Economic Evaluation of Pediatric Tracheostomy: A Cost of Illness Analysis.

Objective: This study aimed to determine the direct costs of pediatric tracheostomy care within a health care system. Study Design: Prospective analysis. Setting: Academic children's hospital. Methods: Costs associated with caring for pediatric tracheostomy patients under 18 years were analyzed between 2015 and 2021. Direct costs were calculated using the Medicare/Medicaid charges-to-costs ratio for various visit types. Costs were estimated using generalized linear equations, accounting for confounders. Results: A total of 297 children underwent tracheostomy at a median age of 0.94 years. The median follow-up was 2.5 years, resulting in 13,966 visits (mean = 41). The total cost was $321 million. The initial admission accounted for 72% ($231 million) of costs while other inpatient admissions added 24% ($78 million). Emergency department, observation, and outpatient visits comprised 4% of costs. The length of stay (LOS) was the primary cost driver for inpatient visits. Each additional hospital day increased costs by roughly $1195, and each extra admission added about $130,223 after adjusting for confounders. Respiratory failure and infections were the primary reasons for 67% of subsequent admissions. Conclusion: Pediatric tracheostomy care generated over $300 million in direct costs over 5 years. Inpatient stays constituted 96% of these costs, with the LOS being a major factor. To reduce direct health expenditures for these patients, the focus should be on minimizing admissions.

Pediatric tracheostomy audiometric outcomes - A quality improvement initiative.

OBJECTIVE: Pediatric tracheostomy patients disproportionately experience hearing loss and are at risk for delayed identification due to their medical complexity. Nonetheless, protocols to monitor hearing in these children are lacking. This quality improvement (QI) initiative aimed to increase the rates of audiometric testing within 12 months of pediatric tracheostomy placement. METHODS: A retrospective cohort study included children who underwent tracheostomy under 18 months of age between 2012 and 2020. Rates of audiometric assessments before and after QI project implementation (2015) were reported along with hearing loss characteristics. RESULTS: A total of 253 children met inclusion. Before project initiation (2012-2014), 32% of children (28/87) obtained audiometric testing within 12 months after tracheostomy. During the first three years of implementation (2015-2017), 39% (38/97) were tested, while 55% (38/69) were tested during the subsequent three years (2018-2020) (P = .01). A passing newborn hearing screen was obtained for 70% of the 210 children with a recorded result, and 198 survived at least 12 months to receive audiometric testing at a median of 11.3 months (IQR: 6.2-22.8) after tracheostomy. Hearing loss was identified for 44% of children (N = 88), of which 42 children initially passed newborn hearing screen. A second assessment was obtained for 62% of children (123/198) at a median of 11.3 months (IQR: 4.5-17.5) after the initial test. In this group, 23% with a previously normal audiometric exam were found to have hearing loss (15/66). CONCLUSIONS: QI initiatives designed to monitor hearing loss in children with a tracheostomy can result in improved rates of audiometric assessments. This population has disproportionately high rates of hearing loss, including delayed onset hearing loss making audiometric protocols valuable to address speech and language development delays.

Oral Cavity Cancer Outcomes in Remote, Betel Nut-Endemic Pacific Islands.

BACKGROUND: Oral cavity carcinomas individually are the fifth-leading cause of overall cancer mortality in the Northern Mariana Islands, which is likely a representative statistic for many other betel-nut-endemic Pacific islands. Factors associated with survival have been minimally evaluated in this region. The purpose of this study is to further characterize oral cavity carcinoma outcomes and associated prognostic factors in the United States commonwealth of the Northern Mariana Islands (CNMI). METHODS: A single-institution retrospective review was undertaken for 81 patients diagnosed with head and neck cancers at the CNMI's only regional hospital complex from 2005 to 2019. A subset of patients diagnosed with oral cavity carcinoma was further evaluated for survival outcomes. Cox proportional hazard regressions were performed to evaluate for variables associated with survival. RESULTS: A majority of patients had cancer of the oral cavity (64/81, 79%). Fifty-five of these patients had sufficient data for review. The average age at the time of diagnosis was 48 and over half were diagnosed with stage IV disease (29/55, 53%). Five-year overall survival (OS) was 49.5% (95% CI, 33.3-63.7%). Factors associated with worse OS were lymph node metastases at presentation (P = .031), higher overall stage (III or IV vs I or II, P = .016), and higher T-stage (III or IV vs I or II, P = .027). Those who used betel nut were diagnosed at a significantly younger age than those who did not (47.2 vs 55.4, P = .001). CONCLUSIONS: The head and neck cancer burden in the CNMI is dominated by betel nut related oral cavity disease that is characterized by delayed presentations in younger patients and decreased OS. Future studies are indicated to improve health literacy as well as to investigate the potential for screening programs.

A Survey of Areca (Betel) Nut Use and Oral Cancer in the Commonwealth of the Northern Mariana Islands.

Areca nut use is a cause of higher rates of oral cavity cancer in the Commonwealth of the Northern Mariana Islands (CNMI). Little is known about patient insights into the risks of areca nut use worldwide. The purpose of this study is to evaluate perceptions of areca nut use and oral cancer among chewers in the CNMI. This is a survey study undertaken at the CNMI's only regional health center-300 adult participants completed a 21-question survey that assessed demographics, chewing behaviors, perceptions of areca nut use and oral cancer, and the willingness to participate in cessation and screening programs. Data was analyzed using chi-squared tests, at a significance value of P < .05. The participant average age was 38, and 41% were male. Almost all (92%) knew that chewing areca nut causes oral cancer, but only 13% correctly identified the actual areca nut as a carcinogen. About half (59%) believed that oral cancer could be treated. Most people (74%) were willing to participate in screening programs for oral cancer. Those who chewed areca nut daily were more likely to be interested in medicated replacement products relative to those who chewed less frequently (P = .048). In conclusion, there are drastic misperceptions about areca nut and oral cancer in the CNMI. Efforts should be made towards promoting awareness of the carcinogenicity of the actual areca nut, and the treatability of oral cancer. Mandated educational warnings should be required with areca nut sales. Further research evaluating substitution methods and screening programs is indicated.

The profound oral cavity cancer burden in the United States Commonwealth of the Northern Mariana Islands: A global health opportunity.

PURPOSE: Betel nut consumption contributes to higher rates of oral cavity cancer throughout Micronesia. The purpose of this study is to review local surveys and cancer data to further characterize these issues in the Northern Mariana Islands (CNMI). METHODS: Two commonwealth-wide health inquiries were reviewed: The Non-Communicable Diseases Survey (NCDS), 2016 and The Youth Risk Behavior Survey (YRBS), 2013. Data pertaining to betel nut, tobacco and alcohol use was extracted. Relevant cancer data from the Commonwealth Healthcare Corporation (CHC) of Saipan and the Surveillance, Epidemiology, and End Results (SEER) databases was assessed. RESULTS: Betel nut chewing was reported by 43% of Asian Pacific Islander (API) adults, with 88% adding tobacco to the chew. Adults aged 20-30 had significantly higher rates of chewing relative to older groups (p < .0001). Tobacco smoking and alcohol use were reported by 25% and 23% of adults, respectively. Betel nut chewing was reported by 33% of high school students. From 2007 to 2016, oral cavity cancers contributed to 9% of all cancer diagnoses and 13% of cancer-related mortalities. SEER data supported oral cavity cancer diagnoses at younger ages in APIs. CONCLUSION: These results demonstrate concerning trends regarding alcohol, tobacco and betel nut use in the CNMI. Betel nut use is prevalent among APIs of nearly all ages, with the majority adding tobacco to their chew. The available data suggests a drastic oral cavity cancer burden in the CNMI. Efforts should be made to evaluate for effective means of primary and secondary prevention in API regions.

Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen.

Periodontitis is a microbial infection that destroys the structures that support the teeth. Although it is typically a chronic condition, rapidly progressing, aggressive forms are associated with the oral pathogen Aggregatibacter actinomycetemcomitans One of this bacterium's key virulence traits is its ability to attach to surfaces and form robust biofilms that resist killing by the host and antibiotics. Though much has been learned about A. actinomycetemcomitans since its initial discovery, we lack insight into a fundamental aspect of its basic biology, as we do not know the full set of genes that it requires for viability (the essential genome). Furthermore, research on A. actinomycetemcomitans is hampered by the field's lack of a mutant collection. To address these gaps, we used rapid transposon mutant sequencing (Tn-seq) to define the essential genomes of two strains of A. actinomycetemcomitans, revealing a core set of 319 genes. We then generated an arrayed mutant library comprising >1,500 unique insertions and used a sequencing-based approach to define each mutant's position (well and plate) in the library. To demonstrate its utility, we screened the library for mutants with weakened resistance to subinhibitory erythromycin, revealing the multidrug efflux pump AcrAB as a critical resistance factor. During the screen, we discovered that erythromycin induces A. actinomycetemcomitans to form biofilms. We therefore devised a novel Tn-seq-based screen to identify specific factors that mediate this phenotype and in follow-up experiments confirmed 4 mutants. Together, these studies present new insights and resources for investigating the basic biology and disease mechanisms of a human pathogen.IMPORTANCE Millions suffer from gum disease, which often is caused by Aggregatibacter actinomycetemcomitans, a bacterium that forms antibiotic-resistant biofilms. To fully understand any organism, we should be able to answer: what genes does it require for life? Here, we address this question for A. actinomycetemcomitans by determining the genes in its genome that cannot be mutated. As for the genes that can be mutated, we archived these mutants into a library, which we used to find genes that contribute to antibiotic resistance, leading us to discover that antibiotics cause A. actinomycetemcomitans to form biofilms. We then devised an approach to find genes that mediate this process and confirmed 4 genes. These results illuminate new fundamental traits of a human pathogen.

Placental Toll-like receptor 3 and Toll-like receptor 7/8 activation contributes to preeclampsia in humans and mice.

Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome characterized by excessive maternal immune system activation, inflammation, and endothelial dysfunction. Toll-like receptor (TLR) 3 activation by double-stranded RNA (dsRNA) and TLR7/8 activation by single-stranded RNA (ssRNA) expressed by viruses and/or released from necrotic cells initiates a pro-inflammatory immune response; however it is unknown whether viral/endogenous RNA is a key initiating signal that contributes to the development of PE. We hypothesized that TLR3/7/8 activation will be evident in placentas of women with PE, and sufficient to induce PE-like symptoms in mice. Placental immunoreactivity and mRNA levels of TLR3, TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women. Treatment of human trophoblasts with the TLR3 agonist polyinosine-polycytidylic acid (poly I:C), the TLR7-specific agonist imiquimod (R-837), or the TLR7/8 agonist CLO97 significantly increased TLR3/7/8 levels. Treatment of mice with poly I:C, R-837, or CLO97 caused pregnancy-dependent hypertension, endothelial dysfunction, splenomegaly, and placental inflammation. These data demonstrate that RNA-mediated activation of TLR3 and TLR7/8 plays a key role in the development of PE.