Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.

Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

Abstract Background The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy. If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. Methods Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. Results One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08). Conclusions The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects. Trial registration Current Controlled Trials ISRCTN04714018

Effectiveness of a multifactorial falls prevention program in community-dwelling older people when compared to usual care: study protocol for a randomised controlled trial (Prevquedas Brazil)

Background Falling in older age is a major public health concern due to its costly and disabling consequences. However very few randomised controlled trials (RCTs) have been conducted in developing countries, in which population ageing is expected to be particularly substantial in coming years. This article describes the design of an RCT to evaluate the effectiveness of a multifactorial falls prevention program in reducing the rate of falls in community-dwelling older people. Methods/design Multicentre parallel-group RCT involving 612 community-dwelling men and women aged 60 years and over, who have fallen at least once in the previous year. Participants will be recruited in multiple settings in Sao Paulo, Brazil and will be randomly allocated to a control group or an intervention group. The usual care control group will undergo a fall risk factor assessment and be referred to their clinicians with the risk assessment report so that individual modifiable risk factors can be managed without any specific guidance. The intervention group will receive a 12-week Multifactorial Falls Prevention Program consisting of: an individualised medical management of modifiable risk factors, a group-based, supervised balance training exercise program plus an unsupervised home-based exercise program, an educational/behavioral intervention. Both groups will receive a leaflet containing general information about fall prevention strategies. Primary outcome measures will be the rate of falls and the proportion of fallers recorded by monthly falls diaries and telephone calls over a 12 month period. Secondary outcomes measures will include risk of falling, fall-related self-efficacy score, measures of balance, mobility and strength, fall-related health services use and independence with daily tasks. Data will be analysed using the intention-to-treat principle.The incidence of falls in the intervention and control groups will be calculated and compared using negative binomial regression analysis. Discussion This study is the first trial to be conducted in Brazil to evaluate the effectiveness of an intervention to prevent falls. If proven to reduce falls this study has the potential to benefit older adults and assist health care practitioners and policy makers to implement and promote effective falls prevention interventions. Trial registration ClinicalTrials.gov (NCT01698580)

O tráfico de animais

A exploração do Brasil-Colônia pelos portugueses, franceses e holandeses teve por intuito contrabandear espécies de fauna e da flora, além de pedras e metais preciosos. Esses povos colaboraram intensamente pela devastação do meio ambiente brasileiro nas fases do ciclo do pau-brasil, dos metais preciosos, da canade- açúcar e do gado. E o Direito brasileiro não poderia ficar alheio a esses dilemas socioculturais com tendência de infinita e crescente transformação ao País. O maior avanço coercitivo foi o advento da Lei n. 9.605, de 1998, à defesa e à proteção do meio ambiente, por meio da criação de novos crimes, instituindo-se, assim, um sistema de proteção penal-administrativo eficaz; porém, um dos maiores obstáculos que vem sendo enfrentado pela Polícia Federal brasileira, considerada uma das melhores corporações do mundo, e o Ministério Público é a fragilidade do único tipo penal versado ao combate ao tráfico dos animais.