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Summary Objective To compare outcome of lower urinary tract symptoms (LUTS) between men with medical and surgical treatment. Materials and methods A questionnaire was mailed to men aged 55, 65 and 75 years living in Tampere region, Finland in 1999 and the survey was repeated in 2004. LUTS were evaluated using DAN-PSS-1 questionnaire. A total of 1679 men (68% of the eligible) responded to both questionnaires. Of them, 114 men reported LUTS at baseline and medical treatment in the repeat survey and 47 men with LUTS had received surgical treatment. Seventy-two men with prostate cancer were excluded. Men with no medical treatment or surgery for LUTS in either questionnaire were included to no-treatment group. Results The men after surgical treatment showed a reduction in all LUTS symptom groups. However, among the medically treated and untreated men, all the symptoms worsened during the follow up. The proportion of symptomatic men after surgery was lower than among the medically treated men. In men with medical treatment, the prevalence of all 12 LUTS increased. Dysuria and postmicturition dribble were the only symptoms that had slightly better results in medical than in surgical treatment group. Conclusions In this population-based study, operative treatment seemed to relieve LUTS, whereas medical treatment only slowed down their progression. These findings suggest that men with surgical treatment experience a more favourable outcome in LUTS than those receiving medical treatment.

SummaryObjective Previous studies suggest that patients with hyperthyroidism remain at an increased risk of cardiovascular morbidity even after restoring euthyroidism. The mechanisms of the increased risk and its dependency on the different treatment modalities of hyperthyroidism remain unclear. The aim of this long-term follow-up study was to compare the rate of hospitalizations for cardiovascular causes and the mortality in hyperthyroid patients treated surgically with an age- and gender-matched reference population. Patients and Measurements A population-based cohort study was conducted among 4334 hyperthyroid patients (median age 46 years) treated with thyroidectomy in 1986–2007 in Finland and among 12 991 reference subjects. Firstly, the hospitalizations due to cardiovascular diseases (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new hospitalization due to CVDs after the thyroidectomy were calculated in Cox regression analysis adjusted with the prevalent CVDs at the time of thyroidectomy. Results The risk of hospitalization due to all CVDs started to increase already 5 years before the thyroidectomy, and by the time of the operation, it was 50% higher in the hyperthyroid patients compared to the controls (P

Background Prevalence of tobacco use is higher in the rural than urban areas of India. Unlike tobacco cessation clinics located in urban areas, community-based smoking cessation intervention has the potential to reach a wider section of the community to assist in smoking cessation in the rural setting. The present study aimed to assess the effectiveness of a cessation intervention in rural Kerala state, India. Materials and methods Current daily smoking resident males in the age group 18-60 years from four community development blocks in rural Kerala were randomly allocated to intervention and control groups. The intervention group received multiple approaches in which priority was given to face-to-face interviews and telephone counselling. Initially educational materials on tobacco hazards were distributed. Further, four rounds of counselling sessions were conducted which included a group counselling with a medical camp as well as individual counselling by trained medical social workers. The control group received general awareness training on tobacco hazards along with an anti-tobacco leaflet. Self-reported smoking status was assessed after 6 and 12 months. Factors associated with tobacco cessation were estimated using binomial regression method. Results Overall prevalence of smoking abstinence was 14.7% in the intervention and 6.8% in the control group (Relative risk: 1.85, 95% CI: 1.05, 3.25). A total of 41.3% subjects in the intervention area and 13.6% in the control area had reduced smoking by 50% or more at the end of 12 months. Lower number of cigarettes/ bidi used, low nicotine dependence and consultation with a doctor for a medical ailment were the statistically significant predictors for smoking cessation. Conclusions Rigorous approaches for smoking cessation programmes can enhance quit rates in smoking in rural areas of India.

Twenty-five years have passed since the Chernobyl accident, but its health consequences remain to be well established. Finland was one of the most heavily affected countries by the radioactive fallout outside the former Soviet Union. We analyzed the relation of the estimated external radiation exposure from the fallout to cancer incidence in Finland in 1988-2007. The study cohort comprised all ∼ 3.8 million Finns who had lived in the same dwelling for 12 months following the accident (May 1986-April 1987). Radiation exposure was estimated using data from an extensive mobile dose rate survey. Cancer incidence data were obtained for the cohort divided into four exposure categories (the lowest with the first-year committed dose

International audience; This paper presents the dosimetry part of the European ELDO project, funded by the DoReMi Network of Excellence, in which a method was developed to estimate cumulative eye lens doses for past practices based on personal dose equivalent values, Hp(10), measured above the lead apron at several positions at the collar, chest and waist levels. Measurement campaigns on anthropomorphic phantoms were carried out in typical interventional settings considering different tube projections and configurations, beam energies and filtration, operator positions and access routes and using both mono-tube and biplane X-ray systems. Measurements showed that eye lens dose correlates best with Hp(10) measured on the left side of the phantom at the level of the collar, although this correlation implicates high spreads (41 %). Nonetheless, for retrospective dose assessment, Hp(10) records are often the only option for eye dose estimates and the typically used chest left whole-body dose measurement remains useful. © The Author 2013. Published by Oxford University Press. All rights reserved.

The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUK—Radiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities.

Objective To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy. Materials and Methods Study subjects were men aged 54–67 years with an elevated PSA (≥4 ng/mL or 3–4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996. A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation. Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry. The median length of follow-up was 10.5 years. Cox regression analysis was used to assess PCa risk after the initial benign biopsy. Results Histological inflammation was found in 66% of the biopsies. Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35–1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46–1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42–1.07; P = 0.092). Conclusions Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance. Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Urinary storage symptoms are the most common and most bothersome urinary symptoms. Many studies on the relation between body weight and urinary symptoms have focused on urinary incontinence in women. We evaluated the association of obesity with urinary storage symptoms in a population based study of men and women age 18 to 79 years old.Questionnaires were mailed to 6,000 adults randomly identified from the Finnish Population Register. Self-reported height and weight were used to calculate body mass index. Urinary frequency, nocturia, urgency, stress urinary incontinence and urgency urinary incontinence were assessed using validated instruments. Multivariate logistic regression analyses (adjusted for age, comorbidity and medications, and sociodemographic, lifestyle and reproductive factors) were performed to evaluate associations between body mass index and each symptom.Of the 6,000 individuals approached 3,727 participated (62.4% response, 53.7% women). In men and women obesity was associated with nocturia (adjusted OR 2.0, 95% CI 1.2-3.3 for men; OR 2.4, 95% CI 1.5-3.8 for women) but not with urgency (adjusted OR 1.2, 95% CI 0.7-2.3 for men; OR 1.2, 95% CI 0.7-2.1 for women). In men obesity was also associated with urinary frequency (OR 2.0, 95% CI 1.0-3.9), and in women it was associated with stress urinary incontinence (OR 1.9, 95% CI 1.2-3.0) and urgency urinary incontinence (OR 3.0, 95% CI 1.2-7.4). However, the number of men with stress urinary incontinence or urgency urinary incontinence was insufficient for precise analyses.This study extends previous research by providing symptom specific associations between obesity and urinary storage symptoms in a population based sample of men and women. Obesity impacts individual urinary storage symptoms differently and these associations may be influenced by gender.

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P.001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.

Background: A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer. In a family-based analysis by The International Consortium for Prostate Cancer Genetics (ICPCG), the G84E mutation was most prevalent in families from the Nordic countries of Finland (22.4%) and Sweden (8.2%). Methods: To further investigate the importance of G84E in the Finns, we determined its frequency in more than 4,000 prostate cancer cases and 5,000 controls. In addition, 986 breast cancer and 442 colorectal cancer (CRC) cases were studied. Genotyping was conducted using TaqMan, MassARRAY iPLEX, and sequencing. Statistical analyses were conducted using Fisher exact test, and overall survival was analyzed using Cox modeling. Results: The frequency of the G84E mutation was significantly higher among patients with prostate cancer and highest among patients with a family history of the disease, hereditary prostate cancer [8.4% vs. 1.0% in controls; OR 8.8; 95% confidence interval (CI), 4.9–15.7]. The mutation contributed significantly to younger age (≤55 years) at onset and high prostate-specific antigen (PSA; ≥20 ng/mL) at diagnosis. An association with increased prostate cancer risk in patients with prior benign prostate hyperplasia (BPH) diagnosis was also revealed. No statistically significant evidence for a contribution in CRC risk was detected, but a suggestive role for the mutation was observed in familial BRCA1/2-negative breast cancer. Conclusions: These findings confirm an increased cancer risk associated with the G84E mutation in the Finnish population, particularly for early-onset prostate cancer and cases with substantially elevated PSA. Impact: This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 22(3); 452–60. ©2012 AACR.

Objective In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial. Methods The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial. Setting The European prostate cancer screening trial (ERSPC). Results In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9–3.6 deaths per 1000 person-years. Conclusions Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.

Anticoagulants, especially vitamin K antagonists (VKAs) such as warfarin, have been hypothesized to have antitumor properties, and use of VKAs has been associated with a lower prostate cancer (PCa) risk. This study estimated PCa risk among users of warfarin and other anticoagulants.All anticoagulant use among 78,615 men during 1995-2009 was analyzed. Cox regression, adjusted for age, screening trial arm and use of other medications, with medication use as a time-dependent variable, was used to estimate PCa risk overall, and by tumor grade and stage.In total, 6537 men were diagnosed with PCa during 1995-2009 (1210 among warfarin users). Compared to non-users, warfarin use was associated with an increased risk of PCa [multivariable-adjusted hazard ratio (HR) = 1.11, 95% confidence interval (CI) 1.01-1.22]. This was limited to short-term, low-dose use, and was not observed in long-term use. A similar overall risk increase was observed for Gleason grade 7-10 PCa. Low-dose, short-term use of warfarin was associated with an increased risk of metastatic PCa. However, the increase in risk vanished with continued use. Compared to other anticoagulants, low-dose use of warfarin was associated with a slightly elevated overall PCa risk (HR = 1.19, 95% CI 1.00-1.43). The increase in risk disappeared in long-term, high-dose use.This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users. A similar risk of PCa was found among warfarin users and the general population, and no difference in risk was found between warfarin and other anticoagulants.

The Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC), the largest component of the European Randomized Study of Screening for Prostate Cancer (ERSPC), showed a smaller, nonsignificant reduction in prostate cancer-specific mortality by systematic prostate-specific antigen (PSA)-based screening compared with the overall ERSPC results. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and also PSA elevations due to intraprostatic inflammation.To explore whether NSAID usage modifies the effects of PSA-based screening on prostate cancer incidence and mortality.A cohort of 78 165 men from the FinRSPC were linked to a comprehensive national prescription database to obtain information on NSAID reimbursements prior to screening.Prostate cancer risk and mortality were compared between the FinRSPC screening arm and the control arm among NSAID users and nonusers using an age-adjusted Cox regression model.Screening increased the detection of Gleason 6 (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.47-1.72 and HR 1.39, 95% CI 1.26-1.54) and localized prostate tumors (HR 1.25, 95% CI 1.18-1.32 and HR 1.11, 95% CI 1.03-1.20) more among baseline NSAID nonusers than among users, respectively (p for interaction0.04 for both). This difference was observed in all three screening rounds. Detection of metastatic prostate cancer was similar in both NSAID users and nonusers. Screening decreased prostate cancer mortality among men using NSAIDs at FinRSPC randomization (HR 0.66, 95% CI 0.49-0.90) but not among nonusers (HR 0.95, 95% CI 0.81-1.12); p for interaction=0.04.Screening detected fewer well-differentiated localized tumors among NSAID users than among nonusers. This suggests that PSA screening may cause less overdiagnosis within this subgroup, whereas mortality benefit may be greater among NSAID users.Prostate cancer screening causes less overdiagnosis of well-differentiated localized prostate tumors among men who use nonsteroidal anti-inflammatory drugs.

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.

Objective To estimate the bother using both population- and individual-level bother of lower urinary tract symptoms (LUTS) across a wide age range among men. Materials and Methods A total of 7470 men aged 30-80 years were approached using a postal questionnaire in 2004. The overall response was 58.7% (4384 respondents). The Danish Prostatic Symptom Score was used to evaluate bother of 12 LUTS. In the population-level analysis, prevalence of bother was calculated by relating the number of men with bother to the population size (instead of only affected men). To evaluate the bother at individual level, its prevalence among the men experiencing the symptom was assessed. Results In the population-level analysis, postmicturition dribble was the most common cause of bother among 30- and 40-year-old men, as 25% of the men experienced small bother and 4.5% had moderate to major bother. Men aged 70-80 years experienced the most bother from urgency followed closely by nocturia, with about 40% reporting small bother and roughly 20% moderate or major bother. When only symptomatic men were evaluated, incontinence symptoms, especially urge incontinence, were the most bothersome as more than 80% of the men with incontinence reported bother. Conclusion At population level, the most bothersome symptom varied by age. Men aged 30-40 years experienced bother most commonly from postmicturition dribble. With increasing age, urgency and nocturia became the most bothersome symptoms by age 70-80 years. At individual level, incontinence symptoms were the most bothersome LUTS, with less influence by age.

Introduction Women with epilepsy (WWE) are generally treated as a risk group during pregnancy, but over 90% of pregnant WWE have favorable pregnancies. However, the risk of some pregnancy and delivery complications may be increased among WWE, especially those on antiepileptic drugs. Material and methods This nationwide, retrospective population-based cohort study includes WWE who gave birth in Finland during 1987–2008 (n = 1737) and the reference cohort of a random sample of women without epilepsy (n = 4357). Identification of the cohorts, and information on hospitalizations and deliveries were obtained from the Finnish Health Registers and population statistics. Multivariate analyses were conducted by binomial regression. Results WWE were more often hospitalized during pregnancy for accidents or other external causes [adjusted risk ratio (aRR) 1.74, 95% confidence interval (CI) 0.98–3.09], premature rupture of membranes (aRR 1.75, 95% CI 1.14–2.69) and premature contractions (aRR 1.75, 95% CI 1.36–2.23). Hospitalizations for infections were more frequent in WWE (1.4% vs. 0.4%, aRR 3.15, 95% CI 1.72–5.76). The risk for induction of delivery or a cesarean section was increased in WWE. There was no difference in premature deliveries between the groups, but the risk of being small for gestational age (aRR 1.57, 95% CI 1.23–2.01), admission to neonatal intensive care unit (aRR 1.66, 95% CI 1.39–1.97), and need for respiratory care (aRR 2.37, 95% CI 1.57–3.60) was clearly increased in the offspring of WWE. Conclusions WWE are at an increased risk of complications and hospitalizations during pregnancy and delivery. However, the majority of WWE have a normal pregnancy and delivery.

