Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study.

BACKGROUND: To counteract the vasoplegia induced by spinal anesthesia (SA) and maintain blood pressure (BP) during cesarean delivery, phenylephrine is currently recommended, but norepinephrine might offer superior preservation of cardiac output. We aimed to compare the hemodynamic effects of phenylephrine and norepinephrine administered by manually adjusted continuous infusion during elective cesarean delivery. METHODS: In this pragmatic, parallel-group, double-blind randomized controlled trial, 124 parturients scheduled for elective cesarean delivery under SA in a tertiary maternity in France, between February 2019 and December 2020, were randomized to receive norepinephrine at a starting rate of 0.05 µg·kg -1 ·min -1 (n = 62) or phenylephrine at a starting rate of 0.5 µg·kg -1 ·min -1 (n = 62). In both groups, the vasopressor infusion rate was then manually adjusted to maintain maternal systolic BP above 90% of the baseline value. The primary outcome, the change in cardiac index (CI) measured by thoracic bioreactance from SA to umbilical cord clamping, was analyzed through repeated measures analysis of variance and post hoc t tests. Secondary outcomes included maternal BP and neonatal outcomes. RESULTS: In the norepinephrine group, cardiac index was maintained between 90% and 100% of baseline from SA to umbilical cord clamping, whereas it was maintained at significantly lower values (81%-88%) in the phenylephrine group ( P = .001). The percentage of elapsed time with a mean maternal BP <65 mm Hg and with systolic BP <80% of the baseline value was higher in the phenylephrine group: 2.9% (7.3) vs 0.5% (1.8) (absolute risk difference [ARD], -2.4%; 95% confidence interval, -4.4 to -0.5; P = .012) and 8.5% (16.6) vs 2.3% (5.2) (ARD, -6.2%; 95% confidence interval, -10.6 to -1.8; P = .006). Excluding parturients with gestational diabetes, severe neonatal hypoglycemia was more common in the phenylephrine group at 19.6% (9/46) vs 4.1% (2/49) ( P = .02). The other neonatal outcomes did not differ significantly between the groups. CONCLUSIONS: When administered by manually adjusted infusion during SA for cesarean delivery, norepinephrine was associated with a higher CI; both infusions were effective for maintaining BP.

Clinical impact of ventilator-associated pneumonia in patients with the acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: The clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS). METHODS: Patients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO2/FiO2 ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes. RESULTS: Among the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO2/FiO2 ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, - 19 [- 20; - 13.5] days) and vasopressor-free days (- 5 [- 9; - 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04-4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11-5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32-4.49, P = 0.80). CONCLUSIONS: VAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.

Developing an HMIS Architecture Framework to Support a National Health Care eHealth Strategy Reform: A Case Study from Morocco.

Abstract-An increasing number of low- and middle-income countries are receiving significant investments to implement health reform strategies featuring a health management information system (HMIS) as a fundamental eHealth intervention. We present the case of Morocco's first step toward the implementation of a national HMIS: the "urbanization" of its health information systems-an information architecture methodology designed to leverage existing capacity while ensuring sustainability of the new HMIS. We report on this process and share lessons learned, applicable to similar countries involved in HMIS interventions, including involving all stakeholders from inception to rollout, encouraging local ownership of the new HMIS, fostering active data usage among users, and leveraging existing personnel rotation policies when developing adoption strategies and facilitating capacity building efforts.

Assessing differential expression in two-color microarrays: a resampling-based empirical Bayes approach.

Microarrays are widely used for examining differential gene expression, identifying single nucleotide polymorphisms, and detecting methylation loci. Multiple testing methods in microarray data analysis aim at controlling both Type I and Type II error rates; however, real microarray data do not always fit their distribution assumptions. Smyth's ubiquitous parametric method, for example, inadequately accommodates violations of normality assumptions, resulting in inflated Type I error rates. The Significance Analysis of Microarrays, another widely used microarray data analysis method, is based on a permutation test and is robust to non-normally distributed data; however, the Significance Analysis of Microarrays method fold change criteria are problematic, and can critically alter the conclusion of a study, as a result of compositional changes of the control data set in the analysis. We propose a novel approach, combining resampling with empirical Bayes methods: the Resampling-based empirical Bayes Methods. This approach not only reduces false discovery rates for non-normally distributed microarray data, but it is also impervious to fold change threshold since no control data set selection is needed. Through simulation studies, sensitivities, specificities, total rejections, and false discovery rates are compared across the Smyth's parametric method, the Significance Analysis of Microarrays, and the Resampling-based empirical Bayes Methods. Differences in false discovery rates controls between each approach are illustrated through a preterm delivery methylation study. The results show that the Resampling-based empirical Bayes Methods offer significantly higher specificity and lower false discovery rates compared to Smyth's parametric method when data are not normally distributed. The Resampling-based empirical Bayes Methods also offers higher statistical power than the Significance Analysis of Microarrays method when the proportion of significantly differentially expressed genes is large for both normally and non-normally distributed data. Finally, the Resampling-based empirical Bayes Methods are generalizable to next generation sequencing RNA-seq data analysis.