An assessment of validity and responsiveness of generic measures of health-related quality of life in hearing impairment

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: This review examines psychometric performance of three widely used generic preference-based measures, that is, EuroQol 5 dimensions (EQ-5D), Health Utility Index 3 (HUI3) and Short-form 6 dimensions (SF-6D) in patients with hearing impairments. Methods: A systematic search was undertaken to identify studies of patients with hearing impairments where health state utility values were measured and reported. Data were extracted and analysed to assess the reliability, validity (known group differences and convergent validity) and responsiveness of the measures across hearing impairments. Results: Fourteen studies (18 papers) were included in the review. HUI3 was the most commonly used utility measures in hearing impairment. In all six studies, the HUI3 detected difference between groups defined by the severity of impairment, and four out of five studies detected statistically significant changes as a result of intervention. The only study available suggested that EQ-5D only had weak ability to discriminate difference between severity groups, and in four out of five studies, EQ-5D failed to detected changes. Only one study involved the SF-6D; thus, the information is too limited to conclude on its performance. Also evidence for the reliability of these measures was not found. Conclusion: Overall, the validity and responsiveness of the HUI3 in hearing impairment was good. The responsiveness of EQ-5D was relatively poor and weak validity was suggested by limited evidence. The evidence on SF-6D was too limited to make any judgment. More head-to-head comparisons of these and other preference measures of health are required.Medical Research Counci

Investigation of the marine compound spongistatin 1 links the inhibition of PKCα translocation to nonmitotic effects of tubulin antagonism in angiogenesis

The aims of the study were to meet the demand of new tubulin antagonists with fewer side effects by characterizing the antiangiogenic properties of the experimental compound spongistatin 1, and to elucidate nonmitotic mechanisms by which tubulin antagonists inhibit angiogenesis. Although tubulin-inhibiting drugs and their antiangiogenic properties have been investigated for a long time, surprisingly little is known about their underlying mechanisms of action. Antiangiogenic effects of spongistatin 1 were investigated in endothelial cells in vitro, including functional cell-based assays, live-cell imaging, and a kinome array, and in the mouse cornea pocket assay in vivo. Spongistatin 1 inhibited angiogenesis at nanomolar concentrations (IC50: cytotoxicity>50 nM, proliferation 100 pM, migration 1.0 nM, tube formation 1.0 nM, chemotaxis 1.0 nM, aortic ring sprouting 500 pM, neovascularization in vivo 10 μg/kg). Further, a kinome array and validating data showed that spongistatin 1 inhibits the phosphorylation activity of protein kinase Cα (PKCα), an essential kinase in angiogenesis, and its translocation to the membrane. Thus, we conclude that PKCα might be an important target for the antiangiogenic effects of tubulin antagonism. In addition, the data from the kinase array suggest that different tubulin antagonists might have individual intracellular actions.—Rothmeier, A. S., Ischenko, I., Joore, J., Garczarczyk, D., Fu¨rst, R., Bruns, C. J., Vollmar, A. M., Zahler, S. Investigation of the marine compound spongistatin 1 links the inhibition of PKCα translocation to nonmitotic effects of tubulin antagonism in angiogenesis

Training in data definitions improves quality of intensive care data

BACKGROUND: Our aim was to assess the contribution of training in data definitions and data extraction guidelines to improving quality of data for use in intensive care scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II in the Dutch National Intensive Care Evaluation (NICE) registry. METHODS: Before and after attending a central training programme, a training group of 31 intensive care physicians from Dutch hospitals who were newly participating in the NICE registry extracted data from three sample patient records. The 5-hour training programme provided participants with guidelines for data extraction and strict data definitions. A control group of 10 intensive care physicians, who were trained according the to train-the-trainer principle at least 6 months before the study, extracted the data twice, without specific training in between. RESULTS: In the training group the mean percentage of accurate data increased significantly after training for all NICE variables (+7%, 95% confidence interval 5%–10%), for APACHE II variables (+6%, 95% confidence interval 4%–9%) and for SAPS II variables (+4%, 95% confidence interval 1%–6%). The percentage data error due to nonadherence to data definitions decreased by 3.5% after training. Deviations from 'gold standard' SAPS II scores and predicted mortalities decreased significantly after training. Data accuracy in the control group did not change between the two data extractions and was equal to post-training data accuracy in the training group. CONCLUSION: Training in data definitions and data extraction guidelines is an effective way to improve quality of intensive care scoring data

HIV testing within general practices in Europe : A mixed-methods systematic review

Funding Information: This work was supported by IWT (Belgium) and the ANRS (France) through the framework of HIVERA JTC 2014. Publisher Copyright: © 2018 The Author(s).Background: Late diagnosis of HIV infection remains a key challenge in Europe. It is acknowledged that general practitioners (GPs) may contribute greatly to early case finding, yet there is evidence that many diagnostic opportunities are being missed. To further promote HIV testing in primary care and to increase the utility of available research, the existing evidence has been synthesised in a systematic review adhering to the PRISMA guidelines. Methods: The databases PubMed, Scopus and Embase were searched for the period 2006-2017. Two authors judged independently on the eligibility of studies. Through a mixed-methods systematic review of 29 studies, we provide a description of HIV testing in general practices in Europe, including barriers and facilitators. Results: The findings of the study show that although various approaches to target patients are used by GPs, most tests are still carried out based on the patient's request. Several barriers obstruct HIV testing in general practice. Included are a lack of communication skills on sexual health, lack of knowledge about HIV testing recommendations and epidemic specificities, difficulties with using the complete list of clinical HIV indicator diseases and lack of experience in delivering and communicating test results. The findings also suggest that the provision of specific training, practical tools and promotion programmes has an impact on the testing performance of GPs. Conclusions: GPs could have an increased role in provider-initiated HIV-testing for early case finding. To achieve this objective, solutions to the reported barriers should be identified and testing criteria adapted to primary healthcare defined. Providing guidance and training to better identify priority groups for HIV testing, as well as information on the HIV epidemic's characteristics, will be fundamental to increasing awareness and testing by GPs.publishersversionPeer reviewe

Selective decontamination of the digestive tract: all questions answered?

Although many studies have shown beneficial effects of SDD on the incidence of respiratory tract infections, SDD did not become routine practice because mortality reduction was not demonstrated in individual trials, beneficial effects on duration of ventilation, ICU stay or hospital stay were not demonstrated, cost-efficacy had not been demonstrated, and selection of antibiotic resistance was considered a serious side-effect. A recent study has now shown improved patient survival and lower prevalence of antibiotic resistance in patients receiving SDD. Why could this study show mortality reduction, where all others studies had failed before? And do the microbiological data unequivocally prove protective effects of SDD on emergence of antibiotic resistance? Interestingly, the reported mortality reductions exceeds even the most optimistic predictions from previous meta-analyses, but a clear explanation is not yet evident. The data on antibiotic resistance, however, are rather superficial and do not allow to interpret the underlying epidemiological dynamics. Therefore, the recent findings are provocative and shed new light on the SDD issue, warranting studies confirming its beneficial effects but also addressing several important aspects related to study design

KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis

__Abstract__ Background: Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost. Objectives: To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone