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Background In prostate cancer (PCa), lower education level is associated with less screening, more advanced stage at diagnosis and worse survival. The aim of this study was to estimate the association between education level and treatment modality and subsequently survival. Methods The 9255 men diagnosed with PCa in the Finnish Randomized Study of Screening for Prostate Cancer were included. Cancer stage, comorbidity, education level and primary treatment modality were extracted from the patient records, the Finnish Cancer Registry, Statistics Finland and the National Institute of Health and Welfare, and these covariates were used in logistic regression (treatment selection) and Cox regression (survival analysis). Results In high-risk cancers, men with tertiary education were more likely to be treated with radical prostatectomy (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.27–2.44) than men with primary education. Men with secondary (OR = 0.57; 95% CI = 0.38–0.84) or tertiary (OR = 0.42; 95% CI = 0.29–0.60) education were managed less frequently with mere hormonal therapy. In locally advanced cases, tertiary education was associated with more curatively aimed therapies and less hormonal therapy (OR for radical prostatectomy = 2.34; 95% CI = 1.49–3.66; OR for radiotherapy = 1.42; 95% CI = 1.09–1.85; OR for hormonal therapy = 0.45; 95% CI = 0.33–0.60). The hazard ratio for PCa death was lower in men with secondary (0.81; 95% CI = 0.69–0.95) and tertiary (0.75; 95% CI = 0.65–0.87) education than in the patients with primary education. Conclusions When controlled for the cancer risk group, comorbidity and patient's age, low education level is independently associated with less curatively aimed treatment in men with high-risk or locally advanced PCa and subsequently worse prognosis.

Introduction: In the Nordic countries, the use of mobile phones increased sharply in the mid-1990s especially among middle-aged men. We investigated time trends in glioma incidence rates (IR) with the perspective to inform about the plausibility of brain tumour risks from mobile phone use reported in some case-control studies. Methods: We analysed IR of glioma in Denmark, Finland, Norway, and Sweden among men aged 40–69 years, using data from national cancer registries and population statistics during 1979–2016, using log-linear joinpoint analysis. Information on regular mobile phone use and amount of call-time was obtained from major studies of mobile phones in these countries. We compared annual observed incidence with that expected under various risk scenarios to assess which of the reported effect sizes are compatible with the observed IR. The expected numbers of cases were computed accounting for an impact of other factors besides mobile phone use, such as improved cancer registration. Results: Based on 18,232 glioma cases, IR increased slightly but steadily with a change of 0.1% (95 %CI 0.0%; 0.3%) per year during 1979–2016 among 40–59-year-old men and for ages 60–69, by 0.6 % (95 %CI 0.4; 0.9) annually. The observed IR trends among men aged 40–59 years were incompatible with risk ratios (RR) 1.08 or higher with a 10-year lag, RR ≥ 1.2 with 15-year lag and RR ≥ 1.5 with 20-year lag. For the age group 60–69 years, corresponding effect sizes RR ≥ 1.4, ≥2 and ≥ 2.5 could be rejected for lag times 10, 15 and 20 years. Discussion: This study confirms and reinforces the conclusions that no changes in glioma incidence in the Nordic countries have occurred that are consistent with a substantial risk attributable to mobile phone use. This particularly applies to virtually all reported risk increases reported by previous case-control studies with positive findings. publishedVersion

Background Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). Objective To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA). Design, setting, and participants A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55–69 yr) at 16 yr of follow-up. Outcome measurements and statistical analysis The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths. Results and limitations The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from −3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] −0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar—0.01% (95% CI −0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available. Conclusions Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms. Patient summary This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.

Within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative, 25 centers across the globe collaborate to standardize active surveillance (AS) protocols for men with low-risk prostate cancer (PCa). A centralized PCa AS database, comprising data of more than 15000 patients worldwide, was created. Comparability of the histopathology between the different cohorts was assessed by a centralized pathology review of 445 biopsies from 15 GAP3 centers. Grade group 1 (Gleason score 6) in 85% and grade group ≥2 (Gleason score ≥7) in 15% showed 89% concordance at review with moderate agreement (κ=0.56). Average biopsy core length was similar among the analyzed cohorts. Recently established highly adverse pathologies, including cribriform and/or intraductal carcinoma, were observed in 3.6% of the reviewed biopsies. In conclusion, the centralized pathology review of 445 biopsies revealed comparable histopathology among the 15 GAP3 centers with a low frequency of high-risk features. This enables further data analyses-without correction-toward uniform global AS guidelines for men with low-risk PCa. PATIENT SUMMARY: Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative combines data from 15000 men with low-risk prostate cancer (PCa) across the globe to standardize active surveillance protocols. Histopathology review confirmed that the histopathology was consistent with low-risk PCa in most men and comparable between different centers.

Background The European Randomised Study of Screening for Prostate Cancer trial has shown a 21% reduction in prostate cancer (PC) mortality with prostate-specific antigen (PSA)-based screening. Sweden used a 2-yr screening interval and showed a larger mortality reduction than Finland with a 4-yr interval and higher PSA cut-off. Objective To evaluate the impact of screening interval and PSA cut-off on PC detection and mortality. Design, setting, and participants We analysed the core age groups (55–69 yr at entry) of the Finnish ( N =31 866) and Swedish ( N =5901) screening arms at 13 yr and 16 yr of follow-up. Sweden used a screening interval of 2 yr and a PSA cut-off of 3.0ng/ml, while in Finland the screening interval was 4 yr and the PSA cut-off 4.0ng/ml (or PSA 3.0–3.9ng/ml with free PSA Outcome measurements and statistical analysis We compared PC detection rate and PC mortality between the Finnish and Swedish centres and estimated the impact of different screening protocols. Results and limitations If the Swedish screening protocol had been followed in Finland, 122 additional PC cases would have been diagnosed at screening, 84% of which would have been low-risk cancers, and four leading to PC death. In contrast, if a lower PSA threshold had been applied in Finland, at least 127 additional PC would have been found, with 19 PC deaths. Conclusions The small number of deaths among cases that would have been potentially detectable in Finland with the Swedish protocol (or those that would have been missed in Sweden with the Finnish approach) is unlikely to explain the differences in mortality in this long of a follow-up. Patient summary A prostate-specific antigen threshold of 3ng/ml versus 4ng/ml or a screening interval of 2 yr instead of 4 yr is unlikely to explain the larger mortality reduction achieved in Sweden compared with Finland.

When evaluating environmental exposures, residential exposures are often most relevant. In most countries, it is impossible to establish full residential histories. In recent publications, childhood leukaemia and background radiation have been studied with and without full residential histories. This paper investigates the consequences of lacking such full data. Data from a nationwide Finnish Case-Control study of Childhood Leukaemia and gamma rays were analysed. This included 1093 children diagnosed with leukaemia in Finland in 1990–2011. Each case was matched by gender and year of birth to three controls. Full residential histories were available. The dose estimates were based on outdoor background radiation measurements. The indoor dose rates were obtained with a dwelling type specific conversion coefficient and the individual time-weighted mean red bone marrow dose rates were calculated using age-specific indoor occupancy and the age and gender of the child. Radiation from Chernobyl fallout was included and a 2-year latency period assumed. The median separation between successive dwellings was 3.4 km and median difference in red bone marrow dose 2.9 nSv/h. The Pearson correlation between the indoor red bone marrow dose rates of successive dwellings was 0.62 (95% CI 0.60, 0.64). The odds ratio for a 10 nSv/h increase in dose rate with full residential histories was 1.01 (95% CI 0.97, 1.05). Similar odds ratios were calculated with dose rates based on only the first dwelling (1.02, 95% CI 0.99, 1.05) and only the last dwelling (1.00, 95% CI 0.98, 1.03) and for subjects who had lived only in a single dwelling (1.05, 95% CI 0.98, 1.10). Knowledge of full residential histories would always be the option of choice. However, due to the strong correlation between exposure estimates in successive dwellings and the uncertainty about the most relevant exposure period, estimation of overall exposure level from a single address is also informative. Error in dose estimation is likely to cause some degree of classical measurement error resulting in bias towards the null.

Background Recent research has suggested that statins have an effect on prostate cancer prognosis. It is currently unclear how prostate cancer screening, tumor and patient characteristics, or treatment selection may affect this association. Objective To evaluate the risk of prostate cancer death among statin users. To determine how disease and treatment characteristics affect the association. Design, setting, and participants This is a population-based cohort study consisting of a general male population of Finland participating in the Finnish Randomized Study for Prostate Cancer Screening. The cohort of consisted of 6537 prostate cancer cases diagnosed in the Finnish Randomized Study of Screening for Prostate Cancer population during 1996–2012. The cohort was linked to the National Prescription Database for information on the use of statins and other drugs. Intervention Statin use before and after prostate cancer diagnosis compared with nonuse. Outcome measurements and statistical analysis Hazard ratios (HRs) for the risk of prostate cancer death by amount, duration, and intensity of statin use. Cox proportional hazards regression with postdiagnostic statin use as a time-dependent variable. Results During the median follow-up of 7.5 yr postdiagnosis 617 men died of prostate cancer. Statin use after diagnosis was associated with a decreased risk of prostate cancer death (HR 0.80; 95% confidence interval 0.65–0.98). A decreasing risk trend was observed by increasing intensity of usage (doses/year). The risk decrease was clearest in men managed with androgen deprivation therapy. Prediagnostic statin use was not associated with risk of prostate cancer death (HR 0.92; 95% confidence interval 0.75–1.12). Conclusions Decreased risk of prostate cancer death by statin use after diagnosis suggests that statins may delay or prevent prostate cancer progression. The risk decrease was significant only in men managed with androgen deprivation therapy, but statistical power was limited to estimate the association in men managed with surgery or radiotherapy. Patient summary Use of statins after prostate cancer diagnosis was associated with a decreased risk of prostate cancer death. The risk decrease was dose-dependent and observed especially among patients treated with hormone therapy.

Background: Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial. Methods: Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N = 442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms. Results: Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95% CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (k = 0.88) in the SA and 95.4% (k = 0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06). Conclusions: A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling. (C) 2016 Elsevier Ltd. All rights reserved.

Background The multicenter European Randomized Study of Screening for Prostate Cancer has shown a 21% reduction in prostate cancer (PC) mortality by prostate-specific antigen-based screening, with substantial overdiagnosis. In the present study, we analyzed the incidence of PC after screening in relation to the number of screening rounds attended in the Finnish section of the trial. Objective To evaluate the possible reduction in PC incidence following completed screening cycles in relation to the number of screening rounds attended. Design, setting, and participants The participants in the screening arm of the Finnish screening trial (29 298 men) were divided into subgroups of men who had participated at one, two, or three screening rounds. A reference group was formed of the 43 151 men in the control arm by selecting age-matched controls for each subgroup of the screening participants. PC cases diagnosed after screening were identified from the Finnish Cancer Registry until the end of 2011. Follow-up of the screened men started 12 mo (365 d) after the last screening attendance and a similar date was assigned to the men in the control arm. Results and limitations A total of 1514 new PCs cases (cumulative incidence 5.2%) were diagnosed among the screened men after the last screening attendance. In the reference group formed from the control arm, 2683 cases (6.2%) occurred. The hazard ratio (HR) for PC among nonparticipants in the screening arm was 0.89 (95% confidence interval [CI] 0.79–0.99) compared with their controls. Among participants, the HR in those who participated once was 1.39 (95% CI 1.22–1.57), among men who participated twice the HR was 0.97 (95% CI 0.86–1.10), and among men screened three times the HR was 0.57 (95% CI 0.49–0.68). A limitation of the study was that the comparison by attendance is not based on randomization. Conclusions The postscreening PC incidence is reduced after attending three screening rounds, but not after only one or two rounds. Thus, the increased cancer detection at screening is compensated by a subsequent risk reduction only after repeated screening cycles. Patient summary The results of the study indicate that at least three prostate-specific antigen-based screening cycles are needed to reduce subsequent prostate cancer incidence.

Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals' behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: "Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds." (C) 2015 International Agency for Research on Cancer; Licensee ELSEVIER Ltd

Summary We evaluated mortality in relation to a panel of autoimmunity-related immunological serum markers in adult patients with epilepsy (PWE), seen in 1996–1997 at the Department of Neurology, Oulu University Hospital in Finland. Blood samples were drawn from 968 volunteers, and baseline measurements included serum immunoglobulins (IgG, IgA, and IgM), and the following antibodies: anticardiolipin, antinuclear, antimitochondrial, antigliadin (IgA and IgG classes), IgA tissue transglutaminase, and IgA endomysial. Hazard ratios (HR) for all-cause mortality in PWE with abnormal immunological markers relative to 413 patients with normal findings were evaluated with adjustment for confounders during a follow-up of nine years. Borderline statistically significant associations were found only for elevated IgA (HR 2.09, 95% CI 0.99–4.42) and for having two or more abnormal antibody titers (HR 1.58, 95% CI 0.98–2.56). The findings of this exploratory study suggested that elevated serum IgA might be associated with excess mortality in PWE.

Background No study has compared the bothersomeness of all lower urinary tract symptoms (LUTS) using a population-based sample of adults. Despite this lack of evidence, investigators have often cited their LUTS of interest as the “most bothersome” or “one of the most bothersome.” Objective To compare the population- and individual-level burden of LUTS in men and women. Design, setting, and participants In this population-based cross-sectional study, questionnaires were mailed to 6000 individuals (18–79 yr of age) randomly identified from the Finnish Population Register. Outcome measurements and statistical analysis The validated Danish Prostatic Symptom Score questionnaire was used for assessment of bother of 12 different LUTS. The age-standardized prevalence of at least moderate bother was calculated for each symptom (population-level burden). Among symptomatic individuals, the proportion of affected individuals with at least moderate bother was calculated for each symptom (individual-level bother). Results and limitations A total of 3727 individuals (62.4%) participated (53.7% female). The LUTS with the greatest population-level burden were urgency (7.9% with at least moderate bother), stress urinary incontinence (SUI) (6.5%), nocturia (6.0%), postmicturition dribble (5.8%), and urgency urinary incontinence (UUI) (5.0%). Burden from incontinence symptoms was higher in women than men, and the opposite was true for voiding and postmicturition symptoms. At the individual level, UUI was the most bothersome for both genders. Although the response proportion was high, approximately a third did not participate. Conclusions Both men and women with UUI report moderate or major bother more frequently than individuals with other LUTS. At the population level, the most prevalent bothersome symptoms are urgency, SUI, and nocturia. Patient summary Urinary urgency was the most common troubling symptom in a large population-based study; however, for individuals, urgency incontinence was the most likely to be rated as bothersome., Take Home Message Population-based study assessing bother of individual lower urinary tract symptoms (LUTS) found the highest age-standardized prevalence for bothersome urgency. However, among individuals affected by LUTS, urgency incontinence was the most likely to cause significant bother. LUTS were generally well tolerated across ages and genders.

Objective To evaluate the natural course of lower urinary tract symptoms (LUTS) by quantifying their longitudinal changes. Methods A population-based study of men aged 55, 65, or 75 years in Pirkanmaa region, Finland was conducted with a 5-year follow-up (1999-2004). Mailed self-administered questionnaire with the Danish Prostatic Symptom Score instrument was used to evaluate LUTS. Men with any treatment for LUTS or a history of prostate cancer were excluded. Results A total of 1331 men were included in the study. All 12 symptoms exhibited considerable fluctuation over time. Incidence of specific symptoms varied by a factor of 10 and remission by a factor of 4. Overall, common symptoms varied most strongly in terms of incidence and remission, whereas the less common ones such as incontinence behaved in a more stable fashion. Remission was more frequent than incidence for all individual LUTS components. The highest incidence was found for post-micturition symptoms and urgency. Remission was most common in weak stream and least frequent in urgency and urgency incontinence. Conclusion LUTS are dynamic conditions with strong spontaneous fluctuation over time. Remission was more common than incidence. The strong propensity for spontaneous resolution should also be borne in mind in treatment decisions including prescription practices.

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.

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.

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.

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.

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.

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.

Background Erectile dysfunction is common among men aged more than 60 years. Its cause involves both physiologic and psychosocial factors. Methods To evaluate the effects of coital frequency on subsequent risk of erectile dysfunction, data were analyzed from a population-based 5-year follow-up study that was conducted in Pirkanmaa, Finland, using postal questionnaires. Assessment was based on the 5-item version of the validated International Index of Erectile Function. Men with erectile dysfunction at entry were excluded from the analysis. The study sample consisted of 989 men aged 55 to 75 years (mean 59.2 years). The most common comorbidities were hypertension (32%), heart disease (12%), depression (7%), diabetes (4%,) and cerebrovascular disorder (4%). Results The overall incidence of moderate or complete erectile dysfunction was 32 cases per 1000 person-years (95% confidence interval [CI], 27-38). After adjustment for comorbidity and other major risk factors, men reporting intercourse less than once per week at baseline had twice the incidence of erectile dysfunction compared with those reporting intercourse once per week (79 vs 33/1000, incidence rate ratio 2.2, 95% CI, 1.3-3.8). The risk of erectile dysfunction was inversely related to the frequency of intercourse. No relationship between morning erections and incidence of moderate or severe erectile dysfunction was found. Conclusion Regular intercourse protects against the development of erectile dysfunction among men aged 55 to 75 years. This may have an impact on general health and quality of life; therefore, doctors should support patients' sexual activity.

Objectives A recent report demonstrated that KLF6 IVS1 -27G>A substitution increases the transcription of alternatively spliced isoforms; this action was suggested to be associated with prostate cancer (pCA). To evaluate these findings among the Finnish population, a total of 3348 samples were analysed. Methods The variant was genotyped in 164 patients with familial pCA, 852 patients with unselected pCA, 459 patients with benign prostate hyperplasia (BPH), 923 male population controls, and 950 men from a Finnish prostate-specific antigen (PSA) screening trial with PSA levels less than 1.0ng/ml. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated by using logistic regression to estimate pCA risk. Results Association testing revealed no significant differences between familial prostate cancer patients and population controls (OR: 0.84; 95%CI, 0.56–1.28; p =0.42), unselected cases and controls (OR: 0.95; 95%CI, 0.76–1.19; p =0.63), or BPH cases and controls (OR: 1.12; 95%CI, 0.86–1.46; p =0.39). pCA and BPH cases were also compared with PSA-screened controls. None of these analyses revealed any significant associations. Conclusions Our results do not support the suggested association of KLF6 IVS1 -27G>A germline polymorphism with pCA risk and also suggest that the variant is not a risk allele for BPH in the Finnish population.

Objectives To quantify the bothersomeness of urinary symptoms in males with lower urinary tract symptoms (LUTS). Methods A population-based postal survey of urinary symptoms among 2837 men aged 55, 65, or 75 years was conducted. The response rate was 75%, and data of both symptom and bother questions were eligible for 1803–2046 men, depending on the question. Bothersomeness of each urinary symptom was measured with a bother index (BI) as a ratio of the number of men with a bother score higher than a symptom score to that with a bother score lower than a symptom score. The BI was compared with the relative risk (RR), the prevalence of men with bother to those with symptom. Results Urgency (46%) and postmicturition dribble (42%) were the most common symptoms. Any type of incontinence was considered highly bothersome (BI: 1.79–3.70). In light of the BI, most voiding and postmicturition symptoms except weak stream (BI: 1.14) were well tolerated. The variation of the BI (0.06–3.70) was substantially larger than that of RR (0.53–0.89) of the urinary symptoms. Conclusions Bothersomeness of a symptom is an independent contribution in the assessment of LUTS. The BI may be a useful indicator of bothersomeness of urinary symptoms. The greater variation of the BI than that of RR indicates that the BI provides information on LUTS that cannot be described by prevalence or prevalence ratio only.

Background: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations. Methods: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-γ-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use. Results: Median uranium concentration in drinking water was 25 μg/L (interquartile range, 5 to 148 μg/L; maximum, 1,500 μg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine. Conclusion: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

Celiac disease (CD) is a common immunologically mediated enteropathic condition manifesting in genetically predisposed individuals after exposure to wheat gluten. CD may be associated with a number of neurological disorders, and the prevalence of epilepsy is reported to be increased in patients with CD. We studied the prevalence of CD-associated antibodies in a cohort of 968 patients with epilepsy and in a population-based reference group of 584 subjects. There was no difference in the prevalence of IgA and IgG class antigliadin antibodies (AGAbA and AGAbG, respectively), endomysial antibodies (EMA), and tissue transglutaminase antibodies (tTGAbA) between patients with epilepsy and the control population. This suggests the presence of CD to be the same in patients with epilepsy and the reference population. However, AGAbA was more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%, relative risk 1.8, 95% confidence interval 1.1–3.0, P = 0.012).

Purpose To evaluate the possible selection bias related to the differential participation of mobile phone users and non-users in a Finnish case–control study on mobile phone use and brain tumors. Methods Mobile phone use was investigated among 777 controls and 726 cases participating in the full personal interview (full participants), and 321 controls and 103 cases giving only a brief phone interview (incomplete participants). To assess selection bias, the Mantel-Haenszel estimate of odds ratio was calculated for three different groups: full study participants, incomplete participants, and a combined group consisting of both full and incomplete participants. Results Among controls, 83% of the full participants and 73% of the incomplete participants had regularly used a mobile phone. Among cases, the figures were 76% and 64%, respectively. The odds ratio for brain tumor based on the combined group of full and incomplete participants was slightly closer to unity than that based only on the full participants. Conclusions Selection bias tends to distort the effect estimates below unity, while analyses based on more comprehensive material gave results close to unity.

Summary Background Retroperitoneal fibrosis (RPF) is an uncommon disease with unknown causation in most cases. The pathognomonic finding is a fibrous mass covering the abdominal aorta and the ureters. Our aim was to clarify the possible role of asbestos exposure in the development of RPF. The hypothesis was based on the ability of asbestos to cause fibrosis in pulmonary and pleural tissue. Methods We undertook a case-control study of 43 patients with the disease (86% of eligible cases) treated in three university hospital districts of Finland in 1990–2001. For every patient, five population-based controls were selected, matched by age, sex, and central hospital district. We assessed asbestos exposure and medical history using a postal questionnaire and a personal interview. Of the 215 eligible controls, 179 (83%) participated in the study. Findings The age-standardised incidence of RPF was 0·10 (95% CI 0·07–0·14) per 100 000 person-years. The disease was strongly associated with asbestos exposure. The odds ratio (OR) was 5·54 (1·64–18·65) for less than 10 fibre-years of asbestos exposure and 8·84 (2·03–38·50) for 10 or more fibre-years, the attributable fraction being 82% and 89%, respectively. Other risk factors were previous use of ergot derivates (OR 9·92 [1·63–60·26]), abdominal aortic aneurysm (OR 6·73 [0·81–56·08]), and smoking for more than 20 pack-years (OR 4·73 [1·28–17·41]). Interpretation Our results show that occupational asbestos exposure is an important causal factor for RPF. For patients with work-related asbestos exposure, RPF should be considered an occupational disease.

Background and Objective: Approximately 70% of the men with an elevated serum prostate-specific antigen (PSA) identified in prostate cancer screening do not have prostate cancer. Other available diagnostic variables may be utilized to reduce the number of false positive PSA results, but few algorithms for calculation of the combined impact of multiple variables are available. The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA, and the percentage of free PSA in serum, prostate volume and digital rectal examination (DRE) findings. Methods: In a randomized, population-based prostate cancer screening trial 10284 men aged 55–67 years were screened during 1996 and 1997 in two metropolitan areas in Finland. Results for men ( n =758) with a serum PSA of 4–20μg/l were used to establish the risk nomograms. Of these 200 (26%) had prostate cancer at biopsy. Results: Prostate cancer probability depended most strongly on the percentage of free PSA. Total PSA, prostate volume, and DRE also contributed to prostate cancer probability, whereas age and family history of prostate cancer did not. More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA ( p p =0.003) alone. Conclusions: Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4–20μg/l was observed. The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4μg/l.

SummaryIn a retrospective study we assessed the outcome of oxcarbazepine (OXC) monotherapy in a naturalistic setting. We identified all adult patients who had been treated with OXC at a single neurological outpatient center. A total of 175 patients were identified, 97 of them used OXC as their first AED (Group I), and 78 as second monotherapy (Group II), after failure of a previous AED. The 1-year retention rates of OXC treatment were 91% for Group I and 77% for Group II. Discontinuations were due to adverse effects in 3 patients (3%) in Group I and in 11 patients (14%) in Group II, and due to lack of efficacy in 2 patients (2%) in Group I and in 6 patients (8%) in Group II. We conclude that OXC monotherapy is effective and well tolerated.

The aims of this study were (a) to estimate the prevalence of pain and eight other common symptoms in a large population of patients with advanced cancer from different palliative care centers, and (b) to assess the differences in prevalence of the symptoms by primary site. In 1990-1991, the prevalence of eight major symptoms and performance status were assessed prospectively among 1840 cancer patients in seven hospices in Europe, the United States, and Australia. The data were collected at each institution using structured data collection sheets from the World Health Organization's (WHO) Cancer and Palliative Care Unit. The prevalence of moderate to severe pain was 51%, ranging from 43% in stomach cancer to 80% in gynecological cancers. Nausea was most prevalent in gynecological (42%) and stomach (36%) cancers, and dyspnea (46%) in lung cancer. There were statistically significant differences in the prevalence of most symptoms depending on the primary site of cancer and the hospice. Population-based follow-up studies are needed to document the incidence and prevalence of symptoms throughout the course of the disease.

The present study deals with retrospective estimation of radiation doses, among Estonian Chernobyl clean-up workers, by means of scoring stable translocations using the FISH technique. All persons investigated in this study were sent to the area in 1986 and the majority of them were selected to be among those with the presumably highest exposure doses. In spite of the selection the estimated average dose is between 0.2–0.3 Gy, thus not clearly above the officially permitted dose level of 0.25 Gy. Due to unforseen conditions during transport of the blood samples, both the number of persons available for analysis and the number of metaphases available for scoring were substantially reduced. However, unless this selection is linked with the potential aberration frequency of the cells involved, no bias is expected.

Neill Booth *, Pekka Rissanen , Teuvo L.J. Tammela , Liisa Maattanen , Kimmo Taari , Anssi Auvinen a a School of Health Sciences, University of Tampere, Tampere, Finland; Department of Surgery, Tampere University Hospital, and School of Medicine, University of Tampere, Tampere, Finland; Mass Screening Registry, Finnish Cancer Registry, Helsinki, Finland; Helsinki University Hospital and University of Helsinki, Helsinki, Finland

PURPOSE: To quantitatively assess the impact of selection bias caused by nonparticipation in a multinational case-control study of mobile phone use and brain tumor. METHODS: Non-response questionnaires (NRQ) were completed by a sub-set of nonparticipants. Selection bias factors were calculated based on the prevalence of mobile phone use reported by nonparticipants with NRQ data, and on scenarios of hypothetical exposure prevalence for other nonparticipants. RESULTS: Regular mobile phone use was reported less frequently by controls and cases who completed the NRQ (controls, 56%; cases, 50%) than by those who completed the full interview (controls, 69%; cases, 66%). This relationship was consistent across study centers, sex, and age groups. Lower education and more recent start of mobile phone use were associated with refusal to participate. Bias factors varied between 0.87 and 0.92 in the most plausible scenarios. CONCLUSIONS: Refusal to participate in brain tumor case-control studies seems to be related to less prevalent use of mobile phones, and this could result in a downward bias of around 10% in odds ratios for regular mobile phone use. The use of simple selection bias estimation methods in case-control studies can give important insights into the extent of any bias, even when nonparticipant information is incomplete.