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The INHALATOR study was a randomized, multicentre, open label, two-period of 7 days each, crossover study, with 7 days of washout in-between, aiming to evaluate the correct use, satisfaction and preference between Breezhaler ® and Respimat ® devices in patients under daily use of open Spiriva ® or open Onbrize ® , as monotherapy for treatment of mild or moderate COPD. Patients aged ≥40 years with a smoking history of at least 10 pack-year were included in the study. Primary endpoint was the rate of correct use of each device at the first day of treatment after reading the drug leaflet information and was evaluated under the supervision of a trained evaluator. At the end of each treatment phase, the inhaler use was re-evaluated and a satisfaction questionnaire was completed. The patients' preference for the inhaler devices was assessed at the end of the study. After exclusions due to screening failures, 140 patients were randomized: 136 received at least one dose of Breezhaler ® and 135 of Respimat ® . At treatment start, the rate of correct inhaler use was 40.4% (95%CI: 32.2%-48.7%) for Breezhaler ® and 36.3% (95%CI: 28.2%-44.4%) for Respimat ® (p = 0.451). After 7 days, the rates were 68.9% (95%CI: 61.1%-76.7%) and 60.4% (95%CI: 52.2%-68.7%), respectively (p = 0.077). According to the Feeling of Satisfaction with Inhaler Questionnaire - FSI 10 patients were more satisfied using Breezhaler ® than Respimat ® and 57.1% preferred using Breezhaler ® (p = 0.001) while 30.1% preferred Respimat ® (p < 0.001)., (Copyright © 2018. Published by Elsevier Ltd.) more...

Objective: To compare subjective sleep evaluation obtained using four questionnaires with polysomnography results for individuals with and without obstructive sleep apnea., Methods: Observational and analytical study in which individuals underwent polysomnography were studied retrospectively to investigate sleep disorders. We compared subjective data from a research database used to predict obstructive sleep apnea based on the STOP-BANG questionnaire, evaluation of excessive daytime sleepiness (Epworth Sleepiness Scale), sleep quality questionnaire (Mini Sleep Questionnaire) and Post-Sleep Data Collection Instrument with the self-reported total sleep time and sleep-onset latency for subjects with and without obstructive sleep apnea., Results: The STOP-BANG questionnaire was a good predictor for the diagnosis of obstructive sleep apnea. However, the other instruments did not show a significant difference between healthy and sick individuals. Patients' perceptions of their sleep onset time were significantly lower than the polysomnographic data, but this difference remained for both subjects with and without obstructive sleep apnea. No difference was found between the subjective duration of sleep and the total sleep time assessed by polysomnography in either the healthy subjects or the patients., Conclusion: Except for the STOP-BANG questionnaire, subjective evaluation of sleepiness, sleep quality, perception of onset, and total sleep time are not important parameters for the diagnosis of obstructive sleep apnea, which reinforces the need for an active search for better management of these patients. more...

N-Acetyltransferase 2 (NAT2) metabolizes a variety of xenobiotics that includes many drugs, chemicals and carcinogens. This enzyme is genetically variable in human populations and polymorphisms in the NAT2 gene have been associated with drug toxicity and efficacy as well as cancer susceptibility. Here, we have focused on the identification of NAT2 variants in Brazilian individuals from two different regions, Rio de Janeiro and Goiás, by direct sequencing, and on the characterization of new haplotypes after cloning and re-sequencing. Upon analysis of DNA samples from 404 individuals, six new SNPs (c.29T>C, c.152G>T, c.203G>A, c.228C>T, c.458C>T and c.600A>G) and seven new NAT2 alleles were identified with different frequencies in Rio de Janeiro and Goiás. All new SNPs were found as singletons (observed only once in 808 genes) and were confirmed by three independent technical replicates. Molecular modeling and structural analysis suggested that p.Gly51Val variant may have an important effect on substrate recognition by NAT2. We also observed that amino acid change p.Cys68Tyr would affect acetylating activity due to the resulting geometric restrictions and incompatibility of the functional group in the Tyr side chain with the admitted chemical mechanism for catalysis by NATs. Moreover, other variants, such like p.Thr153Ile, p.Thr193Met, p.Pro228Leu and p.Val280Met, may lead to the presence of hydrophobic residues on NAT2 surface involved in protein aggregation and/or targeted degradation. Finally, the new alleles NAT2*6H and NAT2*5N, which showed the highest frequency in the Brazilian populations considered in this study, may code for a slow activity. Functional studies are needed to clarify the mechanisms by which new SNPs interfere with acetylation. more...

Arylamine N-acetyltranferase 2 is the main enzyme responsible for the isoniazid metabolization into hepatotoxic intermediates and the degree of hepatotoxicity severity has been attributed to genetic variability in the NAT2 gene. The main goal of this study was to describe the genetic profile of the NAT2 gene in individuals from two different regions of Brazil: Rio de Janeiro and Goiás States. Therefore, after preparation of DNA samples from 404 individuals, genotyping of the coding region of NAT2 was performed by direct PCR sequencing. Thirteen previously described SNPs were detected in these Brazilian populations, from which seven: 191 G>A; 282 C>T; 341 T>C; 481 C>T; 590 G>A; 803 A>G and 857 G>A are the most frequent in other populations. The presence of so-called ethnic-specific SNPs in our population is in accordance with the Brazilians' multiple ancestry. Upon allele and genotype analysis, the most frequent NAT2 alleles were respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the more prevalent genotype (31.7%). These results clearly demonstrate the predominance in the studied Brazilian groups of NAT2 alleles associated with slow over the fast and intermediate acetylator genotypes. Additionally, in Rio de Janeiro, a significantly higher frequency of intermediate acetylation status was found when compared to Goiás (42.5% versus 25%) (p=0.05), demonstrating that different regions of a country with a population characterized by a multi-ethnic ancestry may present a large degree of variability in NAT2 allelic frequencies. This finding has implications in the determination of nationwide policies for use of appropriate anti-TB drugs. more...