HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia.

Iron deficiency anemia is caused by many pathological conditions like chronic kidney disease (CKD), inflammation, malnutrition and gastrointestinal abnormality. Current treatments that are erythropoiesis stimulating agents (ESAs) and iron supplementation are inadequate and often lead to tolerance and/or toxicity. Desidustat, a prolyl hydroxylase (PHD) inhibitor, is clinically used for the treatment of anemia with CKD. In this study, we investigated the effect of desidustat on iron deficiency anemia (IDA). IDA was induced in C57BL6/J mice by iron deficient diet feeding. These mice were then treated with desidustat (15 mg/kg, PO) and FeSO4 (20 mg/kg) for five weeks and effect of the treatment on hematology, iron homeostasis, and bone marrow histology was observed. Effect of desidustat on iron metabolism in inflammation (LPS)-induced iron deficiency was also assessed. Both, Desidustat and FeSO4, increased MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), hemoglobin, and HCT (hematocrit) in blood and increased iron in serum, liver, and spleen. Desidustat increased MCHC (mean corpuscular hemoglobin concentration) while FeSO4 treatment did not alter it. FeSO4 treatment significantly increased iron deposition in liver, and spleen, while desidustat increased iron in circulation and demonstrated efficient iron utilization. Desidustat increased iron absorption, serum iron and decreased hepcidin without altering tissue iron, while FeSO4 increased serum and tissue iron by increasing hepcidin in LPS-induced iron deficiency. Desidustat increased erythroid population, especially iron-dependent polychromatic normoblasts and orthochromatic normoblasts, while FeSO4 did not improve cell architecture. PHD inhibition by desidustat improved iron utilization in iron deficiency anemia, by efficient erythropoiesis.

Meritus Health: Driving Data-Informed Decision-Making at Every Level.

With so much data available, health system leaders are challenged with sifting through it all to find the most useful information for decision-making. Meritus Health implemented effective approaches to understand, use, and communicate large amounts of data to alleviate some of this burden. These processes include system-wide daily huddles, dashboards, and standardized communication write-ups.

DNA-based fluorescent probes of NOS2 activity in live brains.

Innate immune cells destroy pathogens within a transient organelle called the phagosome. When pathogen-associated molecular patterns (PAMPs) displayed on the pathogen are recognized by Toll-like receptors (TLRs) on the host cell, it activates inducible nitric oxide synthase (NOS2) which instantly fills the phagosome with nitric oxide (NO) to clear the pathogen. Selected pathogens avoid activating NOS2 by concealing key PAMPs from their cognate TLRs. Thus, the ability to map NOS2 activity triggered by PAMPs can reveal critical mechanisms underlying pathogen susceptibility. Here, we describe DNA-based probes that ratiometrically report phagosomal and endosomal NO, and can be molecularly programmed to display precise stoichiometries of any desired PAMP. By mapping phagosomal NO produced in microglia of live zebrafish brains, we found that single-stranded RNA of bacterial origin acts as a PAMP and activates NOS2 by engaging TLR-7. This technology can be applied to study PAMP-TLR interactions in diverse organisms.

A DNA-based fluorescent probe maps NOS3 activity with subcellular spatial resolution.

Nitric oxide synthase 3 (NOS3) produces the gasotransmitter nitric oxide (NO), which drives critical cellular signaling pathways by S-nitrosylating target proteins. Endogenous NOS3 resides at two distinct subcellular locations: the plasma membrane and the trans-Golgi network (TGN). However, NO generation arising from the activities of both these pools of NOS3 and its relative contribution to physiology or disease is not yet resolvable. We describe a fluorescent DNA-based probe technology, NOckout, that can be targeted either to the plasma membrane or the TGN, where it can quantitatively map the activities of endogenous NOS3 at these locations in live cells. We found that, although NOS3 at the Golgi is tenfold less active than at the plasma membrane, its activity is essential for the structural integrity of the Golgi. The newfound ability to spatially map NOS3 activity provides a platform to discover selective regulators of the distinct pools of NOS3.

A DNA-based fluorescent reporter maps HOCl production in the maturing phagosome.

Phagocytes destroy pathogens by trapping them in a transient organelle called the phagosome, where they are bombarded with reactive oxygen species (ROS) and reactive nitrogen species (RNS). Imaging reactive species within the phagosome would directly reveal the chemical dynamics underlying pathogen destruction. Here we introduce a fluorescent, DNA-based combination reporter, cHOClate, which simultaneously images hypochlorous acid (HOCl) and pH quantitatively. Using cHOClate targeted to phagosomes in live cells, we successfully map phagosomal production of a specific ROS, HOCl, as a function of phagosome maturation. We found that phagosomal acidification was gradual in macrophages and upon completion, HOCl was released in a burst. This revealed that phagosome-lysosome fusion was essential not only for phagosome acidification, but also for providing the chloride necessary for myeloperoxidase activity. This method can be expanded to image several kinds of ROS and RNS and be readily applied to identify how resistant pathogens evade phagosomal killing.

Chemical control over membrane-initiated steroid signaling with a DNA nanocapsule.

Membrane-initiated steroid signaling (MISS) is a recently discovered aspect of steroidal control over cell function that has proved highly challenging to study due to its rapidity and ultrasensitivity to the steroid trigger [Chow RWY, Handelsman DJ, Ng MKC (2010) Endocrinology 151:2411-2422]. Fundamental aspects underlying MISS, such as receptor binding, kinetics of ion-channel opening, and production of downstream effector molecules remain obscure because a pristine molecular technology that could trigger the release of signaling steroids was not available. We have recently described a prototype DNA nanocapsule which can be programmed to release small molecules upon photoirradiation [Veetil AT, et al. (2017) Nat Nanotechnol 12:1183-1189]. Here we show that this DNA-based molecular technology can now be programmed to chemically trigger MISS, significantly expanding its applicability to systems that are refractory to photoirradiation.

Prolyl hydroxylase inhibitor desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines and oxidative stress.

Chronic kidney disease (CKD) is associated with activated inflammatory responses. Desidustat, a prolyl hydroxylase (PHD) inhibitor is useful for treatment of anemia associated with CKD, but its effect on the inflammatory and fibrotic changes in CKD is not evaluated. In this study, we investigated the effect of desidustat on the inflammatory and fibrotic changes in preclinical models of acute and chronic kidney injury. Acute kidney injury was induced in male Sprague Dawley rats by ischemia-reperfusion, in which effect of desidustat (15 mg/kg, PO) was estimated. In a separate experiment, male C57 mice were treated with adenine for 14 days to induce CKD. These mice were treated with desidustat (15 mg/kg, PO, alternate day) treatment for 14 days, with adenine continued. Desidustat prevented elevation of serum creatinine, urea, IL-1ß, IL-6, and kidney injury molecule-1 (KIM-1), and elevated the erythropoietin levels in rats that were subjected to acute kidney injury. Mice treated with adenine developed CKD and anemia, and desidustat treatment caused improvement in serum creatinine, urea, and also improved hemoglobin and reduced hepatic and serum hepcidin. A significant reduction in IL-1ß, IL-6, myeloperoxidase (MPO) and oxidative stress was observed by desidustat treatment. Desidustat treatment also reduced renal fibrosis as observed by histological analysis and hydroxyproline content. Desidustat treatment reduced the renal fibrosis and inflammation along with a reduction in anemia in preclinical models of kidney injury, which may translate to protective effects in CKD patients.

Differences in Perioperative Outcomes and Complications Between African American and White Patients After Total Joint Arthroplasty.

BACKGROUND: Racial disparities in healthcare utilization and outcomes have been reported and have wide-reaching implications for individual patient and healthcare system; as providers we bear an ethical burden to address this disparity and provide culturally competent care. This study will examine the influence of race on length of stay, discharge disposition, and complications requiring reoperation following total joint arthroplasty (TJA). METHODS: Single institution retrospective analysis of a consecutive series of 7208 primary TJA procedures performed between July 2013 and June 2017 was conducted. Chi-squared and t-tests were used to quantify differences between the groups and multiple logistic regression was used to identify race as an independent risk factor. RESULTS: In total, 6182 (84.3%) white and 1026 (14.0%) African American (AA) patients were included. AA patients were younger (63.62 vs 66.84 years, P < .001), more likely female (68.8% vs 57.0%, P < .001), had a longer length of stay (2.19 vs 2.00 days, P < .001), more likely to experience septic complications (1.3% vs 0.5%, P = .002) and manipulation under anesthesia (3.9% vs 1.8%, P < .001), and less likely to discharge home (67.1% vs 81.1%, P < .001). Multiple logistic regression showed that AA patients were more likely to discharge to a facility (adjusted odds ratio 2.63, 95% confidence interval 2.19-3.16, P < .001) and experience a manipulation under anesthesia (adjusted odds ratio 1.90, 95% confidence interval 1.26-2.85, P = .002). CONCLUSION: AA patients undergoing TJA were younger with longer length of stay and a higher rate of nonhome discharge; AA race was identified as an independent risk factor. Further study is required to understand the differences identified in this study. Targeted interventions should be developed to attempt to eliminate the disparity.

Protective effect of thymoquinone against high-fructose diet-induced metabolic syndrome in rats.

PURPOSE: Thymoquinone (TQ), a bioactive constituent of Nigella sativa (Linn.) seed, which is commonly used as a spice in Asian food, has been reported to possess a wide range of biological effects. The present study evaluated the effect of TQ on high-fructose diet (HFD)-induced metabolic syndrome (MetS) in male Wistar rats. METHODS: MetS was induced by 60% HFD over 42 days. TQ (25, 50 and 100 mg/kg, p.o. once daily) was administered along with HFD for 42 days. Pioglitazone (10 mg/kg, p.o. once daily) was used as a standard drug. Plasma glucose, triglycerides, total cholesterol and HDL-cholesterol were estimated on days 0 and 42. Change in blood pressure, oral glucose tolerance and insulin resistance were measured. Hepatic thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase levels were estimated as measures of hepatic oxidative stress. Hepatic mRNA of PPAR-α and PPAR-γ was also studied. RESULTS: TQ prevented the characteristic features of HFD-induced MetS, such as hyperglycaemia, hypertriglyceridemia, hypercholesterolaemia and elevated systolic blood pressure. TQ also prevented impaired glucose tolerance and insulin resistance. It also ameliorated HFD-induced increase in hepatic TBARS and depletion of SOD, catalase and GSH. TQ prevented reduction in hepatic mRNA of PPAR-α and PPAR-γ in HFD rats, and the effects were comparable to those of pioglitazone. CONCLUSIONS: This study demonstrates protective effect of TQ against HFD-induced MetS on rats which might have been mediated via PPAR mechanism.

Accountable Care Organizations and Population Health Organizations.

Accountable care organizations (ACOs) and hospitals are investing in improving "population health," by which they nearly always mean the health of the "population" of patients "attributed" by Medicare, Medicaid, or private health insurers to their organizations. But population health can and should also mean "the health of the entire population in a geographic area." We present arguments for and against ACOs and hospitals investing in affecting the socioeconomic determinants of health to improve the health of the population in their geographic area, and we provide examples of ACOs and hospitals that are doing so in a limited way. These examples suggest that ACOs and hospitals can work with other organizations in their community to improve population health. We briefly present recent proposals for such coalitions and for how they could be financed to be sustainable.

Next generation sequencing in cardiomyopathy: towards personalized genomics and medicine.

Next generation sequencing (NGS) is perhaps one of the most exciting advances in the field of life sciences and biomedical research in the last decade. With the availability of massive parallel sequencing, human DNA blueprint can be decoded to explore the hidden information with reduced time and cost. This technology has been used to understand the genetic aspects of various diseases including cardiomyopathies. Mutations for different cardiomyopathies have been identified and cataloging mutations on phenotypic basis are underway and are expected to lead to new discoveries that may translate to novel diagnostic, prognostic and therapeutic targets. With ease in handling NGS, cost effectiveness and fast data output, NGS is now considered as a diagnostic tool for cardiomyopathy by providing targeted gene sequencing. In addition to the number of genetic variants that are identified in cardiomyopathies, there is a need of quicker and easy way to screen multiple genes associated with the disease. In this review, an attempt has been made to explain the NGS technology, methods and applications in cardiomyopathies and their perspective in clinical practice and challenges which are to be addressed.

Prolyl hydroxylase inhibitor desidustat attenuates autoimmune hemolytic anemia in mice.

Autoimmune hemolytic anemia (AIHA) is a heterogeneous group of diseases mediated by autoantibody directed against RBCs causing hemolysis and anemia. AIHA develops rapidly or over time, depending on the triggering factor. Desidustat is a prolyl hydroxylase inhibitor clinically used for the treatment of chronic kidney disease (CKD)-induced anemia. In this study, we investigated the effect of desidustat in preclinical model of AIHA. We used rat RBC for induction of AIHA in mice. These mice were then treated with desidustat (15 mg/kg, PO, once a day) for eight weeks. Desidustat treatment increased hemoglobin, RBC and hematocrit and decreased WBC and lymphocytes. This treatment suppressed serum LDH, oxidative stress in RBCs, antibody titer and antibody deposition on RBC surface, and increased RBC lifespan. Serum and spleen iron along with spleen mass and oxidative stress were decreased by desidustat. Bone marrow iron was increased and expression of CD71 (cell surface marker for early erythroid progenitor) and TER-119 (cell surface marker for late erythroid progenitor) in bone marrow were found to be elevated by desidustat by treatment. This treatment also suppressed deposition of membrane-bound antibody in late erythroid cells. The treatment showed reduction in total splenic cells, CD71 and TER-119 positive cells in the spleen. Thus, desidustat treatment increased erythropoiesis, early maturation of bone marrow erythroid cells having longer RBC life span due to decrease in the antibody-mediated lysis of RBCs and its progenitors leading to reduced oxidative stress. Thus, desidustat can be a good therapeutic option for treatment of AIHA.

HIF Stabilizer Desidustat Protects against Complement-Mediated Diseases.

Complement cascade is a defence mechanism useful for eliminating pathogenic microorganisms and damaged cells. However, activation of alternative complement system can also cause inflammation and promote kidney and retinal disease progression. Inflammation causes tissue hypoxia, which induces hypoxia-inducible factor (HIF) and HIF helps the body to adapt to inflammation. In this study, we investigated the effect of HIF stabilizer desidustat in complement-mediated diseases. Oral administration of desidustat (15 mg/kg) was effective to reduce the kidney injury in mice that was induced by either lipopolysaccharide (LPS), doxorubicin or bovine serum albumin (BSA)-overload. Complement activation-induced membrane attack complex (MAC) formation and factor B activity were also reduced by desidustat treatment. In addition, desidustat was effective against membranous nephropathy caused by cationic BSA and retinal degeneration induced by sodium iodate in mice. C3-deposition, proteinuria, malondialdehyde, and interleukin-1ß were decreased and superoxide dismutase was increased by desidustat treatment in cBSA-induced membranous nephropathy. Desidustat specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway. This effect appears to be mediated by inhibition of factor B. These data demonstrate the potential therapeutic value of HIF stabilization by desidustat in treatment of complement-mediated diseases.

Burden of respiratory tract infections among paediatric in and out-patient units during 2010-11.

INTRODUCTION: Respiratory tract infections due to viral etiology were studied with an objective to identify and compare the pathogens between Hospital Indoor and Outdoor Units. MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted among children below 12 years over a period of one year. The throat and nasal swabs were collected from both the Units and screened for viral infections by real time RT-PCR technique. RESULTS: Out of 880 samples collected, 87% and 13% were from outdoor and indoor Department with total viral positivity rate of 30% and 25% respectively. Influenza B virus (IBV) (n=126, 16%) was more prevalent in Outdoor Unit, whereas respiratory syncytial virus (RSV) (n=18, 16%) among indoor admitted cases. The multinomial logistic regression analysis revealed that both RSV and Influenza viruses were predominant in children of pre-school age groups < 5 years. In the year 2010-11, the prevalence of human metapneumovirus (HMPV) was low. The pandemic influenza A virus (pH1N1/2009) accounted for 4% (n=29) and 0.8% (n=1) cases among Outdoor and Indoor Units respectively. CONCLUSIONS: The Outdoor Department outnumbered the Indoor Unit in terms of patient attendees and the rate of viral infections. An effective vaccination and continuous surveillance program is the need of the hour.

Hospitals on the path to accountable care: highlights from a 2011 national survey of hospital readiness to participate in an accountable care organization.

Accountable care organizations (ACOs) are forming in communities across the country. In ACOs, health care providers take responsibility for a defined patient popu­lation, coordinate their care across settings, and are held jointly accountable for the quality and cost of care. This issue brief reports on results from a survey that assesses hospitals' readiness to participate in ACOs. Results show we are at the beginning of the ACO adop­tion curve. As of September 2011, only 13 percent of hospital respondents reported partici­pating in an ACO or planning to participate within a year, while 75 percent reported not considering participation at all. Survey results indicate that physician-led ACOs are the second most common governance model, far exceeding payer-led models, highlighting an encouraging paradigm shift away from acute care and toward primary care. Findings also point to significant gaps, including the infrastructure needed to take on financial risks and to manage population health.

Moderately Hypofractionated Radiotherapy and Androgen Deprivation Therapy for High-risk Localised Prostate Cancer: Predictors of Long-term Biochemical Control and Toxicity.

AIMS: There is a paucity of long-term data on outcomes of high-risk prostatic adenocarcinoma after moderately hypofractionated radiotherapy with elective nodal treatment and long-term androgen deprivation therapy (ADT). We report long-term control and toxicity outcomes and analyse the predictors of failure and toxicity. MATERIALS AND METHODS: The records of 120 consecutive high-risk prostate cancer patients treated in a single institution between February 2012 and December 2016 were retrospectively analysed. A moderately hypofractionted radiotherapy (HypoRT) regimen of 60 Gy in 20 fractions over 4 weeks with simultaneous elective pelvic irradiation to 44 Gy in 20 fractions with intensity-modulated radiotherapy was used, together with long-term ADT with either orchiectomy or medical castration for a total duration of 2-3 years. We analysed biochemical control, metastasis-free survival and late toxicities and their predictive factors using survival analysis. RESULTS: Patients had locally advanced cancers (cT3 77.5%, median pretreatment prostate-specific antigen 30 ng/ml, Gleason score 8-10 in 45.8%). The median follow-up time was 70 months. The 3- and 5-year probability of freedom from biochemical progression was 93% and 80%, respectively. The 5-year probability of freedom from local relapse/intra-pelvic nodal relapse/distant metastases as the site of first failure was 96%/97%/86%, respectively. Gleason score 8-10 and medical ADT for 2-3 years (as opposed to orchidectomy) were independent risk factors for distant metastases. A total of 18 grade 2 and above late gastrointestinal toxicity events and a total of 23 grade 2 and above late genitourinary toxicity events were documented. Patients who underwent a transurethral resection of prostate prior to radiotherapy had worse urological toxicity. CONCLUSIONS: HypoRT with elective nodal treatment results in excellent pelvic control. Distant metastases are the primary mode of failure. Risk of metastases is associated with Gleason score and the duration of ADT. Late urinary toxicities are more common in those with prior transurethral resection of prostate.

Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state.

Many anemic chronic kidney disease (CKD) patients are refractory to erythropoietin (EPO) effects due to inflammation, deranged iron utilization, and generation of EPO antibodies. This work assessed the effect of desidustat, an inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase (PHD), on EPO-refractory renal anemia. Sprague Dawley rats were made anemic by cisplatin (5 â€‹mg/kg, IP, single dose) and turpentine oil (5 â€‹mL/kg, SC, once a week). These rats were given recombinant human EPO (rhEPO, 1 â€‹µg/kg) and desidustat (15 or 30 â€‹mg/kg) for eight weeks. Separately, rhEPO (1-5 â€‹µg/kg) was given to anemic rats to sustain the normal hemoglobin levels and desidustat (15 â€‹mg/kg) for eight weeks. In another experiment, the anemic rats were treated rhEPO (5 â€‹µg/kg) for two weeks and then desidustat (15 â€‹mg/kg) for the next two weeks. Dosing of rhEPO was thrice a week, and for desidustat, it was on alternate days. Desidustat inhibited EPO-resistance caused by rhEPO treatment, decreased hepcidin, IL-6, IL-1ß, and increased iron and liver ferroportin. Desidustat reduced EPO requirement and anti-EPO antibodies. Desidustat also maintained normal hemoglobin levels after cessation of rhEPO treatment. Thus, novel prolyl hydroxylase inhibitor desidustat can treat EPO resistance via improved iron utilization and decreased inflammation.

Efficacy and Safety of Pregabalin Prolonged Release-Etoricoxib Combination Compared to Etoricoxib for Chronic Low Back Pain: Phase 3, Randomized Study.

INTRODUCTION: Currently available treatments for chronic lower back pain (CLBP) do not adequately address both nociceptive and neuropathic components of pain. We evaluated efficacy and safety of fixed-dose combination (FDC) of low-dose pregabalin prolonged release 75 mg-etoricoxib 60 mg to address both pain components. METHODS: This randomized phase 3 trial conducted at 12 centres across India evaluated efficacy (based on mean change in numeric rating scale [NRS], Roland-Morris disability questionnaire [RDQ], visual analogue scale [VAS], patient global impression of improvement [PGI-I], clinical global impression of improvement [CGI-I] and rescue medication consumption) and safety of FDC in comparison to etoricoxib alone in adult patients with CLBP. Treatment duration was 8 weeks. RESULTS: Of the 371 patients screened, 319 were randomized and considered for efficacy and safety analysis. Both treatment groups had no significant difference in terms of demography and baseline disease characteristics. Significantly better outcomes with FDC compared to etoricoxib were observed at week 4 onwards. At week 8, both groups showed significant reduction in mean NRS score from baseline (- 4.00 ± 1.65 in FDC; - 2.92 ± 1.59 in etoricoxib) with mean NRS score being significantly less in the FDC group compared to etoricoxib group (3.26 ± 1.56 vs 4.31 ± 1.56; p < 0.0001). The FDC was more effective than etoricoxib in terms of significantly greater reduction in RDQ score (- 9.28 ± 4.48 vs - 6.78 ± 4.34; p < 0.0001) and VAS score (- 37.66 ± 18.7 vs - 28.50 ± 16.31; p < 0.0001) at week 8. The FDC was also better in terms of significantly more patients reporting their condition as 'very much better' (36.9% vs 5.0%; p < 0.0001) and clinicians reporting patient's condition as 'very much improved' (36.3% vs 5.7%; p < 0.0001). Overall, study medications were well tolerated. CONCLUSION: FDC of pregabalin and etoricoxib provided significant benefits in reducing pain and improving functional status compared with etoricoxib alone in patients with CLBP. Pregabalin prolonged release-etoricoxib FDC could be one of the treatment options for early and sustained pain relief and improvement in quality-of-life in treating CLBP as it addresses both neuropathic and nociceptive components of pain. TRIAL REGISTRATION: CTRI/2018/10/015886.

Low back pain is one of the most common causes of loss of productivity worldwide. About 60% of Indians suffer from low back pain at some point. Low back pain that persists for more than 3 months is classified as chronic low back pain which mostly includes both nociceptive and neuropathic components. Monotherapies, if prescribed, are not completely effective, as they generally only target either nociceptive or neuropathic components of pain. Multiple drugs are usually needed at multiple times a day, at higher doses for optimal effectiveness, and in most cases they have significant side effects if taken over prolonged periods and also add to the pill burden. To minimize treatment-associated adverse effects, and to increase treatment compliance, while addressing both the components of pain, we developed a fixed-dose combination of low-dose pregabalin prolonged release and etoricoxib. A phase 3 trial was designed to assess the efficacy and safety of the fixed-dose combination in comparison with etoricoxib alone in treating chronic low back pain. The combination demonstrated statistically and clinically significant improvement in patient-reported outcomes­pain, functionality and quality of life­as early as 4 weeks after starting the medication. No severe or serious adverse effects were reported. Thus, the combination of low-dose pregabalin prolonged release and etoricoxib could provide an option for optimal management of chronic low back pain. This would provide multiple benefits, such as addressing both nociceptive and neuropathic components of chronic low back pain, reducing drug-related adverse effects because of low dose, reducing pill burden and thereby increasing drug compliance.

Hospitals of the future.

Hospitals and health systems face unprecedented demand to change in both the near- and longer-term future, ranging from demographic changes to increasing reliance on value-based payment, and to the uncertainty surrounding governmental reform. the American Hospital Association Board Committee on Performance Improvement embarked on an initiative to identify the top ten strategies all hospitals must adopt in order to be successful care systems of the future. As a result of the committee's survey research, four top strategies were identified: (1) Aligning hospitals, physicians, and other providers across the continuum of care; (2) Using evidenced-based practices to improve quality and patient safety; (3) Improving efficiency through productivity and financial management; and (4) Developing integrated information systems. This article summarizes ten strategies and the measures to assess the accomplishment of these strategies.

Effect of dual PPAR-α/γ agonist saroglitazar on diabetic retinopathy and oxygen-induced retinopathy.

Diabetic retinopathy is a serious complication of diabetes, marked by retinal vascular damage, inflammation, and angiogenesis. This study's objective was to assess the potential benefits of saroglitazar, a peroxisome proliferator-activated receptor-alpha/gamma (PPAR-α/γ) agonist in diabetic retinopathy. Diabetic retinopathy was induced by streptozotocin in Sprague Dawley rats. The effect of saroglitazar was also assessed in the oxygen-induced retinopathy model in newborn rats and VEGF-induced angiogenesis in the chick chorioallantoic membrane (CAM) assay. Treatment of saroglitazar (1 and 4 mg/kg, oral) for 12 weeks significantly ameliorated retinal vascular leakage and leukostasis in the diabetic rats. Saroglitazar decreased oxidative stress, VEGF receptor signalling, NF-κBp65, and ICAM-1 in the retina of diabetic rats. The beneficial effects of saroglitazar (1 and 4 mg/kg, oral) were also observed on the neovascularization in oxygen-induced retinopathy in newborn rats. Saroglitazar also reduced VEGF-induced angiogenesis in CAM assay. This study reveals that saroglitazar has the potential to prevent the progression of retinopathy in diabetic patients.