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Abstract Systematic review and meta-analysis applying PRISMA guidelines with a PICOS format was constructed to provide an overview of changes in physical performance, body composition and physical training in soldiers during prolonged (≥ 3 months) military operations. Twenty-four studies out of the screened 4431 records filled the inclusion criteria. A small decrease in endurance performance was the most consistent finding (Hedge's g [g] − 0.21, 95% CI − 0.01 to − 0.41) while small overall increases in maximal strength of the lower (g 0.33, 95% CI 0.16–0.50) and upper body (g 0.33, 95% CI 0.19–0.46) were observed. In addition, small increases in strength endurance (push-up, g 0.34, 95% CI 0.15–0.52; sit-up g 0.26, 95% CI 0.07–0.44) were observed. The overall changes in body composition were trivial. Heterogeneity in the outcome variables varied mainly between low to moderate. Large inter-individual variations were observed in physical training volume, including decrements especially in endurance training frequency and volume. A reduction in total training load was often associated with negative changes in body composition and physical performance according to the principle of training specificity. Individuals with higher initial fitness level were more susceptible to decrements in their physical performance during operation.

Abstract Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual’s subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Background Use of mobile telephones has been suggested as a possible risk factor for intracranial tumours. To evaluate the effect of mobile phones on risk of meningioma, we carried out an international, collaborative case-control study of 1209 meningioma cases and 3299 population-based controls. Methods Population-based cases were identified, mostly from hospitals, and controls from national population registers and general practitioners’ patient lists. Detailed history of mobile phone use was obtained by personal interview. Regular mobile phone use (at least once a week for at least 6 months), duration of use, cumulative number and hours of use, and several other indicators of mobile phone use were assessed in relation to meningioma risk using conditional logistic regression with strata defined by age, sex, country and region. Results Risk of meningioma among regular users of mobile phones was apparently lower than among never or non-regular users (odds ratio, OR = 0.76, 95% confidence interval, CI 0.65, 0.89). The risk was not increased in relation to years since first use, lifetime years of use, cumulative hours of use or cumulative number of calls. The findings were similar regardless of telephone network type (analogue/digital), age or sex. Conclusions Our results do not provide support for an association between mobile phone use and risk of meningioma. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy., Patients and Methods: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.0 ng/mL and a benign systematic TRUS-guided biopsy result. The cumulative prostate cancer mortality of men stratified by a PSAD cutoff of 0.15 ng/mL/cm 3 was modelled with competing risk functions. The ability of PSAD, PSA, and base variables (age at biopsy, DRE result, socioeconomic status, 5α-reductase inhibitor usage, family history, and Charlson Comorbidity Index (CCI)) to predict prostate cancer death was compared using c-statistics and a likelihood ratio test., Results: After excluding 10 men without PSA data within 2 years of the biopsy and 65 without prostate volume data, 2276 men were eligible for inclusion in the study. A total of 50 men died from prostate cancer and 1028 from other causes during a median (interquartile range) follow-up of 17.4 (13.2-20.9) years. The cumulative prostate cancer mortality of men with PSAD <0.15 ng/mL/cm 3 was significantly lower than that of men with PSAD ≥0.15 ng/mL/cm 3 : 0.5% (95% confidence interval [CI] 0.2%-1.1%) vs 2.0% (95% CI 1.2%-3.1%) at 15 years (Grey's test, P = 0.001). The model consisting of PSAD, PSA and the base variables predicted prostate cancer mortality (c-statistic 0.781) significantly better than either the base variables alone (c-statistic 0.737; likelihood-ratio test, P = 0.003) or the base variables and PSA (c-statistic 0.765; likelihood-ratio test, P = 0.039)., Conclusion: Prostate cancer mortality after a benign systematic TRUS-guided biopsy is low. In these patients, PSAD predicts prostate cancer mortality and provides additional value to other clinical variables. PSAD-based stratification can be used to guide follow-up strategy., (© 2025 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Multimorbidity creates challenges for care and increases health care utilization and costs. People with dementia often have multiple comorbidities, but little is known about the role of these comorbidities in hospitalizations., Aims: This study examines the frequency of hospitalizations during the last two years of life in older adults with and without dementia, the impact of comorbidities on hospitalizations, and their time trends., Methods: The data came from national registers and covered all persons 70 and above who died in Finland in 2002-2017. The effect of dementia and comorbidities on hospitalizations in the last two years of life was determined using binary logistic regression and negative binomial regression., Results: At all levels of comorbidity, people with dementia were less likely to be hospitalized and had a lower number of hospitalizations than people at the same level of comorbidity but no dementia. Hospitalizations were strongly associated with multimorbidity. During the study period, the overall hospitalization rates from home and LTC have declined., Discussion: The declining trend of hospitalization during the 15-year study period should be interpreted in the context of the health and long-term care system., Conclusion: Among people with dementia, comorbidities were the main driver for hospitalizations. Regardless of the number of comorbidities, people with dementia were hospitalized less often than people without dementia in last two years of life. It remains unclear whether the lower hospitalization rate is due to the improved ability to care for people with dementia outside the hospital or to the lack of sufficient medical care for them., Competing Interests: Declarations. Ethics approval and consent to participate: Permission to access the registers was obtained from the register maintainers (National Institute for Health and Welfare and Statistics Finland). Approval obtained from The Ethics Committee of Pirkanmaa Hospital District (R09089). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objective: Despite the evidence for prostate-specific antigen (PSA) screening reducing prostate cancer (PCa) mortality, the optimal PSA cutoff and the clinical significance of low initial PSA levels in predicting long-term PCa mortality remain subjects of ongoing research. We assessed PCa mortality among men with initial PSA levels below 3 ng/ml during the first screening round of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC)., Methods: A retrospective cohort study was conducted, including 20 268 men from the screening arm of the FinRSPC with an initial PSA level of <3 ng/ml, with follow-up spanning up to 20 yr. Hazard ratios (HRs) and their 95% corresponding confidence intervals (CIs) were estimated using a Cox regression analysis., Key Findings and Limitations: During a median follow-up of 17.8 yr, 1840 PCa cases were diagnosed and 128 PCa deaths occurred, with the cumulative PCa mortality of 0.6% and a mortality rate of four per 10 000 person-years. PCa mortality was five-fold higher at PSA levels of 2-2.99 ng/ml (HR 5.0, 95% CI 3.1-8.1) than at <1 ng/ml. Deaths from cases with Gleason score <7 and European Association of Urology low-risk group tumors showed a stronger association with PSA, particularly in the 2-2.99 ng/ml range versus <1 ng/ml. Additionally, PCa mortality in younger men (55-58 yr at entry) exhibited a stronger association with PSA than that in older men (67-71 yr at baseline). Addition of the cumulative number of PSA tests slightly improved the overall prediction of PCa death based on Harrell's C-statistic (base model 0.683 vs 0.717). The relatively small number of deaths, particularly among men with low-risk disease, may potentially limit the statistical precision of the results., Conclusions and Clinical Implications: Our findings highlight the importance of a nuanced approach to PSA in PCa screening, suggesting utility for combining PSA with other tests at low levels and indicating minimal risk associated with discontinuing screening at ages 67-71 yr when PSA is low., Patient Summary: In this study, we analyzed prostate cancer deaths in Finnish men with low initial prostate-specific antigen (PSA) levels. We found that the risk of prostate cancer death increases in relation to PSA, especially in younger men. Screening might safely be stopped at ages 67-71 yr if PSA remains low., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Migrant mortality advantage is established in various studies, but there is a lack of evidence on migrant mortality trends in old age. Previous studies have primarily concentrated on all-cause mortality, and few include older age groups. Discussions about the migrant mortality advantage continue due to concerns about data availability and accuracy. Additionally, the mechanisms explaining the migrant mortality advantage remain unclear. This study examines all-cause and cause-specific mortality among older migrant and nonmigrant adults aged 70 and above using Finnish Cause of Death register data (2002-20) and the corresponding risk population. We investigate differences in overall and cause-specific mortality between migrant and Finnish-born population and by geographical region of origin. We calculated direct age-standardized mortality rates and age group-specific death rates followed by Poisson regression to study relative mortality differences. Age at death, sex, income, region of residence, and year of death were controlled for in the regression analysis. We found evidence of migrant mortality advantage across various causes of death, but there was variation by regions of origin groups and sex. Notably, women exhibit the strongest advantage in respiratory and digestive system diseases, while men demonstrated pronounced advantages in external causes and respiratory diseases. Our study challenges the notion of a general diminishing healthy migrant effect in old age. Our findings emphasize the need for nuanced investigations into socioeconomic factors and tailored interventions for older migrants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The effect of vagus nerve stimulation (VNS) on cognitive domain of attention and executive functions (AEFs) has not been extensively researched. This study was set up to investigate performance variability on cognitive tests assessing AEFs in drug-resistant epilepsy (DRE) patients receiving VNS therapy during a follow-up of up to 5 years., Methods: Thirty-three DRE patients were assessed with the interference, maze, and written verbal fluency tests as a part of EpiTrack screening before and after VNS implantation through repeated follow-ups according to the clinical VNS protocol. A linear mixed-effects model was used to analyse changes in test scores., Results: Maze performance improved significantly by an average of 0.20 s per month (95% confidence interval (CI): -0.365 to -0.041; p = 0.014). Interference performance improved by an average of 0.05 s per month (p = 0.207) and number of words increased by an average of 0.03 words per month (p = 0.079) on the verbal fluency test. On the maze test, patients with psychiatric comorbidities improved the most (0.52 s/month, p = 0.001), while on the interference test, patients with frontal lobe epilepsy (FLE), those taking 1-2 antiseizure medications (ASMs) and patients with focal to bilateral tonic-clonic seizures improved the most (0.14 s/month, p = 0.005; 0.14 s/month, p = 0.033 and 0.16 s/month, p = 0.087, respectively). For verbal fluency, no clinically meaningful improvement was noted in any of the groups., Conclusion: During the follow-up, maze performance markedly improved, while performance on the interference and verbal fluency tasks remained relatively stable at the group level. Accordingly, visual anticipation and planning improved during VNS therapy whereas response inhibition was unchanged at the group level despite significant enhancements in patients with FLE and those taking 1-2 ASM. Furthermore, the presence of psychiatric comorbidities correlated with even greater improvement on maze performance., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Radiometals play an important role in nuclear medicine, both for imaging and therapy. Binding studies represent an important step in the development of new radiolabeled ligands, as valuable insights into the binding properties can be gained. However, this technique requires high radiochemical purity, otherwise results may lead to wrong assumptions or misinterpretations of affinities or uptake rates. Therefore, this in vitro study aimed at investigating the cell binding and internalization characteristics of different radiometal chlorides ([ 111 In]InCl 3 , [ 68 Ga]GaCl 3 and [ 177 Lu]LuCl 3 ) commonly applied in nuclear medicine, as well as the clinically applied [ 177 Lu]Lu-PSMA-I&T in comparison, by using prostate cancer cells. PC-3 and LNCaP cells were incubated with 100 kBq of the respective radiometal chloride or [ 177 Lu]Lu-PSMA-I&T for 1 h. For [ 177 Lu]LuCl 3 , nuclei isolations and colloid determinations in saline and cell medium were also performed. Results showed that [ 111 In]InCl 3 and [ 68 Ga]GaCl 3 bind and are internalized up to 3 % to PC-3 and LNCaP cells, whereas [ 177 Lu]LuCl 3 showed cell binding of up to 25 %, internalization up to 2.5 % and a nuclear uptake below 0.3 %. In comparison, [ 177 Lu]Lu-PSMA-I&T showed only 3 % total cell binding to LNCaP cells. Further analysis of [ 177 Lu]LuCl 3 stability in NaCl and cell medium showed only low amounts of colloids, which are not increasing over time, and negligible unspecific binding to the used cell culture plates. In conclusion, the results demonstrate the importance of high radiochemical purity, especially with regard to Lu-177 labeled compounds. Even if radiopharmaceuticals comply with common release-criteria, significant uptake can be derived from [ 177 Lu]LuCl 3 impurities and lead to wrong estimations of a compound's uptake behavior. Assuming an experimental result of 2 % membrane binding of the applied product, and 5 % residual [ 177 Lu]LuCl 3 in the final product (thereof 25 % membrane binding, as described above), would lead to 1.25 % membrane binding resulting from [ 177 Lu]LuCl 3 and only 0.75 % from the radiopharmaceutical., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prior studies on longevity often examine predictors in isolation and rely solely on baseline information, limiting our understanding of the most important predictors and their dynamic nature. In this study, we used an innovative regression tree model to explore the common characteristics of those who lived longer than their age and sex peers in 35-years follow-up. We identified different pathways leading to a long life, and examined to how changes in characteristics over 10 years (from 1979 to 1989) affect the findings on longevity predictors., Methods: Data was obtained from the "Tampere Longitudinal Study on Ageing" (TamELSA) in Finland. Survey data was collected in 1979 from 1056 participants aged 60-89 years (49.8% men). In 1989, a second survey was conducted among 432 survivors from the 1979 cohort (40.2% men). Dates of death were provided by the Finnish Population Register until 2015. We employed an individual measure of longevity known as the realized probability of dying (RPD), which was calculated based on each participant's age and sex, utilizing population life tables. RPD is based on a comparison of the survival time of each individual of a specific age and sex with the survival time of his/her peers in the total population. A regression tree analysis was used to examine individual-based longevity with RPD as an outcome., Results: This relative measure of longevity (RPD) provided a complex regression tree where the most important characteristics were self-rated health, years of education, history of smoking, and functional ability. We identified several pathways leading to a long life such as individuals with (1) good self-rated health (SRH), short smoking history, and higher education, (2) good SRH, short smoking history, lower education, and excellent mobility, and (3) poor SRH but able to perform less demanding functions, aged 75 or older, willing to do things, and sleeping difficulties. Changes in the characteristics over time did not change the main results., Conclusion: The simultaneous examination of a broad range of potential predictors revealed that longevity can be achieved under very different conditions and is achieved by heterogeneous groups of people., (© 2024. The Author(s).)

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., Competing Interests: Authors declare no competing interests. Dr. Halmela has received a travel grant from the State funding for university-level health research, Tampere University Hospital, Wellbeing services county of Pirkanmaa, in order to present part of this work at the 2024 annual meeting of the Scandinavian Neurosurgical Society in Aalborg, Denmark. Dr. Auvinen has received research grants for a prostate cancer screening trial from the following sources: Cancer Foundation Finland, Sohlberg Fooundation, and State funding for university-level health research, Tampere University Hospital, Wellbeing services county of Pirkanmaa. Dr. Auvinen has also received a travel grant from the European Society of Urology, and is a board member for the Finnish Society of Epidemiology, for the PRAISE-U study, for the ProBase trial, and the UN committee UNSCEAR. Dr. Frösen has received research grants from The Research Council of Finland (Academy of Finland, Clinical Investigator grant), from the Kuopio University Hospital, and by State funding for university-level health research, Tampere University Hospital, Wellbeing services county of Pirkanmaa. In addition, Dr. Frösen has received travel grants to participate to the ARISE I consensus meeting in May 2023 in Arlington, VA, USA and the ARISE II consensus meeting in May 2024 in Washington D.C., USA., (© 2024 The Authors.)

Background: Musculoskeletal (MSK) disorders represent a significant burden to society and can be unpleasant for the affected individuals. Physical activity (PA) can prevent MSK disorders while conferring other health benefits. The present study aimed to investigate associations between device-measured PA and perceived MSK disorders among young adult men., Methods: PA at different intensity levels, standing, and sedentary behavior were measured with a hip-worn accelerometer in a cohort of 422 young adult Finnish men aged 26 years on average. The incidences of three common MSK disorders (viz., knee pain, lumbar radicular pain, and lumbago pain) during the last month were inquired by a questionnaire. Binary logistic regression was used to examine the associations between the MSK outcomes and explanatory PA variables (PA times at different intensity levels, standing, and sedentary times). The models were controlled for age, education, smoking, BMI, and maximal oxygen uptake., Results: PA, standing, and sedentary times were not significantly associated with the incidence of perceived MSK pain during the last month, except for lumbago pain. Lumbago pain was slightly more probable if the time spent in light PA increased, even after controlling for potential confounding factors, including moderate-to-vigorous PA, with an odds ratio (OR) of 1.07 (95% CI: 1.02-1.14). Sedentary time showed an opposite association, with an OR of 0.98 (95% CI: 0.96-1.00)., Conclusions: There were neither positive nor negative clinically meaningful associations between PA and recent MSK disorders among young adult men. The result is surprising and requires further confirmation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sipilä, Sievänen, Raitanen, Kyröläinen, Vasankari, Vaara and Honkanen.)

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.

Background: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies., Methods: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups., Results: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05)., Conclusions: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression., (© 2024. The Author(s).)

Aim: To describe long-term care (LTC) use in Finland and Sweden in 2020, by reporting residential entry and exit patterns including hospital admissions and mortality, compared with the 2018-2019 period and community-living individuals., Methods: From national registers in Finland and Sweden, all individuals 70+ were included. Using the Finnish and Swedish study populations in January 2018 as the standard population, we reported changes in sex- and age-standardized monthly rates of entry into and exit from LTC facilities, mortality and hospital admission among LTC residents and community-living individuals in 2020., Results: Around 850,000 Finns and 1.4 million Swedes 70+ were included. LTC use decreased in both countries from 2018 to 2020. In the first wave (March/April 2020), Finland experienced a decrease in LTC entry rates and an increase in LTC exit rates, both more marked than Sweden. This was largely due to short-term movements. Mortality rates peaked in April and December 2020 for LTC residents in Finland, while mortality peaked for both community-living individuals and LTC residents in Sweden. A decrease in hospital admissions from LTC facilities occurred in April 2020 and was less marked in Finland versus Sweden., Conclusions: During the first wave of the pandemic mortality was consistently higher in Sweden. We also found a larger decrease in LTC use and, among LTC residents, a smaller decrease in hospital admissions in Finland than in Sweden. This study calls for assessing the health consequences of the differences observed between these two Scandinavian countries as part of the lessons from the COVID-19 pandemic., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

This study aims to estimate direct health-related costs for victims of intimate partner violence (IPV) using nationwide linked data based on police reports and two healthcare registers in Finland from 2015 to 2020 ( N  = 21,073). We used a unique register dataset to identify IPV victims from the data based on police reports and estimated the attributable costs by applying econometric models to individual-level data. We used exact matching to create a reference group who had not been exposed to IPV. The mean, unadjusted, attributable healthcare cost for victims of IPV was €6,910 per individual over the 5-year period after being first identified as a victim. When adjusting for gender, age, education, occupation, and mental-health- and pregnancy-related diagnoses, the mean attributable health-related cost for the 5 years was €3,280. The annual attributable costs of the victims were consistently higher than those for nonvictims during the entire study period. Thus, our results suggest that the adverse health consequences of IPV persist and are associated with excess health service use for 5 years after exposure to IPV. Most victims of IPV were women, but men were also exposed to IPV, although the estimates were statistically significant only for female victims. Victims of IPV were over-represented among individuals outside the labor force and lower among those who were educated. The total healthcare costs of victims of IPV varied according to the socioeconomic factors. This study highlights the need for using linked register data to understand the characteristics of IPV and to assess its healthcare costs. The study results suggest that there is a significant socioeconomic gradient in victimization, which could also be useful to address future IPV prevention and resource allocation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

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.

Introduction: There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years., Methods: The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes., Results: On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p  = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p  = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p  < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p  = 0.036 and 0.028 units/month, p  = 0.003, respectively). TMT-A z scores improved the most in patients taking 1-2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p  = 0.002 and p  = 0.003, respectively)., Conclusion: Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities., Competing Interests: NL has participated in a clinical trial for UCB; received speaker’s honoraria from LivaNova (OmaMedical). LK has received speaker’s honoraria from UCB, Merck, and Eisai; received support for travel to congress from UCB and Angelini Pharma. KL has received speaker’s honoraria from Medtronic. ER-O has received speaker’s honoraria from Novartis and Biogen. JP has participated in clinical trials for Eisai, UCB, and Bial; received research grants from Angelini Pharma, Eisai, Medtronic, UCB, and LivaNova; received speaker’s honoraria from LivaNova, Angelini Pharma, Eisai, Jazz Pharma, Medtronic, Orion Pharma, and UCB; received support for travel to congresses from LivaNova, Eisai, Medtronic, and UCB; and participated in advisory boards for LivaNova, Angelini Pharma, Jazz Pharma, Eisai, Medtronic, UCB, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lähde, Basnyat, Raitanen, Kämppi, Lehtimäki, Rosti-Otajärvi and Peltola.)

Objective: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years., Methods: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years., Results: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs., Significance: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs., Plain Language Summary: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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., Competing Interests: Competing interests: AR declares receipt of lecture and consultation fees from Janssen and Orion., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [ 177 Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.

[ 177 Lu]Lu-PSMA I&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [ 177 Lu]Lu-PSMA I&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [ 177 Lu]Lu-PSMA I&T . Finally, a prospective cost reduction through an optimization of the production process was shown.

Background: Female healthcare workers have a high prevalence of low back pain (LBP)-related sickness absence. Here, we report findings of a 24-month follow-up of a previously published 6-month randomized controlled trial (RCT)., Methods: By adopting an RCT with 6 months of intervention and follow-up at 6, 12, and 24 months, we assessed the maintenance of changes in the effectiveness (LBP and fear of pain) of the interventions (neuromuscular exercise [NME], back-care counseling, both combined) using a generalized linear mixed model adjusted for baseline covariates. The incremental cost-effectiveness ratio was calculated in terms of quality-adjusted life years (QALY). A bootstrap technique was used to estimate the uncertainty around a cost-effectiveness acceptability curve., Results: Of the 219 females, 71% had data at 24 months. Between 6 and 24 months, LBP intensity (primary outcome) remained low in all intervention arms (-20% to -48%) compared to the control (-10% to -16%). Pain interfering with work remained low in the combined and exercise arms for up to 24 months. At 24 months, the total costs were lowest in the combined arm (€484 vs. €613-948, p < 0.001), as were the number of back-related sickness absence days (0.16 vs. 1.14-3.26, p = 0.003). The analysis indicated a 95% probability of the combined arm to be cost-effective per QALY gained at €1120., Conclusions: Six months of weekly NME combined with four counseling sessions was cost-effective for treating LBP and the effect was maintained over 24 months., Trial Registration: ClinicalTrials.gov, NCT01465698, 7/11/2011, prospective., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Meningiomas are the most common primary neoplasm of the central nervous system. Previous research on the incidence of meningioma in Finland showed an increase in the age-standardized incidence rate over three decades (1968-1997). In this study, we analysed meningioma incidence in Finland during 1990-2017., Materials and Methods: Data on 9842 meningioma patients were obtained from the Finnish Cancer Registry, and population size by calendar year, sex, and age group from Statistics Finland. The European Standard Population was used to calculate age-standardized incidence rates. Poisson regression was used to evaluate differences by sex and age, and joinpoint regression to examine changes in trend., Results: At the beginning of the study period, the age-standardized incidence of meningioma for men was 2.35/100,000 and for women 6.96/100,000. In the end, it was 4.09/100,000 and 10.19/100,000, respectively. The annual percent change (APC) for women was +4.6 (95% confidence interval, CI 3.10 to 6.20) from 1990 to 2001 and -1.0 (95% CI -1.70 to -0.30) from 2001 to 2017. For men, the APC was +3.1 (95% CI 0.80-5.40) during 1990-2002 and -0.9 (95% CI -2.10 to 0.30) in 2002-2017. The incidence of meningioma in women was 2.8 times higher than in men (rate ratio 2.81; 95% CI 2.68-2.94)., Conclusions: Meningioma incidence increased in both sexes from 1990, but the trend reversed in 2001-2002. Medical imaging or risk factors do not appear to explain the changes.

Objectives: To investigate the antiseizure medication (ASM) doses required to achieve seizure freedom and their correlation with the World Health Organization's defined daily doses (DDDs) in patients aged 16 years or older with newly diagnosed epilepsy., Methods: The study included 459 patients with a validated diagnosis of new-onset epilepsy. Patient records were retrospectively analyzed to determine the ASM doses in patients with or without seizure freedom during follow-up. The DDD of the relevant ASM was then retrieved., Results: The seizure-freedom rate with first and subsequent ASMs was 88% (404/459 patients) during the follow-up. The mean prescribed doses (PDDs) and PDD/DDD ratio of the most commonly used ASMs, ie, oxcarbazepine (OXC), carbamazepine (CBZ), and valproic acid (VPA), differed significantly between seizure-free and non-seizure-free status (992 mg and 0.99 vs 1132 mg and 1.13; 547 mg and 0.55 vs 659 mg and 0.66; and 953 mg and 0.64 vs 1260 mg and 0.84, respectively). The effect of the OXC dose as the first failed ASM on the possibility of achieving seizure freedom was significant (Fisher's exact test, p = 0.002). Thirty-four of 43 patients (79%) in which an OXC dose of ≤900 mg failed became seizure-free, as compared with 24 of 54 patients (44%) with a failed OXC dose >900 mg., Significance: The present study provides new insights into the doses of the commonly used ASMs such as OXC, CBZ, and VPA that can lead to seizure freedom as monotherapy or as combination therapy. The higher PDD/DDD ratio of OXC (0.99) than that of CBZ or VPA renders a generalized PDD/DDD comparison highly problematic., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: We evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset epilepsy., Materials and Methods: This study included 459 patients with a validated diagnosis of epilepsy. The most prescribed ASMs were oxcarbazepine (OXC; n = 307), followed by valproic acid (VPA; n = 115), carbamazepine (CBZ; n = 81), and lamotrigine (LTG; n = 67). The seizure freedom rate with their first or subsequent ASM was 88.0%. A retrospective analysis of patient records was performed to determine any association between doses of ASMs and patient characteristics., Results: The median OXC dose in seizure-free patients aged >60 years was 600 mg compared to 900 mg in younger patients. When controlling for age but not in an unadjusted model, the median dose of OXC was lower (300 mg, p = 0.018) for seizure-free patients compared to non-seizure-free patients, and the median dose of OXC was also 300 mg lower among older patients aged >60 years ( p < 0.001). The median OXC doses for men aged ≤60 years were 300 mg higher than for women aged >60 years (900 mg vs. 600 mg, p = 0.021). The median dose of VPA was 400 mg higher in men than in women ( p < 0.001) and 400 mg higher in not seizure-free patients compared to seizure-free patients only when adjusting for sex ( p < 0.001). Higher median doses for CBZ were registered with FAS compared with FBTCS (difference in median doses of 200 mg; p = 0.017)., Conclusion: Significant OXC dose differences were detected between age groups, whereas VPA dosing was different in men and women. Moreover, CBZ doses were dependent on some seizure types. These data allow for the individualization of the initial target dosing based on key clinical characteristics., Competing Interests: JP has participated in clinical trials for Eisai, UCB, and Bial, received research grants from Eisai, Medtronic, UCB, and LivaNova, received speaker honoraria from Angelini Pharma, LivaNova, Eisai, Medtronic, Orion Pharma, and UCB, received support for travel to congresses from LivaNova, Eisai, Medtronic, and UCB, and participated in advisory boards for Angelini Pharma, Jazz Pharma, Novartis, LivaNova, Eisai, Medtronic, UCB, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hersi, Peltola, Raitanen and Saarinen.)

Background: The purpose of our study was to analyze the impact of time interval from referral to surgery and from surgery to adjuvant treatment on survival of adult isocitrate dehydrogenase-wild-type (IDH-wt) glioblastomas., Methods: Data on 392 IDH-wt glioblastomas diagnosed at the Tampere University Hospital in 2004-2016 were obtained from the electronic patient record system. Piecewise Cox regression was used to calculate hazard ratios for different time intervals between referral and surgery, as well as between surgery and adjuvant treatments., Results: The median survival time from primary surgery was 9.5 months (interquartile range: 3.8-16.0). Survival among patients with an interval exceeding 4 weeks from referral to surgery was no worse compared to <2 weeks (hazard ratio: 0.78, 95% confidence interval: 0.54-1.14). We found indications of poorer outcome when the interval from surgery to radiotherapy exceeded 30 days (hazard ratio: 1.42, 95% confidence interval: 0.91-2.21 for 31-44 days; and 1.59, 0.94-2.67 for over 45 days)., Conclusions: Interval from referral to surgery in the range of 4-10 weeks was not associated with decreased survivals in IDH-wt glioblastomas. In contrast, delay exceeding 30 days from surgery to adjuvant treatment may decrease long-term survival., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation., Competing Interests: GG, SK, VP, JR, AR, LS, LC, MB, AH No competing interests declared, WW declares to having received speaker honoraria from the GE Healthcare and research grants from Ipsen Pharma, Eckert-Ziegler AG, Scintomics, and ITG; and working as a part time employee of CBmed Ltd. (Center for Biomarker Research in Medicine, Graz, Austria), MH received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers, RL received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MRI. He is a shareholder of the start-up company BM Health GmbH since 2019, (© 2023, Godbersen et al.)

Background: The burden of dementia, multimorbidity, and disability is high in the oldest old. However, the contribution of dementia and comorbidities to functional ability in this age group remains unclear. We examined the combined effects of dementia and comorbidities on ADL and mobility disability and differences between dementia-related disability between 2001, 2010, and 2018., Methods: Our data came from three repeated cross-sectional surveys in the population aged 90 + in the Finnish Vitality 90 + Study. The associations of dementia with disability and the combined effects of dementia and comorbidity on disability adjusted for age, gender, occupational class, number of chronic conditions, and study year were determined by generalized estimating equations. An interaction term was calculated to assess differences in the effects of dementia on disability over time., Results: In people with dementia, the odds of ADL disability were almost five-fold compared to people with three other diseases but no dementia. Among those with dementia, comorbidities did not increase ADL disability but did increase mobility disability. Differences in disability between people with and without dementia were greater in 2010 and 2018 than in 2001., Conclusion: We found a widening gap in disability between people with and without dementia over time as functional ability improved mainly in people without dementia. Dementia was the main driver of disability and among those with dementia, comorbidities were associated with mobility disability but not with ADL disability. These results imply the need for strategies to maintain functioning and for clinical updates, rehabilitative services, care planning, and capacity building among care providers., (© 2023. The Author(s).)

Purpose: To examine the association of residential mobility, as a proxy for environmental influences, with childhood inflammatory bowel disease (IBD) risk., Methods: Using nationwide register-based dataset, all 2038 IBD cases in Finland diagnosed at ages less than 15 years in 1992-2016 were individually matched by sex and age with five controls employing risk set sampling. Complete residential histories of the subjects were constructed from birth until the index date (diagnosis date of the case). Movement patterns were assessed by age, distance, and demographics of the departure and destination municipalities. Conditional logistic regression was employed to estimate the association between movements and IBD risk., Results: Overall, residential movement was associated with a slightly decreased odds ratio (OR) for childhood IBD (OR 0.97, 95% confidence interval (CI) 0.95-1.00 for each movement). Further examination showed reduced ORs for moving to rural municipalities (OR 0.94, 95% CI 0.90-0.98) and to distances less than 50 km (OR 0.96, 95% CI 0.93-0.99). In disease subtype analyses, the effect mainly persisted in ulcerative colitis., Conclusions: Our findings suggest lower childhood IBD risk associated with residential mobility. The effect was found in ulcerative colitis, but not in Crohn's disease. Movements to nearby and rural areas may reduce IBD risk, though this requires further investigation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antibodies against glutamic acid decarboxylase (GADA) are present in multiple neurological manifestations, such as stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Increasing data support the clinical significance of GADA as an autoimmune etiology of epilepsy, however, there is not yet definitive evidence to confirm the pathogenic link between GADA and epilepsy., Objective: Interleukin-6 (IL-6), a pro-convulsive and neurotoxic cytokine, and interleukin-10 (IL-10), an anti-inflammatory and neuroprotective cytokine, are crucial inflammatory mediators in the brain. Increased production of IL-6 and its association with epileptic disease profiles are well established, suggesting the presence of chronic systemic inflammation in epilepsy. Therefore, in this study, we investigated the association of plasma cytokine concentrations of IL-6 and IL-10 and their ratio with GADA in patients with drug-resistant epilepsy., Methods: Interleukin-6 and IL-10 concentrations were measured by ELISA in plasma, and the IL-6/IL-10 ratio was calculated in a cross-sectional cohort of 247 patients with epilepsy who had their GADA titers measured previously for their clinical significance in epilepsy. Based on GADA titers, patients were grouped as GADA negative ( n = 238), GADA low positive (antibody titers < 1,000 RU/mL, n = 5), and GADA high positive (antibody titers ≥ 1,000 RU/mL, n = 4)., Results: Median IL-6 concentrations were significantly higher in patients with high GADA positivity [2.86 pg/mL, interquartile range (IQR) = 1.90-5.34 pg/mL] than in GADA-negative patients [1.18 pg/mL, interquartile range (IQR) = 0.54-2.32 pg/mL; p = 0.039]. Similarly, IL-10 concentrations were also higher in GADA high-positive patients [1.45 pg/mL, interquartile range (IQR) = 0.53-14.32 pg/mL] than in GADA-negative patients [0.50 pg/mL, interquartile range (IQR) = 0.24-1.00 pg/mL], however, the difference was not statistically significant ( p = 0.110). Neither IL-6 nor IL-10 concentrations were different between GADA-negative and GADA low-positive patients ( p > 0.05) or between GADA low-positive or GADA high-positive patients ( p > 0.05). The IL-6/IL-10 ratio was also similar among all the study groups., Conclusion: Increased circulatory concentrations of IL-6 are associated with high GADA titers in patients with epilepsy. These data provide additional pathophysiological significance of IL-6 and help to further describe the immune mechanisms involved in the pathogenesis of GADA-associated autoimmune epilepsy., Competing Interests: MPes was employed by Fimlab Laboratories Ltd., and Gilead Sciences, Finland. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Basnyat, Peltola, Raitanen, Liimatainen, Rainesalo, Pesu and Peltola.)

Background: There are a very few studies focusing on the individual-based survival with a long follow-up time., Aim: To identify predictors and determine their joint predictive value for longevity using individual-based outcome measures., Methods: Data were drawn from Tampere Longitudinal Study on Aging (TamELSA), a study of individuals' age 60-89 years (N = 1450) with a mortality follow-up of up to 35 years. Two measures of longevity were used: the longevity difference (LD) and realized probability of dying (RPD), both of which compare each individual's longevity with their life expectancy as derived from population life tables. Independent variables were categorized into five domains: sociodemographic, health and functioning, subjective experiences, social activities, and living conditions. Linear regression models were used in three steps: bivariate analysis for each variable, multivariate analysis based on backward elimination for each domain, and one final model., Results: The most important predictors of both outcomes were marital status, years smoked regularly, mobility, self-rated health, endocrine and metabolic diseases, respiratory diseases, and unwillingness to do things or lack of energy. The explained variance in longevity was 13.8% for LD and 14.1% for RPD. This demonstrated a large proportion of unexplained error margins for the prediction of individual longevity, even though many known predictors were used., Discussion and Conclusions: Several predictors associated with longer life were found. Yet, on an individual level, it remains difficult to predict who will live longer than their age peers. The stochastic element in the process of aging and in death may affect this prediction., (© 2022. The Author(s).)

Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves overdetection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA <3 ng/mL, cumulative PCa incidence was 9.1% after 17.6 years median follow-up. Cumulative incidence was 3.6% among men with baseline PSA 0 to 0.99 ng/mL, 11.5% in those with PSA 1.0 to 1.99 ng/mL and 25.7% among men with PSA 2 to 2.99 ng/mL (hazard ratio 9.0, 95% CI: 7.9-10.2 for the latter). The differences by PSA level were most striking for low-risk disease based on Gleason score and EAU risk group. PSA values <1 ng/mL indicate a very low 20-year risk, while at PSA 2 to 2.99 ng/mL risks are materially higher, with 4- to 5-fold risk for aggressive disease. Using risk-stratification and appropriate rescreening intervals will reduce screening intensity and overdetection. Using cumulative incidence of clinically significant PCa (csPCa) as the criterion, rescreening intervals could range from approximately 3 years for men with initial PSA 2 to 2.99 ng/mL, 6 years for men with PSA 1 to 1.99 ng/mL to 10 years for men with PSA <1 ng/mL., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Vitality 90+ is an ongoing population-based study with repeated cross-sectional data collections. The study was designed to examine trends in health, functioning, living conditions, quality of life and care needs among the oldest old in Finland., Participants: Nine mailed surveys have been conducted in the city of Tampere between 1995 and 2018. The first three surveys in 1995, 1996 and 1998 included all community-dwelling individuals aged 90 years or older; and the following six surveys in 2001, 2003, 2007, 2010, 2014 and 2018 covered all individuals in Tampere regardless of their living arrangements. In total, the surveys have included 5935 participants (8840 observations). Around 80% of the participants have been women. The participants' age range has been between 90 and 107 years., Findings to Date: The surveys have consistently asked the same questions over time, covering basic sociodemographic factors, morbidity, functioning, self-rated health (SRH), living arrangements, social relations, quality of life, care needs and providers of care. Survey data have been linked with national register data on health and social service use, mortality and medication. The main findings regarding the time trends show an increase in the proportion of people independent in activities of daily living and mobility. Along with improved functioning, the number of chronic conditions has increased, and SRH has shown a tendency to decline. In addition, we have found increasing occupational class inequalities in functioning and SRH over time., Future Plans: The next round of data collection will be completed by the end of 2022. The Vitality 90+ Study welcomes research collaborations that fall within the general aims of the project. The research data 1995-2014 are archived at the Finnish Social Science Data Archive and the data for years 2018 and 2022 will be archived in 2023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17-82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker., (© 2022. The Author(s).)

Radiation therapy is one of the most effective tools in cancer therapy. However, success varies individually, necessitating improved understanding of radiobiology. Three-dimensional (3D) tumor spheroids are increasingly gaining attention, being a superior in vitro cancer model compared to 2D cell cultures. This in vitro study aimed at comparing radiation responses in 2D and 3D cell culture models of different human cancer cell lines (PC-3, LNCaP and T-47D) irradiated with varying doses (1, 2, 4, 6, 8 or 20 Gy) of X-ray beams. Radiation response was analyzed by growth analysis, various cell viability assays (e.g., clonogenic assay, resazurin assay) and amount of DNA damage (γH2AX Western Blot). Results showed decreasing cell proliferation with the increase of radiation doses for all cell lines in monolayers and spheroids of LNCaP and T-47D. However, significantly lower radiosensitivity was detected in spheroids, most pronounced in PC-3, evincing radiation resistance of PC-3 spheroids up to 8 Gy and significant growth inhibition only by a dose escalation of 20 Gy. Cell line comparison showed highest radiosensitivity in LNCaP, followed by T-47D and PC-3 in 2D, whereas, in 3D, T-47D showed highest sensitivity. The results substantiate the significant differences in radiobiological response to X-rays between 2D and 3D cell culture models.

Objective: There is a lack of studies using the International League Against Epilepsy (ILAE) recommendation to define drug-resistant epilepsy (DRE). This study evaluated the seizure freedom rates of substitution or add-on and subsequent antiseizure medication (ASM) therapies using different proposed definitions of DRE or ASM trials in patients with a failed first ASM. We also identified prognostic factors for 1-year seizure freedom., Methods: This study included 459 patients with epilepsy of whom 151 were not seizure-free after the first ASM. Multilevel mixed-effects logistic regression was used to examine the correlation between observations from the same patient., Results: The overall seizure freedom rate with the first and subsequent ASMs was 88.0% (404/459). The rate of DRE when defined as the failure of two ASMs for any reason was 20.0%, and according to the ILAE definition of DRE, it was 16.3%. After failing the first ASM, 63.6% of patients (96/151) became seizure free with subsequent ASMs and tried an average of 1.9 ASMs (range 1-5). Of the patients who achieved 1-year seizure freedom, 10.1% (41/404) were taking polytherapy and there was no difference between substitution and add-on. All the patients with generalized epilepsy were seizure-free. A favorable prognostic factor was age >60 years and an EEG without epileptiform activity. The efficacies of the different ASMs were largely similar, but drugs that enhanced GABA-mediated inhibitory neurotransmission had the lowest seizure freedom rate., Significance: In adults with newly-diagnosed epilepsy, 1-year seizure freedom was achieved for almost 90% of the patients. After failing the first ASM, two-thirds of the patients responded to subsequent ASM regimens. Our results support the feasibility and applicability of the ILAE concept of an adequate ASM trial and the failure of two ASMs as a definition of DRE., Competing Interests: Author JP has participated in clinical trials for Eisai, UCB, and Bial; received research grants from Eisai, Medtronic, UCB, and Liva-Nova; received speaker honoraria from LivaNova, Eisai, Medtronic, Orion Pharma, and UCB; received support for travel to congresses from LivaNova, Eisai, Medtronic, and UCB; and participated in advisory boards for Arvelle, Novartis, LivaNova, Eisai, Medtronic, UCB, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hersi, Saarinen, Raitanen and Peltola.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Physical activity may sustain the physical aspect of work ability despite health problems such as musculoskeletal disorders and anxiety, which are the most prevalent work-related health problem in Europe., Aims: To evaluate the association of Finnish municipal workers' accelerometer-measured physical activity, sedentary behaviour, and cardiorespiratory and muscular fitness with their sickness absence levels, perceived work ability and health-related quality of life., Methods: In connection with a randomized controlled trial recruiting 185 municipal workers, the authors performed baseline data analysis utilizing quantile regression to examine relationships between the outcome variables (all-cause sickness absence for 6 months, perceived work ability and health-related quality of life) and cardiorespiratory fitness, muscular fitness, and physical activity, and sedentary behaviour. All results were adjusted for age, sex and education level., Results: The median duration of all-cause sickness absence over the preceding 6 months was lowest among participants with high cardiorespiratory fitness relative to the lowest tertile (2.0 versus 6.0 days; P < 0.05), and the highest perceived work ability was found among those with high or moderate cardiorespiratory fitness as compared to the lowest tertile (8.0 versus 7.0; P < 0.001). Moderate-to-vigorous physical activity correlated positively with the physical component of health-related quality of life (P < 0.01) and with a high cardiorespiratory-fitness level (P < 0.05)., Conclusions: High cardiorespiratory fitness was associated with decreased all-cause sickness absence days and improved work ability among municipal workers., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Occupational Medicine.)

Abstract: Pihlainen, K, Kyröläinen, H, Santtila, M, Ojanen, T, Raitanen, J, and Häkkinen, K. Effects of combined strength and endurance training on body composition, physical fitness, and serum hormones during a 6-month crisis management operation. J Strength Cond Res 36(9): 2361-2370, 2022-Very few studies have examined the impact of training interventions on soldier readiness during an international military operation. Therefore, the present study investigated the effects of combined strength and endurance training on body composition, physical performance, and hormonal status during a 6-month international military deployment consisting of typical peacekeeping tasks, e.g., patrolling, observation, and on-base duties. Soldiers ( n = 78) were randomly allocated to a control group (C) or one of 3 combined whole-body strength and endurance training groups with varying strength-to-endurance training emphasis (Es = 25/75%, SE = 50/50% or Se = 75/25% of strength/endurance training). Body composition, physical performance (3000-m run, standing long jump [SLJ], isometric maximal voluntary contraction of the lower [MVC lower] and upper extremities [MVC upper ], muscle endurance tests), and selected serum hormone concentrations were determined prior to training (PRE), and after 9 (MID) and 19 (POST) weeks of training. Within- and between-group changes were analyzed using linear regression models. The average combined strength and endurance training frequency of the total subject group was 3 ± 2 training sessions per week. No changes were observed in physical performance variables in the intervention groups, whereas SLJ decreased by 1.9% in C ( p < 0.05). Maximal voluntary contraction lower increased by 12.8% in the combined intervention group ( p < 0.05), and this was significantly different to C ( p < 0.05). Testosterone-to-cortisol ratio increased in SE and Se ( p < 0.05), whereas no change was observed in C. The intervention groups maintained or improved their physical performance during deployment, which is beneficial for operational readiness. However, the high interindividual variation observed in training adaptations highlights the importance of training individualization during prolonged military operations., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the National Strength and Conditioning Association.)

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1 / nc886 , in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.

Objectives: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit., Patients and Methods: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies., Results: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%., Conclusion: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal., (© 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Physical activity (PA) has been shown to associate with many health benefits but studies with metabolome-wide associations with PA are still lacking. Metabolome studies may deepen the mechanistic understanding of PA on the metabolic pathways related to health outcomes. The aim of the present study was to study the association of accelerometer based sedentary time (SB) and PA with metabolome measures. SB and PA were measured by a hip-worn accelerometer in 314 young adult men (age: mean 28, standard deviation 7 years). Metabolome was analyzed from fasting serum samples consisting of 66 metabolome measures (nuclear magnetic resonance-based metabolomics). The associations were analyzed using a single and compositional approach with regression analysis. The compositional analysis revealed that 4 metabolome variables were significantly (γ: 0.32−0.44, p ≤ 0.002), and 13 variables with a trend towards significance (p < 0.05), associated with SB with varying metabolic pathways. Trends towards significant associations (p < 0.05) were observed with 5 variables with moderate-to-vigorous and 1 variable with light intensity PA with varying metabolic pathways. The present study revealed possible mechanistic pathways relevant for the interaction between especially SB but also PA of moderate-to-vigorous intensity with ketone bodies and amino acid concentration related to exercised-induced energy production and lipid metabolism.

Introduction: Central nervous system (CNS) tumors are a leading cause of cancer-related morbidity and mortality in children. Our aim is to characterize incidence trends of pediatric CNS tumors in Finland over the last three decades., Methods: Data on all benign and malignant incident CNS tumors diagnosed in children aged 0-14 years in 1990-2017 were extracted from the Finnish Cancer Registry and classified according to the 2016 WHO classification of CNS tumors. We analyzed age-standardized incidence rates (ASR) for pediatric CNS tumors overall and by sex, age, tumor histology, grade, and location using Poisson regression. We used joinpoint regression to evaluate changes in trends., Results: Overall, 1117 pediatric CNS tumor cases were registered in Finland with a 1.2:1 male to female ratio. The average annual ASR was 4.3 per 100,000 person-years (95% CI 4.26, 4.34). The most common tumor type was pilocytic astrocytoma (30% of tumors), followed by medulloblastoma (10%) with incidence rates of 1.30 and 0.45 per 100,000 person-years, respectively. The overall incidence of pediatric CNS tumors increased by an annual percentage change (APC) of 0.8% (95% CI 0.2, 1.4). We observed no major changes in incidence trends of tumor histology groups or tumor location groups. The ASR of benign tumors increased by an APC of 1.0 (95% CI 0.1, 2.0)., Conclusions: Utilizing the high-quality and completeness of data in the Finnish Cancer registry, we found that the incidence of pediatric CNS tumors in Finland has increased slightly from 1990 until 2017. Although variations in diagnostic and registration practices over time might have affected the rates, the trend may also reflect a true increase in incidence., (© 2022. The Author(s).)

Background: Low physical activity and high sedentary behaviour are unquestionably relevant for public health while also increasing direct and indirect costs., Methods: The authors examined the direct and indirect costs attributable to low physical activity and high sedentary behaviour in Finland in 2017. Costs related to major non-communicable diseases drawn from Finnish registries covered direct costs (outpatient visits, days of inpatient care, medication and institutional eldercare) and indirect costs (sickness-related absences, disability pensions, unemployment benefits, all-cause mortality and losses of income tax revenue). Prevalences of low physical activity and high sedentary behaviour (≥8 hours per 16 waking hours) were based on self-reports among adolescents or accelerometer data among adults and the elderly from three Finnish population studies: FINFIT 2017, Health 2011 and the Cardiovascular Risk in Young Finns Study. Cost calculations used adjusted population attributable fractions (PAF) and regression models. Total annual costs were obtained by multiplying PAF by the total costs of the given disease., Results: The total costs of low physical activity in Finland in 2017 came to approximately €3.2 billion, of which direct costs accounted for €683 million and indirect ones for €2.5 billion. Costs attributable to high sedentary behaviour totalled roughly €1.5 billion., Conclusion: The findings suggest that low physical activity and high sedentary behaviour levels create substantial societal costs. Therefore, actions intended to increase physical activity and reduce excessive sedentary behaviour throughout life may yield not only better health but also considerable savings to society., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)