A qualitative study of barriers and facilitators to pediatric early warning score (PEWS) implementation in a resource-limited setting.

Objectives: Globally, pediatric hospitals have implemented Pediatric Early Warning Scores (PEWS) to standardize escalation of care and improve detection of clinical deterioration in pediatric patients. This study aims to utilize qualitative methodology to understand barriers and facilitators of PEWS implementation at Philippine Children's Medical Center (PCMC), a tertiary care hospital in Manila, Philippines. Methods: Semi-structured interviews querying current processes for clinical monitoring, Pediatric Intensive Care Unit (PICU) transfer, and clinician attitudes towards PEWS implementation were audio recorded. In-person hospital observations served to triangulate interview findings. The Systems Engineering Initiative for Patient Safety (SEIPS) framework guided content coding of interviews to characterize work systems, processes, and outcomes related to patient monitoring and care escalation. Thematic coding was performed using Dedoose software. This model allowed identification of barriers and facilitators to PEWS implementation. Results: Barriers within PCMC workflow included: limited bed capacity, delay in referral, patient overflow, limited monitoring equipment, and high patient to staff ratio. Facilitators of PEWS implementation included support for PEWS adaptation and existence of systems for vital sign monitoring. Observations by study personnel confirmed validity of themes. Conclusion: Utilizing qualitative methodology to understand barriers and facilitators to PEWS in specific contexts can guide implementation at resource-limited hospitals.

Implementation and evaluation of a shock curriculum using simulation in Manila, Philippines: a prospective cohort study.

BACKGROUND: Shock causes significant morbidity and mortality in children living in resource-limited settings. Simulation has been successfully used as an educational tool for medical professionals internationally. We sought to improve comfort and knowledge regarding shock recognition and fluid management by implementing a pediatric shock curriculum using simulation as an assessment for trainees in Manila, Philippines. METHODS: We assessed a shock curriculum focused on patients with malnutrition in a prospective cohort study, using a written test and a videotaped simulation-based objective standardized clinical examination. Implementation occurred in March 2020 with 24 Filipino pediatric residents at a single institution in Manila. Outcomes included time to initiation of fluid resuscitation, improvement in confidence, knowledge on a written assessment, and performance in simulation. Results were compared pre- and post-intervention using Wilcoxon signed-rank test. RESULTS: The time to initiation of fluids did not change between the baseline simulation (median [interquartile range] = 71.5 seconds [52-116.5]) and the final simulation (68 seconds [52.5-89]; P = 0.42). Confidence in identifying shock and malnutrition, managing hypovolemic shock, managing septic shock, and placing intraosseous access all increased (P < 0.01) post-intervention. Written test scores showed no improvement, but performance in simulation, measured using a checklist, improved from a total score of 10 [8.5-11] to 15 [13-16] (P < 0.01). CONCLUSION: In our study of a simulation-based shock education program, we showed improvement in confidence and knowledge as measured by a resuscitation checklist. It is feasible to establish a successful simulation-based education program in a low-resource setting.

Evolution of a Bidirectional Pediatric Critical Care Educational Partnership in a Resource-Limited Setting.

Introduction: Children in resource-limited settings are disproportionately affected by common childhood illnesses, resulting in high rates of mortality. A major barrier to improving child health in such regions is limited pediatric-specific training, particularly in the care of children with critical illness. While global health rotations for trainees from North America and Europe have become commonplace, residency and fellowship programs struggle to ensure that these rotations are mutually beneficial and do not place an undue burden on host countries. We created a bidirectional, multimodal educational program between trainees in Manila, Philippines, and Baltimore, Maryland, United States, to improve the longitudinal educational experience for all participants. Program Components: Based on stakeholder input and a needs assessment, we established a global health training program in which pediatricians from the Philippines traveled to the United States for observerships, and pediatric residents from a tertiary care center in Baltimore traveled to Manila. Additionally, we created and implemented a contextualized simulation-based shock curriculum for pediatric trainees in Manila that can be disseminated locally. This bidirectional program was adapted to include telemedicine and regularly scheduled "virtual rounds" and educational case conferences during the COVID-19 pandemic. Providers from the two institutions have collaborated on educational and clinical research projects, offering opportunities for resource sharing, bidirectional professional development, and institutional improvements. Conclusion: Although creating a mutually beneficial global health partnership requires careful planning and investment over time, establishment of a successful bidirectional educational and professional development program in a limited-resource setting is feasible and benefits learners in both countries.

Information and Communication Technology Access and Use Among Low-Income Latino Immigrant Parents.

INTRODUCTION: Development of mHealth interventions to address health disparities for Latino children in immigrant families requires understanding access to and use of information and communication technology. METHODS: We examined access to information and communication technology and use of common applications/programs by low-income immigrant Latino parents of infants to inform development of mHealth interventions for this population. Latino immigrant parents reported technology use and access of common applications/software via survey. RESULTS: Of the 157 participants, we found nearly all parents owned a smartphone and that 60% accessed the internet only via their smartphone. Around one-quarter of participants had access to unlimited data. Frequent use of text messaging was common, but frequent email use was less common. Less than 10% of participants frequently used health-oriented applications. DISCUSSION: Our findings suggest that mHealth interventions that use data, email, or an application interface may not have the intended reach or effectiveness among low-income immigrant Latino parents. Consideration of these findings is important in guiding the development of future mHealth programs for the low-income Latino population. This study was registered at clinicaltrials.gov (NCT02647814).

Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.

BACKGROUND: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; P = .020) and body mass index (BMI) ≥25 kg/m2 (aHR, 0.37; 95% CI, 0.18-0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; P = .044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients.

BACKGROUND: Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m 2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Self-Collected Oral Fluid Saliva Is Insensitive Compared With Nasal-Oropharyngeal Swabs in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Outpatients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared with the nasopharyngeal swab. METHODS: We compared real-time reverse-transcription polymerase chain reaction Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a nonhospitalized, ambulatory cohort of coronavirus disease 2019 (COVID-19) patients at multiple time points. These 2 sentences should be at the beginning of the results. RESULTS: There were 171 matched specimen pairs. Compared with nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid percent collection device increased the percent positive agreement from 37.2% (16 of 43) to 44.6% (29 of 65). The positive percent agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample. CONCLUSIONS: In this study of nonhospitalized SARS-CoV-2-infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared with nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection and the time from symptom onset especially in outpatient populations.

Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection.

In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.

Synergy between plasminogen activator inhibitor-1, α-synuclein, and neuroinflammation in Parkinson's disease.

Parkinson's disease (PD) is a progressive degenerative nervous system disorder and is the second most common neurodegenerative disorder in the elderly population. The disease originates from the loss of dopamine-producing neurons in the substantia nigra in the brain, resulting in unregulated activity of the basal ganglia. Αlpha-synuclein (α-syn) is a protein found to aggregate in the substantia nigra region of patients with PD, forming Lewy Body inclusions; its aggregation may contribute to neuronal cell death in PD. This work hypothesizes about the synergistic relationship between α-syn aggregation and neuroinflammation to up-regulate expression of the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1). The protease, plasmin, has been shown to cleave extracellular α-syn (including its monomeric, oligomeric, and fibrillary forms), resulting in less aggregation and Lewy Body formation. The zymogen plasminogen is converted to its active serine protease form, plasmin, either by tissue plasminogen activator (tPA) or by urokinase plasminogen activator (uPA) bound to urokinase receptor (uPAR). Both tPA and uPA/uPAR are inhibited by PAI-1. Thus, when PAI-1 levels increase, less plasmin is generated, which would lead to reduced proteolysis of α-syn. Expression of PAI-1 is increased both in inflammatory environments and in the presence of extracellular α-syn aggregates. This scenario suggests a pathological amplification loop: increased extracellular α-syn aggregation activates an inflammatory response from microglia and astrocytes, increasing PAI-1 levels, and decreasing the generation of plasmin. With reduced plasmin, less α-syn can be cleaved, and aggregation continues, sustaining the pathological process. Understanding this putative pathogenic loop could provide insight into the means by which neurodegeneration progresses in PD, and it may offer possible novel therapeutic strategies.