Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Impacts of 4D BIM on Construction Project Performance

A significant proportion of construction projects are failing to achieve their deadline finish dates. This advocate for solutions that could address the root causes of time impacting risks, leading to the use of 4D BIM for project planning. This study investigates the impacts of 4D BIM on construction projects. An exploratory sequential mixed method research was conducted to initially explore the topic via interviews and literature review, and, subsequently, the themes derived were put into questionnaires to elicit expert knowledge on a wider industry scale. The data were analysed using thematic analysis, reliability analysis, Kruskal-Wallis test and factor analysis. Across the objectives around the impacts of 4D BIM on project reliability, monitoring and diagnosis, the findings presented eight key ways the 4D BIM support project performance. Examples of component factors that were raised was planning efficiency to enhance planner output, assessment and directive with a better comparison of planned and actual progress, and thorough/comprehensive risk reflection to cover wide ranges of issues. Upon further reflection, the finding highlighted the issues of the lack of shared responsibility outside of the planner and BIM coordinator, severe lack of understanding and training regarding 4D BIM and complexity of carrying out the process effectively

A bootstrap approach for assessing the uncertainty of outcome probabilities when using a scoring system

Background: Scoring systems are a very attractive family of clinical predictive models, because the patient score can be calculated without using any data processing system. Their weakness lies in the difficulty of associating a reliable prognostic probability with each score. In this study a bootstrap approach for estimating confidence intervals of outcome probabilities is described and applied to design and optimize the performance of a scoring system for morbidity in intensive care units after heart surgery. Methods: The bias-corrected and accelerated bootstrap method was used to estimate the 95% confidence intervals of outcome probabilities associated with a scoring system. These confidence intervals were calculated for each score and each step of the scoring-system design by means of one thousand bootstrapped samples. 1090 consecutive adult patients who underwent coronary artery bypass graft were assigned at random to two groups of equal size, so as to define random training and testing sets with equal percentage morbidities. A collection of 78 preoperative, intraoperative and postoperative variables were considered as likely morbidity predictors. Results: Several competing scoring systems were compared on the basis of discrimination, generalization and uncertainty associated with the prognostic probabilities. The results showed that confidence intervals corresponding to different scores often overlapped, making it convenient to unite and thus reduce the score classes. After uniting two adjacent classes, a model with six score groups not only gave a satisfactory trade-off between discrimination and generalization, but also enabled patients to be allocated to classes, most of which were characterized by well separated confidence intervals of prognostic probabilities. Conclusions: Scoring systems are often designed solely on the basis of discrimination and generalization characteristics, to the detriment of prediction of a trustworthy outcome probability. The present example demonstrates that using a bootstrap method for the estimation of outcome-probability confidence intervals provides useful additional information about score-class statistics, guiding physicians towards the most convenient model for predicting morbidity outcomes in their clinical context

Prevalence and pattern of HIV-related malnutrition among women in sub-Saharan Africa: a meta-analysis of demographic health surveys

<p>Abstract</p> <p>Background</p> <p>The world's highest HIV infection rates are found in Sub-Saharan Africa (SSA), where adult prevalence in most countries exceeds 25%. Food shortages and malnutrition have combined with HIV/AIDS to bring some countries to the brink of crisis. The aim of this study was to describe prevalence of malnutrition among HIV-infected women and variations across socioeconomic status using data from 11 countries in SSA.</p> <p>Methods</p> <p>This study uses meta-analytic procedures to synthesize the results of most recent data sets available from Demographic and Health Surveys of 11 countries in SSA. Pooled prevalence estimates and 95% confidence intervals were calculated using random-and fixed-effects models. Subgroup and leave-one-country-out sensitivity analyses were also carried out.</p> <p>Results</p> <p>Pooling the prevalence estimates of HIV-related malnutrition yielded an overall prevalence of 10.3% (95% CI 7.4% to 14.1%) with no statistically significant heterogeneity (<it>I</it>²= 0.0%, p = .903). The prevalence estimates decreased with increasing wealth index and education attainment. The pooled prevalence of HIV-related malnutrition was higher among women residing in rural areas than among women residing in urban areas; and lower among women that were professionally employed than unemployed or women in agricultural or manual work.</p> <p>Conclusion</p> <p>Prevalence of HIV-related malnutrition among women varies by wealth status, education attainment, occupation, and type of residence (rural/urban). The observed socioeconomic disparities can help provide more information about population subgroups in particular need and high risk groups, which may in turn lead to the development and implementation of more effective intervention programs.</p

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Integrated psychological treatment for substance use and co-morbid anxiety or depression vs. treatment for substance use alone. A systematic review of the published literature

<p>Abstract</p> <p>Background</p> <p>There is an increasing consensus in favour of integrated treatment of substance use disorders and co-morbid conditions, such as depression or anxiety. However, up till now no systematic reviews have been published.</p> <p>Methods</p> <p>Based on a systematic search of MedLine and PsychInfo, 9 trials of integrated treatment for depression or anxiety plus substance use disorder were identified. Where possible, meta-analyses were carried out, using random effects models.</p> <p>Results</p> <p>Meta-analyses were carried out for integrated treatment for depression and substance use disorders on a number of outcomes. No meta-analysis could be carried out for integrated treatment for anxiety and substance use disorders, due to multivariate reporting of outcomes in original articles. Integrated treatment for depression and substance abuse produced significant effects on percent days abstinent at follow-up. Differences in retention and symptoms were non-significant, but favoured the experimental condition. For studies of integrated treatment for co-morbid anxiety disorders and substance use disorders, no meta-analysis could be carried out. Several studies of integrated treatment for anxiety and substance use disorders reported that patients assigned to substance use treatment only fared better.</p> <p>Conclusion</p> <p>Psychotherapeutic treatment for co-morbid depression and substance use disorders is a promising approach, but is not sufficiently empirically supported at this point. Psychotherapeutic treatment for co-morbid anxiety and substance use disorders is not empirically supported. There is a need for more trials to replicate the findings from studies of integrated treatment for depression and substance use disorders, and for the development of new treatment options for co-morbid anxiety and substance use disorders.</p

Sex disparities in attitudes towards intimate partner violence against women in sub-Saharan Africa: a socio-ecological analysis

<p>Abstract</p> <p>Background</p> <p>Attitudes towards intimate partner violence against women (IPVAW) has been suggested as one of the prominent predictor of IPVAW. In this study, we take a step back from individual-level variables and examine relationship between societal-level measures and sex differences in attitudes towards IPVAW.</p> <p>Methods</p> <p>We used meta-analytic procedure to synthesize the results of most recent data sets available from Demographic and Health Survey (DHS) of 17 countries in sub-Saharan Africa conducted between 2003 and 2007. Pooled odds ratio (OR) and 95% confidence intervals (CI) were computed for all countries. Test of heterogeneity, sensitivity analysis, and meta-regression were also carried out.</p> <p>Results</p> <p>Women were twice as likely to justify wife beating than men (pooled OR = 1.97; 95% CI 1.53- 2.53) with statistically significant heterogeneity. The magnitude in sex disparities in attitudes towards IPVAW increased with increasing percentage of men practicing polygamy in each country. Furthermore, magnitude in sex disparities in attitudes towards IPVAW decreased monotonically with increasing adult male and female literacy rate, gender development index, gross domestic product and human development index.</p> <p>Conclusion</p> <p>This meta-analysis has provided evidence that women were more likely to justify IPVAW than men in sub-Saharan Africa. Our results revealed that country's socio-economic factors may be associated with sex differential in attitudes towards IPVAW.</p

Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

<p>Abstract</p> <p>Background</p> <p>Hypertonic saline (HTS) reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury.</p> <p>Methods</p> <p>Adult male Sprague Dawley rats were used in all experiments. <b><it>Series 1 </it></b>examined the potential for HTS to reduce the severity of evolving oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12) or hypertonic saline (HTS, n = 12), and the extent of lung injury assessed after 6 hours. <b><it>Series 2 </it></b>examined the potential for HTS to enhance the resolution of oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6) or hypertonic saline (HTS, n = 6), and the extent of lung injury assessed after 6 hours.</p> <p>Results</p> <p>In <b><it>Series I</it></b>, HTS significantly reduced bronchoalveolar lavage (BAL) neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 10³ cells.ml^-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in <b><it>Series 2</it></b>, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 10³ cells.ml^-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml^-1].</p> <p>Conclusion</p> <p>These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.</p