Understanding breathlessness burden and psychophysiological correlates in asthma.

BACKGROUND: Breathlessness is a disabling symptom, with complexity that is often under recognised and under treated in asthma. OBJECTIVE: To highlight the burden of breathlessness in people with severe compared with mild-to-moderate asthma and identify psychophysiological correlates of breathlessness. METHODS: This was a cross-sectional study of people with mild-to-severe asthma, who attended two in-person visits to complete a multidimensional assessment. The proportion of people with mild-to-moderate versus severe asthma who reported physically limiting breathlessness (modified Medical Research Council [mMRC] dyspnoea score ≥2) was compared. Psychophysiological factors associated with breathlessness in people with asthma were identified via a directed acyclic graph and explored with multivariate logistic regression to predict breathlessness. RESULTS: 144 participants were included, of which, 74 (51%) had mild-to-moderate asthma and 70 (49%) severe asthma. Participants were predominantly female (n=103, 72%) with a median (quartile 1, quartile 3) age of 63.4 (50.5,69.5) years and body mass index (BMI) of 31.3 (26.2, 36.0) kg/m2. The proportion of people reporting mMRC ≥2 was significantly higher in those with severe- (n=37, 53%) compared with mild-to-moderate (n=21, 31%) asthma (p=0.013). Dyspnoea-12 Total (8.00 [4.75, 17.00] versus 5.00 [2.00, 11.00], p=0.037) score was also significantly higher in the severe asthma group. Significant predictors of physically limiting breathlessness were: BMI, asthma control, exercise capacity, and hyperventilation symptoms. Airflow limitation and type-2 inflammation were poor breathlessness predictors. CONCLUSION: Over half of people with severe asthma experience physically limiting breathlessness despite treatment. Targeting psychophysiological factors, or traits, associated with breathlessness may help relieve this distressing symptom, which is of high priority to people with asthma.

The illness burden of severe asthma contrasted to people with mild-to-moderate asthma: a qualitative study.

Background: Disabling symptoms of asthma including breathlessness, cough, wheeze and chest tightness largely impact quality of life; however, how these symptoms impact people with asthma of different severity levels remains unknown. This study aimed to compare and characterise patients' symptom experience and the burden caused, their quality of life, and the medication preferences of people with severe asthma against those of people with mild-to-moderate asthma. Methods: This was a multisite qualitative study involving two focus groups and semistructured interviews of adults with severe asthma undertaken in Australia and UK. Interviews were also undertaken in people with mild-to-moderate asthma. Audio recordings were transcribed and analysed thematically. Results: Participants in both severe asthma and mild-to-moderate asthma groups had a mean±sd age of 57±12 years. Between the severe asthma and mild-to-moderate asthma groups, 62% of participants were female and 86% lived with family. Themes were identified: 1) what is asthma and most bothersome symptoms: both groups reported breathlessness as the most bothersome symptom; 2) impacts on life: disease-related impact differed as people with severe asthma reported significant burden in their quality of life, which encompassed emotional, physical, social and financial wellbeing; and 3) personalised and responsive care: severe asthma interviewees preferred injectable biological therapy as a mode of treatment administration. Conclusions: People with asthma are burdened by breathlessness and cough and other disabling symptoms resulting in impaired quality of life. Understanding the experiences of people with asthma of different severities can improve the patient-clinician partnership.

Adverse events associated with umbilical vascular catheters in the neonatal intensive care unit: A retrospective cohort study.

BACKGROUND: Umbilical catheters are commonly inserted in newborns in the neonatal intensive care unit (NICU) yet are associated with serious adverse events (AEs) such as malposition, migration, infection, thrombosis, hepatic complications, cardiac effusion, and cardiac tamponade. There is a need to determine the incidence and risk factors for AEs to inform safe practice. OBJECTIVES: The objective of this study was to determine the incidence and risk factors for AEs (all-cause and individual types) associated with umbilical venous catheters (UVCs) and umbilical arterial catheters (UACs) in the NICU. METHODS: A retrospective cohort study was conducted in an Australian level-VI NICU over a 3-year period. Any newborn who had both a UVC and UAC insertion attempt was included. RESULTS: There were 236 neonates who had 494 catheters (245 UVCs and 249 UACs). Of these, 71% of UVCs (95% confidence interval [CI]: 65.6-76.9%; incidence rate: 181.1-237.3 per 1000 catheter days) and 43.8% of UACs (95% CI: 38-50.5%; incidence rate: 102.0-146.3 per 1000 catheter days) were associated with an AE. The most common AE was malposition on first X-ray for UVCs (60.1%, 95% CI: 55.1-67.3) and UACs (32.6%, 95% CI: 26.8-39.6). A dwell time of ≥7 days was a significant predictor of UAC failure (incidence risk ratio: 1.5, 95% CI: 1.1-2.1, p = 0.006) and migration of the UVC (incidence risk ratio: 3.5, 95% CI: 1.0-11.5, p = 0.043). CONCLUSION: Adverse events related to insertion occurred in a relatively high percentage of umbilical catheters placed. Increased dwell time remains a significant risk factor for catheter migration and overall failure. Practice change and consideration of risk factors for both individual and overall AE risk are necessary to reduce complications.

