Exploring overcrowding trends in an inner city emergence department in the UK before and during COVID-19 epidemic.

BACKGROUND: The COVID-19 pandemic and the associated lockdowns have caused significant disruptions across society, including changes in the number of emergency department (ED) visits. This study aims to investigate the impact of three pre-COVID-19 interventions and of the COVID-19 UK-epidemic and the first UK national lockdown on overcrowding within University College London Hospital Emergency Department (UCLH ED). The three interventions: target the influx of patients at ED (A), reduce the pressure on in-patients' beds (B) and improve ED processes to improve the flow of patents out from ED (C). METHODS: We collected overcrowding metrics (daily attendances, the proportion of people leaving within 4 h of arrival (four-hours target) and the reduction in overall waiting time) during 01/04/2017-31/05/2020. We then performed three different analyses, considering three different timeframes. The first analysis used data 01/04/2017-31/12-2019 to calculate changes over a period of 6 months before and after the start of interventions A-C. The second and third analyses focused on evaluating the impact of the COVID-19 epidemic, comparing the first 10 months in 2020 and 2019, and of the first national lockdown (23/03/2020-31/05/2020). RESULTS: Pre-COVID-19 all interventions led to small reductions in waiting time (17%, p < 0.001 for A and C; an 9%, p = 0.322 for B) but also to a small decrease in the number of patients leaving within 4 h of arrival (6.6,7.4,6.2% respectively A-C,p < 0.001). In presence of the COVID-19 pandemic, attendance and waiting time were reduced (40% and 8%; p < 0.001), and the number of people leaving within 4 h of arrival was increased (6%,p < 0.001). During the first lockdown, there was 65% reduction in attendance, 22% reduction in waiting time and 8% increase in number of people leaving within 4 h of arrival (p < 0.001). Crucially, when the lockdown was lifted, there was an increase (6.5%,p < 0.001) in the percentage of people leaving within 4 h, together with a larger (12.5%,p < 0.001) decrease in waiting time. This occurred despite the increase of 49.6%(p < 0.001) in attendance after lockdown ended. CONCLUSIONS: The mixed results pre-COVID-19 (significant improvements in waiting time with some interventions but not improvement in the four-hours target), may be due to indirect impacts of these interventions, where increasing pressure on one part of the ED system affected other parts. This underlines the need for multifaceted interventions and a system-wide approach to improve the pathway of flow through the ED system is necessary. During 2020 and in presence of the COVID-19 epidemic, a shift in public behaviour with anxiety over attending hospitals and higher use of virtual consultations, led to notable drop in UCLH ED attendance and consequential curbing of overcrowding. Importantly, once the lockdown was lifted, although there was an increase in arrivals at UCLH ED, overcrowding metrics were reduced. Thus, the combination of shifted public behaviour and the restructuring changes during COVID-19 epidemic, maybe be able to curb future ED overcrowding, but longer timeframe analysis is required to confirm this.

Analysis of menisci formed on cones for single field of view parasite egg microscopy.

Parasite ova caused to accumulate in a single microscopic field simplifies monitoring soil-transmitted helminthiasis by optical microscopy. Here we demonstrate new egg-accumulating geometries based on annular menisci formed on the surface of a wetted cone. Fluidic features extracted from profile images of the system provided mathematical representations of the meniscus gradient that were compared quantitatively to numerical solutions of an axisymmetric Young-Laplace equation. Our results show that the governing dynamics of these systems is dominated by the surface tension of the fluid. These image analysis and mathematical tools provide simple quantitative methods for system analysis and optimization.

Acute neurological presentation due to copper deficiency in a hemodialysis patient following gastric bypass surgery.

Acquired copper deficiency has been recently recognized as a cause of myelopathy, and has been reported to occur many years after gastric bypass surgery performed to aid weight reduction in morbidly obese patients. We report a case of a young woman treated by hemodialysis who presented with acute neurological symptoms 5 months after gastric bypass surgery for severe obesity. She had symptoms and signs of cerebellar, spinal cord and peripheral nerve disease, which improved following parenteral copper supplementation. Now that gastric bypass surgery is being offered to morbidly obese hemodialysis patients, this case highlights the importance of monitoring copper levels in hemodialysis patients following gastric bypass surgery.

Transient Turing patterns in a neural field model.

We investigate Turing bifurcations in a neural field model with one spatial dimension. For some parameter values the resulting Turing patterns are stable, while for others the patterns appear transiently. We show that this difference is due to the relative position in parameter space of the saddle-node bifurcation of a spatially periodic pattern and the Turing bifurcation point. By varying parameters we are able to observe transient patterns whose duration scales in the same way as type-I intermittency. Similar behavior occurs in two spatial dimensions.

Modeling electrocortical activity through improved local approximations of integral neural field equations.

Neural field models of firing rate activity typically take the form of integral equations with space-dependent axonal delays. Under natural assumptions on the synaptic connectivity we show how one can derive an equivalent partial differential equation (PDE) model that properly treats the axonal delay terms of the integral formulation. Our analysis avoids the so-called long-wavelength approximation that has previously been used to formulate PDE models for neural activity in two spatial dimensions. Direct numerical simulations of this PDE model show instabilities of the homogeneous steady state that are in full agreement with a Turing instability analysis of the original integral model. We discuss the benefits of such a local model and its usefulness in modeling electrocortical activity. In particular, we are able to treat "patchy" connections, whereby a homogeneous and isotropic system is modulated in a spatially periodic fashion. In this case the emergence of a "lattice-directed" traveling wave predicted by a linear instability analysis is confirmed by the numerical simulation of an appropriate set of coupled PDEs.

Renal tubular acidosis.

Renal tubular acidosis (RTA) is a form of metabolic acidosis due to abnormal alkali (bicarbonate) loss by the kidneys or their failure to excrete net acid. While the latter does occur in chronic renal failure, the term RTA is usually applied only when the glomerular filtration rate is normal or near normal. As well as a cause of metabolic acidosis, RTA often presents as renal stone disease with nephrocalcinosis, rickets/osteomalacia, and growth retardation in children. In this brief review, we have summarized the classification, clinical features and the underlying cell and molecular pathophysiology of RTA. However, despite significant advances in our understanding of the mechanisms of RTA, its treatment is still empirical and based largely on alkali replacement therapy; but its wider significance in renal stone and bone disease is becoming increasingly recognized.

Activity of lymphoid cells separated from mammary tumors in blastogenesis and Winn assays.

Lymphoid cells isolated from mouse mammary tumors by isokinetic gradients were not stimulated in vitro by either phytohemagglutinin or a soluble, tumor-associated antigen extract even though splenocytes from the tumor-bearing mice were responsive to both. In in vivo Winn assays, lymphoid cells isolated from tumors markedly stimulated tumor growth rate. The effect on growth rate was abrogated by exposure of the isolated lymphoid cells to antilymphocyte serum and complement.

Jasplakinolide's inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton.

BACKGROUND: Jasplakinolide, a cyclodepsipeptide produced by an Indo-Pacific sponge, Jaspis johnstoni, has been reported to inhibit the growth of breast cancer cells. PURPOSE: The effects of jasplakinolide on the proliferation of three human immortalized prostate carcinoma cell lines (PC-3, LNCaP, and TSU-Pr1) were studied. The growth-inhibitory effect of jasplakinolide on the PC-3 cell line was studied in detail to elucidate its mechanism of action. METHODS: Cell counts were used to study growth inhibition. A protein-based microplate assay was used to assess the time of exposure needed to cause persistent growth inhibition and to study the effects of jasplakinolide analogues. Metabolic changes were assessed by following the incorporation of radiolabeled precursors. The effects of jasplakinolide on the cytoskeleton were studied by fluorescent microscopy, using rhodamine phalloidin (RP) and antibodies to cytoskeletal components. Changes in RP binding were quantified by extracting bound fluorescent material from fixed cells and measuring the amount of fluorescence in a spectrofluorometer. RESULTS: The growth of PC-3, LNCaP, and TSU-Pr1 cells was potently inhibited by exposure to jasplakinolide for 48 hours; doses of jasplakinolide that led to 50% growth inhibition were 65 nM for PC-3 cells, 41 nM for LNCaP cells, and 170 nM for TSU-Pr1 cells. In PC-3 cells, exposure to 160 nM for 48 hours led to total growth inhibition, which persisted for several days even after drug removal. Several jasplakinolide analogues also inhibited the growth of PC-3 cells, although analogues in which the rigidity of the macrolide ring was altered were ineffective. No early changes in the synthesis of DNA, RNA, or protein or in intracellular adenosine triphosphate levels were seen in the PC-3 cells after exposure to jasplakinolide. Growth inhibition by jasplakinolide was accompanied by striking morphologic changes. Exposure for several doublings led to multinucleated cells. Further investigation of these changes in the PC-3 cells revealed a dramatic and early disruption of the actin cytoskeleton and a statistically significant decrease in RP binding. The doses of jasplakinolide, the time of exposure, and the pattern of growth inhibition by structural analogues corresponded with the changes seen in actin distribution. CONCLUSIONS: Jasplakinolide represents a novel marine natural product with potent in vitro antiproliferative activity against human prostate carcinoma cell lines, and it appears to target the actin cytoskeleton. IMPLICATIONS: Jasplakinolide is a potential candidate for further preclinical development and a lead structure for a novel class of therapeutic agents that can disrupt the actin cytoskeleton in mammalian cells.

Acute kidney injury among HIV-infected patients admitted to the intensive care unit.

We describe the incidence, associations and outcomes of acute kidney injury (AKI) among HIV-infected patients admitted to the intensive care unit (ICU). We retrospectively analysed 223 admissions to an inner-London, University-affiliated ICU between 1999 and 2012, and identified those with AKI and performed multivariate analysis to determine associations with AKI. Of all admissions, 66% were affected by AKI of any severity and 35% developed stage 3 AKI. In multivariate analysis, AKI was associated with chronic kidney disease (odds ratio [OR] = 3.19; p = 0.014), a previous AIDS-defining illness (OR = 1.93; p = 0.039) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score, (OR = 3.49; p = 0.018, if > 30). No associations were demonstrated with use of anti-retroviral medication (including tenofovir), or an individual's HIV viral load or CD4 count. AKI was associated with higher inpatient mortality and longer duration of ICU admission. Among patients with stage 3 AKI, only 41% were alive 90 days after ICU admission. Among survivors, 74% regained good renal function, the remainder were dependent on renal replacement therapy or were left with significant ongoing renal dysfunction. Of note, many patients had baseline serum creatinine concentrations well below published reference ranges. AKI among HIV-infected patients admitted to ICU carries a poor prognosis.

Lymphocytopenia in high cancer risk population: evidence in automobile pattern makers.

A total of 1454 automobile pattern makers were studied to determine the degree of lymphocyte reduction. These occupational workers have been known to be at high risk for colorectal cancer. As a group, pattern makers had significantly lower lymphocyte counts than the comparison group. The proportion of lymphocytopenia (less than 1500/mm3) in pattern makers was 26.2% as compared with 5.6% in the comparison group. Continuous monitoring of lymphocyte reduction in pattern makers may be worthwhile to evaluate whether these workers face a high risk for deficiency in lymphocytes in association with their risk for high rates of colorectal cancer.

Optimized determination of malondialdehyde in plasma lipid extracts using 1,3-diethyl-2-thiobarbituric acid: influence of detection method and relations with lipids and fatty acids in plasma from healthy adults.

We investigated the influence of different concentrations of Fe3+, phosphoric acid, butylated hydroxytoluene and glutathione on the production of the malondialdehyde-1,3-diethyl-2-thiobarbituric acid adduct in plasma lipid extracts. Following organic solvent extraction the stable product was analyzed by spectrophotometry (537 nm), fluorometry (547 nm) and high-performance liquid chromatography with fluorometric detection. Using optimized reaction conditions there was good agreement between the three methods, with slightly higher values for the spectrophotometric method. Plasma total lipid malondialdehyde reference values for 24 healthy adults amounted to 1.30 +/- 0.23 mumol/l (spectrophotometric method) and 1.11 +/- 0.31 mumol/l (fluorometric method). Plasma lipid malondialdehyde concentrations correlated significantly with plasma triglycerides (r = 0.527), total cholesterol (r = 0.612) and total fatty acids (r = 0.810) and with the total number of double bonds present in plasma fatty acids with three or more double bonds (r = 0.923).

Dialysis leucopenia--no correction after prolonged washing of the membrane.

Re-use of hemodialysers diminishes the extent of leucopenia observed during hemodialysis. A possible cause of this change is the prolonged washing of the membrane by an aqueous solution on both sides and by protein contained solutions on the blood side which removes some substance from the membrane which affects leucocytes directly or by activation of complement. A series of studies to test this hypothesis were performed using two hemodialysis membranes -Cuprophan (Enka AG) and Cellulate (Cordis Dow Corporation) and the results obtained demonstrate no elution of any water soluble substance from the dialyser membrane.

Seasonal vitamin D status of Greyhounds in Sydney.

OBJECTIVES: To survey the vitamin D status of a population of Greyhounds in New South Wales, and to establish a reference range for plasma 25(OH)D. To investigate whether any seasonal fluctuation in vitamin D status is detectable in these animals. DESIGN: Vitamin D status was assessed in Greyhounds and crossbred dogs presented to the University of Sydney for teaching purposes over a 24 month period. PROCEDURES: Plasma 25(OH)D concentration was measured as an estimate of vitamin D status. Physical examination and plasma calcium concentration were used to verify the health of the animals, particularly with respect to metabolic bone disease. RESULTS: A plasma 25(OH)D concentration range of 10 to 76 nmol/L was found in healthy adult Greyhounds. There was no sex- or season-dependent variation in vitamin D status in Greyhounds. Concentrations in crossbred dogs did not differ significantly from those in Greyhounds. CONCLUSION: The reference range for plasma 25(OH)D concentration in Greyhound dogs is similar to that previously reported for humans. It would seem that healthy dogs in the Sydney region do not exhibit a seasonal fluctuation in their vitamin D status.

Rickets in a litter of racing greyhounds.

Rickets was diagnosed in six 14-week-old racing greyhound littermates presented with musculoskeletal disease. Physical findings included listlessness, profound muscle weakness, lameness, lateral bowing of the antebrachii and focal hard swellings proximal to the tarsi and carpi. Radiological findings included generalised osteopenia, axial and radial thickening of growth plates, and "cupping' of the adjacent metaphyses; the distal ulnar growth plates were most severely and consistently affected. The diagnosis was confirmed by demonstrating subnormal concentrations of 25-hydroxycholecalciferol in serum samples collected at admission. The pups' diet consisted of an inexpensive generic kibble formulated for adult dogs, porridge, milk, pasta, minced beef, vegetables and a small quantity of calcium carbonate powder. The pups were successfully treated by feeding a nutritionally complete, vitamin D-containing ration formulated for growing pups. Bilateral growth retardation of distal ulnar physes occurred as a sequel in one pup.

The requirement for natural sunlight to prevent vitamin D deficiency in iguanian lizards.

To investigate possible causes of embryonic and neonatal mortality in a group of captive Fijian iguanas (Brachylophus fasciatus and Brachylophus vitiensis), the vitamin D status of adults in the colony was compared with that of agamid and iguanid lizards either housed in indoor enclosures under artificial ultraviolet light or exposed to natural sunlight (wild-caught or captive animals housed outdoors). Those under artificial lighting had a significantly lower vitamin D status than those housed exclusively outdoors, whereas the vitamin D status of Fijian iguanas that had received intermittent exposure to natural sunlight was intermediate and not significantly different from that of animals housed exclusively outdoors. However, eggs from some of these Fijian iguanas had substantially lower vitamin D content than eggs from outdoor iguanid and agamid animals. Artificial ultraviolet light, therefore, might not be an adequate substitute for natural sunlight to maintain vitamin D status of lizards. This possible inadequacy may be because either artificial ultraviolet light has a lower intensity of the wavelengths that induce vitamin D than does sunlight or the intensity of the artificial lighting is not sufficient.

Fibrous osteodystrophy in dromedary camels (Camelus dromedarius).

Fibrous osteodystrophy of the facial and long bones was diagnosed in four dromedary camels (Camelus dromedarius). None of the animals responded to treatment with antiinflammatory medications or calcium supplements. The lesions were probably caused by multiple factors, including inappropriate diet and gastrointestinal parasitism. A critical factor in lesion formation may have been vitamin D deficiency secondary to gastrointestinal malabsorption and inadequate winter exposure to ultraviolet light.