Association Between Inability to Stand at ICU Discharge and Readmission: A Historical Cohort Study.

OBJECTIVES: The aim of this study was to determine if being unable to stand at ICU discharge was associated with an increased probability of ICU readmission. DESIGN: A multicenter retrospective cohort study was conducted using the Toronto Intensive Care Observational Registry (iCORE) project. SETTING: Nine tertiary academic ICUs in Toronto, Canada, affiliated with the University of Toronto. PATIENTS: All patients admitted to ICUs participating in iCORE from September 2014 to January 2020 were included. Patients had to be mechanically ventilated for more than 4 hours to be included in iCORE. Exclusion criteria were death during the initial ICU stay, transfer to another institution not included in iCORE at ICU discharge, and a short ICU stay defined as less than 2 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure in this study was the inability of the patient to stand at ICU discharge, documented daily in the database within the ICU Mobility Scale. The primary outcome of this study was readmission to the ICU. After adjusting for potential confounders, being unable to stand at ICU discharge was associated with increased odds of readmission (odds ratio, 1.85; 95% CI, 1.31-2.62; p < 0.001). CONCLUSIONS: In patients with an ICU stay of 2 days or more, being unable to stand at ICU discharge is associated with increased odds of readmission to the ICU.

A Canadian survey of perceptions and practices related to ordering of blood tests in the intensive care unit.

PURPOSE: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients. METHODS: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate. RESULTS: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets. CONCLUSION: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests.

RéSUMé: OBJECTIF: La prescription à l'avance de tests sanguins de routine est courante dans les unités de soins intensifs (USI), avec une prise en compte limitée de la probabilité de découverte d'anomalies avant le test. Cette pratique contribue à l'anémie, aux résultats faussement positifs et aux coûts des soins de santé. Nous avons cherché à comprendre les pratiques et les attitudes des intensivistes pour adultes au Canada en ce qui concerne la prescription d'analyses sanguines chez la patientèle gravement malade. MéTHODE: Nous avons mené un sondage transversal à l'échelle nationale au Canada en posant 15 questions évaluant trois domaines (perceptions globales, commande de tests, pratique quotidienne), ainsi que 11 questions démographiques. L'échantillon cible était composé d'un·e intensiviste par unité de soins intensifs pour adultes au Canada. Nous avons résumé les réponses à l'aide de statistiques descriptives et présenté les données sous forme de moyennes avec écarts type (ET) ou de dénombrements avec pourcentages, selon le cas. RéSULTATS: Sur une période de sept mois, 80 médecins sur 131 (61%) ont répondu dans 77 unités de soins intensifs, dont 50% en Ontario. Les répondant·es avaient une expérience clinique moyenne (ET) de 12 (9) ans, et 61% travaillaient dans des centres universitaires. Lorsqu'on leur a demandé ce qu'ils ou elles pensaient de la fréquence à laquelle des tests sanguins inutiles étaient prescrits, 61% ont répondu « parfois ¼ et 23% ont répondu « presque toujours ¼. Cinquante-sept pour cent étaient en faveur de la réalisation d'une formule sanguine complète un jour à l'avance. Seulement 24% des personnes interrogées estimaient que la prescription de tests sanguins à l'avance entraînait fréquemment des changements dans la prise en charge. Les facteurs les plus souvent perçus comme influençant la prescription d'analyses sanguines à l'unité de soins intensifs étaient les préférences des médecins, les habitudes institutionnelles et les ensembles d'ordonnances. CONCLUSION: La plupart des répondant·es à ce sondage ont l'impression que des tests sanguins inutiles sont prescrits aux soins intensifs. L'enquête a permis d'identifier des stratégies possibles pour réduire le nombre de tests sanguins.

Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease (BOLD) study.

Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO)-a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low-income and middle-income countries.

Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS.

INTRODUCTION: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. METHODS: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. RESULTS: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. CONCLUSION: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (ß=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (ß=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income. CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. METHODS: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). RESULTS: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. CONCLUSION: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

Effect of Ward-Based High-Flow Nasal Cannula (HFNC) Oxygen Therapy on Critical Care Utilization During the COVID-19 Pandemic: A Retrospective Cohort Analysis.

