Mothers' reports of the difficulties that their children experience in taking methotrexate for Juvenile Idiopathic Arthritis and how these impact on quality of life

BACKGROUND: Children who take methotrexate for juvenile idiopathic arthritis may experience side effects, including nausea and vomiting, leading to anticipatory nausea in some children, and fear of injections or blood tests. The aim of this study was to examine the prevalence and extent of these difficulties and their impact on quality of life. METHODS: Participants were mothers of children with JIA who were currently taking methotrexate (MTX). Mothers completed a questionnaire about MTX that was developed for the study, two questions from the treatment subscale of the Pediatric Quality of Life Inventory (PedsQL) Rheumatology scale to assess needle-related problems and the Child Health Questionnaire 50-item parent version (CHQ-PF50) to assess health-related quality of life (HRQoL). RESULTS: 171 mothers participated in the study. More than half of children were reported to have experienced one or more of: nausea or vomiting after taking MTX, anticipatory nausea, fear of blood tests or fear of injections. There was no significant difference in reported rates of sickness or needle-related problems between MTX responders (ACR70 or above), partial responders (ACR30 or ACR50) and non-responders. In multivariate analyses, variables that were significant independent predictors of one or more MTX-related difficulties included younger age, taking MTX subcutaneously and having a larger number of currently active joints. Feeling sick after taking MTX was a significant independent predictor of poorer scores on the physical summary scale of the CHQ-PF50. Anxiety about injections and feeling sick after taking MTX were significant independent predictors of poorer scores on the psychosocial summary scale. CONCLUSIONS: Difficulties in taking MTX are experienced by a significant proportion of children with JIA and these have an adverse impact on HRQoL. Approaches to help minimize these difficulties are required

Domestic ventilation rates, indoor humidity and dust mite allergens : are our homes causing the asthma pandemic?

This paper is concerned with historical changes in domestic ventilation rates, relative humidity and the associated risk of house dust mite colonization. A controlled trial evaluated allergen and water vapour control measures on the level of house dust mite (HDM) Der p1 allergen and indoor humidity, concurrently with changes in lung function in 54 subjects who completed the protocol. Mechanical heat recovery ventilation units significantly reduced moisture content in the active group, while HDM allergen reservoirs in carpets and beds were reduced by circa 96%. Self reported health status confirmed a significant clinical improvement in the active group. The study can form the basis for assessing minimum winter ventilation rates that can suppress RH below the critical ambient equilibrium humidity of 60% and thus inhibit dust mite colonization and activity in temperate and maritime in' uenced climatic regions

A 60 yr record of atmospheric carbon monoxide reconstructed from Greenland firn air

We present the first reconstruction of the Northern Hemisphere (NH) high latitude atmospheric carbon monoxide (CO) mole fraction from Greenland firn air. Firn air samples were collected at three deep ice core sites in Greenland (NGRIP in 2001, Summit in 2006 and NEEM in 2008). CO records from the three sites agree well with each other as well as with recent atmospheric measurements, indicating that CO is well preserved in the firn at these sites. CO atmospheric history was reconstructed back to the year 1950 from the measurements using a combination of two forward models of gas transport in firn and an inverse model. The reconstructed history suggests that Arctic CO in 1950 was 140–150 nmol mol-1, which is higher than today's values. CO mole fractions rose by 10–15 nmol mol-1 from 1950 to the 1970s and peaked in the 1970s or early 1980s, followed by a ˜ 30 nmol mol-1 decline to today's levels. We compare the CO history with the atmospheric histories of methane, light hydrocarbons, molecular hydrogen, CO stable isotopes and hydroxyl radicals (OH), as well as with published CO emission inventories and results of a historical run from a chemistry-transport model. We find that the reconstructed Greenland CO history cannot be reconciled with available emission inventories unless unrealistically large changes in OH are assumed. We argue that the available CO emission inventories strongly underestimate historical NH emissions, and fail to capture the emission decline starting in the late 1970s, which was most likely due to reduced emissions from road transportation in North America and Europe

The Impact of Response to MTX on the Illness and Treatment Beliefs of Parents of Children with JIA

Background: Research on adult patients with chronic illness has shown that their illness beliefs are associated with patient reported outcomes. There is limited research focusing on the illness and treatment beliefs of parents of ill children. The aim of this study was to discern if treatment success, as measured by the ACR Pediatric (Ped) criteria has an impact upon parents’ beliefs about their child’s illness and treatment. Methods: The data of 157 mothers and 75 fathers was used in this cross-sectional study. Parents were asked to complete a series of questionnaires including the Illness Perception Questionnaire Revised (IPQ-R) and the Treatment Representation Inventory (TRI). Parents of children, who reached the ACR Ped 70 level of improvement in arthritis were compared to parents of non-responders using Chi-Square Tests and ANOVAs. Results: A number of significant differences in parents’ illness perceptions were found. Mothers of non-responders had a stronger belief in the unpredictable nature of the arthritis (p = 0.01) and mothers of ACR Ped 70 responders showed a stronger belief in their ability to control the arthritis (p = 0.03). Fathers of ACR Pediatric 70 responders had a stronger belief in their child’s understanding of the arthritis (p = 0.01) and in the arthritis being an acute condition (p = 0.03). Only one significant difference was found in parents’ treatment representations. Mothers of ACR Ped 70 responders had a stronger belief in the ability of the treatment to cure the arthritis. The means of the scale assessing the value of treatment were high for all mothers and fathers. Other treatment and illness beliefs were in the mid-range reflecting uncertain beliefs. Conclusions: With the exception of mothers’ beliefs in the ability of the treatment to cure the arthritis, no differences were found in the treatment beliefs between parents of ACR Ped 70 responders and parents of non-responders. This suggests that with exception of beliefs in cure, the treatment success is not generally reflected in parents’ treatment beliefs. However, treatment success influenced a number of parents’ beliefs about their child’s illness. These differences were all in the expected direction. Notably, on a number of the scales mothers and fathers consistently showed a degree of uncertainty in their beliefs about their child’s illness and treatment, regardless of treatment success. This uncertainty may reflect the fact that currently there is no cure for JIA. Illness uncertainty has been found to be positively associated with negative psychological outcomes in patients with chronic illness. The findings in this study suggest that parents of children with JIA may require additional support to deal with the uncertainty in relation to their child’s illness and treatment

Possible charge inhomogeneities in the CuO2 planes of YBa2Cu3O6+x (x=0.25, 0.45, 0.65, 0.94) from pulsed neutron diffraction

The atomic pair distribution functions (PDF) of four powder samples of YBa2Cu3O6+x (x=0.25, 0.45, 0.65, 0.94) at 15 K have been measured by means of pulsed neutron diffraction. The PDF is modelled using a full-profile fitting approach to yield structural parameters. In contrast to earlier XAFS work we find no evidence of a split apical oxygen site. However, a slightly improved fit over the average crystallographic model results when the planar Cu(2) site is split along the z-direction. This is interpreted in terms of charge inhomogeneities in the CuO2 planes.Comment: 8 pages, 3 figure

The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation

Purpose: Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. Patients and methods: Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS. The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated. Functional effects of common VDR variants were also evaluated in experimental assays in human cell lines. Results: The rs2853564 variant in VDR was associated with OS in patients from both the Mayo Clinic (HR 0.81, 95% CI 0.70–0.94, p = 0.0059) and CALGB 80303 (HR 0.74, 0.63–0.87, p = 0.0002). rs2853564 interacted with high pre-treatment levels of 25-hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer increased OS. rs2853564 increased transcriptional activity in luciferase assays and reduced the binding of the IRF4 transcription factor. Conclusion: Our findings propose VDR as a novel determinant of survival in advanced pancreatic cancer patients. Common functional variation in this gene might interact with endogenous vitamin D and gemcitabine treatment to determine improved patient survival. These results support evidence for a modulatory role of the vitamin D pathway for the survival of advanced pancreatic cancer patients.</p

The hearing of fitness to practice cases by the General Medical Council: Current trends and future research agendas

Over the last three decades a risk-based model of medical regulation has emerged in the United Kingdom. To promote a risk-averse operational culture of transparency and professional accountability the regulatory state has intervened in medical governance and introduced best-evidenced practice frameworks, audit and performance appraisal, Against this background the paper analyses descriptive statistical data pertaining to the General Medical Council’s management of the process by which fitness to practice complaints against doctors are dealt with from initial receipt through to subsequent investigative and adjudication stages. Statistical trends are outlined regarding complaint data in relation to a doctor’s gender and race and ethnicity. The data shows that there has been an increase in rehabilitative and/or punitive action against doctors. In light of its findings the paper considers what the long-term consequences may be, for both patients and doctors, of the increasing use of risk-averse administrative systems to reform medical regulation and ensure professional accountability

Human cell dedifferentiation in mesenchymal condensates through controlled autophagy

Tissue and whole organ regeneration is a dramatic biological response to injury that occurs across different plant and animal phyla. It frequently requires the dedifferentiation of mature cells to a condensed mesenchymal blastema, from which replacement tissues develop. Human somatic cells cannot regenerate in this way and differentiation is considered irreversible under normal developmental conditions. Here, we sought to establish in vitro conditions to mimic blastema formation by generating different three-dimensional (3D) condensates of human mesenchymal stromal cells (MSCs). We identified specific 3D growth environments that were sufficient to dedifferentiate aged human MSCs to an early mesendoderm-like state with reversal of age-associated cell hypertrophy and restoration of organized tissue regenerating capacity in vivo. An optimal auophagic response was required to promote cytoplasmic remodeling, mitochondrial regression, and a bioenergetic shift from oxidative phosphorylation to anaerobic metabolism. Our evidence suggests that human cell dedifferentiation can be achieved through autonomously controlled autophagic flux