Impact of Funding Source on Clinical Trial Results Including Cardiovascular Outcome Trials.

Previous authors have suggested a higher likelihood for industry-sponsored (IS) studies to have positive outcomes than non-IS studies, though the influence of publication bias was believed to be a likely confounder. We attempted to control for the latter using a prepublication database to compare the primary outcome of recent trials based on sponsorship. We used the "advanced search" feature in the clinicaltrials.gov website to identify recently completed phase III studies involving the implementation of a pharmaceutical agent or device for which primary data were available. Studies were categorized as either National Institutes of Health (NIH) sponsored or IS. Results were labeled "favorable" if the results favored the intervention under investigation or "unfavorable" if the intervention fared worse than standard medical treatment. We also performed an independent literature search to identify the cardiovascular trials as a case example and again categorized them into IS versus NIH sponsored. A total of 226 studies sponsored by NIH were found. When these were compared with the latest 226 IS studies, it was found that IS studies were almost 4 times more likely to report a positive outcome (odds ratio [OR] 3.90, 95% confidence interval [CI] 2.6087 to 5.9680, p <0.0001). As a case example of a specialty, we also identified 25 NIH-sponsored and 215 IS cardiovascular trials, with most focusing on hypertension therapy (31.6%) and anticoagulation (17.9%). IS studies were 7 times more likely to report favorable outcomes (OR 7.54, 95% CI 2.19 to 25.94, p = 0.0014). They were also considerably less likely to report unfavorable outcomes (OR 0.11, 95% CI 0.04 to 0.26, p <0.0001). In conclusion, the outcomes of large clinical studies especially cardiovascular differ considerably on the basis of their funding source, and publication bias appears to have limited influence on these findings.

Application of the Intervention Mapping protocol to develop Keys, a family child care home intervention to prevent early childhood obesity.

BACKGROUND: Many families rely on child care outside the home, making these settings important influences on child development. Nearly 1.5 million children in the U.S. spend time in family child care homes (FCCHs), where providers care for children in their own residences. There is some evidence that children in FCCHs are heavier than those cared for in centers. However, few interventions have targeted FCCHs for obesity prevention. This paper will describe the application of the Intervention Mapping (IM) framework to the development of a childhood obesity prevention intervention for FCCHs METHODS: Following the IM protocol, six steps were completed in the planning and development of an intervention targeting FCCHs: needs assessment, formulation of change objectives matrices, selection of theory-based methods and strategies, creation of intervention components and materials, adoption and implementation planning, and evaluation planning RESULTS: Application of the IM process resulted in the creation of the Keys to Healthy Family Child Care Homes program (Keys), which includes three modules: Healthy You, Healthy Home, and Healthy Business. Delivery of each module includes a workshop, educational binder and tool-kit resources, and four coaching contacts. Social Cognitive Theory and Self-Determination Theory helped guide development of change objective matrices, selection of behavior change strategies, and identification of outcome measures. The Keys program is currently being evaluated through a cluster-randomized controlled trial CONCLUSIONS: The IM process, while time-consuming, enabled rigorous and systematic development of intervention components that are directly tied to behavior change theory and may increase the potential for behavior change within the FCCHs.

Conflicts of Interest and Outcomes of Cardiovascular Trials.

Conflicts of interests have long been recognized as potential sources of influence in the conduct and reporting of clinical trials. This controversy was again rekindled after the publication of the latest statin guidelines and a series of studies regarding competing interests in leading medical journals. We investigate the association between declared author conflicts and the outcomes of large cardiovascular trials. We searched the Medline (PubMed) database to identify "phase 2" and "phase 3" clinical trials using the search term "cardiovascular" over the past decade using "10 years" as the filter. We perceived the competing interest as present regardless of the nature such as consulting fees, honoraria, travel imbursements, stock holding, and employment. Of the 699 titles retrieved, 114 studies met the inclusion criteria. Nearly 80% of studies had at least a single author with competing interests. The 114 studies had a total of 1,433 investigators, of which 725 had declared conflicts of interests (50.6%). A total of 66 studies (58%) had half or >50 percent of investigators who had some conflicts of interests. Of these studies, 54 studies had favorable outcomes and only 12 had unfavorable outcomes (p <0.001). Among the type of competing interests, consulting or personal fees was the most common present in 58 investigators (51%). This was followed by research grants present in 55 the researchers (48%). Among 25 (22%) studies, at least one investigator reported stakes in the industry, of which only 2 studies had unfavorable outcomes for the intervention being investigated. Just 1 of the 25 clinical trials with a sample size of >1,000 had no investigators with competing interests. In conclusion, authors conflicts are associated with favorable outcomes in cardiovascular outcome trials.

A modelling approach for coupling numerical analytical techniques applied in microsystems

In this paper, a method for the integration of several numerical analytical techniques that are used in microsystems design and failure analysis is presented. The analytical techniques are categorized into four groups in the discussion, namely the high-fidelity analytical tools, i.e. finite element (FE) method, the fast analytical tools referring to reduced order modeling (ROM); the optimization tools, and probability based analytical tools. The characteristics of these four tools are investigated. The interactions between the four tools are discussed and a methodology for the coupling of these four tools is offered. This methodology consists of three stages, namely reduced order modeling, deterministic optimization and probabilistic optimization. Using this methodology, a case study for optimization of a solder joint is conducted. It is shown that these analysis techniques have mutual relationship of interaction and complementation. Synthetic application of these techniques can fully utilize the advantages of these techniques and satisfy various design requirements. The case study shows that the coupling method of different tools provided by this paper is effective and efficient and it is highly relevant in the design and reliability analysis of microsystems

Fracture mechanics analysis of cracks in solder joint intermetallic compounds

The trend towards miniaturization of electronic products leads to the need for very small sized solder joints. Therefore, there is a higher reliability risk that too large a fraction of solder joints will transform into Intermetallic Compounds (IMCs) at the solder interface. In this paper, fracture mechanics study of the IMC layer for SnPb and Pb-free solder joints was carried out using finite element numerical computer modelling method. It is assumed that only one crack is present in the IMC layer. Linear Elastic Fracture Mechanics (LEFM) approach is used for parametric study of the Stress Intensity Factors (SIF, KI and KII), at the predefined crack in the IMC layer of solder butt joint tensile sample. Contrary to intuition, it is revealed that a thicker IMC layer in fact increases the reliability of solder joint for a cracked IMC. Value of KI and KII are found to decrease with the location of the crack further away from the solder interfaces while other parameters are constant. Solder thickness and strain rate were also found to have a significant influence on the SIF values. It has been found that soft solder matrix generates non-uniform plastic deformation across the solder-IMC interface near the crack tip that is responsible to obtain higher KI and KII.

A fast, streaming SIMD extensions 2, logistic squashing function

Schraudolph proposed an excellent exponential approximation providing increased performance particularly suited to the logistic squashing function used within many neural networking applications. This note applies Intel's streaming SIMD Extensions 2 (SSE2), where SIMD is single instruction multiple data, of the Pentum IV class processor to Schraudolph's technique, further increasing the performance of the logistic squashing function. It was found that the calculation of the new 32-bit SSE2 logistic squashing function described here was up to 38 times faster than the conventional exponential function and up to 16 times faster than a Schraudolph-style 32-bit method on an Intel Pentum D 3.6 GHz CPU.

Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Methods: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age > 6.0 yr, FEV1 ? 40% predicted, and corticosteroid use > 3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.

Measurements and Main Results: Fluticasone group: n = 84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n = 87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23–1.48) fluticasone versus placebo.

Conclusions: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Modelling of Unsteady Gas-Dynamic Flow in a Pipe and at its Exit Using CFD

Traditionally the simulation of the thermodynamic aspects of the internal combustion engine has been undertaken using one-dimensional gas-dynamic models to represent the intake and exhaust systems. CFD analysis of engines has been restricted to modelling of in-cylinder flow structures. With the increasing accessibility of CFD software it is now worth considering its use for complete gas-dynamic engine simulation. This paper appraises the accuracy of various CFD models in comparison to a 1D gas-dynamic simulation. All of the models are compared to experimental data acquired on an apparatus that generates a single gas-dynamic pressure wave. The progress of the wave along a constant area pipe and its subsequent reflection from the open pipe end are recorded with a number of high speed pressure transducers. It was found that there was little to choose between the accuracy of the 1D model and the best CFD model. The CFD model did not require experimentally derived loss coefficients to accurately represent the open pipe end; however, it took several hundred times longer to complete its analysis. The best congruency between the CFD models and the experimental data was achieved using the RNG k-e turbulence model. The open end of the pipe was most effectively represented by surrounding it with a relatively small volume of cells connected to the rest of the environment using a pressure boundary.