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.

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.

Long-term care use, hospitalizations and mortality during COVID-19 in Finland and Sweden: A nationwide register-based study in 2020.

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.

Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

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.

Complex executive functions assessed by the trail making test (TMT) part B improve more than those assessed by the TMT part A or digit span backward task during vagus nerve stimulation in patients with drug-resistant epilepsy.

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.

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.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

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.

Health-Related Costs of Intimate Partner Violence: Using Linked Police and Health Registers.

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.

Changes in incidence trends of meningioma in Finland, 1990-2017: analysis of Finnish Cancer Registry data.

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.

Effect of clinical features on antiseizure medication doses in patients with newly diagnosed 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.

Impact of Timing of Surgery and Adjuvant Treatment on Survival of Adult IDH-wild-type Glioblastoma: A Single-center Study of 392 Patients.

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.

Neuromuscular exercise and counseling for treating recurrent low back pain in female healthcare workers-Findings from a 24-month follow-up study of a randomized controlled trial.

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.

Dementia-related disability in the population aged 90 years and over: differences over time and the role of comorbidity in the vitality 90 + study.

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.

Prescribed antiseizure medication doses and their relation to defined daily doses for achieving seizure freedom in newly diagnosed patients with epilepsy.

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.

Elevated IL-6 plasma levels are associated with GAD antibodies-associated autoimmune epilepsy.

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.

Residential mobility and childhood inflammatory bowel disease: a nationwide case-control study.

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.

Cohort profile: The Vitality 90+ Study-a cohort study on health and living conditions of the oldest old in Tampere, Finland.

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.

Who live longer than their age peers: individual predictors of longevity among older individuals.

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.

Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics.

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.

Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL: The Finnish Randomized Study of Screening for Prostate Cancer.

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.