European journal of clinical investigation
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Eur. J. Clin. Invest. · Sep 2012
ReviewDevelopmental Therapeutics Consortium report on study design effects on trial outcomes in chronic myeloid leukaemia.
Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukaemia (CML). Results from ongoing phase 3 trials with nilotinib [Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd)] and dasatinib [Dasatinib Versus Imatinib Study in Treatment-Naive CML-CP Patients (DASISION)] in newly diagnosed patients with CML in chronic phase have demonstrated that these TKIs resulted in significant improvements in responses vs. imatinib. ⋯ Despite potential bias from differences in patient populations and study design, indirect cross-trial comparisons to determine the relative effectiveness of these agents will be performed by physicians. This DTC report provides a comprehensive summary of the study designs, protocols and results of the ENESTnd and DASISION trials, which will assist physicians in making informed decisions on the best treatment approach for their patients.
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Eur. J. Clin. Invest. · Sep 2012
ReviewImmunological pathways in virus-induced COPD exacerbations: a role for IL-15.
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of antiviral type 1 cytokine interferon-γ and activated CD8(+) T cells. COPD exacerbations are the major cause of morbidity and mortality, have a prolonged and intense effect on quality of life and may result in accelerated loss of lung function. Respiratory virus infections, frequently within a state of colonization by bacteria, are the major cause of COPD exacerbations, and there is also evidence of virus latency in 'stable' disease, suggesting that latent infection might be a cause of chronic inflammation in COPD. ⋯ Interleukin-15 could play a major role in the airway inflammation in COPD directly, via its own receptors, by amplifying the type 1 immune responses and decreasing apoptosis or indirectly, via modulating molecules associated with cytotoxic activity of natural killer and CD8(+) T cells, such as major histocompatibility complex class I-related chain A and B.
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Prevalence of metabolic syndrome (MetS) increases with age, but its association with all-cause mortality in older persons remains uncertain. This study investigated the association of all-cause mortality with MetS and its individual components in older men and women. ⋯ Metabolic Syndrome is associated with all-cause mortality in older women but not in men. The association, however, is limited to a narrow age range.
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Eur. J. Clin. Invest. · Sep 2012
Dysregulated adipokine metabolism in chronic obstructive pulmonary disease.
Research concerning the involvement of body composition and systemic inflammatory markers in adipokine metabolism in chronic obstructive pulmonary disease (COPD) is still limited. Therefore, we primarily aimed to investigate the adipokine metabolism in relation to these systemic inflammatory biomarkers and to evaluate possible gender-related differences in the adipokine metabolism in patients with COPD. ⋯ This study shows a gender-dependent dysregulation of adipokine metabolism in patients with COPD compared with BMI-matched controls. Furthermore, results from this study suggest a more prominent role of adiponectin in the systemic response to COPD.
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While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. ⋯ The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare.