Lars Pedersen

Aarhus University Hospital, Aarhus, Central Jutland, Denmark

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Publications (151)813.13 Total impact

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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: 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. · 3.73 Impact Factor
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    ABSTRACT: Purpose To examine the association between young adulthood obesity and long-term risk of ischemic heart disease (IHD) and non-ischemic congestive heart failure (CHF). Methods 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 31 December 2012, whichever came first. We used Cox regression to compute hazard ratios (HRs). Results 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. Conclusions Young adulthood obesity was an important risk factor for IHD, but also for CHF without pre-existing IHD.
    Annals of Epidemiology. 01/2014;
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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: 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
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    ABSTRACT: BACKGROUND: Colorectal cancer (CRC) is common, with surgery as the main curative treatment. The prevalence of chronic liver disease has increased, but knowledge is limited on postoperative mortality in patients with liver disease who undergo CRC surgery. Hence, we examined 30-day mortality after CRC surgery in patients with liver disease compared to those without liver disease. METHODS: We used medical databases to conduct a nationwide cohort study of all patients undergoing CRC surgery in Denmark from 1996 through 2009. We further identified patients diagnosed with any liver disease before CRC surgery and categorized them into two cohorts: patients with non-cirrhotic liver disease and patients with liver cirrhosis. Patients without liver disease were defined as the comparison cohort. Using the Kaplan-Meier method, we computed 30-day mortality after CRC surgery in each cohort. We used a Cox regression model to compute hazard ratios as measures of the relative risk (RR) of death, controlling for potential confounders including comorbidities. In order to examine the impact of liver disease in different subgroups, we stratified patients by gender, age, cancer stage, cancer site, timing of admission, type of surgery, comorbidity level, and non-hepatic alcohol-related disease. RESULTS: Overall, 39,840 patients underwent CRC surgery: 369 (0.9%) had non-cirrhotic liver disease and 158 (0.4 %) had liver cirrhosis. Thirty-day mortality after CRC surgery was 8.7% in patients without liver disease and 13.3% in patients with non-cirrhotic liver disease (adjusted RR of 1.49 (95% confidence interval (CI): 1.12-1.98)). Among patients with liver cirrhosis, mortality was 24.1%, corresponding to an adjusted RR of 2.59 (95% CI: 1.86-3.61). The negative impact of liver disease on postoperative mortality was found in all subgroups. CONCLUSIONS: Pre-existing liver disease was associated with a markedly increased 30-day mortality following CRC surgery.
    BMC Gastroenterology 04/2013; 13(1):66. · 2.11 Impact Factor
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    ABSTRACT: BACKGROUND: Concerns have been raised about the risk of dementia associated with anti-estrogen adjuvant therapy in breast cancer, but study results have been inconsistent. We examined whether tamoxifen or other endocrine therapy was associated with dementia risk in a large population of breast cancer patients. METHODS: We used Danish nationwide medical registries to identify breast cancer patients diagnosed between 1990 and 2004, use of endocrine therapy and subsequent diagnoses of dementia. We used Cox regression to estimate the risk of dementia among patients who received five years of tamoxifen or other endocrine therapies. RESULTS: The study included 16,419 breast cancer patients. In this cohort, 37% were unexposed to endocrine therapy, 9% had five years of tamoxifen therapy and 54% had other endocrine regimens, some of them containing tamoxifen for less than five years with subsequent aromatase inhibitor therapy. Tamoxifen therapy was associated with a near-null risk of dementia (hazard ratio (HR): 1.4, 95% CI: 1.0, 1.9), and a null association was observed after death was taken into account as a competing risk (Sub-HR=1.0, 95%CI: 0.76, 1.4). CONCLUSIONS: No clinically relevant association between use of tamoxifen or other endocrine therapy and risk of dementia was observed.
    Cancer Epidemiology Biomarkers &amp Prevention 04/2013; · 4.56 Impact Factor
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    ABSTRACT: IMPORTANCE Excess endogenous cortisol has been linked to venous thromboembolism (VTE) risk, but whether this relationship applies to exogenous glucocorticoids remains uncertain. Because the prevalence of glucocorticoid use and the incidence of VTE are high, an increased risk of VTE associated with glucocorticoid use would have important implications. BACKGROUND To examine the association between glucocorticoid use and VTE. DESIGN Population-based case-control study using nationwide databases. SETTING Denmark (population 5.6 million). PARTICIPANTS We identified 38 765 VTE cases diagnosed from January 1, 2005, through December 31, 2011, and 387 650 population controls included through risk-set sampling and matched by birth year and sex. The VTE diagnosis date for the case was the index date for cases and matched controls. EXPOSURE We classified individuals who filled their most recent glucocorticoid prescription 90 days or less, 91 to 365 days, and more than 365 days before the index date as present, recent, and former users, respectively. Present users were subdivided into new (first-ever prescription 90 days or less before the index date) and continuing users (others). MAIN OUTCOMES AND MEASURES We used conditional logistic regression adjusted for VTE risk factors to estimate incidence rate ratios (IRRs) and 95% CIs for glucocorticoid users vs nonusers. RESULTS Systemic glucocorticoids increased VTE risk among present (adjusted IRR, 2.31; 95% CI, 2.18-2.45), new (3.06; 2.77-3.38), continuing (2.02; 1.88-2.17), and recent (1.18; 1.10-1.26) users but not among former users (0.94; 0.90-0.99). The adjusted IRR increased from 1.00 (95% CI, 0.93-1.07) for a prednisolone-equivalent cumulative dose of 10 mg or less to 1.98 (1.78-2.20) for more than 1000 to 2000 mg, and to 1.60 (1.49-1.71) for doses higher than 2000 mg. New use of inhaled (adjusted IRR, 2.21; 95% CI, 1.72-2.86) and intestinal-acting (2.17; 1.27-3.71) glucocorticoids also increased VTE risk. CONCLUSIONS AND RELEVANCE The risk of VTE is increased among glucocorticoid users. Although residual confounding may partly explain this finding, we consider a biological mechanism likely because the association followed a clear temporal gradient, persisted after adjustment for indicators of severity of underlying disease, and existed also for noninflammatory conditions. Hence, our observations merit clinical attention.
    JAMA Internal Medicine 04/2013; · 10.58 Impact Factor
  • Epidemiology (Cambridge, Mass.) 03/2013; 24(2):331-2. · 5.51 Impact Factor
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    ABSTRACT: X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by hypohidrosis, sparse hair, and teeth abnormalities. Infants with XLHED have an increased risk of death by hyperpyrexia. XLHED is the most common form of hypohidrotic ectodermal dysplasia (HED); however, no population-based prevalence estimates are available. We aimed to: 1) estimate the prevalence of XLHED in the Danish population per January 1, 2011; 2) identify the most frequent age at time of diagnosis; and 3) quantify the most frequent clinical feature associated with XLHED. MATERIALS AND METHODS: We conducted a nationwide cross-sectional study (1995-2010). We leveraged national medical registries and data from clinical departments to categorize XLHED cases into three groups: 1) Molecularly-confirmed XLHED; 2) Clinically-diagnosed HED (registered with ICD-10 Q82.4); and 3) Possible HED (registered with sufficient clinical features based on a clinical algorithm that we designed). RESULTS: We identified 90 molecularly-confirmed XLHED, 146 clinically-diagnosed HED, and 988 possible HED cases between 1995 and 2010 (total n= 1224). The prevalence was 21.9 per 100,000 overall and 1.6 per 100,000 when restricting to molecularly-confirmed XLHED cases. The most frequent age at time of XLHED diagnosis occurred between the ages of 11-18 years. Teeth abnormalities occurred in 79% of all cases and 52% of molecularly-confirmed cases as a primary clinical marker. CONCLUSION: We present the first ever population-based prevalence estimates of XLHED and suggest that the prevalence of XLHED may be higher than previously estimated. Diagnosis occurs most frequently during adolescence and teeth abnormalities were the most frequent clinical marker of XLHED.
    European journal of medical genetics 02/2013; · 1.57 Impact Factor
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    ABSTRACT: To develop and validate a case definition of eosinophilic esophagitis (EoE) in the linked Danish health registries. For case definition development, we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark. All International Classification of Diseases-10 (ICD-10) and prescription codes were obtained, and archived pathology slides were obtained and re-reviewed to determine case status. We used an iterative process to select inclusion/exclusion codes, refine the case definition, and optimize sensitivity and specificity. We then re-queried the registries from 2008-2009 to yield a validation set. The case definition algorithm was applied, and sensitivity and specificity were calculated. Of the 51 and 49 candidate cases identified in both the development and validation sets, 21 and 24 had EoE, respectively. Characteristics of EoE cases in the development set [mean age 35 years; 76% male; 86% dysphagia; 103 eosinophils per high-power field (eos/hpf)] were similar to those in the validation set (mean age 42 years; 83% male; 67% dysphagia; 77 eos/hpf). Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases. Two registry-based case algorithms based on pathology, ICD-10, and pharmacy codes were successfully generated in the development set, one that was sensitive (90%) and one that was specific (97%). When these algorithms were applied to the validation set, they remained sensitive (88%) and specific (96%). Two registry-based definitions, one highly sensitive and one highly specific, were developed and validated for the linked Danish national health databases, making future population-based studies feasible.
    World Journal of Gastroenterology 01/2013; 19(4):503-10. · 2.55 Impact Factor
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    ABSTRACT: Lifestyle factors may influence observed associations between proton pump inhibitor (PPI) usage and health outcomes. The aim of the study reported here was to examine characteristics and differences in lifestyle among PPI users and nonusers. This cross-sectional study utilized data from a 2006 population-based health survey of 21,637 persons in the Central Danish Region. All persons using prescribed PPIs were identified through linkage to a population-based prescription database. Biometric measures and prevalence of smoking, excessive alcohol consumption, diet, and physical exercise were analyzed, comparing PPI users with nonusers. Among 10,129 (46.8%) male and 11,508 (53.2%) female survey respondents, 1,356 (13.4%) males and 1,691 (14.7%) females reported ever use of PPIs. PPI users were more obese (16.7%) than nonusers (13.1%), with an age- and sex-standardized prevalence ratio (PR) of 1.3 (95% confidence interval [CI]: 1.2-1.4). The prevalence of smokers was also higher in the PPI group (26.2% vs 22.3% [PR =1.2, 95% CI: 1.1-1.3]), as was the prevalence of ex-smokers (41.0% vs 32.0% [PR =1.2, 95% CI: 1.1-1.2]). Unhealthy diet was slightly more common among PPI users than among nonusers (15.4% vs 13.0%), with a PR of 1.2 (95% CI: 1.1-1.3). Physical exercise level and alcohol consumption were similar in the two groups. Hospital-diagnosed comorbidity was observed in 35% of PPI users (a Charlson Comorbidity Index score of 1 or more) compared with only 15% among nonusers. PPI users are more obese, smoke more, and have significantly more comorbidities than PPI nonusers. These data are important when evaluating unmeasured confounding in observational studies of PPI effects.
    Clinical Epidemiology 01/2013; 5:493-499.
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    ABSTRACT: Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11 284 patients with enlarged lymph nodes during median follow up of 4·7 years. Only 389 cases were expected. Cancer risk was 11·5% [95% confidence interval (CI): 10·9-12·1%] during the first year of follow up, corresponding to an age- and sex-standardized incidence ratio (SIR) of 21·1 (95% CI: 20·0-22·3). One-year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1·4-fold (95% CI: 1·3-1·5-fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long-term risk of cancer.
    British Journal of Haematology 12/2012; · 4.94 Impact Factor
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    ABSTRACT: OBJECTIVES: To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases.METHODS: A population-based cohort of parent-offspring triads from Denmark (1977-2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history.RESULTS: Among 3 513 817 parent-offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS).CONCLUSIONS: The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.
    Annals of the rheumatic diseases 05/2012; · 8.11 Impact Factor
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    ABSTRACT: Proton pump inhibitors (PPIs) are increasingly used in reflux disease treatment also among pregnant women. Hypospadias prevalence is increasing and the birth defect is diagnosed in 0.3%-0.8% of male births, but the association with maternal PPI use during pregnancy is virtually unknown. Therefore, we decided to estimate the hypospadias risk in male offspring after maternal PPI use during pregnancy. We used Danish nationwide registries to conduct a population-based prevalence study including all live-born boys from 1997 through 2009. Maternal PPI use was classified according to exposure time: early pregnancy (30 days before conception through the end of the first trimester) and entire pregnancy (30 days before and throughout pregnancy). Outcome was defined as a hospital hypospadias diagnosis recorded any time after delivery. We calculated prevalence ratios and 95% confidence intervals associating maternal PPI use with hypospadias in male offspring using Cox proportional hazard regression analysis and adjusted for confounding factors. We identified a total of 430,569 live-born boys of whom 2926 were exposed to maternal PPI use during early pregnancy. Among the exposed boys, 20 (0.7%) were diagnosed with hypospadias, whereas 2683 (0.6%) of the nonexposed had hypospadias (adjusted prevalence ratio = 1.1; 95% confidence interval, 0.7-1.7). A total of 5227 boys were exposed during the entire pregnancy, and 32 (0.6%) had hypospadias corresponding to a prevalence ratio of 1.0 (95% confidence interval, 0.7-1.4). The subanalysis restricted to omeprazole exposure showed similar results. We thus conclude that maternal PPI use during pregnancy was not associated with hypospadias in boy offspring.
    American journal of therapeutics 02/2012; · 1.29 Impact Factor
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    ABSTRACT: Glucocorticoids are widely prescribed drugs. In the human body, glucocorticoid is the main stress hormone and controls a variety of physiological and cellular processes, including metabolism and immune response. It belongs to the same steroid superfamily as estrogens, which are known to play a role in breast cancer. However, the effect of glucocorticoid use on the risk of breast cancer is not clear. We conducted a case-control study using population-based medical databases from Northern Denmark (1.8 million inhabitants) to investigate the association between glucocorticoid prescriptions and breast cancer risk. The study included 9,488 incident breast cancer cases diagnosed between 1994 and 2008 and 94,876 population controls. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating glucocorticoid use with breast cancer occurrence, controlling for prescriptions of postmenopausal hormone replacement therapy, anti-diabetics, immunosuppressive drugs, and hospital diagnosis of obesity, diabetes, chronic pulmonary diseases and autoimmune diseases. We found no effect on breast cancer risk in ever users (> 2 prescriptions) of any glucocorticoids (adjusted odds ratio (aOR) = 1.0; 95% CI: 0.96, 1.1), systemic glucocorticoids (aOR = 1.0; 95% CI: 0.96, 1.1), or inhaled glucocorticoids (aOR = 1.0; 95% CI: 0.95, 1.1), each compared to never users of any glucocorticoids. Associations for recent use (preceding two years) and former use (more than two years earlier) were near null in all dose categories (low, medium and high number of prescriptions). Intensity of systemic glucocorticoid use (cumulative prednisolone equivalent doses), regardless of duration (< 1, 1 to 5, 5+ years), was also not associated with breast cancer risk. Overall, our study provides no evidence that glucocorticoid use affects the risk of breast cancer.
    Breast cancer research: BCR 02/2012; 14(1):R21. · 5.87 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) patients may be at increased risk of venous thromboembolism (VTE), but evidence is limited. To examine long-term risk of VTE among MS patients. We conducted a population-based cohort study among 17,418 Danish MS patients and 87,090 comparison cohort members from the general population. Data on MS, VTE and comorbidities were obtained from the Danish National Registry of Patients including all admissions to Danish hospitals since 1977. We computed cumulative risks for VTE and adjusted incidence rate ratios (IRRs). A total of 34 (0.2%) MS patients and 36 (0.04%) comparison cohort members had a deep venous thrombosis (DVT) within 1 year following the date of initial MS diagnosis/index date [adjusted IRR = 3.02 (95% CI: 2.14-4.27)]. During this period, 16 (0.09%) MS patients and 26 (0.03%) comparison cohort members had a documented pulmonary embolism (PE) [adjusted IRR = 2.85 (95% CI: 1.72-4.70)]. During the subsequent up to 29 years, 315 (1.9% of MS patients alive at year 1) MS patients had a record of a DVT [adjusted IRR = 2.28 (95% CI: 2.01-2.59)] and 129 (0.8%) had PE [IRR = 1.58 (95% CI: 1.31-1.92]. MS is a risk factor for VTE, but the absolute risk is low.
    Neuroepidemiology 01/2012; 38(2):76-83. · 2.37 Impact Factor

Publication Stats

2k Citations
521 Downloads
813.13 Total Impact Points

Institutions

  • 2002–2014
    • Aarhus University Hospital
      • • Department of Clinical Epidemiology
      • • Department of Cardiology
      • • Department of Infectious Diseases
      Aarhus, Central Jutland, Denmark
  • 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
  • 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
  • 2007–2010
    • White River Junction VA Medical Center
      White River Junction, Vermont, United States
    • Pfizer Inc.
      New York City, New York, United States
  • 2009
    • Nordic Africa Institute
      Goeteborg, Västra Götaland, Sweden
    • Regionspsykiatrien Viborg-Skive
      Viborg, Central Jutland, Denmark
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2001–2009
    • Aalborg University Hospital
      • Department of Clinical Microbiology
      Ålborg, North Denmark, Denmark
  • 2008
    • Rutgers New Jersey Medical School
      • Department of Epidemiology
      Newark, NJ, United States
  • 2003–2007
    • Aarhus University
      • • Department of Clinical Epidemiology
      • • Department of Epidemiology and Social Medicine
      Aars, Region North Jutland, Denmark