High doses of ionizing radiation are an established cause of childhood leukemia. However, substantial uncertainty remains about the effect of low doses of radiation, including background radiation and potential differences between genetic subgroups of leukemia have rarely been explored. We investigated the effect of the background gamma radiation on childhood leukemia using a nationwide register-based case-control study. For each of the 1,093 cases, three age- and gender matched controls were selected (N = 3,279). Conditional logistic regression analyses were adjusted for confounding by Down syndrome, birth weight (large for gestational age), and maternal smoking. Complete residential histories and previously collected survey data of the background gamma radiation in Finland were used to assess the exposure of the study subjects to indoor and outdoor gamma radiation. Overall, background gamma radiation showed a non-significant association with the OR of childhood leukemia (OR 1.01, 95% CI 0.97, 1.05 for 10 nSv/h increase in average equivalent dose rate to red bone marrow). In subgroup analyses, age group 2-7 years displayed a larger effect (OR 1.27, 95% CI 1.01, 1.60 for 1 mSv increase in equivalent cumulative dose to red bone marrow). Suggestive difference in OR by genetic subtype was found. Our results provide further support to the notion that low doses of ionizing radiation increase the risk for childhood leukemia, particularly at age 2-7 years. Our findings suggest a larger effect of radiation on leukemia with high hyperpdiploidy than other subgroups, but this result requires further confirmation.

Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. Design, setting, and participants: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA ( 100 ng/ml) was used as the indicator of metastasis. Outcome measurements and statistical analysis: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. Results and limitations: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. Conclusions: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. Patient summary: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded Public Library of Science open access

Background Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. Objective To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. Design, setting, and participants Data were available for 76 813 men aged 55–69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. Intervention Regular screening based on serum PSA measurements was offered to 36270 men randomized to the screening arm, while no screening was provided to the 40543 men in the control arm. Outcome measurements and statistical analysis The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. Results and limitations After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively ( p p =0.001) in the intention-to-screen analysis and a 42% ( p =0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41–0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. Conclusions PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736.

What's known on the subject? and What does the study add? The ICS has divided LUTS into three groups: storage, voiding and post-micturition symptoms. The classification is based on anatomical, physiological and urodynamic considerations of a theoretical nature. We used principal component analysis (PCA) to determine the inter-correlations of various LUTS, which is a novel approach to research and can strengthen existing knowledge of the phenomenology of LUTS. After we had completed our analyses, another study was published that used a similar approach and results were very similar to those of the present study. We evaluated the constellation of LUTS using PCA of the data from a population-based study that included >4000 men. In our analysis, three components emerged from the 12 LUTS: voiding, storage and incontinence components. Our results indicated that incontinence may be separate from the other storage symptoms and post-micturition symptoms should perhaps be regarded as voiding symptoms. Objective To determine how lower urinary tract symptoms (LUTS) relate to each other and assess if the classification proposed by the International Continence Society (ICS) is consistent with empirical findings. Materials And Methods The information on urinary symptoms for this population-based study was collected using a self-administered postal questionnaire in 2004. The questionnaire was sent to 7470 men, aged 30–80 years, from Pirkanmaa County (Finland), of whom 4384 (58.7%) returned the questionnaire. The Danish Prostatic Symptom Score-1 questionnaire was used to evaluate urinary symptoms. Principal component analysis (PCA) was used to evaluate the inter-correlations among various urinary symptoms. Results The PCA produced a grouping of 12 LUTS into three categories consisting of voiding, storage and incontinence symptoms. Post-micturition symptoms were related to voiding symptoms, but incontinence symptoms were separate from storage symptoms. In the analyses by age group, similar categorization was found at ages 40, 50, 60 and 80 years, but only two groups of symptoms emerged among men aged 70 years. The prevalence among men aged 30 was too low for meaningful analysis. Conclusions This population-based study suggests that LUTS can be divided into three subgroups consisting of voiding, storage and incontinence symptoms based on their inter-correlations. Our empirical findings suggest an alternative grouping of LUTS. The potential utility of such an approach requires careful consideration.

Background Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention. Objective To assess the impact of client-oriented decision on long-term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP). Methods With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease-specific and disease-free survival, biochemical failure with elevated prostate-specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model. Results Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87–2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72–1.79)] and for having disease progression by 2% [HR, 1.02 (0.61–1.70)] compared with those in the TP arm. All the differences were non-significant. Conclusions Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed.

Background Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials. Objective Assess the impact of the above-mentioned factors on screening efficacy. Design, setting, and participants Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up. Intervention PSA screening. Measurements The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed. Results and limitations With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1–13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3–9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9–3.5%) and 1.8% (95% CI, 1.4–2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening. Conclusions We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1–4 yr) had a greater impact on mortality reduction than did the age at start of screening (55–65 yr). Clinical trial registration International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736.

The authors conducted a nationwide cohort study to evaluate the association between postmenopausal hormone therapy and meningioma incidence in Finland. All women who had used hormone therapy at least for 6 months at the age of 50 years or older during 1994-2009 were included. Women who had used postmenopausal hormone therapy were identified from the medical reimbursement register of the Social Insurance Institution (131,480 estradiol users and 131,248 estradiol-progestin users), and meningioma cases were identified from the Finnish Cancer Registry. During the average 9 years of follow-up, 289 estradiol users and 196 estradiol-progestin users were diagnosed with meningioma. Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P < 0.001) than in the background population. In contrast, this risk was not increased in users of combination therapy (standardized incidence ratio = 0.93, 95% confidence interval: 0.80, 1.06). There was no difference in risk between continuous and sequential use of hormone therapy. Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.

Background After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain. Methods On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled. Results Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56). Conclusions The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.)

Objective Peer review is the gold standard for evaluating scientific quality. Compared with studies on inter-reviewer variability, research on panel evaluation is scarce. To appraise the reliability of panel evaluations in grant review, we compared scores by two expert panels reviewing the same grant proposals. Our main interest was to evaluate whether panel discussion improves reliability. Methods Thirty reviewers were randomly allocated to one of the two panels. Sixty-five grant proposals in the fields of clinical medicine and epidemiology were reviewed by both panels. All reviewers received 5–12 proposals. Each proposal was evaluated by two reviewers, using a six-point scale. The reliability of reviewer and panel scores was evaluated using Cohen's kappa with linear weighting. In addition, reliability was also evaluated for the panel mean scores (mean of reviewer scores was used as panel score). Results The proportion of large differences (at least two points) was 40% for reviewers in panel A, 36% for reviewers in panel B, 26% for the panel discussion scores, and 14% when the means of the two reviewer scores were used. The kappa for panel score after discussion was 0.23 (95% confidence interval: 0.08, 0.39). By using the mean of the reviewer scores, the panel coefficient was similarly 0.23 (0.00, 0.46). Conclusion The reliability between panel scores was higher than between reviewer scores. The similar interpanel reliability, when using the final panel score or the mean value of reviewer scores, indicates that panel discussions per se did not improve the reliability of the evaluation.

Objectives The aim of this study was to explore possible environmental factors behind the regional differences in the incidence of pediatric inflammatory bowel disease (IBD). Methods All of the patients diagnosed with IBD who were aged 0 to 14 years in Finland between 1987 and 2003 were identified from the Social Insurance Institution database. Finland was divided into squares of 250 × 250 m, and spatial variations of incidence rates were evaluated accordingly. The role of the environmental determinants (pediatric population density, agricultural industry, chemical contaminants of tap water and proximity to the sea or paper mills) in the geographic variations of the incidence rates was evaluated. Results During the study period, the overall incidence of pediatric IBD was 6.5 of 100,000 (95% confidence interval [CI] 6.1-6.9). The incidence in very sparsely populated areas (≤10 person-years per 250 × 250 m) was 9.2 of 100,000 (95% CI 6.3-13.1) and 5.6 of 100,000 (95% CI 4.8-6.4) in the districts with the highest population density (>800 person-years per 250 × 250 m). A nonsignificant trend toward the same direction was also seen for ulcerative colitis (trend P = 0.09). Chemical contaminant concentrations of tap water, residence near the seaside, or proximity to paper mills were not associated with the incidence of pediatric IBD. Conclusions Our findings suggest higher incidence rates of pediatric IBD in the districts with low compared with high density of child population, but the differences cannot be explained by variations in the environmental exposures evaluated here.

The 4th edition of the European Code against Cancer recommends limiting – or avoiding when possible – the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen–progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen–progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit–risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

Background: The reported incidence rates of vestibular schwannomas (VS) vary substantially, but it is unclear as to what extent the variation reflects differences in risk or recording practices. Our aim was to describe the incidence rates of VS in Denmark, Finland, Norway and Sweden between 1987 and 2007. Methods: Comprehensive data were available from all registries only for the period from 1987 to 2007. An analysis of a longer time period (1965–2007) was conducted with the Norwegian and Swedish data. Results: The average age-standardised incidence rates during 1987–2007 varied from 6.1 per 1 000 000 person-years (95% confidence interval (CI), 5.4–6.7) among Finnish men to 11.6 (95% CI, 10.4–12.7) in Danish men, and from 6.4 per 1 000 000 person-years (95% CI, 5.7–7.0) among Swedish women to 11.6 (95% CI, 10.5–12.8) among Danish women. An overall annual increase of 3.0% (95% CI 2.1–3.9) was observed when all countries and both sexes were combined, with considerable differences between countries. However, the practices of both reporting and coding VS cases varied markedly between countries and over time, which poses a challenge for interpretation of the results. Conclusion: The overall incidence of VS increased in all the four Nordic countries combined between 1987 and 2007, with marked differences between countries. However, the incidence rates more or less stabilised in the late 1990s, showing relatively constant incidence rates and even some decline after 2000.

Study Type – Therapy (symptom prevalence) Level of Evidence 2a What's known on the subject? and What does the study add? In several population-based studies the prevalence of hesitancy has varied from 20% to 52%. Studies concern mostly older men ≥50-years-old. Knowledge of troublesomeness that hesitancy causes is very scarce. This is a large population-based study on hesitancy in men with a wide age range. This study reports the prevalence of hesitancy from 30-year-old men to 80-year-old men. The bother of hesitancy is reported and this is also presented in different age groups. OBJECTIVE • To estimate the prevalence and bother of hesitancy by age group. MATERIALS AND METHODS • In this population-based study, the target population was 30- to 80-year-old men from Pirkanmaa County, Finland. • Information was collected by means of a mailed self-administered questionnaire in 2004. The overall participation proportion was 58.7% (4384 men out of 7470). • The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire was used to evaluate urinary symptoms, particularly hesitancy. Logistic regression was used for multivariate analysis. RESULTS • Almost half of the men (46.8%, 95% CI 45.3–48.3%) reported hesitancy at least occasionally, but only 0.5% (95% CI 0.3–0.7%) had hesitancy every time they urinated. The prevalence of any hesitancy was 42.3% at 30 years and 50.5% at 80 years of age (trend P < 0.001). Only a few men reported hesitancy often or always, prevalence increasing with age from 2.6% to 11.4% (trend P < 0.001). • Hesitancy caused a small problem for 18.3% of the men and a moderate or major problem for 0.9–5.3%. Only 3% of the men with infrequent hesitancy reported more than a small problem, whereas 59% of the men with hesitancy often or always reported a small problem and 32% reported a moderate or major problem. • Two other voiding symptoms, straining and weak stream, were strongly associated with hesitancy (with odds ratios exceeding 80). CONCLUSIONS • Mild hesitancy is very common in men of all ages. • Severe cases are rare, but the prevalence increases with age. • Hesitancy is a well-tolerated urinary symptom.

Background: The present study aimed to characterize the incidence of pediatric inflammatory bowel disease (IBD) in Finland and determine its temporal trends. Methods: The patients' data were based on the database of the Social Insurance Institution. New cases diagnosed with IBD at the age

The energy absorbed from the radio-frequency fields of mobile telephones depends strongly on distance from the source. The authors' objective in this study was to evaluate whether gliomas occur preferentially in the areas of the brain having the highest radio-frequency exposure. The authors used 2 approaches: In a case-case analysis, tumor locations were compared with varying exposure levels; in a case-specular analysis, a hypothetical reference location was assigned for each glioma, and the distances from the actual and specular locations to the handset were compared. The study included 888 gliomas from 7 European countries (2000-2004), with tumor midpoints defined on a 3-dimensional grid based on radiologic images. The case-case analyses were carried out using unconditional logistic regression, whereas in the case-specular analysis, conditional logistic regression was used. In the case-case analyses, tumors were located closest to the source of exposure among never-regular and contralateral users, but not statistically significantly. In the case-specular analysis, the mean distances between exposure source and location were similar for cases and speculars. These results do not suggest that gliomas in mobile phone users are preferentially located in the parts of the brain with the highest radio-frequency fields from mobile phones.

Background : There is continuing public and scientific interest in the possibility that exposure to radiofrequency (RF) electromagnetic fields (EMF) from mobile telephones or other wireless devices and applications might increase the risk of certain cancers or other diseases. The interest is amplified by the rapid world-wide penetration of such technologies. The evidence from epidemiological studies published to date have not been consistent and, in particular, further studies are required to identify whether longer term (well beyond 10 years) RF exposure might pose some health risk. Methods : The “Cosmos” study described here is a large prospective cohort study of mobile telephone users (ongoing recruitment of 250,000 men and women aged 18+ years in five European countries – Denmark, Finland, Sweden, The Netherlands, UK) who will be followed up for 25+ years. Information on mobile telephone use is collected prospectively through questionnaires and objective traffic data from network operators. Associations with disease risks will be studied by linking cohort members to existing disease registries, while changes in symptoms such as headache and sleep quality and of general well-being are assessed by baseline and follow-up questionnaires. Conclusions : A prospective cohort study conducted with appropriate diligence and a sufficient sample size, overcomes many of the shortcomings of previous studies. Its major advantages are exposure assessment prior to the diagnosis of disease, the prospective collection of objective exposure information, long-term follow-up of multiple health outcomes, and the flexibility to investigate future changes in technologies or new research questions.

Background: Screening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial. Materials and methods: We included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2-7 year interval depending on the centre; PSA cut-off was 3.0-4.0 ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1 year was defined as an FP result. Results: Of the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6-2.7% of men with negative screen, risk ratio 3.8-3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result. Conclusions: Our results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels. (C) 2011 Elsevier Ltd. All rights reserved.

The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prostate cancer has emerged as the most frequent cancer amongst men in Europe, with incidence increasing rapidly over the past two decades. Incidence has been uniformly increasing in the 24 countries with comparable data available, although in a few countries with very high rates (Sweden, Finland and The Netherlands), incidence has begun to fall during the last 3–4 years. The highest prostate cancer mortality rates are in the Baltic region (Estonia, Latvia and Lithuania) and in Denmark, Norway and Sweden. Prostate cancer mortality has been decreasing in 13 of the 37 European countries considered – predominantly in higher-resource countries within each region – beginning in England and Wales (1992) and more recently in the Czech Republic (2004). There was considerable variability in the magnitude of the annual declines, varying from approximately 1% in Scotland (from 1994) to over 4% for the more recent declines in Hungary, France and the Czech Republic. There appears little relation between the extent of the increases in incidence (in the late 1990s) and the recent mortality declines. It remains unclear to what extent the increasing trends in incidence indicate true risk and how much is due to detection of latent disease. The decreasing mortality after 1990 may be attributable to improvements in treatment and to an effect of prostate specific antigen (PSA) testing. The increase in mortality observed in the Baltic region and in several Central and Eastern European countries appear to reflect a real increase in risk and requires further monitoring.

Study Type – Harm (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Prostate biopsy can potentially have fatal outcome. This is, however, rare. In the literature a few fatal cases of septicaemia have been reported as well as life-threatening rectal bleeding. Prostate biopsy is not associated with excess mortality and fatal complications seem to be very rare in a screening setting. OBJECTIVE • To assess possible excess mortality associated with prostate biopsy among screening participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC). patientS AND METHODS • From three centres in the ERSPC (Finland, The Netherlands and Sweden) 50 194 screened men aged 50.2–78.4 years were prospectively followed. A cohort of 12 959 first-time screening-positive men (i.e. with biopsy indication) was compared with another cohort of 37 235 first-time screening-negative men. • Overall mortality rates (i.e. other cause than prostate cancer mortality) were calculated and the 120-day and 1-year cumulative mortality were calculated by the Kaplan–Meier method, with a log-rank test for statistical significance. • Incidence rate ratios (RR) and statistical significance were evaluated using Poisson regression analyses, adjusting for age, total PSA level, screening centre and whether a biopsy indication was present, or whether a biopsy was actually performed or not. RESULTS • There was no statistically significant difference in cumulative 120-day other cause mortality between the two groups of men: 0.24% (95% CI, 0.17–0.34) for screening-positive men vs 0.24% (95% CI, 0.20–0.30) for screening-negative men (P= 0.96). This implied no excess mortality for screening-positive men. • Screening-positive men who were not biopsied (n= 1238) had a more than fourfold risk of other cause mortality during the first 120 days compared to screening-negative men: RR, 4.52 (95% CI, 2.63–7.74) (P < 0.001), adjusted for age, whereas men who were actually biopsied (n= 11 721) had half the risk: RR, 0.41 (95% CI, 0.23–0.73) (P= 0.002), adjusted for age. • Only 14/31 (45%) of the screening-positive men who died within 120 days were biopsied and none died as an obvious complication to the biopsy. CONCLUSION • Prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare.

Ilkka Laaksi, Juha-Petri Ruohola, Ville Mattila, Anssi Auvinen, Timo Ylikomi, and Harri Pihlajamaki Department of Cell Biology, Medical School, and Department of Epidemiology, Tampere School of Public Health, University of Tampere, and Department of Clinical Chemistry, Tampere University Hospital, Tampere, and Finnish Defence Forces and Research Department, Centre for Military Medicine, Helsinki, Finland

Objectives People in the Arctic regions are one of the most heavily exposed population from the global fallout from atmospheric atomic bomb testing of the 1950s and 1960s due to their diet rich in reindeer meat in which radionuclides accumulate. We estimated the effect of the radioactive fallout and ethnicity on the cancer incidence in Northern Finland. Methods A cohort of the Arctic population in Finland (n=34 653) was identified through the Population Register Centre with grouping by reindeer herding status, ethnicity and radiation exposure. Annual average radiation doses, based on 137 Cs whole-body measurements, were assigned by birth year, gender and reindeer herder status. Incident cancer cases of a priori selected cancer types in the study cohort during 1971–2005 were identified from the Finnish Cancer Registry. Results A total of 2630 cancer cases were observed versus 3073 expected on the basis of incidence rates in Northern Finland (standardised incidence ratio (SIR) was 0.86 with 95% CI of 0.82 to 0.89). For the indigenous Sami people SIR was even lower, 0.60 (95% CI 0.50 to 0.71). None of the cancer sites was significantly associated with the lifetime cumulative radiation dose. The SIR for the combined group of radiation-related cancer sites increased with the cumulative radiation dose received before 15 years of age (p=0.004). Conclusion Despite the low overall cancer incidence in the Arctic population and ethnic Sami people in Finland and lack of association between the lifetime cumulative radiation exposure from global radioactive fallout and cancer incidence, we found some indication of an increased cancer risk associated with radiation exposure received during childhood. Potential underestimation and misclassification of the radiation dose may affect the results and the findings should be interpreted with caution.

We study the association between non-steroidal anti-inflammatory drugs (NSAIDs), Statins, and Bisphosphonates (BPs), and prostate cancer (PCa) survival during androgen deprivation therapy (ADT). STAMPEDE trial has demonstrated better PCa-specific survival in men using combination of celecoxib (CEL) and zoledronic acid (ZA) during ADT compared to ADT alone. The mechanism is unclear. ZA inhibits mevalonate pathway (MevP) previously linked with cancer growth. We evaluated PCa survival among men on ADT and simultaneously using BPs including ZA or statins, another drug group inhibiting MevP, and NSAIDs including CEL. We hypothesized that combined use of a MevP inhibitor and NSAID would be associated with improved PCa survival. Our study cohort includes 4,428 men from the Finnish Randomized Study of PCa Screening (FinRSPC) initiating ADT in 1995-2015. Cox proportional hazards model with adjustment for age, FinRSPC study arm, tumor clinical characteristics and co-morbidities (obtained from national registries) was used to calculate HRs and 95% CI for PCa death. Medication use was analyzed as time-dependent variable. Compared to non-users, the risk of PCa death was increased in users of NSAIDs or acetaminophen, and lowered in statin users. Use of BPs or coxibs alone were not associated with the risk. Coxibs and statins together were associated with lowered risk to a similar degree as statins alone. No statistically significant risk differences were observed for other combinations. Statin users with high-risk prostate cancer undergoing ADT have lowered risk of PCa death. NSAID users have increased risk of PCa death, which becomes statistically insignificant when used with statins. Statin and BP use together shows no statistically significant evidence of negating the effects of statin. No clear additive benefit was observed for statins and coxibs together over statins alone. Our findings do not support additive benefits of MevP inhibitor and NSAIDs. Statistical significance codes: *** : p = 0.001, ** : p = 0.01, * : p = 0.1DrugHR95 % CISignificanceStatin0.780.680.90***Acetylsalisylic acid0.900.761.07Coxib1.070.941.22NSAID1.171.041.31**Acetaminophen1.661.511.82***Bisphosphonate0.790.381.64Bisphosphonate and NSAID0.890.551.42Statin and NSAID1.070.901.27Statin and Bisphosphonate1.140.861.50Coxib and Bisphosphonate0.850.421.74Coxib and Statin0.800.621.02*EAU tumor Risk Group2.662.353.00*** Citation Format: Paavo V. Raittinen, Kirsi Talala, Kimmo Taari, Teuvo L. Tammela, Pauliina Ilmonen, Anssi Auvinen, Teemu J. Murtola. Association between NSAID, statins, and bisphosphonates and prostate cancer survival during androgen deprivation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4226.

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis.

Nocturia (ie, waking at night to void) is common and disrupts sleep. Traditionally, one nightly episode has been regarded as clinically meaningless, yet the justification for this belief remains weak.To evaluate the association among frequency of nocturia and bother and health-related quality of life (HRQoL).In 2003-2004, a survey was mailed to a random sample of 6000 subjects aged 18-79 yr who were identified from the Finnish Population Register Centre (response proportion was 62.4%; 53.7% were females).HRQoL and bother from nocturia were examined in relation to self-reported nocturia frequency (using the American Urological Association Symptom Index and the Danish Prostatic Symptom Score). Bother from nocturia was assessed on a four-point scale (none, small, moderate, major). HRQoL was measured with the generic 15D instrument on a 0-1 scale with a minimum clinically important difference of 0.03.Degree of bother increased with nocturia frequency (p0.01). The most commonly cited degree of bother for those with one, two, and three nightly voids was no bother, small bother, and moderate bother, respectively. The mean age-adjusted 15D score for men (and women) without nocturia was 0.953 (0.950) and 0.925 (0.927) with one void per night, 0.898 (0.890) with two voids per night, and 0.833 (0.840) with three or more voids per night. Statistically significant decreases were found in 15D score and in all 15D dimensions except eating. Although the response rate was high, approximately one third of those contacted did not participate in the study.At least two voids per night is associated with impaired HRQoL. The majority of people report having bother when the number of nocturia episodes is two and moderate or major bother when the number is three or more. One void per night does not identify subjects with interference from nocturia and, thus, is not a suitable criterion for clinically relevant nocturia.

Study Type – Decision analysis (patient preference) Level of Evidence 4 OBJECTIVE To evaluate attitudes to prostate cancer screening with prostate-specific antigen (PSA) of men who complied with offered screening and those who declined it within the Finnish randomized population-based screening trial, and to compare general health-related quality of life (HRQL) between participants and non-participants. SUBJECTS AND METHODS Self-administered questionnaires were sent to 500 men randomized into the screening arm in 1996–99 within the Finnish component of the European Randomized Study on Screening for Prostate Cancer. A similar survey was conducted among 500 non-participants. RESULTS Response proportions among the screening participants and non-participants were 59% and 28%, respectively. Current smoking was less frequent (P < 0.05) among the participants. In terms of attitude, the participants regarded the prostate cancer study as more important and the invitation letter as more informative than the non-participants (P < 0.001). There was no clear difference in worry about treatment consequences. The most commonly given reasons for not participating included previous PSA testing (41%), forgetting the invitation (51%), or not wanting to think of prostate cancer (39%) and regarding possible further diagnostic examinations as unpleasant (28%). The non-participants had a lower mental health score (P < 0.001) than the participants in the RAND-36 Survey. CONCLUSION Most men who chose not to attend screening had a positive attitude, but did not participate due to practical reasons. However, two-thirds of the non-participants indicated a willingness to participate in the next screening round.