    Storck-Lindholm, Elisabeth
    Department of Obstetrics and Gynaecology, Södersjukhuset, Stockholm, Sweden.
    Sengpiel, Verena
    Department of Obstetricsand Gynaecology, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wennerholm, Ulla-Britt
    Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy,University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ahlsson, Fredrik
    Department of Women’s and Children’s health, Uppsala University, Uppsala, Sweden.
    Wikström, Anna-Karin
    Women’s and Children’s Health, Uppsala university, Uppsala, Sweden.
    Strevens, Helena
    Department of Obstetrics and Gynaecology, Skåne University Hospital, Clinical Research Center Lund, Lund University, Lund, Sweden.
    Petersson, Kerstin
    Department of Clinical Sciences, Obstetrics and Gynaecology, Umeå University, Umeå, Sweden.
    Ryen, Linda
    Örebro University, School of Health Sciences. Center for Health Care Science.
    Hildén, Karin
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology.
    Ursing, Carina
    Department of Endocrinology, Södersjukhuset, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: a stepped wedge cluster randomised controlled trial2023Conference paper (Other academic)
  • 113.
    Fadl, Helena
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Obstetrics and Gynaecology.
    Saeedi, Maryam
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, University Hospital Örebro, Örebro, Sweden.
    Schwarcz, Erik
    Department of Internal Medicine, Schoolof medical health and sciences, Örebro University Hospital, Örebro, Sweden.
    Berntorp, Kerstin
    Department of Endocrinology, Skåne University Hospital, Clinical Research Center Malmö, Lund University, Lund, Sweden.
    Sengpiel, Verena
    Department of Obstetricsand Gynaecology, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Storck-Lindholm, Elisabeth
    Department of Obstetrics and Gynaecology, Södersjukhuset, Stockholm, Sweden.
    Strevens, Helena
    Department of Obstetrics and Gynaecology, Skåne University Hospital, Clinical Research Center Lund, Lund University, Lund, Sweden.
    Wikström, Anna-Karin
    Women’s and Children’s Health, Uppsala university, Uppsala, Sweden.
    Brismar-Wendel, Sophia
    Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
    Persson, Martina
    Department of Paediatrics, Sachsska Children’s and Youth hospital and Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden.
    Jansson, Stefan P. O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Center.
    Ahlsson, Fredrik
    Department of Women’s and Children’s health, Uppsala University, Uppsala, Sweden.
    Ursing, Carina
    Department of Endocrinology, Södersjukhuset, Stockholm, Sweden.
    Ryen, Linda
    Örebro University, School of Health Sciences. Center for Health Care Science.
    Petersson, Kerstin
    Department of Clinical Sciences, Obstetrics and Gynaecology, Umeå University, Umeå, Sweden.
    Wennerholm, Ulla-Britt
    Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy,University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hildén, Karin
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology.
    Simmons, David
    Örebro University, School of Medical Sciences. Macarthur Clinical School, Western Sydney University, Campbelltown, Australia.
    Changing diagnostic criteria for gestational diabetes in Sweden: a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol2019In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 19, no 1, article id 398Article in journal (Refereed)
    Abstract [en]

    Background: The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches.

    Methods: This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included.

    Discussion: The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.

  • 114.
    Fang, X.
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Han, H.
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Li, M.
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Liang, C.
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Fan, Z.
    Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
    Aaseth, J.
    Kongsvinger Hospital Division, Innlandet Hospital Trust, Kongsvinger, Norway; Kongsvinger Hospital Division, Innlandet Hospital Trust, Kongsvinger, Norway.
    He, J.
    Department of Health Statistics, Second Military Medical University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Cao, Yang
    Örebro University, School of Medical Sciences. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies2016In: Nutrients, E-ISSN 2072-6643, Vol. 8, no 11, article id 739Article, review/survey (Refereed)
    Abstract [en]

    The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  • 115.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Liang, Chun
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Li, Mei
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Fall, Katja
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Aaseth, Jan
    Faculty of Public Health, Hedmark University College, Elverum, Norway; Kongsvinger Hospital Division, Innlandet Hospital Trust, Kongsvinger, Norway.
    Cao, Yang
    Örebro University, School of Medical Sciences. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies2016In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, p. 64-73Article, review/survey (Refereed)
    Abstract [en]

    Background: Although epidemiology studies have reported the relationship, including a dose-response relationship, between dietary magnesium intake and risk of cardiovascular disease (CVD), the risk for CVD mortality is inconclusive and the evidence for a dose-response relationship has not been summarized.

    Objective: We conducted a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the association of dietary magnesium intake with risk of CVD mortality and describe their dose-response relationship.

    Design: We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to August 2015, and reviewed references lists of retrieved articles. We included population-based studies that reported mortality risks, i.e. relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs) of CVD mortality or cause-specific CVD death. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines.

    Results: Out of 3002 articles, 9 articles from 8 independent studies met the eligibility criteria. These studies comprised 449,748 individuals and 10,313 CVD deaths. Compared with the lowest dietary magnesium consumption group in the population, the risk of CVD mortality was reduced by 16% in women and 8% in men. No significant linear dose-response relationship was found between increment in dietary magnesium intake and CVD mortality across all the studies. After adjusting for age and BMI, the risk of CVD mortality was reduced by 24-25% per 100 mg/d increment in dietary magnesium intake in women of all the participants and in all the US participants.

    Conclusion: Although the combined data confirm the role of dietary magnesium intake in reducing CVD mortality, the dose-response relationship was only found among women and in US population.

  • 116.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wang, Lei
    Department of Oral & Maxillofacial-Head & Neck Oncology, the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
    Wu, Chunhua
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Shi, Huijing
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Zhou, Zhijun
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sex Hormones, Gonadotropins, and Sex Hormone-binding Globulin in Infants Fed Breast Milk, Cow Milk Formula, or Soy Formula2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 4332Article in journal (Refereed)
    Abstract [en]

    Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.

  • 117.
    Forsgård, Richard A.
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lobenius Palmér, Karin
    Örebro University, School of Health Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kamm, Annalena
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Patil, Snehal
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tacken, Mirriam G. J.
    Wageningen Bioveterinary Research, Wageningen University and Research, Lelystad, The Netherlands.
    Lentjes, Marleen A. H.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Axelsson, Jakob
    BioGaia AB, Stockholm and Lund, Sweden.
    Grompone, Gianfranco
    BioGaia AB, Stockholm and Lund, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial2023In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 15, no 1, article id 2229938Article in journal (Refereed)
    Abstract [en]

    Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

  • 118. Färnert, Anna
    et al.
    Williams, Thomas N.
    Mwangi, Tabitha W.
    Ehlin, Anna
    Fegan, Greg
    Macharia, Alex
    Lowe, Brett S.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Marsh, Kevin
    Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection2009In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 200, no 7, p. 1166-1175Article in journal (Refereed)
    Abstract [en]

    Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.

  • 119.
    Gagatek, S.
    et al.
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Wijnant, S. R. A.
    Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
    Ställberg, B.
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Lisspers, K.
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Brusselle, G.
    Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherland; Department of Respiratory Medicine, Erasmus Medical Centre, Rotterdam, Netherlands .
    Zhou, X.
    Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden .
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine.
    Janson, C.
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Emilsson, Ö.
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Lahousse, L.
    Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
    Malinovschi, A.
    Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
    Validation of Clinical COPD Phenotypes for Prognosis of Long-Term Mortality in Swedish and Dutch Cohorts2022In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 19, no 1, p. 330-338Article in journal (Refereed)
    Abstract [en]

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

  • 120.
    Gagatek, Sebastian Grzegorz
    et al.
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Wijnant, Sara
    Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
    Ställberg, Björn
    Department of Public Health and Caring Sciences, Family Medicine and Preventive medicine, Uppsala University, Uppsala, Sweden.
    Lisspers, Karin
    Department of Public Health and Caring Sciences, Family Medicine and Preventive medicine, Uppsala University, Uppsala, Sweden.
    Brusselle, Guy
    Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
    Zhou, Xing Wu
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine.
    Christer, Janson
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Emilsson, Össur
    Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Lahousse, Lies
    Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.
    Malinovschi, Andrei
    Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
    Validation of clinical clusters for long-term mortality in two European COPD cohorts2020In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 56, no Suppl. 64Article in journal (Other academic)
    Abstract [en]

    Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a variable mortality risk. A simple clinical algorithm has been validated for short-term mortality by Burgel et al. (ERJ 2017).

    Aim: To study if Burgel’s clinical algorithm is valid to predict long-term mortality.

    Methods: Data from two COPD cohorts, the Swedish PRAXIS Study (PS) (n=784, mean age (SD) 64.0 years (7.5), 42% males) and the Rotterdam Study (RS) (n=735, mean age (SD) 72 years (9.2), 57% males), with 9-years of follow-up data including mortality was used. The five clinical clusters were derived from baseline data on age, body mass index, dyspnea grade (mMRC), FEV 1 (%pred) and comorbidity (cardiovascular disease or diabetes). Mortality risk was estimated by unadjusted Cox models.

    Results: The distribution of clinical clusters (1-5) was: 29%/45%/8%/6%/12% in PS and 23%/26%/36%/0/15% in RS. The cumulative proportion of deaths after 9-years of follow-up was highest among COPD clusters 1 (65%) and 4 (72%), and lowest among cluster 5 (10%) in the PS cohort. In RS, Cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared to cluster 5, the meta-analysed hazard ratio (HR) (95%CI) for cluster 1 was 9.95 (6.52–15.19) and for cluster 4, 13.49 (6.41–28.38). The meta-analysed HR for clusters 2 and 3, compared with cluster 5, were: 2.80 (1.77 – 4.36) and 4.73 (3.02 – 7.42), respectively.

    Conclusions: Burgel’s clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with best prognosis and clusters 2 and 3 with intermediate prognosis in two independent COPD cohorts from Sweden and Netherlands.

  • 121.
    Garcia-Argibay, Miguel
    et al.
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hiyoshi, Ayako
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom; Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
    Fall, Katja
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom; Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide2022In: JAMA Network Open, E-ISSN 2574-3805, Vol. 5, no 12, article id e2248135Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia.

    OBJECTIVE: To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide.

    DESIGN, SETTING, AND PARTICIPANTS: This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022.

    MAIN OUTCOMES AND MEASURES: A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide.

    EXPOSURES: A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use.

    RESULTS: Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]).

    CONCLUSIONS AND RELEVANCE: This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.

  • 122.
    Garcia-Argibay, Miguel
    et al.
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro universitet, Örebro, Sweden.
    Hiyoshi, Ayako
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro universitet, Örebro, Sweden; Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro universitet, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden .
    Acute appendicitis and ulcerative colitis: a population-based sibling comparison study2022In: BMJ Open Gastroenterology, E-ISSN 2054-4774, Vol. 9, no 1, article id e001041Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the inverse relationship between acute appendicitis and ulcerative colitis (UC) using a sibling comparison design to adjust for unmeasured familial genetic and environmental factors.

    Design: The cohort comprised 3.1 million individuals resident in Sweden between 1984 and 2018 with the linkage of several Swedish national registers. Fitting Cox hazards models, we calculated the risk for developing UC in individuals with and without acute appendicitis by the age 20 years adjusting for several potential confounding factors. Further, we performed sibling-stratified analyses to adjust for shared unmeasured familial confounding factors.

    Results: During 57.7 million person-years of follow-up, 20 848/3 125 232 developed UC among those without appendicitis (3.63 (3.59-3.68) per 10 000 person-years), whereas only 59/35 848 people developed UC among those with appendicitis before age 20 years (1.66 (1.28-2.14) per 10 000 person-years). We found a decreased risk for developing UC in those with acute appendicitis by the age 20 years compared with individuals who did not have appendicitis by this age (HR=0.37 (95% CI 0.29 to 0.48)). When adjusting for shared familial confounders, we observed only a slight attenuation in this association (HR=0.46 (95% CI 0.32 to 0.66)).

    Conclusion: Individuals who had acute appendicitis by late adolescence showed a decreased risk for developing UC compared with those who did not. Genetic and shared familial environmental factors seem to potentially play only a small role in this relationship. Our results suggest an independent association of acute appendicitis, or its underlying causes, with UC risk.

  • 123.
    Garcia-Argibay, Miguel
    et al.
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Hiyoshi, Ayako
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Public Health Sciences, Stockholm University, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Association between dementia risk and ulcerative colitis, with and without colectomy: a Swedish population-based register study2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 12, article id e074110Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aims to investigate the association of ulcerative colitis (UC) with all-cause dementia and assess differences in those with and without a total colectomy.

    DESIGN, SETTING AND PARTICIPANTS: This Swedish prospective register-based study comprised 4.8 million individuals aged at least 59 years between 1964 and 2018 with the linkage of several Swedish national registers.

    PRIMARY AND SECONDARY OUTCOME MEASURES: Individuals with dementia were defined according to International Classification of Diseases diagnostic codes and Anatomical Therapeutic Classification codes for medication prescriptions. Fitting Cox hazards models, the risk of developing all-cause dementia in individuals with and without UC was estimated. Further, we compared the risk of all-cause dementia among those with and without a colectomy.

    RESULTS: Among 4 821 488 individuals (52.6% females) followed for 84.1 million person-years between 1964 and 2018, the incidence rate of all-cause dementia was 63.90 (63.73-64.07) events per 10 000 person-years in individuals without UC, 94.80 (92.04-97.64) among those with UC, 95.01 (92.25-97.86) in those with UC but without colectomy and 63.42 (40.92-98.31) in those with UC and a colectomy. Adjusted Cox models showed an increased all-cause dementia risk in individuals with UC (HR 1.07, 95% CI 1.04 to 1.10). We found no differences between unexposed individuals and those with UC and a colectomy (HR 0.89, 95% CI 0.57 to 1.38).

    CONCLUSION: The findings are consistent with previous evidence suggesting a slightly increased dementia risk among individuals with UC. This study provided no evidence of further risk increase of dementia among those who had a colectomy.

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  • 124.
    Giezeman, Maaike
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden.
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences.
    Lisspers, Karin
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Ställberg, Björn
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College, London, UK.
    Janson, Christer
    Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Influence of comorbid heart disease on dyspnea and health status in patients with COPD - a cohort study2018In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, p. 3857-3865Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to examine the changing influence over time of comorbid heart disease on symptoms and health status in patients with COPD.

    Patients and methods: This is a prospective cohort study of 495 COPD patients with a baseline in 2005 and follow-up in 2012. The study population was divided into three groups: patients without heart disease (no-HD), those diagnosed with heart disease during the study period (new-HD) and those with heart disease at baseline (HD). Symptoms were measured using the mMRC. Health status was measured using the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT; only available in 2012). Logistic regression with mMRC $2 and linear regression with CCQ and CAT scores in 2012 as dependent variables were performed unadjusted, adjusted for potential confounders, and additionally adjusted for baseline mMRC, respectively, CCQ scores.

    Results: Mean mMRC worsened from 2005 to 2012 as follows: for the no-HD group from 1.8 (+/- 1.3) to 2.0 (+/- 1.4), (P=0.003), for new-HD from 2.2 (+/- 1.3) to 2.4 (+/- 1.4), (P=0.16), and for HD from 2.2 (+/- 1.3) to 2.5 (+/- 1.4), (P=0.03). In logistic regression adjusted for potential confounding factors, HD (OR 1.71; 95% CI: 1.03-2.86) was associated with mMRC $ 2. Health status worsened from mean CCQ as follows: for no-HD from 1.9 (+/- 1.2) to 2.1 (+/- 1.3) with (P=0.01), for new-HD from 2.3 (+/- 1.5) to 2.6 (+/- 1.6) with (P=0.07), and for HD from 2.4 (+/- 1.1) to 2.5 (+/- 1.2) with (P=0.57). In linear regression adjusted for potential confounders, HD (regression coefficient 0.12; 95% CI: 0.04-5.91) and new-HD (0.15; 0.89-5.92) were associated with higher CAT scores. In CCQ functional state domain, new-HD (0.14; 0.18-1.16) and HD (0.12; 0.04-0.92) were associated with higher scores. After additional correction for baseline mMRC and CCQ, no statistically significant associations were found.

    Conclusion: Heart disease contributes to lower health status and higher symptom burden in COPD but does not accelerate the worsening over time.

  • 125.
    Giezeman, Maaike
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Athlin, Åsa
    Örebro University, School of Medical Sciences.
    Lisspers, Karin
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Ställberg, Björn
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Janson, Christer
    Department of Medical Sciences, Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Kisiel, Marta A.
    Department of Medical Sciences, Occupational and Environment Medicine, Uppsala University, Uppsala, Sweden.
    Nager, Anna
    Division of Family Medicine and Primary Care, Inst NVS, Karolinska Institutet, Stockholm, Sweden.
    Sandelowsky, Hanna
    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Family Medicine and Primary Care, Inst NVS, Karolinska Institutet, Stockholm, Sweden; Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden .
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences.
    Comorbid heart disease in patients with COPD is associated with increased hospitalization and mortality – a 15 year follow-upManuscript (preprint) (Other academic)
  • 126.
    Giezeman, Maaike
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research and Education, Karlstad, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Athlin, Åsa
    Örebro University, School of Medical Sciences. School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lisspers, Karin
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Ställberg, Björn
    Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Janson, Christer
    Department of Medical Sciences, Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Kisiel, Marta A.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Nager, Anna
    Division of Family Medicine and Primary Care, Inst NVS, Karolinska Institutet, Stockholm, Sweden.
    Sandelowsky, Hanna
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Division of Family Medicine and Primary Care, Inst NVS, Karolinska Institutet, Stockholm, Sweden; Academic Primary Health Care Centre, Region Stockholm, Sweden.
    Hasselgren, Mikael
    Örebro University, School of Medical Sciences. School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Centre for Clinical Research and Education, Karlstad, Sweden.
    Comorbid Heart Disease in Patients with COPD is Associated with Increased Hospitalization and Mortality: A 15-Year Follow-Up2023In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 18, p. 11-21Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to examine the association of comorbid heart disease, defined as chronic heart failure or ischemic heart disease, on all-cause and cause-specific hospitalization and mortality in patients with COPD over a period of nearly 15 years.

    MATERIALS AND METHODS: The cohort study included patients with COPD from primary and secondary care in 2005 with data from questionnaires and medical record reviews. The Swedish Board of Health and Welfare provided hospitalization and mortality data from 2005 through 2019. Cox regression analyses, adjusted for sex, age, educational level, smoking status, BMI, exacerbations, dyspnea score and comorbid diabetes or hypertension, assessed the association of comorbid heart disease with all-cause and cause-specific time to first hospitalization and death. Linear regression analyses, adjusted for the same variables, assessed this association with hospitalization days per year for those patients that had been hospitalized.

    RESULTS: Of the 1071 patients, 262 (25%) had heart disease at baseline. Cox regression analysis showed a higher risk of hospitalization for patients with heart disease for all-cause (HR (95% CI) 1.55; 1.32-1.82), cardiovascular (2.14; 1.70-2.70) and other causes (1.27; 1.06-1.52). Patients with heart disease also had an increased risk of all-cause (1.77; 1.48-2.12), cardiovascular (3.40; 2.41-4.78) and other (1.50; 1.09-2.06) mortality. Heart disease was significantly associated with more hospitalization days per year of all-cause (regression coefficient 0.37; 95% CI 0.15-0.59), cardiovascular (0.57; 0.27-0.86) and other (0.37; 0.12-0.62) causes. No significant associations were found between heart disease and respiratory causes of hospitalization and death.

    CONCLUSION: Comorbid heart disease in patients with COPD is associated with an increased risk for all-cause hospitalization and mortality, mainly due to an increase of hospitalization and death of cardiovascular and other causes, but not because of respiratory disease. This finding advocates the need of a strong clinical focus on primary and secondary prevention of cardiovascular disease in patients with COPD.

  • 127.
    Gunnarsson, Martin
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bahmanyar, S.
    Clinical Epidemiology Unit and Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran .
    Nilsagård, Ylva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Research Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study2015In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, no 7, p. 1131-1137Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated.

    Methods: A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination.

    Results and conclusions: Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P=0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P=0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS.

  • 128.
    Gupta, Sunjai
    et al.
    Freelance Researcher, London, United Kingdom.
    Xu, Yin
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK.
    The role of inflammation in the relationship of self-rated health with mortality and implications for public health: Data from the English Longitudinal Study of Aging (ELSA)2020In: Brain, Behavior, & Immunity, ISSN 0889-1591, Vol. 8, p. 100139-100139Article in journal (Refereed)
    Abstract [en]

    Self-rated health (SRH) predicts mortality after adjustment for potential confounders, including measures of health status. Prodromal disease might lead to worsened SRH and higher mortality. But no study of SRH and mortality has focussed on inflammation. The objective of this study is to investigate the influence of inflammation upon the association between SRH and mortality in a British cohort. The English Longitudinal Study of Ageing (ELSA) involves interviewing participants aged over 50 every two years. We analysed data for 3405 men and 4139 women. Mortality for consenting members was detected by linkage with UK National Health Care registry up to March 2012. Demographic, clinical, and health behaviours at wave 2 were treated as confounders, as well as inflammation-related disease and C-reactive protein (CRP). A five-step hierarchical multivariable logistic regression was estimated. An association was observed between SRH and mortality after adjusting for all variables. In men, compared to those with excellent health, CRP only, and CRP and inflammation-related disease combined, could explain 7.03% and 24.35% of increased risk of dying associated with poor health, respectively. For women, the corresponding figures were 8.95% and 24.28%, respectively. Inflammation is associated with increased risk of death, and may help to explain approximately a quarter of the association between SRH and mortality. Individuals with relatively poor SRH may be aware of underlying inflammation that increases the risk of illness and death, and this may lead to increased use of services, for example. Identifying the cause and treating inflammation in those without a diagnosis may help to increase survival and life quality among those who perceive their health to be relatively poor.

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    The role of inflammation in the relationship of self-rated health with mortality and implications for public health: Data from the English Longitudinal Study of Aging (ELSA)
  • 129.
    Göthlin Eremo, Anna
    et al.
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Lagergren, Kajsa
    School of Medical Sciences, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.
    Othman, Lana
    School of Medical Sciences, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Göran
    Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Huddinge, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences.
    Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 1451Article in journal (Refereed)
    Abstract [en]

    Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor- positive (ER+) breast cancer tissue. Tamoxifen- treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30-4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45-9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.

  • 130.
    Göthlin Eremo, Anna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tina, Elisabet
    Örebro University Hospital, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Fransén, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wegman, Pia
    Linköping University Hospital, Linköping, Sweden.
    Repsilber, Dirk
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK .
    Sollie, Tomas
    Örebro University Hospital, Örebro, Sweden.
    Wingren, Sten
    Örebro University, School of Medicine, Örebro University, Sweden.
    Gene expression profiles in breast tumors from tamoxifen treated patients with and without distant recurrenceManuscript (preprint) (Other academic)
  • 131.
    Hailer, Yasmin D.
    et al.
    Department of Orthopaedics, Uppsala University Hospital, Uppsala, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Olof
    Department of Orthopaedics, Uppsala University Hospital, Uppsala, Sweden.
    Bahmanyar, Shahram
    Clinical Epidemiology Unit & Center for Pharmacoepidemiology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
    Legg-Calvé-Perthes disease and the risk of injuries requiring hospitalization: a register study involving 2579 patients2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 6, p. 572-576Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Previous studies have suggested that Legg-Calvé-Perthes disease (LCPD) is associated with repetitive trauma, coagulation problems and anatomical abnormalities of the blood supply to the femoral head. The hypothesis that repetitive trauma can affect the blood supply of the femoral head, leading to LCPD, is supported by an animal model. For evidence of an increased risk of repetitive trauma, we investigated whether patients with LCPD have a higher risk for severe injuries requiring hospitalization.

    Patients and methods: We identified 2579 patients with LCPD in Sweden during the period 1964-2005. 13,748 individuals without LCPD were randomly selected from the Swedish general population, matched by year of birth, sex and region (control group). Cox proportional hazard regression estimated the risks.

    Results: Compared to the control group, patients with LCPD had a modestly raised hazard ratio (HR) of 1.2 (95% CI 1.1-1.3) for injury requiring hospitalization. The risks were slightly higher for soft tissue injuries (HR = 1.3, 95% CI:1.1-1.4) than for fractures (HR = 1.1, 95% CI: 1.0-1.3) and more pronounced among females. Compared to the control group, the higher risk for injury only applied to the lower extremities (HR = 1.2, 95% CI: 1.0-1.4) in patients with LCPD.

    Interpretation: Patients with LCPD are vulnerable to injuries which could be interpreted as a marker of hyperactive behavior. It could also implicate that anatomical changes in the bone formation or blood supply of the femoral head - increasing its sensibility for trauma - contribute to the etiology of LCPD.

  • 132.
    Hajiebrahimi, Mohammadhossein
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Public Health, Health Faculty, Golestan University of Medical Sciences, Gorgan, Iran .
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Burkill, Sarah
    Center for Pharmacoepidemiology & Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, Shahram
    Center for Pharmacoepidemiology & Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Public Health, Health Faculty, Golestan University of Medical Sciences, Gorgan, Iran .
    Risk of Premenopausal and Postmenopausal Breast Cancer among Multiple Sclerosis Patients2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 10, article id e0165027Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate risk of premenopausal and postmenopausal breast cancer among Multiple Sclerosis (MS) patients, considering tumor stage.

    Methods: The Swedish Patient Register identified 19,330 women with MS between 1968 and 2012, matched individually with a cohort of 193,458 without MS. Matching variables were year of birth, sex, region of residence and vital status at the time of diagnosis. The cancer register identified 471 and 5,753 breast cancer cases among the MS and non-MS cohorts, respectively. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal and postmenopausal breast cancer.

    Results: Overall risk of postmenopausal breast cancer was 13% higher among MS patients compared with women without MS (HR = 1.13, 95% CI 1.02-1.26). Stratified analyses showed that the risk was statistically significantly increased in women diagnosed between 1968 and 1980 and those who were diagnosed at age 65 or older age. We observed a non-statistically significant risk only for stage 0-1 postmenopausal breast cancer (HR = 1.17, 95% CI 0.93-1.48). MS was not associated with premenopausal breast cancer.

    Conclusion: The modest increased risk of postmenopausal breast cancer in women with MS may be due to surveillance bias, where contact with health services for one disease increases the risk of a second diagnosis being recorded.

  • 133.
    Hakkarainen, Katja Marja
    et al.
    StatFinn EPID Research, Mölndal, Sweden.
    Juuti, Rosa
    StatFinn EPID Research, Espoo, Finland.
    Burkill, Sarah
    Karolinska Institute, Stockholm, Sweden.
    Geissbühler, Yvonne
    Novartis Pharma AG, Evidence and Launch Excellence, Basel, Switzerland.
    Sabidó, Meritxell
    Merck KGaA, Darmstadt, Germany.
    Popescu, Catrinel
    Biogen Idec Ltd, Maidenhead, United Kingdom.
    Suzart-Woischnik, Kiliana
    Bayer AG, Berlin, Germany.
    Hillert, Jan
    Karolinska Institute, Stockholm, Sweden.
    Artama, Miia
    University of Helsinki, Helsinki, Finland.
    Verkkoniemi-Ahola, Auli
    Clinical Neurosciences, Neurology, University of Helsinki, Helsinki, Finland.
    Myhr, Kjell-Morten
    Department of Clinical Medicine, University of Bergen, Bergen, Norway.
    Mehtälä, Juha
    StatFinn EPID Research, Espoo, Finland.
    Bahmanyar, Shahram
    Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK.
    Korhonen, Pasi
    StatFinn EPID Research, Espoo, Finland.
    Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden2020In: Therapeutic advances in neurological disorders, ISSN 1756-2856, Vol. 13, article id 1756286420951072Article in journal (Refereed)
    Abstract [en]

    Background: Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD).

