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This article discusses the re-emergence of diphtheria in Nigeria and the challenges faced in managing the crisis. Diphtheria is a highly infectious disease caused by toxigenic Corynebacteria species. The outbreak in Nigeria has been attributed to low vaccination rates, inadequate healthcare facilities, and socioeconomic factors. The COVID-19 pandemic has also had a negative impact on routine immunization efforts. The article highlights the efforts made by the government, healthcare workers, and international organizations to address the outbreak, including increasing vaccination coverage and strengthening surveillance systems. The authors recommend improving the national immunization program, implementing telehealth services, and strengthening the supply and storage of vaccines. [Extracted from the article]

Abstract Introduction Despite ongoing programs to improve young people’s Sexual and Reproductive Health Services (SRHS) in the conflict plagued North West and South West Regions of Cameroon, there is limited evidence-based information evaluating SRHS. This study, therefore, aims to investigate the availability, accessibility, and quality of SRHS provided to young people in the North West and South West Regions of Cameroon. Method This is a cross-sectional mixed-methods sequential explanatory study conducted among healthcare providers and young people between 10 and 24 years in 6 selected urban and rural areas in North West and South West regions. Data was collected between December 2021 and September 2022 using an adopted checklist. A descriptive analysis was conducted for quantitative data. An inductive analysis was conducted for the qualitative data to construct themes. The findings from the quantitative and qualitative responses were triangulated. Results There were 114 participants, 28 healthcare providers and 86 young people. Most provider participants were nurses (n = 18, 64.3%), working in religious facilities (n = 14, 50.0%), with diplomas as state registered nurses (n = 9, 32.1%). Also, more than half of young people (51.2%) were less than 20 years old, while there were more male young people (51.2%) than female young people (48.8%). Most respondents agreed that SRHS services were available, though they think they are not designed for young people and have limited awareness campaigns about the services. Reasons such as limited use of written guidelines, affected quality of SRHS. Participants revealed shyness, resistance from religious groups and families, insecurities from political instability, and inadequate training, among others, as barriers to SRH accessibility. Conclusion The study shows that SRHS are available but are not specifically designed for young people. Inadequate publicity for these services, coupled with the political crises and the ongoing COVID-19 pandemic, has increased young people’s inaccessibility to SRHS. Young people usually have to finance the cost of most of the SRHS. The quality of service delivery in the facilities is inadequate and must therefore be improved by developing safe, youth-friendly centers staffed with well-trained service providers.

BACKGROUND: With the resumption of physical learning activities across Nigeria's higher education institutions, tertiary-level students, a prioritized group according to the WHO SAGE in the deployment of the COVID-19 vaccines, face circumstances that necessitate widespread vaccination coverage among them. This is critical in view of vaccine hesitancy attitude and low vaccination coverage that has been reported among this subpopulation and the larger Nigerian populace. Surmounting these barriers is necessary to achieving a successful national vaccination program and for future pandemic preparedness and response. To this end, this study aimed to assess Nigerian undergraduate students' knowledge, coverage, and barriers to COVID-19 vaccination. METHODS: A cross-sectional survey of Nigerian undergraduates was conducted in October 2021, using an online questionnaire and a non-probability convenient sampling technique. The questionnaire included sections on respondents' demographic characteristics, COVID-19 vaccine awareness, coverage, barriers, and recommendations. A total of 326 respondents electronically completed and returned the informed consent form along with the questionnaire. Microsoft Excel spreadsheet and statistical package for the social sciences (SPSS) version 25 were used to code and analyze the data, respectively. RESULTS: The overall awareness of COVID-19 vaccines among the sampled students were high, with 62.3% having good knowledge, 20.9% having average knowledge, and 16.9% having poor knowledge. However, the majority of the respondents (81.3%) had not received the vaccines. The most prominent barrier to vaccination was misinformation about vaccine safety (23.6%). Opening vaccination centers on campuses (18.6%), demonstrating vaccine effectiveness and safety (18.7%), and organizing awareness campaigns (17.2%) were the most frequently recommended actions. CONCLUSION: Most respondents were aware of the availability and potential benefits of COVID-19 vaccines; however, coverage remained extremely low. Our findings emphasize the importance of addressing vaccination barriers by public health stakeholders to achieve optimal COVID-19 vaccine coverage.

The role of medical laboratory scientists has been critical in the early identification of the causative agent of the COVID-19 global pandemic, and the ongoing management and surveillance of the disease. Lessons from the Nigerian experience include the need to improve the capacity of laboratories in molecular diagnosis, increase the number of laboratories within the Nigerian Centre for Disease Control network, and establish more viral laboratories across the country. Keywords: COVID-19, infectious disease, health care reform, pandemic, medical laboratory scientist

BackgroundAdverse obstetric outcomes have been commonly associated with early childbearing in many low-and middle-income countries. Despite this evidence, scholarly information on early childbearing in the sub-Saharan African region, especially Nigeria, is limited. This study examines the predictors of young maternal age at first birth among women of reproductive age in Nigeria using multi-level analysis.MethodsData from the most recent Nigeria Demographic and Health Survey conducted in 2018 were analyzed. A total of 29,949 women of reproductive age (15-49 years) were considered for the study. Descriptive statistics using weighted percentage and chi-square test of independence (χ2) were first used to describe the variables of interest. This procedure was followed by a multilevel analysis of factors associated with young maternal age at first birth in Nigeria at pResultsApproximately 36.80% of the sample population had their first birth before the age of 18. Mothers residing in the North-East region [aOR = 1.26; 95% (CI = 1.13-1.42)] and practicing Islam [aOR = 1.17; 95% (CI = 1.05-1.29] were more likely to have their first birth before the age of 18 than those in the North-Central region and those practicing Christianity. Living in communities with medium literacy level [aOR = 0.90; 95% (CI = 0.82-0.99)] and high literacy level [aOR = 0.71; 95% (CI = 0.62-0.81)], being within richest wealth index [aOR = 0.61; 95% (CI = 0.53-0.71)] and being Yoruba [aOR = 0.46; 95% (CI = 0.39-0.56)] were associated with lower odds of young maternal age at first birth.ConclusionMore than one-third of women of reproductive age in Nigeria had given birth to their first child before 18 years. Thus, there is a need for the Nigerian government and other stakeholders, including Non-Governmental Organisations and Civil Society Organisations to formulate and implement policy interventions targeted at reducing early childbearing among women of reproductive age in Nigeria.

This research paper analyses the management and prevention of pre-eclampsia in Nigeria. Although efforts have been made to reduce outcomes due to pre-eclampsia, it still rears its head in the form of high maternal and perinatal morbidity and mortality. The aim of this review was to identify the main obstacles, gaps, and interventions related to the prevention and management of pre-eclampsia in order to be fully knowledgeable of the magnitude of the issue at the national level, to assess if current government policies are adequate and to recommend solutions. A search was performed on online databases and it was completed with hand searches related to the subject matter. Screening tests for early detection of pre-eclampsia are hardly available in Nigeria as many hospitals rely on the history of previous and current pregnancies, blood pressure monitoring and urinalysis–proteinuria. The administration of low-dose aspirin, antihypertensive drugs and magnesium sulphate, coupled with calcium in calcium deficit regions, was recommended. The main barriers to the wider implementation of these strategies are inadequacy of the antenatal care services in providing appropriate care, lack of resources and trained personnel, high healthcare costs, and low antennal care attendance. Improving education and awareness, use of low-cost screening modalities and low-dose aspirin can be deployed in developing countries to curb pre-eclampsia.

Poliomyelitis is the leading infectious cause of acute flaccid paralysis among children under five years of age, caused by the Wild Poliovirus, with no medical cure other than prevention through vaccination. The advent of mass vaccination campaigns against polio disease worldwide has greatly decreased the number of global cases and limited the rate of transmission. However, the emergence of Vaccine-derived Poliovirus due to genetic reversions in the live attenuated oral polio vaccine has posed a significant impediment to global polio eradication efforts. Therefore, There is a need to modify the vaccination regimen by utilizing more doses of inactivated poliovirus vaccine or adopting the bivalent oral polio vaccine in order to eliminate the transmission of Vaccine-derived Poliovirus. In addition, collective efforts from governments, health policymakers, vaccination groups and health-related bodies are required to improve vaccine coverage and suppress the circulation of Vaccine-derived Poliovirus.

Background Recurrence of hepatitis C virus ( HCV) following liver transplantation ( LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear. Aim To evaluate the comparative cost-effectiveness of treating HCV pre- LT vs. post- LT (pre-emptive or after HCV recurrence). Methods A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir ( LDV/ SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre- LT; (ii) post- LT preemptively prior to HCV recurrence; or (iii) post- LT after HCV recurrence. Results In the base-case analysis using a median model for end-stage liver disease ( MELD) score <25 at the time of transplant, we found that pre- LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre- LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post- LT strategy was more cost-effective. Conclusions Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy. [ABSTRACT FROM AUTHOR]

Purpose Reflectance within the retinal nerve fiber layer (RNFL) may change prior to, or concurrent with, RNFL thinning in glaucoma. We hypothesize that reductions in RNFL reflectance intensity may be observed by optical coherence tomography (OCT), and may provide useful additional information beyond RNFL thickness. Methods Participants enrolled in an ongoing longitudinal study of glaucomatous progression had peripapillary circle scans acquired using spectral-domain OCT, and performed automated perimetry, every 6 months. Data were analyzed from the most recent 8 visits with reliable results, from 211 eyes of 143 individuals. For each of the 52 visual field locations, intensity ratio and RNFL thickness were calculated within a 30º sector centered at the average location where corresponding nerve fibers enter the disc. Intensity ratio was defined as the mean intensity of pixels within the delineated RNFL boundaries divided by the mean intensity of pixels between the outer RNFL boundary and Bruch's Membrane. Rates of localized change were defined as the rate of change within each sector/location, minus the rate of global change. A mixed effects model was used to predict the rate of localized functional change from the rates of localized thickness and intensity ratio change within the corresponding sector. Results In a combined model, the rate of localized functional loss was predicted by both rate of thinning and the interaction between the rates of thinning and intensity ratio change (both p < 0.0001). For a given rate of RNFL thinning, a more negative rate of intensity ratio change predicted more rapid loss of sensitivity. Conclusions Reduction of RNFL reflectance over time is associated with loss of sensitivity at corresponding locations. While these are early results, they suggest potential improvements to the interpretation and quantification of OCT scans. [ABSTRACT FROM AUTHOR]

Purpose Decreased reflectance within the retinal nerve fiber layer (RNFL), observable using optical coherence tomography (OCT), appears to be related to functional loss in glaucoma. In order to investigate this in a quantitative manner, reliable measurements of reflectance intensity are needed. However, reflectance may not only be affected by pathophysiological changes in tissue properties but also confounded by other effects of ocular media and image quality. This study assesses the repeatability of intensity measurements, before and after normalization aimed to reduce test-retest variability. Methods Data were taken from participants with glaucoma in a test-retest study. Each had peripapillary circle scans acquired from both eyes 5 times within 10 weeks. For each scan, the following were extracted: average RNFL thickness; RNFL intensity, defined as the mean reflectance intensity of pixels within the delineated RNFL; sub- RNFL intensity, defined as the mean intensity of pixels between the outer boundary of the RNFL and Bruch's Membrane; and intensity ratio, defined as RNFL intensity divided by sub- RNFL intensity. For each parameter, deviations from the per-eye mean were calculated. The intra-eye standard deviations ( SD) were expressed as percentage of the width of the range of observed measurements. Results The intra-eye SD of RNFL intensity was 12.5% of the range. Normalization reduced the intra-eye SD of intensity ratio to 4.9% of the range, representing a significant reduction in absolute deviations with p < 0.0001 (Wilcoxon signed rank test). RNFL thickness was more repeatable, with intra-eye SD 0.8% of its range. Conclusions RNFL reflectance intensity varies substantially between scans. However, dividing by the intensity of sub- RNFL tissue greatly reduces this variability. Such normalization allows useful measurements to be obtained. [ABSTRACT FROM AUTHOR]

Purpose: IOP-induced mechanical insult on retinal ganglion cell axons within the optic nerve head (ONH) is believed to be a key factor in axonal damage and glaucoma. However, most studies focus on tissue-level mechanical deformations, overlooking that axons are long and thin, and that their susceptibility to damage likely depends on the insult's type (e.g. stretch/compression) and orientation (longitudinal/transverse). We propose an axon-centric approach to quantify IOP-induced mechanical insult from an axon perspective., Methods: We used optical coherence tomography (OCT) scans from a healthy monkey eye along with histological images of cryosections to reconstruct the axon-occupied volume including detailed lamina cribrosa (LC) pores. Tissue-level strains were determined experimentally using digital volume correlation from OCT scans at baseline and elevated IOPs, then transformed into axonal strains using axon paths estimated by a fluid mechanics simulation., Results: Axons in the LC and post-LC regions predominantly experienced longitudinal compression and transverse stretch, whereas those in the pre-LC and ONH rim mainly suffered longitudinal stretch and transverse compression. No clear patterns were observed for tissue-level strains., Conclusions: Our approach allowed discerning axonal longitudinal and transverse mechanical insults, which are likely associated with different mechanisms of axonal damage. The technique also enabled quantifying insult along individual axon paths, providing a novel link relating the retinal nerve fiber layer and the optic nerve through the LC via individual axons. This is a promising approach to establish a clearer connection between IOP-induced insult and glaucoma. Further studies should evaluate a larger cohort.

Retinal vascular resistance is of interest in glaucoma research, as a potential link between retinal ganglion cell loss and observed phenomena including disrupted vascular autoregulation, altered biomechanical stiffness, and impaired neurovascular coupling. It can now be assessed in vivo, using laser speckle flowgraphy. However, continued progress in the field requires better understanding of its physiology. In this study, we test the hypothesis of homogeneity of vascular resistance indices between regions of the retina: specifically, between superior and inferior hemifields. The resistivity index (maximum flow minus minimum flow, as a proportion of the maximum) and pulsatility index (maximum minus minimum, as a proportion of the mean) were measured in major vessels within the optic nerve head, in the remaining tissue within the optic nerve head, and in peripapillary branch retinal arteries, separated in each case into superior and inferior quadrants. This was performed in 378 eyes of 189 participants with suspected, early or moderate glaucoma; and in 99 eyes of 50 participants without any ocular pathology. In the glaucoma cohort, the resistivity index was on average 9% higher superiorly than inferiorly in vessels within the optic nerve head; 8% higher superiorly in remaining tissue; and 8% higher superiorly in peripapillary vessels (all p < 0.001). The pulsatility index was on average 11% higher superiorly in all three locations (all p < 0.001). Average flow was slightly higher superiorly in major vessels in the nerve head, but higher inferiorly elsewhere. In the healthy control cohort, resistivity index was higher superiorly by 10% in vessels and 8% in tissue within the optic nerve head; pulsatility index was 12% and 10% higher superiorly respectively (all p < 0.001). The fact that these differences were similar between the two cohorts suggests that they are not caused by the disease process. However, it is notable that glaucomatous loss most frequently occurs first in the superior visual field, corresponding with the inferior retina. The finding that vascular resistance indices are consistently higher in the superior retina warrants further investigation, both for its causes and consequences., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis., Methods: For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations., Results: Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356)., Conclusions: Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Background and Aims: Timely transition of care amongst patients with a first diagnosis of cirrhosis in a hospital to an outpatient visit is important. We evaluated rates of outpatient follow-up after a first diagnosis of cirrhosis during an inpatient setting, and its association with subsequent rates of rehospitalisation and mortality., Methods: We conducted a population-based cohort study identifying all hospitalised patients in Sweden diagnosed with cirrhosis between 2002 and 2020 from the Swedish National Patient Register. The primary outcome was any outpatient visit related to cirrhosis within 90 days after hospital discharge. Secondary outcomes were rates of rehospitalisation and mortality within 1 year of discharge in patients receiving outpatient follow-up within 90 days or not. Cox regression was used for all analyses, and incidence rates per 1000 person-years were calculated for mortality and rehospitalisation., Results: Of 8852 patients, 3759 (42%) had outpatient follow-up within 90 days of discharge. Patients who received follow-up within 90 days of discharge were younger, had a higher level of education and were more likely to have liver decompensation or hepatocellular carcinoma compared to those without timely follow-up. We found that follow-up within 90 days was associated with lower rates of all-cause mortality within 1 year (aHR = 0.86, 95%CI = 0.78-0.96) but with no significant impact on rehospitalisations (aHR = 0.97, 95%CI = 0.91-1.03)., Conclusions: In Sweden, 42% of hospitalised patients with newly diagnosed cirrhosis receive outpatient follow-up within 90 days of their hospital discharge. These patients may experience lower mortality but no change in rehospitalisations within 1 year., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Liver transplantation (LT) is the only curative treatment for end-stage liver disease and significantly improves patient outcomes. However, LT is resource-intensive and costly, with expenditures rising dramatically in recent years. Factors contributing to this increase in cost include expanded transplant criteria, utilization of marginal organs, and broader organ distribution, resulting in significant logistical expenses. Advanced technologies like organ perfusion devices, while promising better outcomes, further inflate costs due to their high price and market monopolization. Moreover, living donor liver transplant (LDLT) and utilization of donation after cardiac death (DCD) organs introduce higher initial expenditures yet potential long-term savings. Despite rising costs, reimbursement has remained largely stagnant, putting financial strain on transplant programs, and threatening their sustainability. This review examines the multifaceted drivers of rising costs in LT, focusing on recent policy changes, the role of organ procurement organizations (OPOs) and the impact of new technologies. We also propose comprehensive solutions at national, OPO, and local levels, including optimizing resource allocation, leveraging regional collaborations, and advocating for revised reimbursement models to curb escalating costs. Addressing these challenges is critical to ensuring the continued viability of LT programs and maintaining patient access to this life-saving intervention., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: To report on the venous abnormalities of a patient with Sturge-Weber syndrome., Method: Case report., Patient: A 29-year-old woman with a history of Sturge-Weber syndrome since infancy was referred for evaluation of possible diffuse choroidal hemangioma. Multimodal imaging, including ultra-widefield fluorescein, indocyanine green, and optical coherence tomography angiography, was performed., Results: Dilated fundus examination was remarkable for increased cupping of the optic disk in the right eye, venous tortuosity, and marked dilation of the choroidal vessels. Ultra-widefield fluorescein angiography confirmed marked venous tortuosity and dilation, as well as anastomoses of the retinal veins ipsilateral to the port wine stain. Indocyanine green angiography revealed marked engorgement of the vortex veins and choroidal vasculature. Optical coherence tomography angiography revealed dilated vascular channels in the deep capillary plexus that were directly anastomosing to the superficial capillary plexus, but not the intermediate capillary plexus. Engorgement of the ampullae of the deep capillary plexus vortex system was also observed. The normal contralateral eye was used as comparison for all imaging studies., Conclusion: These findings support the notion of generalized venous hypertension state in adult eyes with Sturge-Weber syndrome and corroborate previous evidence that the deep capillary plexus acts as a venous outflow system., Competing Interests: B. Fortune: Heidelberg Engineering, GmbH (equipment support). The remaining authors have no conflicts of interest.