Toward mechanistic medical digital twins: some use cases in immunology.

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clinician. Such personalized models are increasingly referred to as medical digital twins. Digital twin technology for health applications is still in its infancy, and extensive research and development is required. This article focuses on several projects in different stages of development that can lead to specific-and practical-medical digital twins or digital twin modeling platforms. It emerged from a two-day forum on problems related to medical digital twins, particularly those involving an immune system component. Open access video recordings of the forum discussions are available.

Forum on immune digital twins: a meeting report.

Medical digital twins are computational models of human biology relevant to a given medical condition, which are tailored to an individual patient, thereby predicting the course of disease and individualized treatments, an important goal of personalized medicine. The immune system, which has a central role in many diseases, is highly heterogeneous between individuals, and thus poses a major challenge for this technology. In February 2023, an international group of experts convened for two days to discuss these challenges related to immune digital twins. The group consisted of clinicians, immunologists, biologists, and mathematical modelers, representative of the interdisciplinary nature of medical digital twin development. A video recording of the entire event is available. This paper presents a synopsis of the discussions, brief descriptions of ongoing digital twin projects at different stages of progress. It also proposes a 5-year action plan for further developing this technology. The main recommendations are to identify and pursue a small number of promising use cases, to develop stimulation-specific assays of immune function in a clinical setting, and to develop a database of existing computational immune models, as well as advanced modeling technology and infrastructure.

Are dietitian recommendations followed? A descriptive study of paediatric hospitalised and ambulatory patients.

BACKGROUND: The primary objective of this cross-sectional retrospective study was to describe the implementation of dietitian prescribed nutrition recommendations in malnourished paediatric patients in the hospital and ambulatory settings. We also aimed to investigate other characteristics that could be associated with differences in implementation. METHODS: Data were collected from 186 hospitalised and 565 ambulatory patients between February 2020 and January 2021. Data included age, hospital or ambulatory specialty departments, primary diagnosis, malnutrition status, hospital length of stay (LOS), and medical nutrition therapy recommendations. Implementation by the medical team in the hospital setting and adherence by the family in the outpatient setting were categorised as "Full", "Partial" or "None". "Partial" and "None" were combined for analysis. RESULTS: Dietitian prescribed recommendations were implemented in 79.6% of hospitalised patients. In the ambulatory population, 46.4% of patients were adherent with nutrition recommendations. Within the hospital, there was a significant difference in implementation of nutrition recommendations based on age (p = 0.047), hospital department (p = 0.002) and LOS (p = 0.04), whereas, in the ambulatory population, there were no significant differences in the rate of adherence among any of the studied characteristics. CONCLUSIONS: Dietitian recommendations are frequently implemented in the hospital, whereas adherence to such recommendations is poor in the outpatient population. Interventions to improve adherence to nutrition recommendations in the ambulatory setting are needed.

Implementation and participation of an online nutrition curriculum for pediatric gastroenterology fellows.

Our team of nutrition experts developed an online nutrition curriculum consisting of 21 modules to serve as a resource for a stand-alone nutrition curriculum or as a supplement to existing nutrition electives during the Pediatric Gastroenterology fellowship. From April 2020 through January 2023, 2090 modules were completed by 436 fellows from 75 different programs across North America. The program was accessed most during tight restrictions on in-person learning during the COVID-19 pandemic. Overall, participants posttest scores improved from baseline pretest scores indicating retention of information from the modules. The overall success of this program suggests that there should be continued efforts to develop and offer online learning opportunities in clinical nutrition. There is an opportunity to expand the audience for the curriculum to include pediatric gastroenterologists from across the globe.

Electronic health record time-tracking provides real-time data to measure and benchmark dietitian productivity.

BACKGROUND: Traditional methods for benchmarking dietitian productivity are time-consuming and fail to accurately measure the total time spent providing nutrition care. An electronic health record (EHR)-based tool that allows for daily tracking of both face-to-face and patient care coordination time for dietitians was created. We assessed whether it provided consistent, continuous measurement of time and productivity. METHODS: This tool was created in an independent paediatric academic healthcare system in the USA. Time spent by dietitians in face-to-face settings and care coordination were tracked. Changes in time spent between the years 2013-2016 versus 2018-2019 were also analysed. RESULTS: The outpatient dietitian spent a mean total of 66.4 min per patient (37.8 ± 6.0 min in face-to-face care and 28.6 ± 5.2 min in care coordination). The total times and fractions spent on face-to-face and care coordination time varied by specialty. Comparison of the two periods of time revealed 75% more productivity on average of dietitians in different outpatient settings after including care coordination tracking. In addition, dietitians were more likely to document time spent in 5-min increments after the institution of this methodology as opposed to 15-min increments. CONCLUSIONS: An EHR-based tool that facilitates the documentation of both face-to-face time and patient care coordination time is feasible and enables consistent, continuous measurement of time and productivity. The real-time data from this tool can be used to support adequate dietitian staffing and be used to create a multicentre database to measure the actual time dietitians need to provide care and generate consistent staffing benchmarks.

Ventilation Heterogeneity Is a Treatable Trait in Severe Asthma.

BACKGROUND: Ventilation heterogeneity (VH) is a feature of asthma and indicates small airway disease. Nuclear imaging methods assess VH, which can facilitate clinical diagnosis and further our understanding of disease aetiology. OBJECTIVE: We sought to assess VH in severe eosinophilic asthma (SEA) using ventilation/perfusion single-photon emission computed tomography (V/P SPECT), and to assess its use as an objective test of the effect of biologic treatment for ventilation defects in SEA. METHODS: Adults (≥18 y) with severe asthma were recruited to participate in a cross-sectional observational study. Participants underwent a clinical assessment and V/P SPECT CT using Technegas as the ventilation agent. Measures were repeated for a nested before-after treatment study in people with SEA commencing biologics. RESULTS: A total of 62 participants with severe asthma were recruited. From this, 38 participants with SEA were included in the before-after study. The VH was associated with clinical variables such as lung function impairment and significantly improved after monoclonal antibody treatment in the severe asthma group. The changes in VH correlated with change in post bronchodilator forced expiratory volume in 1 second (FEV1) %predicted (r = -0.503; P = .001) and post bronchodilator FEV1/FVC (forced vital capacity) (r = -0.415; P = .01). CONCLUSIONS: The VH is clinically significant, measurable, and treatable, which establishes VH as a treatable trait in severe asthma.

Nutrition Screening in the Pediatric Intensive Care Unit: Evaluation of an Electronic Medical Record-Based Tool.

Hospitalized, critically ill children are at increased risk of developing malnutrition. While several pediatric nutrition screening tools exist, none have been validated in the pediatric intensive care units (PICU). The Children's Wisconsin Nutrition Screening Tool (CWNST) is a unique nutrition screening tool that includes the Pediatric Nutrition Screening Tool (PNST) and predictive elements from the electronic medical record and was found to be more sensitive than the PNST in acute care units. The aim of this study was to assess the performance of the tool in detecting possible malnutrition in critically ill children. The data analysis, including the results of the current nutrition screening, diagnosis, and nutrition status was performed on all patients admitted to PICUs at Children's Wisconsin in 2019. All 250 patients with ≥1 nutrition assessment by a dietitian were included. The screening elements that were predictive of malnutrition included parenteral nutrition, positive PNST, and BMI-for-age/weight-for-length z-score. The current screen had a sensitivity of 0.985, specificity of 0.06, positive predictive value (PPV) of 0.249, and negative predictive value of 0.929 compared to the PNST alone which had a sensitivity of 0.1, specificity of 0.981, PPV of 0.658, and NPV of 0.749. However, of the 250 included patients, 97.2% (243) had a positive nutrition screen. The CWNST can be easily applied through EMRs and predicts the nutrition risk in PICU patients but needs further improvement to improve specificity.

Perioperative Pressure Injury Prevention Program in a Military Medical Treatment Facility: A Quality Improvement Project.

INTRODUCTION: The incidence of perioperative pressure injuries (PPIs) at a military medical treatment facility (MTF) increased from three PPI events in 2018 to five PPI events in the first half of 2019. The purpose of this quality improvement initiative was to determine whether an evidence-based PPI prevention program introduced during the second half of 2019 reduced pressure injuries compared to the previous 1.5 years that followed the standard of care for perioperative patient positioning. METHODS: We used a multidisciplinary quality improvement PPI prevention approach that included education, Scott Triggers® patient risk assessment, application of a five-layer silicone dressing to at-risk surgical position sites, and feedback via multidisciplinary postoperative rounding. RESULTS: There was an observed decrease in the rate of PPIs from 0.62 to 0.00 per 1,000 patient surgeries during the 26-month period that this protocol was implemented. CONCLUSION: This project was conducted at a major MTF using a multidisciplinary PPI prevention approach that may be of value in reducing PPIs in other settings. This approach seems worthy of further investigation and may be applicable to other military MTFs and in deployed settings.

Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis.

Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling to evaluate candidate oncogenic loci identified via integrative computational analysis of extreme copy gains overlapping with extreme expression dysregulation in The Cancer Genome Atlas. Subsets of "outlier" candidates were contextually screened as tissue-specific cDNA lentiviral libraries within cognate esophagus, oral cavity, colon, stomach, pancreas, and lung organoids bearing initial oncogenic mutations. Iterative analysis nominated the kinase DYRK2 at 12q15 as an amplified head and neck squamous carcinoma oncogene in p53-/- oral mucosal organoids. Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, promoted p53-/- esophageal organoid growth reversible by small molecule and soluble receptor antagonism of FGFRs. Our studies establish organoid-based contextual screening of candidate genomic drivers, enabling functional evaluation during early tumorigenesis.

Best Practices and Educator Strategies for Facilitating a Flipped Classroom in Graduate Medical Education.

OBJECTIVE: Effective flipped classroom (FC) education fosters learner engagement, promoting higher-level cognitive skills. FC learning in graduate medical education (GME) has increased, but few educators have significant experience with FC facilitation. There are no evidence-based practices to support professional development of FC facilitation skills in GME. The objective of this study is to identify best practices for effective FC facilitation in GME. STUDY DESIGN: We conducted a mixed-methods, cross-sectional study of faculty educators who participated in a randomized controlled trial (RCT) using FC for physiology education in neonatal-perinatal medicine. Educators completed a 25-question survey about effective strategies for FC facilitation. A subset of educators participated in interviews to share their FC facilitation experiences and strategies to maximize learner engagement. Quantitative survey data were analyzed with descriptive statistics. Qualitative survey and interview data were coded and analyzed inductively to identify themes. RESULTS: Seventy-five educators completed the survey (75/136, 55% response rate), and 11 participated in semistructured interviews. While educators facilitated a median of two FC sessions (interquartile range: 1, 5) during the RCT, 43 (57%) had not received prior training in FC facilitation. Qualitative data analyses generated five themes that aligned with quantitative survey results: (1) educator preferences, (2) unique FC facilitation skills, (3) learning environment optimization, (4) subject matter expertise, and (5) learner behavior management. Sixty-two educators (83%) felt they were well prepared to lead FC sessions. Thirty-six educators (48%) reported that unprepared learners disrupt the learning environment, and the provision of clear expectations and adequate time to prepare for FCs improves learner preparation. Strategies to facilitate effective FC sessions included creating a safe learning environment and engaging learners in critical thinking. CONCLUSION: Educators highlighted faculty development needs, strategies, and actions to promote effective FC facilitation. Further exploration through learner interviews will provide additional evidence for the development of best practices and resources for FC facilitation. KEY POINTS: · Educators prefer the FC educational modality over traditional didactic lectures.. · Prior experiences in simulation debriefing provide foundational skills for new FC facilitators.. · Setting learner expectations and ensuring safe space in the classroom encourage learner engagement.. · Educator and learner preparation for FC is essential to optimize the learning experience.. · Unique approaches in facilitation are required to support all types of learners..

Ectoparasites associated with the Bushveld gerbil (Gerbilliscus leucogaster) and the role of the host and habitat in shaping ectoparasite diversity and infestations.

Rodents are known hosts for various ectoparasite taxa such as fleas, lice, ticks and mites. South Africa is recognized for its animal diversity, yet little is published about the parasite diversity associated with wild rodent species. By focusing on a wildlife-human/domestic animal interface, the study aims to record ectoparasite diversity and levels of infestations of the Bushveld gerbil, Gerbilliscus leucogaster, and to establish the relationship between ectoparasite infestation parameters and host- and habitat factors. Rodents (n = 127) were trapped in 2 habitat types (natural and agricultural) during 2014­2020. More than 6500 individuals of 32 epifaunistic species represented by 21 genera and belonging to 5 taxonomic groups (fleas, sucking lice, ticks, mesostigmatan mites and trombiculid mites) were collected. Mesostigmatan mites and lice were the most abundant and fleas and mesostigmatan mites the most prevalent groups. Flea and mesostigmatan mite numbers and mesostigmatan mite species richness was significantly higher on reproductively active male than female rodents. Only ticks were significantly associated with habitat type, with significantly higher tick numbers and more tick species on rodents in the natural compared to the agricultural habitat. We conclude that the level of infestation by ectoparasites closely associated with the host (fleas and mites) was affected by host-associated factors, while infestation by ectoparasite that spend most of their life in the external environment (ticks) was affected by habitat type.

How Interactions during Viral-Viral Coinfection Can Shape Infection Kinetics.

Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20-30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.

Evaluation of an electronic medical record-based Paediatric Nutrition Screening Tool.

BACKGROUND: Nutrition screening is recommended to identify children at risk for malnutrition. A unique screening tool was developed based on American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations and embedded in the electronic medical record to assess for nutrition risk. METHODS: The components of the tool included the Paediatric Nutrition Screening Tool (PNST) and other elements recommended by ASPEN. To evaluate the screening tool, retrospective data were analysed on all patients admitted to acute care units of Children's Wisconsin in 2019. Data collected included nutrition screen results, diagnosis and nutrition status. All patients who received at least one full nutrition assessment by a registered dietitian (RD) were included in analysis. RESULTS: One thousand five hundred seventy-five patients were included in analysis. The following screen elements were significantly associated with a diagnosis of malnutrition: any positive screen (p < 0.001), >2 food allergies (p = 0.009), intubation (p < 0.001), parenteral nutrition (p = 0.005), RD-identified risk (p < 0.001), positive risk per the PNST (p < 0.001), BMI-for-age or weight-for-length z-score (p < 0.001), intake <50% for 3 days (p = 0.012) and NPO > 3 days (p = 0.009). The current screen had a sensitivity of 93.9%, specificity of 20.3%, positive predictive value (PPV) of 30.9% and negative predictive value (NPV) of 89.8%. This is compared with the PNST which had a sensitivity of 32%, specificity of 94.2%, PPV of 71% and NPV of 75.8% in this study population. CONCLUSION: This unique screening tool is useful for predicting nutrition risk and has a greater sensitivity than the PNST alone.

How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics.

Respiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV) followed by influenza A virus (IAV) after 3 days. The results suggested that IAV reduced the rate of RSV production while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios not examined experimentally, including different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis showed that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to slower clearance of IAV infected cells by the other viruses. On the contrary, the improved outcome when IAV followed RV could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.

Virtually the Same? Evaluating the Effectiveness of Remote Undergraduate Research Experiences.

In-person undergraduate research experiences (UREs) promote students' integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration and whether they might perceive doing research less favorably (i.e., not beneficial or too costly). To address these questions, we examined indicators of scientific integration and perceptions of the benefits and costs of doing research among students who participated in remote life science URE programs in Summer 2020. We found that students experienced gains in scientific self-efficacy pre- to post-URE, similar to results reported for in-person UREs. We also found that students experienced gains in scientific identity, graduate and career intentions, and perceptions of the benefits of doing research only if they started their remote UREs at lower levels on these variables. Collectively, students did not change in their perceptions of the costs of doing research despite the challenges of working remotely. Yet students who started with low cost perceptions increased in these perceptions. These findings indicate that remote UREs can support students' self-efficacy development, but may otherwise be limited in their potential to promote scientific integration.