Psychological impact of lymphoma on adolescents and young adults:Not a matter of black or white

Contains fulltext : 171302.pdf (publisher's version ) (Open Access)PURPOSE: The purpose of the study is to examine differences in perceived impact of cancer (IOC) between adolescents and young adults (AYAs; 18-35 years at cancer diagnosis), adults (36-64 years) and elderly (65-84 years) with a history of (non-)Hodgkin lymphoma. Furthermore, to investigate the association of socio-demographic, clinical and psychological characteristics with IOC; and the association between IOC and health-related quality of life (HRQoL) among AYAs only. METHODS: This study is part of a population-based PROFILES registry survey among lymphoma patients diagnosed between 1999 and 2009. Patients (n = 1.281) were invited to complete the IOCv1 and EORTC-QLQ-C30 questionnaires. Response rate was 67 % (n = 861). RESULTS: AYA lymphoma survivors scored higher on the positive IOC summary scale, compared to adult and elderly patients (p < 0.001), while no significant differences were observed for negative IOC. Among AYAs, females, survivors with a partner, and survivors with elevated psychological distress levels scored significantly higher on the negative IOC summary scale. The negative IOC summary scale was negatively associated with all EORTC QLQ-C30 functioning scales (beta ranging from -0.39 to -0.063; p < 0.05). The positive IOC summary scale was negatively associated with the EORTC QLQ-C30 subscale 'Emotional functioning' (beta = -0.24; p < 0.05). CONCLUSION: AYA, adult and elderly with a history of (non-)Hodgkin lymphoma experienced different types of IOC in terms of positive and negative aspects. IMPLICATIONS FOR CANCER SURVIVORS: Although AYAs experience a more positive IOC compared to older survivors, some AYAs experience more negative IOC and may require developmentally appropriate interventions to address their specific concerns

Phase transitions in a ferrofluid at magnetic field induced microphase separation

In the presence of a magnetic field applied perpendicular to a thin sample layer, a suspension of magnetic colloidal particles (ferrofluid) can form spatially modulated phases with a characteristic length determined by the competition between dipolar forces and short-range forces opposing density variations. We introduce models for thin-film ferrofluids in which magnetization and particle density are viewed as independent variables and in which the non-magnetic properties of the colloidal particles are described either by a lattice-gas entropy or by the Carnahan-Starling free energy. Our description is particularly well suited to the low-particle density regions studied in many experiments. Within mean-field theory, we find isotropic, hexagonal and stripe phases, separated in general by first-order phase boundaries.Comment: 12 pages, RevTex, to appear in PR

Dexamethasone implant for non-infectious uveitis: is it cost-effective?

BACKGROUND: Uveitis is inflammation inside the eye. The objective of this study is to assess the cost-effectiveness of a dexamethasone implant plus current practice (immunosuppressants and systemic corticosteroids) compared with current practice alone, in patients with non-infectious intermediate, posterior or pan-uveitis and to identify areas for future research. METHODS: A Markov model was built to estimate the costs and benefits of dexamethasone. Systematic reviews were performed to identify available relevant evidence. Quality of life data from the key randomised-controlled trial (HURON) was used to estimate the interventions' effectiveness compared with the trial's comparator arm (placebo plus limited current practice (LCP)). The analysis took a National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant compared with LCP is estimated as £19 509 per quality-adjusted life year (QALY) gained. The factors with the largest impact on the results were rate of blindness and relative proportion of blindness cases avoided by dexamethasone. Using plausible alternative assumptions, dexamethasone could be cost saving or it may be associated with an ICER of £56 329 per QALY gained compared with LCP. CONCLUSIONS: Dexamethasone is estimated to be cost-effective using generally accepted UK thresholds. However, there is substantial uncertainty around these results due to scarcity of evidence. Future research on the following would help provide more reliable estimates: effectiveness of dexamethasone versus current practice (instead of LCP), with subgroup analyses for unilateral and bilateral uveitis, incidence of long-term blindness and effectiveness of dexamethasone in avoiding blindness

Adalimumab for non-infectious uveitis: is it cost-effective?

BACKGROUND/AIMS: Uveitis is inflammation inside the eye. Our objective was to assess the cost-effectiveness of adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or panuveitis and to identify areas for future research. METHODS: A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the available relevant clinical and cost-effectiveness evidence. Data collected in two key randomised controlled trials (VISUAL I and VISUAL II) were used to estimate the interventions' effectiveness compared with the trials' comparator arms (placebo plus limited current practice (LCP)). The analysis was performed from the National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The estimated incremental cost-effectiveness ratios (ICERs) of adalimumab versus LCP for the base case are £92 600 and £318 075 per quality-adjusted life year (QALY) gained for active and inactive uveitis, respectively. In sensitivity analyses, the ICER varied from £15 579 to £120 653 and £35 642 to £800 775 per QALY for active and inactive uveitis. CONCLUSION: The estimated ICERs of adalimumab versus LCP are above generally accepted thresholds for cost-effectiveness in the UK. Adalimumab may be more cost-effective in patients with active uveitis at greater risk of blindness. However, there is an unmet need for additional primary data to provide more reliable estimates in several important areas, including effectiveness of adalimumab versus current practice (instead of LCP), incidence of long-term blindness, adalimumab effectiveness in avoiding blindness, and rates and time to remission while on adalimumab

Modeling complement activation on human glomerular microvascular endothelial cells

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease caused by dysregulation of the complement alternative pathway. The complement dysregulation specifically leads to damage to the glomerular endothelium. To further understand aHUS pathophysiology, we validated an ex vivo model for measuring complement deposition on both control and patient human glomerular microvascular endothelial cells (GMVECs). Methods: Endothelial cells were incubated with human test sera and stained with an anti-C5b-9 antibody to visualize and quantify complement depositions on the cells with immunofluorescence microscopy.Results: First, we showed that zymosan-activated sera resulted in increased endothelial C5b-9 depositions compared to normal human serum (NHS). The levels of C5b-9 depositions were similar between conditionally immortalized (ci)GMVECs and primary control GMVECs. The protocol with ciGMVECs was further validated and we additionally generated ciGMVECs from an aHUS patient. The increased C5b-9 deposition on control ciGMVECs by zymosan-activated serum could be dose-dependently inhibited by adding the C5 inhibitor eculizumab. Next, sera from five aHUS patients were tested on control ciGMVECs. Sera from acute disease phases of all patients showed increased endothelial C5b-9 deposition levels compared to NHS. The remission samples showed normalized C5b-9 depositions, whether remission was reached with or without complement blockage by eculizumab. We also monitored the glomerular endothelial complement deposition of an aHUS patient with a hybrid complement factor H (CFH)/CFH-related 1 gene during follow-up. This patient had already chronic kidney failure and an ongoing deterioration of kidney function despite absence of markers indicating an aHUS flare. Increased C5b-9 depositions on ciGMVECs were observed in all samples obtained throughout different diseases phases, except for the samples with eculizumab levels above target. We then tested the samples on the patient’s own ciGMVECs. The C5b-9 deposition pattern was comparable and these aHUS patient ciGMVECs also responded similar to NHS as control ciGMVECs. Discussion: In conclusion, we demonstrate a robust and reliable model to adequately measure C5b-9-based complement deposition on human control and patient ciGMVECs. This model can be used to study the pathophysiological mechanisms of aHUS or other diseases associated with endothelial complement activation ex vivo.</p

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis

Background: Women who engage in sex work in sub-Saharan Africa have a high risk of acquiring HIV infection. HIV incidence has declined among all women in sub-Saharan Africa, but trends among women who engage in sex work are poorly characterised. We synthesised data on HIV incidence among women who engage in sex work in sub-Saharan Africa and compared these with the total female population to understand relative incidence and trends over time. Methods: We searched MEDLINE, Embase, Global Health, and Google Scholar from Jan 1, 1990, to Feb 28, 2024, and grey literature for studies that reported empirical estimates of HIV incidence among women who engage in sex work in any sub-Saharan Africa country. We calculated incidence rate ratios (IRRs) compared with total female population incidence estimates matched for age, district, and year, did a meta-analysis of IRRs, and used a continuous mixed-effects model to estimate changes in IRR over time. Findings: From 32 studies done between 1985 and 2020, 2194 new HIV infections were observed among women who engage in sex work over 51 490 person-years. Median HIV incidence was 4·3 per 100 person years (IQR 2·8–7·0 per 100 person-years). Incidence among women who engage in sex work was eight times higher than matched total population women (IRR 7·8 [95% CI 5·1–11·8]), with larger relative difference in western and central Africa (19·9 [9·6–41·0]) than in eastern and southern Africa (4·9 [3·4–7·1]). There was no evidence that IRRs changed over time (IRR per 5 years: 0·9 [0·7–1·2]). Interpretation: Across sub-Saharan Africa, HIV incidence among women who engage in sex work remains disproportionately high compared with the total female population. However, constant relative incidence over time indicates HIV incidence among women who engage in sex work has declined at a similar rate. Location-specific data for women who engage in sex work incidence are sparse, but improved surveillance and standardisation of incidence measurement approaches could fill these gaps. Sustained and enhanced HIV prevention for women who engage in sex work is crucial to address continuing inequalities and ensure declines in new HIV infections. Funding: Bill & Melinda Gates Foundation, UK Research and Innovation, National Institutes of Health. Translation: For the French translation of the abstract see Supplementary Materials section

Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS. Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor.What is Known:• According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night.• Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited.What is New:• In general, children with a chronic condition sleep according to the recommended hours of sleep.• A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis

Angle-integrated measurements of the 26Al (d, n)27Si reaction cross section: a probe of spectroscopic factors and astrophysical resonance strengths

Measurements of angle-integrated cross sections to discrete states in 27Si have been performed studying the 26Al (d, n) reaction in inverse kinematics by tagging states by their characteristic $\gamma$ -decays using the GRETINA array. Transfer reaction theory has been applied to derive spectroscopic factors for strong single-particle states below the proton threshold, and astrophysical resonances in the 26Al (p,$\gamma$) 27Si reaction. Comparisons are made between predictions of the shell model and known characteristics of the resonances. Overall very good agreement is obtained, indicating this method can be used to make estimates of resonance strengths for key reactions currently largely unconstrained by experiment