Lars Pedersen

Aarhus University Hospital, Aarhus, Central Jutland, Denmark

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Publications (207)1214.31 Total impact

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    ABSTRACT: Recently it has become apparent that superficial vein thrombosis (SVT) can have serious complications. However, the magnitude of the risk of subsequent deep venous and arterial thrombotic events remains unknown. We examined this in a nationwide population-based setting during a period when SVT was not treated routinely with anticoagulants. The Danish National Registry of Patients, covering all Danish hospitals, was used to identify 10,973 patients with a first-time diagnosis of SVT during 1980-2012. A comparison cohort of 515,067 subjects, matched on age, sex and calendar year, was selected from the general Danish population. Outcomes were venous thromboembolism (VTE), acute myocardial infarction (AMI), ischaemic stroke, and death. During median follow-up of 7 years, the incidence rate of VTE was 18.0/1000 person-years (95% confidence interval (CI) 17.2-18.9). The highest risk occurred in the first 3 months (3.4%; 95%CI 3.0-3.7). Compared with the general population, the hazard ratio (HR) was 71.4 (95%CI 60.2-84.7) in this period, steadily decreasing to 5.1 (95%CI 4.6-5.5), 5 years after the SVT. HRs for AMI, stroke and death were 1.2 (95%CI 1.1-1.3), 1.3 (95%CI 1.2-1.4) and 1.3 (95%CI 1.2-1.3) respectively, with the highest risk also shortly after SVT. These data indicate the prognostic importance of SVT and may form the basis for clinical decision-making regarding anticoagulation.
    Blood 11/2014; · 9.78 Impact Factor
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    ABSTRACT: Patients with acute myocardial infarction or stroke are at high risk of venous thromboembolism, which is traditionally considered a complication rather than a marker of occult cancer. We examined the association between venous thromboembolism and cancer in patients with acute myocardial infarction or stroke.Methods We used medical databases to conduct a population-based cohort study including all patients with a first-time venous thromboembolism from 1978 through 2011 who also had a diagnosis of acute myocardial infarction (n = 2,878) or stroke (n = 1,971) recorded on the same day or within the previous 90 days. We followed patients until a first-time cancer diagnosis, emigration, death, or December 31, 2011, whichever came first. We computed 1-year absolute risks and standardised incidence ratios for cancer based on national incidence rates.ResultsThe 1-year absolute cancer risk was 2.7% in the acute myocardial infarction cohort and 3.7% in the stroke cohort. The corresponding standardised incidence ratios were 3.22 (95% confidence interval [CI]: 2.54–4.03) and 3.76 (95% CI: 2.95–4.74), respectively. For cancers diagnosed in the first year, the estimated number of venous thromboembolism patients needed to examine to detect one excess cancer was 25 in the acute myocardial infarction cohort and 19 in the stroke cohort.Conclusion Among acute myocardial infarction and stroke patients, venous thromboembolism can be a marker of occult cancer. We suggest that current guidelines for cancer screening in patients with unprovoked venous thromboembolism could be applied to this group of patients.
    Thrombosis Research 11/2014; · 3.13 Impact Factor
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    ABSTRACT: The prognostic impact of ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on stroke mortality remains unclear. We aimed to examine whether prestroke use of ACE-Is or ARBs was associated with improved short-term mortality following ischaemic stroke, intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH).
    Journal of Neurology Neurosurgery & Psychiatry 09/2014; · 4.92 Impact Factor
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    ABSTRACT: Prenatal termination of pregnancy may underestimate risks or cause bias in epidemiological studies of birth defects if such studies measure only defects diagnosed postnatally. We aimed to estimate the proportion of all fetuses with birth defects terminated in the second trimester of pregnancy-overall and for specific defects.
    Epidemiology (Cambridge, Mass.) 08/2014; · 5.51 Impact Factor
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    ABSTRACT: -Studies on long-term mortality following venous thromboembolism (VTE) are sparse.
    Circulation 06/2014; · 15.20 Impact Factor
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    ABSTRACT: The methodological advances in epidemiology have facilitated the use of the Danish Civil Registration System (CRS) in ways not previously described systematically. We reviewed the CRS and its use as a research tool in epidemiology. We obtained information from the Danish Law on Civil Registration and the Central Office of Civil Registration, and used existing literature to provide illustrative examples of its use. The CRS is an administrative register established on April 2, 1968. It contains individual-level information on all persons residing in Denmark (and Greenland as of May 1, 1972). By January 2014, the CRS had cumulatively registered 9.5 million individuals and more than 400 million person-years of follow-up. A unique ten-digit Civil Personal Register number assigned to all persons in the CRS allows for technically easy, cost-effective, and unambiguous individual-level record linkage of Danish registers. Daily updated information on migration and vital status allows for nationwide cohort studies with virtually complete long-term follow-up on emigration and death. The CRS facilitates sampling of general population comparison cohorts, controls in case-control studies, family cohorts, and target groups in population surveys. The data in the CRS are virtually complete, have high accuracy, and can be retrieved for research purposes while protecting the anonymity of Danish residents. In conclusion, the CRS is a key tool for epidemiological research in Denmark.
    European Journal of Epidemiology 06/2014; · 5.12 Impact Factor
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    ABSTRACT: Pruritus is a frequent complaint in cancer patients. However, no large study has examined pruritus as a marker of undiagnosed cancer.
    British Journal of Dermatology 06/2014; · 3.76 Impact Factor
  • American journal of epidemiology. 05/2014;
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    ABSTRACT: To examine the risk of a subsequent pulmonary or extra-pulmonary cancer diagnosis following a first-time hospital-based diagnosis of pneumonia. Population-based cohort study using Danish medical registries. All hospitals in Denmark. A total of 342,609 patients with a first-time hospital-based (inpatient, emergency room or outpatient clinic) diagnosis of pneumonia between 1995 and 2011. We quantified the excess risk of various cancers among pneumonia patients compared to the expected risk in the general population, using relative [standardised incidence ratios (SIRs)] and absolute risk calculations. Follow-up started 1 month after a hospital-based diagnosis of pneumonia, and ended on 31 December 2011. A total of 28,496 cancers were observed, compared with 21,625 expected, among 342,609 pneumonia patients followed for a median of 4.2 years. The absolute risk of a cancer diagnosis 1 to <6 months following a pneumonia diagnosis was 1.4%, with a corresponding SIR of 2.48 [95% confidence interval (CI) 2.41-2.55]. This was mainly due to an increased risk of lung cancer (8-fold) and haematological cancers (4-fold). The SIR for any cancer remained increased at 1.35 (95% CI 1.30-1.40) during 6-12 months of follow-up, and 1.20 (95% CI 1.18-1.22) during 1-5 years of follow-up. Beyond 5 years, an increased risk was maintained for lung, oesophageal, liver and bladder cancers, squamous cell carcinoma of the skin, lymphoma and multiple myeloma. A hospital-based pneumonia diagnosis was associated with an increased risk of a cancer diagnosis, especially in the ensuing months, but the absolute risk was small. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 05/2014; · 6.46 Impact Factor
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    ABSTRACT: To examine the association between young adulthood obesity and long-term risk of ischemic heart disease (IHD) and nonischemic congestive heart failure (CHF). We conducted a population-based cohort study of 12,850 male conscripts whose fitness for military service was examined by Draft Boards in Northern Denmark. Outcomes were obtained from the Danish National Patient Registry, covering all Danish hospitals since 1977. Follow-up began on the 22nd birthday of each subject and continued until occurrence of an outcome, emigration, death, or on December 31, 2012, whichever came first. We used Cox regression to compute hazard ratios (HRs). The 36-year risk was 7.3% for IHD and 0.8% for CHF without pre-existing IHD among men of normal weight and 11.1% and 4.0% among obese men, respectively. Comparing obese men with men of normal weight, the adjusted HR was 1.63 (95% confidence interval [CI], 0.98-2.73) for IHD overall, 2.86 (95% CI, 1.56-5.25) for myocardial infarction, 5.52 (95% CI, 2.38-12.82) for unstable angina, 1.29 (95% CI, 0.69-2.41) for stable angina, and 6.68 (95% CI, 2.85-15.66) for CHF without pre-existing IHD. Young adulthood obesity was an important risk factor for IHD but also for CHF without pre-existing IHD.
    Annals of epidemiology 05/2014; 24(5):356-361.e1. · 2.95 Impact Factor
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    ABSTRACT: Proton pump inhibitors (PPI) may potentially modify and decrease the risk for development of oesophageal adenocarcinoma in Barrett's oesophagus (BO). To investigate if the intensity and adherence of PPI use among all patients with BO in Denmark affected the risk of oesophageal adenocarcinoma. We performed a nationwide case-control study in Denmark among 9883 patients with a new diagnosis of BO. All incident oesophageal adenocarcinomas and high-grade dysplasias were identified, and risk ratios were estimated on the basis of prior use of PPIs. Sex- and age-matched BO patients without dysplasia or malignancies in a 10:1 ratio were used for comparison. Conditional logistic regression was used for analysis, adjusting for low-grade dysplasia, gender and medication. We identified 140 cases with incident oesophageal adenocarcinomas and/or high-grade dysplasia, with a median follow-up time of 10.2 years. The relative risk of oesophageal adenocarcinoma or high-grade dysplasia was 2.2 (0.7-6.7) and 3.4 (95% CI: 1.1-10.5) in long-term low- and high-adherence PPI users respectively. No cancer-protective effects from PPI's were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia. This could partly be due to confounding by indication or a true negative effect from PPIs. Until the results from future studies hopefully can elucidate the association further, continuous PPI therapy should be directed at symptom control and additional modalities considered as aid or replacement.
    Alimentary Pharmacology & Therapeutics 03/2014; · 4.55 Impact Factor
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    ABSTRACT: The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP) becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD) codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0) as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data.
    Clinical Epidemiology 01/2014; 6:295-9.
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    ABSTRACT: Recent studies suggest that cancer increases risk of atrial fibrillation. Whether atrial fibrillation is a marker for underlying occult cancer is unknown.
    PLoS ONE 01/2014; 9(8):e102861. · 3.53 Impact Factor
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    ABSTRACT: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses. We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR. The frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively. Our findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo.
    PLoS ONE 01/2014; 9(1):e87450. · 3.53 Impact Factor
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    ABSTRACT: Few studies have associated height with cardiovascular diseases other than myocardial infarction. We conducted a population-based 36-year cohort study of 12,859 men born in 1955 or 1965 whose fitness for military service was assessed by Draft Boards in Northern Denmark. Hospital diagnoses for ischemic heart diseases, atrial fibrillation, stroke, and venous thromboembolism were obtained from the Danish National Patient Registry, covering all Danish hospitals since 1977. Mortality data were obtained from the Danish Civil Registration System. We began follow-up on the 22nd birthday of each subject and continued until occurrence of an outcome, emigration, death, or 31 December 2012, whichever came first. We used Cox regression to compute hazard ratios (HRs) with 95 % confidence intervals (CIs). Compared with short stature, the education-adjusted HR among tall men was 0.67 (95 % CI 0.54-0.84) for ischemic heart disease (similar for myocardial infarction, angina pectoris, and heart failure), 1.60 (95 % CI 1.11-2.33) for atrial fibrillation, 1.05 (95 % CI 0.75-1.46) for stroke, 1.04 (95 % CI 0.67-1.64) for venous thromboembolism, and 0.70 (95 % CI 0.58-0.86) for death. In conclusion, short stature was a risk factor for ischemic heart disease and premature death, but a protective factor for atrial fibrillation. Stature was not substantially associated with stroke or venous thromboembolism.
    European Journal of Epidemiology 12/2013; · 5.12 Impact Factor
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    ABSTRACT: The association between body mass index (BMI) in young adulthood and long-term risk of atrial fibrillation (AF) has not yet been examined for men. We conducted a population-based 36-year cohort study to examine the BMI-associated risk of AF in 12,850 young men who had BMI measured at their examination of fitness for military service. AF was identified from the Danish National Registry of Patients, covering all Danish hospitals since 1977. We began follow-up on the twenty-second birthday of each subject and continued until the occurrence of AF, emigration, death, or December 31, 2012. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for education and height. The cohort contributed a total of 375,888 person-years of follow-up and the median follow-up time was 26 years (mean 29 years). The incidence of AF per 100,000 person-years was 53 for men of normal weight (BMI: 18.5 to 24.9 kg/m(2)), 54 for underweight men (BMI <18.5 kg/m(2)), 106 for overweight men (BMI: 25.0 to 24.9 kg/m(2)), and 144 for obese men (BMI ≥30 kg/m(2)). With normal weight as the reference group, the adjusted HR for AF was 0.99 (95% CI 0.52 to 1.87) for underweight men, 2.08 (95% CI 1.48 to 2.92) for overweight men, and 2.87 (95% CI 1.46 to 5.62) for obese men. The adjusted HR associating 1 unit increase in BMI with AF was 1.12 (95% CI 1.07 to 1.16). In conclusion, overweight and obese young men had more than twice the risk of AF compared with young men of normal weight.
    The American journal of cardiology 12/2013; · 3.58 Impact Factor
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    ABSTRACT: Diverticular disease and cardiovascular disease share several risk factors. Inflammation associated with diverticular disease could predispose to cardiovascular disease. We assessed the association between a diagnosis of diverticular disease and subsequent arterial and venous thromboembolic events, adjusting for related comorbidities to explore a possible causal relationship. We identified 77,065 incident cases of diverticular disease, from 1980 through 2011, from Danish nationwide medical registries; these were matched for age and sex with 302,572 population comparison cohort members. Individuals with a prior history of cardiovascular disease were excluded. We used Cox proportional hazards regression to compute incidence rate ratios, comparing the incidence of acute myocardial infarction, stroke, venous thromboembolism, and subarachnoid hemorrhage in patients with diverticular disease to those of the population cohort members, adjusting for age, sex, obesity, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, connective tissue disease, renal disease, and treatments and medications. The adjusted incidence rate ratios for patients with diverticular disease, compared to population cohort members was, 1.11 (95% Confidence Interval [CI], 1.07-1.14) for acute myocardial infarction, 1.11 (95% CI, 1.08-1.15) for overall stroke, 1.36 (95% CI, 1.30-1.43) for overall venous thromboembolism and 1.27 (95% CI, 1.09-1.48) for subarachnoid hemorrhage. The relative risk of each event remained increased after we adjusted for changes in aspirin use or for endoscopy or colorectal surgery following the diagnosis of diverticular disease. These findings also held after excluding the first year of follow-up and limiting the analysis to patients with diverticulitis. Based on an analysis of Danish medical registries, a diagnosis of diverticular disease is associated with a modest increase in risk of arterial and venous thromboembolic events, after adjustment for related disorders.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2013; · 5.64 Impact Factor
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    ABSTRACT: A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined. We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population. Data on cancer incidence (follow-up 1998-2010), Cbl treatment, and prior diagnoses were obtained from medical registries. Patients receiving Cbl treatment were excluded. Cancer risks were calculated as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), stratified by plasma Cbl levels. All statistical tests were two-sided. We identified 333 667 persons without prevalent cancer and not receiving Cbl treatment. Six percent had Cbl levels greater than the upper reference limit (≥601 pmol/L). Cancer risk increased with higher Cbl levels and was highest during the first year of follow-up (Cbl 601-800 pmol/L: SIR = 3.44, 95% CI = 3.14 to 3.76; Cbl >800 pmol/L: SIR = 6.27, 95% CI = 5.70 to 6.88; both P < .001). The risks were particularly elevated for hematological and smoking- and alcohol-related cancers for persons with high Cbl levels. High Cbl levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high Cbl levels.
    CancerSpectrum Knowledge Environment 11/2013; · 14.07 Impact Factor
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    ABSTRACT: Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction increases myocardial salvage. We investigated the effect of remote ischaemic conditioning on long-term clinical outcome. From February 2007 to November 2008, 333 patients with a suspected first acute ST-elevation myocardial infarction were randomized to receive primary percutaneous coronary intervention with (n = 166) or without (n = 167) remote ischaemic conditioning (intermittent arm ischaemia through four cycles of 5-min inflation followed by 5-min deflation of a blood-pressure cuff). Patient follow-up extended from the randomization date until an outcome, emigration or January 2012 (median follow-up = 3.8 years). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE)-a composite of all-cause mortality, myocardial infarction, readmission for heart failure, and ischaemic stroke/transient ischaemic attack. The individual components of the primary endpoint comprised the secondary endpoints. Outcomes were obtained from Danish nationwide medical registries and validated by medical record review and contact to patients' general practitioner. In the per-protocol analysis of 251 patient fulfilling trial criteria, MACCE occurred for 17 (13.5%) patients in the intervention group compared with 32 (25.6%) patients in the control group, yielding a hazard ratio (HR) of 0.49 (95% confidence interval: 0.27-0.89, P = 0.018). The HR for all-cause mortality was 0.32 (95% confidence interval: 0.12-0.88, P = 0.027). Although lower precision, the HRs were also directionally lower for all other secondary endpoints. Remote ischaemic conditioning before primary percutaneous coronary intervention seemed to improve long-term clinical outcomes in patients with ST-elevation myocardial infarction.
    European Heart Journal 09/2013; · 14.72 Impact Factor
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    ABSTRACT: PURPOSETo estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort. PATIENTS AND METHODS We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year.ResultsCompared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3). CONCLUSION Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.
    Journal of Clinical Oncology 05/2013; · 18.04 Impact Factor

Publication Stats

4k Citations
1,214.31 Total Impact Points

Institutions

  • 2001–2014
    • Aarhus University Hospital
      • • Department of Clinical Epidemiology
      • • Department of Cardiology
      • • Department of Infectious Diseases
      Aarhus, Central Jutland, Denmark
    • Foundation for the Community Control of Hereditary Diseases
      Budapeŝto, Budapest, Hungary
  • 2013
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2012
    • University of Michigan
      • Division of Rheumatology
      Ann Arbor, MI, United States
  • 2004–2012
    • Odense University Hospital
      • • Department of Cardiology - B
      • • Department of Infectious Diseases - Q
      Odense, South Denmark, Denmark
  • 2011
    • University of North Carolina at Chapel Hill
      • Department of Pediatrics
      Chapel Hill, NC, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • Cancer Prevention Institute of California
      Fremont, California, United States
  • 2010–2011
    • Karolinska Institutet
      • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 2006–2011
    • Boston University
      • • Department of Medicine
      • • Department of Epidemiology
      Boston, MA, United States
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 2007–2010
    • White River Junction VA Medical Center
      White River Junction, Vermont, United States
    • Pfizer Inc.
      New York City, New York, United States
  • 2009
    • Regionspsykiatrien Viborg-Skive
      Viborg, Central Jutland, Denmark
    • Nordic Africa Institute
      Goeteborg, Västra Götaland, Sweden
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2004–2009
    • Aalborg University Hospital
      • Department of Clinical Microbiology
      Ålborg, North Denmark, Denmark
  • 2008
    • Rutgers New Jersey Medical School
      • Department of Epidemiology
      Newark, NJ, United States
  • 2000–2007
    • Aarhus University
      • • Department of Clinical Epidemiology
      • • Department of Epidemiology and Social Medicine
      Aars, Region North Jutland, Denmark