Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.

Food and Drug Administration perspective: Advancing product development for non-healing chronic wounds.

The US Food and Drug Administration (FDA) understands that innovative product development is essential to addressing the unmet medical need of non-healing chronic wounds. Barriers to product development for non-healing chronic wounds may involve but are not limited to a dearth of biological models, challenges in drug delivery, challenges in clinical trial execution, and limited commercial viability. This perspective article discusses FDA's renewed focus on non-healing chronic wounds and outlines efforts to address identified barriers to product development for non-healing chronic wounds. In collaboration with key wound healing stakeholders including academia, professional associations, patient groups, reimbursement organizations and industry, FDA intends to help advance product development for non-healing chronic wounds for the ultimate betterment of patients.

Transparency in the Ophthalmology Residency Match: Background, Study, and Implications.

Background Medical students are applying to dramatically more ophthalmology residency programs than in the past, causing an increased administrative burden for programs and financial harm to students. This study considers the background of this situation and looks at how a lack of transparency surrounding potential residency match filters contributes. Furthermore, this study raises several potential solutions to this lack of transparency that may increase the functionality of the ophthalmology residency match. Objective The purpose of this study was to determine the availability and consistency of potential ophthalmology residency match filters through training program websites and the American Medical Association's (AMA) Residency & Fellowship Database (FREIDA). Methods This study was a cross-sectional observational study of ophthalmology residency program websites and AMA's FREIDA database entries. For 119 ophthalmology residency programs, five potential filters were evaluated for both availability and consistency on individual residency websites and FREIDA. These filters were: (1) whether a program required a minimum United States Medical Licensing Examination (USMLE) Step 1 score; (2) minimum number of letters of recommendation required; 3) whether a minimum USMLE Step 2 score was required; (4) if the program accepts the Comprehensive Osteopathic Medical Licensing Examination (COMLEX) sequence in lieu of the USMLE; and (5) ability of the residency to sponsor a visa (J-1, H-1B, or F-1). Each program's website and FREIDA entry were independently evaluated by two authors to increase validity, with a third author brought in to break the tie in case of a disagreement. Results Only two ophthalmology residency programs had information about all five filters both available and consistent on their website and FREIDA. Inter-reviewer reliability was 92.5%. Conclusions Information about potential filters used in the ophthalmology residency match is neither publicly available nor consistent. This lack of transparency may contribute to the phenomenon of medical students applying to dramatically more ophthalmology residency programs. A standardized database of these filters is needed to increase transparency to applicants, which may reduce the expenses of medical students and the workload of program directors.

The Covid-19 pandemic and India's cardiovascular disease burden: Finding the right balance.

The national lockdown in India has (thus far) prevented a surge of Covid-19 cases. Due to crowded living conditions and poor social security, infectious spread may be difficult to contain and mitigate. India's healthcare system must respond to impending Covid-19 cases, as well as chronic, non-communicable diseases. Acute and chronic cardiovascular disease care have drastically decreased, suggesting reduced accessibility during the current pandemic. Neglecting chronic diseases may lead to permanent health damage and deaths that far exceed the negative outcomes of the pandemic alone. As businesses start to reopen, the healthcare system must find a balance in attending to Covid-19 rises amidst a significant chronic disease backdrop.

Keywords: India, Covid-19, cardiovascular disease, pandemic.

Repeated Remote Ischemic Conditioning Reduces Doxorubicin-Induced Cardiotoxicity.

OBJECTIVES: This study investigated the cardioprotective effect of repeated remote ischemic preconditioning (rRIC) on doxorubicin-induced cardiotoxicity in mice. BACKGROUND: Doxorubicin is an effective chemotherapeutic agent for a wide range of tumor types but its use and dosing are limited by acute and chronic cardiotoxicity. Remote ischemic conditioning (RIC) is cardioprotective in multiple cardiovascular injury models, but the effectiveness of rRIC in doxorubicin-induced cardiotoxicity has not been fully elucidated. METHODS: rRIC was performed on mice before and after doxorubicin administration. Cardiac function was assessed by echocardiography and myocardial biology was tested by molecular approaches. RESULTS: Doxorubicin administration induced acute cardiotoxicity, as indicated by reduced cardiac function, reduced myocyte cross-section area and increased extracellular collagen deposition, increased circulating cardiac muscle damage markers, and decreased heart weight. Doxorubicin also adversely affected other organs, including the kidney, liver, and spleen, as evaluated by circulating markers or organ weight loss. rRIC not only abrogated doxorubicin-induced cardiotoxicity (left ventricular ejection fraction, doxorubicin 47.5 ± 1.1%, doxorubicin + rRIC 51.6 ± 0.7%, p = 0.017), but also was associated with multiorgan protection. Within the myocardium, rRIC attenuated doxorubicin-induced cardiomyocyte apoptosis, reduced inflammation, and increased autophagy signaling. CONCLUSIONS: rRIC may be a promising approach to reduce doxorubicin-induced cardiotoxicity.

An Interscholastic Network To Generate LexA Enhancer Trap Lines in Drosophila.

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StanEx1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.

Staphylococcal Infection-Related Glomerulonephritis With Cryoglobulinemic Features.

INTRODUCTION: Staphylococcal infection-related glomerulonephritis (GN) has been shown to represent a unique form of infection-related GN that contains IgA-dominant deposits and is often seen concurrently with the bacterial infection. Biopsies commonly reveal an endocapillary proliferative and/or exudative or mesangial proliferative GN. Rare cases have been reported to show cryoglobulin-like features, including hyaline pseudothrombi and wireloop deposits; however, detailed characterization of these cases is lacking. METHODS: The pathology archives from the University of Utah and Sharp Memorial Hospital were reviewed from January 2016 to September 2017 in search of cases with GN containing IgA-dominant deposits and features of cryoglobulinemia. RESULTS: Of 1965 native kidney biopsies, 5 showed IgA-dominant GN with cryoglobulinemic features. All patients had active staphylococcal infections at the time of biopsy. All presented with acute kidney injury (serum creatinine range: 1.7-6 mg/dl), and all had proteinuria and hematuria. All biopsies showed exudative GN, and 4 biopsies had focal crescents. All had focally prominent hyaline pseudothrombi with or without wireloop deposits, and all showed co-dominant staining for IgA and C3 on immunofluorescence microscopy. Serologic testing for cryoglobulinemia was performed in 3 patients and was transiently positive in 1 patient. Four patients required hemodialysis at last follow-up, whereas 1 patient returned to baseline kidney function. CONCLUSION: IgA-dominant GN with cryoglobulinemic features is an uncommon but severe form of glomerular injury in patients with staphylococcal infections. Four of 5 patients had crescentic glomerular injuries, all of whom required hemodialysis at last follow-up. Patients with IgA-dominant GN with features of cryoglobulinemia should be evaluated for active staphylococcal infection.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PLAIN ENGLISH SUMMARY: People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. ABSTRACT: The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

A pilot study to evaluate the effect of splanchnic nerve stimulation on body composition and food intake in rats.

BACKGROUND: Systemic sympathetic stimulation with caffeine and ephedrine increased metabolic rate, reduced food intake, and improved body composition but had systemic adverse events. We hypothesize that selective sympathetic stimulation of the upper gastrointestinal tract will preserve the advantages of systemic sympathetic stimulation without its adverse events. This study evaluated the effect of splanchnic nerve stimulation on metabolic rate, food intake, and body composition. METHODS: Sixteen Sprague Dawley rats had monopolar electrodes placed on the superior common splanchnic nerve innervating the celiac ganglia. An indifferent electrode was placed subcutaneously on the back. The animals were placed on a 60% fat diet, and eight rats were stimulated for 6 weeks. The stimulation was advanced over 3 days from 0.6 mA to 3 mA. Metabolic rate and food intake were measured daily; weight change was monitored weekly, and body composition was determined by nuclear magnetic resonance (NMR) at the end of the study. Four of the eight animals had metabolic rate measured three times over 2-day periods at 0 mA, 1 mA, and 3 mA of stimulation in a metabolic chamber. RESULTS: Except for the first week of stimulation, there was no difference in body weight between the stimulated and control groups. Cumulative food intake was less in the stimulated group (p<0. 001). The lean-to-fat ratio was greater in the stimulated group (p<0. 01), and the animals that received incremental stimulation showed significantly augmented metabolic rate (p<0. 02). CONCLUSIONS: Splanchnic nerve stimulation decreased food intake, increased metabolic rate, and improved body composition.

Purinergic receptors in gastrointestinal inflammation.

Purinergic receptors comprise a family of transmembrane receptors that are activated by extracellular nucleosides and nucleotides. The two major classes of purinergic receptors, P1 and P2, are expressed widely in the gastrointestinal tract as well as immune cells. The purinergic receptors serve a variety of functions from acting as neurotransmitters, to autocoid and paracrine signaling, to cell activation and immune response. Nucleosides and nucleotide agonist of purinergic receptors are released by many cell types in response to specific physiological signals, and their levels are increased during inflammation. In the past decade, the advent of genetic knockout mice and the development of highly potent and selective agonists and antagonists for the purinergic receptors have significantly advanced the understanding of purinergic receptor signaling in health and inflammation. In fact, agonist/antagonists of purinergic receptors are emerging as therapeutic modalities to treat intestinal inflammation. In this article, the distribution of the purinergic receptors in the gastrointestinal tract and their physiological and pathophysiological role in intestinal inflammation will be reviewed.