A solid-reagent dispenser for use in the azocoll protease assay (and other insoluble substrate analyses).

A solid-reagent dispenser for use in the azocoll protease assay (and other insoluble substrate analyses)

Evaluating the discriminatory power of EQ-5D, HUI2 and HUI3 in a US general population survey using Shannon’s indices

OBJECTIVES: To compare quantitatively the discriminatory power of the EQ-5D, HUI2 and HUI3 in terms of absolute and relative informativity, using Shannon's indices. METHODS: EQ-5D and HUI2/3 data completed by a sample of the general adult US population (N = 3,691) were used. Five dimensions allowed head-to-head comparison of informativity: Mobility/Ambulation; Anxiety/Depression/Emotion; Pain/Discomfort (EQ-5D; HUI2; HUI3); Self-Care (EQ-5D; HUI2); and Cognition (HUI2; HUI3). Shannon's index and Shannon's Evenness index were used to assess absolute and relative informativity, both by dimension and by instrument as a whole. RESULTS: Absolute informativity was highest for HUI3, with the largest differences in Pain/Discomfort and Cognition. Relative informativity was highest for EQ-5D, with the largest differences in Mobility/Ambulation and Anxiety/Depression/Emotion. Absolute informativity by instrument was consistently highest for HUI3 and lowest for EQ-5D, and relative informativity was highest for EQ-5D and lowest for HUI3. DISCUSSION: Performance in terms of absolute and relative informativity of the common dimensions of the three instruments varies over dimensions. Several dimensions are suboptimal: Pain/Discomfort (EQ-5D) seems too crude with only 3 levels, and the level descriptions of Ambulation (HUI3) and Self-Care (HUI2) could be improved. In absence of a formal measure, Shannon's indices provide useful measures for assessing discriminatory power of utility instrument

Prioritisation of patients on waiting lists for hip and knee arthroplasties and cataract surgery: Instruments validation

<p>Abstract</p> <p>Background</p> <p>Prioritisation instruments were developed for patients on waiting list for hip and knee arthroplasties (AI) and cataract surgery (CI). The aim of the study was to assess their convergent and discriminant validity and inter-observer reliability.</p> <p>Methods</p> <p>Multicentre validation study which included orthopaedic surgeons and ophthalmologists from 10 hospitals. Participating doctors were asked to include all eligible patients placed in the waiting list for the procedures under study during the medical visit. Doctors assessed patients' priority through a visual analogue scale (VAS) and administered the prioritisation instrument. Information on socio-demographic data and health-related quality of life (HRQOL) (HUI3, EQ-5D, WOMAC and VF-14) was obtained through a telephone interview with patients. The correlation coefficients between the prioritisation instrument score and VAS and HRQOL were calculated. For the reliability study a self-administered questionnaire, which included hypothetic patients' scenarios, was sent via postal mail to the doctors. The priority of these scenarios was assessed through the prioritisation instrument. The intraclass correlation coefficient (ICC) between doctors was calculated.</p> <p>Results</p> <p>Correlations with VAS were strong for the AI (0.64, CI95%: 0.59–0.68) and for the CI (0.65, CI95%: 0.62–0.69), and moderate between the WOMAC and the AI (0.39, CI95%: 0.33–0.45) and the VF-14 and the CI (0.38, IC95%: 0.33–0.43). The results of the discriminant analysis were in general as expected. Inter-observer reliability was 0.79 (CI95%: 0.64–0.94) for the AI, and 0.79 (CI95%: 0.63–0.95) for the CI.</p> <p>Conclusion</p> <p>The results show acceptable validity and reliability of the prioritisation instruments in establishing priority for surgery.</p

Choosing between measures: comparison of EQ-5D, HUI2 and HUI3 in persons with hearing complaints

OBJECTIVES: To generate insight into the differences between utility measures EuroQol 5D (EQ-5D), Health Utilities Index Mark II (HUI2) and Mark III (HUI3) and their impact on the incremental cost-effectiveness ratio (ICER) for hearing aid fitting METHODS: Persons with hearing complaints completed EQ-5D, HUI2 and HUI3 at baseline and, when applicable, after hearing aid fitting. Practicality, construct validity, agreement, responsiveness and impact on the ICER were examined. RESULTS: All measures had high completion rates. HUI3 was capable of discriminating between clinically distinctive groups. Utility scores (n = 315) for EQ-5D UK and Dutch tariff (0.83; 0.86), HUI2 (0.77) and HUI3 (0.61) were significantly different, agreement was low to moderate. Change after hearing aid fitting (n = 70) for HUI2 (0.07) and HUI3 (0.12) was statistically significant, unlike the EQ-5D UK (0.01) and Dutch (0.00) tariff. ICERs varied from 647,209 euros/QALY for the EQ-5D Dutch tariff to 15,811 euros/QALY for HUI3. CONCLUSION: Utility scores, utility gain and ICERs heavily depend on the measure that is used to elicit them. This study indicates HUI3 as the instrument of first choice when measuring utility in a population with hearing complaints, but emphasizes the importance of a clear notion of what constitutes utility with regard to economic analyse

Polymorphism in the Tyrosine Hydroxylase (TH) Gene Is Associated with Activity-Impulsivity in German Shepherd Dogs

We investigated the association between repeat polymorphism in intron 4 of the tyrosine hydroxylase (TH) gene and two personality traits, activity-impulsivity and inattention, in German Shepherd Dogs. The behaviour of 104 dogs was characterized by two instruments: (1) the previously validated Dog-Attention Deficit Hyperactivity Disorder Rating Scale (Dog-ADHD RS) filled in by the dog owners and (2) the newly developed Activity-impulsivity Behavioural Scale (AIBS) containing four subtests, scored by the experimenters. Internal consistency, inter-observer reliability, test-retest reliability and convergent validity were demonstrated for AIBS

Feasibility test of a UK-scalable electronic system for regular collection of patient-reported outcome measures and linkage with clinical cancer registry data: The electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system

<p>Abstract</p> <p>Background</p> <p>Cancer survivors can face significant physical and psychosocial challenges; there is a need to identify and predict which survivors experience what sorts of difficulties. As highlighted in the UK National Cancer Survivorship Initiative, routine post-diagnostic collection of patient reported outcome measures (PROMs) is required; to be most informative, PROMs must be linked and analysed with patients' diagnostic and treatment information. We have designed and built a potentially cost-efficient UK-scalable electronic system for collecting PROMs via the internet, at regular post-diagnostic time-points, for linking these data with patients' clinical data in cancer registries, and for electronically managing the associated patient monitoring and communications; the electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system. This study aims to test the feasibility of the ePOCS system, by running it for 2 years in two Yorkshire NHS Trusts, and using the Northern and Yorkshire Cancer Registry and Information Service.</p> <p>Methods/Design</p> <p>Non-metastatic breast, colorectal and prostate cancer patients (largest survivor groups), within 6 months post-diagnosis, will be recruited from hospitals in the Yorkshire Cancer Network. Participants will be asked to complete PROMS, assessing a range of health-related quality-of-life outcomes, at three time-points up to 15 months post-diagnosis, and subsequently to provide opinion on the ePOCS system via a feedback questionnaire. Feasibility will be examined primarily in terms of patient recruitment and retention rates, the representativeness of participating patients, the quantity and quality of collected PROMs data, patients' feedback, the success and reliability of the underpinning informatics, and the system running costs. If sufficient data are generated during system testing, these will be analysed to assess the health-related quality-of-life outcomes reported by patients, and to explore if and how they relate to disease, treatment and/or individual differences characteristics.</p> <p>Discussion</p> <p>There is currently no system in the UK for collecting PROMs online and linking these with patients' clinical data in cancer registries. If feasible, ePOCS has potential to provide an affordable UK-scalable technical platform to facilitate and support longitudinal cohort research, and improve understanding of cancer survivors' experiences. Comprehensive understanding of survivorship difficulties is vital to inform the development and provision of supportive services and interventions.</p

Insights into the Molecular Mechanisms of the Anti-Atherogenic Actions of Flavonoids in Normal and Obese Mice

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state

Ethical issues in autologous stem cell transplantation (ASCT) in advanced breast cancer: A systematic literature review

BACKGROUND: An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. METHODS: We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. RESULTS: Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud), which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. CONCLUSIONS: The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature

Whole-genome sequences of Malawi cichlids reveal multiple radiations interconnected by gene flow.

The hundreds of cichlid fish species in Lake Malawi constitute the most extensive recent vertebrate adaptive radiation. Here we characterize its genomic diversity by sequencing 134 individuals covering 73 species across all major lineages. The average sequence divergence between species pairs is only 0.1-0.25%. These divergence values overlap diversity within species, with 82% of heterozygosity shared between species. Phylogenetic analyses suggest that diversification initially proceeded by serial branching from a generalist Astatotilapia-like ancestor. However, no single species tree adequately represents all species relationships, with evidence for substantial gene flow at multiple times. Common signatures of selection on visual and oxygen transport genes shared by distantly related deep-water species point to both adaptive introgression and independent selection. These findings enhance our understanding of genomic processes underlying rapid species diversification, and provide a platform for future genetic analysis of the Malawi radiation