An Overview of the Impact of the Covid-19 Pandemic on the Provision of Palliative Care.

The Sars-Cov-2 pandemic had an immeasurable impact on the provision of palliative care in Ireland, and continues to do so. Patients and families were affected by stringent infectious disease measures. Healthcare professionals were also impacted, with recent research demonstrating the psychological impact that the pandemic had on some of those working in palliative care during the pandemic. The services provided by palliative care services also shifted. Many patients opted to stay at home to receive end-of-life care or symptom management from their GP and community palliative homecare teams where possible. Palliative care services in the acute hospital setting were increasingly utilised to support teams to provide end-of-life care in a developing and challenging clinical environment. Communication technology was used to for multidisciplinary team meetings, to communicate with families and by community home care teams for some patient assessments. Our article outlines some of the major ways in which palliative care was impacted by the Sars-Cov-2 pandemic.

Anticholinergic drug use and risk of mortality for people with dementia in Northern Ireland.

OBJECTIVE: Anticholinergic burden refers to the cumulative effect of medications which contain anticholinergic properties. We assessed how anticholinergic burden and different types of anticholinergic medications influence mortality rates among people with dementia in Northern Ireland. Our secondary aim was to determine what demographic characteristics predict the anticholinergic burden of people with dementia. METHODS: Data were extracted from the Enhanced Prescribing database for 25,418 people who were prescribed at least one dementia management medication between 2010 and 2016. Information was also extracted on the number of times each available anticholinergic drug was prescribed between 2010 and 2016, allowing the calculation of an overall anticholinergic burden. Cox proportional hazard models were used to determine how anticholinergic burden influenced mortality whilst multilevel model regression determined what demographic characteristics influence overall anticholinergic burden. RESULTS: Of the 25,418 people with dementia, only 15% (n = 3880) had no anticholinergic burden. Diazepam (42%) and risperidone (18%) were the two most commonly prescribed drugs. Unadjusted Cox proportional hazard models indicated that higher anticholinergic burden was associated with significantly higher mortality rates in comparison to people with dementia who had no anticholinergic burden (HR = 1.59: 95% CI = 1.07-2.36). In particular, urological (HR = 1.20: 95% CI = 1.05-1.38) and respiratory (HR = 1.17: 95% CI = 1.08-1.27) drugs significantly increased mortality rates. People with dementia living in areas with low levels of deprivation had significantly lower anticholinergic burden (HR=-.39: 95% CI=-.47:-30). CONCLUSIONS: Reducing anticholinergic burden is essential for people with dementia. Further research should address the unfavourable prognosis of people living with dementia in highly deprived areas.

A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10-5 ). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.

Correction to: Process-induced degradation of bioresorbable PDLGA in bone tissue scaffold production.

The original version of this article unfortunately contained a mistake. E. Themistou was missing from the author group and so is now included with this erratum.

Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005-2014: The HITS-p study.

Hepatitis C virus (HCV) transmission is high in prisons. This study investigated trends in HCV incidence and associated factors among a cohort of prisoners with a history of injecting drug use in New South Wales, Australia. Data were available from the Hepatitis C Incidence and Transmission Study-prisons (HITS-p) from 2005 to 2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion among people with ongoing injecting was assessed using Cox proportional hazards. Among 320 antibody-negative participants with a history of injecting drug use (mean age 26; 72% male), 62% (n=197) reported injecting drug use during follow-up. Overall, 93 infections were observed. HCV incidence was 11.4/100 person-years in the overall population and 6.3/100 person-years among the continually imprisoned population. A stable trend in HCV incidence was observed. Among the overall population with ongoing injecting during follow-up, ≥weekly injecting drug use frequency was independently associated with time to HCV seroconversion. Among continuously imprisoned injectors with ongoing injecting during follow-up, needle/syringe sharing was independently associated with time to HCV seroconversion. This study demonstrates that prison is a high-risk environment for acquisition of HCV infection. Needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. These findings highlight the need for the evaluation of improved HCV prevention strategies in prison, including needle/syringe programmes and HCV treatment.

Between-individual variation in nematode burden among juveniles in a wild host.

