DNA and Inflammatory Mediators in Bronchoalveolar Lavage Fluid From Children With Acute Inhalational Injuries:

Assess the feasibility of using serial bronchoalveolar lavage fluids (BALF) to characterize the course of cell damage and inflammation in airways of pediatric patients with acute burn or inhalation injury

Combating HIV stigma in low- and middle-income healthcare settings: a scoping review.

IntroductionNearly 40 years into the HIV epidemic, the persistence of HIV stigma is a matter of grave urgency. Discrimination (i.e. enacted stigma) in healthcare settings is particularly problematic as it deprives people of critical healthcare services while also discouraging preventive care seeking by confirming fears of anticipated stigma. We review existing research on the effectiveness of stigma interventions in healthcare settings of low- and middle-income countries (LMIC), where stigma control efforts are often further complicated by heavy HIV burdens, less developed healthcare systems, and the layering of HIV stigma with discrimination towards other marginalized identities. This review describes progress in this field to date and identifies research gaps to guide future directions for research.MethodsWe conducted a scoping review of HIV reduction interventions in LMIC healthcare settings using Embase, Ovid MEDLINE, PsycINFO and Scopus (through March 5, 2020). Information regarding study design, stigma measurement techniques, intervention features and study findings were extracted. We also assessed methodological rigor using the Joanna Briggs Institute checklist for systematic reviews.Results and discussionOur search identified 8766 studies, of which 19 were included in the final analysis. All but one study reported reductions in stigma following the intervention. The studies demonstrated broad regional distribution across LMIC and many employed designs that made use of a control condition. However, these strengths masked key shortcomings including a dearth of research from the lowest income category of LMIC and a lack of interventions to address institutional or structural determinants of stigma. Lastly, despite the fact that most stigma measures were based on existing instruments, only three studies described steps taken to validate or adapt the stigma measures to local settings.ConclusionsCombating healthcare stigma in LMIC demands interventions that can simultaneously address resource constraints, high HIV burden and more severe stigma. Our findings suggest that this will require more objective, reliable and culturally adaptable stigma measures to facilitate meaningful programme evaluation and comparison across studies. All but one study concluded that their interventions were effective in reducing healthcare stigma. Though encouraging, the fact that most studies measured impact using self-reported measures suggests that social desirability may bias results upwards. Homogeneity of study results also hindered our ability to draw substantive conclusions about potential best practices to guide the design of future stigma reduction programmes

DNA and Inflammatory Mediators in Bronchoalveolar Lavage Fluid From Children With Acute Inhalational Injuries

OBJECTIVE: Assess the feasibility of using serial bronchoalveolar lavage fluids (BALF) to characterize the course of cell damage and inflammation in airways of pediatric patients with acute burn or inhalation injury. DESIGN: Prospective, longitudinal descriptive pilot study. SETTING: Burn and Pediatric Intensive Care Units in a tertiary-care medical center. SUBJECTS: Six consecutive intubated, mechanically ventilated pediatric patients with acute inhalational injuries were studied. INTERVENTIONS: Serial BALF specimens from clinically-indicated bronchoscopies were used to measure DNA and cytokine levels. MEASUREMENTS AND MAIN RESULTS: BALF DNA levels for the 6 pediatric burn subjects were highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170,11917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients, and higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF IL-6, IL-8, and TGF-β1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11917ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. CONCLUSIONS: In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burns or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for treatment of acute inhalational injuries

A National Approach to Pediatric Sepsis Surveillance

Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of age-dependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment

Comparison of airway injury score (graded for soot, inflammation, epithelial sloughing and secretions at <72 hr post injury), between patients with the lowest PaO₂/FiO₂ ratios during the first 2 weeks post injury (PaO₂/FiO₂) of <200 (N = 16), and patients with PaO₂/FiO₂ ≥200 (N = 24).

<p>Bars represent mean ± SE. P = 0.11, t-test with Welch's correction for unequal variances.</p

Mediator concentrations in mainstem bronchial washings, averaged for samples obtained during the first 72 hr post injury.

<p>Data are shown as mean ± SE.</p

Comparison of averaged early (<72 hr post injury) IL-12p70 concentrations in mainstem bronchial washings, between the lowest PaO₂/FiO₂ ratios during the first 2 weeks post injury (PaO₂/FiO₂) of <200 (N = 16), and patients with PaO₂/FiO₂ ≥200 (N = 24).

<p>Bars represent mean ± SE.</p