Bimodal release ondansetron for acute gastroenteritis among adolescents and adults: A randomized clinical trial

Importance: Vomiting resulting from acute gastroenteritis is commonly treated with intravenous antiemetics in acute care settings. If oral treatment were beneficial, patients might not need intravenous administered hydration or medication. Furthermore, a long-acting treatment could provide sustained relief from nausea and vomiting. Objective: To determine whether an experimental long-acting bimodal release ondansetron tablet decreases gastroenteritis-related vomiting and eliminates the need for intravenous therapy for 24 hours after administration. Design, Setting, and Participants: This placebo-controlled, double-blind, randomized clinical trial included patients from 19 emergency departments and 2 urgent care centers in the United States from December 8, 2014, to February 17, 2017. Patients 12 years and older with at least 2 vomiting episodes from presumed gastroenteritis in the previous 4 hours and symptoms with less than 36 hours\u27 duration were randomized using a 3:2 active to placebo ratio. Analyses were performed on an intent-to-treat basis and conducted from June 1, 2017, to November 1, 2017. Intervention: Bimodal release ondansetron tablet containing 6 mg of immediate release ondansetron and 18 mg of a 24-hour release matrix for a total of 24 mg of ondansetron. Main Outcomes and Measures: Treatment success was defined as no further vomiting, no need for rescue medication, and no intravenous hydration for 24 hours after bimodal release ondansetron administration. Results: Analysis included 321 patients (mean [SD] age, 29.0 [11.1] years; 195 [60.7%] women), with 192 patients in the bimodal release ondansetron group and 129 patients in the placebo group. Treatment successes were observed in 126 patients in the bimodal release ondansetron group (65.6%) compared with 70 patients in the placebo group (54.3%), with an 11.4% (95% CI, 0.3%-22.4%) absolute probability difference. The proportion of treatment success was 21% higher among patients who received bimodal release ondansetron compared with those who received a placebo (relative risk, 1.21; 95% CI, 1.00-1.46; P = .04). In an analysis including only patients with a discharge diagnosis of acute gastroenteritis and no major protocol violations, there were 123 treatment successes (69.5%) in the bimodal release ondansetron group compared with 67 treatment successes (54.9%) in the placebo group (relative risk, 1.27; 95% CI, 1.05-1.53; P = .01). Adverse effects were infrequent and similar to the known safety profile of ondansetron. Conclusions and Relevance: This randomized clinical trial found that a long-acting bimodal release oral ondansetron tablet was an effective antiemetic among adolescents and adults with moderate to severe vomiting from acute gastroenteritis. The drug benefits extended to 24 hours after administration. Bimodal release ondansetron may decrease the need for intravenous access and emergency department care to manage acute gastroenteritis. Trial Registration: ClinicalTrials.gov identifier: NCT02246439

Comportamento de células do sistema imune frente ao desafio com Salmonella Enteritidis em aves tratadas e não tratadas com ácidos orgânicos