Parasite infection in young animals can affect host traits related to demographic processes such as survival and reproduction, and is therefore crucial to population viability. However, variation in infection among juvenile hosts is poorly understood. Experimental studies have indicated that effects of parasitism can vary with host sex, hatching order and hatch date, yet it remains unclear whether this is linked to differences in parasite burdens. We quantified gastrointestinal nematode burdens of wild juvenile European shags (Phalacrocorax aristotelis) using two in situ measures (endoscopy of live birds and necropsy of birds that died naturally) and one non-invasive proxy measure (fecal egg counts (FECs)). In situ methods revealed that almost all chicks were infected (98%), that infections established at an early age and that older chicks hosted more worms, but FECs underestimated prevalence. We found no strong evidence that burdens differed with host sex, rank or hatch date. Heavier chicks had higher burdens, demonstrating that the relationship between burdens and their costs is not straightforward. In situ measures of infection are therefore a valuable tool in building our understanding of the role that parasites play in the dynamics of structured natural populations.

Process-induced degradation of bioresorbable PDLGA in bone tissue scaffold production.

Process-induced degradation of clinically relevant resorbable polymers was investigated for two thermal techniques, filament extrusion followed by fused deposition modelling (FDM). The aim was to develop a clear understanding of the relationship between temperature, processing time and resultant process-induced degradation. This acts to address the current knowledge gap in studies involving thermal processing of resorbable polymers. Poly(DL-lactide-co-glycolide) (PDLGA) was chosen for its clinically relevant resorption properties. Furthermore, a comparative study of controlled thermal exposure was conducted through compression moulding PDLGA at a selected range of temperatures (150-225 °C) and times (0.5-20 min). Differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) were used to characterise thermally induced degradation behaviour. DSC proved insensitive to degradation effects, whereas GPC demonstrated distinct reductions in molecular weight allowing for the quantification of degradation. A near-exponential pattern of degradation was identified. Through the application of statistical chain scission equations, a predictive plot of theoretical degradation was created. Thermal degradation was found to have a significant effect on the molecular weight with a reduction of up to 96% experienced in the controlled processing study. The proposed empirical model may assist prediction of changes in molecular weight, however, accuracy limitations are highlighted for twin-screw extrusion, accredited to high-shear mixing. The results from this study highlight the process sensitivity of PDLGA and proposes a methodology for quantification and prediction, which contributes to efforts in understanding the influence of manufacture on performance of degradable medical implants.

Osteogenic cell response to 3-D hydroxyapatite scaffolds developed via replication of natural marine sponges.

Bone tissue engineering may provide an alternative to autograft, however scaffold optimisation is required to maximize bone ingrowth. In designing scaffolds, pore architecture is important and there is evidence that cells prefer a degree of non-uniformity. The aim of this study was to compare scaffolds derived from a natural porous marine sponge (Spongia agaricina) with unique architecture to those derived from a synthetic polyurethane foam. Hydroxyapatite scaffolds of 1 cm(3) were prepared via ceramic infiltration of a marine sponge and a polyurethane (PU) foam. Human foetal osteoblasts (hFOB) were seeded at 1 × 10(5) cells/scaffold for up to 14 days. Cytotoxicity, cell number, morphology and differentiation were investigated. PU-derived scaffolds had 84-91% porosity and 99.99% pore interconnectivity. In comparison marine sponge-derived scaffolds had 56-61% porosity and 99.9% pore interconnectivity. hFOB studies showed that a greater number of cells were found on marine sponge-derived scaffolds at than on the PU scaffold but there was no significant difference in cell differentiation. X-ray diffraction and inductively coupled plasma mass spectrometry showed that Si ions were released from the marine-derived scaffold. In summary, three dimensional porous constructs have been manufactured that support cell attachment, proliferation and differentiation but significantly more cells were seen on marine-derived scaffolds. This could be due both to the chemistry and pore architecture of the scaffolds with an additional biological stimulus from presence of Si ions. Further in vivo tests in orthotopic models are required but this marine-derived scaffold shows promise for applications in bone tissue engineering.

Racial disparities with PRN medication usage in inpatient psychiatric treatment.

Racial disparities in psychiatric diagnoses and treatment have significant public health implications, contributing to inequities in healthcare outcomes. We specifically examined racial disparities regarding pro re nata (PRN), or as needed, medications. Data from 14,616 encounters across 2019-2020 within Community Health Network's inpatient psychiatric setting in Indianapolis, Indiana were included in this study. Due to the demographic sample size, analyses were narrowed to Black and White patients. Primary outcomes included comparisons across race for all PRN administrations and PRN administrations of antipsychotics vs. non-antipsychotics. Logistic regression was used to examine associations between race and PRN administrations by medication category, including all antipsychotics vs. non-antipsychotics overall, hydroxyzine, and lorazepam, independently. Significant differences in the percentage of administrations between Black and White patients were observed. Black patients received more PRN medications overall (71.0%) compared to White patients (67.7%) (p < 0.01). Further, while 17.7% of Black patients were administered PRN antipsychotics, this was true for only 8.2% of White patients (p < 0.001). When comparing antipsychotic PRNs with non-antipsychotic, hydroxyzine, and lorazepam PRNs, independently, Black patients were 58% (OR 1.58, p < 0.001), 109% (OR 2.09, p < 0.001), and 32% (OR 1.32, p < 0.001), more likely to receive antipsychotic PRNs, respectively, than White patients, controlling for sex, age, length of stay, and psychotic disorder diagnosis. Our study identifies yet another area of medical care with significant racial disparities. In this analysis of PRN medications during psychiatric admission, we identified significant differences in medication utilization by race. This information provides a basis for further investigation of disparities in patient-centered data.

Nosocomial acquisition of influenza is associated with significant morbidity and mortality: Results of a prospective observational study.

BACKGROUND: Nosocomial acquisition of influenza is known to occur but the risk after exposure to a known case and the outcomes after acquisition are poorly defined. METHODS: Prospective observational study of patients exposed to influenza from another patient in a multi-site healthcare organisation, with follow-up of 7 days or until discharge, and PCR-confirmation of symptomatic disease. Multivariable analysis was used to investigate association of influenza acquisition with high dependency unit/intensive care unit (HDU/ITU) admission and in-hospital mortality. RESULTS: 23/298 (7.7%) contacts of 11 cases were subsequently symptomatic and tested influenza-positive during follow-up. HDU/ITU admission was significantly higher in these secondary cases (6/23, 26%) compared to flu-negative contacts (20/275, 7.2%; p = 0.002). In-hospital mortality was significantly higher in secondary cases (5/23, 21.7%) compared to flu-negative contacts (11/275, 4%; p < 0.001). In multivariable analysis, age (OR 1.25 95% CI: 1.01-1.54, p = 0.02) and being a secondary case (OR 4.77, 95% CI: 1.63-13.9, p = 0.008) were significantly associated with HDU/ITU admission in contacts. Age (OR 1.00, 95% CI: 0.93-1.00, p = 0.02), being a secondary case after exposure to influenza (OR 3.81, 95% CI 1.09-13.3, p = 0.049) and co-morbidity (OR 1.29 per unit increment in the Charlson score, 95% CI 1.02-1.61, p = 0.03) were significantly associated with in-hospital mortality in contacts. CONCLUSIONS: Nosocomial acquisition of influenza was significantly associated with increased risk of HDU/ITU admission and in-hospital mortality.

2D monochromatic x-ray imaging for beam monitoring of an x-ray free electron laser and a high-power femtosecond laser.

In pump-probe experiments with an X-ray Free Electron Laser (XFEL) and a high-power optical laser, spatial overlap of the two beams must be ensured to probe a pumped area with the x-ray beam. A beam monitoring diagnostic is particularly important in short-pulse laser experiments where a tightly focused beam is required to achieve a relativistic laser intensity for generation of energetic particles. Here, we report the demonstration of on-shot beam pointing measurements of an XFEL and a terawatt class femtosecond laser using 2D monochromatic Kα imaging at the Matter in Extreme Conditions end-station of the Linac Coherent Light Source. A thin solid titanium foil was irradiated by a 25-TW laser for fast electron isochoric heating, while a 7.0 keV XFEL beam was used to probe the laser-heated region. Using a spherical crystal imager (SCI), the beam overlap was examined by measuring 4.51 keV Kα x rays produced by laser-accelerated fast electrons and the x-ray beam. Measurements were made for XFEL-only at various focus lens positions, laser-only, and two-beam shots. Successful beam overlapping was observed on ∼58% of all two-beam shots for 10 µm thick samples. It is found that large spatial offsets of laser-induced Kα spots are attributed to imprecise target positioning rather than shot-to-shot laser pointing variations. By applying the Kα measurements to x-ray Thomson scattering measurements, we found an optimum x-ray beam spot size that maximizes scattering signals. Monochromatic x-ray imaging with the SCI could be used as an on-shot beam pointing monitor for XFEL-laser or multiple short-pulse laser experiments.

Real-world deployment of lateral flow SARS-CoV-2 antigen detection in the emergency department to provide rapid, accurate and safe diagnosis of COVID-19.

BACKGROUND: Point-of-care (POC) SARS-CoV-2 lateral-flow antigen detection (LFD) testing in the emergency department (ED) could inform rapid infection control decisions but requirements for safe deployment have not been fully defined. METHODS: Review of LFD test results, laboratory and POC-RT-PCR results and ED-performance metrics during a two-week high SARS-CoV-2 prevalence period followed by several months of falling prevalence. AIM: Determine whether LFD testing can be safely deployed in ED to provide an effective universal SARS-CoV-2 testing capability. FINDINGS: 93% (345/371) of COVID-19 patients left ED with a virological diagnosis during the 2-week universal LFD evaluation period compared to 77% with targeted POC-RT-PCR deployment alone, on background of approximately one-third having an NHS Track and Trace RT-PCR test-result at presentation. LFD sensitivity and specificity was 70.7% and 99.1% respectively providing a PPV of 97.7% and NPV of 86.4% with disease prevalence of 34.7%. ED discharge-delays (breaches) attributable to COVID-19 fell to 33/3532 (0.94%) compared with the preceding POC-RT-PCR period (107/4114 (2.6%); p=<0.0001). Importantly, LFD testing identified 1 or 2 clinically-unsuspected COVID-19 patients/day. Three clinically-confirmed LFD false positive patients were appropriately triaged based on LFD action-card flowchart, and only 5 of 95 false-negative LFD results were inappropriately admitted to non-COVID-19 areas where no onward-transmission was identified. LFD testing was restricted to asymptomatic patients when disease prevalence fell below 5% and detected 1-3 cases/week. CONCLUSION: Universal SARS-CoV-2 LFD testing can be safely and effectively deployed in ED alongside POC-RT-PCR testing during periods of high and low disease prevalence.

Measuring the structure and equation of state of polyethylene terephthalate at megabar pressures.

We present structure and equation of state (EOS) measurements of biaxially orientated polyethylene terephthalate (PET, [Formula: see text], also called mylar) shock-compressed to ([Formula: see text]) GPa and ([Formula: see text]) K using in situ X-ray diffraction, Doppler velocimetry, and optical pyrometry. Comparing to density functional theory molecular dynamics (DFT-MD) simulations, we find a highly correlated liquid at conditions differing from predictions by some equations of state tables, which underlines the influence of complex chemical interactions in this regime. EOS calculations from ab initio DFT-MD simulations and shock Hugoniot measurements of density, pressure and temperature confirm the discrepancy to these tables and present an experimentally benchmarked correction to the description of PET as an exemplary material to represent the mixture of light elements at planetary interior conditions.

Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling.

Stimulation of phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis is a widespread mechanism for receptor-mediated signaling in eukaryotes. Cytosolic phosphatidylinositol transfer protein (PITP) is necessary for guanosine triphosphate (GTP)-dependent hydrolysis of PIP2 by phospholipase C-beta (PLC-beta), but the role of PITP is unclear. Stimulation of phospholipase C-gamma (PLC-gamma) in A431 human epidermoid carcinoma cells treated with epidermal growth factor (EGF) required PITP. Stimulation of PI-4 kinase in cells treated with EGF also required PITP. Coprecipitation studies revealed an EGF-dependent association of PITP with the EGF receptor, with PI-4 kinase, and with PLC-gamma.

Phospholipase D: a downstream effector of ARF in granulocytes.

Activation of the phospholipase D (PLD) pathway is a widespread response when cells are activated by agonists that bind receptors on the cell surface. A 16-kD cytosolic component can reconstitute guanosine triphosphate (GTP)-mediated activation of phospholipase D in HL60 cells depleted of their cytosol by permeabilization. This factor was purified and identified as two small GTP-binding proteins, ARF1 and ARF3. Recombinant ARF1 substituted for purified ARF proteins in the reconstitution assay. These results indicate that phospholipase D is a downstream effector of ARF1 and ARF3. The well-established role of ARF in vesicular traffic would suggest that alterations in lipid content by PLD are an important determinant in vesicular dynamics.

Social ideological influences on food consumption, physical activity and BMI.

We investigated relationships between ideological beliefs (i.e., diaphanous body image and environmental concerns), food attitudes, evening meal patterns, physical activity, and Body Mass Index (BMI). A behavioural model was hypothesized based on the Theory of Reasoned Action. A survey was conducted among shoppers aged 40-70 years at Eastland Shopping Centre, Melbourne, Australia. The hypothesized model was tested among female baby boomers (n=547) for younger (n=245) and older (n=302) age groups using structural equation modeling. Findings showed that diaphanous body image had a direct and positive influence on negative food attitudes, which is likely to lead to higher BMI for both age groups. Body image beliefs were positively related to physical activity only for women aged 56-70 years. In contrast, among women aged 40-55 years, strong pro-environmental concerns suggested less consumption of both healthy (e.g., fruit and vegetables) and unhealthy (e.g., sugar and fats) foods. Moreover, strong pro-animal concerns resulted in higher BMI for the younger women. As expected, increased physical activity negatively influenced BMI. Importantly, the associations between ideological beliefs, attitudes, evening meal patterns, and BMI differed between younger and older female baby boomers.

Measuring the effect of change in selection indices.

Genetic selection goals for dairy cattle, originally aimed at production traits only, have been expanded in stages over the past 30 yr to include up to 12 target traits covering production, functionality, and health and fertility. Each addition to the selection goal often involves the use of additional measured phenotypic variates. The net effect of these additions is usually described as causing change in the relative emphasis on different traits, though there are varying definitions of what this means. This paper suggests that the current definitions of this term may be inappropriate and shows that, as usually used, it tends to overstate the net effect of the changes. A new definition of the relative emphasis of each target trait is proposed. It is defined as the percentage of total economic value of genetic gain in all traits attributable to gain in that particular trait. A useful parallel statistic measures the relative contribution of each phenotypic variate recorded. The result of applying these measures is contrasted with the use of current methods using United States Holstein data.

High-solid-content hydroxyapatite slurry for the production of bone substitute scaffolds.

Key to various bone substitute scaffold production techniques is the development of free-flowing ceramic slurry with optimum theological properties. The aim is to achieve a colloidal suspension with as high a solid content as possible while maintaining a low viscosity which easily penetrates the pores of relevant sacrificial templates. The following investigation describes the optimization of a hydroxyapatite slip and demonstrates its potential application in scaffold production. Using predominantly spherical particles of hydroxyapatite of between 0.82 microm and 16.2 microm, coupled with a 2 wt % addition of the anionic polyelectrolyte, ammonium polyacrylate, an 80 wt % (55.9 vol%) hydroxyapatite solid loaded slip with a viscosity of approximately 126mPas has been developed. Its ability to infiltrate and replicate porous preforms has been shown using polyurethane foam. The enhanced particle packing achieved has allowed for the production of scaffolds with highly dense and uniform grain structures. The results represent a significant improvement in current slurry production techniques and can be utilized to develop high-density ceramic bone substitute scaffolds.