Marina Moreno

Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression

BACKGROUND We compared transcranial direct‐current stimulation (tDCS) with a selective serotonin‐reuptake inhibitor for the treatment of depression. METHODS In a single‐center, double‐blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30‐minute, 2‐mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17‐item Hamilton Depression Rating Scale (HDRS‐17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention‐to‐treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, ‐2.3 points; 95% confidence interval [CI], ‐4.3 to ‐0.4; P=0.69) was lower than the noninferiority margin of ‐2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new‐onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS In a single‐center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10‐week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT‐TDCS ClinicalTrials.gov number, NCT01894815.)

Does Non-Invasive Brain Stimulation Improve Cognition in Major Depressive Disorder? A Systematic Review

Non-invasive brain stimulation (NIBS) techniques, such as repeated transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have been increasingly used in different contexts to improve cognitive performance and ameliorate depression symptoms. Considering that major depression is usually accompanied by cognitive deficits, NIBS technique could be also helpful to improve cognition in depressed patients. In this systematic review, we researched for articles published in PubMed/MEDLINE from the first date available to June 2014 that assessed cognitive performance in patients with depression before and after NIBS. Out of 191 references, 25 (16 for rTMS and 9 for tDCS) studies matched our eligibility criteria. Non-invasive brain stimulation interventions, such as rTMS and tDCS seem to be a promising tool for cognitive enhancement in MDD, although several issues and biases (e.g., blinding issues, tests without correction for multiple comparisons, placebo effects and exploratory analyses, practice effects) hinder us to conclude that NIBS technique improve cognition in patients with depression. We discussed possible shortcomings of the included studies, such as the use of different depression treatment protocols, the possibility that some findings were false-positive results of the employed cognitive tasks and whether cognition improvement could have been an epiphenomenon secondary to depression improvement. To conclude, whereas these non-pharmacological, non-invasive techniques are particularly appealing for cognitive improvement in depression, further studies are still warranted to disentangle whether NIBS technique induce positive effects on cognition beyond their antidepressant effects.

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

CONTEXT AND OBJECTIVE Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). DESIGN AND SETTING Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in São Paulo, Brazil. METHODS ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3:3:2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging. RESULTS Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS. CONCLUSION Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression.

Virulence Genes and Antimicrobial Resistance Profiles of Pasteurella multocida Strains Isolated from Rabbits in Brazil

Pasteurella multocida is responsible for a wide range of diseases in domestic animals. In rabbits, the agent is related to nasal discharge, pneumonia, otitis media, pyometra, orchitis, abscess, and septicemia. One hundred and forty rabbits with respiratory diseases from four rabbitries in São Paulo State, Brazil were evaluated for the detection of P. multocida in their nasal cavities. A total of twenty-nine animals were positive to P. multocida isolation, and 46 strains were selected and characterized by means of biochemical tests and PCR. P. multocida strains were tested for capsular type, virulence genes, and resistance profile. A total of 45.6% (21/46) of isolates belonged to capsular type A, and 54.34% (25/46) of the isolates were untypeable. None of the strains harboured toxA or pfhA genes. The frequency of the other twenty genes tested was variable, and the data generated was used to build a dendrogram, showing the relatedness of strains, which were clustered according to origin. Resistance revealed to be more common against sulfonamides and cotrimoxazole, followed by erythromycin, penicillin, and amoxicillin.

First Characterization of CTX-M-15-Producing Escherichia coli Strains Belonging to Sequence Type (ST) 410, ST224, and ST1284 from Commercial Swine in South America.

ABSTRACT We report for the first time the isolation of CTX-M-15-producing Escherichia coli strains belonging to sequence type (ST) 410, ST224, and ST1284 in commercial swine in Brazil. The blaCTX-M-15 gene was located on F-::A9::B1 and C1::A9::B1 IncF-type plasmids, surrounded by a new genetic context comprising the IS26 insertion sequence truncated with the ISEcp1 element upstream of blaCTX-M-15. These results reveal that commercial swine have become a new reservoir of CTX-M-15-producing bacteria in South America.

Virulence and molecular aspects of Bordetella avium isolated from cockatiel chicks (Nymphicus hollandicus) in Brazil

Bordetella avium is an opportunistic pathogen that presents tropism for ciliated epithelia, leading to upper respiratory tract disease in turkeys. This agent has also been associated with Lockjaw Syndrome in psittacine birds, but literatures describing the importance of this agent in such species are rare. The purpose of the present study was to report the first outbreak of B. avium infection in juvenile cockatiels demonstrating the Lockjaw Syndrome in Brazil and to investigate the antimicrobial resistance profile and phenotypic and genotypic characteristics of these strains. Surprising, the strains obtained from five infected cockatiel chicks from three different breeders from different Brazilian states showed a clonal relationship using the Pulsed Field Gel Electrophoresis and Single Enzyme Amplified Fragment Length Polymorphism techniques. The virulence potentials of the B. avium strains were assessed using tracheal adherence and cytotoxic effects on a VERO cell monolayer.

