Impact of COVID-19 vaccinations on emergency department presentations.

OBJECTIVE: The aim of the present study was to describe the burden of patients presenting to the ED with symptoms occurring after receiving a COVID-19 vaccination. METHODS: This was a retrospective cohort study performed over a 4-month period across two EDs. Participants were eligible for inclusion if it was documented in the ED triage record that their ED attendance was associated with the receipt of a COVID-19 vaccination. Data regarding the type of vaccine (Comirnaty or ChAdOx1) were subsequently extracted from their electronic medical record. Primary outcome was ED length of stay (LOS) and secondary outcomes included requests for imaging and ED disposition destination. RESULTS: During the study period of 22 February 2021 to 21 June 2021, 632 patients were identified for inclusion in the present study, of which 543 (85.9%) had received the ChAdOx1 vaccination. The highest proportion of COVID-19 vaccine-related attendances occurred in June 2021 and accounted for 21 (8%) of 262 total daily ED attendances. Patients who had an ED presentation related to ChAdOx1 had a longer median ED LOS (253 vs 180 min, P < 0.001) compared to Comirnaty and a higher proportion had haematology tests and imaging requested in the ED. Most patients (n = 588, 88.8%) were discharged home from the ED. CONCLUSION: There was a notable proportion of ED attendances related to recent COVID-19 vaccination administration, many of which were associated with lengthy ED stays and had multiple investigations. In the majority of cases, the patients were able to be discharged home from the ED.

Informing the Alfred Registry for Emergency Care Project: An analysis of presenting complaint documentation in an emergency department.

OBJECTIVE: To assess the feasibility of an ED presenting complaint (PC) tool that categorised all ED PCs into 10 categories. METHODS: A retrospective analysis of 1445 consecutive patient encounters was conducted. The primary outcome was the frequency of use of the 10 PC categories. RESULTS: Of the 1203 patient encounters meeting inclusion criteria, the PC tool was completed by clinicians in 574 (47.7%). When completed, the tool's 10 options were selected for most presentations (72.3%). CONCLUSION: The PC tool captured the majority of presenting complaints in 10 categories. External validation is recommended.

Routine Catheter Lock Solutions in Pediatric Cancer Care: A Pilot Randomized Controlled Trial of Heparin vs Saline.

BACKGROUND: Central venous access devices (CVADs) are integral to cancer care provision. Despite the high prevalence of CVAD complications in children with cancer, preventative strategies are understudied. OBJECTIVE: The aim of this study was to assess study feasibility, occlusive events, thrombolytic use, adverse events, and direct costs of catheter lock solutions. METHODS: A single-center, parallel-group, pilot randomized controlled trial was undertaken at a tertiary-referral pediatric hospital in Australia. Children 18 years or younger with an oncological or malignant hematological condition and a CVAD were eligible. Participants were 1:1 randomized to (1) normal or (2) heparinized (10-100 U/mL; CVAD-type dependent) saline lock solutions. RESULTS: Of 217 children assessed for eligibility, 61 were recruited and randomized to normal (n = 30; 3850 CVAD days) or heparinized (n = 31; 4036 CVAD days) saline. Eligibility (52%) and recruitment (54%) feasibility targets were not met. Protocol adherence was high (95% assessments), with no attrition. Parent/clinician satisfaction of interventions was high (median, 10/10 clinicians/parents). Complete CVAD occlusion occurred in heparin only (n = 2, 6.7% CVADs; incidence rate [IR], 0.49/1000 CVAD days [0.06-1.78]). Central venous access device partial occlusion was detected in 23.3% of CVADs in heparin (n = 7; IR, 2.73/1000 CVAD days [1.36-4.87]) and 13.8% of CVADs in normal saline (n = 4; IR, 2.59/1000 CVAD days [1.24-4.77]). Thrombolytic agents were used in 16.7% heparin (5 CVADs) and 3.5% normal saline (1 CVAD). Adverse events did not differ between groups. CONCLUSION: Multisite randomized controlled trials examining CVAD locks are safe, but strategies and resources to increase recruitment and eligibility are required. IMPLICATIONS FOR PRACTICE: Both routine CVAD lock solutions seem safe but may not prevent all forms of CVAD-associated harm.

Episome-Based Gene Expression Modulation Platform in the Model Diatom Phaeodactylum tricornutum.

Chemically inducible gene expression systems have been an integral part of the advanced synthetic genetic circuit design and are employed for precise dynamic control over genetically engineered traits. However, the current systems for controlling transgene expression in most algae are limited to endogenous promoters that respond to different environmental factors. We developed a highly efficient, tunable, and reversible episome-based transcriptional control system in the model diatom alga, Phaeodactylum tricornutum. We assessed the time- and dose-response dynamics of each expression system using a reporter protein (eYFP) as a readout. Using our circuit configuration, we found two inducible expression systems with a high dynamic range and confirmed the suitability of an episome expression platform for synthetic biological applications in diatoms. These systems are controlled by the presence of ß-estradiol and digoxin. Addition of either chemical to transgenic strains activates transcription with a dynamic range of up to ∼180-fold and ∼90-fold, respectively. We demonstrated that our episome-based transcriptional control systems are tunable and reversible in a dose- and time-dependent manner. Using droplet digital polymerase chain reaction (PCR), we also confirmed that inducer-dependent transcriptional activation starts within minutes of inducer application without any detectable transcript in the uninduced controls. The system described here expands the molecular and synthetic biology toolkits in algae and will facilitate future gene discovery and metabolic engineering efforts.

Epidemiology and clinical features of emergency department patients with suspected and confirmed COVID-19: A multisite report from the COVID-19 Emergency Department Quality Improvement Project for July 2020 (COVED-3).

OBJECTIVE: The aim of the present study was to describe the epidemiology and clinical features of patients presenting to the ED with suspected and confirmed COVID-19. METHODS: The COVID-19 ED (COVED) Project is an ongoing prospective cohort study in Australian EDs. This analysis presents data from eight sites across Victoria and Tasmania for July 2020 (during Australia's 'second wave'). All adult patients who met criteria for 'suspected COVID-19' and underwent testing for SARS-CoV-2 in the ED were eligible for inclusion. Study outcomes included a positive SARS-CoV-2 test result and mechanical ventilation. RESULTS: In the period 1 July to 31 July 2020, there were 30 378 presentations to the participating EDs and 2917 (9.6%; 95% confidence interval 9.3-9.9) underwent testing for SARS-CoV-2. Of these, 50 (2%) patients returned a positive result. Among positive cases, two (4%) received mechanical ventilation during their hospital admission compared to 45 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.3; P = 0.47). Two (4%) SARS-CoV-2 positive patients died in hospital compared to 46 (2%) of the SARS-CoV-2 negative patients (odds ratio 1.7, 95% confidence interval 0.4-7.1; P = 0.49). Strong clinical predictors of a positive SARS-CoV-2 result included self-reported fever, non-smoking status, bilateral infiltrates on chest X-ray and absence of a leucocytosis on first ED blood tests (P < 0.05). CONCLUSION: In this prospective multi-site study from July 2020, a substantial proportion of ED patients required SARS-CoV-2 testing, isolation and enhanced infection prevention and control precautions. Presence of SARS-CoV-2 on nasopharyngeal swab was not associated with death or mechanical ventilation.

Impact of patient isolation on emergency department length of stay: A retrospective cohort study using the Registry for Emergency Care.

OBJECTIVE: The number of patients with suspected COVID-19 presenting to Australian EDs continues to impose a burden on healthcare services. Isolation is an important aspect of infection prevention and control, but has been associated with undesirable consequences among hospital inpatients. The aim of the present study was to determine if isolation is associated with an increased length of stay (LOS) in the ED. METHODS: The Registry for Emergency Care Project is a prospective cohort study with a series of nested sub-studies. The present study was a retrospective analysis of adult patients allocated an Australasian Triage Scale category of 1 or 2 who presented to a tertiary ED between 18 and 31 May 2020. The primary outcome was ED LOS. Regression methods were used to determine the independent association between ED isolation and LOS. RESULTS: There were 447 patients who met inclusion criteria, of which 123 (28%) were managed in isolation. The median (interquartile range) ED LOS was 259 (210-377) min for the isolation group and 204 (126-297) min for the non-isolation group, a difference in median ED LOS of 55 min (P < 0.001). Isolation was independently associated with a 23% increase in ED LOS (P = 0.002) and doubled the odds of an ED stay of more than 4 h (adjusted odds ratio 2.2 [1.4-3.4], P = 0.001). CONCLUSION: Consistent with the anecdotal experience of Australian ED clinicians, the present study demonstrated an increased ED LOS for patients managed in isolation. Enhanced infection prevention and control precautions will be required during and beyond the current pandemic, creating significant ongoing challenges for emergency care systems.

Epidemiology and clinical features of emergency department patients with suspected COVID-19: Results from the first month of the COVID-19 Emergency Department Quality Improvement Project (COVED-2).

OBJECTIVE: The aim of the present study was to describe the epidemiological and clinical features of ED patients with suspected and confirmed COVID-19. METHODS: The COVID-19 Emergency Department (COVED) Project is an ongoing prospective cohort study that includes all adult patients presenting to The Alfred Hospital ED who undergo testing for SARS-CoV-2. Current guidelines recommend testing for patients with fevers or chills, acute respiratory symptoms or a high-risk exposure history, as well as implementation of infection prevention and control precautions for all suspected and confirmed cases. Study outcomes include a positive SARS-CoV-2 test result and intensive respiratory support. RESULTS: In the period 1-30 April 2020, 702 of 3453 ED patients (20%; 95% CI 19-22) were tested, with a significant increase during the study period (incident rate ratio 1.019; 95% confidence interval 1.017-1.021, P < 0.001). The primary outcome of a positive SARS-CoV-2 test was recorded in 14 patients (2%; 95% confidence interval 1-3). Shortness of breath (77%), fatigue (100%), myalgia (67%) and diarrhoea (67%) were common among positive cases, while close contact (9%), fever (0%) and healthcare occupation (0%) were not. No positive cases required intensive respiratory support in the ED. CONCLUSIONS: The volume of ED patients with suspected COVID-19 is increasing. Low numbers of positive cases precluded development of accurate predictive tools, but the COVED Project is fulfilling an important role in monitoring the burden of infection prevention and control requirements on the ED. The increasing number of patients meeting isolation criteria has the potential to impact on patient flow and may lead to ED overcrowding.

Epidemiology and clinical features of emergency department patients with suspected COVID-19: Initial results from the COVID-19 Emergency Department Quality Improvement Project (COVED-1).

OBJECTIVE: The COVID-19 Emergency Department (COVED) Quality Improvement Project aims to provide regular and real-time clinical information to ED clinicians caring for patients with suspected and confirmed COVID-19. The present study summarises data from the first 2 weeks of the study. METHODS: COVED is an ongoing prospective cohort study that commenced on 1 April 2020. It includes all adult patients presenting to a participating ED who undergo testing for SARS-CoV-2. Data are collected prospectively and entered into a bespoke registry. Outcomes include a positive SARS-CoV-2 polymerase chain reaction test result and requirement for intensive respiratory support. RESULTS: In the period 1-14 April 2020, 240 (16%) of 1508 patients presenting to The Alfred Emergency and Trauma Centre met inclusion criteria. Of these, 11 (5%) tested positive for SARS-CoV-2. The mean age of patients was 60 years and the commonest symptoms were acute shortness of breath (n = 122 [67%]), cough (n = 108 [56%]) or fever (n = 98 [51%]). Overseas travel or known contact with a confirmed case was reported by 24 (14%) and 16 (10%) patients, respectively. Fever or hypoxia was recorded in 23 (10%) and 11 (5%) patients, respectively. Eleven (5%) patients received mechanical ventilation in the ED, of whom none tested positive for SARS-CoV-2. CONCLUSIONS: Among patients presenting to a tertiary ED with suspected COVID-19, only a small proportion tested positive for SARS-CoV-2. Although the low incidence of positive cases currently precludes the development of predictive tools, the COVED Project demonstrates that the rapid establishment of an agile clinical registry for emergency care is feasible.

Informing emergency care for all patients: The Registry for Emergency Care (REC) Project protocol.

OBJECTIVE: In Australia, the current ED burden related to COVID-19 is from 'suspected' rather than 'confirmed' cases. The initial aim of the Registry for Emergency Care (REC) Project is to determine the impact of isolation processes on the emergency care of all patients. METHODS: The REC Project builds on the COVID-19 Emergency Department Quality Improvement (COVED) Project. Outcomes measured include times to critical assessment and management. RESULTS: Clinical tools will be generated to inform emergency care, both during and beyond the COVID-19 pandemic. CONCLUSIONS: The REC Project will support ED clinicians in the emergency care of all patients.

Informing emergency care for COVID-19 patients: The COVID-19 Emergency Department Quality Improvement Project protocol.

OBJECTIVES: There is an urgency to support Australian ED clinicians with real-time tools as the COVID-19 pandemic evolves. The COVID-19 Emergency Department (COVED) Quality Improvement Project has commenced and will provide flexible and responsive clinical tools to determine the predictors of key ED-relevant clinical outcomes. METHODS: The COVED Project includes all adult patients presenting to a participating ED and meeting contemporary testing criteria for COVID-19. The dataset has been embedded in the electronic medical record and the COVED Registry has been developed. RESULTS: Outcomes measured include being COVID-19 positive and requiring intensive respiratory support. Regression methodology will be used to generate clinical prediction tools. CONCLUSION: This project will support EDs during this pandemic.

Inter-ligand energy transfer in dye chromophores attached to high bandgap SiO2 nanoparticles.

Artificial light harvesters require ordered arrangement of chromophores. We covalently attach three organic chromophore ligands to silicon dioxide nanoparticles. This allows us to study inter-ligand energy transfer when attached to SiO2 nanoparticles, creating a simple system with a large ratio of donors to acceptors. Using steady-state and transient spectroscopy measurements we quantify this energy transfer between ligands. We show a maximum transfer efficiency of 30% and measure the 2D diffusion length of anthracene carboxylic acid on SiO2 to be between 0.6 and 2.2 nm.

Longer time to transfer from the emergency department after bed request is associated with worse outcomes.

OBJECTIVE: To determine the relationships between: (i) total ED length of stay (EDLOS) and in-hospital mortality, ward clinical deterioration; and (ii) between time of bed request, ward transfer and in-hospital mortality, with a particular focus on patients transferred just prior to a 4 h EDLOS. METHODS: Retrospective cohort study using data from three acute care hospitals in Melbourne, Australia. Adult patients admitted from the ED to a non-monitored ward within 8 h. Patients were sub-grouped by EDLOS; EDLOS 3.5-4 h compared to 0-3.5 h and 4-8 h. In-hospital mortality, number of medical emergency team (MET)/cardiac arrest team (CAT) events. RESULTS: A total of 24 746 patients were included: 4396 patients with EDLOS <210 min; 4090 patients with EDLOS of 210-240 min; and 16 260 patients with EDLOS >240 min. Mortality overall was 2.2% (n = 545), highest mortality was seen with EDLOS >4 h (2.4%, n = 399) and lowest in patients with EDLOS 3.5-4 h (1.5%, n = 63, OR 0.67 [95% CI: 0.47-0.93, P = 0.02]). Time from bed request to transfer of >240 min was associated with increased odds of death at hospital discharge (adjusted OR 1.39 [95% CI: 1.08-1.78]). There was no difference in rate of MET calls within 24 h between groups (3.5-4 h = 64 [1.5%], <3.5 h = 60 [1.5%], 4-8 h = 235 [1.4%]). CONCLUSIONS: Both shorter time in ED and shorter time between bed request and ward transfer were independently associated with improved outcomes. Whole of hospital measures to reduce length of stay in the ED should focus on shorter ward transfer times after bed request.

Process for the synthesis of symmetric and unsymmetric oxygen bridged dimers of boron subphthalocyanines (µ-oxo-(BsubPc)2s).

A process for the gram scale synthesis of the oxygen bridged dimer of boron subphthalocyanine, µ-oxo-(BsubPc)2, has been developed. During the development it was found that a wide range of reaction pathways under diverse conditions lead to µ-oxo-(BsubPc)2 formation. However, obtaining µ-oxo-(BsubPc)2 as the main reaction product in appreciable yields and its subsequent isolation were extremely challenging. The best balance of purity, yield and conversion was achieved with a time controlled reaction of an equimolar reaction of HO-BsubPc with Br-BsubPc in the presence of K3PO4. The purification involved sequentially Soxhlet extraction, Kauffman column chromatography and train sublimation. We have repeated the process and yields ranged from 27 to 30% of pure, doubly-sublimed µ-oxo-(BsubPc)2. This process also enabled the synthesis of unsymmetric µ-oxo-(BsubPc)2s by reaction of HO-BsubPc with Br-F12BsubPc, Cl-Cl6BsubPc and Cl-Cl12BsubPc. After synthesis the solution-state properties of the unsymmetric µ-oxo-(BsubPc)2s were investigated, and compared to the symmetric µ-oxo-(BsubPc)2 and more broadly to other BsubPcs. The electronic properties of µ-oxo-(BsubPc)2 were found to differ from its unsymmetric counterparts, but were found to be similar to halo-BsubPcs. Furthermore, the photophysical properties of µ-oxo-(BsubPc)2, both symmetric and unsymmetric, differed greatly from all other known BsubPcs.

Modulation of reactive oxygen species photogeneration of bacteriopheophorbide a derivatives by exocyclic E-ring opening and charge modifications.

With the knowledge that the dominant photodynamic therapy (PDT) mechanism of 1a (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring opening, we hypothesized that taurine-driven E-ring opening of bacteriochlorophyll derivatives and net-charge variations would modulate reactive oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives were synthesized with varying charges that either contained the E ring (2a-5a) or were synthesized by taurine-driven E-ring opening (2b-5b). Time-dependent density functional theory (TDDFT) modeling showed that all derivatives would be type 2 PDT-active, and ROS-activated fluorescent probes were used to investigate the photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and aqueous-based solutions. These investigations validated our predictive modeling calculations and showed that taurine-driven E-ring opening and increasing negative charge generally enhanced ROS photogeneration in aqueous solutions. We propose that these structure-activity relationships may provide simple strategies for designing bacteriochlorins that efficiently generate ROS upon photoirradiation.

Sulfonate pseudohalides of boron subphthalocyanine.

The crystal structures of three sulfonate pseudohalide derivatives of boron subphthalocyanine (BsubPc) are described and compared with four structures of three published sulfonate derivatives. Benzenesulfonate boron subphthalocyanine [(benzenesulfonato)(subphthalocyaninato)boron, C(30)H(17)BN(6)O(3)S, (I)] crystallizes in the space group P-1 with Z = 2. The structure contains two centrosymmetric π-stacking interactions between the concave faces of the isoindoline units in the BsubPc ligands. 3-Nitrobenzenesulfonate boron subphthalocyanine [(3-nitrobenzenesulfonato)(subphthalocyaninato)boron, C(30)H(16)BN(7)O(5)S, (II)] crystallizes in the space group P2(1)/c with Z = 4. The structure contains an intermolecular S-O···π interaction from the sulfonate group to a five-membered N-containing ring of an isoindoline unit on the concave side of a neighbouring BsubPc ligand, at a distance of 3.151 (3) Å. The crystal of methanesulfonate boron subphthalocyanine [(methanesulfonato)(subphthalocyaninato)boron, C(25)H(15)BN(6)O(3)S, (III)] was produced via sublimation and it is not a solvate, in contrast with two previously published structures of the same compound. Compound (III) crystallizes in the space group P2(1)/n with Z = 2, and its structure is similar to that of the more common compound Cl-BsubPc.

Pseudohalides of boron subphthalocyanine.

The synthesis and study of a series of pseudohalides of boron subphthalocyanine (BsubPc) are reported. Each pseudohalide has been compared to the more common chloride and bromide of BsubPc, and we have found that most react slower under standard phenoxylation and hydrolysis conditions. Three pseudohalides (TsO-BsubPc, MsO-BsubPc, and BsO-BsubPc) do not hydrolyze at all even after prolonged periods of time in the presence of water. Single crystals of TsO-, MsO-, and ClsO-BsubPc were obtained, and their structures were unambiguously determined.

(4-Cyano-phenolato)(subphthalocyaninato)boron.

The crystal structure of the title compound, C(31)H(16)BN(7)O, (CNPhO-BsubPc) is characterized by pairs of π-π stacking inter-actions between the concave faces of inversion-related BsubPc fragments with a centroid-centroid distance of 3.600 (1) Å. In addition, these pairs of mol-ecules are linked into chains along [101] through further weak π-π stacking inter-actions with a centroid-centroid distance of 3.8587 (9) Å. There are also weak C-H⋯π(arene) inter-actions within the chains.

Chloro boron subphthalocyanine and its derivatives: dyes, pigments or somewhere in between?

Nine derivatives of chloro boron subphthalocyanine (Cl-BsubPc, 1) have been synthesized and characterized. Seven dimers of Cl-BsubPc have been synthesized by reaction with biphenol (2a), bisphenol A (2b), bisphenol F (2c), bisphenol O (2d), bisphenol P (2e), bisphenol S (2f) and bisphenol Z (2g). For comparison two monomeric phenoxy- (3a) and 4-methylphenoxy (3b) BsubPcs have also been synthesized. Crystals were grown for dimer 2c, whereas all attempts to grow crystals of the remaining dimers resulted in the formation of molecular glasses or amorphous precipitates. Analysis on the structure of 2c suggests that the rigidity and aromatic nature of the central bisphenolic directs the crystal packing. The solubility of the BsubPc dimers in a variety of common organic solvents was measured and compared to that of Cl-BsubPc (2) and monomers 3a and 3b. We have defined ranges for classifying BsubPc derivatives based on their solubility in these solvents: pigment < or = 1 x 10(-8) M, 1 x 10(-3) M < or = pigment-like > 1 x 10(-8) M, 1 x 10(-2) M < or = dye-like > 1 x 10(-3) M, and dye > 1 x 10(-2) M. From this Cl-BsubPc (1) and compounds 2a, 2b, 2c, 2e and 2g are pigment-like while compounds 2d, 2f, 3a and 3b are dye-like. None are exclusively pigments or dyes. In this first approximation of this dye versus pigment classification we have not considered other processes besides solvation which could be undesirable such as polymorphic changes or Ostwald ripening. We have concluded that derivatization of Cl-BsubPc (1) with bisphenols and phenols can be used to control the solubility of BsubPc derivatives. We have also concluded that Cl-BsubPc (1) should not be considered a dye rather is pigment-like in its solubility.

(4-Nitro-phenolato)(subphthalo-cyaninato)boron(III).

The main feature of the structure of the title compound, C(30)H(16)BN(7)O(3) or NO(2)PhO-BsubPc, are pairs of mol-ecules linked through π-inter-actions between the concave faces of the BsubPc fragments at a distance of 3.5430 (11) Šacross an inversion centre. However, the angle between the planes of the five- and six-menbered rings involved in this inter-action is 1.44 (10)°, causing the inter-acting BsubPcs units to be slightly askew rather than parallel as is typical for π-stacking inter-actions.

(Dodecafluorosubphthalocyaninato)(4-methylphenolato)boron(III).

In the title compound, C(31)H(7)BF(12)N(6)O, mol-ecules are arranged into one-dimensional columns with an inter-molecular B⋯B distance of 5.3176 (8) Å. Bowl-shaped mol-ecules are arranged within the columns in a concave bowl-to-ligand arrangement separated by a ring centroid distance of 3.532 (2) Šbetween the benzene ring of the 4-methyl-phen-oxy ligand and one of the three five-membered rings of a symmetry-related mol-ecule.