Simulation Training in a Lower Middle-Income Country: Supporting a New Center and Developing Low-Cost Models for Critical Skill Acquisition.

INTRODUCTION:  There is a demand for surgical simulation training to be made accessible in low-resource countries. We conducted a pilot workshop at a new state-of-the-art simulation center and evaluated two novel low-cost surgical simulation models in a lower middle-income country (LMIC). METHODS: A hands-on workshop to train local educators about simulation training was held at a new simulation center. Participant surveys were analyzed following the "training-the-trainer" workshop. Low-cost, hybrid-fidelity pericardiocentesis and thoracic cavity simulation training models were created using locally available materials. These models recreated the pertinent anatomy at a cost under 20 US dollars each. The models were used to train 109 postgraduate anesthesiology trainees during two hands-on medical education workshops. Participant surveys were collected and analyzed. RESULTS: Of the local educators who participated in the "training-the-trainer" workshop, 65% "agreed" and 35% "strongly agreed" with the claim that the simulations better prepared the trainees to teach the clinical scenarios. Additionally, 65% of local educators "agreed" and 35% "strongly agreed" that the simulations prepared them to navigate interprofessional care in those scenarios. The low-cost pericardiocentesis simulation was ranked as "good" or "outstanding" by 100% of survey respondents. The low-cost thoracostomy simulation was ranked as "good" or "outstanding" by 64% of survey respondents. Both the pericardiocentesis and thoracostomy simulators were valued for their low-cost design, the recreation of essential anatomy, and immersive design elements. CONCLUSION: Our team successfully implemented novel simulators for skill training in an LMIC by working in close collaboration with local experts, with the advancement of local simulation instruction practices. Collaboration is key to increasing access to surgical simulations, particularly in low- to middle-income countries.

Sofa and bed-related pediatric trauma injuries treated in United States emergency departments.

INTRODUCTION: Children under the age of 5 years suffer from the highest rates of fall-related injuries. Caretakers often leave young children on sofas and beds, however, falling and rolling off these fixtures can lead to serious injury. We investigated the epidemiologic characteristics and trends of bed and sofa-related injuries among children aged <5 years treated in US emergency departments (EDs). METHODS: We conducted a retrospective analysis of data from the National Electronic Injury Surveillance System from 2007 through 2021 using sample weights to estimate national numbers and rates of bed and sofa-related injuries. Descriptive statistics and regression analyses were employed. RESULTS: An estimated 3,414,007 children aged <5 years were treated for bed and sofa-related injuries in emergency departments (EDs) in the United States from 2007 through 2021, averaging 115.2 injuries per 10,000 persons annually. Closed head injuries (30%) and lacerations (24%) comprised the majority of injuries. The primary location of injury was the head (71%) and upper extremity (17%). Children <1 year of age accounted for most injuries, with a 67% increase in incidence within the age group between 2007 and 2021 (p < 0.001). Falling, jumping, and rolling off beds and sofas were the primary mechanisms of injury. The proportion of jumping injuries increased with age. Approximately 4% of all injuries required hospitalization. Children <1 year of age were 1.58 times more likely to be hospitalized after injury than all other age groups (p < 0.001). CONCLUSION: Beds and sofas can be associated with injury among young children, especially infants. The annual rate of bed and sofa-related injuries among infants <1 year old is increasing, which underscores the need for increased prevention efforts, including parental education and improved safety design, to decrease these injuries.

Rising incidence of stair-related upper extremity fractures among older adults in the United States: a 10-year nationwide analysis.

