Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Development planning and medical policy: a case study of the development of renal treatment in Hong Kong

published_or_final_versionPublic AdministrationMasterMaster of Social Science

Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaoundé, Cameroon.

BACKGROUND:Effects of antiretroviral therapy (ART) on birth outcomes remain controversial. OBJECTIVE:To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW). METHODS:A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant. RESULTS:Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253-535] cells/mm3. Median duration of ART at onset of delivery was 13 [IQR: 10-17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART-group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB. CONCLUSION:cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW

Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory Performance after a Daytime Nap.

The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy

Poxvirus-encoded TNF receptor homolog dampens inflammation and protects from uncontrolled lung pathology during respiratory infection

Ectromelia virus (ECTV) causes mousepox, a surrogate mouse model for smallpox caused by variola virus in humans. Both orthopoxviruses encode tumor necrosis factor receptor (TNFR) homologs or viral TNFR (vTNFR). These homologs are termed cytokine response modifier (Crm) proteins, containing a TNF-binding domain and a chemokine-binding domain called smallpox virus-encoded chemokine receptor (SECRET) domain. ECTV encodes one vTNFR known as CrmD. Infection of ECTV-resistant C57BL/6 mice with a CrmD deletion mutant virus resulted in uniform mortality due to excessive TNF secretion and dysregulated inflammatory cytokine production. CrmD dampened pathology, leukocyte recruitment, and inflammatory cytokine production in lungs including TNF, IL-6, IL-10, and IFN-γ. Blockade of TNF, IL-6, or IL-10R function with monoclonal antibodies reduced lung pathology and provided 60 to 100% protection from otherwise lethal infection. IFN-γ caused lung pathology only when both the TNF-binding and SECRET domains were absent. Presence of the SECRET domain alone induced significantly higher levels of IL-1β, IL-6, and IL-10, likely overcoming any protective effects that might have been afforded by anti–IFN-γ treatment. The use of TNF-deficient mice and those that express only membrane-associated but not secreted TNF revealed that CrmD is critically dependent on host TNF for its function. In vitro, recombinant Crm proteins from different orthopoxviruses bound to membrane-associated TNF and dampened inflammatory gene expression through reverse signaling. CrmD does not affect virus replication; however, it provides the host advantage by enabling survival. Host survival would facilitate virus spread, which would also provide an advantage to the virus.National Health and Medical Research Council of Australia to G.K. and G.C. (Grants 1007980 and 471426). The laboratory of A. Alcamí was funded by the Spanish Ministry of Science and Innovation and European Union (European Regional Development’s Funds

Outcomes of protease inhibitor-based antiretroviral therapy amongst children and associated-factors in Yaoundé, Cameroon.

BACKGROUND:There are limited data on protease inhibitor (PI)-based antiretroviral therapy (ART) amongst children in resource-limited settings, for informing on optimal paediatric regimens. OBJECTIVE:To evaluate therapeutic response to PI-based ART amongst HIV-infected Cameroonian children. METHODS:A retrospective study was conducted amongst children aged 2-18 years receiving a PI-based ART at the Essos Hospital Centre (EHC), Yaounde, Cameroon. Primary end points were therapeutic success on PI-based ART, defined as clinical success (WHO I/II clinical stage), immunological success (CD4 ≥ 500/mm3) and viral suppression (viral load [VL]<1000 copies/ml). Factors associated with therapeutic success were assessed in uni- and multivariate analysis using SPSS software v.2.0; with p<0.05 considered statistically significant. RESULTS:A total of 71 eligible children on PI-based ART were enrolled (42 on initial and 29 on substituted regimens), with a median age of 8 [IQR: 5-12] years and mean duration on ART of 7 years. Following therapeutic responses, all (100%) experienced clinical success, 95.2% experienced immunological success (91.7% on initial and 97.2% on substituted PI/r-based regimens) and 74.7% viral suppression. In univariate analysis, viral suppression was associated with: younger age (p<0.0001), living with parents as opposed to guardians (p = 0.049), and the educational level (p<0.0001). In multivariate analysis, only the age ranges of 10-14 years (OR: 0.22 [0.07-0.73]) and 15-18 years (OR: 0.08 [0.02-0.57]), were determinants of poor viral suppression. CONCLUSION:Among these Cameroonian children, PI-based ART confers favourable clinical and immunological outcomes. The poor rate of viral suppression was mainly attributed to adolescence (10-18 years)

Immuno-virological response and associated factors amongst HIV-1 vertically infected adolescents in Yaoundé-Cameroon.

Limited studies have reported the outcomes of lifelong antiretroviral therapy (ART) amongst adolescents living with HIV (ALWHIV) in resource-limited settings (RLS), thus classifying this population as underserved. We therefore aimed to ascertain the immunological and virological responses, and associated factors amongst Cameroonian ALWHIV.A cross-sectional and observational study was conducted from January through May 2016 at the National Social Insurance Fund Health Centre in Yaoundé-Cameroon. Immunological and virological responses were evaluated using CD4 cell count and viral load respectively, with viral suppression (VS) defined as <50 copies/ml. Adherence was evaluated using self-reported missing doses during the past 14 days. Data were analyzed using R v.3.3.0, with p<0.05 considered statistically significant.Of the 145 ALWHIV on ART enrolled in the study, 52% were female, median age [interquartile (IQR)] was 13 [11-16] years, median [IQR] time-on-ART was 7 [5-10] years, 48% were orphans, 92% were on first-line ART and 36% were adherent to ART. Following ART response, 79% (114/145) had CD4 ≥500/mm3, 71.0% (103/145) were on VS of whom 52.4% (76/145) had a sustained VS. Duration of ART was associated with immune restoration (Odd Ratio 3.73 [1.26-12.21]) but not with virological response. Risks of poor adherence were greater in orphans of both parents (p = 0.078).In this urban setting of Cameroon, ALWHIV receiving ART show favorable immunological and virological response in a medium run. For long-term ART success, implementing a close monitoring of adherence and risks of viral rebound would be highly relevant, especially for orphans of both parents

Flowchart of the HIV-positive mothers enrolled in the study, 2008 to 2011, Cameroon.

<p>Flowchart of the HIV-positive mothers enrolled in the study, 2008 to 2011, Cameroon.</p

Bivariate and multivariate analysis between maternal characteristics and premature birth, 2008 to 2011, Cameroon.

<p>Bivariate and multivariate analysis between maternal characteristics and premature birth, 2008 to 2011, Cameroon.</p

Description and comparison of maternal and infants characteristics according to type of antiretroviral exposure during pregnancy, 2008 to 2011, Cameroon.

<p>Description and comparison of maternal and infants characteristics according to type of antiretroviral exposure during pregnancy, 2008 to 2011, Cameroon.</p