Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease - A meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials

Background-Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results-We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P = 0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions-In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.

Ramp and constant power trials produce equivalent critical power estimates

The standard critical power test protocol on the cycle prescribes a series of trials to exhaustion, each at a different but constant power setting. Recently the protocol has been modified and applied to a series of trials to exhaustion each at a different ramp incremental rate. This study was undertaken to compare critical power and anaerobic work capacity estimates in the same group of subjects when derived from the two protocols. Ten male subjects of mixed athletic ability cycled to exhaustion on eight occasions in randomized order over a 3-wk period. Four trials were performed at differing constant power settings and four trials on differing ramp incremental rates. Both critical power and anaerobic work capacity were estimated for each subject by curve fitting of the ramp model and of three versions of the constant power model. After adjusting for inter-subject variability, no significant differences were detected between critical power estimates or between anaerobic work capacity estimates from any model formulation or from the two protocols. It is concluded that both the ramp and constant power protocols produce equivalent estimates for critical power and anaerobic work capacity.

Clinical trials profile: Professionals and sites

Clinical trial is considered a breakthrough method in medicine and essential to the development of new drugs. Clinical trials that comply with international and national regulations require an appropriate infrastructure and team qualification. The goal of this study was to evaluate clinical trial groups in Brazil: professional qualification, site structure regulatory knowledge and Good Clinical Practice (GCP) adherence. This is a transversal study with investigators (PI) and sub investigator (SI). PI and SI data were initially identified from Curriculum Lattes from National Advice of Scientific and Technological Development. The study participants were submitted to a questionnaire, which was composed of qualitative and quantitative questions. A hundred PI and SI were interviewed. The most representative Brazilian regions were Southeast (68%) and South (18%). The main institutions involved were HCFMUSP complex and UNIFESP among others institutions. Academic graduation is observed in 86% of them and the higher degree is Doctorate (62%). 91% had GCP knowledge although only 74% had formal training. About the team, all of them are multidisciplinary with majority of nurses and pharmaceuticals. 88% had GCP knowledge although only 77% had formal training. 36%, 60% and 44% of clinical trials were in phase II,III and IV. In conclusion, researchers have appropriate skills and knowledge to perform clinical studies however there is still a need for training. The centers where the researchers work, have trained staff and adequate infrastructure for conducting clinical trials phase II,III and IV. (C) 2010 Elsevier Inc. All rights reserved.

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine A Report of the International Placebo Symposium Working Group

Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice Part II. Understanding parameters for acne treatment with photodynamic therapy

Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are ""target"" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAT.) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009. (J Am Acad Dermatol 2010;63:195-211.)

International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors Few studies have described the international epidemiology of pre-existing immunity to adenoviruses We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36 Clinical trial samples were used to assess NA titers from the US and Europe The proportions of participants that were negative were 14 8%(Ad5), 31 5%(Ad6),41 2%(Ad26) and 53.6% (Ad36) Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers, participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR = 3 53,95% CI 224,557) Regardless of location. titers of Ad5NA were the highest and Ad36 NA were the lowest Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations (C) 2009 Published by Elsevier Ltd

Increased Vascular Permeability, Angiogenesis and Wound Healing Induced by the Serum of Natural Latex of the Rubber Tree Hevea brasiliensis

Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile`s method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex. Copyright (C) 2009 John Wiley & Sons, Ltd.

The Provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

Objective. To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). Methods. In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordce in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results. The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician`s global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent`s global assessment of patient`s well-being, 5) functional ability, and 6) health-related quality of life. Conclusion. The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European Leauge Against Rheumatism, propose a core set of criteria for the evaluation of response of therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.