Mapping Functions in Health-Related Quality of Life: Mapping From Two Cancer-Specific Health-Related Quality-of-Life Instruments to EQ-5D-3L.

BACKGROUND: Clinical trials in cancer frequently include cancer-specific measures of health but not preference-based measures such as the EQ-5D that are suitable for economic evaluation. Mapping functions have been developed to predict EQ-5D values from these measures, but there is considerable uncertainty about the most appropriate model to use, and many existing models are poor at predicting EQ-5D values. This study aims to investigate a range of potential models to develop mapping functions from 2 widely used cancer-specific measures (FACT-G and EORTC-QLQ-C30) and to identify the best model. METHODS: Mapping models are fitted to predict EQ-5D-3L values using ordinary least squares (OLS), tobit, 2-part models, splining, and to EQ-5D item-level responses using response mapping from the FACT-G and QLQ-C30. A variety of model specifications are estimated. Model performance and predictive ability are compared. Analysis is based on 530 patients with various cancers for the FACT-G and 771 patients with multiple myeloma, breast cancer, and lung cancer for the QLQ-C30. RESULTS: For FACT-G, OLS models most accurately predict mean EQ-5D values with the best predicting model using FACT-G items with similar results using tobit. Response mapping has low predictive ability. In contrast, for the QLQ-C30, response mapping has the most accurate predictions using QLQ-C30 dimensions. The QLQ-C30 has better predicted EQ-5D values across the range of possible values; however, few respondents in the FACT-G data set have low EQ-5D values, which reduces the accuracy at the severe end. CONCLUSIONS: OLS and tobit mapping functions perform well for both instruments. Response mapping gives the best model predictions for QLQ-C30. The generalizability of the FACT-G mapping function is limited to populations in moderate to good health

A paediatric telecardiology service for district hospitals in south-east England: an observational study.

The attached article is a Publisher version of the final published version which may be accessed at the link below. Copyright © 2010 BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reservedOBJECTIVES: To compare caseloads of new patients assessed by paediatric cardiologists face-to-face or during teleconferences, and assess NHS costs for the alternative referral arrangements. DESIGN: Prospective cohort study over 15 months. SETTING: Four district hospitals in south-east England and a London paediatric cardiology centre. PATIENTS: Babies and children. INTERVENTION: A telecardiology service introduced alongside outreach clinics. MEASUREMENTS: Clinical outcomes and mean NHS costs per patient. RESULTS: 266 new patients were studied: 75 had teleconsultations (19 of 42 newborns and 56 of 224 infants and children). Teleconsultation patients generally were younger (49% being under 1 year compared with 32% seen personally (p = 0.025)) and their symptoms were not as severe. A cardiac intervention was undertaken immediately or planned for five telemedicine patients (7%) and 30 conventional patients (16%). However, similar proportions of patients were discharged after being assessed (32% telemedicine and 39% conventional). During scheduled teleconferences the mean duration of time per patient in sessions involving real-time echocardiography was 14.4 min, and 8.5 min in sessions where pre-recorded videos were transmitted. Mean cost comparisons for telemedicine and face-to-face patients over 14-day and 6-month follow-up showed the telecardiology service to be cost-neutral for the three hospitals with infrequently-held outreach clinics (1519 UK pounds vs 1724 UK pounds respectively after 14 days). CONCLUSION: Paediatric cardiology centres with small cadres of specialists are under pressure to cope with ever-expanding caseloads of new patients with suspected anomalies. Innovative use of telecardiology alongside conventional outreach services should suitably, and economically, enhance access to these specialists.The Department of Health and the Charitable Funds Committee of the Royal Brompton and Harefield NHS Trust funded the project

Playing with nonuniform grids

Numerical experiments with discretization methods on nonuniform grids are presented for the convection-diffusion equation. These show that the accuracy of the discrete solution is not very well predicted by the local truncation error. The diagonal entries in the discrete coefficient matrix give a better clue: the convective term should not reduce the diagonal. Also, iterative solution of the discrete set of equations is discussed. The same criterion appears to be favourable.

Le Companion curriculum : la perception des étudiants en médecine de l’intégration des sciences humaines dans l’enseignement médical

Background: The contributions of arts and humanities to medical education are known in the medical education community, but medical schools’ offerings vary. The Companion Curriculum (CC) is a student-curated set of optional humanities content for medical students at the University of Toronto. This study evaluates integration of the CC to identify key enabling conditions for medical humanities engagement. Methods: A mixed-methods evaluation gauged usage and perceptions of integration of the CC among medical students using an online survey and focus groups. Narrative data underwent thematic analysis, supported by summary statistics of quantitative data. Results: Half of survey respondents were aware of the CC (n = 67/130; 52%), and, once prompted with a description, 14% had discussed it in their tutorial groups. Of students using the CC, 80% reported learning something new regarding their roles as communicators and health advocates. Themes were the perceived value of the humanities, internal student barriers, institutional neglect of the humanities, and student critiques and recommendations. Conclusion: Despite participants’ interest in medical humanities, our CC remains underused. To improve humanities’ visibility in the MD curriculum, our results indicate that greater institutional support, including faculty development and early curricular integration, is required. Further study should explore reasons for gaps between interest and participation.Contexte : L’apport des arts et des sciences humaines à l’éducation médicale est bien connu du milieu de l’enseignement médical, mais l’offre des programmes à cet égard varie d’une faculté à l’autre. Le Companion curriculum (CC) est un recueil de contenu facultatif en sciences humaines, préparé par des étudiants et destiné aux étudiants en médecine de l’Université de Toronto. En évaluant l’intégration du CC au programme, cette étude vise à dégager les conditions principales qui favorisent l’enseignement des humanités médicales. Méthodes : Une évaluation à méthode mixte a permis de mesurer l’utilisation du CC par les étudiants en médecine et leur perception quant à l’intégration de cet outil, à l’aide d’un sondage en ligne et de groupes de discussion. Les données narratives ont fait l’objet d’une analyse thématique, étayée par des statistiques sommaires de données quantitatives. Résultats : La moitié des répondants à l’enquête connaissaient le CC (n=67/130 ; 52%) et 14 % en avaient discuté dans leurs groupes de tutorat. Parmi les étudiants qui l’avaient utilisé, 80 % ont déclaré avoir appris quelque chose de nouveau concernant leurs rôles de communicateurs et de promoteurs de la santé. Les thèmes abordés étaient la valeur perçue des sciences humaines, les freins internes des étudiants, la méconnaissance des sciences humaines au sein des établissements d’enseignement médical, ainsi que les critiques et les recommandations des étudiants. Conclusion : Malgré l’intérêt des participants pour les humanités médicales, notre CC demeure sous-utilisé. Nos résultats indiquent que le renforcement de la visibilité des sciences humaines dans le programme d’études médicales nécessite plus de soutien de la part des établissements, y compris par la formation des enseignants et par l’intégration des sciences humaines plus tôt dans le cursus du programme. Une étude plus approfondie permettrait d’explorer les raisons de l’écart entre l’intérêt et la participation

Acquired trichostasis in postoperative site: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of Quality Adjusted Life Years in people with common mental health problems

AGE-BSA down-regulates endothelial connexin43 gap junctions

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.</p> <p>Results</p> <p>In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.</p> <p>Conclusions</p> <p>AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.</p

Diffusion Mechanism of Lithium Ion through Basal Plane of Layered Graphene

International audienceCoexistence of both edge plane and basal plane in graphite often hinders the understanding of lithium ion diffusion mechanism. In this report, two types of graphene samples were prepared by chemical vapor deposition (CVD): (i) well-defined basal plane graphene grown on Cu foil and (ii) edge plane-enriched graphene layers grown on Ni film. Electrochemical performance of the graphene electrode can be split into two regimes depending on the number of graphene layers: (i) the corrosion-dominant regime and (ii) the lithiation-dominant regime. Li ion diffusion perpendicular to the basal plane of graphene is facilitated by defects, whereas diffusion parallel to the plane is limited by the steric hindrance that originates from aggregated Li ions adsorbed on the abundant defect sites. The critical layer thickness (lc) to effectively prohibit substrate reaction using CVD-grown graphene layers was predicted to be ∼6 layers, independent of defect population. Our density functional theory calculations demonstrate that divacancies and higher order defects have reasonable diffusion barrier heights allowing lithium diffusion through the basal plane but neither monovacancies nor Stone-Wales defect

Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon