Risk Assessment Matrices for Workplace Hazards: Design for Usability.

In occupational safety and health (OSH), the process of assessing risks of identified hazards considers both the (i) foreseeable events and exposures that can cause harm and (ii) the likelihood or probability of occurrence. To account for both, a table format known as a risk assessment matrix uses rows and columns for ordered categories of the foreseeable severity of harm and likelihood/probability of that occurrence. The cells within the table indicate level of risk. Each category has a text description separate from the matrix as well as a word or phrase heading each row and column. Ideally, these header terms will help the risk assessment team distinguish among the categories. A previous project provided recommended sets of header terms for common matrices based on findings from a survey of undergraduate OSH students. This paper provides background on risk assessment matrices, discusses usability issues, and presents findings from a survey of people with OSH-related experience. The aim of the survey was to confirm or improve the prior recommended sets of terms. The prior recommendations for severity, likelihood, and extent of exposure were confirmed with minor modifications. Improvements in the probability terms were recommended.

Novel neutrophil phenotypic signature in pediatric patients with type 1 diabetes and diabetic ketoacidosis.

Type 1 diabetes (T1D) is a chronic inflammatory condition sometimes complicated by acute diabetic ketoacidosis (DKA). A subset of patients with T1D develop DKA independent of known risk factors. This study tested the hypothesis that circulating polymorphonuclear leukocytes (PMN) from children with T1D and DKA would exhibit a primed phenotype and that the signature would be unique in patients predisposed to have DKA. Using a prospective cohort study design, neutrophil phenotype was assessed in 30 patients with T1D seen in endocrinology clinic for routine care, 30 patients with acute DKA, and 36 healthy donors. Circulating PMN from patients with DKA display a primed phenotype with increased basal cell-surface CD11b, L-selectin shedding, and enhanced fMLF-elicited reactive oxygen species (ROS) production. Moreover, PMN from T1D patients both with and without DKA lack the capacity to be further primed by incubation with TNF-α, a classic priming stimulus. Primed PMN phenotypic signatures demonstrated are independent of hemoglobin A1c, the premier biological marker for DKA risk, and are consistent with a hyperinflammatory state. A single nucleotide polymorphism in TLR-1 (1805G>T), known to be associated with a hyperinflammatory PMN phenotype, correlated with DKA. This study elucidated a novel phenotypic signature in circulating PMN from children with T1D with and without DKA, and suggests the possibility of a previously unrecognized PMN phenotype with potential clinical implications. Immunophenotype and genotype may be applicable as biomarkers for DKA risk stratification in patients with T1D.

Improving handover competency in preclinical medical and health professions students: establishing the reliability and construct validity of an assessment instrument.

BACKGROUND: As part of the worldwide call to enhance the safety of patient handovers of care, the Association of American Medical Colleges (AAMC) requires that all graduating students "give or receive a patient handover to transition care responsibly" as one of its Core Entrustable Professional Activities (EPAs) for Entering Residency. Students therefore require educational activities that build the necessary teamwork skills to perform structured handovers. To date, a reliable instrument designed to assess teamwork competencies, like structured communication, throughout their preclinical and clinical years does not exist. METHOD: Our team developed an assessment instrument that evaluates both the use of structured communication and two additional teamwork competencies necessary to perform safe patient handovers. This instrument was utilized to assess 192 handovers that were recorded from a sample of 229 preclinical medical students and 25 health professions students who participated in a virtual course on safe patient handovers. Five raters were trained on utilization of the assessment instrument, and consensus was established. Each handover was reviewed independently by two separate raters. RESULTS: The raters achieved 72.22 % agreement across items in the reviewed handovers. Krippendorff's alpha coefficient to assess inter-rater reliability was 0.6245, indicating substantial agreement among the raters. A confirmatory factor analysis (CFA) demonstrated the orthogonal characteristics of items in this instrument with rotated item loadings onto three distinct factors providing preliminary evidence of construct validity. CONCLUSIONS: We present an assessment instrument with substantial reliability and preliminary evidence of construct validity designed to evaluate both use of structured handover format as well as two team competencies necessary for safe patient handovers. Our assessment instrument can be used by educators to evaluate learners' handoff performance as early as their preclinical years and is broadly applicable in the clinical context in which it is utilized. In the journey to optimize safe patient care through improved teamwork during handovers, our instrument achieves a critical step in the process of developing a validated assessment instrument to evaluate learners as they seek to accomplish this goal.