    Methods: This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity.

    Results: Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78).

    Conclusion: In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

  • 134. Halfvarson, Jonas
    et al.
    Jess, Tine
    Magnuson, Anders
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Orholm, Marianne
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Binder, Vibeke
    Järnerot, Gunnar
    Environmental factors in inflammatory bowel disease: a co-twin control study of a Swedish-Danish twin population2006In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 12, no 10, p. 925-933Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method.

    SUBJECTS AND METHODS:

    A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups.

    RESULTS:

    The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1).

    CONCLUSIONS:

    The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

  • 135. Hildebrand, Hans
    et al.
    Malmborg, Petter
    Askling, Johan
    Ekbom, Anders
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 8, p. 961-966Article in journal (Refereed)
    Abstract [en]

    Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease.

    Material and methods. Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data.

    Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04–7.21) and 4.94 (1.83–13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease.

    Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.

  • 136.
    Hildon, Zoe
    et al.
    Department of Clinical, Educational and Health Psychology, Centre for Outcomes Research and Effectiveness, University College Londone, London, United Kingdom.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences. Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden; Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Blane, David
    Department of Clinical, Educational and Health Psychology, Centre for Outcomes Research and Effectiveness, University College London, London, United Kingdom.
    Wiggins, Richard D.
    Social Science Research Unit, Institute of Education, University of London, London, United Kingdom.
    Netuveli, Gopalakrishnan
    Department of Primary Care and Social Medicine, Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom.
    Examining resilience of quality of life in the face of health-related and psychosocial adversity at older ages: what is "right" about the way we age?2010In: The Gerontologist, ISSN 0016-9013, E-ISSN 1758-5341, Vol. 50, no 1, p. 36-47Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This article examines resilience at older ages, focusing on the relationships between quality of life (qol) and adversity. Our objectives are to identify (a) the basis of adversity, (b) the characteristics of resilient individuals, and (c) the attributes that attenuate the full impact of adversity. DESIGN AND METHODS: Resilience is defined as flourishing despite adversity. Analysis is carried out in a subsample of the Boyd Orr cohort (aged between 68 and 82 years) using questionnaire data. Adversity was identified as circumstances that produce a significant average decrease in qol (CASP-19 scores). Participants were classified into resilient and vulnerable groups based on high or low qol (CASP-19 scores dichotomized at the median) in the face of significant adversity. Shared characteristics that define these outcomes are reported. Attributes that attenuate the negative impact of adversity were analyzed using stratified logistic regression. RESULTS: Adversity was typified by functional limitation; life getting worse in the domains of health, stress, and general living circumstances; and experiencing a negative life event. The resilient tended to report fewer multiple adversities. Indicators of protective attributes, which also characterized resilient outcomes relative to qol, included good quality relationships (5.105, confidence interval [CI] 95% 1.323-19.699), integration in the community (10.800, 95% CI 1.227-95.014), developmental coping (3.397, 95% CI 1.079-10.690), and adaptive coping styles (3.211, 95% CI 1.041-9.910). IMPLICATION: Overall results indicate that policies that offer access to protection and help minimize adversity exposure where possible will promote resilience.

  • 137.
    Hildén, Karin
    et al.
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Schwarcz, E.
    Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hanson, U.
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Faculty of Medicine, Health Örebro University, Örebro, Sweden.
    Simmons, D.
    Faculty of Medicine, Health Örebro University, Örebro, Sweden; School of Medicine, Western Sydney University, Campbelltown, Australia.
    Backman, Helena
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Obstetrics and Gynaecology.
    Previous pre-eclampsia, gestational diabetes mellitus and the risk of cardiovascular disease: A nested case-control study in Sweden2023In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 130, no 10, p. 1209-1216Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Pre-eclampsia and gestational diabetes mellitus (GDM) are two common pregnancy complications that affect birth outcomes and are associated with a long-term risk of cardiovascular disease (CVD). The aims of this study were to investigate if the pre-eclampsia association with CVD is independent of GDM and modified by body mass index (BMI) or GDM. DESIGN: Case-control study.

    SETTING: Sweden.

    POPULATION: Cases were women with a first CVD event between 1991 and 2008 and a previous pregnancy who were matched with controls without CVD (1:5) by year of birth, age and region of birth. METHODS: Conditional logistic regression was used to evaluate the associations of GDM, pre-eclampsia and maternal BMI with CVD adjusted for potential confounders and effect modifications with interaction tests.

    MAIN OUTCOME MEASURES: CVD.

    RESULTS: There were 2639 cases and 13 310 controls with complete data. Pre-eclampsia and GDM were independent risk factors for CVD (adjusted odds ratio [aOR] 2.59, 95% CI 2.12-3.17 and aOR 1.47, 95% CI 1.04-2.09, respectively). After stratifying by maternal BMI, the adjusted association of pre-eclampsia with CVD did not differ notably between BMI groups: normal weight (aOR 2.65, 95% CI 1.90-3.69), overweight (aOR 2.67, 95% CI 1.52-4.68) and obesity (aOR 3.03, 95% CI 0.74-12.4). Similar findings were seen when stratifying on GDM/non-GDM.

    CONCLUSIONS: Pre-eclampsia and GDM are independent risk factors for later CVD and having both during pregnancy is a major risk factor for later CVD. The association between pre-eclampsia and CVD is not modified by BMI. Effective CVD preventive programs for high-risk women are urgently needed in order to improve women's long-term health.

  • 138.
    Hildén, Karin
    et al.
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynaecology.
    Magnuson, A.
    Clinical Epidemiology and Biostatistics, Örebro University Hosptial, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
    Schwarcz, E.
    Department of Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Hanson, U.
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden .
    Simmons, David
    Örebro University, School of Medical Sciences. School of Medicine, Western Sydney University, Campbelltown New South Wales, Australia.
    Fadl, Helena
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Obstetrics and Gynaecology.
    Cardiovascular disease among women with previous preeclampsia and/or gestational diabetes mellitus: a national case control studyManuscript (preprint) (Other academic)
  • 139.
    Hildén, Karin
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Obstetrics and Gynaecology.
    Simmons, David
    School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
    Hanson, Ulf
    Uppsala Universitet Institutionen for kvinnors och barns halsa, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, Örebro University Faculty of Medicine and Health, Örebro, Sweden.
    Magnuson, Anders
    School of Health Medical Sciences, Örebro University Faculty of Medicine and Health, Örebro, Sweden.
    Schwarcz, Erik
    Department of Internal Medicine, Faculty of Medicine and Health, Örebro Universitet, Örebro, Sweden.
    Backman, Helena
    Örebro University, School of Health Sciences. Obstetrics and Gynaecology, Örebro University, Örebro, Sweden.
    Author reply2024In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528Article in journal (Other academic)
  • 140.
    Hillert, J.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Bove, R.
    University of California, San Francisco, United States.
    Haddad, L. B.
    Population Council, Center for Biomedical Research, New York, United States.
    Hellwig, K.
    Katholisches Klinikum Bochum gGmbH, Nordrhein-Westfalen, Germany.
    Houtchens, M.
    Harvard Medical School and Brigham and Women’s Hospital, Boston, United States.
    Magyari, M.
    Danish Multiple Sclerosis Center, Copenhagen, Denmark.
    Merki-Feld, G. S.
    Clinic of Reproductive Endocrinology, University Hospital Zürich, Zürich, Switzerland.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Nappi, R. E.
    Research Center of Reproductive Medicine, IRCCS San Matteo Foundation, Pavia, Italy; University of Pavia, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Pavia, Italy.
    Stenager, E.
    University of Southern Denmark, Department of Regional Research, Odense, Denmark; MS-clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding), Jutland, Denmark.
    Thompson, H.
    Southern Health & Social Care Trust, Portadown, United Kingdom.
    Tulek, Z.
    Istanbul University-Cerrahpaşa, Florence Nightingale Faculty of Nursing, Istanbul, Turkey.
    Di Cantogno, E. Verdun
    EMD Serono Research & Development Institute (an affiliate of Merck KGaA), Billerica, United States.
    Simoni, M.
    University of Modena and Reggio Emilia, Unit of Endocrinology, Department of Medical Specialties, University Hospital and Department of Biomedical, Metabolic and Neural Sciences, Modena, Italy.
    Expert opinion on the use of contraception in people with multiple sclerosis2022In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, no Suppl. 3, p. 187-188, article id P080Article in journal (Other academic)
    Abstract [en]

    Introduction: The most appropriate use, type, and timing of contraception in people with multiple sclerosis (PwMS) is poorly understood, and specific guidance is absent.

    Aims  and  Objectives: To  provide  insight  into  potential  clinical  guidelines for the use of contraception by PwMS through development  of  recommendations  by a  consensus-based  program  led  by international clinical experts.

    Methods:  A  multidisciplinary  steering  committee  (SC)  of  13  international expert healthcare professionals (HCPs) identified 15 key clinical questions on the use of contraception in PwMS, which addressed issues relating to patient-centred care, selection of contraception for PwMS, and time needed to use contraception since the last dose of disease modifying therapies (DMTs). Twenty-five clinical recommendations  addressing  the  questions  were  drafted  using evidence obtained from a comprehensive systematic literature  review  combined  with expert  opinion  from  the  SC.  An  extended faculty of 32 HCPs from 18 countries including a patient association representative, and the SC members (n=12), voted on the   recommendations.   Consensus   on   recommendations   was   achieved when  ⩾75%  of  respondents  expressed  an  agreement  score of 7–9, on a 9-point scale.

    Results: Overall, consensus was achieved on 24 out of 25 clinical recommendations. In detail, consensus in the range of 90–100% was  achieved on 11  recommendations,  12  recommendations  achieved  80–89%  consensus,  and 1  recommendation  achieved  75–79%  consensus  (n=44).  The  strength  of recommendations  ranged from 7–9. The one statement failing to achieve consensus scored 74.1%. Clinical recommendations are provided on the process of prescribing contraception for PwMS, including the recommended types of HCPs involved and optimal topics to discuss; the range of contraceptive options and the key considerations involved in selecting an appropriate method of contraception; and the timing of starting and stopping contraception in relation to the use of DMTs.

    Conclusions: These  expert  recommendations  were  based  on  a  robust consensus approach, providing timely and practical guidance on the use of contraception for HCPs treating PwMS and will form the basis of further publications and clinical tools.

  • 141.
    Hillert, Jan
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bove, Riley
    UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
    Haddad, Lisa B.
    Center for Biomedical Research, Population Council, New York, NY, USA.
    Hellwig, Kerstin
    Katholisches Klinikum Bochum GmbH, Nordrhein-Westfalen, Bochum, Germany.
    Houtchens, Maria
    Brigham and Women's Hospital, Boston, MA, USA/ Harvard Medical School, Boston, MA, USA.
    Magyari, Melinda
    Danish Multiple Sclerosis Center, University Hospital Boston, MA, USA/ Rigshospitalet, Copenhagen, Denmark.
    Merki-Feld, Gabriele S.
    Clinic of Reproductive Endocrinology, University Hospital Zürich, Zürich, Switzerland.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nappi, Rossella E.
    Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy; Research Center of Reproductive Medicine, IRCCS San Matteo Foundation, Pavia, Italy.
    Stenager, Egon
    Department of Regional Research, University of Southern Denmark, Odense, Denmark; MS-Clinic of Southern Jutland (Aabenraa, Esbjerg, Kolding), Sønderborg, Denmark.
    Thompson, Heidi
    Southern Health & Social Care Trust, Portadown, Northern Ireland.
    Tulek, Zeliha
    Istanbul University-Cerrahpasa, Florence Nightingale Faculty of Nursing, Istanbul University-Cerrahpasa, Istanbul, Turkey.
    Verdun Di Cantogno, Elisabetta
    EMD Serono Research & Development Institute, Inc., Billerica, MA, USA.
    Simoni, Manuela
    Unit of Endocrinology, Department of Medical Specialties, University Hospital and Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
    Expert opinion on the use of contraception in people with multiple sclerosis2024In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, article id 13524585241228103Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking.

    OBJECTIVE: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS).

    METHODS: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation.

    RESULTS: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs.

    CONCLUSION: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.

  • 142.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences. Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
    Berg, Lisa
    Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Centre for Health Equity Studies, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Saarela, Jan
    Demography Unit, Åbo Akademi University, Vaasa, Finland.
    Fall, Katja
    Örebro University, School of Medical Sciences. Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Grotta, Alessandra
    Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Centre for Health Equity Studies, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Shebehe, Jacques
    Örebro University, School of Medical Sciences.
    Kawachi, Ichiro
    Harvard TH Chan School of Public Health, Boston, MA, USA.
    Rostila, Mikael
    Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Centre for Health Equity Studies, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Department of Epidemiology and Public Health, University College London, London, UK; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Substance use disorder and suicide-related behaviour around dates of parental death and its anniversaries: a register-based cohort study2022In: The Lancet Public Health, ISSN 2468-2667, Vol. 7, no 8, p. e683-e693Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Parental death and its anniversaries, including anticipation of these dates, might cause distress and increase the risk of substance use disorder and suicide-related behaviour in bereaved adolescents and young adults. We examined whether the risk of substance use disorder and suicide-related behaviour increases around the date of parental death and subsequent anniversaries.

    METHODS: Using Swedish national registers, we conducted a cohort study of individuals aged 12-24 years. We included individuals aged 12-24 years between Jan 1, 2001, and Dec 31, 2014, whose parents were alive at entry (n=1 858 327) and followed up with them until the end of age 24 years. We excluded individuals with a half-sibling, a history of emigration, a previous record of the outcome events, a parental death before study entry, two parental deaths on the same day during the follow-up, or missing data for relevant variables. Follow-up ended on the day of an outcome event or on Dec 31, 2014; at age 25 years, emigration, or death; or a year before the second parental death. We studied substance use disorder and suicide-related behaviour outcomes separately and included non-fatal and fatal events in both outcomes. We used Cox regression to estimate hazard ratios (HRs), controlling for baseline psychiatric, demographic, and socioeconomic characteristics. Parental death was modelled as a time-varying exposure over 72 monthly periods, starting from 1 year before the parental death to the fifth year and later after the death. Unmeasured confounding was also addressed in within-individual comparisons using a case-crossover design.

    FINDINGS: During follow-up (median 7·5 [IQR 4·3-10·6] years), there were 42 854 substance use disorder events, with a crude rate of 3·1 per 1000 person-years. For suicide-related behaviour, there were 19 827 events, with a crude rate of 1·4 per 1000 person-years. Most of the events studied were non-fatal. In the month of parental death, the HR for substance use disorder risk was 1·89 (95% CI 1·07-3·33) among male participants, and, for suicide-related behaviour, was 3·76 (1·79-7·89) among male participants and 2·90 (1·61-5·24) among female participants. In male participants, there was an increased risk around the first anniversary (substance use disorder: HR 2·64 [95% CI 1·56-4·46] during the anniversary month; 2·21 [1·25-3·89] for the subsequent month; and for suicide-related behaviour: 3·18 [1·32-7·66] for the subsequent month). Among female participants, an increased risk of substance use disorder recurred around every year consistently in the month before the anniversary of the death and there was an increased risk for suicide-related behaviour in the months of the first and second anniversaries.

    INTERPRETATION: Although effect sizes were large in this cohort study, the number of individuals who had the outcomes was small. Nevertheless, adolescents and young adults, especially women and girls, who had the death of a parent showed increased risk of substance use disorder and suicide-related behaviour around the first few death anniversaries. Adolescents and young adults, especially women and girls, who had the death of a parent could benefit from preventive measures to reduce distress around the first few years of death anniversaries.

  • 143.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bergh, Cecilia
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Comorbidity trajectories in working age cancer survivors: A national study of Swedish men2017In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 48, p. 48-55, article id S1877-7821(17)30039-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A large proportion of cancer survivors are of working age, and maintaining health is of interest both for their working and private life. However, patterns and determinants of comorbidity over time among adult cancer survivors are incompletely described. We aimed to identify distinct comorbidity trajectories and their potential determinants.

    METHODS: In a cohort study of Swedish men born between 1952 and 1956, men diagnosed with cancer between 2000 and 2003 (n=878) were matched with cancer-free men (n=4340) and followed over five years after their first year of survival. Comorbid diseases were identified using hospital diagnoses and included in the analysis using group-based trajectory modelling. The association of socioeconomic and developmental characteristics were assessed using multinomial logit models.

    RESULTS: Four distinct comorbidity trajectories were identified. As many as 84% of cancer survivors remained at very low levels of comorbidity, and the distribution of trajectories was similar among the cancer survivors and the cancer-free men. Increases in comorbidity were seen among those who had comorbid disease at baseline and among those with poor summary disease scores in adolescence. Socioeconomic characteristics and physical, cognitive and psychological function were associated with types of trajectory in unadjusted models but did not retain independent relationships with them after simultaneous adjustment.

    CONCLUSIONS: Among working-age male cancer survivors, the majority remained free or had very low levels of comorbidity. Those with poorer health in adolescence and pre-existing comorbid diseases at cancer diagnosis may, however, benefit from follow-up to prevent further increases in comorbidity.

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    Comorbidity trajectories in working age cancer survivors: a national study of Swedish men
  • 144.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Netuveli, G.
    International Centre for Life Course Studies in Society and Health, University College London, London, United Kingdom: Institute for Health and Human Development (IHHD), University of East London, London, United Kingdom.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Remarriage after divorce and depression risk2015In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 141, p. 109-114Article in journal (Refereed)
    Abstract [en]

    As marriage is associated with lower depression rates compared with being single in men, we aimed to examine if remarriage compared with remaining divorced is also associated with a reduced depression risk. Swedish register data were used to define a cohort of men who were born between 1952 and 1956 and underwent a compulsory military conscription assessment in adolescence. This study population comprised men who were divorced in 1985 (n = 72,246). The risk of pharmaceutically treated depression from 2005 to 2009 was compared for those who remarried or remained divorced between 1986 and 2004. Cox proportional hazards analysis was used to estimate hazard ratios for the risk of depression identified by pharmaceutical treatment, with adjustment for a range of potential confounding factors including childhood and adulthood socioeconomic circumstances, cognitive, physical, psychological and medical characteristics at the conscription assessment. The results showed that, even though divorced men who remarried had markers of lower depression risk in earlier life such as higher cognitive and physical function, higher stress resilience and socioeconomic advantages than men who remained divorced, remarriage was associated with a statistically significant elevated risk of depression with an adjusted hazard ratio (and 95% confidence interval) of 1.27(1.03 1.55), compared with men who remained divorced. Remarriage following divorce is not associated with a reduced risk of depression identified by pharmaceutical treatment, compared with remaining divorced. Interpersonal or financial difficulties resulting from remarriage may outweigh the benefits of marriage in terms of depression risk.

  • 145.
    Hiyoshi, Ayako
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Örebro University, Sweden; University College London, United Kingdom.
    Hawkes, Christopher H.
    Neffendorf, James E.
    Olsson, Tomas
    Giovannoni, Gavin
    Montgomery, Scott
    Myopia in late adolescence and subsequent multiple sclerosis among men2023In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 71, article id 104577Article in journal (Refereed)
    Abstract [en]

    Background: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS.

    Methods: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969–1997 and 1997–2010.

    Results: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997–2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969–1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]).

    Conclusion: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

  • 146.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Public Health Sciences, Stockholm University, Stockholm SE-106 91, Sweden; Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 7HB, United Kingdom.
    Hawkes, Christopher H.
    Neuroimmunology Unit, Blizard Institute, Queen Mary, University of London, UK.
    Neffendorf, James E.
    Department of Ophthalmology, King's College Hospital, London SE5 9RS, UK.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 171 77, Sweden.
    Giovannoni, Gavin
    Neuroimmunology Unit, Blizard Institute, Queen Mary, University of London, UK.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 7HB, United Kingdom; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
    Myopia in late adolescence and subsequent multiple sclerosis among men2023In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 71, article id 104577Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS.

    METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010.

    RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]).

    CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

  • 147.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Bottai, Matteo
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Hoven, Emma I.
    Division of Childhood Cancer Research, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Trajectories of Income and Social Benefits for Mothers and Fathers of Children With Cancer: A National Cohort Study in Sweden2018In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 124, no 7, p. 1492-1500Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The contribution of different income sources from work and social benefits to trajectories of income for the parents of children with cancer has not been empirically investigated.

    METHODS: Using Swedish registers, parents of children with an incidence cancer diagnosis between 2004 and 2009 were identified and matched with parents of children without cancer (reference parents). A total of 20,091 families were followed from the year before the diagnosis to a maximum of 8 years. Generalized linear models estimated the ratios of mean incomes from work and social benefits and of its total.

    RESULTS: Around the time of the child's cancer diagnosis, the total income was on average up to 6% higher among the mothers of children with cancer compared with reference mothers, but no differences were noted among fathers. Income from work dropped to the lowest level around the time of a cancer diagnosis, with swift recovery noted for fathers but not for mothers. Sickness and childcare-related benefits were up to 6 times larger for the parents of children with cancer than reference parents. As social benefits diminished after approximately 3 years, the total income of mothers of children with cancer became lower than that of reference mothers, and the gap widened over time.

    CONCLUSIONS: Social benefits appeared to ease the financial burden during the years around a cancer diagnosis. However, mothers experienced persistently lower income after benefits diminished. Experiences differed by single-parent versus dual-parent households, the survival of the child with cancer, and other relevant characteristics. Further investigation is needed for potential long-term consequences for mothers, including their career and future pension in retirement.

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    Trajectories of income and social benefits for mothers and fathers of children with cancer: a national cohort study in Sweden
  • 148.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
    Rostila, Mikael
    Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Centre for Health Equity Studies, Stockholm University/Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, UK; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Grotta, Alessandra
    Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; Centre for Health Equity Studies, Stockholm University/Karolinska Institutet, Stockholm, Sweden.
    Caregiving and changes in health-related behaviour2023In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 322, article id 115830Article in journal (Refereed)
    Abstract [en]

    Potential health risks for informal caregivers have been hypothesised to be partly related to adverse changes in health-related behaviour, but evidence is limited. We examined whether smoking, drinking, eating, physical activity or leisure pursuits change in relation to co-resident or out-of-home caregiving (for someone outside the household), and if associations differ by sex, educational attainment, and welfare state typology. We conducted a longitudinal study using six waves of the Survey of Health, Ageing and Retirement in Europe, collecting data repeatedly from 2004 to 2017 for adults aged 50 years and older living in 17 European countries (57,962 individuals). To control for measured and unmeasured within-individual time-invariant confounders, we used fixed effects logistic models to analyse the repeated measures of caregiving, behaviour and covariates and estimated odds ratios (OR) with 95% confidence intervals (95%CI). Among male participants, unhealthy eating increased while smoking decreased [ORs 1.26 (95%CI 1.01-1.58) and 0.53 (0.36-0.78), respectively] in survey waves in which they provided co-resident care, compared with the waves that they did not. Among female participants, there was little change in behaviour between waves with and without co-resident caregiving. When providing out-of-home care, lacks of physical activity and leisure pursuits declined. But in the same time, drinking increased both men and women, and especially among individuals with lower educational attainment and residing in non-Nordic countries. To conclude, overall, increased drinking when providing out-of-home care was most consistent, especially among individuals with lower educational attainment and residing in non-Nordic countries. Otherwise, the associations varied by the type of care, behaviour and population subgroups. These findings indicated that not all caregivers are susceptible to behavioural changes, and that not all behaviour may be involved similarly in linking caregiving to health risks. This opens possibilities to target specific behaviour and groups to prevent adverse changes in health behaviour in caregivers.

  • 149.
    Hiyoshi, Ayako
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Örebro University, Sweden; University College London, UK; Osaka University Graduate School of Medicine, Japan.
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    Fall, Katja
    Montgomery, Scott
    Grotta, Alessandra
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    Caregiving and changes in health-related behaviour2023In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 322, article id 115830Article in journal (Refereed)
    Abstract [en]

    Potential health risks for informal caregivers have been hypothesised to be partly related to adverse changes in health-related behaviour, but evidence is limited. We examined whether smoking, drinking, eating, physical activity or leisure pursuits change in relation to co-resident or out-of-home caregiving (for someone outside the household), and if associations differ by sex, educational attainment, and welfare state typology. We conducted a longitudinal study using six waves of the Survey of Health, Ageing and Retirement in Europe, collecting data repeatedly from 2004 to 2017 for adults aged 50 years and older living in 17 European countries (57,962 individuals). To control for measured and unmeasured within-individual time-invariant confounders, we used fixed effects logistic models to analyse the repeated measures of caregiving, behaviour and covariates and estimated odds ratios (OR) with 95% confidence intervals (95%CI). Among male participants, unhealthy eating increased while smoking decreased [ORs 1.26 (95%CI 1.01–1.58) and 0.53 (0.36–0.78), respectively] in survey waves in which they provided co-resident care, compared with the waves that they did not. Among female participants, there was little change in behaviour between waves with and without co-resident caregiving. When providing out-of-home care, lacks of physical activity and leisure pursuits declined. But in the same time, drinking increased both men and women, and especially among individuals with lower educational attainment and residing in non-Nordic countries. To conclude, overall, increased drinking when providing out-of-home care was most consistent, especially among individuals with lower educational attainment and residing in non-Nordic countries. Otherwise, the associations varied by the type of care, behaviour and population subgroups. These findings indicated that not all caregivers are susceptible to behavioural changes, and that not all behaviour may be involved similarly in linking caregiving to health risks. This opens possibilities to target specific behaviour and groups to prevent adverse changes in health behaviour in caregivers.

  • 150.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences.
    Sabet, Julia A.
    Örebro University, School of Medical Sciences.
    Sjöqvist, Hugo
    Örebro University, Örebro University School of Business.
    Melinder, Carren
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK .
    Precursors in adolescence of adult-onset bipolar disorder2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 218, p. 353-358Article in journal (Refereed)
    Abstract [en]

    Background: Although the estimated contribution of genetic factors is high in bipolar disorder, environmental factors may also play a role. This Swedish register-based cohort study of men examined if physical and psychological characteristics in late adolescence, including factors previously linked with bipolar disorder (body mass index, asthma and allergy), are associated with subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are analysed as additional outcomes to identify bipolar disorder-specific associations.

    Methods: A total of 213,693 men born between 1952 and 1956, who participated in compulsory military conscription assessments in late adolescence were followed up to 2009, excluding men with any psychiatric diagnoses at baseline. Cox regression estimated risk of bipolar disorder, depression and anxiety in adulthood associated with body mass index, asthma, allergy, muscular strength stress resilience and cognitive function in adolescence.

    Results: BMI, asthma and allergy were not associated with bipolar disorder. Higher grip strength, cognitive function and stress resilience were associated with a reduced risk of bipolar disorder and the other disease outcomes.

    Limitations: The sample consisted only of men; even though the characteristics in adolescence pre-dated disease onset, they may have been the consequence of prodromal disease.

    Conclusions: Associations with body mass index and asthma found by previous studies may be consequences of bipolar disorder or its treatment rather than risk factors. Inverse associations with all the outcome diagnoses for stress resilience, muscular strength and cognitive function may reflect general risks for these psychiatric disorders or intermediary factors.

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