Bioinformatics characterization of variants of uncertain significance in pediatric sensorineural hearing loss.

Introduction: Rapid advancements in Next Generation Sequencing (NGS) and bioinformatics tools have allowed physicians to obtain genetic testing results in a more rapid, cost-effective, and comprehensive manner than ever before. Around 50% of pediatric sensorineural hearing loss (SNHL) cases are due to a genetic etiology, thus physicians regularly utilize targeted sequencing panels that identify variants in genes related to SNHL. These panels allow for early detection of pathogenic variants which allows physicians to provide anticipatory guidance to families. Molecular testing does not always reveal a clear etiology due to the presence of multigenic variants with varying classifications, including the presence of Variants of Uncertain Significance (VUS). This study aims to perform a preliminary bioinformatics characterization of patients with variants associated with Type II Usher Syndrome in the presence of other multigenic variants. We also provide an interpretation algorithm for physicians reviewing molecular results with medical geneticists. Methods: Review of records for multigenic and/or VUS results identified several potential subjects of interest. For the purposes of this study, two ADGRV1 compound heterozygotes met inclusion criteria. Sequencing, data processing, and variant calling (the process by which variants are identified from sequence data) was performed at Invitae (San Francisco CA). The preliminary analysis followed the recommendations outlined by the American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) in 2015 and 2019. The present study utilizes computational analysis, predictive data, and population data as well as clinical information from chart review and publicly available information in the ClinVar database. Results: Two subjects were identified as compound heterozygotes for variants in the gene ADGRV1. Subject 1's variants were predicted as deleterious, while Subject 2's variants were predicted as non-deleterious. These results were based on known information of the variants from ClinVar, multiple lines of computational data, population databases, as well as the clinical presentation. Discussion: Early molecular diagnosis through NGS is ideal, as families are then able to access a wide range of resources that will ultimately support the child as their condition progresses. We recommend that physicians build strong relationships with medical geneticists and carefully review their interpretation before making recommendations to families, particularly when addressing the VUS. Reclassification efforts of VUS are supported by studies like ours that provide evidence of pathogenic or benign effects of variants.

Non-protective immunity after standard pneumococcal vaccination series identified as a potential contributing risk factor for refractory otolaryngologic conditions in children.

OBJECTIVE: To examine the relationship between conferred immunity after standard pneumococcal series and refractory otolaryngologic infections in pediatric patients using post-vaccination antibody titers, and to identify contributory underlying conditions revealed when vaccination/re-vaccination fails to confer protective immunity. STUDY DESIGN: IRB-reviewed and "exempt" retrospective case series with chart review using the Epic® Electronic Medical Record system from 2013 to 2021. SETTING: Dedicated tertiary referral children's hospital. METHODS: Pneumococcal antibody titer results were assessed for children ages 0 to 21 years and: (1) at least 1 of 7 otolaryngologic disease diagnoses and (2) having received the 4-dose schedule of pneumococcal conjugate vaccine (PCV 7 or 13). RESULTS: A total of 241 subjects met inclusion criteria with 356 laboratory tests. Recurrent acute otitis media, chronic rhinitis, and chronic otitis media with effusion were the 3 most frequent diagnoses. At presentation, only 27.0% of subjects had titers conferring immunity from their prior vaccinations with PCV. About 85 subjects had been subsequently revaccinated with Pneumococcal Polysaccharide Vaccine (PPSV), and antibody responses conferring immunity reached 91.8%. Seven subjects never developed adequate responses; 5 of these had recurrent acute otitis media as the primary otolaryngologic diagnosis. Secondary "revealed" diagnoses included Juvenile Rheumatoid Arthritis (n = 1), unresolved specific antibody deficiency (n = 2), and Hypogammaglobulinemia (n = 1). CONCLUSION: In pediatric patients with recurrent infectious otolaryngologic disease refractory to traditional medical and surgical therapy, inadequate responses to pneumococcal vaccination may be revealed. This correlation represents a potential pathway for diagnosis and therapy.

Case Report: Transient Auditory Neuropathy (TAN) with resurgence of electrophysiologic waveforms observed between the neonatal period and age 3 years.

Auditory neuropathy spectrum disorder (ANSD) is a spectrum of conditions marked by diminished auditory function and believed to be caused by the impaired neural transmission of auditory stimulation in the setting of functional outer hair cells (Rance1). There are reports of "spontaneously resolving" or "transient" ANSD (TAN) in the literature. In this case report of TAN, we demonstrate the resurgence of the ABR waveform morphology over a 3-year period to reveal electrophysiologic testing consistent with the subject's functional hearing level by age 3 years.

Practical recommendations for planning and running live online education workshops for the rural health workforce.

AIM: This commentary presents practical and evidenced based guidelines for the development and delivery of real-time online training workshops aimed at rural health professionals. CONTEXT: Online learning is increasingly being used as an avenue for delivering education, particularly to rural and remote sites where barriers persist in upskilling health workers. Further, online learning has become essential during the coronavirus disease 2019 (COVID-19) pandemic. In response to the Australian 2020 COVID-19 social distancing requirements, our team rapidly transformed face-to-face educational workshops into an online format, to deliver over 20 workshops to more than 150 multidisciplinary staff across our large rural district. APPROACH: There are no published guidelines regarding the conversion of face-to-face education programs into an online format within health care. We conducted a review of the literature regarding the implementation of online education programs. Three broad categories of evidence were identified: participant qualities, content development and content deliverance. CONCLUSION: We present a set of practical and evidenced based recommendations, which will enhance live online workshops for a rural health workforce. These recommendations are derived both from published literature and our experience delivering our workshops. We argue that rural health professionals and organisations need relevant, up-to-date practical guidelines and more institutional support and training focused on creating and implementing live online educational programs in rural Australia.

Telehealth Adoption and Perspectives Among Pediatric Otolaryngologists Following the COVID-19 Pandemic.

OBJECTIVES: To assess use of and physician experiences with pediatric otolaryngology telehealth visits as impacted by the COVID-19 pandemic. STUDY DESIGN/SETTING: Cross sectional survey. METHODS: A 15-question survey was electronically distributed to 656 members of the American Society of Pediatric Otolaryngology in August 2021, addressing member demographics, experiential practice elements, and use pre-pandemic, during the initial shutdown period of March-May 2020, and current use at the time of survey inquiry. RESULTS: There were 124 respondents (response rate = 18.9%). Incident use pre-pandemic and during the shutdown were 21.0% (n = 26), and 92.7% (n = 115), respectively. Current use was 83.9% (n = 104) and the percentage of new current users (79.5%, n = 78) was significant (P < .0001,95% CI = 70.6%-86.4%). Estimated median telehealth visit rates pre-pandemic, during shutdown, and currently were 0 to 1, 4 to 5, and 2 to 3 per week, respectively (P < .0001). A difference in post-covid adoption rates was noted only for location (P = .008), with no differences for years out of training or practice type. Compared to in-person visits, physician satisfaction with telehealth visits was rated equivalent (49.0%) or worse/much worse (48.1%). The most common telehealth uses were follow-up visits (83.7%), pre-operative counseling (76.9%), and post-operative evaluation (69.2%). The need for a detailed exam (89.4%) and initial visits (32.7%) were reasons a telehealth visit was not offered. CONCLUSIONS: The COVID-19 pandemic appears to have precipitated a rapid increase in telehealth adoption among surveyed pediatric otolaryngologists, regardless of age or practice type. The most significant limitations remain the need for a detailed exam, perceived low patient technological literacy, and limitations to interpretive services. Technology-based optimization of these barriers could lead to increased use and physician satisfaction.

Racial identification represents significant risk factor for healthcare disparity among patients with severe bronchopulmonary dysplasia treated with tracheostomy.

OBJECTIVES: To characterize the patient population with severe bronchopulmonary dysplasia (BPD) requiring tracheostomy in a large tertiary level 4 neonatal intensive care unit (NICU) and to identify potential targets for improvement in the delivery of high-quality healthcare. METHODS: An IRB-exempt but IRB-registered retrospective review of medical records. Study inclusion criteria: patients treated for severe BPD with tracheostomy under 2 years of age in our tertiary referral center NICU. Control group criteria: 4-year aggregate NICU patient demographics. Basic demographics, maternal history, clinical data points, and outcomes variables were collected. RESULTS: There was a statistically significant difference between the two groups in only one variable: racial identification (p-value = 0.036). All data points were then analyzed against racial identification, and statistically significant differences appeared in 4 categories: 1) illicit drug use, 2) birth head circumference and length, 3) days to readmission, and 4) child opportunity index scores. There was not a statistically significant difference in any other maternal characteristics or medical comorbidities, NICU length of stay, age at tracheostomy, or decannulation status. CONCLUSION: The incidence of our tracheostomy in infants with severe BPD was significantly higher (p = 0.036) in the subjects whose families identified as racially African American or Black, a marked contrast to our general NICU population and our overall tracheostomy population. The timing of the first readmission to the hospital was shorter for Caucasian or White infants compared to African American or Black infants. COI demonstrated statistically significantly poorer resources for African American or Black infants compared to White infants with tracheostomy. All other perinatal and outcome measurements did not differ significantly between the two racial groups. This suggests that this racial disparity is present and needs further investigation to better assess its impact on risk and outcomes as we develop pathways for high-quality healthcare delivery.

Multifractal Analysis to Determine the Effect of Surface Topography on the Distribution, Density, Dispersion and Clustering of Differently Organised Coccal-Shaped Bacteria.

The topographic features of surfaces are known to affect bacterial retention on a surface, but the precise mechanisms of this phenomenon are little understood. Four coccal-shaped bacteria, Staphylococcus sciuri, Streptococcus pyogenes, Micrococcus luteus, and Staphylococcus aureus, that organise in different cellular groupings (grape-like clusters, tetrad-arranging clusters, short chains, and diploid arrangement, respectively) were used. These differently grouped cells were used to determine how surface topography affected their distribution, density, dispersion, and clustering when retained on titanium surfaces with defined topographies. Titanium-coated surfaces that were smooth and had grooved features of 1.02 µm-wide, 0.21 µm-deep grooves, and 0.59 µm-wide, 0.17 µm-deep grooves were used. The average contact angle of the surfaces was 91°. All bacterial species were overall of a hydrophobic nature, although M. luteus was the least hydrophobic. It was demonstrated that the 1.02 µm-wide featured surface most affected Strep. pyogenes and S. sciuri, and hence the surfaces with the larger surface features most affected the cells with smaller dimensions. The 0.59 µm featured surface only affected the density of the bacteria, and it may be suggested that the surfaces with the smaller features reduced bacterial retention. These results demonstrate that the size of the topographical surface features affect the distribution, density, dispersion, and clustering of bacteria across surfaces, and this is related to the cellular organisation of the bacterial species. The results from this work inform how surface topographical and bacterial properties affect the distribution, density, dispersion, and clustering of bacterial retention.

The Removal of Meat Exudate and Escherichia coli from Stainless Steel and Titanium Surfaces with Irregular and Regular Linear Topographies.

Bacterial retention and organic fouling on meat preparation surfaces can be influenced by several factors. Surfaces with linear topographies and defined chemistries were used to determine how the orientation of the surface features affected cleaning efficacy. Fine polished (irregular linear) stainless steel (FPSS), titanium coated fine polished (irregular linear) stainless steel (TiFP), and topographically regular, linear titanium coated surfaces (RG) were fouled with Escherichia coli mixed with a meat exudate (which was utilised as a conditioning film). Surfaces were cleaned along or perpendicular to the linear features for one, five, or ten wipes. The bacteria were most easily removed from the titanium coated and regular featured surfaces. The direction of cleaning (along or perpendicular to the surface features) did not influence the amount of bacteria retained, but meat extract was more easily removed from the surfaces when cleaned in the direction along the linear surface features. Following ten cleans, there was no significant difference in the amount of cells or meat exudate retained on the surfaces cleaned in either direction. This study demonstrated that for the E. coli cells, the TiFP and RG surfaces were easiest to clean. However, the direction of the clean was important for the removal of the meat exudate from the surfaces.

Health literacy rates among pediatric tracheostomy caregivers.

INTRODUCTION: As health outcomes and disparities become more important in national healthcare, physicians must be aware of every patient's health literacy in order to deliver effective care. Our goal was to measure the health literacy rates in the caregivers of our pediatric tracheostomy population. These caregivers specifically have an immense responsibility that requires a certain capacity for understanding and learning complex skills. Thus far there have been no studies or surveys investigating the rates of health literacy in this population or tracheostomy patients in general. Caregivers' literacy rates were measured by administering a Test of Functional Health Literacy in Adults (TOFHLA). This test uses actual materials that patients might encounter in a typical clinic and consists of a reading comprehension and numeracy section. To assess impact of the complex care on caregiver quality of life, we simultaneously administered the Pediatric Tracheostomy Health Status Instrument (PTHSI), a validated caregiver quality of life measurement. METHODS: Caregivers of children with tracheostomies were recruited and surveyed during the Pediatric Tracheostomy Clinic between July 2019-October 2019. Twenty - six caregivers completed the TOFHLA; 24 completed all three parts - the TOFHLA, the demographic survey, and the PTHSI. RESULTS: Health literacy rates among patient families in the out-patient setting with experience with tracheostomy were deemed "adequate" in 85% of caregivers; the remaining 15% of caregivers scored "inadequate". Overall adult literacy rates in the general population in this state are 26% "inadequate." Approximately 80% of our caregivers rely solely on Medicaid for healthcare insurance and nearly half of participants reported an annual household income less than $5000. Ages of caregivers ranged from 20 to 61 years, with no significant correlation to health literacy. The average PTHSI score was 36 (SD 8.6), denoting a moderate level of caregiver burden but no correlation to the caregiver health literacy score was found. When comparing caregiver health literacy scores in relation to education level, caregivers with college and post-graduate education had higher literacy scores than those with a high school education, p = .0086. In addition, when comparing African American to white caregivers, white caregivers were found to have higher health literacy scores, p = .036. Notably, caregiver burden as measured by the PTHSI score did not differ significantly between caregivers in lower income and higher income levels, p = .91. CONCLUSION: Health literacy measurements for caregivers of children with complex medical conditions exceed the health literacy rates of the general population in our state, potentially biased by the intensive training provided to families during their prolonged hospitalization. Healthcare disparities may impact the medically complex child differently from the healthy child. Assumptions about health, wealth and caregiver burden may be inaccurate and warrant further evaluation. Assessing health literacy before institutionalization has occurred may enable us to more accurately design caregiver training programs to further augment literacy and health literacy.