Characterizing The Patient Population With 30-Day Readmissions From COPD and Heart Failure

Under the Hospital Readmission Reduction Program (HRRP), hospitals with high readmission rates are penalized by reductions in Medicare reimbursements. In particular, Parkview Noble hospital has experienced high readmission rates for chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and acute myocardial infarction (AMI). Parkview Noble’s combined 30-day readmission rates for these conditions is 18.19% compared to the national average of 15.86%. Objective: In order to effectively reduce the readmission rate for COPD and CHF patients at Parkview Noble, this study examined the socioeconomic and clinical factors that can be used to target this patient population for healthcare driven interventions. Design/Methods: Data was collected in the form of a retrospective chart review and phone interview of 260 patients. The data obtained was then analyzed using student t-test, chi-square test, and multi-variable regression to determine statistically promising variables. A linear regression using statistically promising variables was performed to obtained preliminary predictive algorithms for COPD and CHF readmission. The sensitivity and specificity of these equations was then plotted using various cut-off values to determine their practical effectiveness. Results: The statistical analysis determined four factors with strong predictive value including: past ED visits in the last 6 months (p=1.4E-6), past ED admissions in the last year (p=0.03), heart failure with coronary artery disease (p=0.05), and stage of COPD (p=0.06). The sensitivity and specificity plots suggest that it is possible to target 20% of readmission patients while still maintaining over 85% specificity. Conclusions: From this preliminary data it is seen that several variables have value in determining a patient’s likelihood of readmission. Using this data as a benchmark, this study will be expanded to include up to 1,028 more patients before a final predictive algorithm is computed and tested

Novel Insights into the Roles of Rho Kinase in Cancer

Rho-associated coiled-coil kinase (ROCK) is a major downstream effector of the small GTPase RhoA. The ROCK family, consisting of ROCK1 and ROCK2, plays a central role in the organization of the actin cytoskeleton, and is involved in a wide range of fundamental cellular functions such as contraction, adhesion, migration, proliferation, and apoptosis. Since the discovery of effective inhibitors such as fasudil and Y27632, the biological roles of ROCK have been extensively explored in numerous diseases, including cancer. Accumulating evidence supports the concept that ROCK plays important roles in tumor development and progression through regulating many key cellular functions associated with malignancy, including tumorigenicity, tumor growth, metastasis, angiogenesis, tumor cell apoptosis/survival and chemoresistance as well. This review focuses on the new advances of the most recent 5 years from the studies on the roles of ROCK in cancer development and progression; the discussion is mainly focused on the potential value of ROCK inhibitors in cancer therapy

Toward laboratory blood test-comparable photometric assessments for anemia in veterinary hematology

Anemia associated with intestinal parasites and malnutrition is the leading cause of morbidity and mortality in small ruminants worldwide. Qualitative scoring of conjunctival redness has been developed so that farmers can gauge anemia in sheep and goats to identify animals that require treatment. For clinically relevant anemia diagnosis, complete blood count-comparable quantitative methods often rely on complicated and expensive optical instruments, requiring detailed spectral information of hemoglobin. We report experimental and numerical results for simple, yet reliable, noninvasive hemoglobin detection that can be correlated with laboratory-based blood hemoglobin testing for anemia diagnosis. In our pilot animal study using calves, we exploit the third eyelid (i.e., palpebral conjunctiva) as an effective sensing site. To further test spectrometer-free (or spectrometerless) hemoglobin assessments, we implement full spectral reconstruction from RGB data and partial least square regression. The unique combination of RGB-based spectral reconstruction and partial least square regression could potentially offer uncomplicated instrumentation and avoid the use of a spectrometer, which is vital for realizing a compact and inexpensive hematology device for quantitative anemia detection in the farm field

Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy

Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1). The multifunctional protein APE1/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections

Retinal Phenotyping of Ferrochelatase Mutant Mice Reveals Protoporphyrin Accumulation and Reduced Neovascular Response

Purpose: Heme depletion, through inhibition of ferrochelatase (FECH), blocks retinal and choroidal neovascularization. Both pharmacologic FECH inhibition and a partial loss-of-function Fech mutation (Fechm1Pas) are associated with decreased neovascularization. However, the ocular physiology of Fechm1Pas mice under basal conditions has not been characterized. Here, we aimed to characterize the retinal phenotype of Fechm1Pas mice. Methods: We monitored retinal vasculature at postnatal day 17, 2 months, and 6 months in Fechm1Pas homozygotes, heterozygotes, and their wild-type littermates. We characterized Fech substrate protoporphyrin (PPIX) fluorescence in the eye (excitation = 403 nm, emission = 628 nm), retinal function by electroretinogram, visual acuity by optomotor reflex, and retinal morphology by optical coherence tomography and histology. We stained vasculature using isolectin B4 and fluorescein angiography. We determined endothelial sprouting of retinal and choroidal tissue ex vivo and bioenergetics of retinal punches using a Seahorse flux analyzer. Results: Fundi, retinal vasculature, venous width, and arterial tortuosity showed no aberrations. However, VEGF-induced retinal and choroidal sprouting was decreased in Fechm1Pas mutants. Homozygous Fechm1Pas mice had pronounced buildup of PPIX in the posterior eye with no damage to visual function, bioenergetics, and integrity of retinal layers. Conclusions: Even with a buildup of PPIX in the retinal vessels in Fechm1Pas homozygotes, the vasculature remains normal. Notably, stimulus-induced ex vivo angiogenesis was decreased in Fechm1Pas mutants, consistent with reduced pathologic angiogenesis seen previously in neovascular animal models. Our findings indicate that Fechm1Pas mice are a useful model for studying the effects of heme deficiency on neovascularization due to Fech blockade

Small-molecule inhibitors of ferrochelatase are antiangiogenic agents

Activity of the heme synthesis enzyme ferrochelatase (FECH) is implicated in multiple diseases. In particular, it is a mediator of neovascularization in the eye and thus an appealing therapeutic target for preventing blindness. However, no drug-like direct FECH inhibitors are known. Here, we set out to identify small-molecule inhibitors of FECH as potential therapeutic leads using a high-throughput screening approach to identify potent inhibitors of FECH activity. A structure-activity relationship study of a class of triazolopyrimidinone hits yielded drug-like FECH inhibitors. These compounds inhibit FECH in cells, bind the active site in cocrystal structures, and are antiangiogenic in multiple in vitro assays. One of these promising compounds was antiangiogenic in vivo in a mouse model of choroidal neovascularization. This foundational work may be the basis for new therapeutic agents to combat not only ocular neovascularization but also other diseases characterized by FECH activity

Impact of Pregnancy Weight Gain on Idiopathic Intracranial Hypertension

Studies suggest that weight gain is a prominent risk factor for recurrence of papilledema in IIH. Given this information, the significant weight gain that occurs during pregnancy, and the fact that pharmacologic therapy is many times discontinued, raises concerns for worsening edema and vision loss. To examine the impact of pregnancy weight gain on IIH, we present preliminary results of a retrospective chart review of patients with IIH and pregnancy. Compared to previous studies we 1) quantified findings with OCT and HVF data, 2) Included baseline data prior to pregnancy, and 3) determined excess pregnancy weight gain using BMI adjusted weight gain goals

Neuroretinitis with Sub-Henle Fiber Layer Exudates

The macular star present in most cases of neuroretinitis is the result of exudates settling in Henle Fiber Layer (HFL). It has been previously reported in the literature that recurrent neuroretinitis can present with atypical retinal exudates that are more drusenoid in appearance and are more peripapillary as opposed to the traditional macular start configuration. Here we present a case of neuroretinitis with these atypical exudates along with imaging to provide a potential anatomic explanation for these findings