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  • 1.
    Al Dabbagh, Z.
    et al.
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Jansson, K. Å.
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Stiller, C. O.
    Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Weiss, R. J.
    Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Long-term pattern of opioid prescriptions after femoral shaft fractures2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 5, p. 634-641Article in journal (Refereed)
    Abstract [en]

    Background: The use of opioids in non-cancer-related pain following skeletal trauma is controversial due to the presumed risk of dose escalation and dependence. We therefore examined the pattern of opioid prescriptions, that is, those actually dispensed, in patients with femoral shaft fractures.

    Methods: We analysed data from the Swedish National Hospital Discharge Register and the Swedish Prescribed Drug Register between 2005 and 2008.

    Results: We identified 1471 patients with isolated femoral shaft fractures. The median age was 75 (16-102) years and 56% were female. In this cohort, 891 patients (61%) received dispensed opioid prescriptions during a median follow-up of 20 months (interquartile range 11-32). In the age- and sex-matched comparison cohort (7339 individuals) without fracture, 25% had opioid prescriptions dispensed during the same period. The proportions of patients receiving opioid analgesics at 6 and 12 months after the fracture were 45% (95% CI 42-49) and 36% (32-39), respectively. The median daily morphine equivalent dose (MED) was between 15 and 17 mg 1-12 months post-fracture. After 3 months, less than 5% used prescription doses higher than 20 mg MED per day. Older age (≥ 70 compared with < 70 years) was a significant predictor of earlier discontinuation of opioid use (Hazard ratio [HR] 1.9).

    Conclusion: A notable proportion of patients continued to receive dispensed prescriptions for opioids for over 6 months (45%) and more than a third of them (36%) continued treatment for at least 12 months. However, the risk of dose escalation seems to be small in opioid-naïve patients.

  • 2.
    Al Dabbagh, Zewar
    et al.
    Dept Mol Med & Surg, Sect Orthopaed & Sports Med, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
    Jansson, Karl-Åke
    Dept Mol Med & Surg, Sect Orthopaed & Sports Med, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
    Stiller, Carl-Olav
    Dept Med, Clin Pharmacol Unit, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Med, Clin Epidemiol Unit, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden; Dept Epidemiol & Publ Hlth, University College London (UCL), London, England .
    Weiss, Rudiger J.
    Dept Mol Med & Surg, Sect Orthopaed & Sports Med, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
    No signs of dose escalations of potent opioids prescribed after tibial shaft fractures: a study of Swedish National Registries2014In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 14, p. 4-Article in journal (Refereed)
    Abstract [en]

    Background: The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures.

    Methods: Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005-2008.

    Results: We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7-27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16-97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17-24) and 14% (11-17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations.

    Conclusions: We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures.

  • 3. Ali, Magdi M. M.
    et al.
    ElGhazali, Gehad
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Farouk, Salah E.
    Nasr, Amre
    Noori, Suzan I. A.
    Shamad, Mahdi M.
    Fadlelseed, Omar E.
    Berzins, Klavs
    Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease: implications for the development of severe reactive onchodermatitis (ROD)2007In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 77, no 6, p. 1074-8Article in journal (Refereed)
    Abstract [en]

    The pathologic manifestations of Onchocerca volvulus infection depend on the interplay between the host and the parasite. A genetic single nucleotide polymorphism in the Fc gamma RIIa gene, resulting in arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses and may influence the clinical variations seen in onchocerciasis. This study investigated the relationship between this polymorphism and disease outcome. Fc gamma RIIa genotyping was performed on clinically characterized onchocerciasis patients (N = 100) and healthy controls (N = 74). Fc gamma RIIa genotype R/R131 frequencies were significantly higher among patients with severe dermatopathology (P < 0.001). Increased risk of developing this form was mostly associated with one tribe (Masalit) (OR = 3.2, 95% CI 1-9.9, P = 0.042). The H131 allele was found to be significantly associated with a reduced risk of having the severe form of the disease (adjusted OR = 0.26, 95% CI = 0.13-0.46, P < 0.001). Our findings suggest that the polymorphism influences the clinical outcome of onchocerciasis.

  • 4. Amoudruz, Petra
    et al.
    Holmlund, Ulrika
    Schollin, Jens
    Örebro University, School of Health and Medical Sciences.
    Sverremark-Ekström, Eva
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Maternal country of birth and previous pregnancies are associated with breast milk characteristics2009In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 20, no 1, p. 19-29Article in journal (Refereed)
    Abstract [en]

    Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

  • 5. Bahmanyar, S.
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Hillert, J.
    Ekbom, A.
    Olsson, T.
    Cancer risk among patients with multiple sclerosis and their parents2009In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 72, no 13, p. 1170-1177Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

  • 6.
    Bahmanyar, Shahram
    et al.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
    Askling, Johan
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
    Johannesson, Marie
    Department, Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden; Department of Primary Care and Social Medicine, Charing Cross Hospital, Imperial College, London, United Kingdom.
    Cystic fibrosis gene mutations and gastrointestinal diseases2010In: Journal of Cystic Fibrosis, ISSN 1569-1993, E-ISSN 1873-5010, Vol. 9, no 4, p. 288-291Article in journal (Refereed)
    Abstract [en]

    Background: This study examined if CF mutation heterozygosity is associated with diseases of gastrointestinal epithelial barrier function. Design and methods: Swedish registers identified 865 patients with a diagnosis of CF between 1968 and 2003 and matched with 8101 individuals without CF. Gastrointestinal disease risk was examined among 1534 biological parents and 1396 siblings of CF patients, compared with 15,526 parents and 15,542 siblings of individuals without CF. Results: First-degree relatives of CF patients were not at lower risk of the gastrointestinal diseases, in contrast with a raised risk among CF patients. Conclusion: Heterozygosity for CF gene mutations does not protect against gastrointestinal diseases where impaired barrier function may be relevant. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  • 7. Bahmanyar, Shahram
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Weiss, Rüdiger J.
    Ekbom, Anders
    Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calvé-Perthes disease2008In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 122, no 2, p. e459-e464Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The causes of Legg-Calvé-Perthes disease are largely unknown, but this pediatric disease seems to result from interruption of the blood supply to the proximal femur and is considered a vascular disease. Because maternal smoking during pregnancy influences fetal development and is associated with cardiovascular diseases in offspring, we hypothesized that this exposure is a risk for Legg-Calvé-Perthes disease and also investigated other markers of impaired fetal development and early-life exposures.

    MATERIALS AND METHODS: The Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg-Calvé-Perthes disease from 1983 to 2005, individually matched by year of birth, age, sex, and region of residence with 4432 randomly selected control subjects. Linkage with the Swedish Medical Birth Register provided information on prenatal factors, including maternal smoking. Conditional logistic regression examined associations of maternal smoking during pregnancy and the other measures with the risk of Legg-Calvé-Perthes disease in offspring, adjusted for socioeconomic index and other potential confounding factors.

    RESULTS: Maternal smoking during pregnancy was associated with an increased Legg-Calvé-Perthes disease risk, and heavy smoking was associated with a risk increase of almost 100%. Very low birth weight and cesarean section were independently associated with approximately 240% and 36% increases in the risk of Legg-Calvé-Perthes disease, respectively.

    CONCLUSION: Maternal smoking during pregnancy and other factors indicated by impaired fetal development may be associated with an increased risk of Legg-Calvé-Perthes disease. 

  • 8. Bereczky, S.
    et al.
    Dolo, A.
    Maiga, B.
    Hayano, M.
    Granath, F.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Daou, M.
    Arama, C.
    Troye-Blomberg, M.
    Doumbo, O. K.
    Färnert, A.
    Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa2006In: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 100, no 3, p. 248-257Article in journal (Refereed)
    Abstract [en]

    The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2–9 years were 75% in the Fulani and 44% in the Dogon (P < 0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P = 0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65–8.15, P = 0.003), but not found in the Fulani, 1.36 (95% CI 0.53–3.48, P = 0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.

  • 9. Bereczky, Sándor
    et al.
    Liljander, Anne
    Rooth, Ingegerd
    Faraja, Lea
    Granath, Fredrik
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Färnert, Anna
    Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population2007In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 9, no 1, p. 103-110Article in journal (Refereed)
    Abstract [en]

    Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.

  • 10.
    Bergh, Cecilia
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Sjöqvist, Hugo
    Örebro University, Örebro University School of Business.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    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.
    Severe infections and subsequent delayed cardiovascular disease2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 18, p. 1958-1966Article in journal (Refereed)
    Abstract [en]

    Background: Severe infections in adulthood are associated with subsequent short-term cardiovascular disease. Whether hospital admission for sepsis or pneumonia is associated with persistent increased risk (over a year after infection) is less well established.

    Design: The design of this study was as a register-based cohort study.

    Methods: Some 236,739 men born between 1952-1956 were followed from conscription assessments in adolescence to 2010. All-cause cardiovascular disease ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n = 3438), was identified through national registers 1970-2010 (at ages 18-58 years).

    Results: Sepsis or pneumonia in adulthood (resulting in hospital admission) are associated with increased risk of cardiovascular disease in the years following infection. The risk is highest during the first year after the infection, with an adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the second and 2.12 (1.71-2.62) for the third year after infection. The risk attenuated with time, but remained raised for at least five years after infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in childhood, cardiovascular risk factors and medical history in adolescence. Similar statistically significant associations were found for coronary heart disease and stroke.

    Conclusions: Raised risks of cardiovascular disease following hospital admission for sepsis or pneumonia were increased for more than five years after the infection, but with the highest magnitude during the first three years following infection, suggesting a period of vulnerability when health professionals and patients should be aware of the heightened risk for cardiovascular disease.

  • 11.
    Bergh, Cecilia
    et al.
    Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Appelros, Peter
    Department of Neurology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    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, United Kingdom.
    Determinants in adolescence of stroke-related hospital stay duration in men: a national cohort study2016In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 47, no 9, p. 2416-2418Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.

    Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.

    Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).

    Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.

  • 12.
    Bergh, Cecilia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Almroth, Henrik
    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, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 8, p. 623-629Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.

    METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.

    RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).

    CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.

  • 13.
    Bergh, Cecilia
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    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.
    Pre-stroke characteristics and stroke severity after first stroke in middle-aged men2015In: Nordic Stroke 2015: 18th Nordic Congress of Cerebrovascular Diseases, 2015Conference paper (Refereed)
  • 14.
    Bergh, Cecilia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Physiotherapy, Örebro University Hospital, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nilsagård, Ylva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Appelros, Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Departnment of Epidemiology and Public Health, University College London, London, UK; Cinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Stress resilience in male adolescents and subsequent stroke risk: cohort study2014In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 12, p. 1331-1336Article in journal (Refereed)
    Abstract [en]

    Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.

    Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.

    Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.

    Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.

  • 15. Bergquist, Annika
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Bahmanyar, Shahram
    Olsson, Rolf
    Danielsson, Åke
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Lööf, Lars
    Sandberg-Gertzén, Hanna
    Almer, Sven
    Askling, Johan
    Ehlin, Anna
    Ekbom, Anders
    Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis2008In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 6, no 8, p. 939-943Article in journal (Refereed)
    Abstract [en]

    Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC. 

  • 16. Bergquist, Annika
    et al.
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Lund, Ulrika
    Ekbom, Anders
    Olsson, Rolf
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Broomé, Ulrika
    Perinatal events and the risk of developing primary sclerosing cholangitis2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 37, p. 6037-6040Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether perinatal events, intrauterine or postpartum, are associated with the development of primary sclerosing cholangitis (PSC) later in life.

    METHODS: Birth records from 97 patients with adult PSC in Sweden were reviewed. Information on perinatal events including medications and complications during pregnancy, gestation length, birth weight and length were collected. Two control children of the same sex were selected for each subject. Conditional multiple logistic regression was used to assess associations of the perinatal measures with development of PSC.

    RESULTS: No significant associations were found between gestational age, birth length, breastfeeding, and the majority of medical complications including infections or medication during pregnancy for the mothers or postpartum for the children. Vaginal bleeding and peripheral oedema showed associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and 2.28 (95% CI, 1.04-5.03), respectively.

     

    CONCLUSION: The associations of vaginal bleeding and oedema with subsequent PSC cannot readily be explained, so our findings do not strongly support the hypothesis of a significant role of perinatal events as a risk for the development of PSC later in life.

  • 17.
    Bergsten, Elisabet
    et al.
    Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden; Theme of Children’s and Women’s Health, Karolinska University Hospital, Stockholm, Sweden.
    Horne, AnnaCarin
    Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden; Theme of Children’s and Women’s Health, Karolinska University Hospital, Stockholm, Sweden.
    Aricó, Maurizio
    Direzione Generale, Azienda Sanitaria Provinciale, Ragusa, Italy.
    Astigarraga, Itziar
    Servicio de Pediatria, BioCruces Health Research Institute, Hospital Universitario Cruces, Universidad del Pais Vasco–Euskal Herriko Unibertsitatea (UPV/EHU), Barakaldo, Spain.
    Egeler, R. Maarten
    Division of Hematology & Oncology, The Hospital for Sick Children, Toronto ON, Canada.
    Filipovich, Alexandra H.
    Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati OH, USA.
    Ishii, Eiichi
    Department of Pediatrics, Graduate School of Medicine, Ehime University, Ehime, Japan.
    Janka, Gritta
    Pediatric Hematology and Oncology, University Medical Center Hamburg, Hamburg, Germany.
    Ladisch, Stephan
    Center for Cancer and Immunology Research, Children’s Research Institute, Children’s National Medical Center, Washington DC, USA.
    Lehmberg, Kai
    Pediatric Hematology and Oncology, University Medical Center Hamburg, Hamburg, Germany.
    McClain, Kenneth L.
    Texas Children’s Cancer Center, Baylor College of Medicine, Houston TX, USA.
    Minkov, Milen
    University Clinic of Pediatrics, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria.
    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.
    Nanduri, Vasanta
    Department of Pediatrics, Watford General Hospital, Watford, United Kingdom.
    Rosso, Diego
    Department of Pediatric Hematology and Oncology, Hospital de Niños Dr Pedro De Elizalde, Buenos Aires, Argentina; Department of Pediatrics, Hospital de Clinicas Jose de San Martin, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
    Henter, Jan-Inge
    Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden; Theme of Children’s and Women’s Health, Karolinska University Hospital, Stockholm, Sweden.
    Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study2017In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 130, no 25, p. 2728-2738Article in journal (Refereed)
    Abstract [en]

    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P =020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly.

  • 18. Bhattarai, Achuyt
    et al.
    Ali, Abdullah S.
    Kachur, S. Patrick
    Mårtensson, Andreas
    Abbas, Ali K.
    Khatib, Rashid
    Al-Mafazy, Abdul-Wahiyd
    Ramsan, Mahdi
    Rotllant, Guida
    Gerstenmaier, Jan F.
    Molteni, Fabrizio
    Abdulla, Salim
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Kaneko, Akira
    Björkman, Anders
    Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar2007In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, no 11, p. e309-Article in journal (Refereed)
    Abstract [en]

    Background

    The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.

    Methods and Findings

    Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.

    Conclusions

    Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

  • 19.
    Björk, Tabita
    et al.
    Psychiatric Research Centre, Örebro County Council, Örebro, Sweden; Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Brus, Ole
    Osika, Walter
    Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Primary Care and Public Health, Charing Cross Hospital, Imperial College, London, UK.
    Laterality, hand control and scholastic performance: a British birth cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 2, article id e000314Article in journal (Refereed)
    Abstract [en]

    Objectives: To use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation.

    Design: Analysis of material from a birth cohort study.

    Setting: Members of the National Child Development Study, a British birth cohort study following people born in 1958.

    Participants: 10 612 children who undertook tests at age 11 years.

    Primary outcome measures: Teacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics.

    Results: Linear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of -1.21 (-1.73 to -0.68; p<0.001), -0.72 (-1.14 to -0.29; p=0.001), -0.70 (-1.06 to -0.35; p<0.001) and -1.32 (-1.90 to -0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (-3.01 to -0.80; p=0.001), -1.25 (-2.15 to -0.35; p=0.007), -1.28 (2.04 to -0.53; p=0.001) and -1.33 (-2.53 to -0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function.

    Conclusions: Measures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.

  • 20.
    Blane, David
    et al.
    Imperial College, London, UK.
    Kelly-Irving, Michelle
    INSERM U1027, Toulouse, France.
    d'Errico, Angelo
    University of Torino, Torino, Italy.
    Bartley, Melanie
    University College London, London, UK.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden; Örebro University, Örebro, Sweden.
    Social-biological transitions: how does the social become biological2013In: Longitudinal and life course studies, ISSN 1757-9597, Vol. 4, no 2Article in journal (Refereed)
    Abstract [en]

    The present discussion paper sets forward a model within the life course perspective of how the social becomes biological.  The model is intended to provide a framework for thinking about such questions as how does social class get into the molecules, cells and tissues of the body to produce social class differences in life expectancy and cause of death?  A categorisation of social exposures and biological processes is suggested; and some principles governing their inter-relations proposed.  The paper ends by suggesting two public health applications of this approach.

  • 21. Blane, David
    et al.
    Netuveli, Gopalakrishnan
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Quality of life, health and physiological status and change at older ages2008In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 66, no 7, p. 1579-1587Article in journal (Refereed)
    Abstract [en]

    The relationship between self-reported health status and quality of life at older ages is well established. The present paper investigates this relationship further, using objective measures of health and their change over time in the English Longitudinal Study of Ageing, where positive quality of life at older ages was measured as CASP-19. Cross-sectionally, lung function and obesity, but not blood pressure, were associated with quality of life; these relationships in path analysis were transmitted primarily via functional limitation and more modestly, and only for lung function, via clinical depression. Longitudinally, the results suggest a stable and long-term influence on quality of life of lung function and, among women, body mass index, to which the influence of change may be cumulative; longer follow-up is required to clarify these processes. Overall, the results show that the relationship between health and quality of life is independent of potential psychological confounders, that functional limitation is the key dimension of health in its relationship with quality of life and that clinical depression may be an important mediator between functional limitation and quality of life.

  • 22.
    Brenner, P.
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Burkill, S.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, J.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Umeå University, Umeå, Sweden.
    Hillert, J.
    Division of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, S.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    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, UK.
    Multiple sclerosis and risk of attempted and completed suicide: a cohort study2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 8, p. 1329-1336Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.

    Methods: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.

    Results: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04).

    Conclusion: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.

  • 23.
    Brenner, P.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Burkill, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Umeå University, Umeå, Sweden.
    Moore, A.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Geissbuehler, Y.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medicine, Örebro University, Sweden. DepDepartment of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Multiple sclerosis and risk of completed and attempted suicide - a national cohort study2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no Suppl. 11, p. 23-24Article in journal (Other academic)
    Abstract [en]

    Introduction: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated.

    Objectives: To estimate attempted suicide and completed suicide risks among MS patients using national registers and to assess if the inverse association of higher-level education with completed suicide is affected by MS.

    Methods: A total of 29,617 Swedish MS patients were identified through the Swedish Patient Register and matched (by birth year, sex, vital status at diagnosis and region) with 296,164 people without MS from the general population. Cox regression estimated hazard ratios (HR) (with 95% confidence intervals) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education level, decade of study entry, and previous suicide attempts.

    Results: The adjusted HR for attempted suicide among MS patients is 2.18 (1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (1.53-2.30). Overall, men were at higher risk of completing suicide, while women were at higher risk of attempting suicide. Higher education is inversely associated with completed suicide among the non-MS cohort with an HR of 0.68, (0.51-0.91), but not among MS patients, where the HR is 1.10, (0.60-2.04). MS patients were less likely to use a violent method than the non-MS cohort.

    Conclusion: MS patients are at higher risk of both attempted and completed suicide, and the risk increase is present in both men and women. Possibly the stress and perceived prognosis associated with an MS diagnosis increases the risk of suicide. MS appears to eliminate the protective association of higher education with completed suicide.

  • 24.
    Burkill, Sarah
    et al.
    Centre for Pharmocoepodemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Iacobaeus, Ellen
    Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, Shahram
    Centre for Pharmocoepodemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Brundin, Lou
    Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
    Fored, Michael
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Pharmacological Treatments Preceding Diagnosis Of Progressive Multifocal Leukencephalopathy2016In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 25, no Suppl. 3, p. 496-497Article in journal (Other academic)
    Abstract [en]

    Background: Progressive multifocal leukencephalopathy (PML) is a rare, often fatal viral disease, which affects the white matter of the brain. It is caused by John Cunningham (JC) polyomavirus, which is present in most people and is usually harm-less. For immunocompromised persons, such as those who are taking immunosuppressive treatments, the risk of JC virus causing PML is increased, although still rare. As PML diagnosis is not always accurate, epidemiology of PML, including the true incidence and patient characteristics, is incompletely described.

    Objectives: To identify pharmacological treatments preceding diagnosis of definitive, probable and possible PML, after excluding incorrect PML diagnoses by medical record review.

    Methods: Patients with a PML diagnosis in Sweden between 1988 and 2013 were identified through the Patient register using ICD 9 code 046D and ICD 10code A81.2 (n = 281). Medical records were reviewed and information on clinical characteristics and pharmacological treatments were collected. Each of the diagnoses was determined as definite PML, possible PML, probable PML or non-PML based on the consensus statement for the AAN neuroinfectious disease section published in 2013. (PMCID: 3662270).

    Results: Medical records for 251 patients (89%) were available and examined. In total, 84 (33%) of the 251 PML diagnoses were confirmed. For those with a record of being exposed to immunosuppressant drugs, 60 (65%) of the 92 records were confirmed as being definite PML. Among 12 patients exposed to rituximab 11 (92%) had definite and 1 (8%) had probable PML. For the 9 natalizumab users, 8 (89%) had definite PML and 1 (11%) was diagnosed incorrectly.

    Conclusions: A substantial proportion of PML diagnoses recorded in Sweden are incorrect, however amongst those exposed to immunosuppressants such as rituximab and natalizumab the majority of diagnoses are correct. Assessing immunosuppressive drug history could be an important part of the diagnostic processes for PML.

  • 25.
    Burkill, Sarah M.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Lofling, Lukas
    Karolinska Institutet, Stockholm, Sweden.
    Kockum, Ingrid
    Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Karolinska Institutet, Stockholm, Sweden.
    Strid, Pernilla
    Karolinska Institutet, Stockholm, Sweden.
    Olsson, Tomas
    Karolinska Institutet, Stockholm, Sweden.
    Hillert, Jan
    Karolinska Institutet, Stockholm, Sweden.
    Alfredsson, Lars
    Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, Shahram
    Karolinska Institutet, Stockholm, Sweden.
    Pain and Painkiller Use Among Multiple Sclerosis Patients in Sweden2017In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 26, no Suppl. 2, p. 634-634Article in journal (Other academic)
    Abstract [en]

    Background: Multiple sclerosis is an autoimmune disease which leads to demyelination and subsequent damage of axons and neurons. Pain is known to commonly affect MS patients, however the clinical characteristics of this pain are not fully described. Prescribed pain medication identifies more severe and chronic pain and different drug types can be used to identify other pain characteristics.

    Objectives: To assess whether MS patients in Sweden are at increased risk of receiving medication for pain relative to non-MS comparators. We aim to study overall pain, neuropathic pain, musculoskeletal pain and migraine.

    Methods: This cohort study using data on 5,555 MS patients in Sweden individually matched to 5,555 non-MS Swedish residents on sex, year of birth and place of residence at the time of MS diagnosis. We used Cox PH models using date of entry or 1stJuly 2006 as the beginning of follow up, whichever occurred later, and end of study was date of death, date of prescription of a painkiller or December 31st 2014, whichever occurred first. Painkillers were identified through relevant ATC codes. For neuropathic pain, pregabalin, gabapentin, amitriptyline, capsaicin or nortriptyline were used for identification, and for migraine prescriptions of anti-migraine preparations were included in the outcome. Musculoskeletal pain was identified primarily through topical products for joint and muscular pain.

    Results: Cox PH models showed MS patients to be at a 2.43 (CI 2.31–2.55) times increased risk of being prescribed any painkiller. The risk increased to 5.63 (CI 5.03–6.31) for neuropathic painkillers, however there was no significant difference for musculoskeletal painkillers (RR = 0.92 (CI 0.79–1.07)). MS patients were at a 1.28 (CI 1.10-1.50) times increased risk of being prescribed anti-migraine preparations. Restricting the data to MS patients showed that exposure to neuropathic painkillers was present in 32.8% of MS patients, and is associated with lower educational attainment and female sex.  

