Spiced RCT: Success and Pain Associated with Intravenous Cannulation in the Emergency Department Randomized Controlled Trial.

BACKGROUND: Peripheral venous cannulation is one of the most common procedures in medicine. A larger cannula allows higher rates of fluid to be provided if needed in a deteriorating patient; however, it is also perceived that larger-gauge cannula placement is associated with increased pain and procedural difficulty. OBJECTIVE: This study aimed to compare the pain and procedural difficulty experienced during insertion between 18-gauge (18G) and 20-gauge (20G) cannulas. METHODS: We conducted a single-blinded, randomized controlled trial on adult patients who required peripheral IV cannulation within a tertiary hospital emergency department between April and October 2018. Patients were randomized to either the 18G or 20G cannula group. The primary outcomes of the study-pain experienced by patients and procedural difficulties experienced by clinical staff-were recorded on two separate 10-cm visual analog scales. Other outcomes include first-attempt success rate, operator designation, complications, and the intent and actual use of the IV cannula were documented on preformatted questionnaires. RESULTS: Data from 178 patients were included in the analysis. Eighty-nine patients were allocated to each cannula group. There were no statistically or clinically significant differences between mean pain score (0.23; 95% CI 0.56-1.02; p = 0.5662) and mean procedural difficulty score (0.12; 95% CI 0.66-0.93; p = 0.7396). between the two groups. There was no difference in first-attempt success rate (73 of 89 vs. 75 of 89; p = 0.1288), complications (2 of 89 vs. 1 of 89) between the 20G group and 18G group, respectively. CONCLUSIONS: There was no significant difference between the 18G or 20G cannula for either pain experienced by patients or procedural difficulty experienced by clinicians.

Mechanosensitive expression of the mesenchymal subtype marker connective tissue growth factor in glioblastoma.

Mechanical forces created by the extracellular environment regulate biochemical signals that modulate the inter-related cellular phenotypes of morphology, proliferation, and migration. A stiff microenvironment induces glioblastoma (GBM) cells to develop prominent actin stress fibres, take on a spread morphology and adopt trapezoid shapes, when cultured in 2D, which are phenotypes characteristic of a mesenchymal cell program. The mesenchymal subtype is the most aggressive among the molecular GBM subtypes. Recurrent GBM have been reported to transition to mesenchymal. We therefore sought to test the hypothesis that stiffer microenvironments-such as those found in different brain anatomical structures and induced following treatment-contribute to the expression of markers characterising the mesenchymal subtype. We cultured primary patient-derived cell lines that reflect the three common GBM subtypes (mesenchymal, proneural and classical) on polyacrylamide (PA) hydrogels with controlled stiffnesses spanning the healthy and pathological tissue range. We then assessed the canonical mesenchymal markers Connective Tissue Growth Factor (CTGF) and yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) expression, via immunofluorescence. Replating techniques and drug-mediated manipulation of the actin cytoskeleton were utilised to ascertain the response of the cells to differing mechanical environments. We demonstrate that CTGF is induced rapidly following adhesion to a rigid substrate and is independent of actin filament formation. Collectively, our data suggest that microenvironmental rigidity can stimulate expression of mesenchymal-associated molecules in GBM.

The neuritic plaque in Alzheimer's disease: perivascular degeneration of neuronal processes.

Cerebrovascular pathology is common in aging and Alzheimer's disease (AD). The microvasculature is particularly vulnerable, with capillary-level microhemorrhages coinciding with amyloid beta deposits in senile plaques. In the current analysis, we assessed the relationship between cerebral microvessels and the neuritic component of the plaque in cortical and hippocampal 50- to 200-µm sections from 11 AD, 3 Down syndrome, and 7 nondemented cases in neuritic disease stages 0-VI. We report that 77%-97% of neuritic plaques are perivascular, independently of disease stage or dementia diagnosis. Within neuritic plaques, dystrophic hyperphosphorylated tau-positive neurites appear as clusters of punctate, bulbous, and thread-like structures focused around capillaries and colocalize with iron deposits characteristic of microhemorrhage. Microvessels within the neuritic plaque are narrowed by 1.0 ± 1.0 µm-4.4 ± 2.0 µm, a difference of 16%-65% compared to blood vessel segments with diameters 7.9 ± 2.0-6.4 ± 0.8 µm (p < 0.01) outside the plaque domain. The reduced capacity of microvessels within plaques, frequently below patency, likely compromises normal microlocal cerebrovascular perfusion. These data link the neuritic and amyloid beta components of the plaque directly to microvascular degeneration. Strategies focused on cerebrovascular antecedents to neuritic dystrophy in AD have immediate potential for prevention, detection, and therapeutic intervention.

Retrospective Analysis of Patient Presentations at the Sydney (Australia) Royal Easter Show from 2012 to 2014.

Introduction Comprehensive studies on the relationship between patient demographics and subsequent treatment and disposition at a single mass-gathering event are lacking. The Sydney Royal Easter Show (SRES; Sydney Olympic Park, New South Wales, Australia) is an annual, 14-day, agricultural mass-gathering event occurring around the Easter weekend, attracting more than 800,000 patrons per year. In this study, patient records from the SRES were analyzed to examine relationships between weather, crowd size, day of week, and demographics on treatment and disposition. This information would help to predict factors affecting patient treatment and disposition to guide ongoing training of first responders and to evaluate the appropriateness of staffing skills mix at future events. Hypothesis Patient demographics, environmental factors, and attendance would influence the nature and severity of presentations at the SRES, which would influence staffing requirements. METHODS: A retrospective analysis of 4,141 patient record forms was performed for patients who presented to St John Ambulance (Australian Capital Territory, Australia) at the SRES between 2012 and 2014 inclusive. Presentation type was classified using a previously published minimum data set. Data on weather and crowd size were obtained from the Australian Bureau of Meteorology (Melbourne, Victoria, Australia) and the SRES, respectively. Statistical analyses were performed using SPSS v22 (IBM; Armonk, New York USA). RESULTS: Between 2012 to 2014, over 2.5 million people attended the SRES with 4,141 patients treated onsite. As expected, the majority of presentations were injuries (49%) and illnesses (46%). Although patient demographics and presentation types did not change over time, the duration of treatment increased. A higher proportion of patients were discharged to hospital or home compared to the proportion of patients discharged back to the event. Patients from rural/regional locations (accounting for 15% of all patients) were more likely to require advanced treatment, health professional review, and were more likely to be discharged to hospital or home rather than discharged back to the event. Extremes of temperature were associated with a lower crowd size and higher patient presentation rate (PPR), but had no impact on transfer or referral rates to hospital. CONCLUSION: This study demonstrated that analyses of patient presentations at an agricultural show provide unique insights on weather, attendance, and demographic features that correlated with treatment and disposition. These data can help guide organizers with information on how to better staff and train health care providers at future mass-gathering events of this type. Crabtree N , Mo S , Ong L , Jegathees T , Wei D , Fahey D , Liu J . Retrospective analysis of patient presentations at the Sydney (Australia) Royal Easter Show from 2012 to 2014. Prehosp Disaster Med. 2017;32(2)187-194.

Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease.

Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged-matched control microglia. In AD cases, on average, 49%-64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged-matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging-related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural-glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease.