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We studied the possible etiological factors of isolated primary congenital glaucoma (IPCG) using data from the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002. The study group consisted of 52 cases with IPCG compared to 52 matched control pairs without any defects, and 22,744 malformed controls with non-ocular defects and 37,837 population controls with no defect. Exposure data and family history were collected (i) prospectively by prenatal logbook and other medical records, (ii) retrospectively through a structured questionnaire completed by mothers, and (iii) from supplementary information obtained by regional nurses visiting the homes of non-respondent mothers. Autosomal recessive inheritance of IPCG was suspected on the basis of sib occurrence and parental consanguinity in 15% of cases. The shorter gestational age (with high proportion of preterm birth), higher birth order, large proportion of births among unmarried women, low socioeconomic status, and high rate of unemployment may be related to Gypsy origin of at least 54% of cases of IPCG. We conclude that the higher incidence of IPCG in the Hungarian Gypsy population is associated with their inbreeding and the possible founder effect of a gene mutation.

BACKGROUND AND STUDY AIMS: Self-expanding metal stents (SEMS) used as a bridge to surgery for obstructive colorectal cancer (CRC) have fallen under suspicion for inducing tumor dissemination, and thereby increasing recurrence risk and long-term mortality. The aim of this study was to compare overall mortality and CRC recurrence in patients receiving preoperative SEMS vs. patients undergoing urgent resection.PATIENTS AND METHODS: This was a Danish, nationwide, population-based cohort study (2005 - 2010). For patients with CRC who survived the first 30 days after resection, the long-term survival in terms of mortality rate ratios was assessed using Cox regression with adjustment for important covariates. For patients with Dukes' A - C disease only, recurrence risk was similarly assessed using incidence rate ratios.RESULTS: The 5-year survival was 49 % among 581 patients with preoperative SEMS and 40 % among 3333 patients undergoing urgent resection, corresponding to an adjusted mortality rate ratio of 0.98 (95 % confidence interval [CI] 0.90 to 1.07). For patients with Dukes' stage A - C disease, the 5-year recurrence risk was 39 % among 286 patients after preoperative SEMS and 30 % among 1627 patients after urgent resection, corresponding to an adjusted incidence rate ratio of 1.12 (95 %CI 0.99 to 1.28).CONCLUSIONS: Long-term mortality associated with the use of SEMS as a bridge to surgery was comparable to that of urgent resection. SEMS use may be associated with an increased CRC recurrence risk.

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 between 1980 and 2012. A comparison cohort of 515 067 subjects, matched by age, gender, and calendar year, was selected from the general Danish population. Outcomes were venous thromboembolism, acute myocardial infarction, ischemic stroke, and death. During median follow-up of 7 years, the incidence rate of venous thromboembolism 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 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. The hazard ratios for acute myocardial infarction, 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.

Background The prognostic impact of preadmission use of calcium channel blockers (CCBs) and beta blockers (BBs) on stroke mortality remains unclear. We aimed to examine whether preadmission use of CCBs or BBs was associated with improved short-term mortality following ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Methods We conducted a nationwide population-based cohort study using Danish medical registries. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012 and their comorbidities. We defined CCB/BB use as current use, former use, or non-use. Current use was further classified as new or long-term use. We used Cox regression modeling to compute 30-day mortality rate ratios (MRRs) with 95% confidence intervals (CIs), controlling for potential confounders. Results We identified 100,043 patients with a first-time stroke. Of these, 83,736 (83.7%) patients had ischemic stroke, 11,779 (11.8%) had ICH, and 4,528 (4.5%) had SAH. Comparing current users of CCBs or BBs with non-users, we found no association with mortality for ischemic stroke [adjusted 30-day MRR = 0.99 (95% CI: 0.94-1.05) for CCBs and 1.01 (95% CI: 0.96-1.07) for BBs], ICH [adjusted 30-day MRR = 1.05 (95% CI: 0.95-1.16) for CCBs and 0.95 (95% CI: 0.87-1.04) for BBs], or SAH [adjusted 30-day MRR = 1.05 (95% CI: 0.85-1.29) for CCBs and 0.89 (95% CI: 0.72-1.11) for BBs]. Former use of CCBs or BBs was not associated with mortality. Conclusions Preadmission use of CCBs or BBs was not associated with 30-day mortality following ischemic stroke, ICH, or SAH. Electronic supplementary material The online version of this article (doi:10.1186/s12883-015-0279-3) contains supplementary material, which is available to authorized users.

Diana Hedevang Christensen,1,2 Erzsébet Horváth-Puhó,1 Morten Schmidt,1 Christian Fynbo Christiansen,1 Lars Pedersen,1 Bente Lomholt Langdahl,2 Reimar Wernich Thomsen1 1Department of Clinical Epidemiology, 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark Purpose: Bisphosphonate use has been associated with increased risk of fatal stroke. We examined the association between preadmission use of oral bisphosphonates and 30-day mortality following hospitalization for stroke. Patients and methods: We conducted a nationwide population-based cohort study using medical databases and identified all patients in Denmark with a first-time hospitalization for stroke between 1 July 2004 and 31 December 2012 (N=100,043). Cox regression was used to compute adjusted hazard ratios as a measure of 30-day mortality rate ratios (MRRs) associated with bisphosphonate current use (prescription filled within 90 days prior to the stroke) or recent use (prescription filled in the 90–180 days prior to the stroke). Current use was further classified as new or long-term use. Results: We found 51,982 patients with acute ischemic stroke (AIS), 11,779 with intracerebral hemorrhage (ICH), 4,528 with subarachnoid hemorrhage (SAH), and 31,754 with unspecified stroke. Absolute 30-day mortality risks were increased among current vs nonusers of bisphosphonates for AIS (11.9% vs 8.5%), ICH (43.2% vs 34.5%), SAH (40.3% vs 23.2%), and unspecified strokes (18.8% vs 14.0%). However, in adjusted analyses, current bisphosphonate use did not increase 30-day mortality from AIS (MRR, 0.87; 95% confidence interval [CI]: 0.75, 1.01); ICH (MRR, 1.05; 95% CI: 0.90, 1.23); SAH (MRR, 1.15; 95% CI: 0.83, 1.61); or unspecified stroke (MRR, 0.94; 95% CI: 0.81, 1.09). Likewise, no association with mortality was found for recent use. Adjusted analyses by type of bisphosphonate showed increased mortality following stroke among new users of etidronate (MRR, 1.40; 95% CI: 1.01, 1.93) and reduced mortality after AIS among current users of alendronate (MRR, 0.87; 95% CI: 0.74, 1.02). Conclusion: We found no overall evidence that preadmission bisphosphonate use increases 30-day mortality following stroke. Keywords: prognosis, oral bisphosphonates, stroke, mortality, cardiovascular disease, osteoporosis treatment

Herpes zoster (HZ) may be a marker of occult cancer (Sorensen et al., 2004; Ho et al., 2011; Liu et al., 2012; Wang et al., 2012; Chiu et al., 2013; Cotton et al., 2013; Iglar et al., 2013) and some authors have advocated increased work-up for cancer in patients with HZ (Zaha et al., 1993; Yamamoto et al., 2003; Cotton et al., 2013). However, limited data are available on whether HZ may be used to predict mortality in patients presenting with subsequent cancer in clinical practice. The two previous studies on the topic overall showed no association (Sorensen et al., 2004; Cotton et al., 2013), but were limited by small sample sizes and lacked information on key prognostic factors, such as cancer stage and comorbidities. The first study, which was conducted by our research group, was furthermore restricted to in-patient HZ diagnoses (Sorensen et al., 2004). Our objective was to provide updated and more detailed analyses of the association between HZ and mortality following a subsequent cancer by extending the period of follow-up, by including inpatient, outpatient and emergency room HZ diagnoses, and by obtaining information on cancer stage, comorbidities and use of immunosuppressive drugs.

Summary Background Data on statins' effect on venous thromboembolism (VTE) recurrence are conflicting. Objectives We examined whether statin use was associated with reduced risk of recurrent VTE in a nationwide population-based setting. Patients/Methods Using the Danish National Patient Registry, we identified first-time and recurrent VTEs between 1 July 2004 and 31 December 2012 (n = 27 862). VTE diagnoses were validated by medical record review of a subsample of patients. We ascertained nationwide prescription data and categorized statin use as current (further divided into new and long-term use), former and no use. We identified statin use at baseline (mimicking an intention-to-treat analysis) and in a time-varying manner during follow-up (mimicking per-protocol analysis) and computed hazard ratios (HRs) for recurrent VTE using Cox regression. In a supplementary nested case–control study, we identified statin use at time of VTE recurrence and computed odds ratios as unbiased estimates of the incidence rate ratios (IRRs) using conditional logistic regression. We adjusted for age, sex, year of diagnosis, provoking factors, co-morbidities and co-medications, including time-varying use of aspirin and anticoagulant drugs. Results The adjusted HR comparing current use with no use was 0.72 (95% confidence interval [CI], 0.59–0.88) for recurrent VTE, with a stronger effect of high (0.40; 95% CI, 0.21–0.78) vs. low potency statins (0.77; 95% CI, 0.63–0.94). Consistently, the recurrence rate was reduced in both the time-varying analysis (HR=0.64; 95% CI, 0.54–0.77) and nested case–control analysis (IRR=0.55; 95% CI, 0.45–0.67). The effect was largest for recurrent deep venous thrombosis. Conclusions Statin use was associated with reduced VTE recurrence.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PCI) is the preferred treatment. In primary PCI patients with multivessel disease, it is unclear whether culprit vessel PCI only is the preferred treatment. We compared mortality among (1) STEMI patients with single-vessel disease and those with multivessel disease and (2) multivessel disease patients with and without additional revascularization of nonculprit lesions within 2 months after the index PCI.METHODS: From January 2002 to June 2009, all patients presenting with STEMI and treated with primary PCI were identified from the Western Denmark Heart Registry, which covers a population of 3.0 million. The hazard ratio (HR) for death was estimated using a Cox regression model, controlling for potential confounding.RESULTS: The study cohort consisted of 8,822 patients: 4,770 (54.1%) had single-vessel disease and 4,052 (45.9%) had multivessel disease. Overall, 1-year cumulative mortality was 7.6%, and 7-year cumulative mortality was 24.0%. Multivessel disease was associated with higher 7-year mortality (adjusted HR 1.45 [95% CI 1.30-1.62], P < .001). Among patients with multivessel disease, lack of additional revascularization beyond the culprit lesion was associated with higher 7-year mortality (adjusted HR 1.50 [95% CI 1.25-1.80], P < .001). In patients with multivessel disease who underwent additional revascularization, 7-year mortality (adjusted HR 1.01 [95% CI 0.84-1.22], P = .89) was similar compared to patients with single-vessel disease.CONCLUSION: In STEMI patients, multivessel disease was associated with a higher mortality compared to single-vessel disease. In multivessel disease patients, additional revascularization was associated with a higher survival compared with culprit vessel PCI only.

Background— Studies on long-term mortality after venous thromboembolism (VTE) are sparse. Methods and Results— Using Danish medical databases, we conducted a 30-year nationwide population-based cohort study of 128 223 patients with first-time VTE (1980–2011) and a comparison cohort of 640 760 people from the general population (without VTE) randomly matched by sex, year of birth, and calendar period. The mortality risks for patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (3.0% and 31% versus 0.4%). Using Cox regression, we assessed mortality rate ratios (MRRs) with 95% confidence intervals (CIs). The overall 30-year MRR was 1.55 (95% CI, 1.53–1.57) for DVT and 2.77 (95% CI, 2.74–2.81) for PE. The 30-day MRR was 5.38 (95% CI, 5.00–5.80) for DVT and 80.87 (95% CI, 76.02–86.02) for PE. Over time, the 30-day MRR was consistently 5- to 6-fold increased for DVT, whereas it improved for PE from 138 (95% CI, 125–153) in 1980 to 1989 to 36.08 (95% CI, 32.65–39.87) in 2000 to 2011. The 1- to 10-year and 11- to 30-year MRRs remained 25% to 40% increased after both DVT and PE but were 3- to 5-fold increased after DVT and 6- to 11-fold increased after PE when VTE was considered the immediate cause of death. Conclusions— Patients with VTE are at increased risk of dying, especially within the first year after diagnosis, but also during the entire 30 years of follow-up, with VTE as an important cause of death. Although 30-day mortality after DVT remained fairly constant over the last 3 decades, it improved markedly for PE.

Although migraine is one of the commonest chronic disorders in women and frequently affects those of reproductive age, its effects on pregnancy have not been studied in detail. The investigators utilized data collected as part of a population-based study of congenital anomalies to evaluate the relationship between a history of maternal migraines and pregnancy outcomes. They reviewed the pregnancy histories of 38,151 structurally normal newborn infants who were born in the years 1980-1996. The mothers of 713 infants, 1.9% of the total, had severe migraine with and without aura during pregnancy. In all cases, migraine had begun before the study pregnancy and one or more episodes occurred during pregnancy-chiefly in the third month of gestation. Pregnant women with severe migraine had a significantly higher prevalence of preeclampsia (odds ratio, 1.4; 95% confidence intervals, 1.1-1.8) and severe nausea and vomiting (OR, 1.5; CI, 1.2-1.8), while rates of threatened abortion (OR, 0.7; CI, 0.6-0.9) and preterm delivery (OR, 0.8; CI, 0.6-0.9) were significantly lower than in migraine-free women. The rates of placental disorders, prolonged pregnancy, gestational diabetes, poly- and oligohydramnios, and anemia were the same in both groups. Pregnant women with and without migraine had a similar incidence of acute medical disorders such as respiratory infections and digestive system or genital tract problems. The incidence of urinary tract infections was lower in women with migraine. The rates of chronic diseases like diabetes and epilepsy were similar in women with and without migraine, while women with migraine were more likely to have cardiac dysrhythmias (OR, 8.8; CI, 5.0-13.6), thyroid disease (OR, 3.0; CI, 1.4-6.4), and panic disorder (OR, 4.7; CI, 2.8-7.8) than those without headaches. In terms of pregnancy outcome, the proportion of male infants, the mean gestational age, the mean birth weight, and the numbers of post term births were comparable in newborn infants whose mothers had or did not have migraine. No difference in these variables was found between male and female infants born to mothers with or without migraine.

OBJECTIVES: To assess the interaction between comorbidity and breast cancer (BC) on the rate of venous thromboembolism (VTE) beyond what can be explained by the independent effects of BC and comorbidity.DESIGN: Population-based matched cohort study.SETTING: Denmark.PARTICIPANTS: Danish patients with BC (n=62 376) diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803) from the general population were matched to the patients with BC on year of birth in 5-year intervals and on the specific diseases included in the Charlson Comorbidity Index (CCI) and atrial fibrillation and obesity.MEASURES: The rate ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels using the CCI, and interaction contrasts (IC) were calculated as a measure of the excess or deficit VTE rate not explained by the independent effects of BC and comorbidity.RESULTS: Among patients with BC with a CCI score of 1, the 0-1 year VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2, 95% CI 0.5 to 5.9). Among patients with BC with CCI ≥4, the VTE rate was 17, and interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was no interaction during 2-5 years of follow-up.CONCLUSIONS: There was only little interaction between BC and the CCI score on the rate of VTE.

Background & Aims 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. Methods We identified 77,065 incident cases of diverticular disease from 1980–2011 from Danish nationwide medical registries; these were matched for age and sex with 302,572 population comparison cohort members. Individuals with a 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 with 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. Results The adjusted incidence rate ratios for patients with diverticular disease, compared with population cohort members, were 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 after 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. Conclusions On the basis of 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.

OBJECTIVES: Population-based studies of site-specific cancer risk in patients with inflammatory bowel disease (IBD) according to IBD phenotype and treatment are lacking. We studied cancer risk in a well-characterized population-based IBD cohort from North Jutland County, Denmark.METHODS: A total of 1,515 patients were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD) during 1978-2002. Patients were followed until 31 December 2010 for occurrence of incident cancer, identified in the Danish Cancer Registry. Observed numbers of cancer were compared with expected numbers (based on age- and sex-specific background rates) and presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs).RESULTS: Patients with UC were not at increased risk of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55% increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young age, colonic disease, smoking, and thiopurine exposure. Patients were at increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis, smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)).CONCLUSIONS: Patients with CD, but not UC, have an overall excess risk of cancer. Clinical characteristics of IBD patients at excess risk differ by cancer subtype.

Background:It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions.Methods:We conducted a cohort study (1995-2010) of all Danish CRC patients (n=56 963), and five times as many persons from the general population (n=271 670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities.Results:Among CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis.Conclusion:Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.British Journal of Cancer advance online publication, 10 September 2013; doi:10.1038/bjc.2013.541 www.bjcancer.com.

Context:Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS.Objective:To examine the risks for mortality, cardiovascular disease, fractures, peptic ulcers, and infections in CS patients before and after treatment.Design:Population-based cohort studySetting:Source population was the entire population of Denmark (1980 to 2010). Data were obtained from the Danish National Registry of Patients and the Danish Civil Registration System.Patients:Benign CS of adrenal or pituitary origin and a matched population comparison cohort were included.Outcome measures:We used Cox-regression, and computed hazard ratios (HR) with 95% confidence intervals (95% CI). Morbidity was investigated in the three years before diagnosis; morbidity and mortality was assessed during complete follow-up after diagnosis and treatment.Results :343 CS patients and 34,300 controls were included. Mortality was twice as high in CS patients (HR 2.3, 95%CI 1.8-2.9) compared with controls. Patients with CS were at increased risk for venous thromboembolism (HR 2.6, 95%CI 1.5-4.7), myocardial infarction (HR 3.7, 95%CI 2.4-5.5), stroke (HR 2.0, 95%CI 1.3-3.2), peptic ulcers (HR 2.0, 95%CI 1.1-3.6), fractures (HR 1.4, 95%CI 1.0-1.9), and infections (HR 4.9, 95%CI 3.7-6.4). This increased multi-morbidity risk was present before diagnosis. Mortality and risk of myocardial infarction remained elevated during long-term follow-up. Mortality and risks for AMI, VTE, stroke and infections were similarly increased in adrenal and pituitary CS.Conclusions :Despite the apparently benign character of the disease, CS is associated with clearly increased mortality and multisystem morbidity, even before diagnosis and treatment.

The pleiotropic effects of statins have been suggested to prevent atrial fibrillation onset. We conducted a population-based case-control study using medical databases from Northern Denmark (population: 1.8 million) to examine the association between statin use and atrial fibrillation or flutter. We identified 51,374 patients with atrial fibrillation or flutter between 1999 and 2010 and 513,670 matched population controls. We collected data on statin prescriptions redeemed within 90 days (current users) or longer (former users) before the diagnosis date of atrial fibrillation or flutter. We stratified statin users by duration of exposure, determined by the number of days between first and last redeemed prescription before the diagnosis date (

Background The impact of inflammatory bowel disease (IBD) on colorectal cancer (CRC) prognosis, taking into account other comorbidities, is not clear. We studied the overall mortality in CRC patients with a history of ulcerative colitis (UC) or Crohn's disease (CD) compared with non-IBD-CRC patients. Methods Data on all CRC and IBD patients diagnosed with CRC between 1977 and 2009 were retrieved from Danish medical registries. One-year and 5-year overall mortality were evaluated with the Kaplan-Meier method and with Cox regression, adjusting for year of CRC diagnosis, sex, Duke's stage, age at CRC diagnosis, and Charlson Comorbidity Index score. Results We identified 653 CRC patients diagnosed with UC, 238 patients with CD, and 107,024 CRC patients without IBD. The patients with IBD were younger at diagnosis than patients without IBD. The Duke's stage distribution was similar for UC-CRC patients and non-IBD-CRC patients. The CD-CRC patients had a lower frequency of Duke's A and B stage tumors (36% versus 42%), a higher frequency of Duke's C stage tumors (31% versus 27%) and Duke's D-stage tumors (23% versus 21%), and a similar frequency of unknown stage tumors (10%) compared with non-IBD-CRC patients. After 5-years of follow-up, 59% of the UC and the non-UC-CRC patients had died compared with 62% of the patients with CD and 56% of the non-CD-CRC patients. The 5-year adjusted mortality rate ratios for patients with UC or CD were 1.14 (95% confidence interval, 1.03-1.27) and 1.26 (95% confidence interval, 1.07-1.49), respectively, compared with patients without IBD. Conclusion A history of IBD in patients with CRC may be associated with increased mortality.

Importance: Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother.Objective: To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality.Design, Setting, and Participants: This population-based cohort study (n = 455 250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41 508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413 742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth.Exposure: Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system.Main Outcomes and Measures: Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004).Results: Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41 508 mothers of a child with a major congenital anomaly vs 10 112 deaths (1.27 per 1000 person-years) among 413 742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]).Conclusions and Relevance: In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.

Sigrun Alba Johannesdottir, Erzsébet Horváth-Puhó, Vera Ehrenstein, Morten Schmidt, Lars Pedersen, Henrik Toft SørensenDepartment of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, DenmarkAbstract: The Danish health care system provides partial reimbursement of most prescription medications in Denmark. The dispensation of prescription medications is registered in administrative databases. Each time a prescription is redeemed at a pharmacy, an electronic record is generated with information related to the user, prescriber, the pharmacy, and the dispensed drug. The National Health Service gathers this information for administration of the drug reimbursement plan. Recently, this information became the basis for the establishment of a new research database, the Danish National Database of Reimbursed Prescriptions (DNDRP). In this paper, we review the content, coverage, quality, linkage, access, and research possibilities of this new database. The database encompasses the reimbursement records of all reimbursed drugs sold in community pharmacies and hospital-based outpatient pharmacies in Denmark since 2004. On average, approximately 3.5 million users are recorded in the database each year. During the coverage period, the number of annual prescription redemptions increased by 15%. Most dispensed prescriptions are in the categories “alimentary tract and metabolism”, “cardiovascular system”, “nervous system”, and “respiratory system”. Individuals are identified by the unique central personal registration (CPR) number assigned to all persons born in or immigrating to Denmark. The new database fully complies with Denmark’s Act on Processing of Personal Data, while avoiding additional restrictions imposed on data use at the Danish National Prescription Registry, administered by Statistics Denmark. Most importantly, CPR numbers are reversibly encrypted, which allows re-identification of drug users; furthermore, the data access is possible outside the servers of Statistics Denmark. These features open additional opportunities for international collaboration, validation studies, studies on adverse drug effects requiring review of medical records, studies involving contact to general practitioners, and linkage of prescription data to other clinical and research databases. The DNDRP thus is a valuable data source for pharmacoepidemiological research.Keywords: Denmark, patient registration, pharmacoepidemiology, registry-based research

Summary. Background: Systemic inflammation is associated with vessel wall damage, upregulation of procoagulants, downregulation of anticoagulants, and suppression of fibrinolysis. Autoimmune diseases may therefore increase the risk of venous thromboembolism (VTE). Objectives: To examine whether autoimmune skin and connective tissue diseases are associated with increased VTE risk. Methods: We conducted this population-based case–control study in northern Denmark, using administrative databases. From 1999 to 2009, we identified 14 721 VTE cases and 147 210 birth year-matched, sex-matched and county-matched population controls. The date of diagnosis/matching was considered to be the index date for cases and controls. For all study subjects, we identified hospital diagnoses of autoimmune skin or connective tissue diseases between 1977 and the index date. We used conditional logistic regression with adjustment for VTE risk factors to calculate odds ratios and 95% confidence intervals (CIs) for patients with vs. without autoimmune disease. Given the risk-set sampling design, odds ratios estimate incidence rate ratios (IRRs). Results: Autoimmune skin disease was not associated with VTE (IRR 1.0; 95% CI 0.9–1.2). Patients with connective tissue disease had an increased VTE risk within 90 days (IRR 2.3; 95% CI 1.5–3.7) and 91–365 days (IRR 2.0; 95% CI 1.5–2.8) after diagnosis, but not thereafter (IRR 1.1; 95% CI 1.0–1.2). Among connective tissue diseases, the greatest overall risk increases were found for juvenile rheumatoid arthritis (IRR 3.0; 95% CI 1.4–6.4) and systemic lupus erythematosus (IRR 2.8; 95% CI 1.7–4.7). Conclusions: Autoimmune connective tissue disease was associated with an increased risk of VTE within 1 year after diagnosis, whereas skin diseases were not.

Aims: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only. Methods and results: From January 2002 to June 2009 all patients treated with PPCI were identified from the Western Denmark Heart Registry. We examined mortality according to timing of multivessel PCI: acute procedure, staged procedure during the index hospitalisation, or staged procedure performed within 60 days. The hazard ratio (HR) for death was estimated using a time-dependent Cox regression model, with time of PCI for the non-culprit lesion as the time-dependent variable. The study cohort consisted of 5,944 patients, of whom 4,770 (80%) had single-vessel disease and 1,174 (20%) had multivessel PCI within 60 days. Among 354 (30.2%) patients with acute multivessel PCI, 194 (16.5%) patients with multivessel PCI during the index hospitalisation, and 626 (53.3%) patients with multivessel PCI within 60 days after the index hospitalisation, the adjusted HRs for one-year mortality were 1.53 (95% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease. Conclusions: Acute multivessel PCI in patients with STEMI was associated with increased mortality.

Background— Heart diseases increase the risk of arterial embolism; whether they increase the risk of pulmonary embolism without peripheral venous thrombosis is less certain. Methods and Results— We conducted a nationwide, population-based case-control study in Denmark using patients diagnosed with pulmonary embolism and/or deep venous thrombosis between 1980 and 2007. We computed odds ratios to estimate relative risks associating preceding heart disease with pulmonary embolism, pulmonary embolism and deep venous thrombosis, or deep venous thrombosis alone. In this study, 45 282 patients had pulmonary embolism alone, 4680 had pulmonary embolism and deep venous thrombosis, and 59 790 had deep venous thrombosis alone; 541 561 were population controls. Myocardial infarction and heart failure in the preceding 3 months conferred high risks of apparently isolated pulmonary embolism (odds ratio, 43.5 [95% confidence interval (CI), 39.6–47.8] and 32.4 [95% CI, 29.8–35.2], respectively), whereas the risks of combined pulmonary embolism and deep venous thrombosis (19.7 [95% CI, 16.0–24.2] and 22.1 [95% CI, 18.7–26.0], respectively) and deep venous thrombosis alone (9.6 [95% CI, 8.6–10.7] and 12.7 [95% CI, 11.6–13.9], respectively) were lower. Left-sided valvular disease was associated with an odds ratio of 13.5 (95% CI, 11.3–16.1), whereas the odds ratio was 74.6 (95% CI, 28.4–195.8) for right-sided valvular disease. Restricting the analysis to cases diagnosed after 2000 led to lower risk estimates but the same overall pattern. Conclusion— Heart diseases increase the near-term risk for pulmonary embolism not associated with diagnosed peripheral vein thrombosis.

