Demographic Influences on Adult HPV Vaccination: Results from a Cross-Sectional Survey in Tennessee.

HPV is the most prevalent sexually transmitted infection in the U.S., with more than 80% of all Americans contracting it by age 45. Effective vaccines for HPV exist and were recently approved for adults aged 27-45 years, though uptake remains low in all age groups, particularly in Tennessee where 1089 cancers were attributed to HPV in 2020. Between 29 June and 17 August 2023, we conducted a cross-sectional survey to gain insights about the barriers and facilitators of HPV in 2011 adults aged 18 to 45 years in Tennessee. We developed our survey based on previous instruments to understand predictors of HPV vaccination in adults. Using descriptive statistics and bivariate and logistic regression analyses, we found higher vaccination rates in females, participants aged 18-38 years, participants with a high school education or higher, Hispanic or Latine individuals, and participants identifying as moderate or liberal. These insights highlight the need for public health interventions that consider demographic differences to successfully increase vaccination rates and reduce HPV-associated cancer risk.

A Narrative Review of Pain in Pediatric Oncology: The Opioid Option.

Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.

Views of the Pharmacists' Role in HPV Vaccinations: A Qualitative Study in Tennessee.

The Human Papillomavirus (HPV) is a frequently occurring sexually transmitted infection in adults and is associated with various cancers that can affect both males and females. Recently, the Advisory Committee on Immunization Practices (ACIP) expanded its recommendations for the HPV vaccine to include patients aged 27-45 years with shared clinical decision-making. A commonly reported obstacle to receiving the HPV vaccine among adults is a lack of healthcare provider recommendations. Considering the suboptimal HPV vaccine coverage figures and noting that the vast majority of hesitancy research has been conducted among children and adolescents, limited research is available on the adult perception of HPV vaccination in pharmacies. This study focuses on understanding adults' opinions and perceptions regarding the role of pharmacists in the uptake of the HPV vaccine and awareness of its availability in the pharmacy setting. METHODS: After receiving approval from the Institutional Review Board (IRB), the qualitative study was initiated using virtual focus groups (FGs). Concepts from the Transtheoretical Model, the Health Belief Model, and the Social Cognitive Theory guided the study design. The corpus of data was collected in 2021 and 2022 by two researchers, and a third party transcribed the FGs to avoid any biases. The data were analyzed using Braun and Clarke's Thematic Analysis. RESULTS: Out of 35 subjects that participated in six FGDs, most identified as female, with ages ranging from 18 to 45 years. The following four themes emerged: (1) HPV vaccine awareness; (2) stigmas leading to reduced education and vaccination rates; (3) education preferences; (4) follow-up in vaccination series reminders and preferences. CONCLUSION: Participants' views of the HPV vaccine and the ability to receive the vaccine in a pharmacy are influenced by a myriad of factors. Common factors include improved awareness, preferences for educational modalities, avoiding stigmas associated with HPV vaccination, combating gender-focused biases, and preferences for the location of vaccination. These barriers provide opportunities for pharmacists to promote and enhance vaccine uptake.

Large-scale gene expression changes in APP/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder with both genetic and non-genetic causes. Animal research models are available for a multitude of diseases and conditions affecting the central nervous system (CNS), and large-scale CNS gene expression data exist for many of these. Although there are several models specifically for AD, each recapitulates different aspects of the human disease. In this study we evaluate over 500 animal models to identify those with CNS gene expression patterns matching human AD datasets. Approaches included a hypergeometric based scoring system that rewards congruent gene expression patterns but penalizes discordant gene expression patterns. The top two models identified were APP/PS1 transgenic mice expressing mutant APP and PSEN1, and mice carrying a GFAP mutation that is causative of Alexander disease, a primary disorder of astrocytes in the CNS. The APP/PS1 and GFAP models both matched over 500 genes moving in the same direction as in human AD, and both had elevated GFAP expression and were highly congruent with one another. Also scoring highly were the 5XFAD model (with five mutations in APP and PSEN1) and mice carrying CK-p25, APP, and MAPT mutations. Animals with the APOE3 and 4 mutations combined with traumatic brain injury ranked highly. Bulbectomized rats scored high, suggesting anosmia could be causative of AD-like gene expression. Other matching models included the SOD1G93A strain and knockouts for SNORD116 (Prader-Willi mutation), GRID2, INSM1, XBP1, and CSTB. Many top models demonstrated increased expression of GFAP, and results were similar across multiple human AD datasets. Heatmap and Uniform Manifold Approximation Plot results were consistent with hypergeometric ranking. Finally, some gene manipulation models, including for TYROBP and ATG7, were identified with reversed AD patterns, suggesting possible neuroprotective effects. This study provides insight for the pathobiology of AD and the potential utility of available animal models.

Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease.

PURPOSE: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR-Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD. METHODS: Multi-shell DWI of age- and sex-matched AxD and wild-type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD. RESULTS: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex. CONCLUSION: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD.

Perspectives Associated with Human Papillomavirus Vaccination in Adults: A Qualitative Study.

BACKGROUND: In the last several decades, vaccine hesitancy has become a significant global public health concern. The human papillomavirus (HPV) vaccine has been on the United States of America (USA) market since 2006, with extended approval up to age 45 granted in 2018. To date, there is limited research evaluating barriers and facilitators related to HPV vaccine initiation among adults and the influence of the COVID-19 pandemic on individuals' vaccine-related behaviors. This study's main objective was to characterize the contributing factors that could promote or inhibit HPV vaccine uptake for adults. METHODS: A qualitative approach consisting of focus group discussions (FGDs) was used for this study. The FGD guide was informed by concepts from the Transtheoretical Model, Health Belief Model, and Social Cognitive Theory. All virtual FGDs were led by two researchers, who recorded audio for data collection. The data were transcribed by a third party, and the transcripts were imported into Dedoose® software and analyzed using the six steps recommended by thematic analysis. RESULTS: A total of 35 individuals participated in 6 focus groups over a 6-month period. Thematic analysis revealed four themes: (1) Intrinsic motivators for HPV vaccination, (2) Extrinsic motivators for HPV vaccination, (3) Vaccine promotion strategies, and (4) Impact of COVID-19 Pandemic on vaccine hesitancy. CONCLUSION: Both intrinsic and extrinsic factors play a role in influencing HPV vaccine uptake, and such considerations can guide efforts to improve the odds of HPV vaccination in working-age adults.

STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease.

Alexander disease (AxD) is caused by mutations in the gene for glial fibrillary acidic protein (GFAP), an intermediate filament expressed by astrocytes in the central nervous system. AxD-associated mutations cause GFAP aggregation and astrogliosis, and GFAP is elevated with the astrocyte stress response, exacerbating mutant protein toxicity. Studies in mouse models suggest disease severity is tied to Gfap expression levels, and signal transducer and activator of transcription (STAT)-3 regulates Gfap during astrocyte development and in response to injury and is activated in astrocytes in rodent models of AxD. In this report, we show that STAT3 is also activated in the human disease. To determine whether STAT3 contributes to GFAP elevation, we used a combination of genetic approaches to knockout or reduce STAT3 activation in AxD mouse models. Conditional knockout of Stat3 in cells expressing Gfap reduced Gfap transactivation and prevented protein accumulation. Astrocyte-specific Stat3 knockout in adult mice with existing pathology reversed GFAP accumulation and aggregation. Preventing STAT3 activation reduced markers of reactive astrocytes, stress-related transcripts, and microglial activation, regardless of disease stage or genetic knockout approach. These results suggest that pharmacological inhibition of STAT3 could potentially reduce GFAP toxicity and provide a therapeutic benefit in patients with AxD.

Impact of patient and provider nudges on addressing herpes zoster vaccine series completion.

