Trends in the incidence of newly diagnosed cerebral cavernous malformations in Finland: a population-based retrospective cohort study.

Background: The few previous studies that have estimated the incidence of cerebral cavernous malformations (cavernomas) have reported incidence rates of 0.2-1.9/100,000 for diagnosed cavernomas. Our aim was to describe incidence trends of cavernomas by clinical presentation. Methods: We conducted a retrospective cohort study of cavernomas diagnosed at two university hospitals in Finland (Kuopio University Hospital, KUH and Tampere University Hospital, TAUH). Cavernoma diagnoses during 2004-2020 were identified from the KUH and TAUH Care registry databases and verified from medical records and diagnostic imaging studies. We calculated the age-standardized incidence rates using the European standard population and analysed incidence trend and changes in trend by sex, age group, and calendar year using Poisson regression. Findings: A total of 669 cavernoma diagnoses were identified during 2004-2020 in the combined KUH and TAUH population. The age-standardized incidence rate was 2.01/100,000 (95% confidence interval (CI) 1.85-2.16) for all cavernoma diagnoses, 1.25/100,000 (1.13-1.37) for asymptomatic, 0.75/100,000 (0.66-0.85) for symptomatic, and 0.46/100,000 (0.39-0.53) for ruptured cavernomas. No significant difference in the incidence of cavernoma diagnoses was seen between the KUH and TAUH populations or between the sexes. Incidence of cavernomas was highest at ages 40-59 years and low in those under 20 or over 80 years of age. Incidence of diagnosed cavernomas, especially asymptomatic, increased during the study period. Interpretation: In our population-based study, incidence of cavernomas was higher than previously reported and increased during the study period. The burden imposed by cavernomas on healthcare system is considerable and increasing. Funding: The Research Council of Finland, Kuopio University Hospital, Tampere University Hospital, and Wellbeing services county of Pirkanmaa.

Prostate cancer incidence and mortality in Europe and implications for screening activities: population based study.

OBJECTIVE: To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives. DESIGN: Population based study. SETTING: 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer's Global Cancer Observatory, and mortality data from the World Health Organization. POPULATION: Men aged 35-84 years from 26 eligible countries. RESULTS: Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in several countries. Mortality rates during 1980-2020 were much lower and less variable than incidence rates, with steady declines in most countries and lesser temporal differences between countries. Overall, the up to 20-fold variation in prostate cancer incidence contrasts with a corresponding fivefold variation in mortality. Also, the inverse U-shape of the age specific curves for incidence contrasted with the mortality pattern, which increased progressively with age. The difference between the highest and lowest incidence rates across countries ranged from 89.6 per 100 000 men in 1985 to 385.8 per 100 000 men in 2007, while mortality rates across countries ranged from 23.7 per 100 000 men in 1983 to 35.6 per 100 000 men in 2006. CONCLUSIONS: The epidemiological features of prostate cancer presented here are indicative of overdiagnosis varying over time and across populations. Although the results are ecological in nature and must be interpreted with caution, they do support previous recommendations that any future implementation of prostate cancer screening must be carefully designed with an emphasis on minimising the harms of overdiagnosis.

Education and employment among patients with childhood-onset epilepsy in adulthood: A population-based cohort study.

OBJECTIVE: This study explored the association of childhood-onset epilepsy (COE) with educational attainment, adulthood employment, and income. METHODS: A population-based cohort of 312 children with COE was identified from Tampere University Hospital, Finland. Population Register Center formed a matched random population sample of 1248 children without COE as a reference cohort. The two cohorts were linked to the Statistics Finland database to obtain information on educational attainment, employment status, and income. Fisher's exact test was used to compare employment and graduation. Independent samples t-test was used for analyzing graduation grades and the Mann-Whitney test was used for analyzing yearly income. Results were stratified by sex and disability. RESULTS: During a follow-up of 25 years, a substantially higher proportion of the patients never entered the workforce, 37 % (109/312) compared with 4 % (44/1248) for the referents without COE (p < 0.001). A two-fold difference was observed for COE patients without other disabilities (7.7 %, 13/169, p = 0.01). No clear difference was found in long-term employment between the COE without disabilities and the referents (67 %, 114/169 versus 74 %, 920/1248, p = 0.087). The patients with COE had worse lower secondary school graduation grade averages (7.36 vs 7.6, p = 0.004) and graduation rates (64 % vs 98 %, p < 0.001), the patients without disabilities had similar results to referents (7.43, p = 0.07, 98 %). Of the patients with COE, 18 % graduated from college compared to 38 % of the referents (p < 0.001). The median income was lower in males and females with COE of all ages compared to the referents. The COE patients without additional mental or physical disabilities had income comparable to the healthy referents. 143 patients (46 %) had additional disabilities. SIGNIFICANCE: Patients with COE have lower educational attainment, stable employment, and income. Patients without disabilities also have an increased risk of unemployment, but those capable of entering the workforce have stable careers with earnings comparable to the rest of the population.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.

Which men benefit from prostate cancer screening? Prostate cancer mortality by subgroup in the European Randomised Study of Screening for Prostate Cancer.

OBJECTIVE: To evaluate whether a subgroup of men can be identified that would benefit more from screening than others. MATERIALS AND METHODS: This retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease. RESULTS: The hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden. CONCLUSION: We were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Risk of childhood neoplasms related to neonatal phototherapy- a systematic review and meta-analysis.

CONTEXT: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer. OBJECTIVE: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy. DATA SOURCES: The CENTRAL, PubMed, Scopus, and Web of Science databases. STUDY SELECTION: Observational studies regardless of design were included. DATA EXTRACTION: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools. RESULTS: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors. CONCLUSIONS: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding. IMPACT STATEMENT: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and.

Incidence of vestibular schwannoma in Finland, 1990-2017.

BACKGROUND: An increasing trend in incidence of vestibular schwannomas (VS) has been reported, though not consistently, across populations.  Materials and methods: We obtained data from the Finnish Cancer Registry on 1,149 VS cases diagnosed in 1990-2017 with tabular data up to 2022. We calculated age-standardised incidence rates (ASR) overall, by sex, and for 10-year age groups. We analysed time trends using Poisson and joinpoint regression. RESULTS: The average ASR of VS in Finland during 1990-2017 was 8.6/1,000,000 person-years for women and 7.5/1,000,000 for men. A declining trend was found with an average annual percent change of -1.7% (95% confidence interval [CI]: -2.8%, -0.6%) for women, -2.2% (95% CI: -3.6%, -0.7%) for men, and -1.9% (95% CI: -2.9%, -1.0%) for both sexes combined. The ASR in women was 11.6/1,000,000 person-years in 1990 and it decreased to 8.2/1,000,000 by 2017. Correspondingly, the incidence in men was 7.1/1,000,000 in 1990 and decreased to 5.1/1,000,000 by 2017. Some decline in incidence over time was found in all age groups below 80 years, but the decline (2.3-3.1% per year) was statistically significant only in age groups 40-49, 50-59, and 60-69 years. In the oldest age group (80+ years), the incidence of VS increased by 16% per year. For 2018-2022, the ASR was 7.6/1,000,000 for both sexes combined, with a decline by -1.7% (95% CI: -2.3%, -1.2%) annually for the entire period 1990-2022. CONCLUSION: In contrast to the increasing incidence reported in some studies, we found a decreasing trend in VS incidence for both sexes in Finland.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Does the duration of diabetes increase the risk of cancer? A nationwide population-based cohort of patients with new-onset diabetes and a matched reference cohort.

Diabetes mellitus and cancer are both common health issues, but the correlation between these two diseases remains unclear. We investigated the association of cumulative exposure of diabetes mellitus as an indication of hyperglycemia in terms of disease duration on multiple cancer types. We hypothesized that the risk of cancer would increase over time after the onset of diabetes. The study population consisted of a population-based cohort of 398,708 people and it was constructed from the Finnish CARING project. The Diabetes group consisted of 185,258 individuals, and the non-diabetic reference group comprised 187,921 individuals. Over 4.1 million person-years were accumulated, and the median follow-up time was 10.55 years. In the diabetes group, 25,899 cancer cases were observed compared with 23,900 cancers in the non-diabetic group. We did not find a clear relationship between the duration of diabetes mellitus and most cancer types examined. However, for cancers of the pancreas, prostate gland, bronchus, and lungs, a temporal relationship was found. Furthermore, even within the cancer types where the relationship was detected, it did not change over time. These findings indicate that diabetes does not independently increase the risk of cancer. Instead, the development of diabetes may be attributed to shared risk factors with cancer, such as obesity and/or insulin resistance accompanied by hyperinsulinemia. Thus, it is likely that the clock for increased cancer risk starts ticking already before onset of diabetes and hyperglycemia.

Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study.

BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Do LUTS Predict Mortality? An Analysis Using Random Forest Algorithms.

Purpose: To evaluate a random forest (RF) algorithm of lower urinary tract symptoms (LUTS) as a predictor of all-cause mortality in a population-based cohort. Materials and Methods: A population-based cohort of 3143 men born in 1924, 1934, and 1944 was evaluated using a mailed questionnaire including the Danish Prostatic Symptom Score (DAN-PSS-1) to assess LUTS as well as questions on medical conditions and behavioral and sociodemographic factors. Surveys were repeated in 1994, 1999, 2004, 2009 and 2015. The cohort was followed-up for vital status until the end of 2018. RF uses an ensemble of classification trees for prediction with a good flexibility and without overfitting. RF algorithms were developed to predict the five-year mortality using LUTS, demographic, medical, and behavioral factors alone and in combinations. Results: A total of 2663 men were included in the study, of whom 917 (34%) died during follow-up (median follow-up time 15.0 years). The LUTS-based RF algorithm showed an area under the curve (AUC) 0.60 (95% CI 0.52-0.69) for five-year mortality. An expanded RF algorithm, including LUTS, medical history, and behavioral and sociodemographic factors, yielded an AUC 0.73 (0.65-0.81), while an algorithm excluding LUTS yielded an AUC 0.71 (0.62-0.78). Conclusion: An exploratory RF algorithm using LUTS can predict all-cause mortality with acceptable discrimination at the group level. In clinical practice, it is unlikely that LUTS will improve the accuracy to predict death if the patient's background is well known.

Improving cancer incidence evaluation through local government area matching: a study of the Edo-Benin cancer registry in Nigeria.

BACKGROUND: Cancer registries in Nigeria, as well as in other sub-Saharan African countries, face challenges in adhering to international cancer registration standards. We aimed to improve cancer incidence estimation by identifying under-reporting of new cancers through matching patient-reported local government areas (LGAs) in Edo state, Nigeria, to their respective catchment populations. METHODS: Information on cancers was obtained from records of hospitals, medical clinics, pathology laboratories, and death certificates according to IARC guidelines. We utilized normalized scores to establish consistency in the number of cancers by calendar time, and standardized incidence ratios (SIR) to assess the variation in cancer incidence across LGAs compared to Edo state average. Subsequently, we estimated sex- and site-specific annual incidence using the average number of cancers from 2016 to 2018 and the predicted mid-year population in three LGAs. Age-standardization was performed using the direct method with the World Standard Population of 1966. RESULTS: The number of incident cancers consistent between 2016-2018 in Egor, Oredo, and Uhunmwonde showed a significantly increased SIR. From 2016 to 2018 in these three LGAs, 1,045 new cancers were reported, with 453 (42.4%) in males and 592 (57.6%) in females. The average annual age-standardized incidence rate (ASR) was 50.6 (95% CI: 45.2 - 56.6) per 105. In men, the highest incidence was prostate cancer (ASR: 22.4 per 105), and in women, it was breast cancer (ASR: 16.5 per 105), and cervical cancer (ASR: 12.0 per 105). Microscopically verified cancers accounted for 98.1%. CONCLUSIONS: We found lower age-standardized incidence rates than those reported earlier for the Edo state population. Collecting information on the local government areas of the cancers allows better matching with the respective target population. We recommend using LGA information to improve the evaluation of population-based cancer incidence in sub-Saharan countries.

Do men adapt to lower urinary tract symptoms? An 11-year longitudinal study of male urinary urgency and associated bother.

OBJECTIVE: The study objective is to evaluate prognosis and predictors of bother caused by urinary urgency among middle-aged and older men. MATERIAL AND METHODS: A population-based sample of men born in 1974, 1964, 1954, 1944, 1934 and 1924 was followed-up from 2004 to 2015. The course of urgency and associated bother was evaluated with the Danish Prostatic Symptom Score at baseline and follow-up. Logistic regression was utilized to explore risk factors of increased bother at follow-up. RESULTS: A total of 2,480 men (39%) who had responded at baseline and follow-up were included in the study. Of them, 1,056 men (43%) had persistent mild urgency and 132 men (5%) persistent moderate or severe urgency at follow-up. The proportions of men experiencing at least moderate bother due to persistent urgency at follow-up were 6% (95% confidence interval 4.5-7.3) of those with mild and 79% (71.7-85.9) of the men with moderate or severe urgency. In multivariable-adjusted logistic regression, moderate to severe urgency was strongly associated with bother (odds ratio, OR 55.2, 95% CI 32.1-95.2). Other predictors of bother included cardiac disease (OR 1.8, 95% CI 1.0-31.1), pulmonary disease (OR 1.9, 95% CI 1.1-3.5) and medical treatment (OR 2.7, 95% CI 1.6-4.6). CONCLUSIONS: Most men with urinary urgency have mild symptoms and bother. Only one out of five men with persistent moderate or severe urgency adapt to the symptoms. Men with a history of medical treatment for lower urinary tract symptoms (LUTS) or impaired cardiopulmonary health are more likely to experience bother from urinary urgency.

Risk of Clinically Significant Prostate Cancer after a Nonsuspicious Prostate MRI-A Comparison with the General Population.

BACKGROUND: We compare the risk of clinically significant (csPCa; ISUP Grade Group ≥ 2) and insignificant prostate cancer (isPCa; ISUP Grade Group 1) in men with a nonsuspicious prostate MRI (nMRI; PI-RADS ≤ 2) with the general population, and assess the value of PSA density (PSAD) in stratification. METHODS: In this retrospective population-based cohort study we identified 1,682 50-79-year-old men, who underwent nMRI at HUS (2016-2019). We compared their age-standardized incidence rates (IR) of csPCa and the odds of isPCa to a local age- and sex-matched general population (n = 230,458) during a six-year follow-up. Comparisons were performed by calculating incidence rate ratios (IRR) and ORs with 95% confidence intervals (CI). We repeated the comparison for the 920 men with nMRI and PSAD < 0.15 ng/mL/cm3. RESULTS: Compared with the general population, the IR of csPCa was significantly higher after nMRI [1,852 vs. 552 per 100,000 person-years; IRR 3.4 (95% CI, 2.8-4.1)]. However, the IR was substantially lower if PSAD was low [778 per 100,000 person-years; IRR 1.4 (95% CI, 0.9-2.0)]. ORs for isPCa were 2.4 (95% CI, 1.7-3.5) for all men with nMRI and 5.0 (95% CI, 2.8-9.1) if PSAD was low. CONCLUSIONS: Compared with the general population, the risk of csPCa is not negligible after nMRI. However, men with nMRI and PSAD <0.15 ng/mL/cm3 have worse harm-benefit balance than men in the general population. IMPACT: Prostate biopsies for men with nMRI should be reserved for cases indicated by additional risk stratification. See related In the Spotlight, p. 641.

Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial.

INTRODUCTION: Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening. METHODS: The trial aims to recruit at least 111 000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray's test using intention-to-screen analysis of randomised men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening. ETHICS AND DISSEMINATION: The trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (2910/2017). Results will be disseminated through publications in international peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03423303.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

Screening history and risk of death from prostate cancer: a nested case-control study within the screening arm of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

PURPOSE: We assessed the risk of death from prostate cancer (PCa) in relation to men's screening histories, i.e., screening attendance among men who were offered screening. METHODS: Men in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) screening arm were invited to up to three screening rounds with the serum prostate-specific antigen (PSA) test at 4-year intervals during 1996-2007. Case subjects (n = 330) were men who died from PCa. Each case was matched to five controls (n = 1544) among the men who were free of PCa. Screening history was defined as (1) never/ever attended screening prior to the case diagnosis; (2) attended at the first screening round; and (3) recency of screening, calculated as the time from last screening attendance to the date of case diagnosis. The association between screening history and the risk of death from PCa was estimated by odds ratios (OR) with 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Having ever attended screening versus never attended was associated with a reduced risk of PCa death (OR 0.60, 95% CI 0.45-0.81) and a similar association was found for those attended (versus not attended) the first screening round (OR 0.67, 95% CI 0.51-0.87). The effect by time since last screen for the risk of PCa death was significantly lower 2-7 years since last screen. CONCLUSION: Among men invited to screening, subjects who attended any PSA screening during the previous 19 years had a 40% reduction in PCa mortality compared to non-screened men.