Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation.

Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rodent model of hypoxia. We thus hypothesised that IVT-Ngb may also be neuroprotective in experimental glaucoma (EG) by mitigating optic nerve (ON) astrogliosis and microgliosis as well as structural damage. In this study using a microbead-induced model of EG in six Cynomolgus primates, optical coherence imaging showed that Ngb-treated EG eyes had significantly less thinning of the peripapillary minimum rim width, retinal nerve fibre layer thickness, and ON head cupping than untreated EG eyes. Immunohistochemistry confirmed that ON astrocytes overexpressed Ngb following Ngb treatment. A reduction in complement 3 and cleaved-caspase 3 activated microglia and astrocytes was also noted. Our findings in higher-order primates recapitulate the effects of neuroprotection by Ngb treatment in rodent EG studies and suggest that Ngb may be a potential candidate for glaucoma neuroprotection in humans.

Psychological Assessment of Family Caregivers of Patients With COVID-19 in the United States of America and India.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic has highlighted the shortcomings worldwide in terms of preparedness protocols related to epidemics. A key area of research that is evidently overlooked across the globe is the mental health of family caregivers taking care of patients with COVID-19. In light of this, this study aimed to engage in a comparative analysis between the two worst affected countries, India and the United States of America (USA), which differ considerably in their demography, socio-epidemiological factors, and health system efficiency. Methods A cross-sectional study was conducted among 1,250 family caregivers of patients with COVID-19 in India and the USA to assess their stress, anxiety, and sleep disturbance levels using the 10-item Perceived Stress Scale (PSS-10), the 7-item Generalized Anxiety Disorder (GAD-7) scale, and the Pittsburgh Sleep Quality Index (PSQI), respectively. Psychological assessment questionnaires were administered through online mode, which gathered demographic information and responses on several self-reporting scales. The main outcome measures were self-reported ratings on PSS, GAD-7 scale, and PSQI. Results We found that 75.4% of the family members of COVID-19 patients suffered from mental health issues. The scores of all three scales were higher in caregivers from the USA than in India, more evident and pronounced in caregivers of hospitalized patients. The test scores were statistically significant (p<0.05) indicating a negative impact of having a dependent member in the family, being married, being of younger age, and having a longer duration of COVID-19 infection. Vaccines were found to have a life-enhancing effect. Conclusion Our findings highlight that the mental health of family caregivers is an ignored aspect and must be addressed. We recommend the implementation of well-researched and appropriate legislation, treatment programs, and health policies that involve not only the patients but also their families.

Pharmacokinetics of Darolutamide in Mouse - Assessment of the Disposition of the Diastereomers, Key Active Metabolite and Interconversion Phenomenon: Implications to Cancer Patients.

BACKGROUND: Darolutamide is recently approved for the treatment of non-metastatic castrate resistance prostate cancer. Hitherto, no stereoselective pharmacokinetic data have been published pertaining to darolutamide and its diastereomers in animals or humans. The key aims of the experiment were to examine darolutamide, S,S-darolutamide and S,R-darolutamide with respect to (a) assessment of in vitro metabolic stability and protein binding and (b) characterization of in vivo oral and intravenous pharmacokinetics in mice. METHODS: In vitro (liver microsomes stability and protein binding) and in vivo experiments (oral/intravenous dosing to mice) were carried out using darolutamide, S,S-darolutamide and S,Rdarolutamide. Besides, tissue levels of darolutamide, S,S-darolutamide and S,R-darolutamide were measured following oral and intravenous dosing. Appropriate plasma/tissue samples served to determine the pharmacokinetics of various analytes in mice. Liquid chromatography in tandem with mass spectrometry procedures enabled the delineation of the plasma pharmacokinetics, in vitro and tissue uptake data of the various analytes. RESULTS: Chiral inversion was absent in the metabolic stability study. However, darolutamide showed profound stereoselectivity (S,S-darolutamide greater than S,R-darolutamide) after either intravenous or oral dosing. S,R-darolutamide but not S,S-darolutamide showed conversion to its antipode post oral and intravenous dosing to mice. Regardless of oral or intravenous dosing, active keto darolutamide formation was evident after administration of darolutamide, S,S-darolutamide or S,R- darolutamide. Tissue data supported the observations in plasma; however, tissue exposure of darolutamide, S,Sdarolutamide and S,R-darolutamide was much lower as compared to plasma. CONCLUSION: In lieu of the human pharmacokinetic data, although the administration of diastereomeric darolutamide was justified, it is proposed to delineate the clinical pharmacokinetics of S,Rdarolutamide and S,S-darolutamide relative to darolutamide in future clinical pharmacology studies.

Regression in polypoidal choroidal vasculopathy treated with ziv-aflibercept monotherapy - short term study.

PURPOSE: The aim of this study was to evaluate the effectiveness of intravitreal ziv-aflibercept (IVZ) in the treatment of polypoidal choroidal vasculopathy (PCV) and its efficacy in regard to polyp regression using optical coherence tomography (OCT) and indocyanine green angiography (ICGA). METHODS: This was a retrospective study of eight eyes of eight patients with treatment-naïve PCV. Patients received IVZ on pro re nata protocol. OCT and ICGA parameters were assessed at baseline and subsequent visits with a minimum follow-up of 6 months. ICGA was repeated at 3-6 months to determine the disease activity and quantify the changes in branching vascular network (BVN) polyps. Quantifiable OCT parameters included central macular thickness, pigment epithelial detachment (PED) height, and subfoveal choroidal thickness. RESULTS: The mean age of the study cohort was 62.3 ± 7.7 years, with a mean follow-up of 7.1 ± 1.2 months. The baseline best-corrected visual acuity improved from 0.70 ± 0.36 logarithm of the minimum angle of resolution (Snellen's equivalent 20/100) to 0.63 ± 0.34 (20/80) at last follow-up which was statistically insignificant (P = 0.5). Post IVZ injections (mean ± standard deviation: 2.6 ± 0.7), the total number of polyps reduced significantly from 3 ± 3.5 to 1 ± 1.7 (P = 0.03) along with a reduction in BVN size (3.9 ± 4.8 to 2.7 ± 3.8mm2; P = 0.07). OCT analysis revealed a significant reduction in PED height from 462.5 ± 353.8 µ to 169.9 ± 127.2 µ (P = 0.02). CONCLUSION: IVZ leads to significant morphological changes on ICGA and OCT in terms of polyp regression and reduction of PED height, respectively, with a limited change in visual acuity. IVZ may serve as a cost-effective alternative to treat eyes with PCV.

Waiting for Godot: A cross sectional survey based analysis of the hydroxychloroquine prophylaxis strategy against COVID-19 in India.

Background: India currently has the second largest burden of infections due to COVID-19. Health Care Worker (HCW) shortages are endemic to Indian healthcare. It should therefore be a huge priority to protect this precious resource as a critical component of the systemic response to this pandemic. Advisories from the Indian Council of Medical Research (ICMR) have focused on using hydroxychloroquine prophylaxis against COVID-19 in at risk HCW. This prophylaxis strategy has no evidence. In further jeopardy there appear to insubstantial attempts to build this evidence as well. In this connection, we commissioned a survey within our Institution to estimate the penetration of hydroxychloroquine (HCQ) use and use this to statistically model the impact of current ongoing studies in India. We also briefly review the literature on HCQ prophylaxis for COVID-19. Design and methods: A structured survey designed using RedCAP application was disseminated among healthcare professionals employed at an academic referral tertiary care centre via online social media platforms. The survey was kept open for the entire month of June 2020. The survey was additionally used to statistically model the size of studies required to comprehensively address the efficacy of HCQ in this setting. Results: 522 responses were received, of which 4 were incomplete. The ICMR strategy of 4 or more doses of HCQ was complete only in 15% of HCW in our survey. The majority of respondents were doctors (238, 46%). Amongst all category of responders, only 12% (n=63) received the full course. A majority of those who initiated the chemoprophylaxis with HCQ turned out to be medical professionals (59/63) with neither nurse nor other categories of healthcare workers accessing the medication. The respondents of our institutional survey did not report any life-threatening side effects. Presuming efficacy as per ICMR modelling for new registry trial on the lines of the published case control study, equal allocation between cases and controls and assuming a RR of 1.3.6, the power of such a study would be very low for n=2000 for event rates from 2.5-12.5%. Conclusion: We report the low penetration of HCQ chemoprophylaxis among the healthcare workers of our institution. We highlight the inherent drawbacks in the study design of current national COVID related trial based on the statistical modelling of our survey results and published literature, and thereby emphasis the need of evidence-based strategies contributing to research policy at national level.

The outcomes of Clostridioides difficile infection in patients with diverticular disease: a nationwide analysis.

Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. It contributes to significant morbidity and mortality among hospitalized patients in the United States. Prior studies suggest worse outcomes of CDI in patients with diverticulitis and increased risk for recurrent CDI. We conducted this study to evaluate the outcomes of CDI in patients with diverticular disease from a nationwide data sample (2012-2015).Methods: The National Inpatient Sample (NIS) database between January 2012 and September 2015 was queried for CDI admissions using the International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 008.45, 562.11, 562.10, 562.12, and 562.13 for diagnoses of CDI and diverticular disease.Results: The study included 1,327,595 patients who were admitted between 2012 and 2105 for CDI. Out of all of the patients, 84,170 (6.34%) had a concurrent diagnosis of diverticular disease. After adjusting for confounding variables, the in-hospital mortality was lower [odd ratio (OR): 0.48, 95% CI: 0.44-0.52, p < .001] for patients with diverticular disease. The length of stay (LOS) was longer [10.5 versus 9.3 days, p < .001] and mean cost of hospitalization was significantly higher in patients without a history of diverticular disease.Discussion: In a nationwide population study, admissions with CDI, patients with a concurrent diagnosis of diverticular disease had lower in-hospital mortality. The observed results are different from prior studies and might be attributed to a higher burden of normal flora in those patients and increased use of antibiotic stewardship program across many hospitals nationwide.

Burden and Depression in Caregivers of Blind Patients in New York State.

PURPOSE: To describe the degree of burden of care and the proportion at risk of depression among individuals caring for legally blind patients. METHODS: We performed a cross-sectional study of 486 individuals providing care to their family members who were legally blind. Best-corrected visual acuity of the better-seeing eye in patients determined group placement: Group 1, 20/200-10/200; group 2, 10/200 to light perception (LP); group 3, no light perception (NLP); group VF, visual field loss to <20 central degrees. Burden was evaluated using the Burden Index of Caregivers (BIC-11) and the prevalence at risk of depression was determined by the Center for Epidemiologic Studies Depression (CES-D) scale. RESULTS: Total mean BIC-11 scores ranged from 8.78 ± 4.82 (group 1) to 12.03 ± 5.22 (group 3; p = 0.04). Daily hours spent on close supervision, intensity of caregiving and presence of multiple chronic illnesses in caregivers were the significant covariates affecting BIC-11 scores (p < 0.05). The prevalence of caregivers at risk of depression increased with vision loss from 6.9% (group 1) to 17.9% (group 3; p < 0.05). Female caregivers had an odds ratio (OR) of 2.89 for depression (95% confidence interval, CI, 1.07-3.97; p = 0.04). Caregivers with ≥2 comorbidities had OR 4.24 (95% CI 2.41-6.11) for risk of depression (p < 0.01). CONCLUSION: Burden of care was highest among caregivers who provided greater hours of supervision. Patients with more limitations in their activities of daily living had caregivers who reported higher burden. Female caregivers and caregivers with multiple chronic illnesses were at higher risk of depression.

Parent education discharge instruction program for care of children at home after cardiac surgery in Southern India.

UNLABELLED: Introduction In many developing countries, children with CHD are now receiving surgical repair or palliation for their complex medical condition. Consequently, parents require more in-depth discharge education programmes to enable them to recognise complications and manage their children's care after hospital discharge. This investigation evaluated the effectiveness of a structured nurse-led parent discharge teaching programme on nurse, parent, and child outcomes in India. Materials and methods A quasi-experimental investigation compared nurse and parent home care knowledge before and at two time points after the parent education discharge instruction program's implementation. Child surgical-site infections and hospital costs were compared for 6 months before and after the discharge programme's implementation. RESULTS: Both nurses (n=63) and parents (n=68) participated in this study. Records of 195 children who had undergone cardiac surgery were reviewed. Nurses had a high-level baseline home care knowledge that increased immediately after the discharge programme's implementation (T1=24.4±2.89; T2=27.4±1.55; p0.05) after the programme's implementation. CONCLUSION: Nurse, parent, and child outcomes were improved after implementation of the structured nurse-led parent discharge programme for parents in India. Structured nurse-led parent discharge programmes may help prepare parents to provide better home care for their children after cardiac surgery. Further investigation of causality and influencing factors is warranted.

Nurse and parent perceptions associated with the Parent Education Discharge Instruction Programme in southern India.

UNLABELLED: Introduction Parents of children with CHD require home care knowledge in order to ensure their child's health and safety, but there has been no research on how to achieve this in a resource-constrained environment. The aim of this investigation was to compare parent and nurse perceptions of parent readiness for discharge after a structured nurse-led parent discharge teaching programme in India. Materials and methods A pre-post design was used to compare parent and nurse perceptions of parental uncertainty and readiness for hospital discharge before and after introduction of the parent education discharge instruction programme in a paediatric cardiac surgery unit. RESULTS: Parents (n=68) and nurses (n=63) participated in this study. After the discharge programme implementation, parents had less uncertainty (M=93.3 SD=10.7 versus M=83.6 SD=4.9, p=0.001) and ambiguity (M=40.8 SD=6.8 versus M=33.4 SD=3.7, p=0.001) about their child's illness; however, they rated themselves as being less able to cope with the transition to home (M=24.3 SD=4.1 versus 23.1 SD=2.2, p=0.001) and as having less support at home than that required (M=31.5 SD=9.9 versus 30.9 SD=3.2, p=0.001). Parents' and nurses' perception of parental readiness for hospital discharge were more closely aligned after implementation of a nurse-led discharge programme (r=0.81, p=0.001). CONCLUSION: The results of this study suggest that the discharge programme had positive and negative effects on parental perceptions of uncertainty and readiness for discharge. Further examination is warranted to delineate these influences and to design methods for supporting parents during the transition to home care.

Optic nerve morphology in normal children.

PURPOSE: To expand the normative database of pediatric eyes analyzed with the Optovue optical coherence tomography (OCT). METHODS: In a community-based, cross-sectional analysis, 77 healthy 5-year-old children were recruited from pediatric practices. No subject had any known ocular disorder. Their optic nerves were assessed using Optovue optical coherence tomography (OCT). Data were compared to the normative database obtained by Optovue for adults, ages 18-25, 40-45, and 55-60. Comparisons included thickness of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), and optic nerve head disk area, vertical (VCD) and horizontal (HCD) cup:disk ratios, and cup area. RESULTS: In comparison to all adult age groups, the children's optic nerve heads were statistically less cupped (cup area, VCD, HCD), all with P values of <0.0003. No statistical difference was identified between the children and adults aged 18-25 and 40-45 with respect to RNFL or GCC. Both RNFL and GCC were thicker in the children compared to adults aged 55-60 (P < 0.003). Children's disk area's were marginally smaller than those of adults, the difference not reaching statistical significance. CONCLUSIONS: Our OCT results demonstrate that young children's optic nerves are statistically less cupped than those of all normal adults. The children's RNFL and GCC are statistically thicker than those of adults aged 55-60.

Heterochromia iridis and pertinent clinical findings in patients with glaucoma associated with Sturge-Weber syndrome.

PURPOSE: To examine the clinical and gonioscopic findings in patients with glaucoma associated with Sturge-Weber syndrome. METHODS: Retrospective review of clinical findings of all patients with Sturge-Weber syndrome who presented between January 1978 and December 2003. Koeppe gonioscopy was performed under general anesthesia and findings were photographed when feasible. Iris color was documented by color sketch or photograph at initial presentation. Fisher exact test was used to determine whether the presence of heterochromia was statistically higher in the glaucomatous group. RESULTS: Fifty-five patients who met inclusion criteria were identified, of whom 44 (80%) had glaucoma. Unilateral glaucoma was diagnosed in 30 eyes and bilateral glaucoma in 14 eyes, yielding 58 eyes with glaucoma and 52 eyes without. Gonioscopic examination revealed distinct anatomic abnormalities in the anterior chamber angle in 32 (55%) of the glaucomatous eyes in contrast to the normal fellow eyes in patients with unilateral glaucoma and to the patients without glaucoma. Heterochromia iridis with darker iris on the glaucomatous side was present in 11 of the 30 patients with unilateral glaucoma (37%, P < .001) but in none of the patients without glaucoma. CONCLUSION: The characteristics observed in the anterior chamber angle in this large, uniquely examined series are the first reported to the authors' knowledge and may support a role for neural crest derived anomalies in the pathogenesis of glaucoma in these infant eyes. Careful examination for heterochromia iridis may be judicious in these patients.

Central corneal thickness and glaucoma in aphakic and pseudophakic children.

BACKGROUND: The risk of glaucoma among aphakic children is as high as 32%, based primarily on intraocular pressure (IOP) measurements. Although IOP may be falsely elevated by increased central corneal thickness, central corneal thickness (CCT) values have not been reported in this population. METHODS: Patients from the practices of 2 pediatric ophthalmologists and 2 glaucoma specialists had measurements of CCT, IOP, and optic nerve cupping, with visual field analysis when possible. Normal fellow eyes of unilateral aphakes and pseudophakes were included as controls. RESULTS: In 36 aphakic and 6 pseudophakic eyes CCT averaged 660 microns compared with 576 microns for phakic fellow eyes (P < 0.0001). Glaucoma, defined by IOP at least 35 mm Hg or by IOP at least 22 mm Hg associated with optic nerve changes, occurred in 21% of 28 aphakic patients but in no pseudophakic patient. CONCLUSIONS: CCT in aphakic/pseudophakic children is substantially increased compared with control patients. These values may be important in interpreting IOP measurements in these children.

Duodenal atresia associated with proximal jejunal perforations: a case report and review of the literature.

Duodenal atresia is associated with Down's syndrome, malrotation, and congenital cardiac defects. Idiopathic intestinal perforations in a newborn, which are not associated with necrotizing enterocolitis (NEC), have been described. The authors report on a full-term neonate who had multiple perforations of the proximal jejunum distal to duodenal atresia. To the best of the authors knowledge, the combination of idiopathic intestinal perforation and duodenal atresia has not been reported previously.

Delayed presentation of splenic injury: still a common syndrome.

The entity of delayed splenic rupture represents an initially missed injury, a delayed presentation of the latter, or an actually delayed development of an initially latent, minor, splenic injury. Having encountered a number of patients presenting with splenic rupture days after what was considered a minor abdominal trauma we review our experience with this entity. This is a retrospective study. During the past 6 years 26 patients were treated at our level II trauma center for blunt splenic injuries. The 8 patients who presented 48 h or more after injury are the focus of this communication. All patients had an underlying medical condition: five were drug addicts (one was HIV positive) and the other three were affected by cirrhosis, sickle cell disease, and HIV. The mechanisms of injury were as follows: blunt assault in 5 patients, a fall in 2 patients, and unknown in 1 patient. The patients presented to our hospital after a mean lag time of 5 days after injury (range, 2-10 days). One patient presented in shock and underwent laparotomy after a positive diagnostic peritoneal lavage. Four presented with a clinical acute abdomen, and three presented with abdominal pain and anemia. Abdominal computed tomography (CT) was performed in the seven hemodynamically stable patients demonstrating hemoperitoneum in all: five had a grade III injury and two had a grade II injury. All patients survived after an emergency splenectomy. Delayed presentation of splenic injury after minor abdominal trauma is not uncommon in our indigenous population. It may be associated with drug abuse and HIV.