Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions

Background

Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.

Results

Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.

Conclusions

Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.

     

The role of PTPN22 in the pathogenesis of autoimmune diseases: A comprehensive review

The incidence of autoimmune diseases is increasing worldwide, thus stimulating studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors. Genetic association studies have shown the PTPN22 gene as a shared genetic risk factor with implications in multiple autoimmune disorders. By encoding a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems, the PTPN22 gene may have a fundamental role in the development of immune dysfunction. PTPN22 polymorphisms are associated with rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and many other autoimmune conditions. In this review, we discuss the progress in our understanding of how PTPN22 impacts autoimmunity in both humans and animal models. In addition, we highlight the pathogenic significance of the PTPN22 gene, with particular emphasis on its role in T and B cells, and its function in innate immune cells, such as monocytes, dendritic and natural killer cells. We focus particularly on the complexity of PTPN22 interplay with biological processes of the immune system. Findings highlight the importance of studying the function of disease-associated PTPN22 variants in different cell types and open new avenues of investigation with the potential to drive further insights into mechanisms of PTPN22. These new insights will reveal important clues to the molecular mechanisms of prevalent autoimmune diseases and propose new potential therapeutic targets.     

Association between brain natriuretic peptide,markers of inflammation and the objective and subjective response to cardiac resynchronization therapy

Introduction: Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from pre-CRT implantation to 14 months follow-up in CRT-responders and nonresponders, defined by two response criteria. Methods: We studied 105 heart failure patients implanted with a CRT-defibrillator (68% men; age = 65.4 ± 10.1 years). The objective CRT-response was defined as a reduction of ⩾15% in left ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points. Results: Pre-implantation concentrations of TNFα were significantly lower for subjective responders compared to nonresponders (p = .05), but there was no difference in BNP and the other inflammatory markers at baseline. Objective CRT-response was significantly associated with lower BNP levels over time (F = 27.31, p < .001), and subjective CRT-response with lower TNFα levels (F = 5.67, p = .019). Conclusion: Objective and subjective response to CRT was associated with lower levels of BNP and TNFα, respectively, but not with other markers of inflammation. This indicates that response to CRT is not automatically related to a stronger overall decrease in inflammation. Large-scale studies are warranted that further examine the relation between the clinical effects of CRT on inflammatory markers, as the latter have been associated with poor prognosis in heart failure.     

Retrieval of overviews of systematic reviews in MEDLINE was improved by the development of an objectively derived and validated search strategy

ObjectivesLocating overviews of systematic reviews is difficult because of an absence of appropriate indexing terms and inconsistent terminology used to describe overviews. Our objective was to develop a validated search strategy to retrieve overviews in MEDLINE.Study Design and SettingWe derived a test set of overviews from the references of two method articles on overviews. Two population sets were used to identify discriminating terms, that is, terms that appear frequently in the test set but infrequently in two population sets of references found in MEDLINE. We used text mining to conduct a frequency analysis of terms appearing in the titles and abstracts. Candidate terms were combined and tested in MEDLINE in various permutations, and the performance of strategies measured using sensitivity and precision.ResultsTwo search strategies were developed: a sensitivity-maximizing strategy, achieving 93% sensitivity (95% confidence interval [CI]: 87, 96) and 7% precision (95% CI: 6, 8), and a sensitivity-and-precision–maximizing strategy, achieving 66% sensitivity (95% CI: 58, 74) and 21% precision (95% CI: 17, 25).ConclusionThe developed search strategies enable users to more efficiently identify overviews of reviews compared to current strategies. Consistent language in describing overviews would aid in their identification, as would a specific MEDLINE Publication Type.