An Electronic Health Record Alert for Inpatient Coronavirus Disease 2019 Vaccinations Increases Vaccination Ordering and Uncovers Workflow Inefficiencies.

BACKGROUND: Despite mortality benefits, only 19.9% of U.S. adults are fully vaccinated against the coronavirus disease 2019 (COVID-19). The inpatient setting is an opportune environment to update vaccinations, and inpatient electronic health record (EHR) alerts have been shown to increase vaccination rates. OBJECTIVE: Our objective was to evaluate whether an EHR alert could increase COVID-19 vaccinations in eligible hospitalized adults by prompting providers to order the vaccine. METHODS: This was a quasiexperimental pre-post-interventional design study at an academic and community hospital in the western United States between 1 January, 2021 and 31 October, 2021. Inclusion criteria were unvaccinated hospitalized adults. A soft-stop, interruptive EHR alert prompted providers to order COVID-19 vaccines for those with an expected discharge date within 48 hours and interest in vaccination. The outcome measured was the proportion of all eligible patients for whom vaccines were ordered and administered before and after alert implementation. RESULTS: Vaccine ordering rates increased from 4.0 to 13.0% at the academic hospital (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 3.39-4.74, p < 0.001) and from 7.4 to 11.6% at the community hospital (OR: 1.62, 95% CI: 1.23-2.13, p < 0.001) after alert implementation. Administration increased postalert from 3.6 to 12.7% at the academic hospital (OR: 3.21, 95% CI: 2.70-3.82, p < 0.001) but was unchanged at the community hospital, 6.7 to 6.7% (OR: 0.99, 95% CI: 0.73-1.37, p = 0.994). Further analysis revealed infrequent vaccine availability at the community hospital. CONCLUSION: Vaccine ordering rates improved at both sites after alert implementation. Vaccine administration rates, however, only improved at the academic hospital, likely due in part to vaccine dispensation inefficiency at the community hospital. This study demonstrates the potential impact of complex workflow patterns on new EHR alert success and provides a rationale for subsequent qualitative workflow analysis with alert implementation.

Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (ß-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

A framework for future national pediatric pandemic respiratory disease severity triage: The HHS pediatric COVID-19 data challenge.

Introduction: With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist. Methods: HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions? Results: This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected. Conclusion: This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.

Nonresuscitation Fluid Accumulation and Outcomes After Pediatric Cardiac Surgery: Single-Center Retrospective Cohort Study.

OBJECTIVES: Postoperative patients after congenital cardiac surgery are at high risk of fluid overload (FO), which is known to be associated with poor outcomes. "Fluid creep," or nonresuscitation IV fluid in excess of maintenance requirement, is recognized as a modifiable factor associated with FO in the general PICU population, but has not been studied in congenital cardiac surgery patients. Our objective was to characterize fluid administration after congenital cardiac surgery, quantify fluid creep, and the association between fluid creep, FO, and outcome. DESIGN: Retrospective, observational cohort study. SETTING: Single-center urban mixed-medical and cardiac PICU. PATIENTS: Patients admitted to the PICU after cardiac surgery between January 2010 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,459 postoperative encounters with 1,224 unique patients. Total fluid intake was greater than maintenance requirements on 3,103 of 4,661 patient days (67%), with fluid creep present on 2,624 patient days (56%). Total nonresuscitation intake was higher in patients with FO (defined as cumulative fluid balance 10% above body weight) versus those without. Fluid creep was higher among patients with FO than those without for each of the first 5 days postoperatively. Each 10 mL/kg of fluid creep in the first 24 hours postoperatively was associated with 26% greater odds of developing FO (odds ratio [OR] 1.26; 95% CI, 1.17-1.35) and 17% greater odds of mortality (OR 1.17; 95% CI, 1.05-1.30) after adjusting for risk of mortality based on surgical procedure, age, and day 1 resuscitation volume. Increasing fluid creep in the first 24 hours postoperatively was associated with increased postoperative duration of mechanical ventilation and PICU length of stay. CONCLUSIONS: Fluid creep is present on most postoperative days for pediatric congenital cardiac surgery patients, and fluid creep is associated with higher-risk procedures. Fluid creep early in the postoperative PICU stay is associated with greater odds of FO, mortality, length of mechanical ventilation, and PICU length of stay. Fluid creep may be under-recognized in this population and thus present a modifiable target for intervention.

How Providers Can Optimize Effective and Safe Scribe Use: a Qualitative Study.

BACKGROUND: The use of electronic health records has generated an increase in after-hours and weekend work for providers. To alleviate this situation, the hiring of medical scribes has rapidly increased. Given the lack of scribe industry standards and the wide variance in how providers and scribes work together, it could potentially create new patient safety-related risks. OBJECTIVE: The purpose of this paper was to identify how providers can optimize the effective and safe use of scribes. DESIGN: The research team conducted a secondary analysis of qualitative data where we reanalyzed data from interview transcripts, field notes, and transcribed group discussions generated by four previous projects related to medical scribes. PARTICIPANTS: Purposively selected participants included subject matter experts, providers, informaticians, medical scribes, medical assistants, administrators, social scientists, medical students, and qualitative researchers. APPROACH: The team used NVivo12 to assist with the qualitative analysis. We used a template method followed by word queries to identify an optimum level of scribe utilization. We then used an inductive interpretive theme-generation process. KEY RESULTS: We identified three themes: (1) communication aspects, (2) teamwork efforts, and (3) provider characteristics. Each theme contained specific practices so providers can use scribes safely and in a standardized way. CONCLUSION: We utilized a secondary qualitative data analysis methodology to develop themes describing how providers can optimize their use of scribes. This new knowledge could increase provider efficiency and safety and be incorporated into further and future training tools for them.

Reducing paediatric unintended extubation: A standardized bundle approach.

BACKGROUND: Unintended extubation (UE) is a serious risk associated with endotracheal intubation. In the paediatric population, UE can lead to significant patient harm. On average, each UE increases ICU and hospital length of stay by 5.5 and 6.5 days respectively and costs an additional $36 000. The international benchmark rate of UE for quality analysis cited in the literature is <1 per 100 ventilator days. The United States organization Solutions for Patient Safety (SPS) developed and introduced a bundle to reduce UE with a goal of ≤0.95 per 100 ventilator days. AIM: The aim of this quality improvement project was to determine the baseline rate of UE in a 20-bed mixed medical/surgical PICU in the Pacific Northwest of the United States, implement the SPS bundle for UE prevention, and assess adherence to the bundle, and subsequent rate of UE. STUDY DESIGN: The IHI Model for Improvement Plan-Do-Study-Act (PDSA) was used to guide the development, implementation, and assessment of the SPS UE Bundle standardizing the management of endotracheal tubes. Adherence to the bundle was measured through peer-to-peer audits. Rates of adherence and UE were monitored on line charts. RESULTS: Baseline rate of UE was 1.83 per 100 ventilator days; 23 weeks post implementation of the bundle the rate of UE was reduced to 0.38 UE per 100 ventilator days, F(7, 9) = 4.685, p = 0.027. The mean bundle adherence was 92%. CONCLUSIONS: This quality improvement initiative confirms that high adherence to the SPS UE Bundle may significantly reduce rates of UE in PICU settings. RELEVANCE TO CLINICAL PRACTISE: Use of the SPS evidence-based discrete UE bundle and high adherence to the bundle can standardize practise and may reduce unintended extubation in the paediatric population.

Translating ethnographic data into knowledge, skills, and attitude statements for medical scribes: a modified Delphi approach.

