Patterns of use of adjunctive therapies in patients with early moderate- severe Acute Respiratory Distress syndrome: Insights from the LUNG SAFE Study

Background: Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent. Research Question: We wished to determine the frequency and patterns of use of adjunctive strategies in patients with moderate to severe ARDS (PaO2/FIO2 [P/F ratio] < 150) enrolled into the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Study Design and Methods: The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio < 150). Results: Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts. Interpretation: Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS. Trial Registry: ClinicalTrials.gov; No.: NCT02010073; URL: www.clinicaltrials.go

A systematic review of mucoadhesive vaginal tablet testing

Drug administration through the vaginal tract is one of the oldest modalities of pharmacotherapy, and it is also one of the most explored. Since the vaginal cavity has a wide surface area, a plentiful blood supply, and a complex network of blood arteries, it can evade hepatic first-pass metabolism and obtain high local drug concentrations. Vaginal pills look to be a good dose form since they are simple to use, portable, and can easily deliver the required amount of medicine. Vaginal formulations, on the other hand, are vulnerable to rapid expulsion due to the vaginal tract’s self-cleaning action, which reduces the formulation’s efficiency. Currently, there is an increasing amount of focus on mucoadhesive vaginal formulation research and development to fix the formulation at the place where the medicine can be released and/or absorbed. This article examines all of the strategies used by researchers to develop a mucoadhesive vaginal tablet that is safe, effective, and comfortable for the user

Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction

Introduction: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability. Methods: Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control. Results: Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin). Conclusions: Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency

Prophylaxis of venous thrombosis in patients with spontaneous intracerebral bleeding

Spontaneous intracerebral haemorrhage (SIH) represents a severe clinical event that is associated with high rates of mortality and morbidity. Only a minority of SIH patients receive surgical treatment, whereas the majority are treated conservatively. Venous thromboembolism (VTE) is one of the most common complications in SIH patients and a potential cause of death. Because of the lack of adequate evidences from the literature, the risk to benefit ratio of pharmacologic prophylaxis of VTE, represented on the one hand by hematoma enlargement and/or rebleeding and on the other hand by an expected reduction of the risk of VTE, remains controversial. Mechanical prophylaxis is a potentially safer alternative, but the efficacy of this approach is uncertain. In the absence of specific clinical guidelines containing clear-cut recommendations, physicians have insufficient tools to assist their therapeutic decisions