M. Hossein Tcharmtchi

Coinfection with Staphylococcus aureus increases risk of severe coagulopathy in critically ill children with influenza A (H1N1) virus infection.

Objectives:H1N1 influenza with coinfections has been implicated to have high morbidity and mortality. We hypothesized that critically ill children with 2009 H1N1 and coinfections are at a higher risk of developing disseminated intravascular coagulation. Design:The chart review included demographics, length-of-stay, severity of illness score (Pediatric Risk of Mortality III acute physiology score), clinical laboratories, and outcomes at hospital day 90 data. Patients were classified as having methicillin-sensitive or -resistant Staphylococcus aureus, other, or no coinfections. Setting:Single-center pediatric intensive care unit. Patients:Sixty-six consecutive patients with 2009 H1N1 and influenza A infection. Interventions:None. Main Results:There were 12, 22, and 32 patients with methicillin-sensitive or -resistant Staphylococcus aureus, other, and no coinfections, respectively. Pediatric critical care unit length-of-stay was 11, 10, and 5.5 days (median), and survival at day 90 was 83%, 96%, and 91% in patients with methicillin-sensitive or -resistant Staphylococcus aureus, other, and no coinfections. Patients with methicillin-sensitive or -resistant Staphylococcus aureus coinfections compared to patients with other, and no coinfections had higher Pediatric Risk of Mortality III acute physiology scores (14 [6–25] vs. 7 [2–10], p = .052 and 6 [2.5–10], p = .008; median [interquartile range]), higher D-dimer (16.1 [7.9–19.3] vs. 1.6 [1.1–4], p = .02 and 2.3 [0.8–8.7] µg/mL, p = .05), longer prothrombin time (19.3 [15.4–25.9] vs. 15.3 [14.8–17.1], p = .04 and 16.6 [14.7–20.4] secs, p < .39) at admission, and lower day-7 platelet counts (90K [26–161K] vs. 277K [98–314], p = .03 and 256K [152–339]/mm3, p < .07). Patients with methicillin-sensitive or -resistant Staphylococcus aureus coinfections compared to patients without coinfections were more likely to be sicker with Pediatric Risk of Mortality III acute physiology score >10 vs. <10 (relative risk 2.4; 95% confidence interval 1.2–4.7; p = .035) and have overt disseminated intravascular coagulation (relative risk 4.4; 95% confidence interval 1.3–15.8, p = .025). Conclusions:During the 2009–2010 H1N1 pandemic, pediatric patients with influenza A and methicillin-sensitive or -resistant Staphylococcus aureus coinfections were sicker and more likely to develop disseminated intravascular coagulation than patients with other or no coinfections.

Impact of resident duty hour limits on safety in the intensive care unit: a national survey of pediatric and neonatal intensivists.

Objective: Resident duty-hour regulations potentially shift the workload from resident to attending physicians. We sought to understand how current or future regulatory changes might impact safety in academic pediatric and neonatal intensive care units. Design: Web-based survey. Setting: U.S. academic pediatric and neonatal intensive care units. Subjects: Attending pediatric and neonatal intensivists. Interventions: We evaluated perceptions on four intensive care unit safety-related risk measures potentially affected by current duty-hour regulations: 1) attending physician and resident fatigue; 2) attending physician workload; 3) errors (self-reported rates by attending physicians or perceived resident error rates); and 4) safety culture. We also evaluated perceptions of how these risks would change with further duty-hour restrictions. Measurements and Main Results: We administered our survey between February and April 2010 to 688 eligible physicians, of whom 360 (52.3%) responded. Most believed that resident error rates were unchanged or worse (91.9%) and safety culture was unchanged or worse (84.4%) with current duty-hour regulations. Of respondents, 61.9% believed their own work-hours providing direct patient care increased and 55.8% believed they were more fatigued while providing direct patient care. Most (85.3%) perceived no increase in their own error rates currently, but in the scenario of further reduction in resident duty-hours, over half (53.3%) believed that safety culture would worsen and a significant proportion (40.3%) believed that their own error rates would increase. Conclusions: Pediatric intensivists do not perceive improved patient safety from current resident duty-hour restrictions. Policies to further restrict resident duty-hours should consider unintended consequences of worsening certain aspects of intensive care unit safety.

Neonatal neutrophil interaction with P-selectin: contribution of P-selectin glycoprotein ligand-1 and sialic acid.

Previously we had determined that neonatal neutrophils had decreased interaction with monolayers expressing P‐selectin compared to adult cells. In this study we examined the function of neonatal P‐selectin glycoprotein ligand‐1 (PSGL‐1). A rabbit polyclonal antibody directed against the amino terminus of human PSGL‐1 was produced and purified (3RB‐PSGL‐1). Neonatal neutrophils expressed the epitope recognized by 3RB‐PSGL‐1 and expression was decreased compared with adult neutrophils (20%, P < 0.05). In addition neonatal neutrophils had decreased interaction with Chinese hamster ovary (CHO)‐P‐selectin under both shear conditions and static adhesion (P < 0.05). Treatment of both neonatal and adult neutrophils with 3RB‐PSGL‐1 similarly inhibited the interaction with P‐selectin monolayers under shear conditions, effects similar to treatment with O‐sialoglycoprotein endopeptidase (OSGE). Neuraminidase treatment of neonatal and adult cells also markedly inhibited the interaction. In a detachment assay marked differences were noted between neonatal and adult cells treated with either 3RB‐PSGL‐1 or neuraminidase. Such treatments had little effect on adult neutrophils until shear stress exceeded 2.8 dynes/cm2. Treated neonatal neutrophils were exquisitely sensitive to shear stress with a marked decrease in interaction noted at a shear stress as low as 0.6 dynes/cm2. Thus the adhesive mechanisms that remain after treatment with neuraminidase or 3RB‐PSGL‐1 have a relatively low avidity and function less well in neonatal neutrophils compared to adult neutrophils. We speculate that this may account for the less efficient adhesion of neonatal neutrophils to P‐selectin under conditions of flow. J. Leukoc. Biol. 67: 73–80; 2000.

Developing a Tool to Assess Placement of Central Venous Catheters in Pediatrics Patients

BACKGROUND Pediatric critical care medicine requires the acquisition of procedural skills, but to date no criteria exist for assessing trainee competence in central venous catheter (CVC) insertion. OBJECTIVE The goal of this study was to create and demonstrate validity evidence for a direct observation tool for assessing CVC insertion. METHODS Ten experts used the modified Delphi technique to create a 15-item direct observation tool to assess 5 scripted and filmed simulated scenarios of CVC placement. The scenarios were hosted on a dedicated website from March to May 2013, and respondents recruited by e-mail completed the observation tool in real time while watching the scenarios. The goal was to obtain 50 respondents and a total of 250 scenario ratings. RESULTS A total of 49 pediatrics intensive care faculty physicians (6.3% of 780 potential subjects) responded and generated 188 scenario observations. Of these, 150 (79.8%) were recorded from participants who scored 4 or more on the 5 scenarios. The tool correctly identified the expected reference standard in 96.8% of assessments with an interrater agreement kappa (standard error) = 0.94 (0.07) and receiver operating characteristic = 0.97 (95% CI 0.94-0.99). CONCLUSIONS This direct observation assessment tool for central venous catheterization demonstrates excellent performance in identifying the reference standard with a high degree of interrater reliability. These assessments support a validity construct for a pediatric critical care medicine faculty member to assess a provider placing a CVC in a pediatrics patient.

P-SELECTIN (P-SEL) SUPPORT OF NEONATAL NEUTROPHIL (N-PMN) ROLLING: CONTRIBTUION OF NEUTROPHIL P-SELECTIN-GYLCOLIGAND-1 (PSGL-1) |[dagger]| 1351

Marginating PMNs roll along the post-capillary wall prior to stopping and emigrating. This process is mediated in part by P-SEL on the endothelial cell and its ligand, PSGL-1, and requires the presence of sialyl Lewisx and sulfation of one or more tyrosine in N-terminal sequence. We have previously shown that while P-SEL supports adult PMN (A-PMN) rolling, N-PMNs demonstrate an impairment in their ability to roll, and require CD11a/CD18 to resist detachment to increased shear stress (Ped Res 1996;39:302A). We hypothesize that these findings are in part due to differences in neonatal PSGL-1. Here we investigate N-PMN rolling on a confluent cell line expressing human P-SEL under two conditions: 1)attachment under continuous flow at a wall shear stress of 2 dyn/cm2; 2)detachment with step-wise increases in shear stress (0.6-22 dyn/cm2) in the presence of an anti-CD11a MoAb after a two minute stationary contact between PMNs and monolayer. We developed and purified a polyclonal antibody directed against the N-terminal sequence of PSGL-1 (anti-PSGL Ig) containing the putative sulfation sites. Using flow cytometry we could detect no statistical differences in the amount of PSGL-1 on N-PMNs compared to A-PMNs (173±43 and 210±60, respectively). In the attachment assay under continuous flow, anti-PSGL Ig inhibited the number of rolling N-PMNs (109±33) and A-PMNs (125±94) significantly compared to control Ig (N-PMN: 599±108; A-PMN: 651±57, p<0.01). In the detachment assay, anti-PSGL Ig decreased the number of both N-PMNs and A-PMNs at 0.6 dyn/cm2 compared to control Ig by 80% and 60% respectively. With anti-PSGL Ig treatment the number of A-PMN rolling was not statistically different than N-PMNs at each shear stress. However, A-PMN and N-PMN rolling after stationary adhesion could be discriminated by two conditions: 1) the number of control Ig treated N-PMNs significantly decreased at shear stress of 12 and 22 dyn/cm2; 2) with anti-PSGL Ig treatment the number of N-PMNs significantly decreased at the highest shear stress. Adult PMN adhesion was not affected. PSGL-1 supports the rolling of both N- and A-PMNs on P-SEL. Nonetheless, there appear to be functional differences in either neonatal PSGL-1 or other ligands for P-SEL which become manifested at increased shear stress.