Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials

There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

Contact force-guided catheter ablation for the treatment of atrial fibrillation: a meta-analysis of randomized, controlled trials

Contact force (CF) sensing technology allows real-time monitoring during catheter ablation for atrial fibrillation (AF). However, the effect of CF sensing technology on procedural parameters and clinical outcomes still needs clarification. Because of the inconsistent results thus far in this area, we performed a meta-analysis to determine whether CF sensing technology can improve procedural parameters and clinical outcomes for the treatment of AF. Studies examining the benefits of CF sensing technology were identified in English-language articles by searching the MEDLINE, Web of Science, and Cochrane Library databases (inception to May 2015). Ten randomized, controlled trials involving 1834 patients (1263 males, 571 females) were included in the meta-analysis (681 in the CF group, 1153 in the control group). Overall, the ablation time was significantly decreased by 7.34 min (95%CI=-12.21 to -2.46; P=0.003, Z test) in the CF group compared with the control group. CF sensing technology was associated with significantly improved freedom from AF after 12 months (OR=1.55, 95%CI=1.20 to 1.99; P=0.0007) and complications were significantly lower in the CF group than in the control group (OR=0.50, 95%CI=0.29 to 0.87; P=0.01). However, fluoroscopy time analysis showed no significantly decreased trend associated with CF-guided catheter ablation (weighted mean difference: -2.59; 95%CI=-9.06 to 3.88; P=0.43). The present meta-analysis shows improvement in ablation time and freedom from AF after 12 months in AF patients treated with CF-guided catheter ablation. However, CF-guided catheter ablation does not decrease fluoroscopy time.

Randomized controlled trials of serotonin-norepinephrine reuptake inhibitor in treating major depressive disorder in children and adolescents: a meta-analysis of efficacy and acceptability

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs), were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to January 2015. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of treatment response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes. Five trials with a total of 973 patients were included. SNRIs were not significantly more effective than placebo for treatment response but were for remission. The comparison of patients taking SNRIs that dropped out for all reasons and those taking placebo did not reach statistical significance. Significantly more patients taking SNRIs dropped out for adverse effects than those taking placebo. No significant difference was found in suicide-related risk outcomes. SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients. However, duloxetine has a potential beneficial effect for depression in young populations, showing a need for further research.

Physicochemical composition, minerals, and pesticide residues in organic grape juices

Demand for organic products is intensified in many countries each year. Following this trend, Brazil produces increasing volumes of organic grape juice. In this way, a survey of organic grape juices made from grapes produced according to this system was carried out where physicochemical composition, minerals, trace elements, and pesticide residues were determined. Variables related to grape juice composition were performed by physicochemical procedures; minerals and trace elements, by inductively plasma optical emission spectrometry; pesticide residues, by liquid chromatography-mass spectrometry. Main results show that the physicochemical composition of organic grape juices was in general in accordance to the Brazilian legislation. The mean concentrations of trace elements were very low, varying from 0.002 (Cd) to 0.970 (Ba) mg L–1. Pesticide residues were not detected in any sample analyzed (MRL= 10 µg L–1). These results show that the Serra Gaúcha viticultural region present conditions to produce organic grape juices, despite the adverse climate factors that occurs in some years. Nevertheless, these products should be made with grape varieties, such as the labrusca ones, less susceptibles to the main grapevine pathogens.

Evaluation of pesticide residues in oranges from São Paulo, Brazil

Pesticides in “PERA” orange samples (N = 57) from São Paulo City, Brazil were assessed and the pesticide intake contribution was estimated for chronic risk assessment. Seventy-six pesticides were evaluated by the gas chromatography multi-residue method, including isomers and metabolites (4.332 determinations). The mean recoveries at the limit of quantification level were in the range of 72-115% and the relative standard deviation for five replicate samples was 1-11%. The limits of detection and quantification ranged from 0.005 to 0.4 mg.kg−1 and from 0.01 to 0.8 mg.kg−1, respectively. Pesticides were found in 42.1% of the samples at levels ranging from 0.06 to 2.9 mg.kg−1. Of the contaminated samples, 3.5% contained residues (bifenthrin and clofentezine) above the maximum residue level and 12.3% contained unauthorized pesticides (azinphos-ethyl, parathion, myclobutanil, profenofos, and fenitrothion). The estimated risk characterization for orange intake by adults and children, respectively, ranged from 0.04 to 6.6% and from 0.1 to 26.5% of the acceptable daily intake. The detection of irregular residues emphasizes the need for better implementation of Good Agriculture Practices and greater control of formulated products. Other pesticides surveyed did not pose a health risk due to consumption.