Changes in parents' psychotropic medication use following child's cancer diagnosis : A fixed-effects register-study in Finland

Background Symptoms of depression and anxiety are elevated among parents of children with cancer. However, knowledge of parents' psychotropic medication use following child's cancer diagnosis is scarce. Methods We use longitudinal Finnish register data on 3266 mothers and 2687 fathers whose child (aged 0-19) was diagnosed with cancer during 2000-2016. We record mothers' and fathers' psychotropic medication use (at least one annual purchase of anxiolytics, hypnotics, sedatives, or antidepressants) 5 years before and after the child's diagnosis and assess within-individual changes in medication use by time since diagnosis, cancer type, child's age, presence of siblings, and parent's living arrangements and education using linear probability models with the individual fixed-effects estimator. The fixed-effects models compare each parent's annual probability of psychotropic medication use after diagnosis to their annual probability of medication use during the 5-year period before the diagnosis. Results Psychotropic medication use was more common among mothers than fathers already before the child's diagnosis, 11.2% versus 7.3%. Immediately after diagnosis, psychotropic medication use increased by 6.0 (95% CI 4.8-7.2) percentage points among mothers and by 3.2 (CI 2.1-4.2) percentage points among fathers. Among fathers, medication use returned to pre-diagnosis level by the second year, except among those whose child was diagnosed with acute lymphoblastic leukemia or lymphoblastic lymphoma. Among mothers of children with a central nervous system cancer, medication use remained persistently elevated during the 5-year follow-up. For mothers with other under-aged children or whose diagnosed child was younger than 10 years, the return to pre-diagnosis level was also slow. Conclusions Having a child with cancer clearly increases parents' psychotropic medication use. The increase is smaller and more short-lived among fathers, but among mothers its duration depends on both cancer type and family characteristics. Our results suggest that an increased care burden poses particular strain to the long-term mental well-being of mothers.Peer reviewe

Intraoperative Complications and Mid-Term Follow-Up of Large-Diameter Head Metal-on-Metal Total Hip Arthroplasty and Hip Resurfacing Arthroplasty

Background and Aims: Large-diameter head total hip arthroplasty and hip resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the treatment of hip osteoarthritis. The aim of this retrospective study was to investigate the mid-term survival of large-diameter head total hip arthroplasty patients operated on in three university hospitals and to compare these results to the survival of hip resurfacing arthroplasty patients. Material and Methods: A total of 3860 hip arthroplasties (3029 large-diameter head total hip arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757 patients) were operated on between January 2004 and December 2009. The mean follow-up was 4.3years (range: 0.3-8.0years) in the total hip arthroplasty group and 5.1years (range: 1.7-7.9years) in the hip resurfacing arthroplasty group. Cox multiple regression model and Kaplan-Meier survival analysis were used to study the survival of the total hip arthroplasties and the hip resurfacing arthroplasties. Intraoperative complications and reasons for revisions were also evaluated. Results: In Cox regression analysis, the hazard ratio for revision of hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip arthroplasty (95% confidence interval: 1.0-2.2) (p=0.029). The cumulative Kaplan-Meier survival rate was 90.7% at 7.7years for the large-diameter head total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6). There were a total of 166/3029 (5.5%) intraoperative complications in the large-diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip resurfacing arthroplasty group (p=0.001). Revision for any reason was performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing arthroplasty group (p=0.04). Conclusion: The mid-term survival of both of these devices was poor, and revisions due to adverse reactions to metal debris will most likely rise at longer follow-up. There were more intraoperative complications in the large-diameter head total hip arthroplasty group than in the hip resurfacing arthroplasty group.Peer reviewe

Measurements of muon flux in the Pyh\"asalmi underground laboratory

The cosmic-ray induced muon flux was measured at several depths in the Pyh\"asalmi mine (Finland) using a plastic scintillator telescope mounted on a trailer. The flux was determined at four different depths underground at 400 m (980 m.w.e), at 660 m (1900 m.w.e), at 990 m (2810 m.w.e) and at 1390 m (3960 m.w.e) with the trailer, and also at the ground surface. In addition, previously measured fluxes from depths of 90 m (210 m.w.e) and 210 m (420 m.w.e) are shown. A relation was obtained for the underground muon flux as a function of the depth. The measured flux follows well the general behaviour and is consistent with results determined in other underground laboratories.Comment: 8 pages, 2 figures. Submitted to Nuclear Instrum. Methods

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

Cut-off values to evaluate exercise-induced asthma in eucapnic voluntary hyperventilation test for children

Background and Aim The eucapnic voluntary hyperventilation (EVH) testing is a diagnostic tool for diagnostics of exercise-induced bronchoconstriction; while the testing has become more common among children, data on the test's feasibility among children remain limited. Our aim was to investigate EVH testing feasibility among children, diagnostic testing cut-off values, and which factors affect testing outcomes. Methods We recruited 134 patients aged 10-16 years with a history of exercise-induced dyspnoea and 100 healthy control children to undergo 6-min EVH testing. Testing feasibility was assessed by the children's ability to achieve >= 70% of the target minute ventilation of 30 times forced expiratory volume in 1 s (FEV1). Bronchoconstriction was assessed as a minimum of 8%, 10%, 12%, 15% or 20% fall in FEV1. Patient characteristics were correlated with EVH outcomes. Results Overall, 98% of the children reached >= 70%, 88% reached >= 80%, 79% reached >= 90% and 62% reached >= 100% of target ventilation in EVH testing; of children with a history of exercise-induced dyspnoea, the decline percentages were as follows: 24% (>= 8% fall), 17% (>= 10% fall), 10% (>= 12% fall), 6% (>= 15% fall) and 5% (>= 20% fall) in FEV1, compared to 11%, 4%, 3%, 1% and 0% among the healthy controls, respectively. Healthy controls and boys performed testing at higher ventilation rates (p < .05). Conclusion Eucapnic voluntary hyperventilation testing is feasible among children aged 10-16 years and has diagnostic value in evaluating exercise-induced dyspnoea among children. A minimum 10% fall in FEV1 is a good diagnostic cut-off value. Disease status appears to be important covariates

Iron Overload in Allogeneic Hematopoietic Cell Transplantation Outcome: A Meta-Analysis

AbstractAn elevated ferritin level before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and nonrelapse mortality. Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC > 7 mg/g dry weight (primary endpoint) was 1.4 (P = .18). In contrast, ferritin >1000 ng/mL was a significant prognostic factor (HR for mortality, 1.7; P = .036). There was, however, no significant association between ferritin > 2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

Genomic prediction of relapse in recipients of allogeneic haematopoietic stem cell transplantation

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the most informative variants while controlling against overfitting. Our results show that germline genetic polymorphisms in patients entail a significant contribution to relapse risk, as judged by the predictive performance of the model (AUC = 0.72 [95% CI: 0.63–0.81]). Furthermore, the top contributing variants were predictive in two independent replication cohorts (n = 258 and n = 125) from the same population. The results can help elucidate relapse mechanisms and suggest novel therapeutic targets. A computational genomic model could provide a step toward individualized prognostic risk assessment, particularly when accompanied by other data modalities.</p

Computational Analysis of HLA-presentation of Non-synonymous Recipient Mismatches Indicates Effect on the Risk of Chronic Graft-vs.-Host Disease After Allogeneic HSCT

Genetic mismatches in protein coding genes between allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipient and donor can elicit an alloimmunity response via peptides presented by the recipient HLA receptors as minor histocompatibility antigens (mHAs). While the impact of individual mHAs on allo-HSCT outcome such as graft-vs.-host and graft-vs.-leukemia effects has been demonstrated, it is likely that established mHAs constitute only a small fraction of all immunogenic non-synonymous variants. In the present study, we have analyzed the genetic mismatching in 157 exome-sequenced sibling allo-HSCT pairs to evaluate the significance of polymorphic HLA class I associated peptides on clinical outcome. We applied computational mismatch estimation approaches based on experimentally verified HLA ligands available in public repositories, published mHAs, and predicted HLA-peptide affinites, and analyzed their associations with chronic graft-vs.-host disease (cGvHD) grades. We found that higher estimated recipient mismatching consistently increased the risk of severe cGvHD, suggesting that HLA-presented mismatching influences the likelihood of long-term complications in the patient. Furthermore, computational approaches focusing on estimation of HLA-presentation instead of all non-synonymous mismatches indiscriminately may be beneficial for analysis sensitivity and could help identify novel mHAs

EMMA - A New Underground Cosmic-Ray Experiment

A new type of cosmic-ray experiment is under construction in the Pyh\"asalmi mine in the underground laboratory of the University of Oulu, Finland. It aims to study the composition of cosmic rays at and above the knee region. The experiment, called EMMA, will cover approximately 150 square-metres of detector area. The array is capable of measuring the multiplicity and the lateral distribution of underground muons, and the arrival direction of the air shower. The full-size detector is expected to run by the end of 2007.Comment: Extended and updated TAUP2005 Proceedings contribution. 8 pages, 5 figures (part in colour). Preprint not submitte