    Conclusions: MS patients are at significantly increased risk of pain overall, with a particularly elevated risk for neuropathic pain. It seems that lower educational attainment and female sex are risk factors of neuropathic pain. However, the reason for this is not fully understood.*We would like to acknowledge the funding from the Science for Life - Astra Zeneca collaborative grant that supported this research

  • 26.
    Burkill, Sarah
    et al.
    Clinical Epidemiology Unit, Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institute, Sweden.
    Hajiebrahimi, Mohammad Hossein
    Clinical Epidemiology Unit, Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden; Biostatistics and Epidemiology Unit, Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
    Hillert, Jan
    Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Olsson, Tomas
    Division of Neurology and Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, Shahram
    Clinical Epidemiology Unit, Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
    Mortality trends for multiple sclerosis patients in Sweden from 1968 to 20122017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 6, p. 555-562Article in journal (Refereed)
    Abstract [en]

    Objective: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden.

    Methods: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS.

    Results: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators.

    Conclusions: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.

  • 27.
    Bécares, Laia
    et al.
    University of Manchester, Manchester, United Kingdom.
    Kelly, Yvonne
    University College London, London, United Kingdom.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Sacker, Amanda
    University College London, London, United Kingdom.
    Bi-directional relationships between body mass index and height from three to seven years of age: an analysis of children in the United Kingdom Millennium Cohort Study2016In: Longitudinal and life course studies, ISSN 1124-9064, E-ISSN 1757-9597, Vol. 7, no 1, p. 41-52Article in journal (Refereed)
    Abstract [en]

    Adiposity and height are known to correlate in childhood but it is less clear whether height and weight gain occur in synergy. We investigate the bidirectional relationships between measures of height and body mass index (BMI) - an indicator of adiposity - and their rates of change. The sample comprises singleton children in the Millennium Cohort Study (N = 11,357). Child anthropometrics measured by trained interviewers at ages three, five and seven years (2003-2009) were transformed to standardised scores based on 1990 British Growth Reference data from which piecewise linear models for height and BMI were jointly fitted. At three years of age, zHeight was positively related to subsequent zBMI velocities, whereas zBMI at three years was positively related to zHeight velocity to age five but inversely related to zHeight velocity from five to seven years of age. Age three zBMI predicted zHeight velocity from three to five years more strongly than age three zHeight predicted zBMI velocity over the same period. The rate of change in zHeight was positively correlated with subsequent zBMI velocity and vice versa. This new evidence on the bidirectional relationships between height and BMI velocities sheds light on the early childhood origins of obesity in adulthood and the need to monitor growth as well as weight gain.

  • 28. Carli, C.
    et al.
    Ehlin, A. G. C.
    Klareskog, L.
    Lindblad, S.
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Trends in disease modifying antirheumatic drug prescription in early rheumatoid arthritis are influenced more by hospital setting than patient or disease characteristics2006In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, no 8, p. 1102-1105Article in journal (Refereed)
    Abstract [en]

    Objective: To characterise temporal trends and factors associated with the prescription of disease modifying antirheumatic drugs (DMARDs) at the initial consultation in early rheumatoid arthritis (RA).

    Methods: Data from 2584 patients with early RA at 19 hospitals were extracted from the Swedish Rheumatoid Arthritis Register for the period 1997–2001. Disease characteristics and DMARD prescription at first consultation with the rheumatologist were investigated using cross tabulation and logistic regression.

    Results: DMARD prescriptions, particularly for methotrexate, increased from 1997 to 2001 independently of patient characteristics. Stratification by hospital type showed that patients in district hospitals were less likely to be prescribed DMARDs than those in university hospitals (adjusted odds ratio (OR) = 0.53 (95% confidence interval (CI) 0.40 to 0.69), p<0.001), independently of confounding factors. Association of the DAS28 with the likelihood of DMARD prescription was greater among patients attending district hospitals (OR = 1.65 (1.34 to 2.02), p<0.001) than those at university hospitals (OR = 1.23 (1.07 to 1.41), p = 0.003) and county hospitals (OR = 1.34 (1.01 to 1.63), p = 0.003). Interaction testing indicated that the difference was significant (p = 0.007).

    Conclusions: Temporal trends in DMARD prescription indicate an increasingly aggressive approach to disease management among Swedish rheumatologists. However, the association of hospital type with DMARD prescription suggests that the adoption of research findings in clinical care varies considerably.

  • 29.
    Cheng, Helen
    et al.
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK; ESRC Centre for Learning and Life Chances in Knowledge Economies and Societies, UCL Institute of Education, London, UK.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Research Department of Epidemiology and Public Health, UCL, London, UK.
    Treglown, Luke
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
    Furnham, Adrian
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK; Norwegian Business School, Oslo, Norway.
    Associations between childhood biomedical factors, maternal smoking, personality traits, Body and Mass Index and the prevalence of asthma in adulthood2018In: Psychology and Health, ISSN 0887-0446, E-ISSN 1476-8321, Vol. 33, no 9, p. 1116-1129Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The study set out to investigate socio-economic, biomedical, health and behavioural and psychological factors in childhood and adulthood associated with the prevalence of asthma in adulthood, drawing data from The National Child Development Studies (NCDS), a birth cohort in the UK.

