Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Improvement of precision of numerical calculations using “multiple precision computation” package

In this work, the program so-called “Multiple Precision Computation” (MPC) proposed by Smith in 2003 is introduced and embedded into conventional codes for considerably improving the precision of numerical calculations. The procedure is evaluated for improvement and validated by using the comparison between calculations incorporating MPC and those using regular double-precision declarations and results obtained with well-known software Mathematica, respectively. Several representatively fundamental problems are taken into account for illustration

Study of the correlations between fractional exhaled nitric oxide in exhaled breath and atopic status, blood eosinophils, FCER2 mutation, and asthma control in Vietnamese children

Hanh Nguyen-Thi-Bich,1 Huong Duong-Thi-Ly,2 Vu Thi Thom,2 Nhung Pham-Thi-Hong,2 Long Doan Dinh,2 Huong Le-Thi-Minh,1 Timothy John Craig,3 Sy Duong-Quy3,4 1Department of Immunology, Allergology, and Rheumatology, National Hospital of Pediatrics, Hanoi, Vietnam; 2School of Medicine and Pharmacy, Vietnam National University Hanoi, Vietnam; 3Department of Medicine, Penn State University, Hershey, PA, USA; 4Department of Respiratory Diseases, Lam Dong Medical College, Dalat, Vietnam Introduction: Fractional exhaled nitric oxide (FENO) is a biomarker of airway inflammation in asthma. The measurement of FENO is utilized to assist in the diagnosis and treatment of children with asthma, especially for those treated with inhaled corticosteroids. Objectives: The aims of this study were to evaluate the correlations between FENO and atopic status, blood eosinophil levels, FCER2 mutation, and asthma control in Vietnamese children. Subjects and methods: This was a prospective and descriptive study approved by the local Ethical Board. All children with uncontrolled asthma, seen in the National Hospital of Pediatrics (Hanoi, Vietnam), were included. Exhaled breath FENO, blood eosinophils, skin prick test, total IgE, asthma control test (ACT), and FCER2 gene polymorphism were performed at inclusion. They were followed up at 3 months to evaluate clinical status, FENO levels, and ACT. Results: Forty-two children with uncontrolled asthma with a mean age of 10±3 years (6–16 years) were included. The male/female ratio was 2.5/1. The mean FENO levels were 26±25 ppb. FENO was significantly higher in patients with a positive skin prick test for respiratory allergens (P<0.05). FENO was significantly correlated with blood eosinophil levels (r=0.5217; P=0.0004). Five of the 32 subjects (15.6%) had a mutation of FCER2 gene (rs28364072 SNP). In this group, the levels of FENO were highest (37±10 ppb; P<0.05). The levels of FENO were significantly decreased after 3 months of treatment (17±8 ppb vs 26±25 ppb; P<0.05). Significant correlations between inhaled corticosteroid doses and FENO levels occurred at 1 and 3 months (r=0.415, P=0.007; r=0.396, P=0.010; respectively). There were no correlations between FENO levels, ACT, and daily use of salbutamol. After 3 months, asthma remained uncontrolled in 22.2% of children.Conclusion: The measurement of FENO levels is a useful and feasible tool to predict clinical, biological, and asthma control in Vietnamese children. Keywords: nitric oxide, FENO, eosinophils, asthma, FCER2, IC

Updated estimation of the burden of fungal disease in Vietnam

BACKGROUND: Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015.OBJECTIVES: In this study, we aimed at estimating the incidence and prevalence of serious fungal infections for the year 2020.METHODS: We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional or global sources.RESULTS: We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1030 of pneumocystis pneumonia, 166 of histoplasmosis and 1612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000 and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively.CONCLUSIONS: The number of patients with mycoses in Vietnam is likely underestimated due to a lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.</p

Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account

Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34/L98H most frequent (34/38)

Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2x2 factorial randomized control trial

Background: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. As tetanus toxin acts within the central nervous system, where there is limited penetration of peripherally-administered antitoxin, intrathecal antitoxin administration may improve clinical outcomes compared to intramuscular injection. Methods: In a 2x2 factorial trial, adults with tetanus in a single-centre in Vietnam were randomized first to 3,000 IU human or 21,000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff blind to treatment allocations. The primary outcome was requirement for mechanical ventilation. Secondary outcomes included in-hospital mortality, death and disability at 240-days, duration of intensive care unit (ICU) stay, and adverse events. The study was registered at ClinicalTrials.gov, NCT 02999815 (status: recruitment completed). Findings: 272 adults were randomized. Mechanical ventilation was given to 56/130 (43%) of patients allocated to intrathecal antitoxin and 65/131 (50%) allocated to sham procedure (RR 0.87; 95% CI 0.66 to 1.13; p=0.29). For the intramuscular allocation 48/107 (45%), patients allocated to human antitoxin received mechanical ventilation compared to 48/108 (44%) patients allocated to equine antitoxin (relative risk (RR) 1.01, 95% confidence interval (CI) 0.75, 1.36, p=0.95). No clinically-relevant differences in secondary outcomes or adverse events were seen except for shorter length of ICU stay in those treated with intrathecal antitoxin compared to sham. Interpretation: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe but did not provide overall benefit in addition to intramuscular antitoxin administration. Funding: The Wellcome Trust, grant number 107367/Z/15/Z