High-Definition Optical Coherence Tomography for the in vivo Detection of Demodex Mites

Background: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. Methods: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. Results: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3-5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. Conclusion: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases. Copyright (C) 2012 S. Karger AG, Base

Vehicles for atopic dermatitis therapies: more than just a placebo

A topical vehicle is a ‘carrier system’ for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition

The (F)utility of the thallium-201 quantitative lung/myocardial ratio in the detection of coronary artery disease

Exercise-induced increases in pulmonary uptake of thallium-201 ( 201 Tl) have been associated with exercise-induced myocardial dysfunction. To evaluate this phenomenon more replicably, a quantitative semi-automated computer program was used to generate, from anterior exercise and delayed views, lung-myocardial ratios (LMR) of 201 Tl uptake in 78 patients [40 normal, 38 with coronary artery disease (CAD)]. Patients with CAD had a significantly higher mean exercise lung myocardial ratio (EXLMR) than normals (30.8 vs. 27.3; P < 0.003). In patients with adequate exercise (≥85% of an age-adjusted maximal heart rate), the EXLMRs of CAD patients were significantly higher than those of normals (29.7 vs. 25.5; P =0.003). However, this difference between CAD and normal patients was not apparent in a patient subgroup with submaximal exercise levels (< 85% of an age-adjusted maximal heart rate). In both normal and CAD patients, EXLMR decreased with increasing exercise levels ( r =-0.555; P =0.007). In patients with 201 Tl scans lacking visually defined perfusion defects (visually normal), an elevated LMR detected 60% of CAD cases with 81% specificity. A considerably elevated EXLMR in patients achieving adequate exercise should suggest the presence of CAD, even if there are no visually apparent cardiac perfusion defects. With submaximal exercise, however, the EXLMR is not a useful discriminator between CAD patients and normals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46823/1/259_2004_Article_BF00638787.pd

Hemodynamic effects of lung recruitment maneuvers in acute respiratory distress syndrome

Background: Clinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood. Methods: A computational model with highly integrated pulmonary and cardiovascular systems was configured to replicate static and dynamic cardio-pulmonary data from clinical trials. Recruitment maneuvers (RMs) were executed in 23 individual in-silico patients with varying levels of ARDS severity and initial cardiac output. Multiple clinical variables were recorded and analyzed, including arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain. Results: The maximal recruitment strategy (MRS) maneuver, which implements gradual increments of positive end expiratory pressure (PEEP) followed by PEEP titration, produced improvements in PF ratio, carbon dioxide elimination and dynamic strain in all 23 in-silico patients considered. Reduced cardiac output in the moderate and mild in silico ARDS patients produced significant drops in oxygen delivery during the RM (average decrease of 423 ml min-1 and 526 ml min-1, respectively). In the in-silico patients with severe ARDS, however, significantly improved gas-exchange led to an average increase of 89 ml min-1 in oxygen delivery during the RM, despite a simultaneous fall in cardiac output of more than 3 l min-1 on average. Post RM increases in oxygen delivery were observed only for the in silico patients with severe ARDS. In patients with high baseline cardiac outputs (>6.5 l min-1), oxygen delivery never fell below 700 ml min-1. Conclusions: Our results support the hypothesis that patients with severe ARDS and significant numbers of alveolar units available for recruitment may benefit more from RMs. Our results also indicate that a higher than normal initial cardiac output may provide protection against the potentially negative effects of high intrathoracic pressures associated with RMs on cardiac function. Results from in silico patients with mild or moderate ARDS suggest that the detrimental effects of RMs on cardiac output can potentially outweigh the positive effects of alveolar recruitment on oxygenation, resulting in overall reductions in tissue oxygen delivery

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky