Clinical review: Sleep measurement in critical care patients: research and clinical implications

Sleep disturbances are common in critically ill patients and have been characterised by numerous studies using polysomnography. Issues regarding patient populations, monitoring duration and timing (nocturnal versus continuous), as well as practical problems encountered in critical care studies using polysomnography are considered with regard to future interventional studies on sleep. Polysomnography is the gold standard in objectively measuring the quality and quantity of sleep. However, it is difficult to undertake, particularly in patients recovering from critical illness in an acute-care area. Therefore, other objective (actigraphy and bispectral index) and subjective (nurse or patient assessment) methods have been used in other critical care studies. Each of these techniques has its own particular advantages and disadvantages. We use data from an interventional study to compare agreement between four of these alternative techniques in the measurement of nocturnal sleep quantity. Recommendations for further developments in sleep monitoring techniques for research and clinical application are made. Also, methodological problems in studies validating various sleep measurement techniques are explored

Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018.

BACKGROUND: There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics. METHODS: Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007-2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity. RESULTS: After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0-2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually. CONCLUSION: Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden

Effect of external PEEP in patients under controlled mechanical ventilation with an auto-PEEP of 5 cmH2O or higher.

In some patients with auto-positive end-expiratory pressure (auto-PEEP), application of PEEP lower than auto-PEEP maintains a constant total PEEP, therefore reducing the inspiratory threshold load without detrimental cardiovascular or respiratory effects. We refer to these patients as complete PEEP-absorbers. Conversely, adverse effects of PEEP application could occur in patients with auto-PEEP when the total PEEP rises as a consequence. From a pathophysiological perspective, all subjects with flow limitation are expected to be complete PEEP-absorbers, whereas PEEP should increase total PEEP in all other patients. This study aimed to empirically assess the extent to which flow limitation alone explains a complete PEEP-absorber behavior (i.e., absence of further hyperinflation with PEEP), and to identify other factors associated with it.One hundred patients with auto-PEEP of at least 5 cmH2O at zero end-expiratory pressure (ZEEP) during controlled mechanical ventilation were enrolled. Total PEEP (i.e., end-expiratory plateau pressure) was measured both at ZEEP and after applied PEEP equal to 80 % of auto-PEEP measured at ZEEP. All measurements were repeated three times, and the average value was used for analysis.Forty-seven percent of the patients suffered from chronic pulmonary disease and 52 % from acute pulmonary disease; 61 % showed flow limitation at ZEEP, assessed by manual compression of the abdomen. The mean total PEEP was 7 ± 2 cmH2O at ZEEP and 9 ± 2 cmH2O after the application of PEEP (p < 0.001). Thirty-three percent of the patients were complete PEEP-absorbers. Multiple logistic regression was used to predict the behavior of complete PEEP-absorber. The best model included a respiratory rate lower than 20 breaths/min and the presence of flow limitation. The predictive ability of the model was excellent, with an overoptimism-corrected area under the receiver operating characteristics curve of 0.89 (95 % CI 0.80-0.97).Expiratory flow limitation was associated with both high and complete PEEP-absorber behavior, but setting a relatively high respiratory rate on the ventilator can prevent from observing complete PEEP-absorption. Therefore, the effect of PEEP application in patients with auto-PEEP can be accurately predicted at the bedside by measuring the respiratory rate and observing the flow-volume loop during manual compression of the abdomen

SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008-2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming ana priorigenetic model: step 1) a machine learning technique [Gradient Boosting Machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step 2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation

BIMAM—a tool for imputing variables missing across datasets using a Bayesian imputation and analysis model

Motivation Combination of multiple datasets is routine in modern epidemiology. However, studies may have measured different sets of variables; this is often inefficiently dealt with by excluding studies or dropping variables. Multilevel multiple imputation methods to impute these ‘systematically’ missing data (as opposed to ‘sporadically’ missing data within a study) are available, but problems may arise when many random effects are needed to allow for heterogeneity across studies. We show that the Bayesian IMputation and Analysis Model (BIMAM) implemented in our tool works well in this situation. General features BIMAM performs imputation and analysis simultaneously. It imputes both binary and continuous systematically and sporadically missing data, and analyses binary and continuous outcomes. BIMAM is a user-friendly, freely available tool that does not require knowledge of Bayesian methods. BIMAM is an R Shiny application. It is downloadable to a local machine and it automatically installs the required freely available packages (R packages, including R2MultiBUGS and MultiBUGS). Availability BIMAM is available at [www.alecstudy.org/bimam]

Contribution to Research with Regard to the Activities of Ruđer Josip Bošković as a Surveyor and Cartographer

U radu je dan pregled života i rada Ruđera Boškovica, a posebno je istaknut njegov rad kao geodeta i kartografa. Boškovic je dao velik doprinos ondašnjoj geodeziji i izmjeri svojim inovacijama koje je potom prvi upotrijebio za postizanje veće točnosti mjerenja. Zaključio je da ondašnje postojeće karte ne zadovoljavaju potrebe zaključivanja u stručnim ekspertizama. Kao rezultat mjerenja i računanja na putovanjima koja je proveo, izradio je kartu Crkvene države i često davao mišljenje uz kritički osvrt prema drugim ekspertizama i stručnjacima.This paper presents an overview of the work of Ruler Josip Boškovic, emphasising his activities as a cartographer and surveyor. Boškovic made a great contribution to the geodesy and surveying of his time through innovations which he initially used to achieve better accuracy of measurement. He concluded that existing maps did not meet the needs of professional and expert use. As a result of his surveying and travels, he made a Map of the Ecclesiastical State, often appending his opinions and criticisms of other experts