OBJECTIVE: While the use of medical scribes is rapidly increasing, there are not widely accepted standards for their training and duties. Because they use electronic health record systems to support providers, inadequately trained scribes can increase patient safety related risks. This paper describes the development of desired core knowledge, skills, and attitudes (KSAs) for scribes that provide the curricular framework for standardized scribe training. MATERIALS AND METHODS: A research team used a sequential mixed qualitative methods approach. First, a rapid ethnographic study of scribe activities was performed at 5 varied health care organizations in the United States to gather qualitative data about knowledge, skills, and attitudes. The team's analysis generated preliminary KSA related themes, which were further refined during a consensus conference of subject-matter experts. This was followed by a modified Delphi study to finalize the KSA lists. RESULTS: The team identified 90 descriptions of scribe-related KSAs and subsequently refined, categorized, and prioritized them for training development purposes. Three lists were ultimately defined as: (1) Hands-On Learning KSA list with 47 items amenable to simulation training, (2) Didactic KSA list consisting of 32 items appropriate for didactic lecture teaching, and (3) Prerequisite KSA list consisting of 11 items centered around items scribes should learn prior to being hired or soon after being hired. CONCLUSION: We utilized a sequential mixed qualitative methodology to successfully develop lists of core medical scribe KSAs, which can be incorporated into scribe training programs.

Recognizing Pediatric ARDS: Provider Use of the PALICC Recommendations in a Tertiary Pediatric ICU.

BACKGROUND: For almost 50 years, pediatricians used adult guidelines to diagnose ARDS. In 2015, specific criteria for pediatric ARDS were defined. However, it remains unclear how frequently providers recognize pediatric ARDS and whether recognition affects adherence to consensus recommendations. METHODS: This was a mixed-method, retrospective study of mechanically ventilated pediatric subjects after the release of the pediatric ARDS recommendation statement. Pediatric ARDS cases were identified according to the new criteria. Provider recognition was defined by documentation in the medical record. Pediatric ARDS subjects with and without provider recognition were compared quantitatively according to clinical characteristics, adherence to lung-protective ventilation (LPV), adjunctive therapies, and outcomes. A qualitative document analysis (QDA) was performed to evaluate knowledge and beliefs surrounding the Pediatric Acute Lung Injury Consensus Conference recommendations. RESULTS: Of 1,983 subject encounters, pediatric ARDS was identified in 321 (16%). Provider recognition was present in 97 (30%) cases and occurred more often in subjects who were older, had worse oxygenation deficits, or were bone marrow transplant recipients. Recognition rates increased each studied year. LPV practices did not differ based on provider recognition; however, subjects who received it were more likely to experience permissive hypoxemia and adherence to extrapulmonary recommendations. Ultimately, there was no differences in outcomes between the provider recognition and non-provider recognition groups. Three themes emerged from the QDA: (1) pediatric ARDS presents within a complex, multidimensional context, with potentially competing organ system failures; (2) similar to historical conceptualizations, pediatric ARDS was often considered a visual diagnosis, with measures of oxygenation unreferenced; and (3) emphasis was placed on non-evidence-based interventions, such as pulmonary clearance techniques, rather than on consensus recommendations. CONCLUSIONS: Among mechanically ventilated children, pediatric ARDS was common but recognized in a minority of cases. Potential opportunities, such as an opt-out approach to LPV, may exist for improved dissemination and implementation of recommended best practices.

A qualitative study of provider burnout: do medical scribes hinder or help?

OBJECTIVE: Provider burnout is a crisis in healthcare and leads to medical errors, a decrease in patient satisfaction, and provider turnover. Many feel that the increased use of electronic health records contributes to the rate of burnout. To avoid provider burnout, many organizations are hiring medical scribes. The goal of this study was to identify relevant elements of the provider-scribe relationship (like decreasing documentation burden, extending providers' careers, and preventing retirement) and describe how and to what extent they may influence provider burnout. MATERIALS AND METHODS: Qualitative methods were used to gain a broad view of the complex landscape surrounding scribes. Data were collected in 3 phases between late 2017 and early 2019. Data from 5 site visits, interviews with medical students who had experience as scribes, and discussions at an expert conference were analyzed utilizing an inductive approach. RESULTS: A total of 184 transcripts were analyzed to identify patterns and themes related to provider burnout. Provider burnout leads to increased provider frustration and exhaustion. Providers reported that medical scribes improve provider job satisfaction and reduce burnout because they reduce the documentation burden. Medical scribes extend providers' careers and may prevent early retirement. Unfortunately, medical scribes themselves may experience similar forms of burnout. CONCLUSION: Our data from providers and managers suggest that medical scribes help to reduce provider burnout. However, scribes are not the only solution for reducing documentation burden and there may be potentially better options for preventing burnout. Interestingly, medical scribes sometimes suffer from burnout themselves, despite their temporary roles.

The future of medical scribes documenting in the electronic health record: results of an expert consensus conference.

BACKGROUND: With the use of electronic health records (EHRs) increasing and causing unintended negative consequences, the medical scribe profession has burgeoned, but it has yet to be regulated. The purpose of this study was to describe scribe workflow as well as identify the threats and opportunities for the future of the scribe industry. METHODS: The first phase of the study used ethnographic methods consisting of interviews and observations by a multi-disciplinary team of researchers at five United States sites. In April 2019, a two-day conference of experts representing different stakeholder perspectives was held to discuss the results from site visits and to predict the future of medical scribing. An interpretive content analysis approach was used to discover threats and opportunities for the future of medical scribes. RESULTS: Threats facing the medical scribe industry were related to changes in the documentation model, EHR usability, different payment structures, the need to acquire disparate data during clinical encounters, and workforce-related changes relevant to the scribing model. Simultaneously, opportunities for medical scribing in the future included extension of their role to include workflow analysis, acting as EHR-related subject-matter-experts, and becoming integrated more effectively into the clinical care delivery team. Experts thought that if EHR usability increases, the need for medical scribes might decrease. Additionally, the scribe role could be expanded to allow scribes to document more or take on more informatics-related tasks. The experts also anticipated an increased use of alternative models of scribing, like tele-scribing. CONCLUSION: Threats and opportunities for medical scribing were identified. Many experts thought that if the scribe role could be expanded to allow scribes to document more or take on more informatics activities, it would be beneficial. With COVID-19 continuing to change workflows, it is critical that medical scribes receive standardized training as tele-scribing continues to grow in popularity and new roles for scribes as medical team members are identified.

Safe use of the EHR by medical scribes: a qualitative study.

OBJECTIVE: Hiring medical scribes to document in the electronic health record (EHR) on behalf of providers could pose patient safety risks because scribes often have no clinical training. The aim of this study was to investigate the effect of scribes on patient safety. This included identification of best practices to assure that scribe use of the EHR is not a patient safety risk. MATERIALS AND METHODS: Using a sociotechnical framework and the Rapid Assessment Process, we conducted ethnographic data gathering at 5 purposively selected sites. Data were analyzed using a grounded inductive/hermeneutic approach. RESULTS: We conducted site visits at 12 clinics and emergency departments within 5 organizations in the US between 2017 and 2019. We did 76 interviews with 81 people and spent 80 person-hours observing scribes working with providers. Interviewees believe and observations indicate that scribes decrease patient safety risks. Analysis of the data yielded 12 themes within a 4-dimension sociotechnical framework. Results about the "technical" dimension indicated that the EHR is not considered overly problematic by either scribes or providers. The "environmental" dimension included the changing scribe industry and need for standards. Within the "personal" dimension, themes included the need for provider diligence and training when using scribes. Finally, the "organizational" dimension highlighted the positive effect scribes have on documentation efficiency, quality, and safety. CONCLUSION: Participants perceived risks related to the EHR can be less with scribes. If healthcare organizations and scribe companies follow best practices and if providers as well as scribes receive training, safety can actually improve.

Positive Cumulative Fluid Balance Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome in the Setting of Acute Kidney Injury.

OBJECTIVES: As acute kidney injury and elevated cumulative fluid balance commonly co-occur in pediatric acute respiratory distress syndrome, we aimed to identify risk factors for their development and evaluate their independent relationships with mortality. We hypothesized that acute kidney injury and elevated cumulative fluid balance would be associated with markers of inflammation and that children with elevated cumulative fluid balance and concomitant acute kidney injury would have worse outcomes than other children. DESIGN: Prospective observational study using the pediatric Risk, Injury, Failure, Loss, End-Stage acute kidney injury classification. SETTING: Five academic PICUs. PATIENTS: Two-hundred sixty patients 1 month to 18 years old meeting the Berlin definition of acute respiratory distress syndrome between 2008 and 2014. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PICU mortality was 13% (34/260). Relative to survivors, nonsurvivors had greater cumulative fluid balance on day 3 of acute respiratory distress syndrome (+90.1 mL/kg; interquartile range 26.6-161.7 vs +44.9 mL/kg; interquartile range 10.0-111.3; p = 0.008) and also had higher prevalence of acute kidney injury on day 3 of acute respiratory distress syndrome (50% vs 23%; p = 0.001). On stratified analysis, greater cumulative fluid balance on day 3 of acute respiratory distress syndrome was associated with mortality among patients with concomitant acute kidney injury (+111.5 mL/kg for nonsurvivors; interquartile range 82.6-236.8 vs +58.5 mL/kg for survivors; interquartile range 0.9-176.2; p = 0.041) but not among patients without acute kidney injury (p = 0.308). The presence of acute kidney injury on acute respiratory distress syndrome day 3 was associated with mortality among patients with positive cumulative fluid balance (29.1% vs 10.4% mortality; p = 0.001) but not among patients with even or negative cumulative fluid balance (p = 0.430). Day 1 plasma interleukin-6 levels were associated with the development of day 3 positive cumulative fluid balance, day 3 acute kidney injury, and PICU mortality and the association between elevated day 1 interleukin-6 and PICU mortality was partially mediated by the interval development of day 3 positive cumulative fluid balance and day 3 acute kidney injury (p < 0.001). CONCLUSIONS: In pediatric acute respiratory distress syndrome, elevated cumulative fluid balance on day 3 of acute respiratory distress syndrome is associated with mortality specifically in patients with concomitant acute kidney injury. Plasma interleukin-6 levels are associated with the development of positive cumulative fluid balance and acute kidney injury, suggesting a potential mechanism by which inflammation might predispose to mortality.

Early Plasma Matrix Metalloproteinase Profiles. A Novel Pathway in Pediatric Acute Respiratory Distress Syndrome.

RATIONALE: MMPs (Matrix metalloproteinases) and their endogenous tissue inhibitors may contribute to lung injury through extracellular matrix degradation and modulation of inflammation and fibrosis. OBJECTIVES: To test for an association between MMP pathway proteins and inflammation, endothelial dysfunction, and clinical outcomes. METHODS: We measured MMPs in plasma collected on acute respiratory distress syndrome (ARDS) Day 1 from 235 children at five hospitals between 2008 and 2017. We used latent class analysis to identify patients with distinct MMP profiles and then associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and -18; macrophage inflammatory protein-1α and -1ß; tumor necrosis factor-α and -R2), endothelial injury (angiopoietin-2, von Willebrand factor, soluble thrombomodulin), impaired oxygenation (PaO2/FiO2 [P/F] ratio, oxygenation index), morbidity, and mortality. MEASUREMENTS AND MAIN RESULTS: In geographically distinct derivation and validation cohorts, approximately one-third of patients demonstrated an MMP profile characterized by elevated MMP-1, -2, -3, -7, and -8 and tissue inhibitor of metalloproteinase-1 and -2; and depressed active and total MMP-9. This MMP profile was associated with multiple markers of inflammation, endothelial injury, and impaired oxygenation on Day 1 of ARDS, and conferred fourfold increased odds of mortality or severe morbidity independent of the P/F ratio and other confounders (95% confidence interval, 2.1-7.6; P < 0.001). Logistic regression using both the P/F ratio and MMP profiles was superior to the P/F ratio alone in prognosticating mortality or severe morbidity (area under the receiver operating characteristic curve, 0.75; 95% confidence interval, 0.68-0.82 vs. area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58-0.73; P = 0.009). CONCLUSIONS: Pediatric patients with ARDS have specific plasma MMP profiles associated with inflammation, endothelial injury, morbidity, and mortality. MMPs may play a role in the pathobiology of children with ARDS.

A Sociotechnical Multiple Perspectives Approach to the Use of Medical Scribes: A Deeper Dive into the Scribe-Provider Interaction.

Because of increased electronic health record use, many organizations are hiring medical scribes as a way to alleviate provider burnout and increase clinical efficiency. The providers and scribes have unique relationships and thus, this study's purpose was to examine the scribe-provider interaction/relationship through the perspectives of scribes, providers, and administrators utilizing qualitative research techniques. Participants included 81 clinicians (30 providers, 27 scribes, and 24 administrators) across five sites. Analysis of the scribe-provider interaction data generated six subthemes: characteristics of an ideal scribe, characteristics of a good provider, provider variability, quality of the scribe-provider relationship, negative side of the scribe-provider relationship, and evaluation and supervision of scribes. Future research should focus on additional facets of the scribe-provider relationship including optimal ergonomic considerations to allow for scribes and providers to work together harmoniously.

Gamification and Microlearning for Engagement With Quality Improvement (GAMEQI): A Bundled Digital Intervention for the Prevention of Central Line-Associated Bloodstream Infection.

Central line-associated bloodstream infections (CLABSIs) cause major patient harm, preventable through attention to line care best practice standards. The objective was to determine if a digital self-assessment application (CLABSI App), bundling line care best practices with social gamification and in-context microlearning, could engage nurses in CLABSI prevention. Nurses caring for children with indwelling central venous catheters in 3 high-risk units were eligible to participate. All other units served as controls. The intervention was a 12-month nonrandomized quality improvement study of CLABSI App implementation with interunit competitions. Compared to the preceding year, the intervention group (9886 line days) CLABSI rate decreased by 48% ( P = .03). Controls (7879 line days) did not change significantly. In all, 105 unique intervention group nurses completed 673 self-assessments. Competitions were associated with increased engagement as measured by self-assessments and unique participants. This model could be extended to other health care-associated infections, and more broadly to process improvement within and across health care systems.

Incorporating Inflammation into Mortality Risk in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: In pediatric acute respiratory distress syndrome, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk stratification of poor outcomes. DESIGN: Multicenter prospective observational study. SETTING: We enrolled patients from five academic PICUs between 2008 and 2015. PATIENTS: Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of acute respiratory distress syndrome. INTERVENTIONS: Eight proinflammatory and anti-inflammatory cytokines were measured on acute respiratory distress syndrome day 1 and correlated with mortality, ICU morbidity as measured by survivor Pediatric Logistic Organ Dysfunction score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin. MEASUREMENTS AND MAIN RESULTS: We measured biomarker levels in 194 patients, including 38 acute respiratory distress syndrome nonsurvivors. Interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating oxygenation index, interleukin-8, and tumor necrosis factor-R2 was superior to a model of oxygenation index alone in predicting the composite outcome of mortality or severe morbidity (area under the receiver operating characteristic, 0.77 [0.70-0.83] vs 0.70 [0.62-0.77]; p = 0.042). CONCLUSIONS: In pediatric acute respiratory distress syndrome, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the oxygenation index to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.

A Simple and Robust Bedside Model for Mortality Risk in Pediatric Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Despite declining mortality, acute respiratory distress syndrome is still involved in up to one third of pediatric intensive care deaths. The recently convened Pediatric Acute Lung Injury Consensus Conference has outlined research priorities for the field, which include the need for accurate bedside risk stratification of patients. We aimed to develop a simple yet robust model of mortality risk among pediatric patients with acute respiratory distress syndrome to facilitate the targeted application of high-risk investigational therapies and stratification for enrollment in clinical trials. DESIGN: Prospective, multicenter cohort. SETTING: Five academic PICUs. PATIENTS: Three hundred eight children greater than 1 month and less than or equal to 18 years old, admitted to the ICU, with bilateral infiltrates on chest radiograph and PaO2/FIO2 ratio less than 300 in the clinical absence of left atrial hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty clinical variables were recorded in the following six categories: demographics, medical history, oxygenation, ventilation, radiographic imaging, and multiple organ dysfunction. Data were measured 0-24 and 48-72 hours after acute respiratory distress syndrome onset (day 1 and 3) and examined for associations with hospital mortality. Among 308 enrolled patients, mortality was 17%. Children with a history of cancer and/or hematopoietic stem cell transplant had higher mortality (47% vs 11%; p < 0.001). Oxygenation index, the PaO2/FIO2 ratio, extrapulmonary organ dysfunction, Pediatric Risk of Mortality-3, and positive cumulative fluid balance were each associated with mortality. Using two statistical approaches, we found that a parsimonious model of mortality risk using only oxygenation index and cancer/hematopoietic stem cell transplant history performed as well as other more complex models that required additional variables. CONCLUSIONS: In the PICU, oxygenation index and cancer/hematopoietic stem cell transplant history can be used on acute respiratory distress syndrome day 1 or day 3 to predict hospital mortality without the need for more complex models. These findings may simplify risk assessment for clinical trials, counseling families, and high-risk interventions such as extracorporeal life support.

Challenging the One-Dose-Fits-All Model for Insulin in the Acute Treatment of Pediatric Diabetic Ketoacidosis. A Critical Appraisal of "Low-Dose Versus Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical Trial" by Nallasamy et al (JAMA Pediatrics 2014; 168:999-1005).

OBJECTIVE: To review the findings and discuss the implications of the use of low-dose insulin infusions in pediatric diabetic ketoacidosis compared with standard-dose insulin. DATA SOURCES: A search of the electronic PubMed database was used to perform the clinical query as well as to search for additional relevant literature. STUDY SELECTION AND DATA EXTRACTION: The article by Nallasamy K et al "Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical Trial. JAMA Pediatrics 2014; 17:e477-e480" was selected for critical appraisal and literature review. DATA SYNTHESIS: The authors performed a randomized controlled trial among 50 consecutive patients of 0-12 years old presenting to the emergency department in diabetic ketoacidosis. They found that low-dose (0.05 U/kg/hr) insulin infusion was noninferior to standard-dose (0.1 U/kg/hr) insulin in terms of resolution of hyperglycemia and acidosis with a trend toward lower rates of therapy-related complications in the low-dose group. CONCLUSIONS: Low-dose insulin infusion is noninferior to standard-dose insulin in the treatment of younger pediatric patients with diabetic ketoacidosis and may lead to fewer therapy-related complications.

Biomarkers in Pediatric ARDS: Future Directions.

Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality.

Angiopoietin-2 (Ang-2) is a key mediator of pulmonary vascular permeability. This study tested the association between plasma Ang-2 and mortality in pediatric acute respiratory distress syndrome (ARDS), with stratification for prior hematopoietic cellular transplantation (HCT), given the severe, yet poorly understood, ARDS phenotype of this subgroup. We enrolled 259 children <18 years of age with ARDS; 25 had prior HCT. Plasma Ang-2, von Willebrand Factor antigen (vWF), and vascular endothelial growth factor (VEGF) were measured on ARDS days 1 and 3 and correlated with patient outcomes. Day 1 and day 3 Ang-2 levels were associated with mortality independent of age, sex, race, and P/F ratio [odds ratio (OR) 3.7, 95% CI 1.1-11.5, P = 0.027; and OR 10.2, 95% confidence interval (CI) 2.2-46.5, P = 0.003, for each log10 increase in Ang-2]. vWF was associated with mortality (P = 0.027), but VEGF was not. The association between day 1 Ang-2 and mortality was independent of levels of both vWF and VEGF (OR 3.6, 95% CI 1.1-12.1, P = 0.039, for each log10 increase in Ang-2). 45% of the cohort had a rising Ang-2 between ARDS day 1 and 3 (adjusted mortality OR 3.3, 95% CI 1.2-9.2, P = 0.026). HCT patients with a rising Ang-2 had 70% mortality compared with 13% mortality for those without (OR 16.3, 95% CI 1.3-197.8, P = 0.028). Elevated plasma levels of Ang-2 were associated with mortality independent of vWF and VEGF. A rising Ang-2 between days 1 and 3 was strongly associated with mortality, particularly in pediatric HCT patients, suggesting vulnerability to ongoing endothelial damage.