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  • 1.
    Johansson, Magdalena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Epidemiology of venous thromboembolism with focus on risk markers2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Venous thromboembolism (VTE) is a vascular disease with an incidence of approximately 140 cases per 100,000 person-years in adults. The incidence of VTE has increased over the last decades, and more than 20% of affected individuals die in the first year after diagnosis. To reduce the incidence of VTE, it is important to identify modifiable risk factors for the condition.

    Aims: The aims of this thesis were a) To study the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, b) To determine the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, and c) To study the association between glucose levels, diabetes, alcohol consumption, physical activity and risk of first-time VTE.

    Methods: To determine the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, a retrospective, population-based cohort study was conducted. The study included all adult residents of Västerbotten County during the year 2006. All other aims were addressed in the prospective, population-based Venous thromboEmbolism In Northern Sweden (VEINS) cohort study. The VEINS cohort included 108,025 residents of Västerbotten County aged 30 to 60 years without previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination within the Västerbotten Intervention Programme where weight, height, blood pressure and glucose levels were measured, and answered a questionnaire regarding smoking, education level, medication use, history of diabetes, alcohol intake and physical activity. VTE diagnoses were validated by review of medical records and radiology reports. To study the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, a registry search for International Classification of Diseases diagnosis codes indicating pulmonary embolism and/or deep vein thrombosis events was made in the Swedish National Patient Registry and the Cause of Death Registry. An additional search using an extended set of International Classification of Diseases diagnosis codes was performed in order to identify misclassified events.

    Results: The incidence of first-time VTE was 137 (95% confidence interval [CI] 122–154) per 100,000 adults per year. The most common risk markers for VTE were recent hospitalization and concurrent malignancy. The positive predictive value for a diagnosis of pulmonary embolism was 80.7% (95% CI 78.4–82.9), and that of deep vein thrombosis 59.2% (95% CI 56.7–61.7). Misclassification occurred in 1.1% (95% CI 0.4–1.7) of pulmonary embolism events and in 16.4% (95% CI 14.2–18.7) of deep vein thrombosis events. In the VEINS cohort, a total of 2,054 participants experienced an objectively verified first-time VTE event during approximately 1.5 million person-years of follow-up. In univariable analysis, there were associations between fasting plasma glucose, oral glucose tolerance test two-hour post-load plasma glucose, diabetes and increased risk of first-time VTE. These associations were attenuated after adjustment for potential confounders, and were no longer significant. There was an association between alcohol consumption and risk of first-time VTE in men (for trend 0.02 after adjustments for increased risk of first-time VTE over quartiles of weekly alcohol consumption). Alcohol dependence was associated with risk of first-time VTE in men (hazard ratio [HR] 1.30; 95% CI 1.07–1.59 after adjustments). In women, there were no significant associations between alcohol consumption and risk of first-time VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (HR 0.83; 95% CI 0.71–0.98 after adjustments) compared to women with less or no physical activity. Women with high occupational physical activity also had a lower risk of first-time VTE (HR 0.85; 95% CI 0.74–0.98 after adjustments). In men, there were no consistent association between either measure of physical activity and risk of first-time VTE. 

    Conclusions: VTE is a common vascular disease. Registry data on diagnoses of pulmonary embolism, but not deep vein thrombosis, is of acceptable quality and can be considered for use in registry-based studies. Glucose levels and diabetes are not associated with risk of first-time VTE. Alcohol intake and alcohol dependence are associated with an increased risk of first-time VTE in men, whereas high leisure time physical activity and occupational physical activity are associated with a decreased risk of first-time VTE in women.

  • 2.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Incidence of venous thromboembolism in northern Sweden (VEINS): a population-based study2014In: Thrombosis Journal, ISSN 1477-9560, E-ISSN 1477-9560, Vol. 12, article id 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The reported incidence of venous thromboembolism (VTE) varies considerably among studies. The primary aim of this study was to describe the incidence of VTE in relation to age and sex. The secondary aim was to describe the risk factor pattern at the time of diagnosis.

    METHODS: This retrospective, population-based cohort study included all adult residents in the County of Västerbotten in northern Sweden during the year 2006 (n = 204,836). All potential VTE events were manually validated and classified according to location. The presence of risk factors for VTE at the time of diagnosis was recorded.

    RESULTS: We identified 517 adult individuals with potential VTE. Among these, 343 individuals (158 men and 185 women) had a verified VTE event in 2006. The mean incidence was 167 individuals per 100,000 person years; 155 for men and 180 for women. The mean age at diagnosis was 67.6 years in men and 72.5 years in women. The incidence of VTE increased with age. The incidence was highest in women aged 85 years or more. Pulmonary embolism with or without concurrent deep vein thrombosis was diagnosed in 161 individuals (46.9%); lower extremity deep vein thrombosis without concurrent pulmonary embolism was diagnosed in 157 individuals (45.8%); and VTE in another location was diagnosed in 25 individuals (7.3%). The most common risk factors for VTE were recent hospitalization and concurrent malignancy.

    CONCLUSION: The incidence of VTE was 167 per 100,000 person years and increased with age. The incidence was highest among older women. Pulmonary embolism was the most common form of VTE; it affected 47% of individuals with VTE. Malignancy and hospitalization were the most prevalent risk factors for VTE.

  • 3.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women2019In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 6, p. 962-970Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.

    OBJECTIVE: This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.

    METHODS: We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.

    RESULTS: The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06-1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01-1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07-1.59). In women, there were no significant associations.

    CONCLUSION: High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.

  • 4.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Physical activity and risk of first-time venous thromboembolism2019In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, no 11, p. 1181-1187Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity may have a protective effect against venous thromboembolism (VTE). The aim of this study was to investigate the association between leisure time physical activity, occupational physical activity, and the risk of VTE in men and women separately.

    Methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 participants of health examinations between 1985 and 2014. Physical activity data were collected by questionnaire. Participants were followed from health examination to first-time VTE event, death, emigration or the end of the study. All VTE events were validated by reviewing medical records and radiology reports.

    Results: During 1,496,669 person-years, 2054 participants experienced VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71–0.98 after adjustments) compared with women with less or no physical activity. Furthermore, women with high occupational physical activity also had a lower risk of VTE (HR 0.85; 95% CI 0.74–0.98). In men, there was no consistent association between either measure of physical activity and the risk of VTE.

    Conclusion: We found an association between increased physical activity and a lower risk of first-time VTE in women.

  • 5.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fhärm, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study2018In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 165, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Introduction: It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. Materials and methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Vasterbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. Results: An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). Conclusions: There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE.

  • 6.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Optical coherence tomography evaluation of macular edema after phacoemulsification surgery with intracameral mydriatics.2007In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 33, no 8, p. 1436-41Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantify the macular edema induced by intracameral mydriatics in phacoemulsification surgery. SETTING: University hospital eye clinic, Umeå, Sweden. METHODS: In a randomized study of 22 patients, 11 patients were given 150 muL of a mixture of phenylephrine 1.5% and lidocaine 1% intracamerally for mydriasis and anesthesia. In a control group (n = 11), conventional topical mydriatics and intracameral lidocaine were given. Multiple preoperative, intraoperative, and postoperative variables were recorded. RESULTS: There were no differences in macular edema between the 2 treatments. A correlation was seen between macular edema and impaired visual acuity 1 week postoperatively. On the first postoperative day, a similar correlation was seen between corneal edema and the degree of visual improvement. CONCLUSIONS: Intracameral lidocaine and phenylephrine for mydriasis and anesthesia did not induce more significant macular edema than the standard regimen of topical mydriatics plus intracameral lidocaine. Macular edema limited visual improvement 1 week after phacoemulsification, while corneal edema appeared to have a larger effect immediately after surgery.

  • 7.
    Öhman, Ludvig
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Magdalena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Positive predictive value and misclassification of diagnosis of pulmonary embolism and deep vein thrombosis in Swedish patient registries2018In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 10, p. 1215-1221Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate diagnoses of pulmonary embolism (PE) and deep vein thrombosis (DVT) in administrative registries. We also estimated the frequency of misclassified PE and DVT events.

    Patients and methods: A registry search for ICD codes representing PE and DVT was performed between 1985 and 2014 in a large population-based cohort in northern Sweden. An additional search using an extended set of ICD codes was performed to identify misclassified events. Diagnoses were validated manually by reviewing medical records and radiology reports.

    Results: Searching ICD codes in the National Patient Registry and Cause of Death Registry identified 2,450 participants with a first-time diagnosis of PE or DVT. The positive predictive value (PPV) for a diagnosis of PE or DVT was 80.7% and 59.2%, respectively. For the period of 2009 to 2014, the PPV was higher for PE (85.8%) but lower for DVT (54.1%). Misclassification occurred in 16.4% of DVT events and 1.1% of PE events.

    Conclusion: Registry-based data on PE, especially in recent years, are of acceptable quality and can be considered for use in registry-based studies. For DVT, we found that data were of low quality in regards to both PPV and misclassification and should not be used without validation.

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