A Salmonelose é uma importante zoonose, considerada a principal causa de infecções bacterianas, sendo associada ao consumo de produtos avícolas. Como alternativa de controle, ácidos orgânicos têm sido amplamente usados. No entanto, pouco se conhece sobre o estado imunológico de aves de produção, e uma avaliação deste status é necessária para proteger frente a enfermidades e para garantir à aplicação segura de agentes terapêuticos ou imunização profilática. Este trabalho teve como objetivo verificar o comportamento do sistema imunológico das aves previamente infectadas com Salmonella Enteritidis (SE) tratadas com um composto de ácidos orgânicos em diferentes concentrações administrado via água e ração comparando com as aves infectadas e não tratadas. Foram inoculados 120 frangos de corte com 1mL de SE, via oral, na concentração de 1,0 x 108 UFC/mL, no 1º e 2º dia de idade, divididos em seis tratamentos com duas repetições, utilizando 200, 400, 500 e 1000ppm do ácido orgânico. Aos 35 dias de vida das aves, foram coletados, de todos os grupos, alíquotas de sangue de 3mL em tubo contendo EDTA para a avaliação das células imunes através de citometria de fluxo. Foram analisadas as porcentagens circulantes de células CD4+, CD8β+, MHC I+, MHC II+, TCRVβ1+, TCRVβ2+ e CD28+. Para análise microbiológica foram coletadas tonsilas cecais destas aves. Observou-se com esse estudo que os ácidos orgânicos nas dosagens 1000ppm na água e 500ppm na ração durante, dois e sete dias respectivamente antes do abate, foram eficazes na redução da infecção por SE em frangos de corte, comprovadas pelo método microbiológico e demonstradas através do comportamento das células do sistema imune. No presente estudo as aves infectadas apresentaram uma proporção menor de células T auxiliares circulantes quando comparadas às aves infectadas, mas tratadas com o AO ou com o grupo não infectado. A mesma tendência pode ser observada para as células CD28+, TCRVβ1+ e MHC IIbright+, e, com menor resolução, para CD8β+

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.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Bottoms Up: Methamphetamine Toxicity from an Unusual Route

Methamphetamine (MA) use is becoming commonplace, and emergency physicians (EPs) are seeing patients with abuse-associated complications. Previous reports have described inhalational and intravenous routes. We present the second case of rectal MA abuse in the literature. Trans-rectal use is important for EPs to consider because ongoing absorption of massive quantities may be averted upon detection. Additionally, trans-rectal abuse risks anorectal trauma and vascular necrosis with colonic perforation.[WestJEM. 2009;10:58-60.

Bottoms Up: Methamphetamine Toxicity from an Unusual Route

Methamphetamine (MA) use is becoming commonplace, and emergency physicians (EPs) are seeing patients with abuse-associated complications. Previous reports have described inhalational and intravenous routes. We present the second case of rectal MA abuse in the literature. Trans-rectal use is important for EPs to consider because ongoing absorption of massive quantities may be averted upon detection. Additionally, trans-rectal abuse risks anorectal trauma and vascular necrosis with colonic perforation.[WestJEM. 2009;10:58-60.

Dilation of peripheral vessels in Marfan syndrome: Importance of thoracoabdominal MR angiography

Objectives: Aim of this study was to assess vascular morphology and dimension of the entire aorta and branch vessels in MFS using thoracoabdominal MR angiography (MRA). Background: Evaluation of vascular involvement in Marfan Syndrome (MFS) is focused to the ascending aorta, which has the major risk of dissection/rupture. Methods: From March 2006 to January 2011, 64 patients (35 \ub1 13 years old) with MFS underwent echocardiography and MRA of thoracic and abdominal aorta. Measurements of ascending aorta, aortic arch, descending thoracic and abdominal aorta, and aortic branch vessels were assessed. In patients with aortic dissection only non dissected vessels were considered for measurements. Results: 64 Marfan patients were divided into 2 groups: patients in natural history (group A, 55%) and patients previously submitted to aortic root and/or ascending aorta replacement because of severe aortic dilation or dissection (group B, 45%). Dilation of the descending aorta, mostly of the aorti

Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

Background: Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, elevated blood pressure, or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS. Methods: We examined MetS risk factors in individuals through body measurements and clinical and biochemical blood analysis. To evaluate intestinal health, gut inflammation was measured by fecal calprotectin, intestinal permeability through the lactulose-mannitol test, and utilized fecal metabolomics to examine alterations in the host–microbiota gut metabolism. Results: No signs of intestinal inflammation or increased intestinal permeability were observed in the MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. Although our MetS cohort showed no signs of intestinal inflammation, they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels and decreasing HDL cholesterol levels. Conclusion: Taken together, our main results show that MetS subjects showed major alterations in fecal lipid profiles suggesting alterations in the intestinal host–microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit that fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD