Medical Record Level-Evaluation of Impact of Demographic and Socioeconomic Factors on Pediatric Neuro-Oncology Outcomes at Children's Hospital Colorado.

Purpose: A medical record-level cohort study to investigate demographic and socioeconomic factors influencing treatment, timing of care, and survival outcomes in pediatric patients diagnosed with central nervous system (CNS) tumors. Methods: Using electronic health records of patients at Children's Hospital Colorado from 1986-2020, we identified 898 patients treated for CNS tumors. The primary outcomes of interest were 5-year survival, timing of diagnosis, and treatment. Multivariable logistic regression and Cox regression were used to identify covariates associated with our outcomes of interest. Results: We found that age, race, tumor type, diagnosis year, and social concerns influenced receipt and timing of treatment. Age, race, patient rural vs. urban residence, and tumor impacted survival outcomes. Time to presentation and treatment were significantly different between White and minority patients. American Indian/Alaska Native and Black patients were less likely to receive chemo compared to White patients (OR 0.28, 0.93 p = 0.037, < 0.001). Patients with 3 + social concerns were more likely to survive after 5 years than children with no or unknown social concerns (OR 1.84, p = 0.011). However, with an adjusted hazards ratio, children with 2 social concerns were less likely to survive to 5 years than children with no or unknown concerns (OR 0.58, p = 0.066). Conclusions: Demographic and socioeconomic factors influence timing of care and survival outcomes in pediatric patients with CNS tumors. Minority status, age, social factors, rural, and urban patients experience differences in care. This emphasizes the importance of considering these factors and addressing disparities to achieve equitable care.

Economic review of point-of-care EEG.

Aims: Point-of-care electroencephalogram (POC-EEG) is an acute care bedside screening tool for the identification of nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE). The objective of this narrative review is to describe the economic themes related to POC-EEG in the United States (US).Materials and methods: We examined peer-reviewed, published manuscripts on the economic findings of POC-EEG for bedside use in US hospitals, which included those found through targeted searches on PubMed and Google Scholar. Conference abstracts, gray literature offerings, frank advertisements, white papers, and studies conducted outside the US were excluded.Results: Twelve manuscripts were identified and reviewed; results were then grouped into four categories of economic evidence. First, POC-EEG usage was associated with clinical management amendments and antiseizure medication reductions. Second, POC-EEG was correlated with fewer unnecessary transfers to other facilities for monitoring and reduced hospital length of stay (LOS). Third, when identifying NCS or NCSE onsite, POC-EEG was associated with greater reimbursement in Medical Severity-Diagnosis Related Group coding. Fourth, POC-EEG may lower labor costs via decreasing after-hours requests to EEG technologists for conventional EEG (convEEG).Limitations: We conducted a narrative review, not a systematic review. The studies were observational and utilized one rapid circumferential headband system, which limited generalizability of the findings and indicated publication bias. Some sample sizes were small and hospital characteristics may not represent all US hospitals. POC-EEG studies in pediatric populations were also lacking. Ultimately, further research is justified.Conclusions: POC-EEG is a rapid screening tool for NCS and NCSE in critical care and emergency medicine with potential financial benefits through refining clinical management, reducing unnecessary patient transfers and hospital LOS, improving reimbursement, and mitigating burdens on healthcare staff and hospitals. Since POC-EEG has limitations (i.e. no video component and reduced montage), the studies asserted that it did not replace convEEG.

Comprehensive Assessment of Blood-Brain Barrier Opening and Sterile Inflammatory Response: Unraveling the Therapeutic Window.

Microbubbles (MBs) combined with focused ultrasound (FUS) have emerged as a promising noninvasive technique to permeabilize the blood-brain barrier (BBB) for drug delivery to the brain. However, the safety and biological consequences of BBB opening remain incompletely understood. This study investigates the effects of varying microbubble volume doses (MVD) and ultrasound mechanical indices (MI) on BBB opening and the sterile inflammatory response (SIR) using high-resolution ultra-high field MRI-guided FUS in mouse brains. The results demonstrate that both MVD and MI significantly influence the extent of BBB opening, with higher doses and mechanical indices leading to increased permeability. Moreover, RNA sequencing reveals upregulated inflammatory pathways and immune cell infiltration after BBB opening, suggesting the presence and extent of SIR. Gene set enrichment analysis identifies 12 gene sets associated with inflammatory responses that are upregulated at higher doses of MVD or MI. A therapeutic window is established between significant BBB opening and the onset of SIR, providing operating regimes for avoiding each three classes of increasing damage from stimulation of the NFκB pathway via TNFL signaling to apoptosis. This study contributes to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and sheds light on the underlying molecular mechanisms of the sterile inflammatory response. Significance Statement: The significance of this study lies in its comprehensive investigation of microbubble-facilitated focused ultrasound for blood-brain barrier (BBB) opening. By systematically exploring various combinations of microbubble volume doses and ultrasound mechanical indices, the study reveals their direct impact on the extent of BBB permeability and the induction of sterile inflammatory response (SIR). The establishment of a therapeutic window between significant BBB opening and the onset of SIR provides critical insights for safe and targeted drug delivery to the brain. These findings advance our understanding of the biological consequences of BBB opening and contribute to optimizing parameters for clinical applications, thus minimizing potential health risks, and maximizing the therapeutic potential of this technique.

Rapid Development and Deployment of an Intensivist-Led Venovenous Extracorporeal Membrane Oxygenation Cannulation Program.

OBJECTIVES: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program. DESIGN: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program. SETTING: An adult ICU in a tertiary academic medical center in Camden, NJ. PATIENTS: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation. INTERVENTIONS: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists. MEASUREMENTS AND MAIN RESULTS: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1). CONCLUSIONS: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates.

Assessment of enrollment characteristics for Children's Oncology Group (COG) upfront therapeutic clinical trials 2004-2015.

BACKGROUND: Improvements in pediatric cancer survival are attributed to cooperative clinical trials. Under-representation of specific demographic groups has been described in adult and pediatric cancer trials and poses a threat to the generalizability of results. An evaluation of data provided by the Children's Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed. METHODS: US cancer cases were estimated using incidence data and US population estimates from the Surveillance, Epidemiology, and End Results Program and compared to observed COG cases. Percent enrollment and standardized ratios of enrollment were calculated across demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available trials and assess age eligibility. RESULTS: 19.9% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were more represented across diseases and races/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors. CONCLUSION: COG trial enrollment rates are declining when compared to previously published data, potentially from challenges in pediatric drug development, difficulty designing feasible trials for highly curable diagnoses, and issues ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/young adult (AYA) population and younger patients with solid and CNS tumors remains a concern. Targeted efforts should focus on these subgroups and further research should evaluate AYA enrollment rates across all available trials.

A U.S. population-based study of insurance disparities in cancer survival among adolescents and young adults.

BACKGROUND: Adolescents and young adults (AYA), patients age 15-39, may experience worse outcomes than pediatric and adult patients. The aim of this paper was to document survival disparities associated with insurance status across the AYA age continuum in the United States. METHODS: We utilized the Surveillance, Epidemiologic, and End Results database to identify 66 556 AYA patients between 2007 and 2014 with 10 International Classification of Childhood Cancer diagnoses and calculated the Cox proportional hazard ratios of death for those with public or no insurance status compared to private insurance. The odds ratios of having a late stage of diagnosis by insurance status were also calculated. RESULTS: Insurance status was a statistically significant predictor of death for lymphoid leukemia (age 15-19, 30-34, and 35-39), acute myeloid leukemia (age 15-19 and 25-29), Hodgkin lymphoma (all ages), non-Hodgkin lymphoma (age 20-24, 25-29, 30-34, and 35-39), astrocytomas (age 30-34), other gliomas (age 25-29, 30-34, and 35-39), hepatic carcinomas (age 25-29), fibrosarcomas, peripheral nerve and other fibrous tumors (age 30-34), malignant gonadal germ cell tumors (age 20-24, 25-29, 30-34, and 35-39), and other and unspecified carcinomas (age 20-24, 25-29, 30-34, and 35-39), independent of stage at diagnosis. This hazard increased with age for most cancer types. Insurance status strongly predicted the odds of a metastatic cancer diagnosis for lymphoma, fibrosarcomas (age 15-19), germ cell tumors, and other carcinomas. CONCLUSIONS: AYA in the US experience disparities in cancer survival based on insurance status, independent of late stage of presentation. Patients age 26-39 may be especially vulnerable to health outcomes associated with poor socioeconomic status, treatment disparities, and poor access to care.

Surgeon Reliability for the Assessment of Lumbar Spinal Stenosis on MRI: The Impact of Surgeon Experience.

BACKGROUND: Treating surgeon's visual assessment of axial MRI images to ascertain the degree of stenosis has a critical impact on surgical decision-making. The purpose of this study was to prospectively analyze the impact of surgeon experience on inter-observer and intra-observer reliability of assessing severity of spinal stenosis on MRIs by spine surgeons directly involved in surgical decision-making. METHODS: Seven fellowship trained spine surgeons reviewed MRI studies of 30 symptomatic patients with lumbar stenosis and graded the stenosis in the central canal, the lateral recess and the foramen at T12-L1 to L5-S1 as none, mild, moderate or severe. No specific instructions were provided to what constituted mild, moderate, or severe stenosis. Two surgeons were "senior" (>fifteen years of practice experience); two were "intermediate" (>four years of practice experience), and three "junior" (< one year of practice experience). The concordance correlation coefficient (CCC) was calculated to assess inter-observer reliability. Seven MRI studies were duplicated and randomly re-read to evaluate inter-observer reliability. RESULTS: Surgeon experience was found to be a strong predictor of inter-observer reliability. Senior inter-observer reliability was significantly higher assessing central(p<0.001), foraminal p=0.005 and lateral p=0.001 than "junior" group.Senior group also showed significantly higher inter-observer reliability that intermediate group assessing foraminal stenosis (p=0.036). In intra-observer reliability the results were contrary to that found in inter-observer reliability. CONCLUSION: Inter-observer reliability of assessing stenosis on MRIs increases with surgeon experience. Lower intra-observer reliability values among the senior group, although not clearly explained, may be due to the small number of MRIs evaluated and quality of MRI images.Level of evidence: Level 3.

Keeping gay and bisexual men safe: The arena of HIV prevention science and praxis.

Abstract In this article, I draw from an ongoing ethnographic study of HIV prevention for gay, bisexual, and 'men who have sex with men' to develop an institutional analysis of HIV behavioral intervention science and praxis. I approach this analysis through the lens of the social worlds framework, focusing on the institutional arena in which HIV behavioral interventions are devised and executed. Toward this end, I focus on two fundamental points of contention that lie at the heart of the prevention enterprise and put its social organization in high relief: (1) conceptions of health and lifestyle practices and (2) attributions of expertise. These core contentions reveal less the steady advance of normal science than an arena of actors ensconced in boundary work and jurisdictional struggles over how to engineer behavior change and reduce the scale of the HIV epidemic. Their resolution, I argue, has occurred in a historically contingent process determined by the political economy of the US HIV prevention arena and the differential structural location of its social worlds.

Correlation of Insurance, Race, and Ethnicity with Pathologic Risk in a Controlled Retinoblastoma Cohort: A Children's Oncology Group Study.

PURPOSE: To determine whether insurance status, race, and ethnicity correlate with increased retinoblastoma invasiveness as a marker of both risk and time to diagnosis. DESIGN: Retrospective case-control study. PARTICIPANTS: All 203 patients from the United States enrolled in the Children's Oncology Group (COG) trial ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. MAIN OUTCOME MEASURES: All surgical specimens underwent pathologic review to determine the presence of well-defined histopathologic features correlating with a higher risk of disease progression. Insurance status, race, and ethnicity were compiled from the study record for each patient. RESULTS: On institutional pathologic review, nonprivate insurance, nonwhite race, and Hispanic ethnicity all correlated significantly with a greater rate of high-risk pathologic findings. Hispanic ethnicity remained a significant predictor on multivariate analysis. On central pathologic review, these correlations remained but did not reach statistical significance. The differences in results from institutional versus central pathologic reviews appeared to be due to a higher likelihood of patients in minority groups of being misclassified as high risk by institutional pathologists. CONCLUSIONS: In this controlled study population of patients with retinoblastoma who had central pathologic review, our findings suggest a higher rate of more advanced disease associated with nonprivate insurance, nonwhite race, and Hispanic ethnicity; these findings may be due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English-language proficiency and socioeconomic status. Further effort also should focus on where in the diagnostic process potential delays exist, so that interventions can be designed to overcome barriers to care for these groups. In addition, potential systematic differences in pathologic reads based on demographic variables deserve further study.

Ethnic, Racial, and Socioeconomic Disparities in Retinoblastoma.

IMPORTANCE: Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation. OBJECTIVE: To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS: A population-based review of 18 Surveillance, Epidemiology, and End Results (SEER) registries. From January 1, 2000, through December 31, 2010, 830 cases of retinoblastoma were recorded for children aged 0 to 9 years. Data were collected and analyzed from January 1, 2000, through December 31, 2010, with the last follow-up on December 31, 2010. EXPOSURES: County-based socioeconomic variables analyzed included poverty level, educational attainment, language isolation, crowding, unemployment, and percentage of immigrants. MAIN OUTCOMES AND MEASURES: Extent of disease, ocular outcome, and children's survival. RESULTS: Of the 830 individuals included, Hispanic children had a higher percentage of extraocular disease (86 of 261 [33.0%] vs. 102 of 510 non-Hispanic children [20.0%]; odds ratio [OR], 1.97 [95% CI, 1.38-2.79]). The percentage of extraocular cases was also higher in counties with the following low socioeconomic status indicators: higher vs. lower poverty status (115 of 413 [27.8%] vs. 73 of 358 [20.4%]; OR, 1.51; 95% CI, 1.06-2.14); lower vs. higher educational attainment (115 of 400 [28.7%] vs. 73 of 371 [19.7%]; OR, 1.65; 95% CI, 1.16-2.34); higher vs. lower levels of crowding (124 of 398 [31.2%] vs. 64 of 373 [17.2%]; OR, 2.18; 95% CI, 1.53-3.13); higher vs. lower unemployment (119 of 411 [28.9%] vs. 69 of 360 [19.2%]; OR, 1.72; 95% CI, 1.21-2.45); higher vs. lower language isolation (117 of 388 [30.2%] vs. 71 of 383 [18.5%]; OR, 1.89; 95% CI, 1.34-2.70); and higher vs. lower percentage of immigrants (109 of 386 [28.2%] vs. 79 of 385 [20.5%]; OR, 1.52; 95% CI, 1.08-2.16). Higher rates of enucleation were associated with low educational attainment (265 of 401 [66.1%] vs 309 of 421 [73.4%]; OR, 1.42; 95% CI, 1.04-1.93), a higher level of crowding (316 of 416 [76.0%] vs. 258 of 406 [63.5%]; OR, 1.81; 95% CI, 1.32-2.48), and Hispanic origin (202 of 271 [74.5%]; OR, 1.41; 95% CI, 1.01-1.98). Relative survival at 5 years was lower among black compared with non-Hispanic white children (92.7% vs. 99.2%; P < .001). CONCLUSIONS AND RELEVANCE: Significant disparities exist in the care and outcomes of children with retinoblastoma. A low socioeconomic status negatively affects disease extent and ocular outcomes, presumably by limiting access to primary and cancer-directed care. Hispanic children in particular have more advanced disease and higher rates of enucleation.

Engineering behaviour change in an epidemic: the epistemology of NIH-funded HIV prevention science.

Social scientific and public health literature on National Institutes of Health-funded HIV behavioural prevention science often assumes that this body of work has a strong biomedical epistemological orientation. We explore this assumption by conducting a systematic content analysis of all NIH-funded HIV behavioural prevention grants for men who have sex with men between 1989 and 2012. We find that while intervention research strongly favours a biomedical orientation, research into the antecedents of HIV risk practices favours a sociological, interpretive and structural orientation. Thus, with respect to NIH-funded HIV prevention science, there exists a major disjunct in the guiding epistemological orientations of how scientists understand HIV risk, on the one hand, and how they engineer behaviour change in behavioural interventions, on the other. Building on the extant literature, we suggest that the cause of this disjunct is probably attributable not to an NIH-wide positivist orientation, but to the specific standards of evidence used to adjudicate HIV intervention grant awards, including randomised controlled trials and other quantitative measures of intervention efficacy.

Assessment of radiolabeled D-glucose and the nonmetabolizable analog 3-O-methyl-D-glucose as tools for in vivo absorption studies.

3-O-methyl-D-glucose has been extensively used as a proxy for d-glucose uptake. This nonmetabolizable analog has lower affinity for transporters, potentially leading to underestimates of glucose absorption rates as well as overestimates of the nutritional significance of passive uptake. Here we sought to precisely quantify the bias, if any, incurred when using 3-O-methyl-D-glucose by comparing relative absorption rates with D-glucose in vivo in a seasonally frugivorous bird, the American robin. By simultaneously administering these D-glucose probes with L-glucose--the latter absorbed only via nonmediated mechanisms and the former absorbed by both mediated and nonmediated mechanisms--using common pharmacokinetic procedures, we were able to estimate the nutritional significance of paracellular uptake in this species. The relative absorption rate of 3-O-methyl-D-glucose calculated over the initial absorptive phase was not significantly different from that of D-glucose, indicating that the former provides reasonable estimates of glucose absorption rates in vivo. The ratio of L-glucose to D-glucose cumulative fractional absorption indicates that around 60% of total glucose absorption in American robins is paracellular and showed no apparent bias in using 3-O-methyl-D-glucose when averaged over the entire initial absorptive phase. Although the absorption and elimination kinetics of radiolabeled D-glucose were appropriate for pharmacokinetic analysis in this study, because of the potential for interspecific differences in loss to catabolism, it should be used in vivo with caution and with independent verification of absorption efficiency.