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Nenita Maganti,1 Natalie Squires,1 Shubhendu Mishra,1 Prithvi Bomdica,1 Divya Nigam,2 Arthur Shapiro,2 Manjot K Gill,1 Alice T Lyon,1 Rukhsana G Mirza1 1Department of Ophthalmology, Northwestern University, Chicago, IL, USA; 2Department of Psychology and Department of Computer Science, American University, Washington, DC, USACorrespondence: Rukhsana G Mirza, Department of Ophthalmology, Northwestern University, Chicago, IL, USA, Tel +1 312-908-8152, Email r-mirza@Northwestern.eduPurpose: This study was performed to characterize changes in contrast sensitivity (CS) that occur in patients with age-related macular degeneration (AMD) using a novel test, the motion diamond stimulus (MDS).Methods: This was a cross-sectional study in which 20 subjects with unilateral exudative AMD (eAMD) and contralateral dry AMD received 3 assessments: the Pelli-Robson (PR) CS Chart, the MDS test, and a visual function questionnaire-25 (VFQ-25). CS results from the PR, and MDS tests were compared across 3 groups: eyes with eAMD vs dry AMD, eAMD vs control, dry AMD vs control. Healthy, undilated eyes from another study served as the control group. Significance was determined using ANOVA analysis for the MDS output parameters (α: overall contrast threshold, β: adaptability of the visual system) and PR logCS. Patients were also administered the VFQ-25 to assess vision-related quality of life.Results: The ANOVA of the MDS data demonstrated a significant difference in visual function according to the β parameter of the 3 groups, but no significant difference in the α parameter. PR CS results for the 3 groups were significantly different, further supporting the MDS results. Post-hoc analysis showed a significant difference in β and PR log CS between the eAMD and control eyes.Conclusion: The MDS test is valuable in discerning CS impairments in patients with AMD. It can provide further insight into the visual changes experienced by patients with AMD and has potential to quantify visual function changes that are not found on visual acuity testing alone.Keywords: age-related macular degeneration, AMD, motion diamond stimulus, MDS, contrast sensitivity, CS

Yaqoob Qaseem,1 Sahej Samra,1 Olga German,1 Elizabeth Gray,2 Manjot K Gill1 1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Biostatistics Collaboration Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Manjot K GillDepartment of Ophthalmology, Feinberg School of Medicine, Northwestern University, Suite 440, 645 N Michigan Avenue, Chicago, IL 60611, USATel +1 312-908-8152Email mgill@nm.orgBackground: Diabetic retinopathy (DR) may be asymptomatic in both mild and advanced stages. A patient’s accurate perception of their DR severity may therefore be critical for effective self-management behaviors and understanding the need for timely intervention and follow-up.Purpose: To evaluate the relationship between self-reported and actual retinopathy severity in diabetic patients.Methods: This study was a single-center cross-sectional survey. Diabetic patients identified by enterprise data warehouse were sent an online questionnaire where they were asked to self-assess for presence of DR and grade their severity. Actual DR grading was determined via chart review. The primary outcome measures were patient-assessed DR severity and agreement with actual DR severity.Results: Of 3208 invitations sent, 324 (10%) patients responded and 319 responses were analyzed. The data showed that 39 of 253 (15%) with no DR, 26 of 40 (65%) with mild/moderate DR, and 24 of 26 (92%) with severe DR believed they had DR (p< 0.001). Of those with no DR, 214 of 253 (85%) accurately assessed absence of DR. Of those with mild/moderate DR, 25 of 40 (63%) accurately assessed their severity, 14 of 40 (35%) believed they had no DR, and 1 of 40 (3%) believed they had severe DR. In patients with severe DR, 9 of 26 (35%) correctly assessed their severity, 15 of 26 (58%) believed they had mild/moderate DR, and 2 of 26 (8%) believed they had no DR.Conclusion: Patients with severe DR were the most likely to report presence of DR, but often underestimated their disease severity. Many with mild/moderate DR did not realize they had DR. This consistent underestimation of severity across all a significant barrier to timely follow-up and treatment necessary to prevent future visual impairment.Keywords: diabetic retinopathy, diabetes, survey, severity, perception, awareness, understanding, anti-VEGF, barriers, screening, accuracy, self-report

Balaji Veluswamy, Andy Lee, Rukhsana G Mirza, Manjot K Gill Northwestern University, Feinberg School of Medicine, Chicago, IL, USACorrespondence: Manjot K Gill Tel +1 312 908-8152Fax +1 312 503-8152Email mgill@nm.orgPurpose: Neovascular age-related macular degeneration (nv-AMD) is the leading cause of blindness in individuals 55 years and older. The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has greatly altered the visual acuity (VA) prognosis in these patients. While many studies have described treatment outcomes, few have explored the impact of early detection on VA outcomes.Patients and Methods: This retrospective cohort study consisted of treatment-naïve eyes with nv-AMD (ICD9 diagnosis code 362.52) that were treated with bevacizumab, ranibizumab, and aflibercept by four physician investigators in a large urban tertiary center from March 2008 to October 2015. Eyes were categorized by baseline VA into good (20/50 or better), intermediate (20/50– 20/200), and poor (20/200 or worse) initial VA. VA and optical coherence tomography (OCT) findings were evaluated throughout the treatment period.Results: 224 eyes were evaluated. Of eyes with good, intermediate, and poor initial VA, 14.1%, 37.2%, and 58.3% showed an increase in 2 or more lines of vision on LogMAR, respectively [p < 0.001], while 71.8%, 40.7%, and 16.7% of eyes had a final VA of 20/50 or better, respectively [p < 0.001]. Average final Snellen VA in eyes with good, intermediate, and poor initial VA was 20/47, 20/96, and 20/277, respectively. Change in VA for good, intermediate, and poor initial VA groups was ΔLogMAR of +0.117, +0.041, and − 0.230, respectively. Of eyes with good, intermediate, and poor baseline VA, 42.3%, 20.9%, and 20.0%, respectively, showed resolution of fluid on OCT [p = 0.003].Conclusion: Patients with good initial VA were more likely to maintain good vision and show resolution of fluid on OCT through follow-up. Patients with poor initial VA tended to gain more vision, however, had poorer final VA. This underscores the importance of early detection and treatment of nv-AMD in maintaining superior outcomes.Keywords: vision, anti-VEGF therapy, AMD

Objective: The study described service utilization among children with emotional and behavioral disorders making a first visit to outpatient mental health clinics in four Midwest cities.Methods: Data were from the Longitudinal Assessment of Manic Symptoms study. A total of 707 youths aged six to 12 years 11 months and their parents completed diagnostic assessments; demographic information and mental health service use was self-reported. Analyses examined the relationship of demographic variables, diagnoses, impairment, and comorbidity with type and level of services utilized.Results: Utilization was multimodal; half the youths had received outpatient and school services during their lifetime. Factors unrelated to need (age, sex, race, and insurance) were associated with service type. Children with a bipolar spectrum disorder had higher use of inpatient services than those with depressive or disruptive disorders and were more likely to currently use two or more services. More than half of youths with bipolar or depressive disorders had lifetime use of both medication and therapy, whereas youths with a disruptive behavior disorder were more likely to have used only therapy. Impairment and comorbidity were not related to service utilization.Conclusions: Use of services began at a very young age and occurred in multiple service sectors. Type of service used was related to insurance and race, underscoring the need for ongoing disparities research. Contrary to findings from administrative data analyses, use of medication alone was infrequent. The low rate of use of combination therapy suggests that clinicians and families need to be educated about the effectiveness of multimodal treatment. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Clinical heterogeneity and complex genetics pose challenges to understanding disease mechanisms and producing effective cures. To model clinical heterogeneity, we generated human induced pluripotent stem cells (iPSCs) from two sporadic ALS patients (sporadic ALS and sporadic ALS with frontotemporal dementia), two familial ALS patients (familial SOD1 mutation positive and familial C9orf72 repeat expansion positive), and four age- and sex-matched healthy controls. These iPSCs can be used to generate 2D and 3D in vitro models of ALS to investigate mechanisms of disease and screen for therapeutics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Timothy J Tracey reports financial support was provided by Motor Neurone Disease Research Australia. Shyuan T Ngo reports financial support was provided by National Health and Medical Research Council. Shyuan T Ngo reports financial support was provided by Motor Neurone Disease Research Australia. Shyuan T Ngo reports financial support was provided by FightMND. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes ( NAT1 and NAT2 ) as well as one pseudogene, all of which are located together on chromosome 8. Although they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases, including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondria. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biologic function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small-molecule drugs. SIGNIFICANCE STATEMENT: The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 share common features in their associations with mitochondrial bioenergetics. This review discusses mitochondrial function as it relates to health and disease, and the importance of NAT in mitochondrial function and dysfunction. It also compares NAT1 and NAT2 to highlight their functional similarities and differences. Both NAT1 and NAT2 are potential drug targets for diseases where mitochondrial dysfunction is a hallmark of onset and progression., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Purpose: To describe abnormal vitreoretinal findings during macular hole repair in Alport syndrome (AS)., Methods: Case report of preoperative, intraoperative, and postoperative findings related to macular hole surgery in a patient with AS., Observations: A 50-year-old woman with Alport syndrome was found to have bilateral full-thickness macular holes. Surgery was recommended for her left eye given recent onset of vision loss and smaller hole size (313 um). Intraoperatively, the vitreous was found to have fine fibrillar strands and to be abnormally adherent to the retinal surface. There was little to no internal limiting membrane (ILM) present. Vitrectomy was performed with posterior cortical hyaloid peeling and 15% C3F8 gas tamponade. Two months after surgery, the macular hole was successfully closed., Conclusions: Abnormal vitreous composition and adherence to the retinal surface may contribute to macular hole formation in AS patients. Standard surgical approaches including ILM peeling may not be feasible, though thorough removal of the posterior cortical hyaloid may be sufficient to achieve macular hole closure., Competing Interests: Conflicts of Interest: None, (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Objectives: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder., Methods: Youth numbering 394 with bipolar disorder who completed ≥2 follow-up assessments (median follow-up length = 13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow-up was assessed via the A-LIFE Self-Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC., Results: There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross-validated relative influence in the model (AUC = 0.82; in order of relative influence): (1) age of mood disorder onset; (2) non-suicidal self-injurious behavior (trichotomized); (3) current age; (4) psychosis (trichotomized); (5) socioeconomic status; (6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); (7) history of suicide attempt (trichotomized); (8) family history of suicidal behavior; (9) substance use disorder (trichotomized); (10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history., Conclusions: This RC holds promise as a clinical and research tool for prospective identification of individualized high-risk periods for suicide attempt in early-onset bipolar disorder.Reprinted from Bipolar Disord 2022; 24:749-757 , with permission from John Wiley and Sons. Copyright © 2022., (Copyright © 2023 by the American Psychiatric Association.)

Purpose: Compared with the general population in North America, Native American/American Indian and Alaska Native (AI/AN) populations experience a disparate prevalence of eye diseases. Visual impairment is a barrier to communication, interferes with academic and social success, and decreases overall quality of life. The prevalence of ocular pathology could serve as an indicator of health and social disparities. Therefore, the objective of this research was to perform a thorough review comparing the prevalence of common ophthalmological pathologies between AI/AN and non-AI/AN individuals in North America., Design: Retrospective, cross-sectional study., Methods: A total of 57 articles were retrieved and reviewed, and 14 met the criteria outlined for inclusion. These articles were retrieved from PubMed, MEDLINE, and ISI Web of Knowledge. Only studies that were peer reviewed in the last 25 years and reported on the prevalence of eye diseases in AI/AN compared with a non-AI/AN population met criteria., Results: Rates of retinopathy, cataracts, visual impairment, and blindness were clearly higher for AI/AN compared with non-AI/AN counterparts. Although rates of macular degeneration and glaucoma were similar between AI/AN and non-AI/AN populations, the treatment rates were lower and associated with poorer outcomes in AI/AN individuals., Conclusions: There are considerable inequities in the prevalence and treatment rates of ophthalmologic conditions in AI/AN individuals. A likely explanation is the barrier of lack of access to adequate health and eye care. Because of substantial underinsurance and geographic variability, attention needs to be brought to expanding eye care access to AI/AN communities. The results are subject to the availability of appropriate technology, health literacy, and language., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess medication adherence and factors associated with poor adherence in youth with bipolar disorder (BD) followed from adolescence through young adulthood., Method: Participants with BD recruited through the Course and Outcome of Bipolar Youth (COBY) study were included in this study if they were prescribed psychotropic medications and had at least 3 follow-up assessments of medication adherence (N= 179, ages 12-36). Medication adherence had been evaluated for a median of 8 years using a questionnaire derived from the Coronary Artery Risk Development in Young Adults (CARDIA) study. For the longitudinal evaluation, adherence was measured as the percentage of follow-up assessments in which the participants did not endorse any of the nonadherence items included in the questionnaire. Concurrent and future predictors of poor adherence were assessed using both univariate and multivariate longitudinal analyses., Results: Among the participants, 51% reported poor adherence in more than 50% of their follow-up assessments. Younger age, family conflicts, polypharmacy, lower functioning, greater severity of mood symptoms, and comorbid disorders were associated with poor adherence in the univariate analyses. In the multivariate analyses, comorbid ADHD was the single most influential factor associated with concurrent and future poor adherence in all age groups. Participants' most reported reasons for poor adherence were forgetfulness (56%), negative attitudes toward medication treatment (10.5%), and disturbed daily routine (7%)., Conclusions: Poor medication adherence is a significant problem in youth with BD with the most influential factor being the presence of comorbid ADHD. Thus, it is important to identify and appropriately treat comorbid ADHD to improve medication adherence and patients' prognosis. Providers should also recommend tools to enhance consistent medication intake and address patients' concerns and negative beliefs about their illness and treatment.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which the TDP-43 protein is believed to play a central role in disease pathophysiology. Using the CRISPR-Cas9 system, we introduced the heterozygous c.1144G > A (p.A382T) missense mutation in exon 6 of the TARDBP gene into an iPSC line derived from a healthy individual. These edited iPSCs displayed normal cellular morphology, expressed major pluripotency markers, were capable of tri-lineage differentiation, and possessed a normal karyotype., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shyuan Ngo reports financial support was provided by National Health and Medical Research Council. Timothy Tracey reports financial support was provided by University of Queensland. Leanne Jiang reports financial support was provided by The University of Western Australia. Shyuan Ngo reports financial support was provided by MND and Me Foundation. Shyuan Ngo reports financial support was provided by Royal Brisbane and Women’s Hospital Foundation. Shyuan Ngo reports financial support was provided by FightMND. Shyuan Ngo reports consultancy fees from Cytokinetics., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the correlation between nonperfusion parameters on OCT angiography (OCTA) and ultrawide-field fluorescein angiography (UWF-FA) in subjects with diabetes mellitus (DM)., Design: Prospective, cross-sectional study., Subjects: Subjects with DM and a wide range of diabetic retinopathy (DR) severity seen at a tertiary referral center., Methods: We used averaged 3 × 3 mm OCTA scans to measure geometric perfusion deficit (GPD), vessel density, and vessel length density in the full retina, superficial capillary plexuses (SCPs), and deep capillary plexuses (DCPs). Nonperfusion was manually delineated on UWF-FA to quantify central, peripheral, and total retinal nonperfusion (mm 2 and % area)., Main Outcome Measures: Correlation between OCTA parameters and UWF-FA nonperfusion, and accuracy of these OCTA and UWF-FA parameters in detecting clinically referable eyes, using receiver operating characteristic (ROC) curve analysis, sensitivity, specificity, and area under the ROC curve (AUC)., Results: The study included 67 eyes (12 eyes with no signs of DR, 8 mild, 22 moderate, 14 severe nonproliferative DR, and 11 treatment-naive proliferative DR). There was a fair-to-moderate correlation between either central or total retinal nonperfusion on UWF-FA (mm 2 ) and GPD in the SCP (r = 0.482 and r = 0.464, respectively) and DCP (r = 0.470 and r = 0.456, respectively). Receiver operating characteristic analysis showed the DCP GPD significantly superior to other OCTA parameters at the DCP with the largest overall AUC on OCTA for distinguishing referable DR (0.905). Furthermore, the GPD parameter had the largest AUC in each respective capillary layer compared with other parameters. Overall, the total UWF-FA nonperfusion area showed a comparable AUC (0.907) and performed significantly better than peripheral nonperfusion (P = 0.041). Comparing the AUC values between GPD and UWF-FA nonperfusion parameters showed no significant difference in discerning referable DR., Conclusions: Nonperfusion as quantified on OCTA (3 × 3 mm) correlated with UWF-FA parameters and both were comparable in detecting referable DR. These macular OCTA metrics, particularly DCP GPD, have the potential for gauging the overall ischemic status of the retina, with an important clinical role in identifying eyes with clinically referable DR., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Injectable collagenase Clostridium histolyticum has been an effective and well-tolerated nonsurgical treatment option for the management of Dupuytren contracture of the hand. The purpose of this study was to determine the efficacy of collagenase injection and adverse event rate in patients who had undergone previous collagenase treatment., Methods: A retrospective chart review was performed on 332 patients treated with collagenase injection for Dupuytren contracture by three fellowship-trained hand surgeons at a single institution from 2009 to 2019. Fifty-nine joints in 45 patients underwent repeat collagenase therapy for recurrent contracture in the same digit. Pretreatment and posttreatment total metacarpophalangeal and proximal interphalangeal joint flexion contractures were recorded, with complete correction defined as <5° residual digital flexion contracture. Postmanipulation skin tears and adverse events were recorded. A comparison was made between average contracture improvement after initial collagenase injection and that after repeat injection., Results: Forty-five patients with an average duration of 30 months (range, 6-73 months) between initial and repeat collagenase therapies were identified. The mean improvement after first collagenase injection was 45° ± 24° (39° for metacarpophalangeal joint and 50° for proximal interphalangeal joint) compared with a mean improvement of 43° ± 23° (41° for metacarpophalangeal joint and 44° for proximal interphalangeal joint) after second injection. Although similar complete correction rates and skin tear rates (32.2 % for initial and 30.5% for repeat) were observed between initial (80%) and repeat injections (73%), the occurrence of adverse events was 3 times higher (3.4% for initial and 10.2% for repeat) in the latter group., Conclusions: Collagenase treatment of Dupuytren contracture yields effective total flexion contracture correction. Repeat collagenase treatment of previously treated digits yields similar deformity correction and complete correction rates but a higher incidence of adverse events., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine whether patients with diabetic retinopathy receiving intravitreal anti-VEGF injections are at increased risk of kidney function decline., Design: Retrospective cohort study., Participants: Included 187 patients who received intravitreal anti-VEGF injections for proliferative diabetic retinopathy (PDR) and/or diabetic macular edema (DME), and 929 controls with non-PDR who did not receive injections, at a large tertiary care center in Chicago, Illinois., Methods: We queried our institutional enterprise data warehouse to identify patients with diabetic retinopathy, determined whether they received intravitreal anti-VEGF injections, and followed kidney function for all patients over time., Main Outcome Measures: We assessed time to sustained 40% decline in estimated glomerular filtration rate (eGFR) from baseline in patients receiving intravitreal anti-VEGF injections and compared it with controls using Kaplan-Meier and multivariable adjusted Cox proportional hazards regression models., Results: This study included 1116 patients (565 female [50.6%]; mean [standard deviation {SD}] age, 57.3 [13.6] years; mean [SD] eGFR, 65.3 [32.1] ml/min/1.73 m 2 ). Of these, 187 patients received ≥ 1 intravitreal anti-VEGF injection (mean [SD], 11.4 [13.1] injections) for PDR and/or DME, and 929 controls with non-PDR received no injections. Intravitreal anti-VEGF injection use was not associated with an increased risk of kidney function decline (hazard ratio [HR], 1.44; 95% confidence interval [CI], 0.97-2.15). Subgroup analyses revealed that use of intravitreal anti-VEGF injections was associated with increased risk of kidney function decline in male patients (HR, 1.87; 95% CI, 1.11-3.14) but not female patients (HR, 0.97; 95% CI, 0.50-1.89). Intravitreal anti-VEGF injection use was also associated with an increased risk of kidney function decline in patients with baseline eGFR > 30 ml/min/1.73 m 2 (HR, 1.86; 95% CI, 1.15-3.01), but not in individuals with baseline eGFR ≤ 30 ml/min/1.73 m 2 (HR, 0.97; 95% CI, 0.45-2.10). Among patients who received injections, receiving ≥ 12 injections was not associated with risk of kidney function decline (HR, 1.13; 95% CI, 0.52-2.49)., Conclusions: Intravitreal anti-VEGF injections for patients with diabetic retinopathy are overall well-tolerated with respect to kidney function, but the use of intravitreal anti-VEGF injections was associated with an increased risk of kidney function decline in certain subgroups of patients., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 by the American Academy of Ophthalmology.)

Purpose: To evaluate applicants' and programs' experiences during the 2019 and 2020 fellowship application seasons. Methods: An anonymous survey of vitreoretinal surgery fellowship program directors (PDs) (n = 21) and applicants from the 2019 traditional (n = 24) and 2020 virtual (n = 17) match cycles (before and during COVID-19 pandemic, respectively) was conducted. The questions assessed demographics, interview experiences, and overall interview costs. Statistical significance was determined using unpaired and paired 2-sided t tests for applicants and PDs, respectively ( P < .05). Results: In 2020, 17.6% of applicants and 15.8% of PDs strongly agreed that they were able to convey themselves well during the interview compared with 50% and 73.7%, respectively, in 2019 ( P = .002 and P < .001, respectively). In 2020, 5.9% of applicants and 10.5% of PDs strongly agreed that they gained a good understanding of their counterpart compared with 41.7% and 47.4%, respectively, in 2019 ( P < .001 and P = .01, respectively). Regarding cost, 83.3% of applicants and 21.1% of programs spent more than $2000 in 2019, whereas 17.6% of applicants and no program did so in 2020. Conclusions: Although virtual interviews allowed fellowship recruitment to continue during the pandemic, both applicants and PDs expressed uncertainty regarding their abilities to portray themselves and gauge those with whom they interviewed. The benefits of virtual interviews, including decreased cost, increased efficiency, and convenience, must be weighed against these factors., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background The objective of this study was to assess the accessibility and content of the critical care fellowship websites provided on the Electronic Residency Application Services (ERAS) website. Methods Using the online information provided by ERAS, we compiled a list of Accreditation Council for Graduate Medical Education (ACGME)-accredited critical care fellowship programs. Each of the links provided by ERAS was evaluated by a standard search on Google as follows: the program name + "critical care fellowship". After assembling the working links, those websites were subsequently evaluated based on the program description, application process, and educational content. Results We reviewed 59 critical care fellowship programs that were obtained from ERAS. Of the 59 programs, one retracted its participation and was not included in the study, and six other programs were excluded due to repeated links on ERAS, nonworking links, and websites without any content. We analyzed the data collected from the remaining 52 programs. Our data shows a general lack of information being provided to prospective critical care candidates. Conclusions ERAS is a major source of information for prospective fellows looking for critical care fellowships in the current match. Unfortunately, the majority of the programs evaluated lack substantial information for prospective candidates. Despite many websites containing adequate information regarding program descriptions, there was a lack of information regarding the application process and educational activities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Donenfeld et al.)

Objectives: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder., Methods: Youth numbering 394 with bipolar disorder who completed ≥2 follow-up assessments (median follow-up length = 13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow-up was assessed via the A-LIFE Self-Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC., Results: There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross-validated relative influence in the model (AUC = 0.82; in order of relative influence): (1) age of mood disorder onset; (2) non-suicidal self-injurious behavior (trichotomized); (3) current age; (4) psychosis (trichotomized); (5) socioeconomic status; (6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); (7) history of suicide attempt (trichotomized); (8) family history of suicidal behavior; (9) substance use disorder (trichotomized); (10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history., Conclusions: This RC holds promise as a clinical and research tool for prospective identification of individualized high-risk periods for suicide attempt in early-onset bipolar disorder., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: No evidence-based guidelines exist for the perioperative use of clopidogrel in elective hip and knee arthroplasty patients. This study compares the preoperative, intraoperative, and postoperative outcomes of total hip and knee arthroplasty in patients maintained on clopidogrel and with patients whose clopidogrel was held before surgery., Methods: We retrospectively identified 158 patients taking clopidogrel before undergoing elective total hip or knee arthroplasty. Patients were stratified for having clopidogrel held or continued, based on the interval between latest dose and date of surgery. The primary end points were receipt of transfusion and readmission within 90 days of surgery. Secondary end points were the incidence of complications such as bleeding, infection, re-operation, and major cardiac or neurologic events such as myocardial infarction or stroke during the 90-day postoperative period., Results: The two cohorts had similar demographics. Patients who continued clopidogrel were more likely to receive a blood transfusion postoperatively (9.1% vs 0%, P = .005), but there was no difference in wound drainage (P = .65), wound infection (P = .24), readmission (P = .74), major complications (P = .64), length of stay (P = .70), or mortality (P = .42). Patients who continued clopidogrel before surgery were more likely to have received general anesthesia (P < .001) per anesthesia protocol, however, three such patients did receive spinal anesthesia without any complications. With cementless implants, blood loss was not different between clopidogrel groups., Conclusion: Patients undergoing elective total hip and knee arthroplasty may be safely maintained on clopidogrel without an increased risk of wound complications, infections, length of stay, readmission, reoperation, major medical complications, or mortality. Further prospective research is warranted to confirm the effects of continuing clopidogrel in patients undergoing elective hip and knee arthroplasty., (Copyright © 2022. Published by Elsevier Inc.)

Background: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals., Methods: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF)., Results: Lower FA in left CB (middle, β = -0.22, P = 0.022; posterior, β = -0.32, P < 0.001), right CB (anterior, β = -0.30, P = 0.003; posterior, β = -0.27, P = 0.005), and right UF (frontal, β = -0.29, P = 0.002; temporal, β = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals., Limitations: Relatively short follow-up., Conclusions: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course., Methods: 82 youths with BD with persistent poor mood symptomatology ("predominantly ill course") were compared to 70 youths with BD who at intake had poor course, but showed improvement during the follow-up ("ill with improving course"), (ages 12.3 ± 3.3, vs. 11.7 ± 3.3 years old, at intake). Improvement was measured by the percentage of time euthymic during a mean follow-up of 12.8 years. Youths and parents were interviewed to assess psychopathology, functioning, treatment, and familial functioning and psychopathology., Results: Compared to the ill group, since intake, the improving group showed significantly lower subthreshold depression and hypo/mania, Attention Deficit Hyperactivity Disorder, and Disruptive Behavior Disorders. Parental Socioeconomic Status (SES) remained unchanged over time in the ill group, but progressively increased in the improving group. Importantly, the change in SES predated the improvement in the mood trajectory. The most influential variables that predicted improvement were higher SES, and absence of parental BD and Substance Use Disorder (SUD). Parental SUD also negatively affected the parental SES, which was directly associated with worse mood course., Limitations: Predominantly self-reported White samples may limit generalizability; other factors potentially associated with outcome (e.g., treatment adherence), were not ascertained., Conclusions: In addition to treating mood/comorbid psychopathology in symptomatic BD youths, to improve their prognosis, it is crucial to address their parent's BD and SUD and promote parental education/employment., (Copyright © 2022. Published by Elsevier B.V.)

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor-β (TGF-β)-driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-β-inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-β induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-β/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.

Purpose: To analyze the characteristics of the choriocapillaris and the choroid in patients with Alport syndrome (AS) and investigate their clinical and demographic associations., Methods: Multicenter, cross-sectional study. Forty-two eyes with AS were consecutively enrolled. A cohort of 33 healthy eyes was included as controls. Demographics and medical history were collected for each participant. Each eye underwent 3 × 3 swept-source optical coherence tomography angiography (PLEX Elite 9000 2.0; Carl Zeiss Meditec, Dublin, CA, USA) and spectral-domain OCT (Spectralis HRA2; Heidelberg Engineering, Heidelberg, Germany). Choriocapillaris flow deficit (FD) number, mean FD size, total FD area, FD density, subfoveal choroidal thickness (CT), total CT, and choroidal vascularity index (CVI) were compared between AS and control eyes. Factors associated with the FD density and the CVI in AS were explored with multivariable linear mixed models., Results: There was high intragroup variability in choriocapillaris and choroidal measurements in patients with AS. Choriocapillaris FD in patients with AS were more numerous compared to controls (P = 0.02). FD density in eyes with AS increased with older age (estimate = 0.31% for each year; 95% confidence interval [CI], 0.06-0.57; P = 0.02) and was higher in patients with a history of kidney transplant (estimate = 9.66% in case of positive history; 95% CI, 3.52-15.8; P = 0.006). The CVI was lower in eyes with dot maculopathy (estimate = -3.30% if present; 95% CI, -6.38 to -0.21; P = 0.04) and anterior lenticonus (estimate = -6.50% if present; 95% CI, -10.99 to -2.00; P = 0.006)., Conclusions: Patients with AS with kidney involvement requiring transplant may present with more severe choriocapillaris impairment. Lower choroidal vascularity was found in the presence of other ocular structural abnormalities., Translational Relevance: An increased load of choriocapillaris flow deficits on optical coherence tomography angiography was found in patients with Alport syndrome who also had severe kidney disease requiring transplant.

Background: Childhood abuse negatively impacts the course of Bipolar Disorder (BD). Yet, no study has examined risk factors associated with prospectively evaluated physical/sexual abuse, specifically, those preceding first abuse among BD youth. We investigate past/intake/follow-up factors preceding first physical/sexual abuse among BD youth., Methods: Childhood-onset BD participants (n = 279 youth, mean age at intake = 12, mean length of follow-up = 12 years) enrolled in the Course and Outcome of Bipolar Youth (COBY) study. Demographic, clinical and family history variables were assessed every 7 months on average using Longitudinal Interval Follow-up Evaluation and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). Abuse was evaluated at intake using the K-SADS-PL, over follow-up with a Traumatic Events Screen. Family psychopathology was assessed using Family History Screen/Structured Clinical Interview for Diagnostic Statistical Manual-IV., Results: Fifteen-percent of youth reported new-onset abuse during follow-up (62% physical, 26% sexual; 12% both). Intake predictors included more severe depressive symptoms (HR = 1.29), low socioeconomic-status (SES) in families with substance abuse (HR = 0.84) (physical abuse), and female sex (HR = 2.41) (sexual abuse). Follow-up predictors preceding physical abuse included: older age (HR = 1.42), disruptive disorders (HR = 1.39), and the interaction between low SES and family substance abuse (HR = 0.86). For sexual abuse, female sex (HR = 4.33) and a non-biologically related father presence in the household (HR = 2.76). Good relationships with friends (prospectively evaluated) protected against physical/sexual abuse (HR = 0.72/0.70, respectively)., Limitations: Prospective data was gathered longitudinally but assessed retrospectively at every follow-up; perpetrator information and abuse severity were not available., Conclusions: Identifying factors temporally preceding new onset physical/sexual abuse may hold promise for identifying high-risk youth with BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance., Methods: Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected., Results: Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%)., Conclusion: Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.

Background: Radio-contrast media are the agents which are used on daily basis in the radiological practice for either diagnostic or therapeutic purpose. Currently used agents are considered to be safe but not devoid of side effects., Objectives: Objectives of the study were to assess the incidence of adverse drug reactions (ADRs) in the patients who receive radiographic contrast media for computed tomography (CT) and intravenous pyelography (IVP), to stratify the ADRs into different types based on their time of appearance and as per their severity., Materials and Methods: A prospective and observational study of 1-year duration was done on all the patients who received radio-contrast media (Iohexol) intravenously for CT and IVP in the radiodiagnosis department. Patients who experienced ADRs were recorded for the basic demographic characteristics and types of ADRs. Stratification of ADRs as per their severity was done using common terminology criteria for adverse events scale and Modified Hartwig and Siegel ADR Severity Assessment Scale, and casualty assessment was done using Naranjo's Algorithm., Results: Out of the total 3522 patients who were included in the study, eight patients got 12 suspected ADRs with some of the patients having more than one type of ADR. The most frequent ADR was nausea and vomiting (25%), followed by fever, chills, or sweating. Incidence of ADRs was 0.23%. All the ADRs were acute and occurred within 30 min of contrast administration. As per the severity scales used, all the ADRs were mild (75%) to moderate (25%) in nature with none of the reactions to be severe. Causality assessment showed 87.5% of the reactions to be "probable" in nature., Conclusion: Low osmolar nonionic radio contrast media are associated with very low incidence of ADRs in the North Indian population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 International Journal of Applied and Basic Medical Research.)

Background: The ability to predict an individual's risk of mood episode recurrence can facilitate personalized medicine in bipolar disorder (BD). We sought to externally validate, in an adult sample, a risk calculator of mood episode recurrence developed in youth/young adults with BD from the Course and Outcome of Bipolar Youth (COBY) study., Methods: Adult participants from the National Institute of Mental Health Collaborative Depression Study (CDS; N=258; mean(SD) age=35.5(12.0) years; mean follow-up=24.9 years) were utilized as a sample to validate the youth COBY risk calculator for onset of depressive, manic, or any mood episodes., Results: In this older validation sample, the risk calculator predicted recurrence of any episode over 1, 2, 3, or 5-year follow-up intervals, with Area Under the Curves (AUCs) approximating 0.77. The AUC for prediction of depressive episodes was about 0.81 for each of the time windows, which was higher than for manic or hypomanic episodes (AUC=0.72). While the risk calculator was well-calibrated across the range of risk scores, it systematically underestimated risk in the CDS sample by about 20%. The length of current remission was a highly significant predictor of recurrence risk in the CDS sample., Limitations: Predominantly self-reported White samples may limit generalizability; the risk calculator does not assess more proximal risk (e.g., 1 month)., Conclusions: Risk of mood episode recurrence can be predicted with good accuracy in youth and adults with BD in remission. The risk calculators may help identify higher risk BD subgroups for treatment and research., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Appropriate antimicrobial prescribing in the emergency department (ED) is a challenge due to diagnostic uncertainty, time pressure, and clinical inertia. Objective To assess the appropriateness of antimicrobial prescribing in the ED. Setting This study was conducted in the inpatient ED of a tertiary hospital in Malaysia. Method We conducted a 6-month retrospective antimicrobial prescriptions analysis among ED patients who received intravenous antimicrobial. Antimicrobial prescriptions of conveniently selected adult patients were evaluated with the medication appropriateness index. Main outcome measure Appropriateness of antimicrobial prescribing was the primary outcome measure. Results We analysed 310 patients with 326 antimicrobial prescriptions. Ceftriaxone (41.1%, n = 134) and amoxicillin-clavulanate (36.5%, n = 119) were the most common antimicrobials prescribed. Respiratory infections (71.5%, n = 233) was the main indication for antimicrobial therapy in the ED. All antimicrobials prescribed were indicated as per the Malaysian antimicrobial guidelines. The overall rate of inappropriate antimicrobial prescribing was 53.1% (n = 173). Thirty-two (9.8%) antimicrobials were prescribed with inappropriate doses; the majority was related to beta-lactam/beta-lactamase dose (p = 0.002). One hundred and forty-three (43.9%) antimicrobials prescribed had alternatives with similar efficacy but were less costly; which referring to ceftriaxone usage (p < 0.001). Conclusions The inappropriate antimicrobial prescribing in the emergency department is prevalent. This emphasises the importance of conducting antimicrobial stewardship initiative in the ED to improve the appropriate dosing of beta-lactam/beta-lactamase inhibitors as well as the judicious use of ceftriaxone., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: To describe a clinical picture resembling classic multiple evanescent white dot syndrome (MEWDS) potentially triggered by previous or concurrent, apparently unrelated, ocular events and to provide a literature review of similar presentations., Design: Retrospective chart series and literature review., Participants: Consecutive patients diagnosed with MEWDS at the Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and the IRCCS San Raffaele Scientific Institute, Milan, Italy, between July 2019 and June 2020., Methods: Charts of patients were reviewed. Ophthalmic history, best-corrected visual acuity, spectral-domain OCT results, OCT angiography results, fundus autofluorescence results, ultra-widefield fluorescein angiography results, and indocyanine green angiography results were collected. A PubMed-based search was carried out for similar presentations using the terms MEWDS and white spot syndromes., Main Outcome Measures: An ocular history positive for previous or concurrent ocular events in patients with MEWDS was sought in our cohort and the existing literature., Results: Five eyes of 4 patients (2 females; age range, 16-81 years) were included. The first eye had a history of bilateral Best vitelliform dystrophy and unilateral choroidal neovascularization. The second eye had angioid streaks complicated by choroidal neovascularization and underwent prior thermal laser photocoagulation. The third eye had a history of high myopia and a scleral buckle procedure for retinal detachment. The fourth patient had bilateral idiopathic retinochoroiditis. We identified 16 case reports from 5 previous publications that support a MEWDS-like reaction to previous ocular insults., Conclusions: We suggest a MEWDS-like reaction may be elicited by ocular events in a subset of susceptible patients. We hypothesize that damage to the outer retina may play a role in triggering the local inflammatory response., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Worldwide, iron deficiency anaemia in pregnancy is a significant problem which can be especially problematic when delivery is by caesarean section, a procedure associated with significant blood loss. Optimising iron stores pre-delivery remains an overarching goal. We aim to measure the incidence of iron deficiency anaemia in patients undergoing elective caesarean section at our institution and determine any associated predictors, as well as adverse outcomes., Methods: A retrospective, observational cohort study of patients presenting for elective caesarean section over a two-year period. Patient data was collected from hospital electronic records. Iron deficiency anaemia was defined a haemoglobin < 110 g/L and a ferritin < 30 μg/L in the three-month period prior to delivery. The primary aim was to establish the incidence of iron deficiency anaemia at the time of delivery and any associated predictors. Secondary outcomes included any association between the primary outcome and complications defined by the hospital discharge complication coding system, as well as an evaluation of the number of blood tests carried out antenatally per trimester., Results: One thousand and ninety-three women underwent caesarean section over the study period and 16.2% had iron deficiency anaemia. Patients with iron deficiency anaemia were more likely to be of Māori and Pacific Island ethnicity, have a greater booking body mass index, be younger and have a greater parity. Pre-operative anaemia was associated with a greater likelihood of post-operative blood transfusion., Conclusions: There remains potential for optimisation of iron deficiency anaemia in our local population undergoing elective caesarean section., (© 2021. The Author(s).)

Objectives: While adults with bipolar disorder (BD) often report symptoms starting in childhood, continuity of mania and/or hypomania (mania/hypomania) from childhood to adulthood has been questioned. Using longitudinal data from the Course and Outcome of Bipolar Youth (COBY) study, we assessed threshold mania/hypomania in young adults who manifested BD as youth., Methods: COBY is a naturalistic, longitudinal study of 446 youth with BD (84% recruited from outpatient clinics), 7-17 years old at intake, and over 11 years of follow-up. Focusing on youth with BD-I/II (n = 297), we examined adult mania/hypomania risk (>18 years old; mean 7.9 years of follow-up) according to child (<13 years old) versus adolescent (13-17 years old) onset. We next used penalized regression to test demographic and clinical predictors of young adult mania/hypomania., Results: Most participants (64%) had child-onset mania/hypomania, 57% of whom also experienced mania/hypomania in adolescence. Among those who experienced an episode in adolescence, over 40% also had mania/hypomania during adulthood; the risk did not differ according to child versus adolescent onset. In contrast, 7% with mania/hypomania in childhood, but not adolescence, experienced mania/hypomania in adulthood. Family history (of mania and suicide attempts) predicted mania/hypomania in young adulthood (p-values <0.05); age of onset was not a significant predictor. Among participants with no mania/hypomania during adulthood, 53% (105/198) still experienced subthreshold manic episodes., Discussion: We find substantial continuity across developmental stage indicating that, in this carefully characterized sample, children who experience mania/hypomania-particularly those who also experience mania/hypomania in adolescence-are likely to experience mania/hypomania in young adulthood., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Age-related macular degeneration (AMD) is a leading cause of blindness. The main risk factor is advancing age, with the severity of vision loss ranging from mild to severe. There is a 25% risk of early AMD and 8% risk of late AMD in patients over the age of 75, with the number of cases expected to increase because of the aging population. Diagnosis of the disease requires a dilated fundus examination. Physicians should be aware of the symptoms, risk factors, and treatment options for AMD to refer appropriately for ophthalmologic evaluation. Early detection can be helpful to prevent disease progression., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the longitudinal changes on optical coherence tomography angiography (OCTA) in retinal vein occlusion (RVO)., Methods: Retrospective study of patients with RVO treated with intravitreal anti-vascular endothelial growth factors (VEGF) for macular edema. Foveal avascular zone (FAZ) area, vessel density (VD), vessel length density (VLD), and adjusted flow index (AFI) were calculated. The unaffected eye of each participant was used as a control., Results: Twelve RVO eyes were included, receiving 6 ± 3 anti-VEGF injections over a follow-up of 10.4 ± 3.1 months. Compared to fellow eyes, RVO eyes had lower VD and VLD at inclusion ( p = 0.07 and p = 0.04) and last visit ( p = 0.002 and p < 0.001). VD, AFI, and VLD did not change over time, while FAZ area increased in RVO eyes (+0.016 ± 0.024 mm 2 , p = 0.04). AFI correlated with duration of disease ( r = 0.63, p = 0.02). Visual acuity was inversely related to VD and VLD over the follow-up., Conclusions: OCTA parameters remained stable with sustained anti-VEGF treatment in RVO, while changes in the FAZ area may suggest capillary remodeling after RVO.

Background: Pediatric bipolar disorders are often characterized by disruptions in cognitive functioning, and exposure to child maltreatment (e.g., physical and sexual abuse) is associated with a significantly poorer course of illness. Although clinical and developmental research has shown maltreatment to be robustly associated with poorer cognitive functioning, it is unclear whether maltreatment and cognitive function jointly influence the clinical course of bipolar symptoms., Methods: This secondary analysis examined moderating effects of lifetime childhood physical and sexual abuse, and cognitive disruptions (sustained attention, affective information processing), on longitudinal ratings of depression symptom severity in youths from the Course and Outcome of Bipolar Youth (COBY) study, examined from intake (M = 12.24 years) through age 22 (N = 198; 43.9% female; Mean age of bipolar onset = 8.85 years)., Results: A significant moderating effect was detected for sustained attention and maltreatment history. In the context of lower sustained attention, maltreatment exposure was associated with higher depression symptom severity during childhood, but not late adolescence. There was no association between maltreatment and symptom severity in the context of higher sustained attention, and no association between attention and depression symptom severity for non-maltreated youths., Limitations: Depression symptom ratings at each assessment were subject to retrospective recall bias despite the longitudinal design. Cognitive assessments were administered at different ages across youths., Conclusions: Depressive symptoms in pediatric bipolar may be jointly moderated by impairments in attention and exposure to maltreatment. Assessment of these risks, particularly in childhood, may be beneficial for considering risk of recurrence or chronicity of depressive symptoms., (Copyright © 2020. Published by Elsevier B.V.)