Trends in the utilisation of emergency departments in California, 2005-2015: a retrospective analysis.

ObjectiveTo examine current trends in the characteristics of patients visiting California emergency departments (EDs) in order to better direct the allocation of acute care resources.DesignA retrospective study.SettingWe analysed ED utilisation trends between 2005 and 2015 in California using non-public patient data from California's Office of Statewide Health Planning and Development.ParticipantsWe included all ED visits in California from 2005 to 2015.Primary and secondary outcome measuresWe analysed ED visits and visit rates by age, sex, race/ethnicity, payer and urban/rural trends. We further examined age, sex, race/ethnicity and urban/rural trends within each payer group for a more granular picture of the patient population. Additionally, we looked at the proportion of patients admitted from the ED and distribution of diagnoses.ResultsBetween 2005 and 2015, the annual number of ED visits increased from 10.2 to 14.2 million in California. ED visit rates increased by 27.8% (p<0.001), with the greatest increases among patients aged 5-19 (37.4%, p<0.001) and 45-64 years (41.1%, p<0.001), non-Hispanic Black and Hispanic patients (56.8% and 48.8%, p<0.001), the uninsured and Medicaid-insured (36.1%, p=0.002; 28.6%, p<0.001) and urban residents (28.3%, p<0.001). The proportion of ED visits resulting in hospitalisation decreased by 18.3%, with decreases across all payer groups.ConclusionsOur findings reveal an increasing demand for emergency care and may reflect current limitations in accessing care in other parts of the healthcare system. Policymakers may need to recognise the increasingly vital role that EDs are playing in the provision of care and consider ways to incorporate this changing reality into the delivery of health services

Do water fountain jets really indicate the onset of the morphological metamorphosis of circumstellar envelopes?

Small-scale bipolar jets with short dynamical ages from 'water-fountain' (WF) sources are regarded as an indication of the onset of circumstellar envelope morphological metamorphosis of intermediate-mass stars. Such a process usually happens at the end of the asymptotic giant branch (AGB) phase. However, recent studies found that WFs could be AGB stars or even early planetary nebulae. This fact prompted the idea that WFs may not necessarily be objects at the beginning of the morphological transition process. In the present work, we show that WFs could have different envelope morphologies by studying their spectral energy distribution profiles. SomeWFs have spherical envelopes that resemble usual AGB stars, while others have aspherical envelopes, which are more common to post-AGB stars. The results imply that WFs may not represent the earliest stage of morphological metamorphosis. We argue further that the dynamical age of a WF jet, which can be calculated from maser proper motions, may not be the real age of the jet. The dynamical age cannot be used to justify the moment when the envelope begins to become aspherical, nor to tell the concrete evolutionary status of the object. A WF jet could be the innermost part of a larger well-developed jet, which is not necessarily a young jet. © 2016 The Authors

Identification of oxygen-rich late/post-asymptotic giant branch stars and water fountains via maser and infrared criteria

The transitional phase between the asymptotic giant branch (AGB) and post-AGB phases holds the key to our understanding of the late-stage metamorphosis of intermediate-mass stars. In particular, high velocity jets forming during this phase are suggested to contribute significantly to the shaping of planetary nebulae. For oxygen-rich stars, the rare "water fountains (WFs)" have been regarded as representative objects in this phase, and it is important to identify more of them for further studies. Here we briefly report the results of our latest OH and H2O maser surveys in which a new WF candidate (IRAS 19356+0754) was found. We also performed radiative transfer modelling on the spectral energy distributions (SEDs) of all known WFs. It is concluded that WFs might in fact not be the transitional objects, as opposed to previous belief. WFs could be AGB or post-AGB stars with no obvious similarities amongst their SEDs. Further efforts are still needed to improve the identification criteria.This work is supported by a grant awarded to JN from the Research Grants Council of Hong Kong (project code: HKU 703308P; HKU 704209P; HKU 704710P)

Effects of Topically Applied Acitretin in Reconstructed Human Epidermis and the Rhino Mouse

Oral acitretin is currently indicated for the treatment of severe psoriasis in adults, but its use is limited by systemic side effects and teratogenicity. Topical administration of acitretin may lessen the risk of systemic toxicity while increasing local bioavailability in the skin. The effects of topical acitretin on reconstructed human epidermis (RHE) and Rhino mice were investigated and compared to those of currently marketed topical retinoids: tretinoin and tazarotene. In acitretin-treated RHE cultures, there was a reduction in keratohyalin granules and filaggrin expression in the stratum granulosum, a loss of keratin 10 expression in the stratum spinosum, and an increase in keratin 19 expression in all viable cell layers. All retinoids showed similar signs of activity in RHE cultures. Furthermore, the release of pro-inflammatory cytokines IL-1α and IL-8 in RHE cultures was less pronounced with acitretin compared to tretinoin- and tazarotene-containing formulations, suggesting that acitretin may be less irritating. In Rhino mice, acitretin induced a local, dose-dependent reduction in utricle diameter after seven daily dermal doses. A similar effect was observed in tretinoin- and tazarotene-treated mice. Our data suggest that topical application of acitretin may have a therapeutic benefit in the local management of keratinization disorders

Collapse of stamps for soft lithography due to interfacial adhesion

Collapse of elastomeric elements used for pattern transfer in soft lithography is studied through experimental measurements and theoretical modehng. The objective is to identify the driving force for such collapse. Two potential driving forces, the self-weight of the stamp and the interfacial adhesion, are investigated. An idealized configuration of periodic rectangular grooves and flat punches is considered. Experimental observations demonstrate that groove collapse occurs regardless of whether the gravitational force promotes or suppresses such collapse, indicating that self-weight is not the driving force. On the other hand, model predictions based on the postulation that interfacial adhesion is the driving force exhibit excellent agreement with the experimentally measured collapse behavior. The interfacial adhesion energy is also evaluated by matching an adhesion parameter in the model with the experimental data.open546

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research

Averages of Fourier coefficients of Siegel modular forms and representation of binary quadratic forms by quadratic forms in four variables

Let $-d$ be a a negative discriminant and let $T$ vary over a set of representatives of the integral equivalence classes of integral binary quadratic forms of discriminant $-d$. We prove an asymptotic formula for $d \to \infty$ for the average over $T$ of the number of representations of $T$ by an integral positive definite quaternary quadratic form and obtain results on averages of Fourier coefficients of linear combinations of Siegel theta series. We also find an asymptotic bound from below on the number of binary forms of fixed discriminant $-d$ which are represented by a given quaternary form. In particular, we can show that for growing $d$ a positive proportion of the binary quadratic forms of discriminant $-d$ is represented by the given quaternary quadratic form.Comment: v5: Some typos correcte

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen

Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study

INTRODUCTION: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial. METHODS: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression. RESULTS: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52. CONCLUSIONS: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02186873

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study

© 2021 Elsevier Inc. Background: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. Study Design: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. Conclusions: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19