The PRECIS-2 tool has good interrater reliability and reasonable discriminant validity

This work was supported by the Chief Scientist Office (CSO) of Scotland grant CZH/4/773, the UK Medical Research Council and the University of Dundee work through the provision of a stipend for KL and from the Health Services Research Unit at the University of Aberdeen, which is core funded by the CSO of the Scottish Government Health Directories. We are grateful to all the participants who assisted in this study: F Althabe, A-W Chan, D Altman, D Bratton, E Brass, M Campbell, G Forbes, B Gaglio, R Glasgow, H Hobbelen, S Hopewell, J Krishnan, D Riddle, J Segal, D Steinfort, P Tugwell, SN Van der Veer, VA. Welch, C Witt.Peer reviewedPostprin

Confirmatory Spirometry for Adults Hospitalized with a Diagnosis of Asthma or Chronic Obstructive Pulmonary Disease Exacerbation

Background: Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation. Methods: Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations. Results: There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007). Conclusions: Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients

A Prospective, Controlled Trial of a Protocol-based Strategy to Discontinue Mechanical Ventilation

Weaning protocols can improve outcomes, but their efficacy may vary with patient and staff characteristics. In this prospective, controlled trial, we compared protocol-based weaning to usual, physiciandirected weaning in a closed medical intensive care unit (ICU) with high physician staffing levels and structured, system-based rounds. Adult patients requiring mechanical ventilation for more than 24 hours were assigned to usual care (UC) or protocol weaning based on their hospital identification number. Patients assigned to UC (n ϭ 145) were managed at their physicians' discretion. Patients assigned to protocol (n ϭ 154) underwent daily screening and a spontaneous breathing trial by respiratory and nursing staff without physician intervention. There were no significant baseline differences in patient characteristics between groups

Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study.

IntroductionPopulation-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD.Methods and analysisThe Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression.Ethics and disseminationThe institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals

Old lessons learned anew: family-based methods for detecting genes responsible for quantitative and qualitative traits in the Genetic Analysis Workshop 17 mini-exome sequence data

Family-based study designs are again becoming popular as new next-generation sequencing technologies make whole-exome and whole-genome sequencing projects economically and temporally feasible. Here we evaluate the statistical properties of linkage analyses and family-based tests of association for the Genetic Analysis Workshop 17 mini-exome sequence data. Based on our results, the linkage methods using relative pairs or nuclear families had low power, with the best results coming from variance components linkage analysis in nuclear families and Elston-Stewart model-based linkage analysis in extended pedigrees. For family-based tests of association, both ASSOC and ROMP performed well for genes with large effects, but ROMP had the advantage of not requiring parental genotypes in the analysis. For the linkage analyses we conclude that genome-wide significance levels appear to control type I error well but that “suggestive” significance levels do not. Methods that make use of the extended pedigrees are well powered to detect major loci segregating in the families even when there is substantial genetic heterogeneity and the trait is mainly polygenic. However, large numbers of such pedigrees will be necessary to detect all major loci. The family-based tests of association found the same major loci as the linkage analyses and detected low-frequency loci with moderate effect sizes, but control of type I error was not as stringent

The REal Life EVidence AssessmeNt Tool (RELEVANT):development of a novel quality assurance asset to rate observational comparative effectiveness research studies

Background Evidence from observational comparative effectiveness research (CER) is ranked below that from randomized controlled trials in traditional evidence hierarchies. However, asthma observational CER studies represent an important complementary evidence source answering different research questions and are particularly valuable in guiding clinical decision making in real-life patient and practice settings. Tools are required to assist in quality appraisal of observational CER to enable identification of and confidence in high-quality CER evidence to inform guideline development.Methods The REal Life EVidence AssessmeNt Tool (RELEVANT) was developed through a step-wise approach. We conducted an iterative refinement of the tool based on Task Force member expertise and feedback from pilot testing the tool until reaching adequate inter-rater agreement percentages. Two distinct pilots were conductedthe first involving six members of the Respiratory Effectiveness Group (REG) and European Academy of Allergy and Clinical Immunology (EAACI) joint Task Force for quality appraisal of observational asthma CER; the second involving 22 members of REG and EAACI membership. The final tool consists of 21 quality sub-items distributed across seven methodology domains: Background, Design, Measures, Analysis, Results, Discussion/Interpretation, and Conflict of Interest. Eleven of these sub-items are considered critical and named primary sub-items.Results Following the second pilot, RELEVANT showed inter-rater agreement 70% for 94% of all primary and 93% for all secondary sub-items tested across three rater groups. For observational CER to be classified as sufficiently high quality for future guideline consideration, all RELEVANT primary sub-items must be fulfilled. The ten secondary sub-items further qualify the relative strengths and weaknesses of the published CER evidence. RELEVANT could also be applicable to general quality appraisal of observational CER across other medical specialties.ConclusionsRELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation. Developed for a REG-EAACI Task Force quality appraisal of recent asthma CER, RELEVANT also has wider utility to support appraisal of CER literature in general (including pre-publication). It may also assist in manuscript development and in educating relevant stakeholders about key quality markers in observational CER.</p

Assessing Asthma Symptoms in Adolescents and Adults : Qualitative Research Supporting Development of the Asthma Daily Symptom Diary

We thank the members of the US Food and Drug Administration’s Qualification Review Team for their feedback during the development of the ADSD. Source of financial support: Funding for this research was provided by the following PRO Consortium member firms: Actelion; Amgen; AstraZeneca; Boehringer-Ingelheim; Forest Laboratories; Genentech; GlaxoSmithKline; Ironwood Pharmaceuticals; Janssen, Merck, Sharp & Dohme Corp.; Novartis; Pfizer; and Sanofi. In addition, Critical-Path Institute’s PRO Consortium is supported by Critical-Path Public-Private Partnerships (grant no. 1U18FD005320) from the US Food and Drug Administration.Peer reviewedPublisher PD

Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks

Development of Technology of Arsenic Removal from Acidic Waste Solutions in the Form of Arsenic Trisulfide

During the laboratory tests the conditions of arsenic removal from acidic waste solutions of metallurgical enterprise in the form of arsenic trisulfide were determined. The technology based on the reduction of pentavalent arsenic to trivalent state with sodium pyrosulfite solution and following arsenic trisulfide precipitation from acidic solution after treatment with sodium sulfide solution was proposed. The arsenic removal proceeds with mechanical stirring, dosing the calculated amounts of reagents and collecting emissions of hydrogen sulfide. With such treatment, about 95% of arsenic, which was in the initial solution, passes into the precipitate. An enlarged laboratory experiment was carried out and the precipitate with 42.6% of arsenic and 46.9% of sulfur was obtained. The precipitate yield was ∼25.7 kg (dry weight) out of 1 m3 of the initial arsenic containing solution. Keywords: arsenic, arsenic trisulfide, acidic waste solutions, sodium sulfide, sodium pyrosulfit