OBJECTIVES: To determine the combined impact of provider-facing and text message-based, patient nudges on herpes zoster vaccine series completion. METHODS: Following a period during which Kroger Health implemented provider facing nudges, select US patients that initiated herpes zoster vaccination were randomized to receive timed text messages when the second dose was due and available as part of a quality improvement exercise. Main comparisons were between patients intervened by provider nudge only and those intervened by both provider and patient nudges. Data were assessed by GEE-basedlogistic and linear regression, controlling for available patient- and store-level characteristics, and geospatial analyses. RESULTS: During the baseline period, 100,627 adults received at least one HZ vaccine dose and 83.9% completed the series within 6 months over 88.6 days (SD: 26.53) on average. In the intervention period, 120,339 adults were vaccinated at least once and series completion was 88.3% (both provider nudges and text messaging) and 85.3% (not texted) during this observation window (both p < 0.0001). Time between doses was shorter for those who received text messages compared to both the baseline period and those in the intervention period that were not texted (both p < 0.001). Controlling for multiple characteristics, the odds of completion improved in the intervention period compared to baseline (OR: 1.07; 95% CI: 1.033-1.111), but a noticeably higher completion odds was observed amongst patients who received a text message in the intervention period (OR: 1.35; 95% CI: 1.286-1.414). Adjusting for patient and pharmacy factors, those who were texted received their second herpes zoster vaccine dose 8.6 days sooner (95% CI: -9.08 - -8.17, p < 0.0001) compared to those intervened by the provider nudge only. CONCLUSION: The combined use of clinical and patient-focused nudges is a simple mechanism by which pharmacies and other health care access points can address the multi-dose vaccine needs of diverse patient populations.

COVID-19 vaccination program at a student-run free clinic: A descriptive study.

People historically excluded from receiving medical care in the United States, in addition to being at greater risk for SARS-CoV-2 infection, have had slower vaccine uptake due to structural barriers to availability. We present one student-run free clinic's SARS-CoV-2 vaccination program from January 15 to August 1, 2021, in Nashville, Tennessee. We tracked SARS-CoV-2 vaccine primary series completion among 273 free clinic patients with the help of medical student volunteers, who scheduled appointments and answered vaccine-related questions. We worked with our academic medical center partner to host a single-dose vaccination event at our clinic. We compared vaccine series completion in our clinic to adult vaccine completion in Davidson County, Tennessee on August 1, 2021. Of the 273 free clinic participants, 144 identified as Spanish-speaking (52.7%) and 172 (63%) had at least one qualifying comorbidity per the December 30, 2020, Tennessee COVID-19 Vaccination Plan. As such, 183 (67%) were characterized as vaccine eligible in Phase 1a2, 1b, or 1c. On August 1, 2021, 63.1% of free clinic patients had completed their primary SARS-CoV-2 vaccination series compared with 58.9% of adults in Davidson County, Tennessee (RD 4.2%, 95% CI: -1.5% to 9.9%). Spanish-speaking free clinic patients were most likely to have completed their vaccination series. We describe a framework for a patient-centered vaccination effort to reach individuals traditionally missed by large vaccination campaigns. We highlight structural hurdles experienced by vulnerable populations, including language barriers, lack of technology or reliable internet access, inflexible working schedules, lack of transportation, and vaccine misinformation.

The Lean Six Sigma Define, Measure, Analyze, Implement, Control (LSS DMAIC) Framework: An Innovative Strategy for Quality Improvement of Pharmacist Vaccine Recommendations in Community Pharmacy.

Community pharmacies represent a highly accessible and convenient setting for vaccination. However, setting-specific barriers exist which contribute to suboptimal vaccination rates, particularly for pneumococcal vaccinations. One proven quality improvement framework growing in use within healthcare settings is Lean Six Sigma (LSS). This paper describes the application of the LSS framework in select locations of a national pharmacy chain. The implementation of a training program for improved recommendation techniques to promote higher rates of pneumococcal vaccinations in high-risk adult populations is also addressed. A mixed-methods approach including pre/post quasi-experimental design and in-depth key informant interviews was used.

Clinical Nudge Impact on Herpes Zoster Vaccine Series Completion in Pharmacies.

INTRODUCTION: A new recombinant herpes zoster vaccine has advanced efforts to prevent shingles, but its multidose regimen introduces potential barriers to full protection that must be managed by community pharmacies. To address this potential patient management challenge, a pharmacy records clinical support tool was implemented to assist pharmacy staff in managing herpes zoster vaccine dose completion. METHODS: Beginning in November 2018, a large community pharmacy chain (operating in 36 states) implemented a provider nudge within its clinical decision support tool across all locations that fit seamlessly into the existing workflow, alerting the pharmacy staff of the need for a patient's second dose. Initial and second doses were followed over 2 overlapping, 10-month periods before and after system launch. Differences in vaccine completion rates before and after the system was operational were assessed by chi-square tests and predictors of completion, controlling for store- and patient-level characteristics, and were analyzed by multivariable logistic regression and generalized linear models throughout 2021. RESULTS: Across 2,271 pharmacies, 71,459 and 41,982 initial doses of the herpes zoster vaccine were given in the baseline and intervention period, respectively. The proportion of patients completing both doses increased slightly after system implementation (before: 71.9%, after: 75.2%; p<0.0001). However, dramatic improvements in time to dose completion were observed (before: 109.8 days, after: 93.3 days; p<0.001), and changes were significant in stores in all but 4 states. CONCLUSIONS: Results suggest that the use of a clinical nudge improved the occurrence of and time to herpes zoster vaccine dose completion in adults across the U.S.

A Comprehensive Review of Vaping Use in Pediatric Patients and Recent Changes in Regulatory Laws.

The use of electronic cigarettes (e-cigarettes), also known as vapes, by adolescents and young adults has dramatically increased over the past several years. E-cigarettes continue to be the most used form of tobacco among youth. As a result of this concerning trend, policies at both the state and federal levels have been implemented to limit availability in this population. Additionally, the coronavirus disease 2019 (COVID-19) pandemic has had some positive and negative effects on the youth vaping epidemic with adolescent consumers reporting limited access to retail sites during the stay-at-home executive orders, but easier access with online purchasing because age verification was often not required. Complications resulting from vaping have been reported and include e-cigarette or vaping product use-associated lung injury (EVALI) and thrombotic events. Data suggest that the use of vaping devices can lead to both short- and long-term respiratory morbidity in the pediatric population. This review serves to provide a comprehensive examination of vaping use in pediatric patients and recent changes in regulatory laws to equip pharmacists with the knowledge to be aware of the different devices and products available, ask their pediatric patients regularly about use, and counsel and educate on the potential harmful effects.

Anastasis Drives Senescence and Non-Cell Autonomous Neurodegeneration in the Astrogliopathy Alexander Disease.

Anastasis is a recently described process in which cells recover after late-stage apoptosis activation. The functional consequences of anastasis for cells and tissues are not clearly understood. Using Drosophila, rat and human cells and tissues, including analyses of both males and females, we present evidence that glia undergoing anastasis in the primary astrogliopathy Alexander disease subsequently express hallmarks of senescence. These senescent glia promote non-cell autonomous death of neurons by secreting interleukin family cytokines. Our findings demonstrate that anastasis can be dysfunctional in neurologic disease by inducing a toxic senescent population of astroglia.SIGNIFICANCE STATEMENT Under some conditions cells otherwise destined to die can be rescued just before death in a process called anastasis, or "rising from the dead." The fate and function of cells undergoing a near death experience is not well understood. Here, we find that in models and patient cells from Alexander disease, an important brain disorder in which glial cells promote neuronal dysfunction and death, anastasis of astrocytic glia leads to secretion of toxic signaling molecules and neurodegeneration. These studies demonstrate a previously unexpected deleterious consequence of rescuing cells on the brink of death and suggest therapeutic strategies for Alexander disease and related disorders of glia.

Social determinants of health and adult influenza vaccination: a nationwide claims analysis.

BACKGROUND: The health and economic benefits of the annual influenza vaccine are well documented, yet vaccination rates in the United States missed the Healthy People 2020 goal and remain a focus of Healthy People 2030 efforts. By identifying underlying reasons for low annual influenza vaccination, social elements that need targeting may be identified and could guide future interventions or policy development to achieve vaccination goals and improve overall public health. OBJECTIVE: To determine the influence of certain social determinants of health on adherence to annual influenza vaccination in American adults. METHODS: This was a retrospective cohort analysis using data from IBM MarketScan Commercial Claims and Encounters Database and national Medicare 5% sample data from 2013 to 2016. Study eligibility criteria included adults (aged 18 years and older) who were continuously enrolled for 3 influenza seasons between 2013 and 2016. Receipt of the influenza vaccine was counted over 3 consecutive influenza seasons, and select social determinants were extracted from publicly available sources. Patient characteristics, health resource utilization, and selected social determinants of health were included in bivariate and multivariate logistic regression analyses to determine their association with annual influenza vaccination. RESULTS: 6,694,571 adults across employer-sponsored and Medicare coverage groups were analyzed, of which 14.7% of Medicare-enrolled adults and 9.2% of commercially enrolled adults were vaccinated in all 3 seasons. Higher proportions of vaccine adherence (ie, all 3 seasons) were observed among females (9.6% vs 8.7% [commercial], 15.0% vs 14.4% [Medicare]), the immunocompromised (11.8% vs 8.3% [commercial], 15.9% vs 13.6% [Medicare]), rural residents (10.5% vs 9.0% [commercial], 15.4% vs 14.6% [Medicare]; all P < 0.0001), and those enrolled in a high-deductible health plan (10.3%). Multivariable logistic regression models indicated that the odds of vaccine adherence tended to be higher in areas of higher poverty (OR=1.012; 95% CI = 1.01-1.02 [commercial], OR=1.01; 95% CI = 1.01-1.01 [Medicare]) yet lower in areas with higher proportions of Democratic voters (OR=0.998; 95% CI = 0.998-0.998 [commercial], OR = 0.996; 95% CI = 0.996-0.997 [Medicare]). Among commercially insured adults, the odds of vaccine adherence were higher in areas of higher health literacy (OR=1.036; 95% CI = 1.036-1.037), but this effect was not observed among Medicare members. Conversely, the odds of vaccine adherence increased as the proportion of those residing in areas of limited Internet access increased (OR=1.007; 95% CI = 1.004-1.010) among Medicare members only. CONCLUSIONS: Key social determinants of health are important factors of vaccine adherence and can guide policy and intervention efforts toward addressing potential hesitancy. A deeper assessment of other contributing social factors is needed in seasonal influenza and other vaccines to better interpret the vaccine-seeking behaviors of adults. DISCLOSURES: This study received no outside funding. Gatwood, Hagemann, Hohmeier, and Chiu declare vaccine-related grant funding from Merck & Co. and GlaxoSmithKline for vaccine research unrelated to the current study. Ramachandran declares vaccine-related grant funding from Glaxo-SmithKline for research unrelated to the current study. Shuvo and Behal have nothing to disclose. Findings described in this study were presented as a poster and podium at the Academy of Managed Care Pharmacy Nexus 2020 Virtual meeting, October 19-23, 2020.

Development of a Remote Public Health Advanced Pharmacy Practice Experience in Response to COVID-19.

OBJECTIVES: In order to meet the needs of the COVID-19 public health crisis and to actively engage students in patient care opportunities, the University of Tennessee Health Science Center College of Pharmacy in partnership with the Tennessee Health Department, developed a remote Public Health Advanced Pharmacy Practice Experience (APPE) Elective. The objectives of this paper are to describe the development of and students' experiences and learning outcomes during the elective. Faculty preceptor and experiential administrator's perspectives are also described. METHODS: This month-long APPE was developed in mid-March and delivered in April and May of 2020. The students volunteered in-person with the State of Tennessee COVID-19 Hotline call centers and conducted topic discussions and assignments virtually with a remote preceptor. RESULTS: A total of 16 students completed this rotation experience. Student ratings of the experience were positive, and their knowledge improved in all topic areas. Students collectively completed approximately 700 hours manning the COVID-19 hotline and logged over 1,000 phone calls. CONCLUSIONS: In a time of unprecedented disruption to experiential learning, the development of this unique public health APPE directly benefited the college, the students, and the citizens of our state. The APPE described in this paper could be replicated in additional waves of the pandemic or adapted for similar disaster response.

Alexander disease: models, mechanisms, and medicine.

Alexander disease is a primary disorder of astrocytes caused by gain-of-function mutations in the gene for glial fibrillary acidic protein (GFAP), which lead to protein aggregation and a reactive astrocyte response, with devastating effects on the central nervous system. Over the past two decades since the discovery of GFAP as the culprit, several cellular and animal models have been generated, and much has been learned about underlying mechanisms contributing to the disease. Despite these efforts, many aspects of Alexander disease have remained enigmatic, particularly the initiating events in GFAP accumulation and astrocyte pathology, the relation between astrocyte dysfunction and myelin deficits, and the variability in age of onset and disease severity. More recent work in both old and new models has begun to address these complex questions and identify new therapeutics that finally offer the promise of effective treatment.

A social media microinfluencer intervention to reduce coronavirus disease 2019 vaccine hesitancy in underserved Tennessee communities: A protocol paper.

BACKGROUND: Central to effective public health policy and practice is the trust between the population served and the governmental body leading health efforts, but that trust has eroded in the years preceding the pandemic. Vaccine hesitancy among adults is also a growing concern across the United States. Recent data suggest that the trustworthiness of information about the coronavirus 2019 (COVID-19) vaccine was a larger concern than the vaccine's adverse effects or risks. OBJECTIVE: This study aims to describe the methods used to create a public health microinfluencer social media vaccine confidence campaign for the COVID-19 vaccine in underserved Tennessee communities. A secondary objective is to describe how the Social-Ecological Model (SEM) and Social Cognitive Theory may address vaccine hesitancy using community pharmacies. METHODS: In late 2020, 50 independent community pharmacies in underserved communities across Tennessee were involved in a public health project with the State of Tennessee Department of Health and the University of Tennessee Health Science Center College of Pharmacy. The project involved a 3-pronged, pharmacy-based COVID-19 vaccination outreach project, including (1) social media messaging (i.e., microinfluencer approach), (2) community partner collaboration, and (3) in-pharmacy promotion. Quantitative and qualitative data will assess the quality and effectiveness of the program. Social media outcomes will also be assessed to measure the impact of the microinfluencer social media training. RESULTS: Project implementation is planned for 6 months (January 2021 to June 2021) after an initial month of planning by the research team (December 2020) and preceding several months of assessment (July 2021 and beyond). CONCLUSIONS: Novel, theory-based approaches will be necessary to improve vaccine confidence. One approach to promoting public health, derived from the SEM, may be to use trusted microinfluencers on social media platforms, such as local community pharmacists and community leaders.

Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment.

Alexander disease (AxD) is a devastating leukodystrophy caused by gain-of-function mutations in GFAP, and the only available treatments are supportive. Recent advances in antisense oligonucleotide (ASO) therapy have demonstrated that transcript targeting can be a successful strategy for human neurodegenerative diseases amenable to this approach. We have previously used mouse models of AxD to show that Gfap-targeted ASO suppresses protein accumulation and reverses pathology; however, the mice have a mild phenotype with no apparent leukodystrophy or overt clinical features and are therefore limited for assessing functional outcomes. In this report, we introduce a rat model of AxD that exhibits hallmark pathology with GFAP aggregation in the form of Rosenthal fibers, widespread astrogliosis, and white matter deficits. These animals develop normally during the first postnatal weeks but fail to thrive after weaning and develop severe motor deficits as they mature, with about 14% dying of unknown cause between 6 and 12 weeks of age. In this model, a single treatment with Gfap-targeted ASO provides long-lasting suppression, reverses GFAP pathology, and, depending on age of treatment, prevents or mitigates white matter deficits and motor impairment. In this report, we characterize an improved animal model of AxD with myelin pathology and motor impairment, recapitulating prominent features of the human disease, and use this model to show that ASO therapy has the potential to not only prevent but also reverse many aspects of disease.

Comparison of Clinical Outcomes and Medication Use of Obese Versus Nonobese Children Admitted to the Pediatric Intensive Care Unit.

Background: Few studies have compared clinical outcomes and medication use between obese and nonobese children in the pediatric intensive care unit (PICU). Objectives: The primary objective was to compare clinical outcomes including mortality, PICU length of stay (LOS), and mechanical ventilation (MV) requirement between obese and nonobese children. Secondary objectives included analysis of factors associated with these outcomes and medication use between groups. Methods: This retrospective study included children 2 to 17 years old admitted to the PICU over a 1-year time frame. Patients were categorized as obese, body mass index (BMI) ≥ 95th percentile, and nonobese (BMI < 95th percentile). Three binary regression models assessed the impact of obesity on clinical outcomes. Results: There were 834 admissions, with 22.1% involving obese children. There was no difference in mortality, MV requirement, or PICU LOS between groups. There were no associations with obesity and clinical outcomes found, but an association was noted for medication classes and receipt of continuous infusions on clinical outcomes. There was no difference noted in the median number (interquartile range [IQR]) of medications between obese and nonobese children, 8 (6-13) versus 9 (6-15), P = .38, but there was a difference in patients receiving a continuous infusion between obese and nonobese children, 24.4% versus 8.8%, P < .01. The 15 most used medications in both groups included analgesics, antimicrobials, corticosteroids, bronchodilators, and gastrointestinal agents. Conclusions: One-fifth of all admissions included obese children. Obesity was not associated with mortality, PICU LOS, and MV requirement, but the number of medication classes and continuous infusions were associated with these outcomes.