Klaus Kaae Andersen

Hemorrhagic and Ischemic Strokes Compared Stroke Severity, Mortality, and Risk Factors

Background and Purpose— Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. Methods— A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39 484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25 123 individuals with a complete data set. Results— Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441–1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Conclusion— Strokes are generally more severe in patients with HS. Within the first 3 months after stroke, HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.

MicroRNA biomarkers in whole blood for detection of pancreatic cancer

IMPORTANCE Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer, 18 patients with chronic pancreatitis, and 69 healthy participants), training cohort (180 patients with pancreatic cancer, 1 patient with chronic pancreatitis, and 199 healthy participants), and validation cohort (86 patients with pancreatic cancer, 7 patients with chronic pancreatitis, and 44 healthy participants); 754 microRNAs were screened in the discovery cohort and 38 microRNAs in the training cohort and 13 microRNAs in the validation cohort. MAIN OUTCOMES AND MEASURES Identification of microRNA panels (classifiers) for diagnosing pancreatic cancer. RESULTS The discovery cohort demonstrated that 38 microRNAs in whole blood were significantly dysregulated in patients with pancreatic cancer compared with controls. These microRNAs were tested in the training cohort and 2 diagnostic panels were constructed comprising 4 microRNAs in index I (miR-145, miR-150, miR-223, miR-636) and 10 in index II (miR-26b, miR-34a, miR-122, miR-126*, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885.5p). The test characteristics for the training cohort were index I area under the curve (AUC) of 0.86 (95% CI, 0.82-0.90), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.64 (95% CI, 0.57-0.71); index II AUC of 0.93 (95% CI, 0.90-0.96), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.85 (95% CI, 0.80-0.85); and CA19-9 AUC of 0.90 (95% CI, 0.87-0.94), sensitivity of 0.86 (95% CI, 0.80-0.90), and specificity of 0.99 (95% CI, 0.96-1.00). Performances were strengthened in the validation cohort by combining panels and CA19-9 (index I AUC of 0.94 [95% CI, 0.90-0.98] and index II AUC of 0.93 [95% CI, 0.89-0.97]). Compared with CA19-9 alone, the AUC for the combination of index I and CA19-9 was significantly higher (P = .01). The performance of the panels in patients with stage IA-IIB pancreatic cancer was index I AUC of 0.80 (95% CI, 0.73-0.87); index I and CA19-9 AUC of 0.83 (95% CI, 0.76-0.90); index II AUC of 0.91 (95% CI, 0.87-0.94); and index II and CA19-9 AUC of 0.91 (95% CI, 0.86-0.95). CONCLUSIONS AND RELEVANCE This study identified 2 diagnostic panels based on microRNA expression in whole blood with the potential to distinguish patients with pancreatic cancer from healthy controls. Further research is necessary to understand whether these have clinical implications for early detection of pancreatic cancer and how much this information adds to serum CA19-9.

Modelling the heat dynamics of a building using stochastic differential equations

This paper describes the continuous time modelling of the heat dynamics of a building. The considered building is a residential like test house divided into two test rooms with a water based central heating. Each test room is divided into thermal zones in order to describe both short and long term variations. Besides modelling the heat transfer between thermal zones, attention is put on modelling the heat input from radiators and solar radiation. The applied modelling procedure is based on collected building performance data and statistical methods. The statistical methods are used in parameter estimation and model validation, while physical knowledge is used in forming the model structure. The suggested lumped parameter model is thus based on thermodynamics and formulated as a system of stochastic differential equations. Due to the continuous time formulation the parameters of the model are directly physical interpretable. Finally, the prediction and simulation performance of the model is illustrated.

Significant decrease in the incidence of genital warts in young Danish women after implementation of a national human papillomavirus vaccination program.

Background Approximately 90% of genital warts (GWs) are caused by human papillomavirus (HPV) types 6 and 11. Denmark has provided the quadrivalent HPV vaccine to all 12-year-old girls since 2009 and catch-up vaccination to girls up to 15 years since 2008, with up to 80% to 85% vaccine coverage. We determined the incidence of GWs in Denmark since 1996, focusing on the period after licensing of HPV vaccination (October 2006). Methods From the Danish National Patient Register, we identified all hospitalizations and outpatient consultations for GWs between January 1995 and July 2011. Poisson regression was used to estimate average annual percentage changes. Results The overall incidence of GWs in women increased significantly until 2007, followed by an average yearly decline of 3.1% (95% confidence interval [CI], −5.5 to −0.7). In men, the incidence increased by 6.2% per year from 2004 (95% CI, 4.6–7.8). Stratifying on age, a significant decline was seen only for young women, particularly those aged 16 to 17 years, in whom GWs were virtually eliminated (average annual percentage change, −45.3%; 95% CI, −55.8 to −33.3). The incidences of genital Chlamydia, syphilis, and gonorrhea were stable or increased during the study period. Conclusions The incidence of GWs decreased substantially among women with high HPV vaccine coverage, pointing to the effect of the national HPV vaccination program.

Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark

AIMS The relevance of ultrafine particles (UFPs, particles <0.1 microm diameter), the smallest fraction of ambient particulate matter, on stroke morbidity has not been documented. We studied the effects of short-term changes in exposure to these particles on stroke, separately for ischaemic and haemorrhagic strokes, mild and severe strokes, and ischaemic strokes with (likely embolic) and without (likely thrombotic) atrial fibrillation (AF). METHODS AND RESULTS We used a time-stratified case-crossover design to study the association between short-term exposure to UFPs, particulate matter <10 microm in diameter (PM(10)), nitrogen oxides (NO(x)) and carbon monoxide (CO) (measured at single background station) and hospital admissions for stroke in Copenhagen (2003-2006). Of 7485 stroke admissions, 6798 were ischaemic and 687 haemorrhagic, 3485 mild, and 2248 severe. Of the ischaemic stroke cases, 1204 had AF and 5273 did not. We found significant positive association with exposure to UFPs, NO(x) and CO, and ischaemic strokes, and UFPs and NO(x) and mild strokes, 4 days before admission. The strongest associations were with UFPs. Exposure to UFPs lead to a 21% increase in hospital admissions (per interquartile range of 5-day averages; 95% confidence interval 4-41%) for mild ischaemic stroke of without AF (likely thrombotic origin). CONCLUSION Our results indicate possible effects of traffic-related air pollution, mainly UFPs, on hospital admissions for ischaemic stroke, especially for mild ischaemic stroke of likely thrombotic origin (without AF). These are novel findings regarding the relevance of UFPs and the heterogeneous effect of air pollution on the severity and origin of stroke, and need confirmation by other data.

Coarse and fine particles but not ultrafine particles in urban air trigger hospital admission for asthma in children

Background Short-term exposure to air pollution can trigger hospital admissions for asthma in children, but it is not known which components of air pollution are most important. There are no available studies on the particular effect of ultrafine particles (UFPs) on paediatric admissions for asthma. Aim To study whether short-term exposure to air pollution is associated with hospital admissions for asthma in children. It is hypothesised that (1) the association between asthma admissions and air pollution is stronger with UFPs than with coarse (PM10) and fine (PM2.5) particles, nitrogen oxides (NOx) or nitrogen dioxide (NO2); and (2) infants are more susceptible to the effects of exposure to air pollution than older children. Method Daily counts of admissions for asthma in children aged 0–18 years to hospitals located within a 15 km radius of the central fixed background urban air pollution measurement station in Copenhagen between 2001 and 2008 were extracted from the Danish National Patient Registry. A time-stratified case crossover design was applied and data were analysed using conditional logistic regression to estimate the effect of air pollution on asthma admissions. Results A significant association was found between hospital admissions for asthma in children aged 0–18 years and NOx (OR 1.11; 95% CI 1.05 to 1.17), NO2 (1.10; 95% CI 1.04 to 1.16), PM10 (1.07; 95% CI 1.03 to 1.12) and PM2.5 (1.09; 95% CI 1.04 to 1.13); there was no association with UFPs. The association was stronger in infants than in older children for all pollutants, but no statistically significant interaction was detected. Conclusion Short-term exposure to air pollution can trigger hospital admission for asthma in children, with infants possibly being most susceptible. These effects seemed to be mediated by larger particles and traffic-related gases, whereas UFPs showed no effect.

Higher Total Serum Cholesterol Levels Are Associated With Less Severe Strokes and Lower All-Cause Mortality Ten-Year Follow-Up of Ischemic Strokes in the Copenhagen Stroke Study

Background and Purpose— Evidence of a causal relation between serum cholesterol and stroke is inconsistent. We investigated the relation between total serum cholesterol and both stroke severity and poststroke mortality to test the hypothesis that hypercholesterolemia is primarily associated with minor stroke. Methods— In the study, 652 unselected patients with ischemic stroke arrived at the hospital within 24 hours of stroke onset. A measure of total serum cholesterol was obtained in 513 (79%) within the 24-hour time window. Stroke severity was measured with the Scandinavian Stroke Scale (0=worst, 58=best); a full cardiovascular risk profile was established for all. Death within 10 years after stroke onset was obtained from the Danish Registry of Persons. Results— Mean±SD age of the 513 patients was 75±10 years, 54% were women, and the mean±SD Scandinavian Stroke Scale score was 39±17. Serum cholesterol was inversely and almost linearly related to stroke severity: an increase of 1 mmol/L in total serum cholesterol resulted in an increase in the Scandinavian Stroke Scale score of 1.32 (95% CI, 0.28 to 2.36, P=0.013), meaning that higher cholesterol levels are associated with less severe strokes. A survival analysis revealed an inverse linear relation between serum cholesterol and mortality, meaning that an increase of 1 mmol/L in cholesterol results in a hazard ratio of 0.89 (95% CI, 0.82 to 0.97, P=0.01). Conclusions— The results of our study support the hypothesis that a higher cholesterol level favors development of minor strokes. Because of selection, therefore, major strokes are more often seen in patients with lower cholesterol levels. Poststroke mortality, therefore, is inversely related to cholesterol.

Body mass index and poststroke mortality

Background: Obesity is an established cardiovascular risk factor. We studied the association between body mass index (BMI) and all-cause mortality after stroke. Methods: A registry started in 2001 with the aim to register all hospitalized stroke patients in Denmark now includes 21,884 patients in whom BMI was recorded. There are five BMI groups: underweight (BMI <18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese (BMI 30.0–34.9) and severely obese (BMI ≧35). All patients underwent an evaluation including stroke severity, computed tomography, and cardiovascular risk factors. Survival was followed up to 5 years after stroke (median 1.5 years). Independent predictors of death were identified by means of a survival model based on 13,242 individuals with a complete data set. Results: Compared to normal-weight patients, mortality was lower in overweight [hazard rate (HR) 0.73, 95% CI 0.66–0.81], obese (HR 0.84, 95% CI 0.73–0.98) and severely obese stroke patients (HR 0.84, 95% CI 0.64–1.10), while mortality was higher in underweight patients (HR 1.63, 95% CI 1.41–1.90). Conclusions: Poststroke mortality is inversely related to BMI: overweight and obese stroke patients have a lower poststroke mortality rate than normal-weight and underweight patients.

The obesity paradox in stroke: Lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients

Background Although associated with excess mortality and morbidity, obesity is associated with lower mortality after stroke. The association between obesity and risk of recurrent stroke is unclear. Aims The study aims to investigate the association in stroke patients between body mass index and risk of death and readmission for recurrent stroke. Methods An administrative Danish quality-control registry designed to collect a predefined dataset on all hospitalized stroke patients in Denmark 2000–2010 includes 45 615 acute first-ever stroke patients with information on body mass index in 29 326. Data include age, gender, civil status, stroke severity, computed tomography, and cardiovascular risk factors. Patients were followed up to 9·8 years (median 2·6 years). We used Cox regression models to compare risk of death and readmission for recurrent stroke in the four body mass index groups: underweight (body mass index < 18·5), normal weight (body mass index 18·5–24·9), overweight (body mass index 25·0–29·9), obese (body mass index ⩾ 30·0). Results Mean age 72·3 years, 48% women. Mean body mass index 23·0. Within follow-up, 7902 (26·9%) patients had died; 2437 (8·3%) were readmitted because of recurrent stroke. Mortality was significantly lower in overweight (hazard ratio 0·72; confidence interval 0·68–0·78) and obese (hazard ratio 0·80; confidence interval 0·73–0·88) patients while significantly higher in underweight patients (hazard ratio 1·66; confidence interval 1·49–1·84) compared with normal weight patients. Risk of readmission for recurrent stroke was significantly lower in obese than in normal weight patients (hazard ratio 0·84; confidence interval 0·72–0·92). Conclusionsx Obesity was not only associated with reduced mortality relative to normal weight patients. Compared with normal weight, risk of readmission for recurrent stroke was also lower in obese stroke patients.

Predictors of Early and Late Case-Fatality in a Nationwide Danish Study of 26 818 Patients With First-Ever Ischemic Stroke

Background and Purpose— Predictors of early case-fatality (3-day, 7-day, and 30-day) in first-ever ischemic stroke were identified and compared with predictors of late case-fatality (90-day and 1-year). Methods— A registry designed to register hospitalized patients with stroke in Denmark 2000 to 2007 holds 26 818 patients with first-ever ischemic stroke with information on stroke severity (Scandinavian Stroke Scale), CT scan, cardiovascular risk factors, marital status, and fatality within 1 year. Multiple logistic regression was used in identifying predictors. Results— Mean age was 71.2 years; 48.5% were women; mean Scandinavian Stroke Scale score was 43.9. Early case-fatality showed stroke severity and age were significant predictors of 3-day, 7-day, and 30-day case-fatality (nonlinear effect). In addition, atrial fibrillation (OR, 1.56) predicted 30-day case-fatality. For late case-fatality, significant predictors of 90-day and 1-year case-fatality were age, stroke severity (nonlinear effect), atrial fibrillation (OR, 1.37 and 1.57), and diabetes (OR, 1.35 and 1.33), respectively. Male gender (OR, 1.28), previous myocardial infarction (OR, 1.40), and smoking (OR, 1.21) were also associated with 1-year case-fatality. Alcohol consumption, hypertension, intermittent arterial claudication, and marital state had no influence. All case-fatality rates accelerated with increasing age, but 3-day and 7-day case-fatality rates tended to level off or decline at the highest ages. Conclusions— Age and stroke severity were the only significant predictors of fatality within the first poststroke week; they were associated with late case-fatality as well. Cardiovascular risk factors were associated with late case-fatality; with the exception of atrial fibrillation, they were not significantly associated with early case-fatality rates.