Water displacement leg volumetry in clinical studies - A discussion of error sources

<p>Abstract</p> <p>Background</p> <p>Water displacement leg volumetry is a highly reproducible method, allowing the confirmation of efficacy of vasoactive substances. Nevertheless errors of its execution and the selection of unsuitable patients are likely to negatively affect the outcome of clinical studies in chronic venous insufficiency (CVI).</p> <p>Discussion</p> <p>Placebo controlled double-blind drug studies in CVI were searched (Cochrane Review 2005, MedLine Search until December 2007) and assessed with regard to efficacy (volume reduction of the leg), patient characteristics, and potential methodological error sources. Almost every second study reported only small drug effects (≤ 30 mL volume reduction). As the most relevant error source the conduct of volumetry was identified. Because the practical use of available equipment varies, volume differences of more than 300 mL - which is a multifold of a potential treatment effect - have been reported between consecutive measurements. Other potential error sources were insufficient patient guidance or difficulties with the transition from the Widmer CVI classification to the CEAP (Clinical Etiological Anatomical Pathophysiological) grading.</p> <p>Summary</p> <p>Patients should be properly diagnosed with CVI and selected for stable oedema and further clinical symptoms relevant for the specific study. Centres require a thorough training on the use of the volumeter and on patient guidance. Volumetry should be performed under constant conditions. The reproducibility of short term repeat measurements has to be ensured.</p

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health

Structural equation modeling in medical research: a primer

<p>Abstract</p> <p>Background</p> <p>Structural equation modeling (SEM) is a set of statistical techniques used to measure and analyze the relationships of observed and latent variables. Similar but more powerful than regression analyses, it examines linear causal relationships among variables, while simultaneously accounting for measurement error. The purpose of the present paper is to explicate SEM to medical and health sciences researchers and exemplify their application.</p> <p>Findings</p> <p>To facilitate its use we provide a series of steps for applying SEM to research problems. We then present three examples of how SEM has been utilized in medical and health sciences research.</p> <p>Conclusion</p> <p>When many considerations are given to research planning, SEM can provide a new perspective on analyzing data and potential for advancing research in medical and health sciences.</p

Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Limited studies have prospectively examined the role of body mass index (BMI) as a major risk factor for asthma during adolescence. This study investigates whether BMI is associated with increased risk of developing physician-diagnosed asthma during 12-month follow-up among adolescents with undiagnosed asthma-like symptoms at baseline.</p> <p>Methods</p> <p>A total of 4,052 adolescents with undiagnosed asthma-like symptoms at baseline were re-examined after a 12-month follow-up. Asthma cases were considered confirmed only after diagnosis by a physician based on the New England core and International Study of Asthma and Allergies in Childhood (ISAAC) criteria video questionnaires, and accompanying pulmonary function tests. Logistic regression analyses were used to evaluate the relationship of BMI and the risk of acquiring asthma.</p> <p>Results</p> <p>The results indicated that girls with higher BMI were at an increased risk of developing asthma during the 12-month follow-up. The odds ratios for girls developing physician-diagnosed asthma were 1.75 (95% CI = 1.18-2.61) and 1.12 (95% CI = 0.76-1.67), respectively, for overweight and obesity as compared to the normal weight reference group after adjustment for other covariates. A similar relationship was not observed for overweight and obese boys who were also significantly more active than their female counterparts.</p> <p>Conclusions</p> <p>Increased BMI exaggerates the risk of acquiring asthma in symptomatic adolescent females but not in adolescent males. Thus, gender is an important modifier of BMI-related asthma risk. Additional research will be required to determine whether the increased asthma risk results from genetic, physiological or behavioural differences.</p

The impact of social networks on knowledge transfer in long-term care facilities: Protocol for a study

<p>Abstract</p> <p>Background</p> <p>Social networks are theorized as significant influences in the innovation adoption and behavior change processes. Our understanding of how social networks operate within healthcare settings is limited. As a result, our ability to design optimal interventions that employ social networks as a method of fostering planned behavior change is also limited. Through this proposed project, we expect to contribute new knowledge about factors influencing uptake of knowledge translation interventions.</p> <p>Objectives</p> <p>Our specific aims include: To collect social network data among staff in two long-term care (LTC) facilities; to characterize social networks in these units; and to describe how social networks influence uptake and use of feedback reports.</p> <p>Methods and design</p> <p>In this prospective study, we will collect data on social networks in nursing units in two LTC facilities, and use social network analysis techniques to characterize and describe the networks. These data will be combined with data from a funded project to explore the impact of social networks on uptake and use of feedback reports. In this parent study, feedback reports using standardized resident assessment data are distributed on a monthly basis. Surveys are administered to assess report uptake. In the proposed project, we will collect data on social networks, analyzing the data using graphical and quantitative techniques. We will combine the social network data with survey data to assess the influence of social networks on uptake of feedback reports.</p> <p>Discussion</p> <p>This study will contribute to understanding mechanisms for knowledge sharing among staff on units to permit more efficient and effective intervention design. A growing number of studies in the social network literature suggest that social networks can be studied not only as influences on knowledge translation, but also as possible mechanisms for fostering knowledge translation. This study will contribute to building theory to design such interventions.</p

Aboriginal premature mortality within South Australia 1999-2006: a cross-sectional analysis of small area results

<p>Abstract</p> <p>Background</p> <p>This paper initially describes premature mortality by Aboriginality in South Australia during 1999 to 2006. It then examines how these outcomes vary across area level socio-economic disadvantage and geographic remoteness.</p> <p>Methods</p> <p>The retrospective, cross-sectional analysis uses estimated resident population by sex, age and small areas based on the 2006 Census, and Unit Record mortality data. Premature mortality outcomes are measured using years of life lost (YLL). Subsequent intrastate comparisons are based on indirect sex and age adjusted YLL results. A multivariate model uses area level socio-economic disadvantage rank, geographic remoteness, and an interaction between the two variables to predict premature mortality outcomes.</p> <p>Results</p> <p>Aboriginal people experienced 1.1% of total deaths but 2.2% of YLL and Aboriginal premature mortality rates were 2.65 times greater than the South Australian average. Premature mortality for Aboriginal and non-Aboriginal people increased significantly as area disadvantage increased. Among Aboriginal people though, a significant main effect for area remoteness was also observed, together with an interaction between disadvantage and remoteness. The synergistic effect shows the social gradient between area disadvantage and premature mortality increased as remoteness increased.</p> <p>Conclusions</p> <p>While confirming the gap in premature mortality rates between Aboriginal South Australians and the rest of the community, the study also found a heterogeneity of outcomes within the Aboriginal community underlie this difference. The results support the existence of relationship between area level socio-economic deprivation, remoteness and premature mortality in the midst of an affluent society. The study concludes that vertically equitable resourcing according to population need is an important response to the stark mortality gap and its exacerbation by area socio-economic position and remoteness.</p

Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease

RATIONALE: Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD). METHODS: Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV(1) % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluorescence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization. RESULTS: Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid. CONCLUSIONS: Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD

Rapid KRAS, EGFR, BRAF and PIK3CA Mutation Analysis of Fine Needle Aspirates from Non-Small-Cell Lung Cancer Using Allele-Specific qPCR

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) and Trans-esophageal Ultrasound Scanning with Fine Needle Aspiration (EUS-FNA) are important, novel techniques for the diagnosis and staging of non-small cell lung cancer (NSCLC) that have been incorporated into lung cancer staging guidelines. To guide and optimize treatment decisions, especially for NSCLC patients in stage III and IV, EGFR and KRAS mutation status is often required. The concordance rate of the mutation analysis between these cytological aspirates and histological samples obtained by surgical staging is unknown. Therefore, we studied the extent to which allele-specific quantitative real-time PCR with hydrolysis probes could be reliably performed on EBUS and EUS fine needle aspirates by comparing the results with histological material from the same patient. We analyzed a series of 43 NSCLC patients for whom cytological and histological material was available. We demonstrated that these standard molecular techniques can be accurately applied on fine needle cytological aspirates from NSCLC patients. Importantly, we show that all mutations detected in the histological material of primary tumor were also identified in the cytological samples. We conclude that molecular profiling can be reliably performed on fine needle cytology aspirates from NSCLC patients