Cognitive effects of transcranial direct current stimulation treatment in patients with major depressive disorder: An individual patient data meta-analysis of randomised, sham-controlled trials

HighlightsIt remains unclear whether tDCS treatment has cognitive benefits in depression.This individual patient data meta‐analysis examined effects from seven RCTs.Active tDCS treatment did not cause cognitive benefits compared to sham. &NA; Transcranial direct current stimulation (tDCS) has emerged as a promising new treatment for major depression. While recent randomised, sham‐controlled studies found tDCS to have antidepressant effects, it remains to be determined whether a tDCS treatment course may also enhance cognitive function independent of mood effects in depressed patients. This systematic review and individual patient data (IPD) meta‐analysis examined cognitive outcomes from randomised, sham‐controlled trials of tDCS treatment for major depression. Seven randomised, sham‐controlled trials (n = 478 participants, 260 in active and 218 in sham) of tDCS for major depression were included. Results showed no cognitive enhancement after active tDCS compared to sham for the 12 cognitive outcomes investigated. Active relative to sham tDCS treatment was associated with reduced performance gains on a measure of processing speed (&bgr; = −0.33, 95% CI −0.58; −0.08, p = 0.011). Active tDCS treatment for depression did not show cognitive benefits independent of mood effects. Rather, tDCS treatment relative to sham stimulation for major depression may instead be associated with a reduced practice effect for processing speed.

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials

Background: Although several studies indicate that placebo response is large to antidepressant pharmacotherapy in major depressive disorder (MDD), no updated meta‐analysis has quantified the magnitude of the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD yet. Objective: To conduct a systematic review and meta‐analysis on this issue in randomized controlled trials (RCTs) involving participants with MDD; and to explore potential moderators. Methodology: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science electronic databases were searched from inception up to March 15, 2017 for RCTs that investigated the efficacy of any rTMS modality compared to sham intervention in participants with acute depressive episodes. Cochrane Risk of Bias Tool was used to estimate risks. We estimated the placebo effect size (Hedgess g, random‐effects model) response using placebo groups baseline and endpoint depressive symptom scores. Meta‐regressions have been employed to explore potential moderators of response. Results: Sixty‐one studies met eligibility criteria (N = 1328; mean age, 47 years; 57% females). Placebo response was large (g = 0.8, 95% CI = 0.65–0.95, p < 0.01) regardless of the modality of intervention. Placebo response was directly associated with publication year and depression improvement of the active group, and inversely associated with higher levels of treatment‐resistant depression. Other moderators, including gender, age, and stimulator type, were not associated with the outcome. Overall, 24.6%, 67.2%, and 8.2% of studies had an overall low, unclear, and high bias risk, respectively. Conclusion: Placebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group. Such result suggests that excluding placebo responders with a run‐in phase may not confer advantage since response to ‘active’ rTMS may decrease as well. Moreover, placebo response may be a component of therapeutic response to rTMS in MDD. In addition, placebo response increase over time could indicate improvement in rTMS trial designs, including better sham rTMS methods. HighlightsWe searched for RCTs of rTMS for MDD.We quantified the magnitude of the placebo response to rTMS in MDD.Placebo response in rTMS depression trials was large.Placebo response may be a component of the therapeutic response to rTMS depression trials.

Vancomycin-intermediate livestock-associated methicillin-resistant Staphylococcus aureus ST398/t9538 from swine in Brazil

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been mainly related with pig farming, in Europe and North America, with the ST398 as the most commonly identified type of LA-MRSA. Here we present the draft genome of the first vancomycin-intermediate MRSA ST398/t9538 isolated from a swine presenting exudative epidermitis in Brazil.

Antimicrobial resistance and virulence gene profiles in P. multocida strains isolated from cats.

Cats are often described as carriers of Pasteurella multocida in their oral microbiota. This agent is thought to cause pneumonia, conjunctivitis, rhinitis, gingivostomatitis, abscess and osteonecrosis in cats. Human infection with P. multocida has been described in several cases affecting cat owners or after cat bites. In Brazil, the cat population is approximately 21 million animals and is increasing, but there are no studies of the presence of P. multocida in the feline population or of human cases of infection associated with cats. In this study, one hundred and ninety-one healthy cats from owners and shelters in São Paulo State, Brazil, were evaluated for the presence of P. multocida in their oral cavities. Twenty animals were positive for P. multocida , and forty-one strains were selected and characterized by means of biochemical tests and PCR. The P. multocida strains were tested for capsular type, virulence genes and resistance profile. A total of 75.6% (31/41) of isolates belonged to capsular type A, and 24.4% (10/41) of the isolates were untypeable. None of the strains harboured toxA, tbpA or pfhA genes. The frequencies of the other genes tested were variable, and the data generated were used to build a dendrogram showing the relatedness of strains, which were clustered according to origin. The most common resistance profile observed was against sulfizoxazole and trimethoprim-sulphamethoxazole.