5 research outputs found

    Crystallization of citrate-stabilized amorphous calcium phosphate to nanocrystalline apatite : a surface-mediated transformation

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    This work explores the mechanisms underlying the crystallization of citrate-functionalized amorphous calcium phosphate (cit-ACP) in two relevant media, combining in situand ex situ characterization techniques. Results demonstrate that citrate desorption from cit-ACP triggers the surface-mediated transformation to nanocrystalline apatite (Ap). Our findings shed light on the key role of citrate, an important component of bone organic matrix, and the medium composition in controlling the rate of transformation and the morphology of the resulting Ap phase

    Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

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    Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

    Nanoparticulate hydroxyapatite and calcium-based CO2 sorbents

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    This thesis is focused on the development of synthesis and characterisation protocols for two different nanoparticulate materials; hydroxyapatite (HA), a biomaterial well recognised as chemically akin to human bone, and CaO, a material often used for the sequestration of CO2 at elevated temperatures. For the analysis of these materials various bulk and particle level characterisation techniques have been employed, which are complemented by the versatile analytical methods available in the transmission electron microscope (TEM). The first chapter of results reveal that a hydrothermal synthesis route achieved phase-pure nanoparticulate HA with Ca/P atomic ratios close to the stoichiometric target (1.67). Impure HA nanopowders were produced by a sol-gel synthesis route with analysis by X-ray diffraction (XRD) revealing secondary phases of calcium phosphates, CaCO3 and CaO. The Ca/P ratios of each powder were determined at the particle level using TEM with energy dispersive X-ray spectroscopy (TEM-EDX), having first established a threshold electron fluence below which significant electron-beam-induced alteration of the composition of HA does not occur. Results showed a greater variability of particle composition from the sol-gel preparation route compared to the hydrothermal route. This technique provides results in reasonable agreement to bulk Ca/P ratio analysis carried out by X-ray fluorescence (XRF) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The second component of the thesis relates to the production of nanoparticulate CaO powder sorbents for the sequestration of CO2 gas. The CaO nanopowders were produced by the thermal decomposition of calcium acetate hydrate (CaAc); this process was analysed by thermogravimetric analysis (TGA) and by in-situ hot-stage XRD. The CO2 uptake capability of the CaO powder sorbents was analysed by TGA following the reaction: CaO + CO2 ↔ CaCO3 Results showed a molar conversion ratio, χ (of CaO to CaCO3) of 0.92, after 15 minutes of carbonation with structural analysis by SEM and TEM showing consistent growth and densification of rounded CaCO3 crystals upon carbonation. Multiple cycles of carbonation and decarbonation were then carried out by TGA to investigate sorbent regenerability. A 0.32 decrease in χ was found after 9 cycles which is attributed to the sintering (reduction in surface area) of the sorbent with progressive decarbonations at 800 °C. Structural analysis of decarbonated samples extracted from the TGA, by XRD, SEM and TEM, highlighted the issue of sorbent hydration upon storage, sample preparation and analysis. A TEM based technique has been developed for the structural analysis of multicycle CO2 capture using an ex-situ environmental cell (E-cell). This technique allows for multicycle capture to be carried out and then analysed in the TEM with minimal exposure to the atmosphere, therefore providing a closer microstructural match to what occurs in the TGA. Results showed that slow, low-vacuum decarbonation (in the E-cell) creates a densified ‘skeleton’ of CaO, consistent with the drop in capture capacity observed by TGA. Finally, modifications of CaO sorbents using spacer materials has been carried out with the aim of declining the decay in sorbent performance during multiple cycles of carbonation and decarbonation in the TGA. Promising results were found using CaO sorbents modified a commercial YSZ powder and also with CaZrO3/ZrO2

    Empagliflozin in Patients with Chronic Kidney Disease

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    Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo
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