CPR during COVID-19: Use of Expert-driven Rapid Cycle Deliberate Practice to Implement PALS Guidelines.

The American Heart Association (AHA) and other national institutions have endorsed modifications to resuscitation guidelines given the risk of healthcare workers' (HCWs) exposure to COVID-19. Institutional implementation of the COVID-19-focused guidelines requires both proof of feasibility and education of HCW. Pediatric critical care medical directors at The University of Texas Southwestern/Children's Health System of Texas (UTSW/CHST) created a guideline for the resuscitation of COVID-19 patients. The simulation team used in situ simulation to demonstrate guideline feasibility and to create educational materials. METHODS: A UTSW/CHST guideline incorporated COVID-19-focused AHA and other national organizational recommendations to fit the institutional needs. A high-fidelity in situ simulation helped test the feasibility and optimize the UTSW/CHST guideline. We developed a novel form of rapid cycle deliberate practice (RCDP), expert-driven RCDP, in which all simulation participants are experts, to debrief the simulation. RESULTS: In situ simulation with expert-driven RCDP demonstrated guideline feasibility in the resuscitation of a COVID-19 patient while balancing the protection of HCW. Expert-driven RCDP allowed for real-time alterations to the guideline during the simulation event. Video recording and dissemination of the simulation allowed for the education of over 300 staff on the new recommendations. CONCLUSIONS: High-fidelity in situ simulation with expert-driven RCDP created a rapid consensus among expert critical care providers to develop the UTSW/CHST guideline and quickly adopt the new AHA recommendations. This debriefing method helped minimize the risk of HCW exposure by minimizing the number of required participants and time for simulation. We recommend using this distinctive, expert-driven RCDP debriefing method for expeditious testing of COVID-19-focused processes at other institutions.Video Abstract available at: [link forthcoming].

Content Evidence for Validity of Time-to-Task Initiation: A Novel Measure of Learner Competence.

INTRODUCTION: Educators require validated tools to assess learner competency in simulation-based mastery learning. We previously created a simulation to incorporate crisis resource management skills after a needs assessment of our pediatric residency program. We present the development of and content evidence for validity of a task list with time-to-task initiation designed to aid in rapid cycle deliberate practice (RCDP) debriefing and assessment of pediatrics resident learners. METHODS: Five board-certified pediatricians developed the initial task list with 30 tasks. We used the Delphi technique to seek content evidence for validity of the initial task list using 17 board-certified pediatricians at 7 institutions across the United States. After finalizing the task list, we video recorded 3 pediatric experts performing the tasks in a simulation. We then used the Delphi technique to establish and to attain agreement on time-to-task initiation. We calculated Cronbach α coefficient to measure internal consistency of the expert responses. After finalizing the task list, we divided it into 3 stages with 5 separate cycles per stage to direct the educator in performance of RCDP debriefing. RESULTS: The group reached 80% agreement after 2 Delphi rounds with a Cronbach α coefficient of 0.95. The resultant list included 25 tasks. The group subsequently achieved 80% agreement on the time-to-task initiation in 2 Delphi rounds. CONCLUSIONS: We present content evidence for validity of a task list with associated time-to-task initiation for a simulation scenario that incorporates crisis resource management skills and is designed to aid educators in RCDP debriefing. This task list may decrease intereducator inconsistencies in delivery of RCDP for a common pediatric resuscitation scenario.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

OBJECTIVES: The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. DESIGN: Retrospective cohort study. SETTING: Non-cardiac PICU. PATIENTS: Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 µg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 µg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 µg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 µg/dL; p = 0.69). In children with random serum total cortisol less than 18 µg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 µg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). CONCLUSIONS: Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

Cooperative interaction of CTGF and TGF-ß in animal models of fibrotic disease.

BACKGROUND: Connective tissue growth factor (CTGF) is widely thought to promote the development of fibrosis in collaboration with transforming growth factor (TGF)-ß; however, most of the evidence for its involvement comes from correlative and culture-based studies. In this study, the importance of CTGF in tissue fibrosis was directly examined in three murine models of fibrotic disease: a novel model of multiorgan fibrosis induced by repeated intraperitoneal injections of CTGF and TGF-ß2; the unilateral ureteral obstruction (UUO) renal fibrosis model; and an intratracheal bleomycin instillation model of pulmonary fibrosis. RESULTS: Intraperitoneal coadministration of CTGF and TGF-ß2 elicited a profound fibrotic response that was inhibited by the human anti-CTGF antibody FG-3019, as indicated by the ability of FG-3019 to ameliorate the histologic signs of fibrosis and reduce the otherwise increased hydroxyproline:proline (Hyp:Pro) ratios by 25% in kidney (P < 0.05), 30% in liver (P < 0.01) and 63% in lung (P < 0.05). Moreover, administration of either cytokine alone failed to elicit a fibrotic response, thus demonstrating that CTGF is both necessary and sufficient to initiate fibrosis in the presence of TGF-ß and vice versa. In keeping with this requirement for CTGF function in fibrosis, FG-3019 also reduced the renal Hyp:Pro response up to 20% after UUO (P < 0.05). In bleomycin-injured animals, a similar trend towards a FG-3019 treatment effect was observed (38% reduction in total lung Hyp, P = 0.056). Thus, FG-3019 antibody treatment consistently reduced excessive collagen deposition and the pathologic severity of fibrosis in all models. CONCLUSION: Cooperative interactions between CTGF and TGF-ß signaling are required to elicit overt tissue fibrosis. This interdependence and the observed anti-fibrotic effects of FG-3019 indicate that anti-CTGF therapy may provide therapeutic benefit in different forms of fibroproliferative disease.

Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons.

Phosphorylation-dependent modulation of the vanilloid receptor TRPV1 is one of the key mechanisms mediating the hyperalgesic effects of inflammatory mediators, such as prostaglandin E(2) (PGE(2)). However, little is known about the molecular organization of the TRPV1 phosphorylation complex and specifically about scaffolding proteins that position the protein kinase A (PKA) holoenzyme proximal to TRPV1 for effective and selective regulation of the receptor. Here, we demonstrate the critical role of the A-kinase anchoring protein AKAP150 in PKA-dependent modulation of TRPV1 function in adult mouse dorsal root ganglion (DRG) neurons. We found that AKAP150 is expressed in approximately 80% of TRPV1-positive DRG neurons and is coimmunoprecipitated with the capsaicin receptor. In functional studies, PKA stimulation with forskolin markedly reduced desensitization of TRPV1. This effect was blocked by the PKA selective inhibitors KT5720 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylicacid hexyl ester] and H89 (N-[2-(p-bromo-cinnamylamino)-ethyl]-5-isoquinoline-sulfon-amide 2HCl), as well as by the AKAP inhibitory peptide Ht31. Similarly, PGE(2) decreased TRPV1 desensitization in a manner sensitive to the PKA inhibitor KT5720. Both the forskolin and PGE(2) effects were strongly impaired in DRG neurons from knock-in mice that express a mutant AKAP150 lacking the PKA-binding domain (Delta36 mice). Protein kinase C-dependent sensitization of TRPV1 remained intact in Delta36 mice. The PGE(2)/PKA signaling defect in DRG neurons from Delta36 mice was rescued by overexpressing the full-length human ortholog of AKAP150 in these cells. In behavioral testing, PGE(2)-induced thermal hyperalgesia was significantly diminished in Delta36 mice. Together, these data suggest that PKA anchoring by AKAP150 is essential for the enhancement of TRPV1 function by activation of the PGE(2)/PKA signaling pathway.

Prostacyclin derivatives prevent the fibrotic response to TGF-beta by inhibiting the Ras/MEK/ERK pathway.

The SMAD-mediated induction of connective tissue growth factor (CTGF), a fibroproliferative cytokine, by transforming growth factor (TGF)beta is required for the development of sustained fibrosis in humans. Here, we show that in fibroblasts, activation of the Ras/MEK/ERK pathway is required for the SMAD-mediated induction of CTGF by TGFbeta2. We then show that activation of protein kinase A (PKA) in fibroblasts is able to block Ras/MEK/ERK signaling and abolish the fibrotic response. Previously, we found that prostacyclin agonists were able to prevent the induction of CTGF in fibroblasts, and in patients with the fibrotic disease scleroderma. Here, we confirm the in vitro and in vivo antifibrotic effects of prostacyclin derivatives and show that these effects are due to PKA-dependent inhibition of the Ras/MEK/ERK pathway. Ras/MEK/ERK does not directly affect SMAD signaling. The coordinate and varied biological responses to TGFbeta are in part due to the interactions of signaling pathways within target cells. Specific inhibition of fibroblast Ras/MEK/ERK signaling might prevent fibrosis while leaving other physiological effects of TGFbeta unaltered.