Upper extremity (UE) fractures are prevalent age-related fractures, and stair-associated falls are a common mechanism for these injuries. Our study has identified an increasing incidence of stair-related UE fractures and associated hospitalization rates among the older United States population between 2012-2021. Targeted prevention efforts should be implemented by health systems. INTRODUCTION: To analyze United States (US) emergency department trends in upper extremity stair-related fractures among older adults and investigate risk factors associated with hospitalization. METHODS: We queried the National Electronic Injury Surveillance System (NEISS) for all stair-related fracture injuries between 2012 and 2021 among adults 65 years or older. The US Census Bureau International Database (IDB) was analyzed to calculate incidence rates. Descriptive analysis, linear regression analysis, and multivariate regression analysis were used to interpret the collected data. RESULTS: Our analysis estimated 251,041 (95% CI: 211,678-290,404) upper extremity stair-related fractures among older adults occurred between 2012 and 2021. The primary anatomical locations were the humeral shaft (27%), wrist (26%), and proximal humerus (18%). We found a 56% increase in injuries (R2 = 0.77, p < 0.001), 7% increase in incidence per 100,000 persons (R2 = 0.42, p < 0.05), and an 38% increase in hospitalization rate (R2 = 0.61, p < 0.01) during the 10-year study period. Women sustained the majority of fractures (76%) and most injuries occurred in homes (89%). Advanced age (p < 0.0001), males (p < 0.0001), proximal humerus fractures (p < 0.0001), humeral shaft fractures (p < 0.0001), and elbow fractures (p < 0.0001) were associated with increased odds of hospitalization after injury. CONCLUSION: Stair-related UE fracture injuries, incidence, and hospitalization rates among older adults are increasing significantly, particularly among older females. Improving bone health, optimizing functional muscle mass, and "fall-proofing" homes of older age groups may help mitigate the rising incidence of these injuries.

Development of an Inducible, Replication-Competent Assay Cell Line for Titration of Infectious Recombinant Adeno-Associated Virus Vectors.

An important quality attribute of a recombinant adeno-associated virus (rAAV) as a therapeutic vector is its infectivity. Current assays to quantify infectious rAAV rely on coinfection with a helper virus such as adenovirus (Ad), which requires helper virus preparation and introduces additional variability. A simple method that has high sensitivity and removes the need for helper virus would improve assay consistency and facilitate high-throughput applications such as rAAV producer cell line development. In this study, we describe a stable assay cell line that was generated by integrating the coding sequences for AAV Rep68 and Ad E4orf6 and DNA binding protein under the control of inducible promoters. The Rep68 protein expression was further modulated by a ligand-responsive destabilization domain. In several benchmarks, the cell line gave comparable titers with those obtained using a classical Ad coinfection method. The cell line was also used to titer vectors of multiple rAAV serotypes. This cell line has the potential to serve as an effective and robust tool for quantifying infectious rAAV titers to advance gene therapy vector biomanufacturing.

Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis.

Background: Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear. Methods: We analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into ≥100 mg/dL (n=249) and <100 mg/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels. Results: Approximately one-third of individuals had a baseline CSF protein ≥100 mg/dL. Those with CSF protein ≥100 mg/dL were more likely to present with Glasgow coma scale scores <15 (P<0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p<0.001), and higher CSF white cells (p<0.001). Moreover, those with a baseline CSF protein ≥100 mg/dL also had a lower baseline CSF fungal burden (p<0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein ≥100 mg/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p<0.05). 18-week mortality risk in individuals with a CSF protein <100 mg/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with ≥100 mg/dL. Conclusion: In cryptococcal meningitis, individuals with CSF protein ≥100 mg/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis.

Construction of an rAAV Producer Cell Line through Synthetic Biology.

Recombinant adeno-associated viruses (rAAV) are important gene delivery vehicles for gene therapy applications. Their production relies on plasmid transfection or virus infection of producer cells, which pose a challenge in process scale-up. Here, we describe a template for a transfection-free, helper virus-free rAAV producer cell line using a synthetic biology approach. Three modules were integrated into HEK293 cells including an rAAV genome and multiple inducible promoters controlling the expression of AAV Rep, Cap, and helper coding sequences. The synthetic cell line generated infectious rAAV vectors upon induction. Independent control over replication and packaging activities allowed for manipulation of the fraction of capsid particles containing viral genomes, affirming the feasibility of tuning gene expression profiles in a synthetic cell line for enhancing the quality of the viral vector produced. The synthetic biology approach for rAAV production presented in this study can be exploited for scalable biomanufacturing.