Mapping SF-36 onto the EQ-5D index: how reliable is the relationship?

<p>Abstract</p> <p>Background</p> <p>Mapping from health status measures onto generic preference-based measures is becoming a common solution when health state utility values are not directly available for economic evaluation. However the accuracy and reliability of the models employed is largely untested, and there is little evidence of their suitability in patient datasets. This paper examines whether mapping approaches are reliable and accurate in terms of their predictions for a large and varied UK patient dataset.</p> <p>Methods</p> <p>SF-36 dimension scores are mapped onto the EQ-5D index using a number of different model specifications. The predicted EQ-5D scores for subsets of the sample are compared across inpatient and outpatient settings and medical conditions. This paper compares the results to those obtained from existing mapping functions.</p> <p>Results</p> <p>The model including SF-36 dimensions, squared and interaction terms estimated using random effects GLS has the most accurate predictions of all models estimated here and existing mapping functions as indicated by MAE (0.127) and MSE (0.030). Mean absolute error in predictions by EQ-5D utility range increases with severity for our models (0.085 to 0.34) and for existing mapping functions (0.123 to 0.272).</p> <p>Conclusion</p> <p>Our results suggest that models mapping the SF-36 onto the EQ-5D have similar predictions across inpatient and outpatient setting and medical conditions. However, the models overpredict for more severe EQ-5D states; this problem is also present in the existing mapping functions.</p

High concentration of childhood deaths in the low-lying areas of Chakaria HDSS, Bangladesh: findings from a spatial analysis

Background: Despite significant reduction of childhood mortality in Bangladesh, large spatial variations persist. Identification of lower level spatial units with higher concentrations of deaths can be useful for strengthening services in these areas. This paper reports findings from a spatial analysis of deaths in Chakaria, a rural subdistrict, where a Health and Demographic Surveillance System has been in place since 1999. Chakaria is an INDEPTH member site. Methods: An analysis was done of 339 deaths among nearly 24,500 children under the age of five during 2005&#x2013;2008. One ward, the lowest level of administrative units, was the unit of spatial analysis. Data from 24 wards were analyzed. The Discrete Poisson Probability Model was used to identify the clustering of deaths. Results: Deaths were concentrated within 12 wards located in the low-lying deltaic flood plains of the Chakaria HDSS area. The risk of death in the low-lying areas was statistically, significantly higher, 1.5 times, than the non-low-lying areas (p&#60;0.02). Conclusion: Spatial analysis can be a useful tool for identifying high-risk mortality areas. An understanding of the risk factors prevalent in the low-lying areas can help design effective interventions to reduce mortality in these areas

Recommended Methods for the Collection of Health State Utility Value Evidence in Clinical Studies

A conceptual model framework and an initial literature review are invaluable when considering what health state utility values (HSUVs) are required to populate health states in decision models. They are the recommended starting point early within a research and development programme, and before development of phase III trial protocols. While clinical trials can provide an opportunity to collect the required evidence, their appropriateness should be reviewed against the requirements of the model structure taking into account population characteristics, time horizon and frequency of clinical events. Alternative sources such as observational studies or registries may be more appropriate when evidence describing changes in HSUVs over time or rare clinical events is required. Phase IV clinical studies may provide the opportunity to collect additional longitudinal real-world evidence. Aspects to consider when designing the collection of the evidence include patient and investigator burden, whom to ask, the representativeness of the population, the exact definitions of health states within the economic model, the timing of data collection, sample size, and mode of administration. Missing data can be an issue, particularly in longitudinal studies, and it is important to determine whether the missing data will bias inferences from analyses. For example, respondents may fail to complete follow-up questionnaires because of a relapse or the severity of their condition. The decision on the preferred study type and the particular quality of life measure should be informed by any evidence currently available in the literature, the design of data collection, and the exact requirements of the model that will be used to support resource allocation decisions (e.g. reimbursement)

The nation and the family: the impact of national identification and perceived importance of family values on homophobic attitudes in Lithuania and Scotland

The meanings attached to the nation can be consequential for group members’ attitudes and beliefs. We examined how national identity definition can influence the extent of individuals’ homophobia with 159 Lithuanian and 176 Scottish university students who completed a questionnaire which measured their national identification, homophobia, and the extent to which they felt traditional family values were central to their nation’s identity. Consistent with nation-wide differences in the significance given to the family, Lithuanian participants perceived family values to be more important for their national identity and expressed higher levels of homophobia than did Scottish participants. Moreover, the relationship between level of national identification and homophobia was stronger in Lithuania than in Scotland. Analyses revealed that the perceived importance of family values helped explain the difference between homophobia levels in Lithuania and Scotland. In both sites we found an indirect effect of national identification on homophobia via the perceived importance of family values, but this effect was significantly stronger for Lithuanian participants. These findings illustrate the ways in which identification with the nation is relevant to attitudes concerning sexuality, and how this varies according to national context. Our work indicates that LGBT rights campaigns should be informed by the knowledge that homophobia may be perpetuated by national valorisation of the family

Biomarkers in T cell therapy clinical trials

T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity

Genetic regulation of Nrnx1 expression: an integrative cross-species analysis of schizophrenia candidate genes

Neurexin 1 (NRXN1) is a large presynaptic transmembrane protein that has complex and variable patterns of expression in the brain. Sequence variants in NRXN1 are associated with differences in cognition, and with schizophrenia and autism. The murine Nrxn1 gene is also highly polymorphic and is associated with significant variation in expression that is under strong genetic control. Here, we use co-expression analysis, high coverage genomic sequence, and expression quantitative trait locus (eQTL) mapping to study the regulation of this gene in the brain. We profiled a family of 72 isogenic progeny strains of a cross between C57BL/6J and DBA/2J (the BXD family) using exon arrays and massively parallel RNA sequencing. Expression of most Nrxn1 exons have high genetic correlation (r>0.6) because of the segregation of a common trans eQTL on chromosome (Chr) 8 and a common cis eQTL on Chr 17. These two loci are also linked to murine phenotypes relevant to schizophrenia and to a novel human schizophrenia candidate gene with high neuronal expression (Pleckstrin and Sec7 domain containing 3). In both human and mice, NRXN1 is co-expressed with numerous synaptic and cell signaling genes, and known schizophrenia candidates. Cross-species co-expression and protein interaction network analyses identified glycogen synthase kinase 3 beta (GSK3B) as one of the most consistent and conserved covariates of NRXN1. By using the Molecular Genetics of Schizophrenia data set, we were able to test and confirm that markers in NRXN1 and GSK3B have epistatic interactions in human populations that can jointly modulate risk of schizophrenia

Clamp loader ATPases and the evolution of DNA replication machinery

Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life