BACKGROUND: Hospitals expanded critical care capacity during the COVID-19 pandemic by treating COVID-19 patients with high-flow nasal cannula oxygen therapy (HFNC) in non-traditional settings, including general internal medicine (GIM) wards. The impact of this practice on intensive care unit (ICU) capacity is unknown. OBJECTIVE: To describe how our hospital operationalized the use of HFNC on GIM wards, assess its impact on ICU capacity, and examine the characteristics and outcomes of treated patients. DESIGN: Retrospective cohort study of all patients treated with HFNC on GIM wards at a Canadian tertiary care hospital. PARTICIPANTS: All patients admitted with COVID-19 and treated with HFNC on GIM wards from December 28, 2020, to June 13, 2021, were included. MAIN MEASURES: We combined administrative data on critical care occupancy daily with chart-abstracted data for included patients to establish the total number of patients receiving ICU-level care at our hospital per day. We also collected data on demographics, medical comorbidities, illness severity, COVID-19 treatments, HFNC care processes, and patient outcomes. KEY RESULTS: We treated 124 patients with HFNC on the GIM wards (median age 66 years; 48% female). Patients were treated with HFNC for a median of 5 days (IQR 3 to 8); collectively, they received HFNC for a total of 740 hospital days, 71% of which were on GIM wards. At peak ICU capacity strain (144%), delivering HFNC on GIM wards added 20% to overall ICU capacity by managing up to 14 patients per day. Patients required a median maximal fraction of inspired oxygen of 80% (IQR 60 to 95). There were 18 deaths (15%) and 85 patients (69%) required critical care admission; of those, 40 (47%) required mechanical ventilation. CONCLUSIONS: With appropriate training and resources, treatment of COVID-19 patients with HFNC on GIM wards appears to be a feasible strategy to increase critical care capacity.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Variability of the Human Serum Metabolome over 3 Months in the EXPOsOMICS Personal Exposure Monitoring Study.

Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and untargeted metabolomics are increasingly used in exposome studies to study the interactions between nongenetic factors and the blood metabolome. To reliably and efficiently link detected compounds to exposures and health phenotypes in such studies, it is important to understand the variability in metabolome measures. We assessed the within- and between-subject variability of untargeted LC-HRMS measurements in 298 nonfasting human serum samples collected on two occasions from 157 subjects. Samples were collected ca. 107 (IQR: 34) days apart as part of the multicenter EXPOsOMICS Personal Exposure Monitoring study. In total, 4294 metabolic features were detected, and 184 unique compounds could be identified with high confidence. The median intraclass correlation coefficient (ICC) across all metabolic features was 0.51 (IQR: 0.29) and 0.64 (IQR: 0.25) for the 184 uniquely identified compounds. For this group, the median ICC marginally changed (0.63) when we included common confounders (age, sex, and body mass index) in the regression model. When grouping compounds by compound class, the ICC was largest among glycerophospholipids (median ICC 0.70) and steroids (0.67), and lowest for amino acids (0.61) and the O-acylcarnitine class (0.44). ICCs varied substantially within chemical classes. Our results suggest that the metabolome as measured with untargeted LC-HRMS is fairly stable (ICC > 0.5) over 100 days for more than half of the features monitored in our study, to reflect average levels across this time period. Variance across the metabolome will result in differential measurement error across the metabolome, which needs to be considered in the interpretation of metabolome results.

Spirometry parameters used to define small airways obstruction in population-based studies: systematic review.

BACKGROUND: The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results. METHODS: We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO. We systematically reviewed these studies and summarised evidence to determine the most widely used spirometry parameter and criteria for defining SAO. In addition, we extracted prevalence estimates and identified associated risk factors. To estimate a pooled prevalence of SAO, we conducted a meta-analysis and explored heterogeneity across studies using meta regression. RESULTS: Twenty-five studies used spirometry to identify SAO. The most widely utilised parameter (15 studies) was FEF25-75, either alone or in combination with other measurements. Ten studies provided criteria for the definition of SAO, of which percent predicted cut-offs were the most common (5 studies). However, there was no agreement on which cut-off value to use. Prevalence of SAO ranged from 7.5% to 45.9%. As a result of high heterogeneity across studies (I2 = 99.3%), explained by choice of spirometry parameter and WHO region, we do not present a pooled prevalence estimate. CONCLUSION: There is a lack of consensus regarding the best spirometry parameter or defining criteria for identification of SAO. The value of continuing to measure SAO using spirometry is unclear without further research using large longitudinal data. PROSPERO registration number CRD42021250206.

Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study.

BACKGROUND: Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. METHODS: A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires. RESULTS: Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37-1.86) for CVD, 1.53 (95% CI 1.40-1.66) for hypertension, and 1.98 (95% CI 1.71-2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33-1.79) for CVD, 1.50 (95% CI 1.39-1.63) for hypertension, and 1.86 (95% CI 1.59-2.17) for diabetes. CONCLUSION: In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.

Farming, pesticide exposure and respiratory health: a cross-sectional study in Thailand.

OBJECTIVE: To assess the association of lung function and respiratory symptoms with farming, particularly pesticide use, in an agricultural province in Thailand. METHODS: We undertook a cross-sectional survey of adults aged 40-65 in Nan province, Thailand, between May and August 2019. We randomly recruited 345 villagers and enriched the sample with 82 government employees. All participants performed post-bronchodilator spirometry and completed a questionnaire covering information on respiratory symptoms, farming activities, pesticide use and known risk factors for respiratory disease. Associations of respiratory outcomes with farming and pesticide exposures were examined by multivariable regression analysis. RESULTS: The response rate was 94%. The prevalence of chronic airflow obstruction among villagers was 5.5%. Villagers had, on average, a lower percent predicted post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) than government employees (98.3% vs 100.3%; p=0.04). There was no evidence of association of lung function with farming activities, the use of specific herbicides (glyphosate and paraquat), insecticides (organophosphates and pyrethroids) or fungicides. The exceptions were poultry farming, associated with chronic cough and an increase of FEV1/FVC, and atrazine, for which duration (p-trend <0.01), intensity (p-trend <0.01) and cumulative hours (p-trend=0.01) of use were all associated with higher FEV1/FVC in an exposure-response manner. Cumulative hours (-280 mL/hour), low duration (-270 mL/year) and intensity (-270 mL/hour/year) of atrazine use were associated with lower FVC. CONCLUSIONS: Chronic airflow obstruction is uncommon among villagers of an agricultural province in Nan, Thailand. Farming and pesticide use are unlikely to be major causes of respiratory problems there.

Impact of using different predictive equations on the prevalence of chronic byssinosis in textile workers in Pakistan.

OBJECTIVE: Byssinosis remains a significant problem among textile workers in low/middle-income countries. Here we share our experience of using different prediction equations for assessing 'chronic' byssinosis according to the standard WHO classification using measurements of forced expiratory volume in 1 s (FEV1). METHODS: We enrolled 1910 workers in a randomised controlled trial of an intervention to improve the health of textile workers in Pakistan. We included in analyses the 1724 (90%) men who performed pre-bronchodilator spirometry tests of acceptable quality. We compared four different equations for deriving lung function percentage predicted values among those with symptoms-based byssinosis: the third US National Health and Nutrition Examination Survey (NHANES-III, with 'North Indian and Pakistani' conversion factor); the Global Lung Function Initiative (GLI, 'other or mixed ethnicities'); a recent equation derived from survey of a western Indian population; and one based on an older and smaller survey of Karachi residents. RESULTS: 58 men (3.4%) had symptoms-based byssinosis according to WHO criteria. Of these, the proportions with a reduced FEV1 (<80% predicted) identified using NHANES and GLI; Indian and Pakistani reference equations were 40%, 41%, 14% and 12%, respectively. Much of this variation was eliminated when we substituted FEV1/forced vital capacity (FVC) ratio (

Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Topical application of melatonin accelerates the maturation of skin wounds and increases collagen deposition in a rat model of diabetes.

AIMS: This study aimed to evaluate the cicatricial potential of melatonin when applied to wounds of diabetic rats. MATHERIALS AND METHODS: The formulation containing melatonin was developed and applied topically to cutaneous wounds of diabetic rats. 48 Wistar rats were used, divided into two groups of 24 diabetic animals each: (i) control group (CG), the animals received topical application of the no-melatonin formulation; (ii) treatment group (TG), the animals received topical application of the melatonin-containing formulation. All animals in each group were treated at four time points: 3, 7, 14, and 21 days. Each subgroup consisted of six animals. RESULTS: The treatment with melatonin improved wound healing by promoting wound closure earlier than the control group evaluated. Also improved a better resolution of the inflammatory phase observed mainly at 7 days, higher tissue maturation and expressive collagen deposition. CONCLUSION: The observed data reveal that the use of melatonin topically could be a promising strategy for the healing of wounds in diabetes. The results of this study elucidate the effects of previously described pathways in which it is proposed that melatonin acts promoting wound healing in diabetes.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

Discordances Between Factors Associated With Withholding Extubation and Extubation Failure After a Successful Spontaneous Breathing Trial.

OBJECTIVES: To identify whether factors associated with withholding extubation in the ICU also predict the risk of extubation failure. DESIGN: Retrospective cohort study. SETTING: Eight medical-surgical ICUs in Toronto. PATIENTS: Adult patients receiving invasive mechanical ventilation, with a first successful spontaneous breathing trial within 28 days of initial ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary end point had three mutually exclusive levels, including: 1) withholding extubation after a successful spontaneous breathing trial, 2) extubation failure within 48 hours, and 3) successful extubation. Among 9,910 patients, 38% of patients were not extubated within 24 hours of their first successful spontaneous breathing trial. A total of 12.9% of patients who were promptly extubated failed within the next 48 hours. Several discrepancies were evident in the association of factors with risk of withholding extubation and extubation failure. Specifically, both age and female sex were associated with withholding extubation (odds ratio, 1.07; 95% CI, 1.03-1.11; and odds ratio, 1.13; 95% CI, 1.02-1.26, respectively) but not a higher risk of failed extubation (odds ratio, 0.99; 95% CI, 0.93-1.05; and odds ratio, 0.93; 95% CI, 0.77-1.11, respectively). Conversely, both acute cardiovascular conditions and intubation for hypoxemic respiratory failure were associated with a higher risk of failed extubation (odds ratio, 1.32; 95% CI, 1.06-1.66; and odds ratio, 1.46; 95% CI, 1.16-1.82, respectively) but not a higher odds of a withheld extubation attempt (odds ratio, 0.79; 95% CI, 0.68-0.91; and odds ratio, 1.07; 95% CI, 0.93-1.23, respectively). CONCLUSIONS: Several factors showed discordance between the decision to withhold extubation and the risk of extubation failure. This discordance may lead to longer duration of mechanical ventilation or higher reintubation rates. Improving the decision-making behind extubation may help to reduce both exposure to invasive mechanical ventilation and extubation failure.

Farnesol: An approach on biofilms and nanotechnology.

Biofilms are important virulence factor in infections caused by microorganisms because of its complex structure, which provide resistance to conventional antimicrobials. Strategies involving the use of molecules capable of inhibiting their formation and also act synergistically with conventional drugs have been explored. Farnesol is a molecule present in essential oils and produced by Candida albicans as a quorum sensing component. This sesquiterpene presents inhibitory properties in the formation of microbial biofilms and synergism with antimicrobials used in clinical practice, and can be exploited even for eradication of biofilms formed by drug-resistant microorganisms. Despite this, farnesol has physical and chemical characteristics that can limit its use, such as high hydrophobicity and volatility. Therefore, nanotechnology may represent an option to improve the efficiency of this molecule in high complex environments such as biofilms. Nanostructured systems present important results in the improvement of treatment with different commercial drugs and molecules with therapeutic or preventive potential. The formation of nanoparticles offers advantages such as protection of the incorporated drugs against degradation, improved biodistribution and residence time in specific treatment sites. The combination of farnesol with nanotechnology may be promising for the development of more effective antibiofilm therapies, as it can improve its solubility, reduce volatility, and increase bioavailability. This review summarizes existing data about farnesol, its action on biofilms, and discusses its encapsulation in nanostructured systems. LAY SUMMARY: Farnesol is a natural compound that inhibits the formation of biofilms from different microbial species. The encapsulation of this molecule in nanoparticles is a promising alternative for the development of more effective therapies against biofilms.

Short-term personal and outdoor exposure to ultrafine and fine particulate air pollution in association with blood pressure and lung function in healthy adults.

Studies reporting on associations between short-term exposure to outdoor fine (PM2.5), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM2.5, and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes. We performed three 24-h personal exposure measurements for UFP, PM2.5, and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM2.5 and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM2.5, and soot and health outcomes were tested using linear mixed effect models. The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM2.5 exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per Interquartile range). No consistent associations between PM2.5 or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM2.5 and soot exposures were associated with blood pressure, but not lung function.

Interventions to enable communication for adult patients requiring an artificial airway with or without mechanical ventilator support.

BACKGROUND: Inability to communicate in a manner that can be understood causes extreme distress for people requiring an artificial airway and has implications for care quality and patient safety. Options for aided communication include non-vocal, speech-generating, and voice-enabling aids. OBJECTIVES: To assess effectiveness of communication aids for people requiring an artificial airway (endotracheal or tracheostomy tube), defined as the proportion of people able to: use a non-vocal communication aid to communicate at least one symptom, need, or preference; or use a voice-enabling communication aid to phonate to produce at least one intelligible word. To assess time to communication/phonation; perceptions of communication; communication quality/success; quality of life; psychological distress; length of stay and costs; and adverse events. SEARCH METHODS: We searched the Cochrane Library (Wiley version), MEDLINE (OvidSP), Embase (OvidSP), three other databases, and grey literature from inception to 30 July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs, controlled non-randomised parallel group, and before-after studies evaluating communication aids used in adults with an artificial airway. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two review authors independently performed data extraction and assessment of risk of bias. MAIN RESULTS: We included 11 studies (1931 participants) conducted in intensive care units (ICUs). Eight evaluated non-vocal communication aids and three voice-enabling aids. Usual care was the comparator for all. For six studies, this comprised no aid; usual care in the remaining five studies comprised use of various communication aids. Overall, our confidence in results regarding effectiveness of communication interventions was very low due to imprecision, measurement heterogeneity, inconsistency in results, and most studies at high or unclear risk of bias across multiple domains. No non-vocal aid studies reported our primary outcome. We are uncertain of the effects of early use of a voice-enabling aid compared to routine use on ability to phonate at least one intelligible word (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.18 to 50.08; 2 studies; very low-certainty evidence). Compared to usual care without aids, we are uncertain about effects of a non-vocal aid (communication board) on patient satisfaction (standardised mean difference (SMD) 2.92, 95% CI 1.52 to 4.33; 4 studies; very low-certainty evidence). No studies of non-vocal aids reported quality of life. Low-certainty evidence from two studies suggests early use of a voice-enabling aid may have no effect on quality of life (MD 2.27, 95% CI -7.21 to 11.75). Conceptual differences in measures of psychological distress precluded data pooling; however, intervention arm participants reported less distress suggesting there might be benefit, but our certainty in the evidence is very low. Low-certainty evidence suggest voice-enabling aids have little or no effect on ICU length of stay; we were unable to determine effects of non-vocal aids. Three studies reported different adverse events (physical restraint use, bleeding following tracheostomy, and respiratory parameters indicating respiratory decompensation). Adverse event rates were similar between arms in all three studies. However, uncertainty remains as to any harm associated with communication aids. AUTHORS' CONCLUSIONS: Due to a lack of high-quality studies, imprecision, inconsistency of results, and measurement heterogeneity,  the evidence provides insufficient information to guide practice as to which communication aid is more appropriate and when to use them. Understanding effectiveness of communication aids would benefit from development of a core outcome measurement set.