Christian Dehlendorff

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.

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.

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.

Sex-related time-dependent variations in post-stroke survival--evidence of a female stroke survival advantage.

Background: Women live longer than men, yet most studies show that gender has no influence on survival after stroke. Methods: A registry was started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, and it now holds 39,484 patients of which 48% are female. We studied the influence of gender on post-stroke mortality, from the time of admission through the subsequent years until death or censoring (mean follow-up time: 538 days). All patients underwent an evaluation including stroke severity, computed tomography and cardiovascular risk factors. Independent predictors of death were identified by means of a survival model based on 22,222 individuals with a complete data set. Results: Females were older and had severer stroke. Interestingly, the risk of death between genders was time dependent. The female/male stroke mortality rate favoured women from the first day of stroke and remained so during the first month suggesting a female survival advantage. Throughout the second month the rate reversed in favour of men suggesting that women in that period are paying a ‘toll’ for their initial survival advantage. Hereafter, the rate steadily decreased, and after 4 months women continued to have the same low risk as in the first week. Conclusions: Our study suggests a female superiority in stroke survival competence.

Incidence and clinical presentation of groin injuries in sub-elite male soccer.

Background Groin injuries cause major problems in the football codes, as they are prevalent and lead to prolonged symptoms and high recurrence. The aim of the present study was to describe the occurrence and clinical presentation of groin injuries in a large cohort of sub-elite soccer players during a season. Methods Physiotherapists allocated to each of the participating 44 soccer clubs recorded baseline characteristics and groin injuries sustained by a cohort of 998 sub-elite male soccer players during a full 10-month season. All players with groin injuries were examined using the clinical entity approach, which utilises standardised reproducible examination techniques to identify the injured anatomical structures. The exposure time and the injury time were also recorded. Injury time was analysed using multiple regression on the log of the injury times as the data were highly skewed. Effects are thus reported at relative injury time (RIT). Results Adductor-related groin injury was the most common entity found followed by iliopsoas-related and abdominal-related injuries. The dominant leg was significantly more often injured. Age and previous groin injury were significant risk factors for sustaining a groin injury. Groin injuries were generally located on the same side as previously reported groin injuries. Adductor-related injuries with no abdominal pain had significantly longer injury times compared to injuries with no adductor and no abdominal pain (RIT 2.28, 95% CI 1.22 to 4.25, p=0.0096). Having both adductor and abdominal pain also increased the injury time significantly when compared to injuries with no adductor and no abdominal pain (RIT=4.56, 95% CI 1.91 to 10.91, p=0.001). Conclusion Adductor-related groin injury was the most common clinical presentation of groin injuries in male soccer players and the cause of long injury time, especially when combined with abdominal-related injury.

Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors: a nationwide case–control study

According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer.

Body Mass Index and Death by Stroke: No Obesity Paradox

IMPORTANCE Reports of an obesity paradox have led to uncertainty about secondary prevention in obese patients with stroke. The paradox is disputed and has been claimed to be an artifact due to selection bias. OBJECTIVE To determine whether the obesity paradox in stroke is real or an artificial finding due to selection bias. DESIGN, SETTING, AND PARTICIPANTS We studied survival after stroke in relation to body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). To overcome selection bias, we studied only deaths caused by the index stroke on the assumption that death by stroke reported on a death certificate was due to the index stroke if death occurred within the first month poststroke. We used the Danish Stroke Register, containing information on all hospital admissions for stroke in Denmark from 2003 to 2012, and the Danish Registry of Causes of Death. The study included all registered Danes (n = 71 617) for whom information was available on BMI (n = 53 812), age, sex, civil status, stroke severity, stroke subtype, a predefined cardiovascular profile, and socioeconomic status. MAIN OUTCOMES AND MEASURES The independent relation between BMI and death by the index stroke within the first week or month by calculating hazard ratios in multivariate Cox regression analysis and multiple imputation for cases for whom information on BMI was missing. RESULTS Of the 71 617 patients, 7878 (11%) had died within the first month; of these, stroke was the cause of death of 5512 (70%). Of the patients for whom information on BMI was available, 9.7% were underweight, 39.0% were of normal weight, 34.5% were overweight, and 16.8% were obese. Body mass index was inversely related to mean age at stroke onset (P < .001). There was no difference in the risk for death by stroke in the first month among patients who were normal weight (reference), overweight (hazard ratio, 0.96; 95% CI, 0.88-1.04), and obese (hazard ratio, 1.0; 95% CI, 0.88-1.13). Analysis of deaths within 1 week gave similar results. CONCLUSIONS AND RELEVANCE We found no evidence of an obesity paradox in patients with stroke. Stroke occurred at a significantly younger age in patients with higher BMI. Hence, obese patients with stroke should continue to aim for normal weight.

Strongly Decreased Risk of Genital Warts After Vaccination Against Human Papillomavirus: Nationwide Follow-up of Vaccinated and Unvaccinated Girls in Denmark

BACKGROUND A reduction in the incidence of genital warts (GWs) is one of the first markers of the effectiveness of vaccination against human papillomavirus (HPV) at the population level. The aim of this cohort study was to use individual information on HPV vaccination status to assess the effect on risk of GWs. METHODS Population-based registries were used to identify all girls in the birth cohorts 1989-1999 in Denmark, and information about HPV vaccination was obtained for the period 2006-2012. The cohort was linked to incident cases of GWs, and vaccinated and unvaccinated girls were compared using Cox proportional hazards models. RESULTS A total of 248 403 girls were vaccinated. The relative risk of GWs among girls who had received at least 1 dose of vaccine compared with unvaccinated girls was 0.12, 0.22, 0.25, and 0.62 for those born in 1995-1996, 1993-1994, 1991-1992, and 1989-1990, respectively (P for trend < .0001). No GWs occurred among vaccinated girls in the youngest birth cohort (1997-1999). CONCLUSIONS The strong, highly significant reduction in the occurrence of GWs among vaccinated girls indicates an early and marked population effect of the national HPV vaccination program and may forecast a similar effect on cervical precancerous lesions.

Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

BACKGROUND There is an unmet need for predictive markers for the antiangiogenic agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess whether the location of the primary tumor is associated with bevacizumab effectiveness when combined with capecitabine and oxaliplatin (CAPEOX) in the first-line treatment of patients with mCRC. PATIENTS AND METHODS A cohort of 667 consecutive patients with mCRC from the general community treated from 2006 to 2011 with CAPEOX and bevacizumab as standard first-line therapy was compared with a cohort of 213 patients treated with CAPEOX from 2003 to 2006, before bevacizumab was approved. Main outcome measures were progression-free survival (PFS) and overall survival (OS). Differences in outcome were tested using Kaplan-Meier curves and log-rank tests, and multivariate analyses were carried out using Cox Proportional Hazards models. RESULTS Patients treated with CAPEOX and bevacizumab with primary tumors originating in the sigmoid colon and rectum had a significantly better outcome than patients with primary tumors originating from the cecum to the descending colon, both for PFS (median PFS 9.3 versus 7.2 months; hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.56-0.82) and for OS (median OS 23.5 versus 13.0 months; HR 0.47, 95% CI 0.38-0.57). This difference was confirmed in multivariate analyses after adjustment for other potentially prognostic factors. For patients treated with CAPEOX, there was no association between primary tumor location and outcome, neither in unadjusted nor adjusted analyses. CONCLUSIONS The addition of bevacizumab to CAPEOX in first-line treatment of patients with mCRC may primarily benefit patients with primary tumors originating in the rectum and sigmoid colon. This hypothesis needs to be validated in data from completed randomized trials. CLINICALTRIALSGOV IDENTIFICATION NUMBER NCT00212615.