Schmidt M, Horvath-Puho E, Thomsen RW, Smeeth L, Sorensen HT (Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; and Department of Non-Communicable Epidemiology, London School of Hygiene and Tropical Medicine, London, UK). Acute infections and venous thromboembolism. J Intern Med 2012; 271: 608–618. Background. Data on the association between acute infections and venous thromboembolism (VTE) are sparse. We examined whether various hospital-diagnosed infections or infections treated in the community increase the risk of VTE. Methods. We conducted this population-based case–control study in Northern Denmark (population 1.8 million) using medical databases. We identified all patients with a first hospital-diagnosed VTE during the period 1999–2009 (n = 15 009). For each case, we selected 10 controls from the general population matched for age, gender and county of residence (n = 150 074). We identified all hospital-diagnosed infections and community prescriptions for antibiotics 1 year predating VTE. We used odds ratios from a conditional logistic regression model to estimate incidence rate ratios (IRRs) of VTE within different time intervals of the first year after infection, controlling for confounding. Results. Respiratory tract, urinary tract, skin, intra-abdominal and bacteraemic infections diagnosed in hospital or treated in the community were associated with a greater than equal to twofold increased VTE risk. The association was strongest within the first 2 weeks after infection onset, gradually declining thereafter. Compared with individuals without infection during the year before VTE, the IRR for VTE within the first 3 months after infection was 12.5 (95% confidence interval (CI): 11.3–13.9) for patients with hospital-diagnosed infection and 4.0 (95% CI: 3.8–4.1) for patients treated with antibiotics in the community. Adjustment for VTE risk factors reduced these IRRs to 3.3 (95% CI: 2.9–3.8) and 2.6 (95% CI: 2.5–2.8), respectively. Similar associations were found for unprovoked VTE and for deep venous thrombosis and pulmonary embolism individually. Conclusions. Infections are a risk factor for VTE.

Udgivelsesdato: 2010-Aug BACKGROUND: Venous thromboembolism is a predictor of subsequent risk of ischemic stroke and intracerebral hemorrhage, but no data are available regarding its association with risk of subarachnoid hemorrhage. OBJECTIVES: To examine this issue, we conducted a nationwide cohort study in Denmark. PATIENTS AND METHODS: Between 1977 and 2007, we identified 97,558 patients with a hospital diagnosis of venous thromboembolism and obtained information on risk of subsequent subarachnoid hemorrhage during follow-up in the Danish Registry of Patients. The incidence of subarachnoid hemorrhage in the venous thromboembolism cohort was compared with that of 453,406 population control cohort members. RESULTS: For patients with pulmonary embolism (PE), there was clearly an increased risk of subarachnoid hemorrhage, both during the first year of follow-up [relative risk 2.69; 95% confidence interval (CI), 1.32-5.48] and during later follow-up of 2-20 years (relative risk 1.40; 95% CI, 1.05-1.87). For patients with deep venous thrombosis (DVT) the risk was likewise clearly increased during the first year of follow-up (relative risk 1.91; 95% CI, 1.13-3.22), but not during later follow-up (relative risk 1.04; 95% CI, 0.81-1.32). CONCLUSIONS: We found evidence that PE is associated with an increased long-term risk of subarachnoid hemorrhage. The two diseases might share etiologic pathways affecting the vessel wall or share unknown risk factors.

Anna K Jönsson1, Erzsebet Horváth-Puhó2, Staffan Hägg3, Lars Pedersen4, Henrik Toft Sørensen41Nordic School of Public Health, Gothenburg, Sweden; 2Centre for Registry Research, Aarhus C, Denmark; 3Division of Clinical Pharmacology, Linköping University, Linköping, Sweden; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus C, DenmarkAbstract: During the last decade, the risk of venous thromboembolism (VTE) has been reported in users of antipsychotic drugs. However, the reports have been inconclusive. This study aimed to determine the relative risk of VTE in antipsychotic drug users. Using data from medical databases in North Jutland and Aarhus Counties, Denmark, and the Danish Civil Registration System, we identified 5,999 cases with a first-time diagnosis of VTE and, based on risk set sampling, 59,990 sex- and age-matched population controls during 1997–2005. Users of antipsychotic drugs were identified from population-based prescription databases and categorized based on filled prescriptions prior to admission date for VTE or index date for controls as current (at least one prescription within 90 days), recent (at least one prescription within 91–180 days), former (at least one prescription within 181–365 days) or nonusers (no recorded prescription within 365 days). Compared with nonusers, current users of any antipsychotic drugs had an increased risk of VTE (adjusted relative risk [ARR]: 1.99, 95% confidence interval [CI]: 1.69–2.34). Former users of any antipsychotic drugs had a nonsignificant elevated risk of VTE compared with nonusers (ARR: 1.54, 95% CI: 0.99–2.40, p-value: 0.056). In conclusion, users of antipsychotic drugs have an increased risk of VTE, compared with nonusers, which might be due to the treatment itself, to lifestyle factors, to the underlying disease, or to residual confounding. Keywords: antipsychotic agents, venous thromboembolism, adverse effects, case-control study

Udgivelsesdato: 2009-Jan OBJECTIVES: It is known that liver disease can cause an imbalance in the coagulation system, but available data on liver disease and risk of venous thromboembolism are conflicting. We examined the risk of venous thromboembolism in patients hospitalized with liver diseases. METHODS: We conducted a nationwide Danish case-control study of incident cases of venous thromboembolism from 1980 to 2005 using population-based data from the National Registry of Patients, and from the Civil Registration System. We used conditional logistic regression to compute the relative risk of venous thromboembolism in patients with liver disease compared to population controls. We then excluded patients with known malignancy (diagnosed either before or up to 3 months after the venous thromboembolism) or fractures, trauma, surgery, or pregnancy within 90 days before the venous thromboembolism to estimate the risk associated with unprovoked venous thromboembolism. RESULTS: A total of 99,444 patients with venous thromboembolism and 496,872 population controls were included in the study. Patients with liver disease had a clearly increased relative risk of venous thromboembolism, varying from 1.74 (95% CI, 1.54-1.95) for liver cirrhosis to 1.87 (95% CI, 1.73-2.03) for non-cirrhotic liver disease. The risks were higher for deep venous thrombosis compared with pulmonary embolism. In the analysis, restricted to 67,519 patients with unprovoked venous thromboembolism and 308,614 population controls, we found slightly higher relative risks: 2.06 (95% CI, 1.79-2.38) for liver cirrhosis and 2.10 (95% CI, 1.91-2.31) for non-cirrhotic liver disease. CONCLUSIONS: Patients with liver disease have a substantially increased risk of venous thromboembolism.

Udgivelsesdato: 2008-Jan-15 In a Danish nationwide cohort study of 292 births from 1973 to 2002 in women with Hodgkin's disease (HD), we compared birth outcome with 14 042 births from a cohort of mothers without cancer. We found no substantially increased risk of preterm birth, low birth weight at term, or stillbirth and no difference in proportion of male newborns for 192 children of women with HD before pregnancy. The prevalence odds ratio (POR) for congenital abnormalities was 1.7 (95% confidence interval (CI): 0.9-3.1). Among 15 newborns of mothers diagnosed during pregnancy, the POR of preterm birth was 26.6 (95% CI: 8.5-83.0), but five out of the eight preterm deliveries among these women were elective. We found no substantially increased risk of adverse birth outcome among 85 newborns of women diagnosed within 2 years postpartum, though effect estimates were imprecise. The overall findings are reassuring, they cannot exclude the possibility of an increased risk of congenital abnormalities for newborns of women diagnosed with HD before pregnancy.

Summary Background In some studies, venous thromboembolism has been associated with atherosclerosis and with the risk of arterial cardiovascular events such as myocardial infarction and stroke. Other studies, however, do not show this association. To help clarify these discrepant findings, we aimed to investigate the risk of arterial cardiovascular events in patients who were diagnosed with venous thromboembolism. Methods We undertook a 20-year population-based cohort study using data from nationwide Danish medical databases. After excluding those with known cardiovascular disease, we assessed the risk of myocardial infarction and stroke in 25 199 patients with deep venous thrombosis, 16 925 patients with pulmonary embolism, and 163 566 population controls. Findings For patients with deep venous thrombosis, the relative risks varied from 1·60 for myocardial infarction (95% CI 1·35–1·91) to 2·19 (1·85–2·60) for stroke in the first year after the thrombotic event. For patients with pulmonary embolism, the relative risks in that year were 2·60 (2·14–3·14) for myocardial infarction and 2·93 (2·34–3·66) for stroke. The relative risks were also raised, though less markedly, during the subsequent 20 years of follow-up, with 20–40% increases in risk for arterial cardiovascular events. Relative risks were similar for those with provoked and unprovoked deep venous thrombosis and pulmonary embolism. Interpretation Patients with venous thromboembolism have a substantially increased long-term risk of subsequent arterial cardiovascular events.

OBJECTIVES: Patients with cirrhosis are at increased risk of venous thromboembolism (VTE), but the impact of cirrhosis on the clinical course following VTE is unclear. In a nationwide cohort study, we examined 30-day mortality among patients with cirrhosis and VTE.METHODS: We used Danish population-based health-care databases (1994-2011) to identify patients with incident VTE, i.e., deep venous thrombosis (DVT), pulmonary embolism (PE), and portal vein thrombosis (PVT). Among these, we identified 745 patients with cirrhosis and 3647 patients without cirrhosis (matched on gender, year of birth, calendar year of VTE diagnosis and VTE type). We assessed the 30-day mortality risk among VTE patients with and without cirrhosis, and the mortality rate ratios (MRRs), using an adjusted Cox model with 95% confidence interval. We obtained information on immediate cause of death for patients who died within 30 days after VTE.RESULTS: The 30-day mortality risk for DVT was 7% for patients with cirrhosis and 3% for patients without cirrhosis. Corresponding PE-related mortality risks were 35% and 16%, and PVT-related mortality risks were 19% and 15%, respectively. The adjusted 30-day MRRs were 2.17 (1.24-3.79) for DVT, 1.83 (1.30-2.56) for PE, and 1.30 (0.80-2.13) for PVT. Though overall mortality was higher in patients with cirrhosis than patients without cirrhosis, the proportions of deaths due to PE were similar among patients (25% and 24%, respectively).CONCLUSIONS: Cirrhosis is a predictor for increased short-term mortality following VTE, with PE as the most frequent cause of death.

BACKGROUND: Migraines occurs frequently during pregnancy; however, there are no published data on their possible teratogenic potential in a controlled epidemiological study. Therefore, we examined the risk of congenital abnormalities in infants born to women who had migraines and other headaches during pregnancy. METHODS: Between 1980 and 1996, the Hungarian Case-Control Surveillance of Congenital Abnormalities evaluated 22,843 cases (newborns or fetuses) with congenital abnormalities, 38,151 control newborn infants without any abnormalities, and 834 malformed controls with Down syndrome. RESULTS: Migraines anytime during pregnancy occurred in 565 (2.5%) mothers of the case group compared with 713 (1.9%) mothers in the control group (crude prevalence odds ratio [POR], 1.3; 95% confidence interval [CI], 1.2-1.5) and 24 (2.9%) pregnant women in the malformed control group (crude POR, 0.9; 95% CI, 0.6-1.3) The mothers of 247 cases, 533 controls, and 21 malformed controls had severe migraines during the second and/or third months of pregnancy. There was only 1 congenital abnormality group: limb deficiencies, which had a higher rate of maternal migraines during the second and third months of pregnancy both at the comparison of cases and matched controls (adjusted POR, 2.5; 95% CI, 1.1-5.8) and of cases and malformed controls (adjusted POR, 1.7; 95% CI, 1.3-3.0). There was no association between other headaches and different congenital abnormalities at the comparison of cases and controls. CONCLUSIONS: Our data showed that maternal severe migraines during the second and/or third months of pregnancy were associated with an increased risk of congenital limb deficiencies. A similar association was not detected between congenital anomalies and other headaches during pregnancy. Our study was not based on a prior hypothesis; therefore, these data can be considered only as a signal that needs confirmation by independent data sets.

To detect the possible etiological factors in the origin of isolated congenital cataracts.The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contained 111 cases with isolated congenital cataract and their 111 matched control pairs without defect, 22744 patient controls with other non-ocular abnormalities and 37837 population controls without any defects. Exposure data and family history were based on (i) medical records, (ii) retrospective maternal information and (iii) information obtained by regional nurses at home visit of nonrespondent families.Positive family history indicated autosomal dominant origin in 9,9% of the cases. Rubella infections occurred more frequently in case mothers than in control mothers before the vaccination against rubella virus. A higher prevalence of influenza/common cold (55.9% in the case and 18.5% in the population control group, adjusted OR with 95% CI: 5.8, 4.0-8.4 and 21.7% in the malformation control group: 4.7, 3.2-6.9) and acute infectious diseases of respiratory system (26.1% in the case and 9.1% in the population control group: 3.8, 2.5-5.8 and 9.3% in the malformation control group: 3.4, 2.2-5.3) related with fever was found during the pregnancy of the case mothers. In addition the higher risk of isolated congenital cataract was prevented by antifever therapy.Some part of isolated congenital cataract is preventable by rubella vaccination and probably by influenza vaccination in the epidemic period, in addition it is worth using an effective antifever therapy of fever related respiratory diseases to restrict the teratogenic risk of fever.

Background: Self-expanding metal stents (SEMS) used as a bridge to surgery for obstructive colorectal cancer (CRC) have fallen under suspicion for inducing tumor dissemination and thereby increasing CRC recurrence and long-term mortality, but data regarding these risks are sparse. Several attempts to compare SEMS with acute surgery in randomized settings have failed and the existing evidence from observational studies is based primarily on singlecenter studies conducted in highly specialized settings with little or no information on potential confounding factors.Methods:We conducted a nationwide population-based cohort study using Danish medical registries (2005-2010) by comparing overall mortality and recurrence after CRC resection in patients with preoperative stenting (n=581) to patients undergoing urgent (n=3,333) or elective resection (n=13,722). For patients surviving the first 30 days after CRC resection, we used the Kaplan Meier method to compute absolute survival. For CRC patients with localized and regional disease, the risk of CRC recurrence was estimated treating death as a competing risk. We computed mortality rate ratios (MRRs) and cause specific hazard ratios of recurrence within 5 years, using Cox regression with adjustment for important covariates. Results: Crude 5-year survival was 49% (95% CI: 43%55%) among patients with preoperative SEMS, 40% (95% CI: 38%-43%) among patients undergoing urgent resection, and 65% (95% CI: 64%-66%) among patients with elective resection. For SEMS vs. urgent resection, the adjusted MRR was 0.99 (95% CI: 0.91-1.07) and for SEMS vs. elective resection, the adjusted MRR was 1.39 (95% CI: 1.19-1.62). The 5-year recurrence risk was 39% (95% CI: 31%-46%) after preoperative SEMS, 30% (95% CI: 27%-32%) after urgent resection, and 22% (95% CI: 21%-24%) after elective surgery. The adjusted cause-specific hazard ratios for recurrence were 1.13 (95% CI: 0.99-1.28) for SEMS vs. urgent resection and 1.81 (95% CI: 1.44-2.28) for SEMS vs. elective resection. Conclusions: Long-term mortality associated with use of SEMS as a bridge to surgery was comparable to that of urgent resection, but higher than that observed following elective resection. SEMS use may be associated with an increased risk of CRC recurrence.

Udgivelsesdato: 2008-Feb OBJECTIVE: We evaluated if acetaminophen, one of the most frequently used drugs among pregnant women is associated with an increased prevalence of congenital abnormalities. STUDY DESIGN: We selected 88,142 pregnant women and their liveborn singletons from the Danish National Birth Cohort who had information on acetaminophen use during the first trimester of pregnancy. We used the National Hospital Registry to identify 3784 (4.3%) children from the cohort diagnosed with 5847 congenital abnormalities. RESULTS: Children exposed to acetaminophen during the first trimester of pregnancy (n = 26,424) did not have an increased prevalence of congenital abnormalities (hazard ratio = 1.01, 0.93-1.08) compared with nonexposed children (n = 61,718). No association was found between congenital abnormalities and duration of use during the first trimester. Increased prevalence was not observed for specific abnormalities, except for "medial cysts, fistula, sinus" (congenital abnormalities of the ear, face, and neck, ICD-10 code Q18.8, n = 43) with an adjusted hazard ratio of 2.15 (1.17-3.95). CONCLUSION: Acetaminophen is not associated with an increased prevalence of congenital abnormalities overall or with any specific group of major abnormalities.

The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67–2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46–1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring.