A Multi-method Exploratory Evaluation of a Service Designed to Improve Medication Safety for Patients with Monitored Dosage Systems Following Hospital Discharge.

BACKGROUND AND OBJECTIVE: Medication safety problems are common post-hospital discharge, and an important global healthcare improvement target. The Transfers of Care Around Medicines (TCAM) service was launched by a National Health Service Trust in the North-West of England, initially focusing on patients with new or existing Monitored Dosage Systems (MDS). The TCAM service is designed to enable the prompt transfer of medication information, with referrals made by hospitals at discharge to a named community pharmacy. This study aimed to explore the utilisation and impact of the TCAM service on medication safety. METHODS: The evaluation included a descriptive analysis of 3033 anonymised patient referrals to 71 community pharmacies over a 1-year period alongside an assessment of the impact of the TCAM service on unintentional medication discrepancies and adverse drug events using a retrospective before-and-after study design. Impact data were collected across 18 general practices by 16 trained clinical pharmacists. RESULTS: Most patient referrals (70%, 2126/3033) were marked as 'completed' by community pharmacies, with 15% of completed referrals delayed beyond 30 days. Screening of 411 patient records by clinical pharmacists yielded no statistically significant difference in unintentional medication discrepancies or adverse drug event rates following TCAM implementation using a multivariable regression analysis (unintentional medication discrepancies adjusted odds ratio = 0.79 [95% confidence interval 0.44-1.44, p = 0.46]; and adverse drug events adjusted odds ratio = 1.19 [95% confidence interval 0.57-2.45, p = 0.63]), although there remained considerable uncertainty. CONCLUSIONS: The TCAM service facilitated a number of community pharmacy services offered to patients with monitored dosage systems; but the impact of the intervention on unintentional medication discrepancies and adverse drug event rates post-hospital discharge for this patient group was uncertain. The results of this exploratory study can inform the ongoing implementation of the TCAM service at hospital discharge and highlight the need to understand service implementation in different contexts, which may influence its impact on medication safety.

Interferon-independent processes constrain measles virus cell-to-cell spread in primary human airway epithelial cells.

Amplification of measles virus (MeV) in human airway epithelia may contribute to its extremely high contagious nature. We use well-differentiated primary cultures of human airway epithelial cells (HAE) to model ex vivo how MeV spreads in human airways. In HAE, MeV spreads cell-to-cell for 3-5 days, but then, infectious center growth is arrested. What stops MeV spread in HAE is not understood, but interferon (IFN) is known to slow MeV spread in other in vitro and in vivo models. Here, we assessed the role of type I and type III IFN in arresting MeV spread in HAE. The addition of IFN-ß or IFN-λ1 to the medium of infected HAE slowed MeV infectious center growth, but when IFN receptor signaling was blocked, infectious center size was not affected. In contrast, blocking type-I IFN receptor signaling enhanced respiratory syncytial virus spread. HAE were also infected with MeV mutants defective for the V protein. The V protein has been demonstrated to interact with both MDA5 and STAT2 to inhibit activation of innate immunity; however, innate immune reactions were unexpectedly muted against the V-defective MeV in HAE. Minimal innate immunity activation was confirmed by deep sequencing, quantitative RT-PCR, and single-cell RNA-seq analyses of the transcription of IFN and IFN-stimulated genes. We conclude that in HAE, IFN-signaling can contribute to slowing infectious center growth; however, IFN-independent processes are most important for limiting cell-to-cell spread. IMPORTANCE Fundamental biological questions remain about the highly contagious measles virus (MeV). MeV amplifies within airway epithelial cells before spreading to the next host. This final step likely contributes to the ability of MeV to spread host-to-host. Over the course of 3-5 days post-infection of airway epithelial cells, MeV spreads directly cell-to-cell and forms infectious centers. Infectious center formation is unique to MeV. In this study, we show that interferon (IFN) signaling does not explain why MeV cell-to-cell spread is ultimately impeded within the cell layer. The ability of MeV to spread cell-to-cell in airway cells without appreciable IFN induction may contribute to its highly contagious nature. This study contributes to the understanding of a significant global health concern by demonstrating that infectious center formation occurs independent of the simplest explanation for limiting viral transmission within a host.

IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia.

BACKGROUND: Chronic pulmonary conditions such as asthma and COPD increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4). METHODS: We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine IL-13, examining how this impacted DPP4 protein levels along with MERS-CoV entry and replication. RESULTS: IL-13 exposure for 3 days led to increased DPP4 protein abundance, while a 21-day treatment increased DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly impacted by IL-13 treatment. CONCLUSIONS: Our results suggest that increased DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13 induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes.

Ethics Education for Nurses: Foundations for an Integrated Curriculum.

BACKGROUND: Complexity in health care environments causes practice problems. Nurses bear responsibility for recognizing, addressing, and preventing ethical problems. Inadequacies in ethics education are partly to blame and contribute to nurse moral distress, attrition, and suboptimal care. Foundational curricula structures adequate for developing nurse moral agency are needed. METHOD: The state of the science of ethics education in nursing was explored in-depth by a subcommittee of the American Nurses Association Ethics Advisory Board. A framework based in nursing goals was designed by nurse ethics experts to address ethics education across levels of curricula and practice. Rest's four-component model of moral behavior structures guidelines. RESULTS: The model captures three facets of nurse moral agency: necessary characteristics, knowledge and skills, and motivation. A case is provided to illustrate its utility. CONCLUSION: This framework provides the means to meet the profession's goal of preparing ethically competent nurses who will exercise moral agency. [J Nurs Educ. 2022;61(3):123-130.].

Work-related and nonwork stressors, PTSD, and psychological distress: Prevalence and attributable burden among Australian police and emergency services employees.

OBJECTIVE: Police and emergency services personnel are at an increased risk of developing mental health issues. We sought to compare patterns of exposure to work-related and nonwork stressors and associations with posttraumatic stress symptoms and psychological distress among police and emergency services employees. METHOD: A total of 14,868 employees from 33 ambulance, fire and rescue, police, and state emergency service agencies around Australia participated in a survey to assess the prevalence of exposure to work-related and nonwork stressors, and the prevalence of mental health conditions. Associations between work and nonwork stressors and mental health problems were estimated using logistic regression models and population attributable risk (PAR) percentages. RESULTS: Traumatic events experienced while working in the police and emergency services sector were the most frequently reported stressor (51%). Stressful events experienced at work in the sector were associated with significantly higher levels of suspected posttraumatic stress symptoms (odds ratio = 4.5, PAR = 65%) and high psychological distress (odds ratio = 2.5, PAR = 40%) compared to stressors experienced away from the sector. CONCLUSIONS: Stressors experienced at work are a risk factor for developing posttraumatic stress symptoms and distress in the sector. Organizations should have comprehensive policies and programs to help prevent the development of mental health problems and to support personnel who develop mental health problems. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mental health and wellbeing of Australian police and emergency services employees.

Answering the Call, the Australian National Police and Emergency Services Mental Health and Wellbeing Study, surveyed 14,868 Australian ambulance, fire and rescue, police, and state emergency service employees. Emergency services personnel had lower rates of mental wellbeing and higher rates of psychological distress and probable PTSD than the general adult population. Overall 30% had low wellbeing, 21% had high and 9% had very high psychological distress, and 10% had probable PTSD. An estimated 5% had suicidal ideation and 2% had a suicide plan in the past 12 months, while 16% binge drink at least weekly. Only one in five of those with very high psychological distress or probable PTSD felt they received adequate support for their condition. These findings highlight the risk of mental health conditions associated with work in the emergency services sector.

The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality on a global scale. The etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiates host cell entry when its spike protein (S) binds to its receptor, angiotensin-converting enzyme 2 (ACE2). In airway epithelia, the spike protein is cleaved by the cell surface protease TMPRSS2, facilitating membrane fusion and entry at the cell surface. This dependence on TMPRSS2 and related proteases suggests that protease inhibitors might limit SARS-CoV-2 infection in the respiratory tract. Here, we tested two serine protease inhibitors, camostat mesylate and nafamostat mesylate, for their ability to inhibit entry of SARS-CoV-2 and that of a second pathogenic coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV). Both camostat and nafamostat reduced infection in primary human airway epithelia and in the Calu-3 2B4 cell line, with nafamostat exhibiting greater potency. We then assessed whether nafamostat was protective against SARS-CoV-2 in vivo using two mouse models. In mice sensitized to SARS-CoV-2 infection by transduction with human ACE2, intranasal nafamostat treatment prior to or shortly after SARS-CoV-2 infection significantly reduced weight loss and lung tissue titers. Similarly, prophylactic intranasal treatment with nafamostat reduced weight loss, viral burden, and mortality in K18-hACE2 transgenic mice. These findings establish nafamostat as a candidate for the prevention or treatment of SARS-CoV-2 infection and disease pathogenesis. IMPORTANCE The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires host cell surface proteases for membrane fusion and entry into airway epithelia. We tested the hypothesis that inhibitors of these proteases, the serine protease inhibitors camostat and nafamostat, block infection by SARS-CoV-2. We found that both camostat and nafamostat reduce infection in human airway epithelia, with nafamostat showing greater potency. We then asked whether nafamostat protects mice against SARS-CoV-2 infection and subsequent COVID-19 lung disease. We performed infections in mice made susceptible to SARS-CoV-2 infection by introducing the human version of ACE2, the SARS-CoV-2 receptor, into their airway epithelia. We observed that pretreating these mice with nafamostat prior to SARS-CoV-2 infection resulted in better outcomes, in the form of less virus-induced weight loss, viral replication, and mortality than that observed in the untreated control mice. These results provide preclinical evidence for the efficacy of nafamostat in treating and/or preventing COVID-19.

Intersubject Variation in ACE2 Protein Expression in Human Airway Epithelia and Its Relationship to Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) initiates entry into airway epithelia by binding its receptor, angiotensin-converting enzyme 2 (ACE2). METHODS: To explore whether interindividual variation in ACE2 abundance contributes to variability in coronavirus disease 2019 (COVID-19) outcomes, we measured ACE2 protein abundance in primary airway epithelial cultures derived from 58 human donor lungs. RESULTS: We found no evidence for sex- or age-dependent differences in ACE2 protein expression. Furthermore, we found that variations in ACE2 abundance had minimal effects on viral replication and induction of the interferon response in airway epithelia infected with SARS-CoV-2. CONCLUSIONS: Our results highlight the relative importance of additional host factors, beyond viral receptor expression, in determining COVID-19 lung disease outcomes.

Sexual orientation and prevalence of mental health difficulties among emergency services employees.

BACKGROUND: LGBQ+ people (Lesbian, Gay, Bisexual, Queer) are at-risk of discrimination and developing mental health issues within general populations. Limited research has assessed their mental health in emergency services occupations, a population which are known to experience poorer mental health. The current study explores the extent to which sexual orientation is associated with higher rates of mental health issues among emergency personnel. METHODS: A stratified random sample of employees from twenty-nine police (N = 8,088), ambulance (N = 3,473), and fire and rescue (N = 2,975) agencies from around Australia participated in a cross-sectional mental health survey (N = 14,536, male = 64.2%, 42.7% over 45 years of age, heterosexual = 92.7%). RESULTS: Employees with a bisexual/pansexual orientation or those who were not sure about their sexual orientation were significantly more likely to report suicidal thoughts, suicide plans, psychological distress, and illicit drug use when compared with heterosexual employees. LGBQ+ employees reported significantly higher rates of lifetime suicide plans and attempts. Specifically, LGBQ+ fire and rescue personnel were roughly six times more likely to report lifetime suicide attempts, and approximately five times more likely to use illicit drugs weekly than their heterosexual colleagues in the fire and rescue sector. Female LGBQ+ personnel were significantly less likely to consume illicit drugs weekly and monthly than male LGBQ+ personnel. CONCLUSIONS: Emergency services personnel are already at-risk of developing pervasive mental health difficulties. It is important that organisations foster positive working environments, particularly for LGBQ+ people who may be more marginalized within organisations.

The paradox of conviction probability: Mock defendants want better deals as risk of conviction increases.

Objective: We examined how probability of conviction affects the maximum plea sentence mock defendants will accept. Hypothesis: Relying on Prospect Theory (Kahneman & Tversky, 1979), we hypothesized that, relative to the expected value of trial, participants would need increasingly better sentences as conviction probability increased and would settle for sentences worse than the expected value of trial when probability was very low. Method: We manipulated conviction probability and potential trial sentence in a series of three between-subjects experiments, with Amazon Mechanical Turk participants assigned to the role of guilty defendants. Participants were majority White (75-82%) and non-Hispanic (92-94%); approximately half (45-51%) identified as female. Study 1 (N = 681) explored the effects of conviction probability (.05, .15, .50, .85, .90) and potential trial sentence (5, 20 years) on the maximum sentence accepted in exchange for a plea. Study 2 (N = 343; X¯age = 37.5) clarified results of Study 1 for the upper range of probabilities for two potential trial sentences (5, 10 years). Study 3 (N = 1,035; X¯age = 37.6) replicated the effects of probability (.05, .10, .15, .50, .85, .90) and potential trial sentence (5, 10 years). Results: Across all three studies, participants wanted increasingly better deals (relative to the expected value of trial) as conviction probability increased. For example, in Study 3, when probability of conviction was 0.90, plea sentences were, on average, 58% better than the expected value of trial; in contrast, when the probability was 0.05, sentences that were nearly 4 times the expected value of trial were acceptable. Conclusions: The most commonly used model of plea decision-making, Shadow of the Trial (SOT) (Mnookin & Kornhauser, 1979), assumes a direct and constant linear relationship between conviction probability and plea sentence. In contrast, our data suggest that the way conviction probability affects mock defendants' appraisals of plea offers may change across the probability spectrum. These results can facilitate development of a more comprehensive model of plea decision-making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Inter-individual Variation in Receptor Expression Influences MERS-CoV Infection and Immune Responses in Airway Epithelia.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory infection in humans, with symptom severity that ranges from asymptomatic to severe pneumonia. Known risk factors for severe MERS include male sex, older age, and the presence of various comorbidities. MERS-CoV gains entry into cells by binding its receptor, dipeptidyl peptidase 4 (DPP4), on the surface of airway epithelia. We hypothesized that expression of this receptor might be an additional determinant of outcomes in different individuals during MERS-CoV infection. To learn more about the role of DPP4 in facilitating MERS-CoV infection and spread, we used ELISA and immunofluorescent staining to characterize DPP4 expression in well-differentiated primary human airway epithelia (HAE). We noted wide inter-individual variation in DPP4 abundance, varying by as much as 1000-fold between HAE donors. This variability appears to influence multiple aspects of MERS-CoV infection and pathogenesis, with greater DPP4 abundance correlating with early, robust virus replication and increased cell sloughing. We also observed increased induction of interferon and some interferon-stimulated genes in response to MERS-CoV infection in epithelia with the greatest DPP4 abundance. Overall, our results indicate that inter-individual differences in DPP4 abundance are one host factor contributing to MERS-CoV replication and host defense responses, and highlight how HAE may serve as a useful model for identifying risk factors associated with heightened susceptibility to serious respiratory pathogens.

Prevalence and predictors of suicidal thoughts and behaviours among Australian police and emergency services employees.

OBJECTIVE: This study presents rates of suicide thoughts and behaviours of police and emergency services personnel around Australia. In addition, it examines personal (i.e. mental health, substance use) and working environment risk and protective factors. METHOD: A stratified random sample of personnel from 33 Australian emergency services organisations were invited to participate in a mental health and wellbeing survey. In total, 14,868 Australian ambulance, fire and rescue, police and state emergency services employees participated and self-reported any suicidal thoughts, plans and/or attempts in the 12 months prior to the survey or at any stage in their life. Logistic regressions assessed factors associated with suicidal thoughts and behaviours. RESULTS: Employees reported notably higher rates of suicidal thoughts and plans than the general Australian adult population, but not attempts. Male, single/divorced, non-heterosexual or longer-serving employees reported higher rates of suicidal thoughts and behaviours across each sector. Perceptions of stigma regarding mental health conditions from others in the workplace, negative impact of work on one's private life and low meaning of work were associated with suicidal thoughts, while bullying significantly differentiated who planned and attempted suicide from those who reported suicidal thoughts only. Higher resilience and social support were associated with lower suicidal thoughts, while intermittent explosive anger and illegal drug use were associated with higher rates of suicidal thoughts. Post-traumatic stress disorder symptoms significantly differentiated who planned suicide, while misuse of prescription drugs and psychological distress differentiated who attempted suicide from those who only reported suicidal thoughts. CONCLUSION: Amid inherently stressful occupations, it is important that workplaces function in a way that supports their personnel. Access to mental health services should be promoted and readily available to personnel.

Experiences of Police and Emergency Services Employees with Workers' Compensation Claims for Mental Health Issues.

Purpose To assess employees' experiences of the workers' compensation claim process for psychological trauma, stress or a mental health condition sustained during the course of work in the police and emergency services sector. Methods 14,868 employees (69.4% male, response rate = 22%) from around Australia participated in Answering the Call: the Beyond Blue National Mental Health and Wellbeing Study of Police and Emergency Services, and were asked questions regarding their workers' compensation experiences for mental health reasons. Results 14% of all employees in police and emergency services organisations had made a workers' compensation claim for mental health reasons. Only 8.2% of employees making a claim had a positive experience (95% CI 6.6-9.8) while 70.3% had a poor experience (95% CI 67.6-73.0). Two-thirds of employees who had made a claim reported that the process was unsupportive and stressful, and over half reported that it had an overall negative impact on their recovery. Employees with poor overall support from their managers and those who perceived negative stigma about mental health in their workplace were more likely to report poor experiences. Conclusions The workers' compensation process is perceived negatively by most police and emergency services employees who have experience with it, and a majority found that it negatively impacted on their recovery. Ways to reform the system to better support employees experiencing significant functional impairments related to mental health issues should be urgently considered.

Large-group, asynchronous, interprofessional simulation: Identifying roles and improving communication with student pharmacists and student nurses.

BACKGROUND: Accreditation standards for health professions training programs continue to require interprofessional education (IPE) activities. Therefore, it is important for faculty collaboration to satisfy these requirements and provide meaningful, mutually beneficial opportunities for students to participate and learn. The medication use process is an integral component of nursing and pharmacy education. When feasible, asynchronous IPE activities that promote medication administration safety and facilitate equal contribution from involved students should be introduced into respective curricula. INTERPROFESSIONAL EDUCATIONAL ACTIVITY: This study employed a retrospective, pretest-posttest design to measure confidence, satisfaction, and communication. The asynchronous simulation included first-year (junior) student nurses (n = 126) and first year (P1) student pharmacists (n = 152). The simulation focused on the role-related knowledge, skills, and attitudes required to accurately call-in, retrieve, and fill a prescription. Details regarding design, setting, participants, facilitation of the simulation, and barriers overcome are described. DISCUSSION: Descriptive statistics are provided for satisfaction and confidence, with changes in confidence analyzed using binomial probability confidence intervals. This IPE simulation was an efficient and effective model for introducing students to the specific activity of communicating prescriptions among key members of the interprofessional team. IMPLICATIONS: Students reported increased confidence and satisfaction with this activity, which supports future iterations of the asynchronous simulation.

Airway Surface Liquid Has Innate Antiviral Activity That Is Reduced in Cystic Fibrosis.

Although chronic bacterial infections and inflammation are associated with progressive lung disease in patients with cystic fibrosis (CF), much less is known regarding the contributions of respiratory viral infections to this process. Clinical studies suggest that antiviral host defenses may be compromised in individuals with CF, and CF airway epithelia exhibit impaired antiviral responses in vitro. Here, we used the CF pig model to test the hypothesis that the antiviral activity of respiratory secretions is reduced in CF. We developed an in vitro assay to measure the innate antiviral activity present in airway surface liquid (ASL) from CF and non-CF pigs. We found that tracheal and nasal ASL from newborn non-CF pigs exhibited dose-dependent inhibitory activity against several enveloped and encapsidated viruses, including Sendai virus, respiratory syncytial virus, influenza A, and adenovirus. Importantly, we found that the anti-Sendai virus activity of nasal ASL from newborn CF pigs was significantly diminished relative to non-CF littermate controls. This diminution of extracellular antiviral defenses appears to be driven, at least in part, by the differences in pH between CF and non-CF ASL. These data highlight the novel antiviral properties of native airway secretions and suggest the possibility that defects in extracellular antiviral defenses contribute to CF pathogenesis.

A Longitudinal and Sustainability Assessment of Pediatric Interfacility Transport Handover Standardization.

INTRODUCTION: Standardization of interfacility transport handover is associated with improved shared mental model development, efficiency, and teaming. We sought to build upon previously published data by evaluating 1-year follow-up data, assessing face-validity, and describing sustainability. METHODS: We performed a pre-post, retrospective cohort study in a stand-alone, tertiary, pediatric referral center for children 0-18 years of age transported to our pediatric intensive care unit, neonatal intensive care unit, or emergency department from October 2016 to November 2017. Handover was standardized using multidisciplinary checklists, didactics, and simulation. Data were collected for three 8-week periods (preintervention, postintervention, and 1-year follow-up). Outcomes included shared mental model index (shared mental model congruence expressed as an index, percent congruence regarding healthcare data), teaming data (efficiency, attendance, interruptions, interdependence), and face validity (5-point, Likert scale questionnaires). Statistics included 1-way analysis of variance, Kruskal-Wallis, chi-square, and descriptive statistics. RESULTS: One hundred forty-eight handovers (50 preintervention, 50 postintervention, and 48 at 1-year) were observed in the emergency department (41%), pediatric intensive care unit (45%), and neonatal intensive care unit (14%). No differences were noted in demographics, diagnoses, PIM-3-ROM, length of stay, mortality, ventilation, or vasoactive use. Sustained improvements were observed in shared mental model congruence expressed as an index (38% to 82%), physician attendance (76% to 92%), punctuality (91.5% to 97.5%), interruptions (40% to 10%), provision of anticipatory guidance (42% to 85%), and handover summarization (42% to 85%, all P < 0.01). Efficiency was maintained throughout (mean duration 4.5 ± 2.1 minutes). Face validity data revealed handover satisfaction, effective communication, and perceived professionalism. CONCLUSIONS: Enhancements in teaming, shared mental model development, and face validity were achieved and sustained 1-year following handover standardization with only minimal reeducation during the study period.

Standardization of Pediatric Interfacility Transport Handover: Measuring the Development of a Shared Mental Model.

OBJECTIVES: To determine if standardization of pediatric interfacility transport handover is associated with the development of a prototypical shared mental model between healthcare providers. DESIGN: A single center, prepost, retrospective cohort study. SETTINGS: A 259-bed, tertiary care, pediatric referral center. PATIENTS: Children 0 to 18 years old transferred to our critical care units or emergency center from October 2016 to February 2017. INTERVENTIONS: Standardization of interfacility handover using a multidisciplinary checklist, didactic teaching, and simulation conducted midway through the study period. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a shared mental model index defined as percent congruence among handover participants regarding key patient healthcare data including patient identification, diagnoses, transport interventions, immediate postadmission care plans, and anticipatory guidance for ongoing care. Secondary outcomes were handover comprehensiveness and teaming metrics such as efficiency, attendance, interruption frequency, and team member inclusion. During the study period, 100 transport handovers were observed of which 50 were preintervention and 50 post. A majority of handovers represented transfers to the emergency center (41%) or PICU (45%). There were no observable differences between prepost intervention cohorts by general characteristics, admission diagnoses, or severity of illness metrics including Pediatric Index of Mortality-3-Risk of Mortality, length of stay, mortality, frequency of invasive and noninvasive ventilation, and vasoactive use. The shared mental model index increased from 38% to 78% following standardization of handover. Attendance (76% vs 94%), punctuality (91.5% vs 98%), attention (82% vs 92%), summarization (42% vs 72%), and provision of anticipatory guidance (42% vs 58%) also improved. Efficiency was unchanged with a mean handover duration of 4 minutes in both cohorts. CONCLUSIONS: Considerable enhancements in handover quality, team participation, and the development of a shared mental model after standardization of interfacility transport handover were noted. These findings were achieved without compromising handover efficiency.

Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus.

RATIONALE: Studies suggest that inappropriate responses to proinflammatory stimuli might contribute to inflammation in cystic fibrosis (CF) lungs. However, technical challenges have made it difficult to distinguish whether altered responses in CF airways are an intrinsic defect or a secondary effect of chronic disease in their tissue of origin. The CF pig model provides an opportunity to study the inflammatory responses of CF airways at birth, before the onset of infection and inflammation. OBJECTIVES: To test the hypothesis that acute inflammatory responses are perturbed in porcine CF airways. METHODS: We investigated the inflammatory responses of newborn CF and non-CF pig airways following a 4-hour exposure to heat-killed Staphylococcus aureus, in vivo and in vitro. MEASUREMENTS AND MAIN RESULTS: Following an in vivo S. aureus challenge, markers of inflammation were similar between CF and littermate control animals through evaluation of bronchoalveolar lavage and tissues. However, transcriptome analysis revealed genotype-dependent differences as CF pigs showed a diminished host defense response compared with their non-CF counterparts. Furthermore, CF pig airways exhibited an increase in apoptotic pathways and a suppression of ciliary and flagellar biosynthetic pathways. Similar differences were observed in cultured airway epithelia from CF and non-CF pigs exposed to the stimulus. CONCLUSIONS: Transcriptome profiling suggests that acute inflammatory responses are dysregulated in the airways of newborn CF pigs.

Increased susceptibility to otitis media in a Splunc1-deficient mouse model.

Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1(-/-) mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear.