A multi-center analysis of visual outcomes following open globe injury.

The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects' demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25-2.20]; P < 0.001) more likely to have monocular blindness relative to White race at follow-up. OTS Class 1 was the strongest predictor of blindness (OR: 38.35 [21.33-68.93]; P < 0.001). Based on multivariable analysis, lower OTS category (OTS Class 1 OR: 23.88 [16.44-45.85]; P < 0.001) moderately predicted visual outcomes (R2 = 0.275, P < 0.001). OGI has many risks of poor visual outcome across patient groups that vary by demographic category, mechanism of injury, and clinical presentation. Our findings validate that a modified OTS remains a strong predictor of visual prognosis following OGI in a large and generalizable sample.

Associations between perinatal risk and physical health in pre-adolescence in the Adolescent Brain Cognitive Development (ABCD) Study®: the unexpected relationship with sleep disruption.

BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Development℠ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.

Spectrum of Cognitive Biases in Diagnostic Radiology.

Cognitive biases are systematic thought processes involving the use of a filter of personal experiences and preferences arising from the tendency of the human brain to simplify information processing, especially when taking in vast amounts of data such as from imaging studies. These biases encompass a wide spectrum of thought processes and frequently overlap in their concepts, with multiple biases usually in operation when interpretive and perceptual errors occur in radiology. The authors review the gamut of cognitive biases that occur in radiology. These biases are organized according to their expected stage of occurrence while the radiologist reads and interprets an imaging study. In addition, the authors propose several additional cognitive biases that have not yet, to their knowledge, been defined in the radiologic literature but are applicable to diagnostic radiology. Case examples are used to illustrate potential biases and their impact, with emergency radiology serving as the clinical paradigm, given the associated high imaging volumes, wide diversity of imaging examinations, and rapid pace, which can further increase a radiologist's reliance on biases and heuristics. Potential strategies to recognize and overcome one's personal biases at each stage of image interpretation are also discussed. Awareness of such biases and their unintended effects on imaging interpretations and patient outcomes may help make radiologists cognizant of their own biases that can result in diagnostic errors. Identification of cognitive bias in departmental and systematic quality improvement practices may represent another tool to prevent diagnostic errors in radiology. ©RSNA, 2024 See the invited commentary by Larson in this issue.

How long does it take to scale-up obesity prevention interventions?

OBJECTIVE: The scale-up of evidence-based interventions is necessary to reverse high rates of obesity. However, scale-up doesn't occur frequently nor in a timely manner. While it has been estimated that takes 14-17 years for research translation to occur, the time taken to scale-up prevention interventions is largely unknown. This study examined the time taken to scale-up obesity prevention interventions across four scale-up pathways. METHODS: A sample of obesity prevention interventions that had been scaled-up or implemented at scale were found using a structured search strategy. Included interventions were mapped against four scale-up pathways and timeframes associated with each stage of the scale-up pathway were identified to determine the time taken to scale-up. RESULTS: Of the 90 interventions found that were scaled-up to at least a city-wide level, less than half reported a comprehensive research pathway to scale-up and a third did not report any evidence of efficacy or effectiveness prior to scale-up. The time taken to scale-up ranged from 0 to 5 years depending on the pathway taken. Those following a comprehensive pathway took approximately 5 years to scale-up, while interventions that had only one evidence generating step took between 1 and 1.5 years to scale-up. For the remaining interventions, scale-up occurred immediately post-development without evidence generation. CONCLUSIONS: Our findings indicate that the scale-up of obesity prevention interventions can occur more quickly than previous estimates of 14-17 years. Our findings support previous research that scale-up of interventions occurs through a variety of pathways and often scale-up occurs in absence of prior evidence of effectiveness.

Pseudoxanthoma elasticum-associated angioid streaks near a scleral buckle.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

Neonatal hypoxia impairs serotonin release and cognitive functions in adult mice.

Children who experienced moderate perinatal asphyxia (MPA) are at risk of developing long lasting subtle cognitive and behavioral deficits, including learning disabilities and emotional problems. The prefrontal cortex (PFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin (5-HT) project to the PFC, and compounds modulating 5-HT activity influence emotion and cognition. Whether 5-HT dysregulations contribute to MPA-induced cognitive problems is unknown. We established a MPA mouse model, which displays recognition and spatial memory impairments and dysfunctional cognitive flexibility. We found that 5-HT expression levels, quantified by immunohistochemistry, and 5-HT release, quantified by in vivo microdialysis in awake mice, are reduced in PFC of adult MPA mice. MPA mice also show impaired body temperature regulation following injection of the 5-HT1A receptor agonist 8-OH-DPAT, suggesting the presence of deficits in 5-HT auto-receptor function on raphe neurons. Finally, chronic treatment of adult MPA mice with fluoxetine, an inhibitor of 5-HT reuptake transporter, or the 5-HT1A receptor agonist tandospirone rescues cognitive flexibility and memory impairments. All together, these data demonstrate that the development of 5-HT system function is vulnerable to moderate perinatal asphyxia. 5-HT hypofunction might in turn contribute to long-term cognitive impairment in adulthood, indicating a potential target for pharmacological therapies.

Systolic hypertension as side effect of topical low dose atropine drops.

Purpose: To present a case of increased systemic hypertension and pupil dilation related to low dose atropine eyedrops. Observations: A thirteen-year-old male with progressive myopia received atropine 0.05% ophthalmic drops to slow down myopia progression. He exhibited systemic systolic hypertension, photophobia, and bilateral nonreactive mydriasis. The atropine drops were discontinued, and his blood pressure and pupillary function normalized. Conclusions and importance: This case demonstrates sensitivity to low dose atropine with increased systemic blood pressure and pupillary dilation.

Sustaining health obesity prevention programs: Lessons from real-world population settings.

Current understanding of what sustains public health programs is derived primarily from evaluations of programs delivered for only a few years. To improve program planning and knowledge on program sustainment, we examined real-world population programs that have been delivered for >2 years. Our focus was physical activity and nutrition programs for obesity prevention. We identified programs through published literature and searched through publicly available information on the theoretical factors determining sustainment. We reviewed 90 programs and explored intervention characteristics, provider, delivery and process level factors, and the outer environment influences. Programs were sustained on average 15 years and more frequently characterised as behavioural change skills programs targeting children, funded by non-government organisations and delivered by community organisations. Most programs had undergone some modification (n = 55). Differences between programs were observed across key factors: Programs sustained 15+ years were mainly behaviour skills programs (n = 21); and characterised by interactive designs (i.e., face-to-face or digital) over static innovations (i.e., print material) compared with those sustained <15 years (p = 0.024). While government funding supported many of the programs (n = 45;), those sustained 15+ years were more likely to have been commercially funded (p = 0.044); and were less likely to have current community involvement (p = 0.013). Differences in ownership and funding were also observed across countries. While multiple factors may influence program sustainment, longer delivered programs where distinguished by their program characteristics and outer contextual factors, suggesting such factors may have an important role in sustaining programs in the longer-term.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Capabilities, opportunities, motivations, and practices of different sector professionals working on community environments to improve health.

OBJECTIVE: With rising healthcare costs in Canada from chronic conditions, individual behaviour change interventions in the clinical settings need to be complemented by a determinants of health approach, where multi-sector professionals assist in the creation of healthier community environments. This study sought to gain insights into capabilities, opportunities, motivations, and behaviours (COM-B) of Canadian multi-sector professionals for working together to improve built environments (BE) for health. METHODS: A cross-sectional study was conducted with 61 multi-sector professionals. A 49-item questionnaire measuring constructs of COM-B for healthy BE practices was administered. RESULTS: Public health (PH) professionals were more motivated by personal interest/values in healthy BE and the presence of scientific evidence on BE design health impacts as compared with planning and policy/program development (PPD) professionals. Planning professionals were more likely to be motivated by healthy BE legislation/regulations/codes than PPD professionals. The practice of taking responsibility for the inclusion of healthy features into BE designs was reported more often by planning and other professionals compared to PH professionals. Results trended towards significance for opportunities as a predictor of healthy BE practices among all professionals. CONCLUSION: Though motivators vary among different sector professionals, opportunities may be the most important driver of healthy BE practices and potentially a target to improve multi-sector professional practices in Canada. Future research should confirm findings of this first study of professional practice drivers guided by a theoretical behaviour change framework.

RéSUMé: OBJECTIF: Avec la hausse des coûts des soins de santé liés aux maladies chroniques au Canada, les interventions visant à changer les comportements individuels en conditions cliniques doivent être complétées par une approche axée sur les déterminants de la santé, où des professionnels de plusieurs secteurs aident à créer des cadres communautaires plus sains. Notre étude vise à approfondir la compréhension des capacités, occasions, motivations et comportements (COM-B) des professionnels canadiens de plusieurs secteurs qui les amènent à travailler ensemble à améliorer les cadres bâtis favorisant la santé. MéTHODE: Nous avons mené une étude transversale auprès de 61 professionnels de plusieurs secteurs. Nous leur avons administré un sondage de 49 questions pour mesurer, selon les concepts du modèle COM-B, les pratiques favorisant des cadres bâtis sains. RéSULTATS: Les professionnels de la santé publique (SP) étaient plus motivés par leurs valeurs/leur intérêt personnel envers les cadres bâtis sains et par l'existence de preuves scientifiques des effets de la conception des cadres bâtis sur la santé que les professionnels de la planification et les professionnels de l'élaboration de politiques/programmes (EPP). Les professionnels de la planification étaient plus susceptibles d'être motivés par les lois, les règlements et les codes sur les cadres bâtis sains que les professionnels de l'EPP. La pratique d'assumer la responsabilité de l'inclusion de caractéristiques saines dans la conception des cadres bâtis a été plus souvent déclarée par les professionnels de la planification et de l'EPP que par les professionnels de la SP. Pour l'ensemble des professionnels, les résultats affichent une tendance presque significative : les occasions pourraient être une variable prédictive de l'utilisation de pratiques saines en matière de cadre bâti. CONCLUSION: Les motivations des professionnels varient selon le secteur, mais les occasions pourraient être le principal moteur d'utilisation de pratiques saines en matière de cadres bâtis, et elles pourraient éventuellement être ciblées pour améliorer les pratiques professionnelles dans plusieurs secteurs au Canada. Les études futures devraient vérifier les constats de cette première étude sur les moteurs des pratiques professionnelles, guidée par un cadre théorique du changement des comportements.

Review of the Disparities in Access to Pediatric Eye Care Among Low Socioeconomic Status and Underrepresented Racial Minority Groups Exacerbated by the Economic Downturn in Pediatric Ophthalmology.

PURPOSE: To explore the association between race and socioeconomic status on health disparities in pediatric eye care, characterize the status of diversity within the pediatric ophthalmology workforce, and propose potential solutions to improve access to vision care, particularly for children from vulnerable populations. METHODS: The major studies examining the socioeconomic and racial disparities in visual outcomes and the impact of diversity in the ophthalmology workforce were reviewed. RESULTS: Currently, the pediatric ophthalmology workforce has limited racial diversity, and increasing the number of underrepresented in medicine providers has potential to improve access to pediatric eye care, particularly for underserved populations. Mobile eye clinics, school-based vision programs, and health literacy initiatives may engage communities to bring eye care directly to children and enhance follow-up. CONCLUSIONS: Families with lower socioeconomic status may represent a vulnerable population facing significant access to pediatric eye care barriers, particularly for asymptomatic pediatric eye conditions. Emphasis on strategies that directly engage communities and bring free vision care to families should be given to improve disparities in visual health outcomes. Ophthalmologists and pediatric ophthalmologists should be aware of the current racial underrepresentation within the pediatric ophthalmology workforce, and the importance of workforce diversity in accelerating physician-patient concordance and access to eye care. [J Pediatr Ophthalmol Strabismus. 2024;61(3):172-178.].

Creating consistency in the diagnosis of convergence insufficiency: screening methods.

PURPOSE: To determine the sensitivity of various clinical tests in the diagnosis of convergence insufficiency. METHODS: A total of 254 patients were recruited with complaints consistent with convergence problems but no prior history of strabismus surgery, eye exercises, prism use, recent concussion, or other ocular or neurological diseases. Each patient completed the convergence insufficiency symptom survey (CISS), and the following data were collected: ocular alignment at distance and near, convergence and divergence fusional amplitudes at distance and near, near-point of convergence (NPC) using an accommodative target and red lens, and assessment of quality of convergence movement (QoCM) and quality of fusional movements (QoFM). The sensitivity of each clinical test was calculated. RESULTS: Measurement of NPC using red lens and subjective assessment of the QoCM and QoFM were the most sensitive diagnostic tools for near symptoms consistent with convergence insufficiency: 93.3%, 98.4%, and 94.5% respectively. CISS score, convergence fusional amplitude at near, and exophoria at near had lower sensitivities: 62.9%, 46.0%, and 72.0%, respectively. Although the majority of our patients had a heterophoria or heterotropia at distance (96.8%) and/or near (98.8%), most presented with only small phorias. Furthermore, of those who had a deviation at near, only 22% had the near exophoria exceeding the distance exophoria by 10Δ. CONCLUSIONS: In our study cohort, NPC with red lens and subjective assessment of QoCM and QoFM proved to be the most sensitive screening tools for near symptoms consistent with convergence insufficiency.

Loading dose vitamin D3 improves vitamin D insufficiency in adults undergoing hematopoietic stem cell transplantation: A randomized controlled trial.

Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D3 pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D3 daily) or the control group (2,000 IU vit D3 daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D3 significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met.

Post-Traumatic Stress Disorder in Patients with Alopecia Areata: A Survey Study in the USA.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. AA is comorbid with mental health disorders including anxiety and depression. This study aimed to evaluate the presence of post-traumatic stress disorder (PTSD) in relation to hair loss in patients with AA. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to complete the PTSD Checklist for the DSM-5 (PCL-5), a validated screening tool for PTSD in the context of their AA. Results: Of the 1,449 completed surveys (completion rate 79.6%), most respondents were female (83.8%) and white (76.6%) with an average age of 50.6 ± 15.6 years. Respondents had AA for an average of 17.7 ± 15.8 years, with 91.4% experiencing current active hair loss. A total of 33.9% of respondents screened positively for PTSD, with an average score of 48.8 ± 12.3 on the PCL-5 in participants who screened positively. Participants with alopecia totalis have the highest average PCL-5 score of 30.1 ± 19.2, followed by participants with alopecia universalis with an average score of 26.0 ± 19.9, and lastly patchy AA with an average score of 24.5 ± 18.3 (p = 0.003). Feelings of intrusion and avoidance were the predominant reported symptoms. Total PTSD scores were significantly higher in respondents who were younger and identified as Black or African American and Hispanic when compared to white and non-Hispanic respondents, respectively. Conclusion: These findings identify that one in 3 patients with AA in this cohort meet the screening criteria for PTSD specifically relating to their hair loss experience. These results further highlight the mental health comorbidities associated with AA and emphasize that these symptoms may persist even after hair regrowth. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations. Finally, respondent's baseline mental health was not assessed; therefore, a causal relationship between AA and PTSD cannot be deduced.

Role of cultural brokering in advancing holistic primary care for diabetes and obesity: a participatory qualitative study.

OBJECTIVES: Diabetes and obesity care for ethnocultural migrant communities is hampered by a lack of understanding of premigration and postmigration stressors and their impact on social and clinical determinants of health within unique cultural contexts. We sought to understand the role of cultural brokering in primary healthcare to enhance chronic disease care for ethnocultural migrant communities. DESIGN AND SETTING: Participatory qualitative descriptive-interpretive study with the Multicultural Health Brokers Cooperative in a Canadian urban centre. Cultural brokers are linguistic and culturally diverse community health workers who bridge cultural distance, support relationships and understanding between providers and patients to improve care outcomes. From 2019 to 2021, we met 16 times to collaborate on research design, analysis and writing. PARTICIPANTS: Purposive sampling of 10 cultural brokers representing eight different major local ethnocultural communities. Data include 10 in-depth interviews and two observation sessions analysed deductively and inductively to collaboratively construct themes. RESULTS: Findings highlight six thematic domains illustrating how cultural brokering enhances holistic primary healthcare. Through family-based relational supports and a trauma-informed care, brokering supports provider-patient interactions. This is achieved through brokers' (1) embeddedness in community relationships with deep knowledge of culture and life realities of ethnocultural immigrant populations; (2) holistic, contextual knowledge; (3) navigation and support of access to care; (4) cultural interpretation to support health assessment and communication; (5) addressing psychosocial needs and social determinants of health and (6) dedication to follow-up and at-home management practices. CONCLUSIONS: Cultural brokers can be key partners in the primary care team to support people living with diabetes and/or obesity from ethnocultural immigrant and refugee communities. They enhance and support provider-patient relationships and communication and respond to the complex psychosocial and economic barriers to improve health. Consideration of how to better enable and expand cultural brokering to support chronic disease management in primary care is warranted.

Visual acuity improvement in the amblyopic eye of a 50-year-old man following strabismus surgery.

It is generally believed that the visual acuity of an amblyopic eye cannot improve significantly in adulthood. However, there have been reports of this occurring following visual loss in the fellow eye. Best-corrected visual acuity improvement in amblyopic eyes of children with strabismic amblyopia following strabismus surgery has also been reported. We present the case of an adult whose visual acuity in his amblyopic eye improved 4 Snellen lines over 28 months following strabismus surgery.

What We Learned About the Economic and Workforce Issues in Pediatric Ophthalmology: Access to Eye Care and Possible Solutions.

PURPOSE: To provide a blueprint reviewing the major economic and workforce issues in pediatric ophthalmology and its effect on access to pediatric eye care, as well as potential solutions. METHODS: This was a systematic review of the landmark studies examining the economic and workforce issues in pediatric ophthalmology was performed. RESULTS: The number of residents pursuing pediatric ophthalmology fellowship has steadily declined since the early 2000s. Increasing overhead costs, low Medicaid reimbursements, practice pattern changes, and workforce shortages have all contributed to a significant crisis in access to pediatric eye care. CONCLUSIONS: Solutions to improve access to pediatric eye care involve pursuing more economical strategies within the confines of the pediatric ophthalmology practice, early exposure to the field during medical education, and enhancing residents' interest through faculty mentorship. Low reimbursements are a major driver contributing to extended appointment wait times for pediatric ophthalmology visits at major academic eye centers. Legislative changes at both the federal and state levels are needed to make appropriate increases in reimbursements, starting with states in the lowest quartile of Medicaid reimbursements. [J Pediatr Ophthalmol Strabismus. 2023;60(5):323-329.].

USP7 Inhibition Suppresses Neuroblastoma Growth via Induction of p53-Mediated Apoptosis and EZH2 and N-Myc Downregulation.

Neuroblastoma (NB) is a pediatric malignancy originating from neural crest cells of the sympathetic nervous system that accounts for 15% of all pediatric cancer deaths. Despite advances in treatment, high-risk NB remains difficult to cure, highlighting the need for novel therapeutic approaches. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that plays a critical role in tumor suppression and DNA repair, and USP7 overexpression has been associated with tumor aggressiveness in a variety of tumors, including NB. Therefore, USP7 is a potential therapeutic target for NB. The tumor suppressor p53 is a known target of USP7, and therefore reactivation of the p53 pathway may be an effective therapeutic strategy for NB treatment. We hypothesized that inhibition of USP7 would be effective against NB tumor growth. Using a novel USP7 inhibitor, Almac4, we have demonstrated significant antitumor activity, with significant decreases in both cell proliferation and cell viability in TP53 wild-type NB cell lines. USP7 inhibition in NB cells activated the p53 pathway via USP7 and MDM2 degradation, leading to reduced p53 ubiquitination and increased p53 expression in all sensitive NB cells. In addition, USP7 inhibition led to decreased N-myc protein levels in both MYCN-amplified and -nonamplified NB cell lines, but no correlation was observed between MYCN amplification and treatment response. USP7 inhibition induced apoptosis in all TP53 wild-type NB cell lines. USP7 inhibition also induced EZH2 ubiquitination and degradation. Lastly, the combination of USP7 and MDM2 inhibition showed enhanced efficacy. Our data suggests that USP7 inhibition may be a promising therapeutic strategy for children with high-risk and relapsed NB.

A Comprehensive Report of Intrinsically Disordered Regions in Inherited Retinal Diseases.

BACKGROUND/PURPOSE: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated. METHODS: IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder. MAIN OUTCOME MEASURES: The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent total missense variation. RESULTS: We included 287 RetNet genes with relevant data available from gnomAD. Mean percent disorder was 26.3% ± 26.0%, mean percent pathogenicity was 5.2% ± 11.0%, mean number of total missense variants was 424.4 ± 450.0, and mean percent total missense was 50.0% ± 13.4%. The percent disorder followed a bimodal distribution with the highest number of occurrences in the 0 to 10th disorder decile. The five outlier proteins in the first disorder decile with a higher-than-expected number of total missense variation were identified (HMCN1, ADGRV, USH2A, DYNC2H1, LAMA1, and SLC38A8). When excluded, % total missense was significantly associated with percent disorder (R = 0.238 and p = 0.0240). CONCLUSIONS: This novel study examining all genes implicated in IRDs found that the majority genes had a disorder in the 0 to 10th decile and were relatively intolerant to missense variation. This may have future utility when interpreting variants of undetermined significance and missense variants.