Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Are cognitive interventions for multiple sclerosis effective and feasible?

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.

Why do we need randomized and epidemiological studies on cardiovascular disease? Evidence-based cardiology VII

Over the last two decades the results of randomized clinical studies, which are powerful aids for correctly assessing therapeutical strategies, have consolidated cardiological practice. In addition, scientifically interesting hypotheses have been generated through the results of epidemiological studies. Properly conducted randomized studies without systematic errors and with statistical power adequate for demonstrating moderate and reasonable benefits in relevant clinical outcomes have provided reliable and strong results altering clinical practice, thus providing adequate treatment for patients with cardiovascular disease (CVD). The dissemination and use of evidence-based medicine in treating coronary artery disease (CAD), heart failure (HF), and in prevention will prevent hundreds of thousands of deaths annually in developed and developing countries. CVD is responsible for approximately 12 million deaths annually throughout the world, and approximately 60% of these deaths occur in developing countries. During recent years, an increase in mortality and morbidity rates due to CVD has occurred in developing countries. This increase is an indication that an epidemiological (demographic, economical, and health-related) transition is taking place in developing countries and this transition implies a global epidemic of CVD, which will require wide-ranging and globally effective strategies for prevention. The identification of conventional and emerging risk factors for CVD, as well as their management in high-risk individuals, has contributed to the decrease in the mortality rate due to CVD. Through a national collaboration, several multi-center and multinational randomized and epidemiological studies have been carried out throughout Brazil, thus contributing not only to a generalized scientific growth in different Brazilian hospitals but also to the consolidation of an increasingly evidence-based clinical practice.

Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study)

OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women) with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years), and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016) as well as an increase in left ventricular shortening fraction (p=0.02) and in left ventricular ejection fraction (p=0.017) occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde

Efeito do exercício na biomecânica da marcha em crianças e adolescentes com paralisia cerebral

Tipo de Estudo: Revisão. Temática: Efeito do exercício na biomecânica da locomoção de crianças e adolescentes com paralisia cerebral que apresentam marcha em agachamento (designada como “crouch gait”). Objetivos: 1) verificar e analisar as metodologias de programas de treino de força que, combinados ou não com outros programas de treino, exercícios ou intervenções, visam melhorar o padrão da marcha e a funcionalidade destes indivíduos; 2) tendo por base os resultados do primeiro objetivo, compilar uma bateria de exercícios e propôr um exemplo de plano de treino adequado a esta população. Métodos: Usou-se o PICOS para a definição de uma estratégia de busca segura e confiável. A “PubMed”, “Cochrane” e “Web of Knowledge", foram as bases de dados selecionadas e utilizadas. A pesquisa aconteceu na Faculdade de Motricidade Humana e no Hospital de Santa Maria em Lisboa. A seleção final dos artigos decorreu no mês de Janeiro, durante uma semana, e foi realizada e rastreada por dois investigadores de forma diferente. Incluíram-se nesta revisão estudos randomizados e controlados, com crianças e adolescentes com paralisia cerebral e que apresentam “crouch gait”, e nos quais foram utilizados protocolos de exercício como método de intervenção nesta população, tendo em vista a melhoria do padrão de marcha. Resultados: Da pesquisa inicial resultaram 223 estudos. Com a leitura dos resumos, selecionaram-se 96. Excluíram-se 85 porque apenas 11 cumpriram com todos os critérios de eligibilidade. Foi avaliada a qualidade metodológica destes 11 estudos com a escala PEDro e excluíram-se 3, resultando em 8 artigos como potenciais estudos para a revisão. Discussão: Um melhor alinhamento biomecânico e a obtenção de uma base mais estável podem afetar positivamente a função da marcha nestas crianças. O treino da força, sozinho, nem sempre melhora a capacidade da marcha. A melhoria da marcha advém dos efeitos e resultados significativos da força muscular, da amplitude de movimento articular, da diminuição da espasticidade, da regulação do tónus e da melhoria do equilíbrio e da postura. Conclusão: O treino da força não é uma contra indicação para estes indivíduos. Este oferece efeitos benéficos para a melhoria das suas funcionalidades. Para um efeito significativo, a intervenção deve ser superior a seis (6) semanas.

Procesos de cambio en la cultura jurídica: análisis desde la experiencia del juicio por jurados. Processes of change in the Legal Culture: Analysis from the Experience of Jury Trials.

El presente proyecto de investigación se orienta a analizar la institución del juicio por jurados, considerada como un punto estratégico para la observación de los procesos de cambio que recorren la cultura jurídica en Argentina. Frente a las múltiples transformaciones y a los intensos procesos de reestructuración de las relaciones sociales observados en el contexto latinoamericano y especialmente en Argentina, la necesidad de reconstruir la legitimidad de los jueces ante la opinión pública se ha vuelto impostergable, y el recurso a la participación popular en el campo judicial aparece como un instrumento útil para ello. Analizar la efectividad de esta estrategia para la legitimación del poder judicial es uno de los objetivos del presente proyecto de investigación. Abordar dicho objetivo implica, indagar en la relación entre la administración de justicia y diferentes actores sociales, especialmente los miembros de la profesión jurídica y la opinión pública.Se explora igualmente la contradicción entre el hecho de que esta institución, nacida para atenuar la dureza de los castigos, se ha implementado recientemente en la provincia de Córdoba en la situación inversa. El modo en que la tensión entre el espíritu garantista de los jueces y la demanda de castigos de los ciudadanos comunes se manejará en la práctica de los juicios por jurado, y su incidencia en el éxito de las estrategias legitimadoras del poder judicial, aparece como una cuestión relevante para el análisis que se propone. Con la utilización de diferentes fuentes de información cuantitativas y cualitativas, se espera que el análisis de la implementación del juicio penal con jurados populares en la provincia de Córdoba propuesto en el presente proyecto, contribuya a documentar los niveles de articulación entre la cultura jurídica interna y externa.

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.

Tai Chi Chuan for Cardiac Rehabilitation in Patients with Coronary Arterial Disease

Background:Several studies have shown that Tai Chi Chuan can improve cardiac function in patients with heart disease.Objective:To conduct a systematic review of the literature to assess the effects of Tai Chi Chuan on cardiac rehabilitation for patients with coronary artery disease.Methods:We performed a search for studies published in English, Portuguese and Spanish in the following databases: MEDLINE, EMBASE, LILACS and Cochrane Register of Controlled Trials. Data were extracted in a standardized manner by three independent investigators, who were responsible for assessing the methodological quality of the manuscripts.Results:The initial search found 201 studies that, after review of titles and abstracts, resulted in a selection of 12 manuscripts. They were fully analyzed and of these, nine were excluded. As a final result, three randomized controlled trials remained. The studies analyzed in this systematic review included patients with a confirmed diagnosis of coronary artery disease, all were clinically stable and able to exercise. The three experiments had a control group that practiced structured exercise training or received counseling for exercise. Follow-up ranged from 2 to 12 months.Conclusion:Preliminary evidence suggests that Tai Chi Chuan can be an unconventional form of cardiac rehabilitation, being an adjunctive therapy in the treatment of patients with stable coronary artery disease. However, the methodological quality of the included articles and the small sample sizes clearly indicate that new randomized controlled trials are needed in this regard.

Effects of Yoga in Patients with Chronic Heart Failure: A Meta-Analysis

The use of yoga as an effective cardiac rehabilitation in patients with chronic heart failure (CHF) remains controversial. We performed a meta-analysis to examine the effects of yoga on exercise capacity and health-related quality of life (HRQOL) in patients with CHF. Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Excerpta Medica database, LILACS, Physiotherapy Evidence Database, The Scientific Electronic Library Online, and Cumulative Index to Nursing and Allied Health (from the earliest date available to December 2013) for randomized controlled trials (RCTs) examining the effects of yoga versus exercise and/or of yoga versus control on exercise capacity (peakVO2) and quality-of-life (HRQOL) in CHF. Two reviewers selected studies independently. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test. Two studies met the selection criteria (total: 30 yoga and 29 control patients). The results suggested that yoga compared with control had a positive impact on peak VO2 and HRQOL. Peak VO2, WMD (3.87 95% CI: 1.95 to 5.80), and global HRQOL standardized mean differences (-12.46 95% CI: -22.49 to -2.43) improved in the yoga group compared to the control group. Yoga enhances peak VO2 and HRQOL in patients with CHF and could be considered for inclusion in cardiac rehabilitation programs. Larger RCTs are required to further investigate the effects of yoga in patients with CHF.

Late Outcome of a Randomized Study on Oral Magnesium for Premature Complexes

Background:Ventricular and supraventricular premature complexes (PC) are frequent and usually symptomatic. According to a previous study, magnesium pidolate (MgP) administration to symptomatic patients can improve the PC density and symptoms.Objective:To assess the late follow-up of that clinical intervention in patients treated with MgP or placebo.Methods:In the first phase of the study, 90 symptomatic and consecutive patients with PC were randomized (double-blind) to receive either MgP or placebo for 30 days. Monthly follow-up visits were conducted for 15 months to assess symptoms and control electrolytes. 24-hour Holter was performed twice, regardless of symptoms, or whenever symptoms were present. In the second phase of the study, relapsing patients, who had received MgP or placebo (crossing-over) in the first phase, were treated with MgP according to the same protocol.Results:Of the 45 patients initially treated with MgP, 17 (37.8%) relapsed during the 15-month follow-up, and the relapse time varied. Relapsing patients treated again had a statistically significant reduction in the PC density of 138.25/hour (p < 0.001). The crossing-over patients reduced it by 247/hour (p < 0.001). Patients who did not relapse, had a low PC frequency (3 PC/hour). Retreated patients had a 76.5% improvement in symptom, and crossing-over patients, 71.4%.Conclusion:Some patients on MgP had relapse of symptoms and PC, indicating that MgP is neither a definitive nor a curative treatment for late follow-up. However, improvement in the PC frequency and symptoms was observed in the second phase of treatment, similar to the response in the first phase of treatment.

Improving Post-Discharge Medication Adherence in Patients with CVD: A Pilot Randomized Trial

Background:Effective interventions to improve medication adherence are usually complex and expensive.Objective:To assess the impact of a low-cost intervention designed to improve medication adherence and clinical outcomes in post-discharge patients with CVD.Method:A pilot RCT was conducted at a teaching hospital. Intervention was based on the four-item Morisky Medication Adherence Scale (MMAS-4). The primary outcome measure was medication adherence assessed using the eight-item MMAS at baseline, at 1 month post hospital discharge and re-assessed 1 year after hospital discharge. Other outcomes included readmission and mortality rates.Results:61 patients were randomized to intervention (n = 30) and control (n = 31) groups. The mean age of the patients was 61 years (SD 12.73), 52.5% were males, and 57.4% were married or living with a partner. Mean number of prescribed medications per patient was 4.5 (SD 3.3). Medication adherence was correlated to intervention (p = 0.04) and after 1 month, 48.4% of patients in the control group and 83.3% in the intervention group were considered adherent. However, this difference decreased after 1 year, when adherence was 34.8% and 60.9%, respectively. Readmission and mortality rates were related to low adherence in both groups.Conclusion:The intervention based on a validated patient self-report instrument for assessing adherence is a potentially effective method to improve adherent behavior and can be successfully used as a tool to guide adherence counseling in the clinical visit. However, a larger study is required to assess the real impact of intervention on these outcomes.

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.