Team Physiological Dynamics: A Critical Review.

OBJECTIVE: Review the use of physiological measurement in team settings and propose recommendations to improve the state of the science. BACKGROUND: New sensor and analytical capabilities enable exploration of relationships between team members' physiological dynamics. We conducted a review of physiological measures used in research on teams to understand (1) how these measures are theoretically and operationally related to team constructs and (2) what types of validity evidence exist for physiological measurement in team settings. METHOD: We identified 32 articles that investigated task-performing teams using physiological data. Articles were coded on several dimensions, including team characteristics. Study findings were categorized by relationships tested between team physiological dynamics (TPD) and team inputs, mediators/processes, outputs, or psychometric properties. RESULTS: TPD researchers overwhelmingly measure single physiological systems. Although there is research linking TPD to inputs and outputs, the research on processes is underdeveloped. CONCLUSION: We recommend several theoretical, methodological, and statistical themes to expand the growth of the TPD field. APPLICATION: Physiological measures, once established as reliable indicators of team functioning, might be used to diagnose suboptimal team states and cue interventions to ameliorate these states.

Automated, Web-Based Solution for Bidirectional EHR-Infusion Pump Communication.

Smart Agent is a web-based solution for establishing bidirectional communication between an infusion pump and an electronic health record (EHR). It eliminates the need for clinician double check of medication administration using an infusion pump. Because the clinician already is using the EHR to review patient health information and update status, the addition of the web service would help eliminate the potential for human error when using a manual system. The Smart Agent process encompasses the reading of pertinent patient data from the EHR, determination of a new medication dosage based on an internal protocol, input of the dosage into an infusion pump, confirmation of the medication dosage acceptance at the infusion pump, and recording the medication change back into the EHR. The widespread use of Smart Agent-type algorithms with bidirectional communication capabilities would result in safer, more efficient provision of care, as well as better value.

Cysteinyl leukotrienes as novel host factors facilitating Cryptococcus neoformans penetration into the brain.

Cryptococcus neoformas infection of the central nervous system (CNS) continues to be an important cause of mortality and morbidity, and a major contributing factor is our incomplete knowledge of the pathogenesis of this disease. Here, we provide the first direct evidence that C. neoformans exploits host cysteinyl leukotrienes (LTs), formed via LT biosynthetic pathways involving cytosolic phospholipase A2 α (cPLA2 α) and 5-lipoxygenase (5-LO) and acting via cysteinyl leukotriene type 1 receptor (CysLT1), for penetration of the blood-brain barrier. Gene deletion of cPLA2 α and 5-LO and pharmacological inhibition of cPLA2 α, 5-LO and CysLT1 were effective in preventing C. neoformans penetration of the blood-brain barrier in vitro and in vivo. A CysLT1 antagonist enhanced the efficacy of an anti-fungal agent in therapy of C. neoformans CNS infection in mice. These findings demonstrate that host cysteinyl LTs, dependent on the actions of cPLA2 α and 5-LO, promote C. neoformans penetration of the blood-brain barrier and represent novel targets for elucidating the pathogenesis and therapeutic development of C. neoformans CNS infection.

Inhibition of soluble epoxide hydrolase augments astrocyte release of vascular endothelial growth factor and neuronal recovery after oxygen-glucose deprivation.

Epoxyeicosatrienoic acids (EETs) are synthesized in astrocytes, and inhibitors of soluble epoxide hydrolase (sEH), which hydrolyzes EETs, reduce infarct volume in ischemic stroke. Astrocytes can release protective neurotrophic factors, such as vascular endothelial growth factor (VEGF). We found that addition of sEH inhibitors to rat cultured astrocytes immediately after oxygen-glucose deprivation (OGD) markedly increased VEGF concentration in the medium 48 h later and the effect was blocked by an EET antagonist. The sEH inhibitors increased EET concentrations to levels capable of increasing VEGF. When the sEH inhibitors were removed from the medium at 48 h, the increase in VEGF persisted for an additional 48 h. Neurons exposed to OGD and subsequently to astrocyte medium previously conditioned with OGD plus sEH inhibitors showed increased phosphorylation of their VEGF receptor-2, less TUNEL staining, and increased phosphorylation of Akt, which was blocked by a VEGF receptor-2 antagonist. Our findings indicate that sEH inhibitors, applied to cultured astrocytes after an ischemia-like insult, can increase VEGF secretion. The released VEGF then enhances Akt-enabled cell survival signaling in neurons through activation of VEGF receptor-2 leading to less neuronal cell death. These results suggest a new strategy by which astrocytes can be leveraged to support neuroprotection.

