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

Ten-year trends in traumatic brain injury: a retrospective cohort study of California emergency department and hospital revisits and readmissions.

OBJECTIVE:To describe visits and visit rates of adults presenting to emergency departments (EDs) with a diagnosis of traumatic brain injury (TBI). TBI is a major cause of death and disability in the USA; yet, current literature is limited because few studies examine longer-term ED revisits and hospital readmission patterns of TBI patients across a broad spectrum of injury severity, which can help inform potential unmet healthcare needs. DESIGN:We performed a retrospective cohort study. SETTING:We analysed non-public patient-level data from California's Office of Statewide Health Planning and Development for years 2005 to 2014. PARTICIPANTS:We identified 1.2 million adult patients aged ≥18 years presenting to California EDs and hospitals with an index diagnosis of TBI. PRIMARY AND SECONDARY OUTCOME MEASURES:Our main outcomes included revisits, readmissions and mortality over time. We also examined demographics, mechanism and severity of injury and disposition at discharge. RESULTS:We found a 57.7% increase in the number of TBI ED visits, representing a 40.5% increase in TBI visit rates over the 10-year period (346-487 per 100 000 residents). During this time, there was also a 33.8% decrease in the proportion of patients admitted to the hospital. Older, publicly insured and black populations had the highest visit rates, and falls were the most common mechanism of injury (45.5% of visits). Of all patients with an index TBI visit, 40.5% of them had a revisit during the first year, with 46.7% of them seeking care at a different hospital from their initial hospital or ED visit. Additionally, of revisits within the first year, 13.4% of them resulted in hospital readmission. CONCLUSIONS:The large proportion of patients with TBI who are discharged directly from the ED, along with the high rates of revisits and readmissions, suggest a role for an established system for follow-up, treatment and care of TBI

Shigella sonnei oligosaccharide-protein conjugates

AbstractSynthetic oligosaccharides composed of several repeats of Shigella dysenteriae type 1 O-specific polysaccharide (O-SP), bound by their reducing ends to a carrier protein (“sun” type configuration), induced in mice significantly higher antibody levels than conjugates of the native O-SP (“lattice” type configuration). Here we present isolation and characterization of low molecular mass oligosaccharides of Shigella sonnei lipopolysaccharides and their conjugation to several carrier proteins. Conjugates were formed by oxime linkages between the terminal Kdo residues of the reducing ends of the saccharides and aminooxy linkers bound to the protein. IgG antibody levels induced in young outbread mice by these conjugates were significantly higher than those prepared with the full length native O-SP. We propose clinical evaluation of the new S. sonnei conjugates

Effect of nano-structural properties of biomimetic hydroxyapatite on osteoimmunomodulation

Immune cells are sensitive to the microstructural and textural properties of materials. Tuning the structural features of synthetic bone grafts could be a valuable strategy to regulate the specific response of the immune system, which in turn modulates the activity of bone cells. The aim of this study was to analyse the effect of the structural characteristics of biomimetic calcium deficient hydroxyapatite (CDHA) on the innate immune response of macrophages and the subsequent impact on osteogenesis and osteoclastogenesis. Murine RAW 264.7¿cells were cultured, under standard and inflammatory conditions, on chemically identical CDHA substrates that varied in microstructure and porosity. The impact on osteogenesis was evaluated by incubating osteoblastic cells (SaOS-2) with RAW-CDHA conditioned extracts. The results showed that macrophages were sensitive to different textural and structural properties of CDHA. Under standard conditions, the impact of inflammatory cytokine production by RAW cells cultured on CDHA played a significant role in the degradation of substrates, suggesting the impact of resorptive behaviour of RAW cells on biomimetic surfaces. Osteoblast differentiation was stimulated by the conditioned media collected from RAW cells cultured on needle-like nanostructured CDHA. The results demonstrated that needle-like nanostructured CDHA was able to generate a favourable osteoimmune environment to regulate osteoblast differentiation and osteogenesis. Under inflammatory conditions, the incubation of RAW cells with less porous CDHA resulted in a decreased gene expression and release of pro-inflammatory cytokines.Peer ReviewedPostprint (author's final draft

Phase of Illness in palliative care: Cross-sectional analysis of clinical data from community, hospital and hospice patients

© 2017, © The Author(s) 2017. Background: Phase of Illness describes stages of advanced illness according to care needs of the individual, family and suitability of care plan. There is limited evidence on its association with other measures of symptoms, and health-related needs, in palliative care. Aims: The aims of the study are as follows. (1) Describe function, pain, other physical problems, psycho-spiritual problems and family and carer support needs by Phase of Illness. (2) Consider strength of associations between these measures and Phase of Illness. Design and setting: Secondary analysis of patient-level data; a total of 1317 patients in three settings. Function measured using Australia-modified Karnofsky Performance Scale. Pain, other physical problems, psycho-spiritual problems and family and carer support needs measured using items on Palliative Care Problem Severity Scale. Results: Australia-modified Karnofsky Performance Scale and Palliative Care Problem Severity Scale items varied significantly by Phase of Illness. Mean function was highest in stable phase (65.9, 95% confidence interval = 63.4–68.3) and lowest in dying phase (16.6, 95% confidence interval = 15.3–17.8). Mean pain was highest in unstable phase (1.43, 95% confidence interval = 1.36–1.51). Multinomial regression: psycho-spiritual problems were not associated with Phase of Illness (χ 2 = 2.940, df = 3, p = 0.401). Family and carer support needs were greater in deteriorating phase than unstable phase (odds ratio (deteriorating vs unstable) = 1.23, 95% confidence interval = 1.01–1.49). Forty-nine percent of the variance in Phase of Illness is explained by Australia-modified Karnofsky Performance Scale and Palliative Care Problem Severity Scale. Conclusion: Phase of Illness has value as a clinical measure of overall palliative need, capturing additional information beyond Australia-modified Karnofsky Performance Scale and Palliative Care Problem Severity Scale. Lack of significant association between psycho-spiritual problems and Phase of Illness warrants further investigation

Frameshift Mutagenesis and Microsatellite Instability Induced by Human Alkyladenine DNA Glycosylase

Human alkyladenine DNA glycosylase (hAAG) excises alkylated purines, hypoxanthine, and etheno bases from DNA to form abasic (AP) sites. Surprisingly, elevated expression of hAAG increases spontaneous frameshift mutagenesis. By random mutagenesis of eight active site residues, we isolated hAAG-Y127I/H136L double mutant that induces even higher rates of frameshift mutation than does the wild-type hAAG; the Y127I mutation accounts for the majority of the hAAG-Y127I/H136L-induced mutator phenotype. The hAAG-Y127I/H136L and hAAG-Y127I mutants increased the rate of spontaneous frameshifts by up to 120-fold in S. cerevisiae and also induced high rates of microsatellite instability (MSI) in human cells. hAAG and its mutants bind DNA containing one and two base-pair loops with significant affinity, thus shielding them from mismatch repair; the strength of such binding correlates with their ability to induce the mutator phenotype. This study provides important insights into the mechanism of hAAG-induced genomic instability.National Institutes of Health (U.S.) (Grant CA055042)National Institutes of Health (U.S.) (Grant CA115802)National Institutes of Health (U.S.) (Grant ES02109

The effect of biomimetic calcium deficient hydroxyapatite and sintered ß-tricalcium phosphate on osteoimmune reaction and osteogenesis

Biomaterial implantation triggers inflammatory reactions. Understanding the effect of physicochemical features of biomaterials on the release of inflammatory cytokines from immune cells would be of great interest in view of designing bone graft materials to enhance the healing of bone defects. The present work investigated the interactions of two chemically and texturally different calcium phosphate (CaPs) substrates with macrophages, one of the main innate immune cells, and its further impact on osteogenic differentiation of bone forming cells. The behaviour of macrophages seeded on biomimetic calcium deficient hydroxyapatite (CDHA) and sintered ß-tricalcium phosphate (ß-TCP) was assessed in terms of the release of inflammatory cytokines and osteoclastogenic factors. The osteogenic differentiation of bone progenitor cells (bone marrow stromal cells (BMSCs) and osteoblastic cell line (SaOS-2)) were subsequently studied by incubating with the conditioned medium induced by macrophage-CaPs interaction in order to reveal the effect of immune cell reaction to CaPs on osteogenic differentiation. It was found that the incubation of macrophages with CaPs substrates caused a decrease of pro-inflammatory cytokines, more pronounced for ß-TCP compared with CDHA showing significantly decreased IL-6, TNF-a, and iNOS. However, the macrophage-CDHA interaction resulted in a more favourable environment for osteogenic differentiation of osteoblasts with more collagen type I production and osteogenic genes (Runx2, BSP) expression, suggesting that osteogenic differentiation of bone cells is not only determined by the nature of biomaterials, but also significantly influenced by the inflammatory environment generated by the interaction of immune cells and biomaterials.Peer ReviewedPostprint (author's final draft

Green Technology and Sustainable Development: Assessment and Green Growth Frameworks

The aim of this study is to investigate the characteristics of a sustainable development assessment methodology being designed in the context of green technology. The methodology in question is based on indicators from the Sustainable Development Goals Index (SGDI), specifically in its ecological component. These indicators underlie an Averaging Sustainable Development Index (ASDI) and a Normalized Sustainable Development Index (NSDI). The resultant methodology was applied to 20 countries from the SDGI ranking. According to the research results, the intensive activity of the brown industries in the United Arab Emirates, Kazakhstan, the United States, Korea, and Russia resulted in significant carbon dioxide emissions. Switzerland, Kazakhstan, and Russia had high scores on sustainable management of water and sanitation. Russia was the only developed country to have an ASDI higher than its SDGI and its gap between NSDI and ASDI indexes was not significant, indicating a positive trend in greentech development. The reason why NSDI was increasingly different from SDGI was that countries leading the socio-economic rankings had higher consumption of energy and resources, and a much greater environmental footprint than those countries that consumed less. The originality of this study is that it identifies gaps between NSDI and ASDI values, which indicate that conditions for greentech adoption in most developing countries are unfavorable

Perspectives of patients, family caregivers and health professionals on the use of outcome measures in palliative care and lessons for implementation: a multi-method qualitative study

Background: Routine use of outcome measures in palliative care is recommended to demonstrate and improve quality of care. The use of outcome measures is relatively recent in UK specialist palliative care services and understanding their use in practice is key to successful implementation. We therefore aimed to explore how patient-centred outcome measures are used in specialist palliative care, and identify key considerations for implementation.Methods: Multi-method qualitative study (semi-structured interviews and non-participant observation). Patients, family caregivers and health professionals were purposively sampled from nine specialist palliative care services (hospice, hospital and community settings) in London, UK. Framework analysis, informed by the Consolidated Framework for Implementation Research (CFIR), was undertaken.Results: Thirty eight interviews and nine observations were conducted. Findings are presented according to the five CFIR domains: 1) Intervention: participants highlighted advantages, disadvantages and appropriateness of outcome measures in palliative care; 2) Outer setting: policy and national drivers are necessary to encourage use of outcome measures; 3) Inner setting: information technology infrastructure, organisational drive, and support from peers and leadership were institutional factors that shaped the use of outcome measures; 4) Individual: clear rationale for using outcome measures and skills to use them in practice were essential; 5) Implementation: stepwise introduction of outcome measures, regular feedback sessions, and champions/facilitators were important to strengthen routine use.Conclusion: All CFIR domains need consideration for effective implementation. Outcome data needs to be fed back to and interpreted for professionals in order to improve and sustain outcome data collection, and drive meaningful improvements in palliative care

Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor

Producción CientíficaThe earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ–CD8 interactions require CD8–MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules