Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography Main Results From the Randomized Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)

Background-It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury. Methods and Results-We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P = 0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P = 0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment. Conclusions-In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.

Clinical trial design in non-invasive brain stimulation psychiatric research

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them. Copyright (C) 2011 John Wiley & Sons, Ltd.

Avaliação dos exercícios proprioceptivos no tratamento dos distúrbios do manguito rotador em profissionais de enfermagem: um estudo clínico controlado e randomizado

CONTEXTUALIZAÇÃO: A dor no ombro em profissionais de enfermagem pode acarretar limitação das atividades diárias e ocupacionais e interferir na qualidade de vida. OBJETIVO: Comparar o efeito da aplicação de dois programas fisioterapêuticos diferenciados pelos exercícios de propriocepção em trabalhadores de enfermagem com desordem do manguito rotador, segundo indicadores de qualidade de vida, satisfação no trabalho e intensidade da dor. MÉTODO: Trata-se de um estudo experimental, randomizado, prospectivo, comparativo, com análise quantitativa dos dados. A coleta de dados foi realizada no período de junho de 2010 a julho de 2011, por meio de um questionário sociodemográfico e profissional, questionário Western Ontario Rotador Cuff Index (WORC), Escala de Satisfação no Trabalho (Occupational Stress Indicator) e Escala Visual Numérica (EVN) para intensidade da dor. Após randomização, os sujeitos foram alocados em dois grupos. No Grupo 1 (controle), foram aplicados exercícios de alongamento, fortalecimento e crioterapia. No Grupo 2 (experimental), foram realizados os mesmos exercícios que no Grupo 1 acrescidos de exercícios proprioceptivos. Os dados foram analisados por meio do Statistical Package for the Social Science, versão 16.0 para Windows. RESULTADOS: Após os tratamentos fisioterapêuticos, houve melhora significativa da dor nos sujeitos dos dois grupos e da qualidade de vida nos trabalhadores do Grupo 2. Não houve alteração dos indicadores de satisfação no trabalho nos dois grupos. CONCLUSÕES: Os exercícios proprioceptivos foram importantes no tratamento dos distúrbios osteomusculares. No entanto, os resultados não permitiram inferir a melhor efetividade deles em relação ao outro tratamento, pois não houve diferença significativa entre os grupos. Ensaio clínico registrado no ClinicalTrials.gov NCT01465932.

Modified constraint-induced movement therapy and modified forced-use therapy for stroke patients are both effective to promote balance and gait improvements

Background: Previous studies show that chronic hemiparetic patients after stroke, presents inabilities to perform movements in paretic hemibody. This inability is induced by positive reinforcement of unsuccessful attempts, a concept called learned non-use. Forced use therapy (FUT) and constraint induced movement therapy (CIMT) were developed with the goal of reversing the learned non-use. These approaches have been proposed for the rehabilitation of the paretic upper limb (PUL). It is unknown what would be the possible effects of these approaches in the rehabilitation of gait and balance. Objectives: To evaluate the effect of Modified FUT (mFUT) and Modified CIMT (mCIMT) on the gait and balance during four weeks of treatment and 3 months follow-up. Methods: This study included thirty-seven hemiparetic post-stroke subjects that were randomly allocated into two groups based on the treatment protocol. The non-paretic UL was immobilized for a period of 23 hours per day, five days a week. Participants were evaluated at Baseline, 1st, 2nd, 3rd and 4th weeks, and three months after randomization. For the evaluation we used: The Stroke Impact Scale (SIS), Berg Balance Scale (BBS) and Fugl-Meyer Motor Assessment (FM). Gait was analyzed by the 10-meter walk test (T10) and Timed Up & Go test (TUG). Results: Both groups revealed a better health status (SIS), better balance, better use of lower limb (BBS and FM) and greater speed in gait (T10 and TUG), during the weeks of treatment and months of follow-up, compared to the baseline. Conclusion: The results show mFUT and mCIMT are effective in the rehabilitation of balance and gait. Trial Registration ACTRN12611000411943.

ABSENCE OF STABILIZATION POINT OF THE SPECIES ACCUMULATION CURVE IN TROPICAL FORESTS

The definition of the sample size is a major problem in studies of phytosociology. The species accumulation curve is used to define the sampling sufficiency, but this method presents some limitations such as the absence of a stabilization point that can be objectively determined and the arbitrariness of the order of sampling units in the curve. A solution to this problem is the use of randomization procedures, e. g. permutation, for obtaining a mean species accumulation curve and empiric confidence intervals. However, the randomization process emphasizes the asymptotical character of the curve. Moreover, the inexistence of an inflection point in the curve makes it impossible to define objectively the point of optimum sample size.

Efeitos de altas temperaturas na germinação de sementes de capim-dourado (Syngonanthus nitens (Bong.) Ruhland, Eriocaulaceae): implicações para o manejo

Este estudo teve por objetivo investigar potenciais efeitos do fogo na germinação de sementes de capim-dourado (Syngonanthus nitens) (Bong.) Ruhland (Eriocaulaceae). Sementes coletadas na região do Jalapão, Tocantins, foram submetidas a choques de temperaturas de 60º, 100 ºC, 150 ºC e 200 ºC durante 1, 3 e 5 minutos. Foram feitas 5 réplicas, com 20 sementes para cada tratamento, e controle. As sementes foram dispostas em placas de Petri e em câmaras de germinação a 28 ºC, fotoperíodo 12h/12h, por 40 dias. As taxas de germinação das sementes foram analisadas por meio de ANOVA com teste de aleatorização. A maioria dos tratamentos resultou em altas taxas de germinação (>85%), exceto 200ºC/3' (50%) e 200ºC/5', que apresentou uma queda significativa (4,5%, P<0,05). Os resultados obtidos indicam que as sementes de S. nitens não são estimuladas nem mortas por altas temperaturas, exceto quando combinados temperatura e tempos de exposição extremos (200ºC/5'). A passagem do fogo é muito rápida durante queimadas nos campos úmidos, onde S. nitens ocorre e as temperaturas frequentemente não atingem os 150 ºC. Nessas condições, estes resultados indicam que as sementes de S. nitens potencialmente sobrevivem à passagem do fogo na maioria das queimadas. Esta informação é de utilidade imediata para o manejo desta espécie de alto valor comercial.

Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder

Objective: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naive adults with obsessive-compulsive disorder (OCD). Method: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. Results: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p = 0.008); higher verbal memory on the California Verbal Learning Test (p = 0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p = 0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p = 0.002). Conclusion: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context. (C) 2012 Elsevier Inc. All rights reserved.

Effectiveness of low-level laser therapy for patients with carpal tunnel syndrome: design of a randomized single-blinded controlled trial

Background: Carpal tunnel syndrome is the most common neuropathy in the upper extremity, resulting from the compression of the median nerve at wrist level. Clinical studies are essentials to present evidence on therapeutic resources use at early restoration on peripheral nerve functionality. Low-level laser therapy has been widely investigated in researches related to nerve regeneration. Therefore, it is suggested that the effect of low-level laser therapy associated with other conservative rehabilitation techniques may positively affect symptoms and overall hand function in compressive neuropathies such as carpal tunnel syndrome. The aim of this study is to evaluate the effectiveness of low-level laser therapy in addition to orthoses therapy and home orientations in patients with carpal tunnel syndrome. Methods/Design: Patients older than 18 years old will be included, with clinical diagnosis of carpal tunnel syndrome, excluding comorbidies. A physiotherapist will conduct intervention, with a blinding evaluator. Randomization will be applied to allocate the patients in each group: with association or not to low-level laser therapy. All of them will be submitted to orthoses therapy and home orientations. Outcome will be assessed through: pain visual analogic scale, Semmes Weinstein monofilaments (TM) threshold sensibility test, Pinch Gauge T, Boston Carpal Tunnel Questionnaire and two point discrimination test. Discussion: This paper describes the design of a randomized controlled trial, which aim to assess the effectiveness of conservative treatment added to low-level laser therapy for patients with carpal tunnel syndrome. Trial registration: Brazilian Clinical Trials Registry (ReBec) - 75ddtf / Universal Trial Number: U1111-1121-5184

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor Insights From the Platelet Inhibition and Patient Outcomes Trial

Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia

Objective Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. Methods Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. Results Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 +/- 2.4 weeks in the FETO group and at 37.4 +/- 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the receivedtreatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). Conclusion FETO improves neonatal survival in cases with isolated severe CDH. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Oral cleft prevention program (OCPP)

Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT00397917

Motivation and frustration in cardiology trial participation: the patient perspective

OBJECTIVE: The participation of humans in clinical cardiology trials remains essential, but little is known regarding participant perceptions of such studies. We examined the factors that motivated participation in such studies, as well as those that led to participant frustration. METHODS: Patients who had participated in hypertension and coronary arterial disease (phases II, III, and IV) clinical trials were invited to answer a questionnaire. They were divided into two groups: Group I, which included participants in placebo-controlled clinical trials after randomization, and Group II, which included participants in clinical trials in which the tested treatment was compared to another drug after randomization and in which a placebo was used in the washout period. RESULTS: Eighty patients (47 patients in Group I and 33 patients in Group II) with different socio-demographic characteristics were interviewed. Approximately 60% of the patients were motivated to participate in the trial with the expectation of personal benefit. Nine participants (11.2%) expressed the desire to withdraw, which was due to their perception of risk during the testing in the clinical trial (Group I) and to the necessity of repeated returns to the institution (Group II). However, the patients did not withdraw due to fear of termination of hospital treatment. CONCLUSIONS: Although this study had a small patient sample, the possibility of receiving a benefit from the new tested treatment was consistently reported as a motivation to participate in the trials.