Preventing Harm in the ICU-Building a Culture of Safety and Engaging Patients and Families.

OBJECTIVE: Preventing harm remains a persistent challenge in the ICU despite evidence-based practices known to reduce the prevalence of adverse events. This review seeks to describe the critical role of safety culture and patient and family engagement in successful quality improvement initiatives in the ICU. We review the evidence supporting the impact of safety culture and provide practical guidance for those wishing to implement initiatives aimed at improving safety culture and more effectively integrate patients and families in such efforts. DATA SOURCES: Literature review using PubMed including evaluation of key studies assessing large-scale quality improvement efforts in the ICU, impact of safety culture on patient outcomes, methodologies for quality improvement commonly used in healthcare, and patient and family engagement. Print and web-based resources from leading patient safety organizations were also searched. STUDY SELECTION: Our group completed a review of original studies, review articles, book chapters, and recommendations from leading patient safety organizations. DATA EXTRACTION: Our group determined by consensus which resources would best inform this review. DATA SYNTHESIS: A strong safety culture is associated with reduced adverse events, lower mortality rates, and lower costs. Quality improvement efforts have been shown to be more effective and sustainable when paired with a strong safety culture. Different methodologies exist for quality improvement in the ICU; a thoughtful approach to implementation that engages frontline providers and administrative leadership is essential for success. Efforts to substantively include patients and families in the processes of quality improvement work in the ICU should be expanded. CONCLUSIONS: Efforts to establish a culture of safety and meaningfully engage patients and families should form the foundation for all safety interventions in the ICU. This review describes an approach that integrates components of several proven quality improvement methodologies to enhance safety culture in the ICU and highlights opportunities to include patients and families.

Data-Driven Implementation of Alarm Reduction Interventions in a Cardiovascular Surgical ICU.

BACKGROUND: Alarm fatigue in the ICU setting has been well documented in the literature. The ICU's high-intensity environment requires staff's vigilant attention, and distraction from false and non-actionable alarms pulls staff away from important tasks, creates dissatisfaction, and is a potential patient safety risk if alarms are missed or ignored. This project was intended to improve patient safety by optimizing alarm systems in a cardiovascular surgical intensive care unit (CVSICU). Specific aims were to examine nurses' attitudes toward clinical alarm signals, assess nurses' ability to discriminate audible alarm signals, and implement a bundled set of best practices for monitor alarm reduction without undermining patient safety. METHODS: CVSICU nurses completed an alarm perception survey and participated in alarm discriminability testing. Nurse survey data and baseline monitor alarm data were used to select targeted alarm reduction interventions, which were progressively phased in. Monitor alarm data and cardiorespiratory event data were trended over one year. RESULTS: Five of the most frequent CVSICU monitor alarm types-pulse oximetry, heart rate, systolic and diastolic blood pressure, pulse oximetry sensor, and ventricular tachycardia > 2-were targeted. After implementation, there was a 61% reduction in average alarms per monitored bed and a downward trend in cardiorespiratory events. CONCLUSION: To reduce alarm fatigue it is important to decrease alarm burden through targeted interventions. Methods to reduce non-actionable alarms include adding short delays to allow alarm self-correction, adjusting default alarm threshold limits, providing alarm notification through a secondary device, and teaching staff to optimize alarm settings for individual patients.

Evaluation of Noninvasive Hemoglobin Monitoring in Surgical Critical Care Patients.

OBJECTIVE: To assess the clinical utility of noninvasive hemoglobin monitoring based on pulse cooximetry in the ICU setting. DESIGN AND SETTING: A total of 358 surgical patients from a large urban, academic hospital had the noninvasive hemoglobin monitoring pulse cooximeter placed at admission to the ICU. Core and stat laboratory hemoglobin measurements were taken at the discretion of the clinicians, who were blinded to noninvasive hemoglobin monitoring values. MEASUREMENT AND MAIN RESULTS: There was a poor correlation between the 2,465 time-matched noninvasive hemoglobin monitoring and laboratory hemoglobin measurements (r = 0.29). Bland-Altman analysis showed a positive bias of 1.0 g/dL and limits of agreement of -2.5 to 4.6 g/dL. Accuracy was best at laboratory values of 10.5-14.5 g/dL and least at laboratory values of 6.5-8 g/dL. At hemoglobin values that would ordinarily identify a patient as requiring a transfusion (< 8 g/dL), noninvasive hemoglobin monitoring consistently overestimated the patient's true hemoglobin. When sequential laboratory values declined below 8 g/dL (n = 102) and 7 g/dL (n = 13), the sensitivity and specificity of noninvasive hemoglobin monitoring at identifying these events were 27% and 7%, respectively. At a threshold of 8 g/dL, continuous noninvasive hemoglobin monitoring values reached the threshold before the labs in 45 of 102 instances (44%) and at 7 g/dL, noninvasive hemoglobin monitoring did so in three of 13 instances (23%). Noninvasive hemoglobin monitoring minus laboratory hemoglobin differences showed an intraclass correlation coefficient of 0.47 within individual patients. Longer length of stay and higher All Patient Refined Diagnostic-Related Groups severity of illness were associated with poor noninvasive hemoglobin monitoring accuracy. CONCLUSIONS: Although noninvasive hemoglobin monitoring technology holds promise, it is not yet an acceptable substitute for laboratory hemoglobin measurements. Noninvasive hemoglobin monitoring performs most poorly in the lower hemoglobin ranges that include commonly used transfusion trigger thresholds and is not consistent within individual patients. Further refinement of the signal acquisition and analysis algorithms and clinical reevaluation are needed.

Group IVA phospholipase A2 optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2.

Female mice lacking group IVA phospholipase A(2) (Pla2g4a(-/-)) have a smaller litter size, which is due, in part, to defective implantation. We examined PLA(2)G4A dependence of the processes of ovulation and fertilization. Following induction of ovulation by equine chorionic gonadotropin (eCG)/human CG (hCG) treatment and mating, ovulation and fertilization rates were reduced significantly in Pla2g4a(-/-) mice as compared to wild-type littermates. Human CG triggered robust ovarian prostaglandin (PG) E(2) production in the preovulatory period that was significantly attenuated in Pla2g4a(-/-) mice. Human CG transiently enhanced ovarian expression of PLA(2)G4A and prostaglandin endoperoxide synthase 2 (PTGS2) in wild-type mice. This PTGS2 induction was decreased in Pla2g4a(-/-) mice and also in immature rats treated with the PLA(2)G4A inhibitor, archidonyl trifluoromethyl ketone. A close spatiotemporal association of PLA(2)G4A with PTGS2 was found in mouse and rat preovulatory follicles examined by immunohistochemistry. Less association was observed with 4 other forms of PLA(2). Our data strongly suggest that PLA(2)G4A amplifies hCG induction of PTGS2 and colocalizes with the induced PTGS2, thus contributing to robust PG production required for optimal ovulation and fertilization in rodents.

Group IVA phospholipase A2 regulates testosterone biosynthesis by murine Leydig cells and is required for timely sexual maturation.

In the present paper, we report that PLA2G4A (Group IVA phospholipase A2) is important in the development and function of rodent testes. Interstitial cells of rat testes had high PLA2 (phospholipase A2) activity that was very sensitive to the PLA2G4A-preferential inhibitor AACOCF3 (arachidonyl trifluoromethyl ketone). PLA2G4A protein was expressed primarily in the interstitial cells of wild-type mouse testes throughout maturation. Although Pla2g4a knockout (Pla2g4a-/-) male mice are fertile, their sexual maturation was delayed, as indicated by cauda epididymal sperm count and seminal vesicle development. Delayed function of Pla2g4a-/- mice testes was associated with histological abnormalities including disorganized architecture, swollen appearance and fewer interstitial cells. Basal secretion of testosterone was attenuated significantly and steroidogenic response to hCG (human chorionic gonadotropin) treatment was reduced in Pla2g4a-/- mice compared with their Pla2g4a+/+ littermates during the sexual maturation period. Chemical inhibition of PLA2G4A activity by AACOCF3 or pyrrophenone significantly reduced hCG-stimulated testosterone production in cultured rat interstitial cells. AACOCF3 inhibited forskolin- and cAMP analogue-stimulated testosterone production. These results provide the first evidence that PLA2G4A plays a role in male testes physiology and development. These results may have implications for the potential clinical use of PLA2G4A inhibitors.

Host cytosolic phospholipase A2α contributes to group B Streptococcus penetration of the blood-brain barrier.

Group B Streptococcus (GBS) is the most common bacterium causing neonatal meningitis, and neonatal GBS meningitis continues to be an important cause of mortality and morbidity. Here we provide the first direct evidence that host cytosolic phospholipase A2α (cPLA2α) contributes to type III GBS invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier and penetration into the brain, the key step required for the development of GBS meningitis. This was shown by our demonstration that pharmacological inhibition and gene deletion of cPLA2α significantly decreased GBS invasion of the HBMEC monolayer and penetration into the brain. cPLA2α releases arachidonic acid from membrane phospholipids, and we showed that the contribution of cPLA2α to GBS invasion of HBMEC involved lipoxygenated metabolites of arachidonic acid, cysteinyl leukotrienes (LTs). In addition, type III GBS invasion of the HBMEC monolayer involves protein kinase Cα (PKCα), as shown by time-dependent PKCα activation in response to GBS as well as decreased GBS invasion in HBMEC expressing dominant-negative PKCα. PKCα activation in response to GBS, however, was abolished by inhibition of cPLA2α and cysteinyl LTs, suggesting that cPLA2α and cysteinyl LTs contribute to type III GBS invasion of the HBMEC monolayer via PKCα. These findings demonstrate that specific host factors involving cPLA2α and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKCα.

Smart agent system for insulin infusion protocol management: a simulation-based human factors evaluation study.

OBJECTIVE: To compare the insulin infusion management of critically ill patients by nurses using either a common standard (ie, human completion of insulin infusion protocol steps) or smart agent (SA) system that integrates the electronic health record and infusion pump and automates insulin dose selection. DESIGN: A within subjects design where participants completed 12 simulation scenarios, in 4 blocks of 3 scenarios each. Each block was performed with either the manual standard or the SA system. The initial starting condition was randomised to manual standard or SA and alternated thereafter. SETTING: A simulation-based human factors evaluation conducted at a large academic medical centre. SUBJECTS: Twenty critical care nurses. INTERVENTIONS: A systems engineering intervention, the SA, for insulin infusion management. MEASUREMENTS: The primary study outcomes were error rates and task completion times. Secondary study outcomes were perceived workload, trust in automation and system usability, all measured with previously validated scales. MAIN RESULTS: The SA system produced significantly fewer dose errors compared with manual calculation (17% (n=20) vs 0, p<0.001). Participants were significantly faster, completing the protocol using the SA system (p<0.001). Overall ratings of workload for the SA system were significantly lower than with the manual system (p<0.001). For trust ratings, there was a significant interaction between time (first or second exposure) and the system used, such that after their second exposure to the two systems, participants had significantly more trust in the SA system. Participants rated the usability of the SA system significantly higher than the manual system (p<0.001). CONCLUSIONS: A systems engineering approach jointly optimised safety, efficiency and workload considerations.

Operational Recommendations for Scarce Resource Allocation in a Public Health Crisis.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.

Arachidonic acid metabolism regulates Escherichia coli penetration of the blood-brain barrier.

Escherichia coli K1 meningitis occurs following penetration of the blood-brain barrier, but the underlying mechanisms involved in E. coli penetration of the blood-brain barrier remain incompletely understood. We have previously shown that host cytosolic phospholipase A(2)α (cPLA(2)α) contributes to E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, but the underlying mechanisms remain unclear. cPLA(2)α selectively liberates arachidonic acid from membrane phospholipids. Here, we provide the first direct evidence that host 5-lipoxygenase and lipoxygenase products of arachidonic acid, cysteinyl leukotrienes (LTs), contribute to E. coli K1 invasion of HBMEC and penetration into the brain, and their contributions involve protein kinase C alpha (PKCα). These findings demonstrate that arachidonic acid metabolism regulates E. coli penetration of the blood-brain barrier, and studies are needed to further elucidate the mechanisms involved with metabolic products of arachidonic acid for their contribution to E. coli invasion of the blood-brain barrier.

Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice.

BACKGROUND: The enzyme cytosolic phospholipase A2 alpha (cPLA2alpha) has been implicated in the progression of cerebral injury following ischemia and reperfusion. Previous studies in rodents suggest that cPLA2alpha enhances delayed injury extension and disruption of the blood brain barrier many hours after reperfusion. In this study we investigated the role of cPLA2alpha in early ischemic cerebral injury. METHODS: Middle cerebral artery occlusion (MCAO) was performed on cPLA2alpha+/+ and cPLA2alpha-/- mice for 2 hours followed by 0, 2, or 6 hours of reperfusion. The levels of cPLA2alpha, cyclooxygenase-2, neuronal morphology and reactive oxygen species in the ischemic and contralateral hemispheres were evaluated by light and fluorescent microscopy. PGE2 content was compared between genotypes and hemispheres after MCAO and MCAO and 6 hours reperfusion. Regional cerebral blood flow was measured during MCAO and phosphorylation of relevant MAPKs in brain protein homogenates was measured by Western analysis after 6 hours of reperfusion. RESULTS: Neuronal cPLA2alpha protein increased by 2-fold immediately after MCAO and returned to pre-MCAO levels after 2 hours reperfusion. Neuronal cyclooxygenase-2 induction and PGE2 concentration were greater in cPLA2alpha+/+ compared to cPLA2alpha-/- ischemic cortex. Neuronal swelling in ischemic regions was significantly greater in the cPLA2alpha+/+ than in cPLA2alpha-/- brains (+/+:2.2+/-0.3 fold vs. -/-:1.7+/-0.4 fold increase; P<0.01). The increase in reactive oxygen species following 2 hours of ischemia was also significantly greater in the cPLA2alpha+/+ ischemic core than in cPLA2alpha-/- (+/+:7.12+/-1.2 fold vs. -/-:3.1+/-1.4 fold; P<0.01). After 6 hours of reperfusion ischemic cortex of cPLA2alpha+/+, but not cPLA2alpha-/-, had disruption of neuron morphology and decreased PGE2 content. Phosphorylation of the MAPKs-p38, ERK 1/2, and MEK 1/2-was significantly greater in cPLA2a+/+ than in cPLA2alpha-/- ischemic cortex 6 hours after reperfusion. CONCLUSIONS: These results indicate that cPLA2alpha modulates the earliest molecular and injury responses after cerebral ischemia and have implications for the potential clinical use of cPLA2alpha inhibitors.

Prioritizing Health Care Solutions for Pressure Ulcers Using the Quality Function Deployment Process.

Reducing the incidence and morbidity of pressure ulcers remains a leading national priority in patient safety. However, the optimal strategy for a hospital or health system to address this safety goal is not straightforward given the number and complexity of available solutions. Leveraging techniques from systems engineering, such as the quality function deployment process, may provide a transparent and objective way to address this challenge. A detailed and practical application of quality function deployment is presented that demonstrates the value of applying engineering practices for prioritizing solutions for pressures ulcers specifically and can easily be adapted to other conditions.

Intensive care unit providers more quickly and accurately assess risk of multiple harms using an engineered safety display.

Project Emerge took a systems engineering approach to reduce avoidable harm in the intensive care unit. We developed a socio-technology solution to aggregate and display information relevant to preventable patient harm. We compared providers' efficiency and ability to assess and assimilate data associated with patient-safety practice compliance using the existing electronic health record to Emerge, and evaluated for speed, accuracy, and the number of mouse clicks required. When compared to the standard electronic health record, clinicians were faster (529 ± 210 s vs 1132 ± 344 s), required fewer mouse clicks (42.3 ± 15.3 vs 101.3 ± 33.9), and were more accurate (24.8 ± 2.7 of 28 correct vs 21.2 ± 2.9 of 28 correct) when using Emerge. All results were statistically significant at a p-value < 0.05 using Wilcoxon signed-rank test (n = 18). Emerge has the potential to make clinicians more productive and patients safer by reducing the time and errors when obtaining information to reduce preventable harm.

Intensivist Presence at Code Events Is Associated with High Survival and Increased Documentation Rates.

To better support the highest function of the Johns Hopkins Hospital adult code and rapid response teams, a team leadership role was created for a faculty intensivist, with the intention to integrate improve processes of care delivery, documentation, and decision-making. This article examines process and outcomes associated with the introduction of this role. It demonstrates that an intensivist has the potential to improve patient care while offsetting costs through improved billing capture.

Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia.

Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion. Vehicle or 1 mg/kg TPPU was administered at reperfusion after 90 minutes of focal ischemia and again 24 hours later. Protein expression and activity of sEH increased after reperfusion and activity was decreased by TPPU administration. TPPU decreased infarct volume by 50%, reduced neurologic deficits and improved performance on sensorimotor tasks. Furthermore, TPPU significantly lowered the mRNA expression of interleukin-1beta by 3.5-fold and tumor necrosis factor-alpha by 2.2-fold, increased transforming growth factor-beta mRNA by 1.8-fold, and augmented immunostaining of vascular endothelial growth factor in peri-infarct cortex. Thus, inhibition of sEH at reperfusion significantly reduces infarction and improves sensorimotor function, possibly by suppressing early proinflammatory cytokines and promoting reparative cytokines and growth factors.