Examining the association between C-Reactive protein and obesity by using the fractional polynomial approach; applying on NHANES dataset from 2001 to 2010

This is the final version of the article. Available from Herbert Publications Ltd via the DOI in this record.Objective: This study uses a flexible nonlinear approach, Fractional polynomial models (FPs), to examine the association between obesity and C-reactive protein to select the best fitted model within 44 potentially FP models. Methods: Data for 5 years (2001-2010) of the National Health Interview Survey (NHANES) was used. All respondents aged between 17 and 74 were included in the analysis. CRP was transformed to ln(CRP) to eliminate skewness and missing values were removed from the analysis. A fractional polynomial approach was applied to measure the relationship between elevated levels of CRP and obesity. A closed test was used to select the best model among the 44 models. Results: The best fitted fractional polynomial regression model contained the powers -2 and -2 for BMI. The association between the ln(CRP) and BMI when estimated using the FP approach exhibited a J-shaped pattern for women and men. Women have a higher risk of elevated CRP level compared to men. A deviance difference test yielded a significant improvement in model fit of -2 and -2 compared to other BMI functions. Conclusion: The fractional polynomial regression model is the most robust estimator of BMI compared to other linear or nonlinear models.The authors would like to acknowledge the European Centre for Environment and Human Health at the University of Exeter Medical School- UK and the School of commerce, Faculty of commerce Ain Shams University , Cairo- Egypt

High urinary tungsten concentration is associated with stroke in the National Health and Nutrition Examination Survey 1999-2010.

Published onlineClinical TrialMulticenter StudyResearch Support, Non-U.S. Gov'tBACKGROUND: In recent years there has been an exponential increase in tungsten demand, potentially increasing human exposure to the metal. Currently, the toxicology of tungsten is poorly understood, but mounting evidence suggests that both the elemental metal and its alloys have cytotoxic effects. Here, we investigate the association between tungsten and cardiovascular disease (CVD) or stroke using six waves of the National Health and Nutrition Examination Survey (NHANES). METHODS: We investigated associations using crude and adjusted logistic regression models in a cohort of 8614 adults (18-74 years) with 193 reported stroke diagnoses and 428 reported diagnoses of CVD. We also stratified our data to characterize associations in a subset of younger individuals (18-50 years). RESULTS: Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (Odds Ratio (OR): 1.66, 95% Confidence Interval (95% CI): 1.17, 2.34). The association between tungsten and stroke in the young age category was still evident (OR: 2.17, 95% CI: 1.33, 3.53). CONCLUSION: This study represents the most comprehensive analysis of the human health effects of tungsten to date. Individuals with higher urinary tungsten concentrations have double the odds of reported stroke. We hypothesize that the pathological pathway resulting from tungsten exposure may involve oxidative stress.This work was supported by funding from University of Exeter Medical School. No funding organization or sponsor played any part in the design or conduct of the study, in the analysis or interpretation of the data, or preparation, review, or approval of the manuscript. The European Centre for the Environment and Human Health (part of the University of Exeter Medical School) is supported by investment from the ERDF (European Regional Development Fund) and ESF (European Social Fund) Convergence Programmed for Cornwall and the Isles of Scilly. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

External validation, update and development of prediction models for pre-eclampsia using an Individual Participant Data (IPD) meta-analysis: the International Prediction of Pregnancy Complication Network (IPPIC pre-eclampsia) protocol.

Background: Pre-eclampsia, a condition with raised blood pressure and proteinuria is associated with an increased risk of maternal and offspring mortality and morbidity. Early identification of mothers at risk is needed to target management. Methods/design: We aim to systematically review the existing literature to identify prediction models for pre-eclampsia. We have established the International Prediction of Pregnancy Complication Network (IPPIC), made up of 72 researchers from 21 countries who have carried out relevant primary studies or have access to existing registry databases, and collectively possess data from more than two million patients. We will use the individual participant data (IPD) from these studies to externally validate these existing prediction models and summarise model performance across studies using random-effects meta-analysis for any, late (after 34 weeks) and early (before 34 weeks) onset pre-eclampsia. If none of the models perform well, we will recalibrate (update), or develop and validate new prediction models using the IPD. We will assess the differential accuracy of the models in various settings and subgroups according to the risk status. We will also validate or develop prediction models based on clinical characteristics only; clinical and biochemical markers; clinical and ultrasound parameters; and clinical, biochemical and ultrasound tests. Discussion: Numerous systematic reviews with aggregate data meta-analysis have evaluated various risk factors separately or in combination for predicting pre-eclampsia, but these are affected by many limitations. Our large-scale collaborative IPD approach encourages consensus towards well developed, and validated prognostic models, rather than a number of competing non-validated ones. The large sample size from our IPD will also allow development and validation of multivariable prediction model for the relatively rare outcome of early onset pre-eclampsia. Trial registration: The project was registered on Prospero on the 27 November 2015 with ID: CRD42015029349

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS)

Background Diabetes–related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD). There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes. Review questions; 1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes? 2. Can the data from each study be adjusted for a consistent set of adjustment factors? 3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? Methods MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained. We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using “study” as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. Discussion This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines

High urinary tungsten concentration is associated with stroke in the National Health and Nutrition Examination Survey 1999-2010

Background: In recent years there has been an exponential increase in tungsten demand, potentially increasing human exposure to the metal. Currently, the toxicology of tungsten is poorly understood, but mounting evidence suggests that both the elemental metal and its alloys have cytotoxic effects. Here, we investigate the association between tungsten and cardiovascular disease (CVD) or stroke using six waves of the National Health and Nutrition Examination Survey (NHANES). Methods: We investigated associations using crude and adjusted logistic regression models in a cohort of 8614 adults (18-74 years) with 193 reported stroke diagnoses and 428 reported diagnoses of CVD. We also stratified our data to characterize associations in a subset of younger individuals (18-50 years). Results: Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (Odds Ratio (OR): 1.66, 95% Confidence Interval (95% CI): 1.17, 2.34). The association between tungsten and stroke in the young age category was still evident (OR: 2.17, 95% CI: 1.33, 3.53). Conclusion: This study represents the most comprehensive analysis of the human health effects of tungsten to date. Individuals with higher urinary tungsten concentrations have double the odds of reported stroke. We hypothesize that the pathological pathway resulting from tungsten exposure may involve oxidative stress. © 2013 Tyrrell et al

Individual participant data meta-analyses should not ignore clustering

OBJECTIVES: Individual participant data (IPD) meta-analyses often analyze their IPD as if coming from a single study. We compare this approach with analyses that rather account for clustering of patients within studies. STUDY DESIGN AND SETTING: Comparison of effect estimates from logistic regression models in real and simulated examples. RESULTS: The estimated prognostic effect of age in patients with traumatic brain injury is similar, regardless of whether clustering is accounted for. However, a family history of thrombophilia is found to be a diagnostic marker of deep vein thrombosis [odds ratio, 1.30; 95% confidence interval (CI): 1.00, 1.70; P = 0.05] when clustering is accounted for but not when it is ignored (odds ratio, 1.06; 95% CI: 0.83, 1.37; P = 0.64). Similarly, the treatment effect of nicotine gum on smoking cessation is severely attenuated when clustering is ignored (odds ratio, 1.40; 95% CI: 1.02, 1.92) rather than accounted for (odds ratio, 1.80; 95% CI: 1.29, 2.52). Simulations show models accounting for clustering perform consistently well, but downwardly biased effect estimates and low coverage can occur when ignoring clustering. CONCLUSION: Researchers must routinely account for clustering in IPD meta-analyses; otherwise, misleading effect estimates and conclusions may arise