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Objectives Background Methods/Materials Results Conclusion Fast thawing for emergency situations and reduction of plasma wastage.Evaluation of plasma units, pooled and pathogen reduced (PR) in “maxi‐pools” with amotosalen and UVA light, and fast thawing.Per replicate, 10 WB‐derived leukocyte depleted plasma units were frozen within 24 h at ≤ −25°C and stored for 7 days. After thawing, a maxi‐pool was constituted from the 10 units. After splitting into 4 sub‐pools of 650 mL, the sub‐pools were PR treated then split into 3 units resulting in 12 PR plasma units at 200 mL. Hundred and twenty PR plasma units were produced in total. The units were frozen at ≤ −25°C for 1 week, then thawed either in a fast plasma thawer for 5 min or in other control devices (17 to 23 min). FVIII:C, Fibrinogen, albumin, IgG, protein S and VWF were measured in plasma units, maxi‐pools and plasmas after PR treatment and thawing.There was a statistically significant (p < 0.001) but still clinically acceptable (over the recommended levels of ≥0.5 IU/mL and ≥2 g/L) reduction of FVIII:C and Fibrinogen after PR with 69% and 87% recovery, respectively. Other proteins were not significantly affected by the processes.Pooling 10 plasma units before the PR treatment standardises volume and protein content of plasma units. Besides the economic value of generating 12 products for transfusion, this procedure combined with a thawing time of about 5 min is of value in emergency situations and may reduce plasma wastage. [ABSTRACT FROM AUTHOR]

Background: Previous findings support the claim intensive care unit (ICU) patients have a higher rate of comorbidities and reduction of health‐ and functional status compared with the normal population. Aim: In this prospective observational study, our aim was to determine those health‐related factors at the age of 31 years which were associated with a later critical illness among previously un‐hospitalized individuals by exploring data obtained from the Northern Finland Birth Cohort 1966 (NFBC1966). Methods: NFBC1966 is a Finnish birth cohort, which includes 12,058 live births with expected dates of delivery during 1966. The study was conducted among cohort participants who had not been hospitalized for any reason before the cohort follow‐up visit at the age of 31. The study group included NFBC1966 participants who were admitted to the ICU of the Oulu University Hospital. The control group included participants who were treated for any reason in regular hospital wards. The data considering the participants' health status and behavior at the age of 31 were collected from the NFBC1966 database. The gathering of ICU and hospitalization data was concluded on December 31, 2016. Results: 849 NFBC1966 participants met the inclusion criteria: 69 were treated in the ICU (study group) and 780 on regular hospital wards (controls). In the study group, the rate of neurological diseases (26% vs. 16%, 95% CI: −21.8%, −0.2%), malignancy (3% vs. 0.7%, 95% CI: −9.7%, 0.0%), alcohol abuse (4.5% vs. 1%, 95% CI: −11.5%, −0.3%) and smoking (77% vs. 65%, 95% CI: −21.6%, −0.3%) were higher compared with the control group. The patients in the ICU group were also more prone to violent injuries, (17% vs. 7%, 95% CI: −20.2%, −1.9%), practiced less hard physical activity (65% vs. 78%, 95% CI: 2.1%, 25.3%) and had lower maximal muscle strength according to the hand grip test (30 vs. 34 kg, 95% CI: −8.2, 8.6 kg). Conclusions: In this study examining previously un‐hospitalized patients, the main factors associated with future critical illness were neurological comorbidities, malignancy, alcohol misuse, smoking, low maximum muscle strength, and less frequent physical exercise compared with those with hospitalization not requiring ICU admission. [ABSTRACT FROM AUTHOR]

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

Abstract Background Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. Methods Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). Results There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Conclusions Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002–2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008–2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022–2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.

ObjectivesThe aim of this longitudinal study was to investigate how intensified job demands (job-related planning demands, career-related planning demands, and learning demands) are associated with burnout. We explored whether affective-identity motivation to lead moderates this association and, thus, functions as a personal resource regardless of leadership status. We further investigated whether the possible buffering effect is stronger for those professionals who became leaders during the follow-up.MethodsOur sample consisted of highly educated Finnish professionals (n = 372): part of them (n = 63, 17%) occupied a leadership position during the 2-year follow-up while the rest maintained their position without formal leadership duties.ResultsThe results of hierarchical linear modeling indicated that intensified learning demands were associated with later burnout. High affective-identity motivation to lead was not found to buffer against the negative effects of intensified job demands - instead, it strengthened the connection of intensified job- and career-related demands to burnout. Nevertheless, among the whole sample, professionals with high affective-identity motivation to lead reported lower burnout when job demands were not highly intensified. The leadership status also played a role: High affective-identity motivation to lead strengthened the connection of career-related demands to burnout in those professionals who became leaders during the follow-up.ConclusionsAltogether, we propose that in certain circumstances, affective-identity motivation to lead might help professionals, with and without formal leadership duties, to be more ready to lead their own work and well-being. However, in order to promote sustainable careers, the vulnerability role of high affective-identity motivation to lead should be considered as well.

Introduction: This is one of the first intervention studies to examine how low- (LIT) and high-intensity endurance training (HIT) affect durability, defined as ‘time of onset and magnitude of deterioration in physiological-profiling characteristics over time during prolonged exercise’.Methods: Sedentary and recreationally active men (n = 16) and women (n = 19) completed either LIT (average weekly training time 6.8 ± 0.7 h) or HIT (1.6 ± 0.2 h) cycling for 10 weeks. Durability was analyzed before and after the training period from three factors during 3-h cycling at 48% of pretraining maximal oxygen uptake (VO2max): 1) by the magnitude and 2) onset of drifts (i.e. gradual change in energy expenditure, heart rate, rate of perceived exertion, ventilation, left ventricular ejection time, and stroke volume), 3) by the ‘physiological strain’, defined to be the absolute responses of heart rate and its variability, lactate, and rate of perceived exertion.Results: When all three factors were averaged the durability was improved similarly (time x group p = 0.42) in both groups (LIT: p = 0.03, g = 0.49; HIT: p = 0.01, g = 0.62). In the LIT group, magnitude of average of drifts and their onset did not reach statistically significance level of p < 0.05 (magnitude: 7.7 ± 6.8% vs. 6.3 ± 6.0%, p = 0.09, g = 0.27; onset: 106 ± 57 min vs. 131 ± 59 min, p = 0.08, g = 0.58), while averaged physiological strain improved (p = 0.01, g = 0.60). In HIT, both magnitude and onset decreased (magnitude: 8.8 ± 7.9% vs. 5.4 ± 6.7%, p = 0.03, g = 0.49; onset: 108 ± 54 min vs. 137 ± 57 min, p = 0.03, g = 0.61), and physiological strain improved (p = 0.005, g = 0.78). VO2max increased only after HIT (time x group p < 0.001, g = 1.51).Conclusion: Durability improved similarly by both LIT and HIT based on reduced physiological drifts, their postponed onsets, and changes in physiological strain. Despite durability enhanced among untrained people, a 10-week intervention did not alter drifts and their onsets in a large amount, even though it attenuated physiological strain.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I2 = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55–69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99–1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

Abstract Gut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms through which drug–microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching circulation in patients with Parkinson’s disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a period of 2 years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, several anti-PD medications, including entacapone, rasagiline, pramipexole, and ropinirole but not levodopa, and gastrointestinal symptoms, warranting further research on the effect of anti-PD medication on microbial changes and gastrointestinal function.

Abstract Background Nowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies. Methods A systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999–2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study. Results Currently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time. Conclusions Our findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.