Transcriptomic and Molecular Docking Analysis Reveal Virulence Gene Regulation-Mediated Antibacterial Effects of Benzyl Isothiocyanate Against Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many serious infections. Thus, efficient and practical techniques to fight S. aureus are required. In this study, transcriptomics was used to evaluate changes in S. aureus following treatment with benzyl isothiocyanate (BITC) to determine its antibacterial action. The results revealed that the BITC at subinhibitory concentrations (1/8th MIC) treated group had 94 differentially expressed genes compared to the control group, with 52 downregulated genes. Moreover, STRING analyses were used to reveal the protein interactions encoded by 36 genes. Then, we verified three significant virulence genes by qRT-PCR, including capsular polysaccharide synthesis enzyme (cp8F), capsular polysaccharide biosynthesis protein (cp5D), and thermonuclease (nuc). Furthermore, molecular docking analysis was performed to investigate the action site of BITC with the encoded proteins of cp8F, cp5D, and nuc. The results showed that the docking fraction of BITC with selected proteins ranged from - 6.00 to - 6.60 kcal/mol, predicting the stability of these complexes. BITC forms hydrophobic, hydrogen-bonded, π-π conjugated interactions with amino acids TRP (130), GLY (10), ILE (406), LYS (368), TYR (192), and ARG (114) of these proteins. These findings will aid future research into the antibacterial effects of BITC against S. aureus.

Identification of circular RNA-Dcaf6 as a therapeutic target for optic nerve crush-induced RGC degeneration.

The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.

Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice.

Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.

Metabolomic profiling of a neurodegenerative retina following optic nerve transection.

The degeneration of retinal ganglion cells (RGCs) often causes irreversible vision impairment. Prevention of RGC degeneration can prevent or delay the deterioration of visual function. The present study aimed to investigate retinal metabolic profiles following optic nerve transection (ONT) injury and identify the potential metabolic targets for the prevention of RGC degeneration. Retinal samples were dissected from ONT group and non­ONT group. The untargeted metabolomics were carried out using liquid chromatography­tandem mass spectrometry. The involved pathways and biomarkers were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and MetaboAnalyst 5.0. In the ONT group, 689 disparate metabolites were detected, including lipids and lipid­like molecules. A total of 122 metabolites were successfully annotated and enriched in 50 KEGG pathways. Among them, 'sphingolipid metabolism' and 'primary bile acid biosynthesis' were identified involved in RGC degeneration. A total of five metabolites were selected as the candidate biomarkers for detecting RGC degeneration with an AUC value of 1. The present study revealed that lipid­related metabolism was involved in the pathogenesis of retinal neurodegeneration. Taurine, taurochenodesoxycholic acid, taurocholic acid (TCA), sphingosine, and galabiosylceramide are shown as the promising biomarkers for the diagnosis of RGC degeneration.

For the Good of the People: an interpretive analysis of Chinese volunteerism in the critical matter of care at the start of the pandemic.

PURPOSE: China employed a unique volunteerism system where health care providers outside of Hubei Province, the epicentre, travelled to reverse the devastation wrought by coronavirus disease 2019 (COVID-19) at its global onset. The aim is to study the unique circumstances of Chinese volunteerism in the context of continuing pandemic threats, specifically exploring the experiences of 20 Chinese nurse and physician volunteers fighting COVID-19 during the outbreak. METHODS: Interviews were done through video calling. RESULTS: Using content analysis with a hermeneutic perspective, emerging patterns showed the ways in which China's particular manifestation of volunteerism teaches us how to engage global threats of this nature. The overarching lesson, For the Good of the People, was manifested in several dynamic and overlapping themes: 1) Reaching for Professional Standards Even in Crisis; 2) Constantly Caring Through Failures and Successes; and 3) Holding Fast to the Common Good. The devastation was met by the resilience of volunteers, who overcame profound challenges managing patient care. CONCLUSIONS: Volunteerism required sacrifice and tremendous support in the form of training and administrative direction, family support, and peer collaboration. Volunteers' physical and psychosocial wellbeing was a priority. Recognizing the representative themes can help societies plan for continuing and future events.

EYE-503: A Novel Retinoic Acid Drug for Treating Retinal Neurodegeneration.

Retinal neurodegeneration is a major cause of vision loss. Retinoic acid signaling is critical for the maintenance of retinal function, and its dysfunction can cause retinal neurodegeneration. However, the therapeutic effects of retinoic acid drugs on retinal neurodegeneration remain unclear. In this study, we designed a novel retinoic acid drug called EYE-503 and investigated its therapeutic effects of EYE-503 on retinal neurodegeneration. The optic nerve crush (ONC) model was selected for the retinal neurodegeneration study. H&E staining, TUNEL staining, immunofluorescence staining, and visual electrophysiology assays were performed to determine the role of EYE-503 in retinal neurodegeneration in vivo. The CCK-8 assay, EdU incorporation assay, PI staining, and flow cytometry assays were performed to investigate the effects of EYE-503 administration on retinal neurodegeneration in vitro. The potential mechanism of EYE-503 in retinal neurodegeneration was investigated by network pharmacology and Western blots. The results showed that EYE-503 administration had no detectable cytotoxicity and tissue toxicity. EYE-503 administration alleviated ONC-induced retinal injury and optic nerve injury in vivo. EYE-503 administration attenuated retinal ganglion cell apoptosis, inhibited reactive gliosis, and retarded the progression of retinal neurodegeneration. Mechanistically, EYE-503 regulated retinal neurodegeneration by targeting the JNK/p38 signaling pathway. This study suggests that EYE-503 is a promising therapeutic agent for retinal neurodegenerative diseases.

Functional Chitosan-Based Composite Film Incorporated with 3-(Methylthio) Propyl Isothiocyanate/α-Cyclodextrin Inclusion Complex for Chicken Meat Preservation.

The 3-(Methylthio) propyl isothiocyanate (MTPITC)-loaded inclusion complex prepared by α-cyclodextrin (α-CD) was incorporated into chitosan (CS) film to fabricate a packaging material for fresh chicken meat preservation. Scanning electron microscope images indicated homogenous dispersion of the MTPITC-α-CD in CS polymer. Fourier-transform infrared and X-ray diffraction techniques revealed that MTPITC-α-CD was incorporated into the CS film matrix by the physical interactions. The introduction of MTPITC-α-CD improved the UV-vis light-blocking ability, with a slight loss of transparency. Although the water solubility and water vapor barrier capacity were not significantly influenced by the addition of MTPITC-α-CD, the antioxidant attribute was significantly enhanced. The CS-MTPITC-α-CD film displayed obvious and sustained suppressive effects against Salmonella typhimurium, with the inhibition zone diameters of 14.7 mm at 12 h and 7.3 mm at 24 h, respectively. Moreover, the quality index analysis indicated that the CS-MTPITC-α-CD film-wrapped fresh chicken, during refrigerated storage, exhibited better preservative efficacy than the control groups, with the total viable counts of 6.5 Log CFU/g, total volatile base nitrogen of 8.4 mg/100 g, pH of 6.6, thiobarbituric acid-reactive substances of 0.2 mg/kg, and the sensory score of 5 at day 16. Collectively, these results suggest that CS-MTPITC-α-CD film is a prospective packaging candidate for delaying the quality deterioration of chicken meat.

The extraction of polycyclic aromatic hydrocarbons from water samples with aromatic-dithiocarbamate modified magnetic nanoparticles.

Considering the urgent need for the analysis of trace-level pollutants in water samples, the pre-concentration of micropollutants in water samples has been the focus of extensive research. Among current pretreatment methods, the solid phase extraction (SPE) technique has received enormous attention because of its low cost, ease of operation and high efficiency. In this work, a new adsorbent (Fe3O4@Au@DTC NPs) was acquired through modification of Fe3O4 nanoparticles (NPs) with gold (Au) and dithiocarbamate (DTC). To investigate their application ability, the adsorbent were utilized as an SPE adsorbent to enrich polycyclic aromatic hydrocarbons in water (PAHs, fluoranthene, pyrene, benzo anthracene, benzo fluoranthene, benzo pyrene). The obtained Fe3O4@Au@DTC NPs were confirmed by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), and UV-Vis spectrum. Under optimal conditions, the calibration curves were obtained in the range of 10-500 ng L-1, while the limit of detection (LOD) ranged in 1.17-2.31 ng L-1. Furthermore, 50 mg of Fe3O4@Au@DTC NPs could extract trace PAHs from 500 mL real water samples into 1 mL eluent, and the spiked recoveries of five PAHs in river water and tap water reached 72-106% with relative standard deviations varying between 3.3-5.18%. Through the conversion of amines into DTC, we acquire desiring group modified Fe3O4 NPs, which showed great prospects in magnetic solid-phase extraction sphere and environmental field.

Regulatory effect of long-stranded non-coding RNA-CRNDE on neurodegeneration during retinal ischemia-reperfusion.

Ischemia/reperfusion (I/R) injury is a common pathological mechanism involved in many ocular diseases. I/R is characterized by microvascular dysfunction and neurodegeneration. However, the mechanisms of neurodegeneration induced by I/R remain largely unknown. This study showed that the expression of long non-coding RNA-CRNDE was significantly upregulated after retinal ischemia-reperfusion (RIR). LncRNA-CRNDE knockdown alleviated retinal neurodegeneration induced by RIR injury, as shown by decreased reactive gliosis and reduced retinal cells loss. Furthermore, lncRNA-CRNDE knockdown directly regulated Müller cell function and indirectly affected RGC function in vitro. In addition, lncRNA-CRNDE knockdown led to a significant reduction in the release of several cytokines after RIR. This study suggests that lncRNA-CRNDE is a promising therapeutic target for RIR.

A Bioactive Chitosan-Based Film Enriched with Benzyl Isothiocyanate/α-Cyclodextrin Inclusion Complex and Its Application for Beef Preservation.

A bioactive packaging material based on chitosan (CS) incorporated with benzyl isothiocyanate (BITC) and α-cyclodextrin (α-CD) was fabricated to evaluate its preservative effects on fresh beef stored at 4 °C for 12 d according to the quality analysis. The Fourier-transform infrared (FTIR) spectrum revealed that the major structural moiety of BITC was embedded in the cavity of α-CD, except for the thiocyanate group. FTIR and X-ray diffraction analysis further verified that intermolecular interactions were formed between the BITC-α-CD and CS film matrix. The addition of BITC-α-CD decreased the UV light transmittance of pure CS film to lower than 63% but still had enough transparency for observing packaged items. The CS-based composite film displayed a sustainable antibacterial capacity and an enhanced antioxidant activity. Moreover, the total viable counts, total volatile base nitrogen, pH, thiobarbituric acid-reactive substances, and sensory evaluation of the raw beef treated with the CS-based composite film were 6.31 log colony-forming unit (CFU)/g, 19.60 mg/100 g, 6.84, 0.26 mg/kg, and 6.5 at 12 days, respectively, indicating the favorable protective efficacy on beef. These results suggested that the fabricated CS-based composite film has the application potential to be developed as a bioactive food packaging material, especially for beef preservation.

Involvement of transient receptor potential channels in ocular diseases: a narrative review.

Background and Objective: Transient receptor potential (TRP) channels are a superfamily of functionally diverse and widely expressed cation channels which exhibit complex regulatory patterns and sensitivity to multiple environmental factors. The involvement of these ion channels is critical in various physiological functions and pathophysiological conditions. In recent decades, a growing number of studies have identified the essential role that TRP channels play in many ocular diseases. In this study, we performed a narrative review of research on the expression and function of TRP channels in various eye diseases. Methods: PubMed, Google Scholar, and Web of Science were searched for all relevant original papers and reviews published from database inception to January 31, 2022. Searches were conducted using the related keywords 'transient receptor potential channels', 'TRPs', 'Ca2+ signaling', 'iron channel', 'TRPV4', 'TRPM1', 'retina', 'optic nerve', 'cornea', 'retinal ganglion cells', 'ON-bipolar', 'TRPs and retina', 'TRP channel and retinal ganglion cells', 'TRPs and cornea', 'diabetes', 'glaucoma', 'dry eye disease', 'cataract', 'retinopathy of prematurity', 'retinoblastoma', and 'congenital stationary night blindness'. Key Content and Findings: In this narrative review, we summarize the history of TRP channels and introduce the TRP channel-related literature in eye disease. Next, we discuss the molecular mechanisms of TRP channels in various eye diseases and suggest future research directions. Conclusions: The relevant studies indicate that TRP channels play vital roles in various eye diseases. However, considerable work is needed to more fully understand the functional and mechanistic aspects of how TRP channels contribute to the pathophysiology of eye disease, especially in the context of animal models and patients. Further investigations will aid in the development of future drugs targeting TRP channels for eye diseases.

Targeting long noncoding RNA-AQP4-AS1 for the treatment of retinal neurovascular dysfunction in diabetes mellitus.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness in the working-age population, which is characterized by retinal neurodegeneration and vascular dysfunction. Long non-coding RNAs (LncRNAs) have emerged as critical regulators in several biological processes and disease progression. Here we investigated the role of lncRNA AQP4-AS1 in retinal neurovascular dysfunction induced by diabetes. METHODS: Quantitative RT-PCR was used to detect the AQP4-AS1 expression pattern upon diabetes mellitus-related stresses. Visual electrophysiology examination, TUNEL staining, Evans blue staining, retinal trypsin digestion and immunofluorescent staining were conducted to detect the role of AQP4-AS1 in retinal neurovascular dysfunction in vivo. MTT assays, TUNEL staining, PI/Calcein-AM staining, EdU incorporation assay transwell assay and tube formation were conducted to detect the role of AQP4-AS1 in retinal cells function in vitro. qRT-PCR, western blot and in vivo studies were conducted to reveal the mechanism of AQP4-AS1-mediated retinal neurovascular dysfunction. FINDINGS: AQP4-AS1 was significantly increased in the clinical samples of diabetic retinopathy patients, high glucose-treated Müller cells, and diabetic retinas of a murine model. AQP4-AS1 silencing in vivo alleviated retinal neurodegeneration and vascular dysfunction as shown by improved retinal capillary degeneration, decreased reactive gliosis, and reduced RGC loss. AQP4-AS1 directly regulated Müller cell function and indirectly affected endothelial cell and RGC function in vitro. Mechanistically, AQP4-AS1 regulated retinal neurovascular dysfunction through affecting AQP4 levels. INTERPRETATION: This study reveals AQP4-AS1 is involved in retinal neurovascular dysfunction and expected to become a promising target for the treatment of neurovascular dysfunction in DR. FUNDING: This work was generously supported by the grants from the National Natural Science Foundation of China (Grant No. 81800858, 82070983, 81870679 and 81970823), grants from the Medical Science and Technology Development Project Fund of Nanjing (Grant No ZKX17053 and YKK19158), grants from Innovation Team Project Fund of Jiangsu Province (No. CXTDB2017010), and the Science and Technology Development Plan Project Fund of Nanjing (Grant No 201716007, 201805007 and 201803058).

Variations in Patient Safety Climate in Chinese Hospitals.

OBJECTIVES: Patient safety climate is associated with patient outcomes in hospitals around the world. A better understanding of how safety climate varies within and across hospitals will help identify improvement opportunities. We examined variations in safety climate by work area and job category in Chinese hospitals. METHODS: We administered the Chinese Hospital Survey on Patient Safety Climate in 2011 to workers in 6 hospitals in China, with completed surveys from 1464 (86% response). We calculated the percent positive response for survey items and dimensions among hospitals and compared this across work areas and job categories using general linear models. RESULTS: Overall, 68% of responses suggested the presence of a positive safety climate. The percent positive responses were highest for organizational learning (86.1%) and unit management support for safety (84.5%) and lowest for staffing (30.6%) and error reporting (44.5%). Workers in surgical units, intensive care units, operating rooms, and emergency departments were slightly more negative regarding overall safety climate than those in medical and ancillary units. Physicians reported worse perceptions than nurses or other hospital workers on all dimensions except for unit management support for safety and communication and peer support. CONCLUSIONS: The perceived problem with staffing in Chinese hospitals was consistent with other studies. The lack of positive responses for error reporting may indicate a lack of awareness of the importance of learning from and reporting minor events and near misses. Variations within and across hospitals in safety climate suggest that improvement interventions should be tailored to individual units and professional groups.

Identification of aberrantly expressed circular RNAs in hyperlipidemia-induced retinal vascular dysfunction in mice.

Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.

Perceptions of Facilitators and Barriers to Measuring and Improving Quality in Palliative Care Programs.

OBJECTIVE: To examine perceptions of facilitators and barriers to quality measurement and improvement in palliative care programs and differences by professional and leadership roles. METHODS: We surveyed team members in diverse US and Canadian palliative care programs using a validated survey addressing teamwork and communication and constructs for educational support and training, leadership, infrastructure, and prioritization for quality measurement and improvement. We defined key facilitators as constructs rated ≥4 (agree) and key barriers as those ≤3 (disagree) on 1 to 5 scales. We conducted multivariable linear regressions for associations between key facilitators and barriers and (1) professional and (2) leadership roles, controlling for key program and respondent factors and clustering by program. RESULTS: We surveyed 103 respondents in 11 programs; 45.6% were physicians and 50% had leadership roles. Key facilitators across sites included teamwork, communication, the implementation climate (or environment), and program focus on quality improvement. Key barriers included educational support and incentives, particularly for quality measurement, and quality improvement infrastructure such as strategies, systems, and skilled staff. In multivariable analyses, perceptions did not differ by leadership role, but physicians and nurse practitioners/nurses/physician assistants rated most constructs statistically significantly more negatively than other team members, especially for quality improvement (6 of the 7 key constructs). CONCLUSIONS: Although participants rated quality improvement focus and environment highly, key barriers included lack of infrastructure, especially for quality measurement. Building on these facilitators and measuring and addressing these barriers might help programs enhance palliative care quality initiatives' acceptability, particularly for physicians and nurses.

Effect of 12-Month Resistance Training on Changes in Abdominal Adipose Tissue and Metabolic Variables in Patients with Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To examine the effects of resistance training relative to aerobic training on abdominal adipose tissue and metabolic variables in adults with prediabetes. METHODS: 105 participants with prediabetes were randomized into the resistance training group (RT, n = 35), aerobic training group (AT, n = 35), and control group (CG, n = 35). The participants completed supervised 12-month exercise; the control group followed the primary lifestyle without exercise intervention. The primary outcomes were visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by computed tomography (CT). Secondary outcomes were body composition, lipid profile, and metabolic variables. RESULTS: A total of 93 participants completed the study. There were nonsignificant differences between groups before intervention. After training, VAT decreased significantly in AT and RT compared with CG (P = 0.001 and P = 0.014, respectively). Although no significant difference in SAT was found across groups, SAT decreased significantly over time within each exercise group (all P = 0.001). Increase in muscle mass was greater in RT than that in AT and CG (P = 0.031 and P = 0.045, respectively). Compared with CG, fasting plasma glucose (FPG) decreased significantly in RT and AT (P = 0.003 and P = 0.014, respectively). There was a significant difference in the number of prediabetes who converted to diabetes among AT and RT, as compared with the control group (P = 0.031 and P = 0.011, respectively). No significant differences were observed in lipid, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin (FI), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), HOMA-IR, and HOMA-ß across groups. CONCLUSION: Both aerobic training and resistance training are effective in reducing abdominal adipose tissue and fasting plasma glucose in adults with prediabetes. Importantly, resistance training but not aerobic training is effective in augmenting muscle mass. TRIAL REGISTRATION: The trial is registered with NCT02561377 (date of registration: 24/09/2015).

Patient isolation for infection control and patient experience.

OBJECTIVE: Hospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication. DESIGN: Retrospective analysis of HCAHPS survey results over 5 years. SETTING: A 1,165-bed, tertiary-care, academic medical center. PATIENTS: Patients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls. METHODS: Multivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and "top-box" experience scores. Dose response to increasing percentage of days in isolation was also analyzed. RESULTS: Patients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed. CONCLUSION: Isolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.

Warfarin use and the risk of stroke, bleeding, and mortality in older adults on dialysis with incident atrial fibrillation.

AIM: There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear. METHODS: Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight. RESULTS: Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03). CONCLUSION: Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.