Marcadores inflamatórios da doença cardiovascular em idosos

A maior parte das informações sobre o papel dos marcadores inflamatórios como preditores de doença cardiovascular envolve apenas indivíduos de meia-idade. Nesta revisão foi avaliado o papel dos marcadores inflamatórios como preditores de doença cardiovascular em idosos. Foram consultadas as bases de dados do Medline (Pubmed) e a base de dados da Cochrane, utilizando as palavras-chave. Após o acréscimo dos seguintes filtros: Limits: Aged 65+ years, Humans, Randomized Controlled Trial, Meta-Analysis, Review, Clinical Trials, foram encontrados 554 artigos. Desses, foram selecionados 120 artigos e avaliados quanto à sua força de evidência (classificação de Oxford Centre for Evidence Based Medicine). Nos pacientes com >65 anos, a interleucina 6 (IL-6), fator de necrose tumoral alfa (TNF α) e interleucina-10 (IL-10) têm se mostrado bons preditores de desfechos cardiovasculares. Em relação à proteína C-reativa (PCR), os dados são inconsistentes e ela parece ter menor poder como preditor em idosos, quando comparada aos indivíduos de meia-idade. Níveis de fibrinogênio parecem ser preditores de mortalidade, porém de uma forma não específica, ou seja, não apenas para mortalidade cardiovascular. Além disso, os marcadores inflamatórios também são indicadores de declínio funcional e mortalidade, independentemente da presença de doença cardiovascular. As evidências atuais são insuficientes para uso rotineiro dos marcadores inflamatórios, em idosos, já que existem poucos estudos nessa faixa etária, sendo a maioria deles de curta duração e com número reduzido de marcadores inflamatórios. A solicitação desses marcadores, de rotina, deve ser considerada individualmente.

Impact of Physical Activity Interventions on Blood Pressure in Brazilian Populations

Background:High blood pressure is associated with cardiovascular disease, which is the leading cause of mortality in the Brazilian population. Lifestyle changes, including physical activity, are important for lowering blood pressure levels and decreasing the costs associated with outcomes.Objective:Assess the impact of physical activity interventions on blood pressure in Brazilian individuals.Methods:Meta-analysis and systematic review of studies published until May 2014, retrieved from several health sciences databases. Seven studies with 493 participants were included. The analysis included parallel studies of physical activity interventions in adult populations in Brazil with a description of blood pressure (mmHg) before and after the intervention in the control and intervention groups.Results:Of 390 retrieved studies, eight matched the proposed inclusion criteria for the systematic review and seven randomized clinical trials were included in the meta-analysis. Physical activity interventions included aerobic and resistance exercises. There was a reduction of -10.09 (95% CI: -18.76 to -1.43 mmHg) in the systolic and -7.47 (95% CI: -11.30 to -3.63 mmHg) in the diastolic blood pressure.Conclusions:Available evidence on the effects of physical activity on blood pressure in the Brazilian population shows a homogeneous and significant effect at both systolic and diastolic blood pressures. However, the strength of the included studies was low and the methodological quality was also low and/or regular. Larger studies with more rigorous methodology are necessary to build robust evidence.

Network Meta-analysis to Synthesize Evidence for Decision Making in Cardiovascular Research

Abstract Clinical decision-making requires synthesis of evidence from literature reviews focused on a specific theme. Evidence synthesis is performed with qualitative assessments and systematic reviews of randomized clinical trials, typically covering statistical pooling with pairwise meta-analyses. These methods include adjusted indirect comparison meta-analysis, network meta-analysis, and mixed-treatment comparison. These tools allow synthesis of evidence and comparison of effectiveness in cardiovascular research.

Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Validity, reliability and responsiveness of the French language translation of the Western Ontario Shoulder Instability Index (WOSI).

BACKGROUND: The WOSI (Western Ontario Shoulder Instability Index) is a self-administered quality of life questionnaire designed to be used as a primary outcome measure in clinical trials on shoulder instability, as well as to measure the effect of an intervention on any particular patient. It is validated and is reliable and sensitive. As it is designed to measure subjective outcome, it is important that translation should be methodologically rigorous, as it is subject to both linguistic and cultural interpretation. OBJECTIVE: To produce a French language version of the WOSI that is culturally adapted to both European and North American French-speaking populations. MATERIALS AND METHODS: A validated protocol was used to create a French language WOSI questionnaire (WOSI-Fr) that would be culturally acceptable for both European and North American French-speaking populations. Reliability and responsiveness analyses were carried out, and the WOSI-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm, Shoulder and Hand-French translation), and Walch-Duplay scores. RESULTS: A French language version of the WOSI (WOSI-Fr) was accepted by a multinational committee. The WOSI-Fr was then validated using a total of 144 native French-speaking subjects from Canada and Switzerland. Comparison of results on two WOSI-Fr questionnaires completed at a mean interval of 16 days showed that the WOSI-Fr had strong reliability, with a Pearson and interclass correlation of r=0.85 (P=0.01) and ICC=0.84 [95% CI=0.78-0.88]. Responsiveness, at a mean 378.9 days after surgical intervention, showed strong correlation with that of the F-QuickDASH-D/S, with r=0.67 (P<0.01). Moreover, a standardized response means analysis to calculate effect size for both the WOSI-Fr and the F-QuickDASH-D/S showed that the WOSI-Fr had a significantly greater ability to detect change (SRM 1.55 versus 0.87 for the WOSI-Fr and F-QuickDASH-D/S respectively, P<0.01). The WOSI-Fr showed fair correlation with the Walch-Duplay. DISCUSSION: A French-language translation of the WOSI questionnaire was created and validated for use in both Canadian and Swiss French-speaking populations. This questionnaire will facilitate outcome assessment in French-speaking settings, collaboration in multinational studies and comparison between studies performed in different countries. TYPE OF STUDY: Multicenter cohort study. LEVEL OF EVIDENCE: II.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials 2008 Issue 4, MEDLINE (1966 to January 2009), and EMBASE (1980 to January 2009). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate a pooled effect was estimated using a Mantel-Haenszel fixed effect method. MAIN RESULTS: We included eleven trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that CO measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other seven trials. One trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12; 95% CI 1.24 to 3.62). One trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77; 95% CI 1.04 to 7.41) but enrolled a population of light smokers. Five trials failed to detect evidence of a significant effect. One of these tested CO feedback alone and CO + genetic susceptibility as two different intervention; none of the three possible comparisons detected significant effects. Three others used a combination of CO and spirometry feedback in different settings, and one tested for a genetic marker. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. Only two pairs of studies were similar enough in term of recruitment, setting, and intervention to allow meta-analysis.

Sommes-nous prêts à prescrire une polypill à nos patients [Are we ready to prescribe a polypill to our patients?].

The all-in-one pill combination (Polypill) of several active components used in primary prevention of cardiovascular disease was a decade ago purposed to reduce the cardiovascular burden by more than 80%. This Polypill could be approved before 2013 in United States. Although controversed, it could answer to the worried situation even observed in Switzerland: the adherence to secondary prevention treatments is clearly insufficient and the cardiovascular events remain in the first row of death's causes. This abstract summarize the results from interventional studies who tried to valid this concept as well as the main stakes to be assessed on the medical side before to consider such a similar approach in Switzerland.

Epidermal growth factor receptor: a re-emerging target in glioblastoma.

PURPOSE OF REVIEW: Amplification and overexpression of the epidermal growth factor receptor (EGFR) gene are a hallmark of primary glioblastoma (45%), making it a prime target for therapy. In addition, these amplifications are frequently associated with oncogenic mutations in the extracellular domain. However, efforts at targeting the EGFR tyrosine kinase using small molecule inhibitors or antibodies have shown disappointing efficacy in clinical trials for newly diagnosed or recurrent glioblastoma. Here, we review recent insights into molecular mechanisms relevant for effective targeting of the EGFR pathway. RECENT FINDINGS: Molecular workup of glioblastoma tissue of patients under treatment with small molecule inhibitors has established drug concentrations in the tumor tissue, and has shed light on the effectiveness of target inhibition and respective effects on pathway signaling. Further, functional analyses of interaction of small molecule inhibitors with distinct properties to bind to the active or inactive form of EGFR have provided new insights that will impact the choice of drugs. Finally, vaccination approaches targeting the EGFRvIII mutant featuring a tumor-specific antigen have shown promising results that warrant larger controlled clinical trials. SUMMARY: A combination of preclinical and clinical studies at the molecular level has provided new insights that will allow refining strategies for targeting the EGFR pathway in glioblastoma.

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Primary ciliary dyskinesia (PCD) is an autosomal recessive disease with an incidence estimated between 1:2,000 and 1:40,000. Ciliated epithelia line the airways, nasal and sinus cavities, Eustachian tube and fallopian tubes. Congenital abnormalities of ciliary structure and function impair mucociliary clearance. As a consequence, patients present with chronic sinopulmonary infections, recurrent glue ear and female subfertility. Similarities in the ultrastructure of respiratory cilia, nodal cilia and sperm result in patients with PCD also presenting with male infertility, abnormalities of left-right asymmetry (most commonly situs inversus totalis) and congenital heart disease. Early diagnosis is essential to ensure specialist management of the respiratory and otological complications of PCD. Diagnostic tests focus on analysis of ciliary function and electron microscopy structure. Analysis is technically difficult and labour intensive. It requires expertise for interpretation, restricting diagnosis to specialist centres. Management is currently based on the consensus of experts, and there is a pressing need for randomised clinical trials to inform treatment.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

Télésurveillance des insuffisants cardiaques: de nouvelles technologies pour améliorer le suivi?: revue Cochrane pour le praticien

Cet article présente les résultats de la revue systématique: Inglis SC, Clark RA, McAlister FA, et al. Structured telephone support or telemonitoring programmes for patients with chronic heart failure. Cochrane Database Systematic Reviews 2010, Issue 8. Art. No.:CD007228. DOI:10.1002/14651858.CD007228.pub2. PMID: 20687083

MET: a promising anticancer therapeutic target.

The MET pathway is dysregulated in many human cancers and promotes tumour growth, invasion and dissemination. Abnormalities in MET signalling have been reported to correlate with poor clinical outcomes and drug resistance in patients with cancer. Thus, MET has emerged as an attractive target for cancer therapy. Several MET inhibitors have been introduced into the clinic, and are currently in all phases of clinical trials. In general, initial results from these studies indicate only a modest benefit in unselected populations. In this Review, we discuss current challenges in developing MET inhibitors--including identification of predictive biomarkers--as well as the most-efficient ways to combine these drugs with other targeted agents or with classic chemotherapy or radiotherapy.

The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis.

OBJECTIVES: To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). METHODS: The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physician's and parent's global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohen's κ agreement. RESULTS: The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohen's κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. CONCLUSION: PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.