Dendrite pathology and synaptic loss result in neural circuit dysfunction, a common feature of neurodegenerative diseases. There is a lack of strategies that target dendritic and synaptic regeneration to promote neurorecovery. We show that daily human recombinant insulin eye drops stimulate retinal ganglion cell (RGC) dendrite and synapse regeneration during ocular hypertension, a risk factor to develop glaucoma. We demonstrate that the ribosomal protein p70S6 kinase (S6K) is essential for insulin-dependent dendritic regrowth. Furthermore, S6K phosphorylation of the stress-activated protein kinase-interacting protein 1 (SIN1), a link between the mammalian target of rapamycin complexes 1 and 2 (mTORC1/2), is required for insulin-induced dendritic regeneration. Using two-photon microscopy live retinal imaging, we show that insulin rescues single-RGC light-evoked calcium (Ca 2+ ) dynamics. We further demonstrate that insulin enhances neuronal survival and retina-brain connectivity leading to improved optomotor reflex-elicited behaviors. Our data support that insulin is a compelling pro-regenerative strategy with potential clinical implications for the treatment and management of glaucoma.

Purpose: It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC)., Methods: The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MDlin) and retinal nerve fiber layer thickness (RNFLT)., Results: Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MDlin (P ≤ 0.05)., Conclusions: The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.

Purpose: To compare the prevalence, location and magnitude of optic nerve head (ONH) OCT-detected, exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT) and exposed scleral flange (ESF) regions in 122 highly myopic (Hi-Myo) versus 362 nonhighly myopic healthy (Non-Hi-Myo-Healthy) eyes., Design: Cross-sectional study., Methods: After OCT radial B-scan, ONH imaging, Bruch's membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented in each B-scan and projected to BMO reference plane. The direction and magnitude of BMO/ASCO offset and BMO/SFO offset as well as the location and magnitude of ENC, EOCBT and ESF regions, perineural canal (pNC) retinal nerve fiber layer thickness (RNFLT) and pNC choroidal thickness (CT) were calculated within 30° sectors relative to the Foveal-BMO (FoBMO) axis. Hi-ESF eyes were defined to be those with an ESF region ≥100 µms in at least 1 sector., Results: Hi-Myo eyes more frequently demonstrated Hi-ESF regions (87/122) than Non-Hi-myo-Healthy eyes (73/362) and contained significantly larger ENC, EOCBT, and ESF regions (P < .001) which were greatest in magnitude and prevalence within the inferior-temporal FoBMO sectors where Hi-Myo pNC-RNFLT and pNCCT were thinnest. BMO/ASCO offset and the BMO/SFO offset were both significantly increased (P < .001) in the Hi-Myo eyes, with the latter demonstrating a greater increase., Conclusions: ENC region tissue remodeling that includes the scleral flange is enhanced in Hi-Myo compared to Non-Hi-Myo-Healthy eyes. Longitudinal studies are necessary to determine whether the presence of an ENC region influences ONH susceptibility to aging and/or glaucoma., (Published by Elsevier Inc.)

Purpose: To determine the prevalence and magnitude of optical coherence tomography (OCT) exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT), and exposed scleral flange (ESF) regions in 362 non-highly myopic (spherical equivalent -6.00 to 5.75 diopters) eyes of 362 healthy subjects., Design: Cross-sectional study., Methods: After OCT optic nerve head (ONH) imaging, Bruch membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented. BMO, ASCO, and SFO points were projected to the BMO reference plane. The direction and magnitude of BMO/ASCO offset as well as the magnitude of ENC, EOCBT, and ESF was calculated within 30° sectors relative to the foveal-BMO axis. Hi-ESF eyes demonstrated an ESF ≥100 µm in at least 1 sector. Sectoral peri-neural canal choroidal thickness (pNC-CT) was measured and correlations between the magnitude of sectoral ESF and proportional pNC-CT were assessed., Results: Seventy-three Hi-ESF (20.2%) and 289 non-Hi-ESF eyes (79.8%) were identified. BMO/ASCO offset as well as ENC, EOCBT, and ESF prevalence and magnitude were greatest inferior temporally where the pNC-CT was thinnest. Among Hi-ESF eyes, the magnitude of each ENC region correlated with the BMO/ASCO offset magnitude, and the sectors with the longest ESF correlated with the sectors with proportionally thinnest pNC-CT., Conclusions: ONH BMO/ASCO offset, either as a cause or result of ONH neural canal remodeling, corresponds with the sectoral location of maximum ESF and minimum pNC-CT in non-highly myopic eyes. Longitudinal studies to characterize the development and clinical implications of ENC Hi-ESF regions in non-highly myopic and highly myopic eyes are indicated., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Goals: To identify factors associated with transplantation and death in alcohol-associated liver disease (ALD) patients presenting with first evidence of ascites., Background: Ascites development is a poor prognostic sign for patients with cirrhosis. Among ALD patients, the baseline factors at time of ascites development that are associated with eventual transplantation or death are currently unknown., Study: Adult patients with ascites in the "Evaluating Alcohol Use in Alcohol-related Liver Disease Prospective Cohort Study" (NCT03267069 clinicaltrials.gov) were identified from 2016 to 2020. Demographic, clinical, and laboratory factors at initial ascites presentation were identified as potential predictors of transplant and death as competing risks., Results: A total of 96 patients were identified. Median (interquartile range) follow-up time was 2.00 years (0.87 to 3.85). By last follow-up, 34/96 patients had been transplanted (35.4%) and 11/96 had died (11.4%). Prognostic factors for transplant included age per decade [hazard ratio (HR): 0.52 (95% CI, 0.33 to 0.83)], employed status [HR: 0.35 (95% CI, 0.14 to 0.90)], and sodium [HR: 0.94 (95% CI, 0.90 to 0.99)], whereas prognostic factors for death were body mass index [HR: 1.11 (95% CI, 1.00 to 1.22)], Charlson index [HR: 2.14 [95% CI, 1.13 to 4.08]), Maddrey Discriminant Function >32 (HR: 5.88 (95% CI, 1.18, 29.39)], aspartate aminotransferase [HR: 0.99 (95% CI, 0.98 to 0.997)], and a prior 12-month abstinence period [HR: 5.53 (95% CI, 1.10 to 27.83)], adjusted for age, sex, and ALD subcategory., Conclusions: Several factors at initial ascites presentation are associated with increased risk of transplantation or death and validation in larger cohorts will allow for improved risk stratification for ALD patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Here, we introduce the Early Relational Health (ERH) Learning Community's bold, large-scale, collaborative, data-driven and practice-informed research agenda focused on furthering our mechanistic understanding of ERH and identifying feasible and effective practices for making ERH promotion a routine and integrated component of pediatric primary care. The ERH Learning Community, formed by a team of parent/caregiver leaders, pediatric care clinicians, researchers, and early childhood development specialists, is a workgroup of Nurture Connection-a hub geared toward promoting ERH, i.e., the positive and nurturing relationship between young children and their parent(s)/caregiver(s), in families and communities nationwide. In response to the current child mental health crisis and the American Academy of Pediatrics (AAP) policy statement promoting ERH, the ERH Learning Community held an in-person meeting at the AAP national headquarters in December 2022 where members collaboratively designed an integrated research agenda to advance ERH. This agenda weaves together community partners, clinicians, and academics, melding the principles of participatory engagement and human-centered design, such as early engagement, co-design, iterative feedback, and cultural humility. Here, we present gaps in the ERH literature that prompted this initiative and the co-design activity that led to this novel and iterative community-focused research agenda, with parents/caregivers at the core, and in close collaboration with pediatric clinicians for real-world promotion of ERH in the pediatric primary care setting., Competing Interests: BB was employed by company Vav Amani Consulting LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dumitriu, Lavallée, Riggs, Frosch, Barker, Best, Blasingame, Bushar, Charlot-Swilley, Erickson, Finkel, Fortune, Gillen, Martinez, Ramachandran, Sanders, Willis and Shearman.)

Retinal ganglion cells, the neurons that die in glaucoma, are endowed with a high metabolism requiring optimal provision of oxygen and nutrients to sustain their activity. The timely regulation of blood flow is, therefore, essential to supply firing neurons in active areas with the oxygen and glucose they need for energy. Many glaucoma patients suffer from vascular deficits including reduced blood flow, impaired autoregulation, neurovascular coupling dysfunction, and blood-retina/brain-barrier breakdown. These processes are tightly regulated by a community of cells known as the neurovascular unit comprising neurons, endothelial cells, pericytes, Müller cells, astrocytes, and microglia. In this review, the neurovascular unit takes center stage as we examine the ability of its members to regulate neurovascular interactions and how their function might be altered during glaucomatous stress. Pericytes receive special attention based on recent data demonstrating their key role in the regulation of neurovascular coupling in physiological and pathological conditions. Of particular interest is the discovery and characterization of tunneling nanotubes, thin actin-based conduits that connect distal pericytes, which play essential roles in the complex spatial and temporal distribution of blood within the retinal capillary network. We discuss cellular and molecular mechanisms of neurovascular interactions and their pathophysiological implications, while highlighting opportunities to develop strategies for vascular protection and regeneration to improve functional outcomes in glaucoma., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interest regarding the content of this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hospital admissions for patients with cirrhosis continue to increase. In New York City, 25% to 30% of hospitalized cirrhotics are readmitted within 30 days. Rehospitalization is associated with increased mortality, poor quality of life, and financial burden to patients, hospitals, and payers. Preventable readmissions are partially accounted for by a well-documented quality gap between evidence-based guidelines for cirrhosis management and real-world adherence to these recommendations., Methods: We performed a prospective cohort study that compared outcomes among cirrhotic patients admitted to 4 internal medicine teams over a 6-month period. An electronic medical record (EMR) note template that outlined best-practice measures for cirrhotics was developed. Inpatient providers on 2 teams were instructed to include it in daily progress notes and discharge summaries. The recommended practices included diagnostic paracentesis and diuretics for ascites, rifaximin, and lactulose for hepatic encephalopathy, beta blockers for esophageal varices, and antibiotic prophylaxis for spontaneous bacterial peritonitis. The remaining 2 teams continued the standard of care for cirrhotic patients. The primary outcome was 30-day readmissions. Secondary outcomes included in-hospital mortality, 30-day mortality, length of stay, and adherence to best-practice guidelines., Results: Over a 6-month period, 108 cirrhotic patients were admitted, 83 in the interventional group and 25 in the control group. MELD-Na scores on admission did not differ between the groups (20.1 vs. 21.1, P =0.56). Thirty-day readmissions were not significantly different between the interventional and control groups (19.3% vs. 24%, P =0.61). However, 30-day mortality was significantly lower in the interventional group (8.4% vs. 28%, P =0.01). There was no difference between the 2 groups in in-hospital mortality (4.8% vs. 0%, P =0.27), 90-day mortality (15.7% vs. 28.0%, P =0.17) or length of stay (10.2 vs. 12.6 d, P =0.34). Adherence to best-practice metrics was similar between the groups, except for rates of diagnostic paracentesis, which were higher in the interventional group (98% vs. 80%, P =0.01)., Conclusion: Implementation of an EMR note template with cirrhosis best practices was associated with lower 30-day mortality and higher rates of diagnostic paracentesis among admitted patients with cirrhosis. These findings suggest that the integration of best-practice measures into the EMR may improve outcomes in hospitalized cirrhotic patients. Larger studies are required to validate these findings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background/objective: Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population., Methods: Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40 IU/mL ≥6 mo apart), and body mass index ≥30 kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135 mm Hg or diastolic blood pressure >85 mm Hg or active treatment for hypertension; high-density lipoprotein <40 g/dL; triglycerides >150 mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling., Results: A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30 kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician., Conclusion: ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies., (© 2023. Editorial Group and BioMed Central Ltd., part of Springer Nature.)

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators., Design and Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds., Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants., Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science., Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Purpose: To compare parameters of electroretinogram (ERG) responses for their ability to detect functional loss in early stages of nonhuman primate (NHP) experimental glaucoma (EG), including photopic negative responses (PhNR) to a standard brief red flash on a blue background (R/B) and 200-ms-long R/B and white-on-white (W/W) flashes, to W/W flicker stimuli (5-50 Hz), and to a dark-adapted intensity series., Methods: Light-adapted ERGs were recorded in 12 anesthetized monkeys with unilateral EG. Amplitudes and implicit times of the a-wave, b-wave, and d-wave were measured, as well as amplitudes of PhNRs and oscillatory potentials for flash onset and offset. Flicker ERGs were measured using peak-trough and fundamental frequency analyses. Dark-adapted ERG parameters were modeled by Naka-Rushton relationships., Results: Only PhNR amplitudes were significantly reduced in EG eyes compared to fellow control (FC) eyes. The d-wave implicit time was delayed in EG versus FC eyes only for the W/W long flash, but in all eyes it was 10 to 20 ms slower for R/B versus the W/W condition. Flicker ERGs were <0.5 ms delayed in EG versus FC overall, but amplitudes were affected only at 5 Hz. The brief R/B PhNR amplitude had the highest sensitivity to detect EG and strongest correlation to parameters of structural damage., Conclusions: The PhNR to the standard brief R/B stimulus was best for detecting and following early-stage functional loss in NHP EG., Translational Relevance: These results suggest that there would be no benefit in using longer duration flashes to separate onset and offset responses for clinical management of glaucoma.

Purpose: To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes., Design: Cross-sectional, case control study., Methods: Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 μm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 μm from the ASCO)., Results: pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes., Conclusions: Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Various infectious disease outbreaks linked to zoonotic sources have been recorded over the years, some of which have resulted in epidemics on a national, regional, or global scale. In Africa, a number of such outbreaks occur intermittently, especially in countries like Nigeria with a high-risk of epidemiological transmission. Three viral outbreaks with zoonotic links have hit the Nigerian healthcare system hardest, which are the Ebola virus disease, Lassa fever and Coronavirus disease 2019. Due to the fragile nature of the Nigerian health system, several challenges were encountered in the process of responding to these viral outbreaks, some of which included inadequate healthcare infrastructure, limited diagnostic capacity, unfledged nature of emergency response, unsatisfactory remuneration of health workers, misinformation trends, amongst others. By reminiscing on the challenges and lessons learnt from these viral disease outbreaks, the Nigerian government and policymakers will be able to adopt more effective approaches towards emergency preparedness for future outbreaks of infectious diseases., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)