    DESIGN: The National Child Development Study, a nationally representative sample of 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33 and 50 years was used.

    MAIN OUTCOME MEASURE: The prevalence of asthma at age 50 was the outcome measure. The analytic sample consists of 5118 participants with complete data on a set of measures at birth, at ages 7, 11, 33 and 50 years.

    RESULTS: Using logistic regression analyses, results showed that childhood asthma (OR = 6.77: 4.38-10.48, p < .001) and respiratory symptoms (OR = 1.83: 1.18-2.86, p < .01), maternal smoking during pregnancy (OR = 1.26: 1.00-1.59, p < .05), Body and Mass Index (BMI) (OR = 1.03: 1.02-1.05, p < .001), traits Neuroticism (OR = 1.13: 1.01-1.21, p < .05) and Conscientiousness (OR = 0.76: 0.76-0.96, p < .01), as well as sex (OR = 1.49: 1.15-1.94, p < .001) were all significantly associated with the prevalence of asthma in adulthood.

    CONCLUSION: The study shows that both childhood and adulthood psychological and sociological factors are significantly associated with the prevalence of asthma in adulthood, though more work need to be done in this area.

  • 30.
    Cheng, Helen
    et al.
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
    Treglown, Luke
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
    Furnham, Adrian
    Research Department of Clinical, Educational and Health Psychology, University College London, London, UK; BI Norwegian Business School, Oslo, Norway.
    Emotional stability, conscientiousness, and self-reported hypertension in adulthood2017In: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 115, p. 159-163Article in journal (Refereed)
    Abstract [en]

    This study aimed to investigate social and psychological factors in childhood and adulthood associated with self-reported hypertension in adulthood. Using data from the National Child Development Study, a nationally representative sample of 17,415 babies born in Great Britain in 1958 and followed up at 11, 33, and 50 years of age. Self-reported diagnosed hypertension by 50 years was the outcome measure. In total, 5753 participants with complete data on parental social class at birth, childhood cognitive ability test scores at 11 years, educational qualifications at 33 years, personality traits, occupational levels, and self-reported hypertension (all measured at age 50 years) were included in the study. Using logistic regression analyses, results showed that sex (OR = 0.60: 0.49–0.73, p < .001), educational qualifications (OR = 0.59: 0.37–0.92, p < .05), and traits emotional stability (OR = 0.84: 0.77–0.91, p < .001) and conscientiousness (OR = 0.89: 0.82–0.98, p < .05) were all significantly associated with the occurrence of self-reported hypertension in adulthood. Both psychological factors and socio-demographic factors were significantly associated with self-reported hypertension in adulthood.

  • 31.
    Cheng, Helen
    et al.
    Department of Psychology, University College London, London, United Kingdom; ESRC Centre for Learning and Life Chances in Knowledge Economies and Societies, Institute of Education, University of London, London, United Kingdom .
    Treglown, Luke
    Department of Psychology, University College London, London, United Kingdom; Department of Psychology, University of Bath, Bath, United Kingdom .
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Research Department of Epidemiology and Public Health, UCL, London, United Kingdom .
    Furnham, Adrian
    Department of Psychology, University College London, London, United Kingdom; Norwegian Business School, Oslo, Norway .
    Associations between familial factor, trait conscientiousness, gender and the occurrence of type 2 diabetes in adulthood: evidence from a British cohort2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0122701Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate social, familial, and psychological factors in influencing the occurrence of type 2 diabetes in adulthood.

    Method: Some 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33, and 50 years of age. The prevalence of type 2 diabetes at age 50 years was the outcome measure.

    Results: Some 5,032 participants with data on parental social class, childhood cognitive ability tests scores at age 11 years, educational qualifications at age 33 years, personality traits, occupational levels, and type 2 diabetes (all measured at age 50 years) were included in the study. Available information also included whether cohort members' parents or siblings had diabetes. Using logistic regression analyses, results showed that sex (OR= 0.63: 0.42-0.92, p<. 05), family history (OR= 3.40: 1.76-6.55, p<. 01), and trait conscientiousness (OR= 0.76: 0.64-0.90, p<. 001) were all significantly and independently associated with the occurrence of type 2 diabetes in adulthood. It appears that the occurrence of type 2 diabetes is greater among men than women (4.3% vs 2.5%).

    Conclusion: Familial (genetic and non-genetic) and psychological factors are significantly associated with the prevalence of type 2 diabetes in adulthood.

  • 32.
    Cheng, Helen
    et al.
    University College London (UCL), London, UK.
    Treglown, Luke
    University College London (UCL), London, UK.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. University College London (UCL), London, UK.
    Kornilaki, Ekaterina N.
    University of Crete, Rethymnon, Greece.
    Tsivrikos, Dimitrios
    University College London (UCL), London, UK.
    Furnham, Adrian
    University College London (UCL), London, UK; BI Norwegian Business School, Oslo, Norway.
    The associations between personality traits, education, occupation and the occurrence of eczema in adulthood2017In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 22, no 7, p. 916-924Article in journal (Refereed)
    Abstract [en]

    There were 5834 participants with complete data on parental social class at birth, childhood cognitive ability tests scores at 11 years, educational qualifications at 33 years, the Big Five-Factor personality traits, occupational levels and eczema (measured at age 50 years). Results showed that eczema in childhood, educational achievement and occupational levels were significantly associated with the occurrence of reported eczema in adulthood. Emotionally Stable people (non-neurotic) were less likely to have eczema, but those with high Agreeableness and Openness more likely to have eczema. Childhood cognitive ability was significantly and positively associated with eczema in adulthood.

  • 33.
    Duberg, Ann-Sofi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Pettersson, Helena
    Smittskyddsinstitutet.
    Aleman, Soo
    Karolinska Sjukhuset.
    Blaxhult, Anders
    Smittskyddsinstitutet.
    Davidsdottir, Loa
    Karolinska sjukhuset.
    Hultcrantz, Rolf
    Karolinska Institutet.
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Ekdahl, Karl
    Karolinska Institutet.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    The burden of hepatitis C in Sweden: a national study of inpatient careManuscript (preprint) (Other academic)
  • 34.
    Duberg, Ann-Sofi
    et al.
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Pettersson, Helena
    Department of Epidemiology, Swedish Institute for Infectious Disease Control Solna, Stockholm, Sweden.
    Aleman, Soo
    Department of Gastroenterology and Hepatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Blaxhult, Anders
    Department of Epidemiology, Swedish Institute for Infectious Disease Control Solna, Stockholm, Sweden.
    Davidsdottir, Loa
    Department of Gastroenterology and Hepatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Hultcrantz, Rolf
    Department of Gastroenterology and Hepatology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ekdahl, Karl
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Örebro University, Örebro, Sweden; Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    The burden of hepatitis C in Sweden: a national study of inpatient care2011In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 18, no 2, p. 106-118Article in journal (Refereed)
    Abstract [en]

    The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43 000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215 000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.

  • 35.
    Ekbäck, Gunnar
    et al.
    Dental Department, Örebro County Council, Örebro, Sweden .
    Näslund, Ingmar
    Department of Surgery, Örebro University Hospital, Örebro, Sweden .
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Primary Care and Social Medicine, Charing Cross Hospital, Imperial College, London, United Kingdom .
    Ordell, Sven
    Dental Commissioning Unit, Östergötland County Council, Linköping, Sweden; Department of Oral Public Health, Malmö University, Malmö, Sweden .
    Self-perceived oral health and obesity among 65 years old in two Swedish counties2010In: Swedish Dental Journal, ISSN 0347-9994, Vol. 34, no 4, p. 207-216Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to explore the association between oral health and obesity. The study was conducted in the spring of 2007 as a postal survey of all inhabitants born in 1942 and living in the two Swedish counties of Orebro and Ostergotland. This questionnaire survey has been conducted every five years since 1992 but has been updated continually with additional questions and for the sweep used here, height and weight data were collected. A total of 8,313 individuals received the questionnaire and 6,078 of those responded (73,1%). The outcome variable oral health was measured using one global question and four detailed questions representing different aspects of oral health. The independent variable Body Mass Index (BMI) was calculated using self-reported height and weight. A difference in oral health between various BMI groups was found. The difference was both statistically significant and of clinical importance, particularly among the group with severe obesity who reported poorer self-perceived chewing capacity, lower satisfaction with dental appearance, increased mouth dryness and fewer teeth and lower overall satisfaction with oral health. In view of the increased risk of poor oral health demonstrated in this study for those with severe obesity, it may be of value to increase cooperation between dental care and primary health care for these patients.

  • 36.
    Elfstrom, Peter
    et al.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Granath, Fredrik
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Smedby, Karin Ekstrom
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences. Department of Primary Care and Public Health, Charing Cross Hospital, Imperial College, London, United Kingdom.
    Askling, Johan
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ekbom, Anders
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease2011In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 103, no 5, p. 436-444Article in journal (Refereed)
    Abstract [en]

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

  • 37.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Granath, Fredrik
    Ekström Smedby, Karin
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Askling, Johan
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Örebro University, School of Health and Medical Sciences.
    Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3Manuscript (Other academic)
    Abstract [en]

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

  • 38.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hamsten, Anders
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 5, p. 545-554Article in journal (Refereed)
    Abstract [en]

    Objectives: We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort.Subjects and methods: Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964–2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease. Main outcome measures: Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according torelevant international classification of disease codes in the Swedish national inpatient register.Results: Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0–1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2–3.7), or pericarditis (HR = 0.4; 95% CI = 0.1–1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology ⁄ internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4–11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4– 6.5) or pericarditis (HR = 1.5; 95% CI = 0.5–4.0).Conclusion: This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis

  • 39.
    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.

  • 40.
    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.

  • 41.
    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)
  • 42.
    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.

  • 43.
    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)
  • 44.
    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)
  • 45.
    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.

  • 46.
    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 study2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-315521Article 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.

  • 47.
    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)
  • 48.
    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.

  • 49.
    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, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 8, no 11, article id 739Article in journal (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.

  • 50.
    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 in journal (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.

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