A qualitative study of barriers and facilitators to using tenecteplase to treat acute ischemic stroke.

BACKGROUND: Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS: Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS: Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION: Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Ensemble species distribution modeling of Culex tarsalis (Diptera: Culicidae) in the continental United States.

West Nile virus (WNV) is the primary mosquito-borne disease in the United States and has had case reports every year since its introduction in 1999. As such, it is critical that we characterize the distribution of WNV vectors. Estimates of Culex tarsalis Coquillett species distribution, a major WNV vector, are scarce. We used ensemble distribution modeling to estimate habitat suitability for this species across the contiguous United States by consolidating presence data from four publicly available mosquito trapping data servers. The central plains region and much of the western US were estimated to have high habitat suitability. We identified multiple metrics of temperature and precipitation to be important in predicting the occurrence of Cx. tarsalis in a given geographic area. Furthermore, we observed habitat suitability for Cx. tarsalis to be significantly higher in areas with a high incidence of West Nile neuroinvasive disease compared to areas with low WN disease incidence, suggesting that Cx. tarsalis is present in regions with a high incidence of disease.

Meta-Analysis of the Relative Abundance of Nuisance and Vector Mosquitoes in Urban and Blue-Green Spaces.

Blue-green spaces (BGSs), urban areas characterized by the presence of vegetation and or water, and infrastructure form a potential solution for public health threats from increasing urbanization. We conducted a meta-analysis to test the hypothesis that blue-green spaces increase the abundance of nuisance and vector mosquito species compared to non-greened urban areas. After screening 7306 studies published since 1992, we identified 18 studies containing sufficient data from both traditional urban areas and BGSs. We found no significant difference in mean abundance of all mosquito taxa in three genera (Aedes, Culex, Anopheles) when comparing blue-green spaces and non-greened urban spaces. Similarly, a separate analysis of each individual genera found no significant differences. An analysis of the taxa by larval habitat guilds found no differences for container-breeding mosquitoes. Flood-water species tended to be more abundant in blue-green spaces, but the differences were not significant. The individual taxa of Aedes albopictus and the Culex pipiens complex showed no differences between blue-green and urban spaces, while the abundance of Aedes aegypti was significantly higher in traditional urban spaces. Due to the variety existing between and among the several types of blue-green spaces, further studies comparing each unique type of blue-green space or infrastructure will be necessary to draw conclusions regarding the influence of each structure on for urban mosquito communities.

Anopheles albimanus (Diptera: Culicidae) Ensemble Distribution Modeling: Applications for Malaria Elimination.

In the absence of entomological information, tools for predicting Anopheles spp. presence can help evaluate the entomological risk of malaria transmission. Here, we illustrate how species distribution models (SDM) could quantify potential dominant vector species presence in malaria elimination settings. We fitted a 250 m resolution ensemble SDM for Anopheles albimanus Wiedemann. The ensemble SDM included predictions based on seven different algorithms, 110 occurrence records and 70 model projections. SDM covariates included nine environmental variables that were selected based on their importance from an original set of 28 layers that included remotely and spatially interpolated locally measured variables for the land surface of Costa Rica. Goodness of fit for the ensemble SDM was very high, with a minimum AUC of 0.79. We used the resulting ensemble SDM to evaluate differences in habitat suitability (HS) between commercial plantations and surrounding landscapes, finding a higher HS in pineapple and oil palm plantations, suggestive of An. albimanus presence, than in surrounding landscapes. The ensemble SDM suggested a low HS for An. albimanus at the presumed epicenter of malaria transmission during 2018-2019 in Costa Rica, yet this vector was likely present at the two main towns also affected by the epidemic. Our results illustrate how ensemble SDMs in malaria elimination settings can provide information that could help to improve vector surveillance and control.

Emx2 and early hair cell development in the mouse inner ear.

Emx2 is a homeodomain protein that plays a critical role in inner ear development. Homozygous null mice die at birth with a range of defects in the CNS, renal system and skeleton. The cochlea is shorter than normal with about 60% fewer auditory hair cells. It appears to lack outer hair cells and some supporting cells are either absent or fail to differentiate. Many of the hair cells differentiate in pairs and although their hair bundles develop normally their planar cell polarity is compromised. Measurements of cell polarity suggest that classic planar cell polarity molecules are not directly influenced by Emx2 and that polarity is compromised by developmental defects in the sensory precursor population or by defects in epithelial cues for cell alignment. Planar cell polarity is normal in the vestibular epithelia although polarity reversal across the striola is absent in both the utricular and saccular maculae. In contrast, cochlear hair cell polarity is disorganized. The expression domain for Bmp4 is expanded and Fgfr1 and Prox1 are expressed in fewer cells in the cochlear sensory epithelium of Emx2 null mice. We conclude that Emx2 regulates early developmental events that balance cell proliferation and differentiation in the sensory precursor population.

A proposed framework for the development and qualitative evaluation of West Nile virus models and their application to local public health decision-making.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

End User Comparison of Anatomically Matched 3-Dimensional Printed and Virtual Haptic Temporal Bone Simulation: A Pilot Study.

OBJECTIVE: Simulation has assumed a prominent role in education. It is important to explore the effectiveness of different modalities. In this article, we directly compare surgical resident impression of 2 distinct temporal bone simulations (physical and haptic). STUDY DESIGN: Research Ethics Board-approved prospective cohort study. SETTING: A haptic voxel-based virtual model (VM) and a physical 3-dimensional printed temporal bone model (PBM) were developed. Participants rated each construct on a number of parameters and performed a direct comparison of the simulations using a survey instrument that employed a 7-point Likert scale and rank lists. SUBJECTS AND METHODS: Ten otolaryngology residents dissected anatomically identical, matched physical and virtual models. Data for both simulations originated from 10 unique cadaveric micro-computed tomography images. RESULTS: Subjects rated the PBM drill quality as being more similar to cadaveric temporal bone than the VM (cortical bone mean: 5.5 vs 3.2, P = .011; trabecular bone mean: 5.2 vs 2.8, P = .004) and with better air cell system representation (mean: 5.4 vs 4.5, P = .003). Subjects strongly agreed that both simulations are effective educational tools, but they rated the PBM higher (mean: 6.7 vs 5.4, P = .019). Notably, subjects agreed that both modalities should be integrated into training, but they were more favorably inclined toward the PBM (mean: 7.0 vs 5.5, P = .002). In direct comparison, the PBM was the preferred simulation in 7 of 9 educational domains. CONCLUSIONS: Appraisal of a PBM and a VM found both to have perceived educational benefit. However, the PBM was considered to have more realistic physical properties and was considered the preferred training instrument.

Comparison of cadaveric and isomorphic three-dimensional printed models in temporal bone education.

OBJECTIVES/HYPOTHESIS: Current three-dimensional (3D) printed simulations are complicated by insufficient void spaces and inconsistent density. We describe a novel simulation with focus on internal anatomic fidelity and evaluate against template/identical cadaveric education. STUDY DESIGN: Research ethics board-approved prospective cohort study. METHODS: Generation of a 3D printed temporal bone was performed using a proprietary algorithm that deconstructs the digital model into slices prior to printing. This supplemental process facilitates removal of residual material from air-containing spaces and permits requisite infiltrative access to the all regions of the model. Ten otolaryngology trainees dissected a cadaveric temporal bone (CTB) followed by a matched/isomorphic 3D printed bone model (PBM), based on derivative micro-computed tomography data. Participants rated 1) physical characteristics, 2) specific anatomic constructs, 3) usefulness in skill development, and 4) perceived educational value. The survey instrument employed a seven-point Likert scale. RESULTS: Trainees felt physical characteristics of the PBM were quite similar to CTB, with highly ranked cortical (5.5 ± 1.5) and trabecular (5.2 ± 1.3) bone drill quality. The overall model was considered comparable to CTB (5.9 ± 0.74), with respectable air cell reproduction (6.1 ± 1.1). Internal constructs were rated as satisfactory (range, 4.9-6.2). The simulation was considered a beneficial training tool for all types of mastoidectomy (range, 5.9-6.6), posterior tympanotomy (6.5 ± 0.71), and skull base approaches (range, 6-6.5). Participants believed the model to be an effective training instrument (6.7 ± 0.68), which should be incorporated into the temporal bone lab (7.0 ± 0.0). The PBM was thought to improve confidence (6.7 ± 0.68) and operative performance (6.7 ± 0.48). CONCLUSIONS: Study participants found the PBM to be an effective platform that compared favorably to CTB. The model was considered a valuable adjunctive training tool with both realistic mechanical and visual character. LEVEL OF EVIDENCE: NA

Design and Validation of 3D Printed Complex Bone Models with Internal Anatomic Fidelity for Surgical Training and Rehearsal.

Physical models of complex bony structures can be used for surgical skills training. Current models focus on surface rendering but suffer from a lack of internal accuracy due to limitations in the manufacturing process. We describe a technique for generating internally accurate rapid-prototyped anatomical models with solid and hollow structures from clinical and microCT data using a 3D printer. In a face validation experiment, otolaryngology residents drilled a cadaveric bone and its corresponding printed model. The printed bone models were deemed highly realistic representations across all measured parameters and the educational value of the models was strongly appreciated.

Comparison of cadaveric and isomorphic virtual haptic simulation in temporal bone training.

BACKGROUND: Virtual surgery may improve learning and provides an opportunity for pre-operative surgical rehearsal. We describe a novel haptic temporal bone simulator specifically developed for multicore processing and improved visual realism. A position locking algorithm for enhanced drill-bone interaction and haptic fidelity is further employed. The simulation construct is evaluated against cadaveric education. METHODS: A voxel-based simulator was designed for multicore architecture employing Marching Cubes and Laplacian smoothing to perform real-time haptic and graphic rendering of virtual bone. RESULTS: Residents were equivocal about the physical properties of the VM, as cortical (3.2 ± 2.0) and trabecular (2.8 ± 1.6) bone drilling character was appraised as dissimilar to CTB. Overall similarity to cadaveric training was moderate (3.5 ± 1.8). Residents generally felt the VM was beneficial in skill development, rating it highest for translabyrinthine skull-base approaches (5.2 ± 1.3). The VM was considered an effective (5.4 ± 1.5) and accurate (5.7 ± 1.4) training tool which should be integrated into resident education (5.5 ± 1.4). The VM was thought to improve performance (5.3 ± 1.8) and confidence (5.3 ± 1.9) and was highly rated for anatomic learning (6.1 ± 1.9). CONCLUSION: Study participants found the VM to be a beneficial and effective platform for learning temporal bone anatomy and surgical techniques. They identify some concern with limited physical realism likely owing to the haptic device interface. This study is the first to compare isomorphic simulation in education. This significantly removes possible confounding features as the haptic simulation was based on derivative imaging.

The homeobox gene Emx2 underlies middle ear and inner ear defects in the deaf mouse mutant pardon.

The semi-dominantly inherited mouse mutation pardon (Pdo) was isolated due to the lack of a Preyer reflex (ear flick) in response to sound from a large-scale N -ethyl- N -nitrosourea (ENU) mutagenesis programme. Dissection of the middle ear revealed malformations in all three ossicles, rendering the ossicular chain incomplete. Hair cell counts in the apical turn of the organ of Corti revealed a significant 22.7% increase in the number of outer hair cells. Raised compound action potential thresholds in Pdo/+ mutants suggested a combined sensorineural/conductive hearing loss. We show that a missense mutation in the homeobox gene Emx2 is responsible for these defects, identifying a new function for this gene in the development of specific structures in the ear.

A Myo7a mutation cosegregates with stereocilia defects and low-frequency hearing impairment.

A phenotype-driven approach was adopted in the mouse to identify molecules involved in ear development and function. Mutant mice were obtained using N-ethyl- N-nitrosourea (ENU) mutagenesis and were screened for dominant mutations that affect hearing and/or balance. Heterozygote headbanger ( Hdb/+) mutants display classic behavior indicative of vestibular dysfunction including hyperactivity and head bobbing, and they show a Preyer reflex in response to sound but have raised cochlear thresholds especially at low frequencies. Scanning electron microscopy of the surface of the organ of Corti revealed abnormal stereocilia bundle development from an early age that was more severe in the apex than the base. Utricular stereocilia were long, thin, and wispy. Homozygotes showed a similar but more severe phenotype. The headbanger mutation has been mapped to a 1.5-cM region on mouse Chromosome 7 in the region of the unconventional myosin gene Myo7a, and mutation screening revealed an A>T transversion that is predicted to cause an isoleucine-to-phenylalanine amino acid substitution (I178F) in a conserved region in the motor-encoding domain of the gene. Protein analysis revealed reduced levels of myosin VIIa expression in inner ears of headbanger mice. Headbanger represents a novel inner ear phenotype and provides a potential model for low-frequency-type human hearing loss.