Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

Development of a novel protocol to evaluate contact-lens related ocular surface health on marmosets (Callithrix jacchus).

Contact lens wear affects the ocular surface and can cause contact lens-induced dry eye (CLIDE). The purpose of this study was bifold: (1) to develop a novel protocol to assess the ocular surface in a non-human primate (NHP) model, the common marmoset (Callithrix jacchus), and (2) to characterize central corneal thickness (CCT), tear osmolarity, blink rate and tear meniscus height (TMH) longitudinally, in untreated marmosets (controls) compared to animals treated with contact lenses (CL). Longitudinal changes in CCT (N = 10 control; N = 10 treated with contact lenses, CL-treated), osmolarity (N = 4 control; N = 6 CL-treated), blink rate (N = 8 control; N = 10 CL-treated) and TMH (N = 8 control; N = 6 CL-treated) were assessed using high frequency A-scan ultrasound, the I-PEN Vet Tear Osmolarity System, a video recording system (745 frames/minute) and Image J respectively, from 70 days to 224 days (5 months) at approx. 9am, and again after 9hrs of CL wear (methafilcon A, 55% water content; Capricornia, Australia) after every 4 weeks of contact lens wear for a total of 22 weeks of treatment. Repeated measures ANOVA was used to compare eyes over time and student t-test was used to compare treated to control eyes at each time point. At baseline, untreated marmosets had a CCT (mean ± SD) of 0.31 ± 0.01 mm, tear osmolarity 311.67 ± 11.48 mOsms/L, blink rate 1.83 ± 1.79 blinks per minute (bpm) and TMH 0.07 ± 0.02 arbitrary units (au), all of which remained stable over 5 months, except blink rate that increased to 5.32 ± 1.58 bpm (p < 0.01) after 5 months. In CL-treated marmosets, however, CCT progressively increased with CL wear (baseline: 0.30 ± 0.01 mm; 5 months: 0.31 ± 0.02 mm, p < 0.05), while osmolarity decreased after 2 and 3 months of CL wear (baseline: 316.11 ± 13.63; 2 months: 302.63 ± 11.27, p < 0.05; 3 months: 302.92 ± 14.58, p < 0.05). The decrease in osmolarity occurred in parallel to an increase in blink rate (baseline: 0.98 ± 1.18 bpm; 2 months: 3.46 ± 3.04 bpm, p < 0.05; 3 months: 3.73 ± 1.50 bpm, p < 0.001). TMH decreased during the third month of CL wear (baseline: 0.06 ± 0.00 au; 3 months: 0.05 ± 0.01 au, p < 0.05), and increased after 4 months (0.08 ± 0.01 au, p < 0.05). As TMH decreased, tear osmolarity increased in both control (R = -0.66, p < 0.05) and CL-treated marmosets (R = -0.64, p < 0.05). The results suggest that marmosets treated with CL for 5 months experienced an increase in blink rate, CCT and TMH, along with a decrease in osmolarity within the first few months of CL treatment that differed from the unaffected stable ocular surface findings observed untreated animals. We hypothesize that CL wear in marmosets might induce an increased blink rate and TMH, in turn delaying the development of hyperosmolarity. These findings confirm that the marmoset is a good novel animal model for ocular surface research for the assessment of novel contact lens materials aimed to alleviate CLIDE.

Person Specific Parameter Heterogeneity in the 2PL IRT Model.

Following Kelderman and Molenaar's demonstration that a factor model with person specific factor loadings is almost indistinguishable from the standard factor model in terms of overall fit, we examined person specific measurement models in Item Response Theory, person specific discrimination and difficulty parameters were created by adding random variation at the item by person level. Using standard fitting algorithms for the 2PL IRT there was modest evidence of person- or item-level misfit using common diagnostic tools. The item difficulties were well-estimated, but the item discriminations were noticeably underestimated. As found by Kelderman and Molenaar, factor scores were estimated with less than expected reliability due to the underlying heterogeneity. The person specific models considered here are basically limiting cases of IRT models with multilevel, mixture, or differential item functioning structure. We conclude with some thoughts regarding real-world sources of heterogeneity that might go unacknowledged in common testing applications.

Validation and clinical usefulness of the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) among French-speaking voice-hearers.

Auditory verbal hallucinations (AVH), also called voices, are often distressing to individuals experiencing them. Valid and reliable instruments are necessary to document the hearing voices experience across cultures. The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) is becoming a widely used self-administered instrument for assessing characteristics, content and subjective effect of AVH. This study investigates the psychometric characteristics of the HPSVQ French version (HPSVQ FV) in a clinical sample of voice-hearers. The results showed that the HPSVQ yields a global score (HPSVQ-Global) as well as a distress (HPSVQ-Distress) and a severity (HPSVQ-Severity) sub-score having good, acceptable and questionable internal consistency respectively. Significant correlations were found between hallucination severity (BPRS 4.0), distress (PSYRATS-AH), voices acceptance (VAAS-9), anxiety and depression (HADS). However, no significant associations were observed between Suspicion and Unusual Thoughts (BPRS 4.0). At a one-week interval, the temporal stability of the three indices was excellent. Moreover, after a brief cognitive intervention, a significant reduction was observed in all indices. Taken together, the HPSVQ FV demonstrated good construct validity, reliability and sensitivity to change. These findings support the use of the HPSVQ in francophone clinical and research settings. However, the bi-factorial solution of the HPSVQ FV should be further examined in larger samples.

Impact of Student Pharmacist-Led Transition-of-Care Services on 30-Day Hospital Readmissions at a University Call Center.

Background: Transition of care (TOC) refers to the movement of patients between different health care settings due to changes in medical conditions and needs. Pharmacists can play an important role in TOC services as polypharmacy is a common reason for hospital readmission that costs the US taxpayers an average of $17 billion annually. Objective: The purpose of this study is to evaluate the impact of TOC telehealth services provided by pharmacy students at a university-based call center on 30-day hospital readmission. Methods: In this retrospective observational study, an electronic chart review was conducted for patients who were discharged from the hospital and received a telephone call from pharmacy students. Patients were referred to the pharmacy team from a primary care provider office. The co-primary endpoints were the number of 30-day all-cause hospital readmissions (including emergency department visits) and 30-day readmission due to initial admission diagnosis in patients who received a telephonic TOC call from a pharmacy student compared with patients who declined or were unable to be reached. Types of pharmacy-related TOC interventions provided by students were also collected. Results: A total of 84 patients were included in this study. All-cause 30-day readmission was similar between groups (13% vs 15.8%), whereas 30-day readmission due to initial admission diagnosis was much lower in the intervention group (5.9% vs 11.1%). Although a positive trend was observed in favor of the intervention group, a statistically significant difference was not observed for both 30-day all-cause readmission and 30-day readmission due to initial admission diagnosis. Medication reconciliation, adherence counseling, and lifestyle education (diet, exercise) are the most common topics discussed with the patients during TOC interventions. Conclusion: Using student pharmacists to provide postdischarge TOC calls can be a benefit to the patient and the health care team while offering pharmacy students valuable learning experience prior to graduation.

Prenatal alcohol exposure and mental health at midlife: A preliminary report on two longitudinal cohorts.

BACKGROUND: Although the effects of prenatal alcohol exposure (PAE) have been studied extensively, there is relatively little information available on adult mental health functioning among exposed individuals. The current study compares the self-reported midlife mental health status of individuals who were prenatally exposed to alcohol and diagnosed in childhood with the effects of this exposure with that of unexposed individuals. METHODS: Participants (N = 292) were recruited from two longitudinal cohorts in Atlanta and Seattle and asked to complete an Adult Health Questionnaire that surveyed their current health and mental health status. The questionnaire was completed either in-person or remotely and included questions about current symptoms of depression and anxiety and mental health disorder diagnoses. The analysis compared a Nonexposed Contrast group to those in two exposure groups: (1) Alcohol Exposed with Fetal Alcohol Effect but not meeting criteria for Fetal Alcohol Syndrome (FAS) and (2) Alcohol Affected and meeting criteria for FAS. RESULTS: Both alcohol-exposed groups reported higher levels of current depressive symptoms and a higher prevalence of diagnoses of depression, anxiety, bipolar disorder, and/or attention deficit/hyperactivity disorder. No differences were noted for psychotic disorders. PAE was also associated with greater environmental stressors, including higher levels of adverse childhood events and lower current socioeconomic status. Path analyses suggested that PAE was indirectly related to mood disorders with its effects being mediated by other environmental factors. CONCLUSIONS: PAE is associated with greater rates of mental health disorders in middle adulthood. These outcomes appear to result from multiple stressors that affect individuals made vulnerable by their early alcohol exposure. Clinical outcomes could be improved by prevention efforts directed at preventing prenatal alcohol use and reducing environmental stressors later in life, and by the early identification of PAE and its effects.

Myopia Alters the Structural Organization of the Retinal Vasculature, GFAP-Positive Glia, and Ganglion Cell Layer Thickness.

To describe the effect of myopic eye growth on the structure and distribution of astrocytes, vasculature, and retinal nerve fiber layer thickness, which are critical for inner retinal tissue homeostasis and survival. Astrocyte and capillary distribution, retinal nerve fiber (RNFL), and ganglion cell layer (GCL) thicknesses were assessed using immunochemistry and spectral domain optical coherence tomography on eleven retinas of juvenile common marmosets (Callithrix Jacchus), six of which were induced with lens-induced myopia (refraction, Rx: -7.01 ± 1.8D). Five untreated age-matched juvenile marmoset retinas were used as controls (Rx: -0.74 ± 0.4D). Untreated marmoset eyes grew normally, their RNFL thickened and their astrocyte numbers were associated with RNFL thickness. Marmosets with induced myopia did not show this trend and, on the contrary, had reduced astrocyte numbers, increased GFAP-immunopositive staining, thinner RNFL, lower peripheral capillary branching, and increased numbers of string vessels. The myopic changes in retinal astrocytes, vasculature, and retinal nerve fiber layer thickness suggest a reorganization of the astrocyte and vascular templates during myopia development and progression. Whether these adaptations are beneficial or harmful to the retina remains to be investigated.

Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth.

Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

Adenotonsillectomy as a treatment for sleep-disordered breathing in children with ADHD.

Sleep-disordered breathing (SDB) and attention deficit hyperactivity disorder (ADHD) are common disorders diagnosed in children. Although these diagnoses were previously considered unrelated, research now is showing that some symptoms of ADHD, specifically oppositional behavior, hyperactivity, and impulsivity, can be related to SDB in children and differs from bona fide ADHD. This article explores the connection between the two disorders and the importance of identifying and screening for SDB in children presenting with similar symptoms related to ADHD. The article also examines symptom improvement in patients with ADHD symptoms after an adenotonsillectomy, one of the first-line treatments for children diagnosed with SDB; this procedure may reduce the need for long-term stimulant use in some children with ADHD.

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.

OBJECTIVE: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening. METHODS: We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH). RESULTS: We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%. SIGNIFICANCE: Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening.

Chemical profile and in vivo hypoglycemic effects of Syzygium jambos, Costus speciosus and Tapeinochilos ananassae plant extracts used as diabetes adjuvants in Puerto Rico.

BACKGROUND: The increasing numbers of people who use plant-based remedies as alternative or complementary medicine call for the validation of less known herbal formulations used to treat their ailments. Since Puerto Rico has the highest rate of Type 2 diabetes within all the states and territories of the United States, and Puerto Ricans commonly use plants as diabetes adjuvants, it is important to study the plants' physiological effects, and identify their bioactive compounds to understand their role in modulation of blood glucose levels. We present the phytochemical profiles and hypoglycemic effects of Tapeinochilus ananassae, Costus speciosus and Syzygium jambos. METHODS: Phytochemicals in methanolic and aqueous extracts were analyzed by thin layer chromatography (TLC). Alkaloids (Bromocresol green, λ=470 nm), flavonoids (AlCl3, λ=415 nm), saponins (DNS, λ=760 nm), tannins (FeCl3/K4Fe(CN)6, λ=395 nm) and phenolics (Folin-Ciocalteau, λ=765 nm) were quantified. Male C57BLKS/J (db/db) and C57BL/J (ob/ob) genetically obese mice were orally gavaged with aqueous extracts of lyophilized plant decoctions for 10 wks. RESULTS: Our results show that T. ananassae had significantly greater amounts of flavonoids and tannins, while S. jambos showed the greatest concentration of phenolics and C. speciosus exhibited higher amounts of alkaloids. C57BLKS/J db/db treated with plant extracts show better glucose modulation when the extracts are administered in complement with an insulin injection. Finally, C57BL/J ob/ob mice on T. ananassae and S. jambos treatments show better blood glucose modulation over time. CONCLUSION: These results document for the first time the chemical profile of T. ananassae and provide evidence for a potential anti-diabetic efficacy of T. ananassae and S. jambos.

Use trends of chlorthalidone and hydrochlorothiazide among United States adults with hypertension: National Health and Nutrition Examination Survey 2009-2018.

OBJECTIVES: To estimate the national prevalence of chlorthalidone and hydrochlorothiazide use among adults diagnosed with hypertension by sociodemographic subgroup, healthcare access status, and clinical factors. METHODS: Data was extracted from the National Health and Nutrition Examination Survey for 2009-2010 through 2017-2018 survey waves. Patients at least 20 years old, diagnosed with hypertension, and on hydrochlorothiazide or chlorthalidone were included. Uni-variable logistic regression models estimated the odds of being on chlorthalidone compared with hydrochlorothiazide use by sociodemographic and clinical factors. Analyses were adjusted for multi-stage complex survey design and are nationally representative. RESULTS: Two thousand five hundred and eighty-five participants were included with 95.2% participants using hydrochlorothiazide and 4.8% using chlorthalidone. Participants over 65 years were more likely to be on chlorthalidone compared with younger counterparts [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.12-2.88]. Participants with hypokalemia (OR 2.62; 95% CI 1.56-4.42) or hyponatremia [OR 2.298; 95% CI 1.23-4.30) were more likely to be using chlorthalidone compared with patients with normal levels. CONCLUSION: Chlorthalidone, a potent and effective first-line antihypertensive agent and thoroughly studied thiazide diuretic with substantial cardiovascular benefits, continues to be underutilized in patients with hypertension. Findings demonstrated that individuals receiving chlorthalidone were more likely to be 65 years or older and to experience hyponatremia or hypokalemia. Sociodemographic factors, healthcare access and use, clinical factors, and medical conditions did not appear to sway the choice in thiazide diuretic use.

Real-World Analysis of Long-Acting and NPH-Containing Insulins on Glycemic Control.

Introduction Affordability of insulin products has become a concern in the past several years as the average price of various insulin products has increased. While awaiting legislation at the federal level that would address issues leading to high insulin costs, providers may have shifted prescribing practices to prescribe the lowest-priced insulin products to achieve patients' treatment goals. Objective To compare the prevalence of hypoglycemic events between patients receiving lower-cost neutral protamine Hagedorn (NPH)-containing human insulins and higher-cost long-acting insulin analogs in Medicare Part D enrollees within a management services organization, as well as assessing glycemic control and changes in body mass index. Methods This was a multicenter, retrospective study conducted at three primary care clinics. The co-primary outcomes were percent difference of documented mild and severe hypoglycemic events between individuals receiving NPH-containing human insulin and long-acting insulin. Results A total of 72 patients met inclusion criteria and were receiving NPH-containing human insulins or the long-acting insulin analogs, 15 and 57 patients, respectively. Severe hypoglycemic events occurred in 3.5% vs 0% of the long-acting insulin analog and NPH-containing human insulin group, respectively (P = 0.999). Mild hypoglycemic episodes were experienced by 31.6% versus 33.3% of long-acting insulin analog and NPH, respectively (P = 0.539). For secondary outcomes, no difference was observed in glycemic control outcomes across insulin groups. Conclusion Among Medicare Part D patients with type 2 diabetes mellitus, the use of NPH-containing human insulins was not associated with an increased risk of mild or severe hypoglycemia-related episodes or reduced glycemic control compared with long-acting insulin. Study findings suggest that lower-cost, NPH-containing human insulins may be an alternative to higher-cost, long-acting insulin analogs.

Toward a person-centered ethics framework for autonomy in spinal cord injury research and rehabilitation.

In this paper, we explore how the concepts of autonomy and autonomous choice are understood in the context of spinal cord injury in the academic literature, both in reporting on research results and more broadly on outcomes and quality of life. We find inconsistent, framework-absent portrayals of autonomy as well as an absence of discourse that draws upon ethical constructs and theory. In response, we advance a person-centered framework for spinal cord injury research that combines both lived experience and a disability ethics approach to fill this gap.

Impact of Pharmacist Transitions of Care on 30-Day Readmissions Within a Primary Care-Based Accountable Care Organization.

Previous studies in the ambulatory care setting have shown inconsistent results in regard to, or with respect to pharmacist telephonic transitions of care (TOC) encounters and reduction in 30-day readmission rates. No studies that have been completed within an accountable care organization (ACO) evaluating the impact of telephonic TOC encounters performed by a pharmacist have been identified. The objective of this study was to analyze the impact of clinical pharmacy telephonic TOC encounters on readmission rates within a primary care-based ACO. In this retrospective chart review, data for those who had a pharmacist telephonic TOC encounter and those who had an attempt were collected. The primary outcome of this study was all-cause 30-day readmission rate. Secondary outcomes included 30-day readmission rate for targeted disease states, time to readmission, and readmission reason the same as previous discharge reason. For subjects who received a telephonic TOC encounter, pharmacist intervention type and provider acceptance of intervention(s) were described. For the final analysis, 154 encounters were included, 83 encounters in the telephonic TOC encounter group, and 71 did not receive a telephonic TOC encounter. The 30-day readmission rates were similar among those who received a telephonic TOC encounter and those who did not: the difference was not significant (15.7% vs. 28.2%; P = 0.059). There was also no statistical difference in the secondary outcomes. Even so, the results of this study suggest that performing a pharmacist telephonic TOC encounter in a primary care-based ACO setting has the potential to reduce 30-day readmission rates and further research appears to be warranted in this important area of practice.

Clinical care for severe and persistent eating disorders in pediatric populations: Perspectives of health professionals.

OBJECTIVE: Models of treatment for adults with severe and enduring eating disorders focus on harm reduction and improving quality of life. However, there is a notable gap in the pediatric literature in this area. The current study set out to assess the perspectives of health professionals regarding clinical care for young people (e.g., ages 10-25 years) with severe and enduring eating disorders, and to explore perceptions about appropriate treatment options for these presentations. METHODS: Health professionals were invited to complete a two-stage online survey about their experiences with clinical care for pediatric eating disorders through Canadian and Australian professional eating disorder networks. Survey 1 included questions about their experiences in supporting individuals with severe and enduring presentations. Participants who completed Survey 2 reviewed clinical vignettes and shared their perspectives about treatment recommendations and models of care, including for a severe and enduring presentation. RESULTS: A total of 85 clinicians responded to questions on Survey 1 about severe and enduring eating disorder presentations. A portion of these respondents (n = 25) also participated in Survey 2. The majority of respondents to Survey 1 reported providing clinical care for pediatric severe and enduring eating disorder presentations. Amongst respondents to Survey 2, there was low consensus amongst respondents for the clinical care that would be most appropriate for young people with a severe and enduring eating disorder presentation. Numerous challenges in models of care for severe and enduring presentations in pediatric settings were raised in responses on Survey 2, with clinicians sharing their awareness of models focusing on quality of life, while also raising concerns about the appropriateness of these models for young people. CONCLUSIONS: The preliminary results of this study demonstrate that the majority of clinicians report that they have provided care to young people with severe and enduring presentations. There is a clear need for establishing guidance for clinicians working in pediatric eating disorder settings around models of care focused on quality of life. Engagement with interested parties, including those with lived experience, can clarify the development of terminology and clinical pathways for severe and enduring presentations of pediatric eating disorders.

Treatment models focusing on harm reduction and quality of life (as opposed to eating disorder recovery) are available for adults with severe and enduring eating disorders. However, these models are not widely available for young people. In fact, there is very limited research on severe and enduring eating disorder presentations in pediatric populations. We assessed the views of health professionals regarding clinical care for young people with severe and enduring eating disorder presentations, and asked professionals about what treatment options might be most appropriate for these presentations. Most participants reported providing clinical care for pediatric severe and enduring eating disorder presentations. However, clinicians had diverse views about the treatment that would be most appropriate for a severe and enduring eating disorder presentation in a young person. Further research and engagement with clinicians and those with lived experience is needed to clarify the terminology and clinical pathways for severe and enduring presentations of pediatric eating disorders.

Early Alterations in Inner-Retina Neural and Glial Saturated Responses in Lens-Induced Myopia.

Purpose: Myopic marmosets are known to exhibit significant inner retinal thinning compared to age-matched controls. The purpose of this study was to assess inner retinal activity in marmosets with lens-induced myopia compared to age-matched controls and evaluate its relationship with induced changes in refractive state and eye growth. Methods: Cycloplegic refractive error (Rx), vitreous chamber depth (VCD), and photopic full-field electroretinogram were measured in 14 marmosets treated binocularly with negative contact lenses compared to 9 untreated controls at different stages throughout the experimental period (from 74 to 369 days of age). The implicit times of the a-, b-, d-, and photopic negative response (PhNR) waves, as well as the saturated amplitude (Vmax), semi-saturation constant (K), and slope (n) estimated from intensity-response functions fitted with Naka-Rushton equations were analyzed. Results: Compared to controls, treated marmosets exhibited attenuated b-, d-, and PhNR waves Vmax amplitudes 7 to 14 days into treatment before compensatory changes in refraction and eye growth occurred. At later time points, when treated marmosets had developed axial myopia, the amplitudes and implicit times of the b-, d-, and PhNR waves were similar between groups. In controls, the PhNR wave saturated amplitude increased as the b + d-wave Vmax increased. This trend was absent in treated marmosets. Conclusions: Marmosets induced with negative defocus exhibit early alterations in inner retinal saturated amplitudes compared to controls, prior to the development of compensatory myopia. These early ERG changes are independent of refraction and eye size and may reflect early changes in bipolar, ganglion, amacrine, or glial cell physiology prior to myopia development. Translational Relevance: The early changes in retinal function identified in the negative lens-treated marmosets may serve as clinical biomarkers to help identify children at risk of developing myopia.

Choroidal Morphology and Photoreceptor Activity Are Related and Affected by Myopia Development.

Purpose: The choroid is critical for the regulation of eye growth and is involved in the pathogenesis of myopia-associated ocular complications. This study explores the relationship among choroidal biometry, photoreceptor activity, and myopic growth in marmosets (Callithrix jacchus) with lens-induced myopia. Methods: A total of 34 common marmosets aged 92 to 273 days old were included in this study. Axial myopia was induced in 17 marmosets using negative soft contact lenses and 17 marmosets served as untreated controls. Cycloplegic refraction (RE) and vitreous chamber depth (VCD) were measured using autorefraction and A-scan ultrasonography, respectively. Choroidal scans were obtained using spectral-domain optical coherence tomography and binarized to calculate subfoveal choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and LA/SA. To assess photoreceptor activity, the a-wave of the full-field electroretinogram was measured. Regression models were used to investigate the relationship between outcome measures. Results: Eyes induced with axial myopia (RE = -7.14 ± 4.03 diopters [D], VCD = 6.86 ± 0.39 mm) showed significant reductions (4.92-21.24%) in all choroidal parameters (ChT, TCA, LA, SA, CVI, and LA/SA) compared to controls (RE = -1.25 ± 0.60 D, VCD = 6.58 ± 0.26 mm, all P < 0.05), which changed as a function of refraction and vitreous elongation, and were associated with a decrease in the a-wave amplitude. Further, multiple regression showed that a combination of ChT and CVI could well predict RE and VCD. Conclusions: This study reports the existence of significant alterations in choroidal morphology in non-human primate eyes induced with myopia. The changes in choroidal anatomy were associated with reduced light-adapted a-wave amplitude. These findings may represent early markers for reduced visual performance and chorioretinal complications known to occur in eyes with large degrees of myopia.