Cone structure in subjects with known genetic relative risk for AMD.

PURPOSE: Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD). METHODS: Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject. RESULTS: Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 had a 12% decrease in density (p < 0.0001) and a 5% increase in spacing (p = 0.0014). No association between genetic RR and either cone density (p = 0.435) or spacing (p = 0.538) was found. Three distinct adaptive optics scanning light ophthalmoscope phenotypical variations of photoreceptor appearance were noted in patients with grade 1 to 3 fundi. These included variable reflectivity of photoreceptors, decreased waveguiding, and altered photoreceptor mosaic overlying drusen. CONCLUSIONS: Our data demonstrate the potential of multimodal assessment in the understanding of early anatomical changes associated with AMD. Adaptive optics scanning light ophthalmoscope imaging reveals a decrease in photoreceptor density and increased spacing in patients with grade 1 to 3 fundi, as well as a spectrum of photoreceptor changes, ranging from variability in reflectivity to decreased density. Future longitudinal studies are needed in genetically characterized subjects to assess the significance of these findings with respect to the development and progression of AMD.

Do Racial and Ethnic Disparities Exist in Intensity of Intracranial Pressure-Directed Therapies and Outcomes Following Pediatric Severe Traumatic Brain Injury?

INTRODUCTION: Studies suggest disparities in outcomes in minoritized children after severe traumatic brain injury. We aimed to evaluate for disparities in intracranial pressure-directed therapies and outcomes after pediatric severe traumatic brain injury. METHODS: We conducted a secondary analysis of the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial, which enrolled pediatric severe traumatic brain injury patients (Glasgow Coma Scale score ≤8) with an intracranial pressure monitor from 2014 to 2018. Patients admitted outside of the United States were excluded. Patients were categorized by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, and "Other"). We evaluated outcomes by assessing mortality and 3-month Glasgow Outcome Score-Extended for Pediatrics. Our analysis involved parametric and nonparametric testing. MAIN RESULTS: A total of 671 children were analyzed. Significant associations included older age in non-Hispanic White patients (P < .001), more surgical evacuations in "Other" (P < .001), and differences in discharge location (P = .040). The "other" cohort received hyperventilation less frequently (P = .046), although clinical status during Paco2 measurement was not known. There were no other significant differences in intracranial pressure-directed therapies. Hispanic ethnicity was associated with lower mortality (P = .004) but did not differ in unfavorable outcome (P = .810). Glasgow Outcome Score-Extended for Pediatrics was less likely to be collected for non-Hispanic Black patients (69%; P = .011). CONCLUSIONS: Our analysis suggests a general lack of disparities in intracranial pressure-directed therapies and outcomes in children after severe traumatic brain injury. Lower mortality in Hispanic patients without a concurrent decrease in unfavorable outcomes, and lower availability of Glasgow Outcome Score-Extended for Pediatrics score for non-Hispanic Black patients merit further investigation.

Adult opioid poisonings by drug, intent, and resource use from the United States National Poison Data System from 2005-2018.

INTRODUCTION: Deaths due to an opioid overdose nearly doubled from 2013 to 2017. Our objective is to describe the trends in intent, healthcare resource use, and clinical outcomes among adults with opioid exposures. MATERIALS AND METHODS: This study is a retrospective analysis of data from the 55 U.S. poison control centers. Adults, >19 years, with an opioid as the primary poisoning agent between 2005 and 2018 were included. These years were divided into three epochs (2005-2009, 2010-2014, and 2015-2018) to describe the trends in frequency, intent, severity, healthcare resource use, and regional differences in U.S. adults affected by prescription and illicit opioid exposures. RESULTS: A total of 546,049 (54.4%) of the 1,002,947 opioid-related cases reported to the U.S. poison centers met inclusion criteria. The percentage of patients with a moderate/major clinical effect increased in each epoch (24.4, 29.13, and 35.3%) as did the proportion of patients with illicit opioids (coded as heroin) as their primary substance (2.89, 5.47, and 13.95%). Illicit opioid use was associated with increased frequency of moderate/major clinical effects (54.2 vs. 27.4%), need for an ICU procedure (11.4 vs. 6.8%), and death (3.9 vs. 1.2%) compared with prescription opioid use. Suicidal intent (34.88%) followed by misuse/abuse (26.26%) were the most frequent intents. Misuse/abuse increased in frequency over each epoch in the study period (23.1 vs. 26.12 vs. 30.3%). Discussion and conclusions: The severity of clinical effects and death following acute opioid poisonings increased over the study period, driven by suicidal intent and an increasing proportion of illicit opioid cases. This study highlights the importance of developing strategies to address suicide prevention in addition to the continued focus on opioid use disorder.

Analysis of 207,543 children with acute opioid poisonings from the United States National Poison Data System.

Introduction: Previous studies using administrative data have demonstrated that the United States opioid epidemic is harming both adults and children, and is straining health care systems. Our objective is to describe the outcomes and trends in resource use among children with acute opioid ingestions using patient-level case report data.Materials and Methods: This study was a retrospective analysis of prospectively collected data from the 55 poison control centers in the United States which comprise the National Poison Data System (NPDS). Children under 19 years of age with a primary opioid ingestion between 1 January 2005 and 31 December 2018 were included in the analysis. Trends over three eras (2005-2009, 2010-2014, 2015-2018) were assessed using a Cochran-Armitage Trend Test. Yearly trends in the proportion of cases were calculated using generalized linear models. Multi-variable logistic regression analysis was used to calculate the adjusted odds of variables associated with having at least one Pediatric Intensive Care Unit (PICU) level intervention.Results: Children were involved in 207,543 (27.54%) of a total of 1,002,947 primary exposure-related opioid poisoning cases reported to US poison centers. The percentage of patients admitted to a critical care unit from these exposures increased in each era (6.6%, 8.5%, 9.6%). Suicidal intent increased in each era (14.0%, 15.3%, 21.2%), and was associated with increased adjusted odds of receiving a PICU procedure (OR 9.68, CI 7.97-11.76). Fentanyl (OR 12, CI 9.2-15.7), heroin (OR 11.1, CI 9.4-13.1), and methadone (OR 15, CI 13-17.3) were the opioids most associated with having a PICU procedure.Discussion and Conclusions: The severity of admissions for acute opioid ingestions, especially following attempted suicide, has increased over the studied time frame. Efforts focused on reducing access, especially to synthetic and illicit opioids, and addressing adolescent suicidality are needed to reduce these serious consequences of the opioid epidemic on children in the United States.

Outer retinal structure in best vitelliform macular dystrophy.

IMPORTANCE: Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD). OBJECTIVE: To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee. INTERVENTION: Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects. MAIN OUTCOME AND MEASURE: Photoreceptor structure. RESULTS: Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers. CONCLUSIONS: AND RELEVANCE: The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation.