Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface

Health, Health-Related Quality of Life, and Quality of Life: What is the Difference?

The terms health, health-related quality of life (HRQoL), and quality of life (QoL) are used interchangeably. Given that these are three key terms in the literature, their appropriate and clear use is important. This paper reviews the history and definitions of the terms and considers how they have been used. It is argued that the definitions of HRQoL in the literature are problematic because some definitions fail to distinguish between HRQoL and health or between HRQoL and QoL. Many so-called HRQoL questionnaires actually measure self-perceived health status and the use of the phrase QoL is unjustified. It is concluded that the concept of HRQoL as used now is confusing. A potential solution is to define HRQoL as the way health is empirically estimated to affect QoL or use the term to only signify the utility associated with a health state

Cancer incidence among the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer

Cancer incidence in the south Asian population of England (1990–92)

Cancer incidence among English south Asians (residents in England with ethnic origins in India, Pakistan or Bangladesh) is described and compared with non-south Asian and Indian subcontinent rates. The setting for the study was areas covered by Thames, Trent, West Midlands and Yorkshire cancer registries. The study identified 356 555 cases of incident cancer (ICD9:140–208) registered between 1990 and 1992, including 3845 classified as English south Asian. The main outcome measures were age specific and directly standardized incidence rates for all cancer sites (ICD9:140–208). English south Asian incidence rates for all sites combined were significantly lower than non-south Asian rates but higher than Indian subcontinent rates. English south Asian rates were substantially higher than Indian subcontinent rates for a number of common sites including lung cancer in males, breast cancer in females and lymphoma in both sexes. English south Asian rates for childhood and early adult cancer (0–29 years) were similar or higher than non-south Asian rates. English south Asian rates were significantly higher than non-south Asian rates for Hodgkin's disease in males, cancer of the tongue, mouth, oesophagus, thyroid gland and myeloid leukaemia in females, and cancer of the hypopharynx, liver and gall bladder in both sexes. The results are consistent with a transition from the lower cancer risk of the country of ethnic origin to that of the country of residence. They suggest that detrimental changes in lifestyle and other exposures have occurred in the migrant south Asian population. © 1999 Cancer Research Campaig

Efficacy, Stability, and Biosafety of Sifuvirtide Gel as a Microbicide Candidate against HIV-1

Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission

Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators

Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods. Methods: Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth. Results: Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status. Conclusions: Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials. © 2011 Dezzutti et al

Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy

<p>Abstract</p> <p>Background</p> <p>The development of safe topical microbicides that can preserve the integrity of cervicovaginal tract epithelial barrier is of great interest as this may minimize the potential for increased susceptibility to STI infections. High resolution imaging to assess epithelial integrity in a noninvasive manner could be a valuable tool for preclinical testing of candidate topical agents.</p> <p>Methods</p> <p>A quantitative approach using confocal fluorescence microendoscopy (CFM) for assessment of microbicide-induced injury to the vaginal epithelium was developed. Sheep were treated intravaginally with one of five agents in solution (PBS; 0.02% benzalkonium chloride (BZK); 0.2% BZK) or gel formulation (hydroxyethyl cellulose (HEC); Gynol II nonoxynol-9 gel (N-9)). After 24 hours the vaginal tract was removed, labeled with propidium iodide (PI), imaged, then fixed for histology. An automated image scoring algorithm was developed for quantitative assessment of injury and applied to the data set. Image-based findings were validated with histological visual gradings that describe degree of injury and measurement of epithelial thickness.</p> <p>Results</p> <p>Distinct differences in PI staining were detected following BZK and N-9 treatment. Images from controls had uniformly distributed nuclei with defined borders, while those after BZK or N-9 showed heavily stained and disrupted nuclei, which increased in proportion to injury detected on histology. The confocal scoring system revealed statistically significant scores for each agent versus PBS controls with the exception of HEC and were consistent with histology scores of injury.</p> <p>Conclusions</p> <p>Confocal microendoscopy provides a sensitive, objective, and quantitative approach for non-invasive assessment of vaginal epithelial integrity and could serve as a tool for real-time safety evaluation of emerging intravaginal topical agents.</p

Functional kinds: a skeptical look

The functionalist approach to kinds has suffered recently due to its association with law-based approaches to induction and explanation. Philosophers of science increasingly view nomological approaches as inappropriate for the special sciences like psychology and biology, which has led to a surge of interest in approaches to natural kinds that are more obviously compatible with mechanistic and model-based methods, especially homeostatic property cluster theory. But can the functionalist approach to kinds be weaned off its dependency on laws? Dan Weiskopf has recently offered a reboot of the functionalist program by replacing its nomological commitments with a model-based approach more closely derived from practice in psychology. Roughly, Weiskopf holds that the natural kinds of psychology will be the functional properties that feature in many empirically successful cognitive models, and that those properties need not be localized to parts of an underlying mechanism. I here skeptically examine the three modeling practices that Weiskopf thinks introduce such non-localizable properties: fictionalization, reification, and functional abstraction. In each case, I argue that recognizing functional properties introduced by these practices as autonomous kinds comes at clear cost to those explanations’ counterfactual explanatory power. At each step, a tempting functionalist response is parochialism: to hold that the false or omitted counterfactuals fall outside the modeler’s explanatory aims, and so should not be counted against functional kinds. I conclude by noting the dangers this attitude poses to scientific disagreement, inviting functionalists to better articulate how the individuation conditions for functional kinds might outstrip the perspective of a single modeler