ORCID Profile
0000-0002-0710-1889
Current Organisations
Cabrini Hospital
,
Ghent University Hospital
,
Monash University
,
Ghent University
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Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.VACCINE.2016.06.077
Abstract: More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia. Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis. Result from 98 BCG-immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-γ(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups. Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.VACCINE.2018.03.066
Abstract: Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, yet current control strategies, including the existing BCG vaccine, have had little impact on disease control. CysVac2, a fusion protein comprising stage-specific Mycobacterium tuberculosis antigens, provided superior protective efficacy against chronic M. tuberculosis infection in mice, compared to BCG. To determine if the delivery of CysVac2 in the context of BCG could improve BCG-induced immunity and protection, we generated a recombinant strain of BCG overexpressing CysVac2 (rBCG:CysVac2). Expression of CysVac2 in BCG was facilitated by the M. tuberculosis hspX promoter, which is highly induced inside phagocytic cells and induces strong cellular immune responses to antigens expressed under its regulation. Intradermal vaccination with rBCG:CysVac2 resulted in increased monocyte/macrophage recruitment and enhanced antigen-specific CD4
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.IJPHARM.2018.04.063
Abstract: Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows reproducible mixing in miliseconds on the nanoliter scale. Here we investigated the feasibility of a microfluidic flow focusing setup built from commercially available fittings to encapsulate phages into liposomes. Two types of Pseudomonas phages, PEV2 (Podovirus, ∼65 nm) and PEV40 (Myovirus, ∼220 nm), were used as model phages. A mixture of soy phosphatidylcholine and cholesterol at a ratio of 4:1 dissolved in absolute ethanol with a total solid content of 17.5 mg/mL was injected through the center inlet channel of a cross mixer. Phage suspensions were injected into the cross mixer from the two side channels intersecting with the center channel. The total flow rate (TFR) varied 160-320 µL/min and the organic/aqueous flow rate ratio (FRR) varied 1:3-2:3. The size of liposomes and the encapsulation efficiency both increased with increasing FRR and slightly decreased with increasing TFR. Due to the different size of the two studied phages, the size of liposomes encapsulating PEV2 were smaller (135-218 nm) than those encapsulating the Myovirus PEV40 (261-448 nm). Highest encapsulation efficiency of PEV2 (59%) and PEV40 (50%) was achieved at a TFR of 160 µL/ml and a FRR of 2:3. Generally, the encapsulation efficiency was slightly higher than that obtained from the conventional thin film hydration followed by extrusion method. In summary, the proposed microfluidic technique was capable of encapsulating phages of different size into liposomes with reasonable encapsulation efficiency and minimal titer reduction.
Publisher: Wiley
Date: 31-05-2022
DOI: 10.1111/IMJ.15262
Abstract: Hospital medical emergency team (MET) activation events involving end‐of‐life care (EOLC) are common. The issues faced by medical staff attending these events are incompletely described. The purpose of this study was to measure the perceptions of Victorian hospital medical staff, training in the speciality of intensive care, about multiple aspects of EOLC MET calls. We sought to determine the overall extent of formal training in MET and EOLC and assess the domains of self‐perceived confidence, barriers to communication, frequency of clinician agreement and trainee distress. We conducted an anonymous, voluntary, Internet‐based survey of registered trainees of the College of Intensive Care Medicine of Australia and New Zealand in May 2019. The participants eligible were those trainees working in an adult intensive care unit in Victoria, Australia, during the study period. The main outcome measures were self‐reported levels of confidence, barriers to communication, frequency of conflict and distress, senior support, supervision and access to training. Of 124 trainees surveyed, 75 (60%) responded. Overall, 78% of respondents felt confident to manage EOLC MET calls, but the frequently reported barriers to effective patient/next of kin communication included: (i) lack of private meeting rooms (ii) resource and time constraints and (iii) lack of patient and family availability during a MET call to discuss medical treatment limitations. Two‐thirds of respondents reported emotional distress at least occasionally, this being frequent in one in five. Most (68%) trainees experienced conflict with other medical teams at least occasionally. Factors associated with experiencing distress at least occasionally include greater trainee age, patients' being unable to participate in discussion due to illness, resource and time constraints and negative encounters with other medical teams. Victorian intensive care trainees were confident managing EOLC MET activation events. However, distress was reported commonly and strategies are required to address the areas of concern.
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/CH16559
Abstract: The total synthesis of norfijimycin A, a simplified analogue of the marine natural product fijimycin A, is described. Fijimycin A is a cyclic depsipeptide that has been shown to possess activity against methicillin-resistant Staphylococcus aureus. The natural product contains a rare N,β-dimethyl leucine unit with unknown stereochemistry at the β-carbon. To evaluate the importance of the β-methyl group for antimicrobial activity, we introduced N-methyl leucine into the natural product scaffold. The resulting norfijimycin A was shown to possess significant activity against Mycobacterium tuberculosis, the etiological agent of tuberculosis.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.NEDT.2019.104265
Abstract: 'Just-in-time training' is an innovative approach to nursing education. It has demonstrated positive outcomes in other industries, such as manufacturing and aviation, but it has limited published application in the acute-care setting. We aimed to implement and evaluate a nursing 'just-in-time training' program for the recognition and response to patient deterioration. To promote consistency, one Clinical Deterioration Educator provided education to nursing staff in both recognising the need for escalation and providing subsequent care for the deteriorating ward patient. Nurses' perception of the 'just-in-time training' program was determined using electronic questionnaire responses. Medical Emergency Team call prevalence and outcome data was compared before and after the program implementation for further evaluation. The 'just-in-time training' program was implemented in a 508-bed acute metropolitan private hospital over a 12-month period. Education was provided in general medical and surgical wards, not specialty areas. Nurses received the just-in-time training based on their patients' perceived risk of deterioration, therefore, participants are not randomised. A quantitative research study investigated nurses' self-perceived confidence after receiving just-in-time training. Medical Emergency Team call frequency data was also examined to identify trends. The 'just-in-time training' program consisted of 534 bedside nursing encounters over 12 months. During the study, the need for the educator to recommend that nurses escalate care reduced in prevalence from 20% to 5.5%. Questionnaire responses demonstrated a self-perceived confidence following intervention of 4.32/5.0. Medical Emergency Team call prevalence, per 1000 patient bed days, increased from 13.6 pre-intervention to 15.4 post-intervention. Just-in-time training' can be effectively implemented to educate ward nursing staff in recognising and responding to the deteriorating patient. The program is well received by nursing staff and leads to high self-perceived confidence to recognise and appropriately care for a deteriorating patient.
Publisher: Massachusetts Medical Society
Date: 18-01-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-02-2022
DOI: 10.1097/ACO.0000000000001102
Abstract: The physiologically difficult airway is one in which physiologic alterations in the patient increase the risk for cardiorespiratory and other complications during tracheal intubation and transition to positive pressure ventilation. This review will summarize the recent literature around the emerging concept of the physiologically difficult airway, describe its relevance and various patient types in which this entity is observed. Physiologic derangements during airway management occur due acute illness, pre-existing disease, effects of anesthetic agents, and positive pressure ventilation. These derangements are especially recognized in critically ill patients, but can also occur in otherwise healthy patients including obese, pregnant and pediatric patients who have certain physiological alterations. Critically ill patients may have a physiologically difficult airway due to the presence of acute respiratory failure, hypoxemia, hypotension, severe metabolic acidosis, right ventricular failure, intracranial hypertension, and risk of aspiration of gastric contents during tracheal intubation. Understanding the physiological alterations and the risks involved in patients with a physiologically difficult airway is necessary to optimize the physiology and adopt strategies to avoid complications during tracheal intubation. Further research will help us better understand the optimal strategies to improve outcomes in these patients.
Publisher: AMPCo
Date: 25-01-2022
DOI: 10.5694/MJA2.50889
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JCRC.2018.09.015
Abstract: Research into team-training within healthcare is growing exponentially. We aim to evaluate the effects of team-training within intensive care medicine (ICM) through a review of the literature and a narrative synthesis of the results. A search of OVID Medline, EMBASE and Scopus databases was undertaken. Keywords and MESH headings included were "team-based learning", "team-training", "interdisciplinary training", "intensive care medicine", "ICU", "intensive care unit", "critical care teams" and "critical care". Relevant papers were then analysed for a narrative synthesis. Our search identified 187 articles. A total of 27 papers were analysed and their outcomes were evaluated based on the Kirkpatrick four step model of evaluation. Team-training has been studied in multiple ICU team types, with crew resource management (CRM) and TeamSTEPPS curricula commonly used to support teaching via simulation. Clinical skills taught have included ALS provision, ECMO initiation, advanced airway management, sepsis management and trauma response skills. Team-training in ICU is well received by staff, facilitates clinical learning, and can positively alter staff behaviors. Few clinical outcomes have been demonstrated and the duration of the behavioral effects is unclear.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JINF.2018.03.006
Abstract: microRNA expression profiles are of interest as a biomarker of tuberculosis (TB). How anti-TB therapy effects miRNA profiles is unknown and was examined. We identified 87 plasma miRNAs that were significantly modified in an exploratory group of 19 Chinese pulmonary TB (PTB) patients compared to 14 healthy controls. We selected 10 of these miRNAs for analysis in a cohort of 100 PTB patients prior to, and at one, two and six months during treatment. Five miRNAs were differentially expressed in PTB patients compared to controls at diagnosis miRs -29a and -99b were up-regulated, whilst miRs -21, -146a and -652 were down-regulated. A combination of 5 miRNA distinguished TB from healthy controls with a sensitivity of 94%, a specificity of 88%, and an AUC of 0.976. Within one month of treatment, significant changes in miRs -29a, -99b, -26a and 146a levels occurred in successfully treated patients, although not all miRNAs returned to baseline by treatment completion. A 5-miRNA signature shows potential for development as a novel biomarker for TB disease with potential to predict response to treatment. The failure of all miRNA to return to baseline levels may reflect ongoing remodelling in the lung parenchyma that continues after completion of anti-TB therapy.
Publisher: American Chemical Society (ACS)
Date: 12-02-2016
DOI: 10.1021/ACS.MOLPHARMACEUT.5B00833
Abstract: Recent studies have demonstrated that efflux pumps of Mycobacterium tuberculosis (M. tb) provide a crucial mechanism in the development of drug resistant to antimycobacterial drugs. Drugs that inhibit these efflux pumps, such as verapamil, have shown the potential in enhancing the treatment success. We therefore hypothesized that the combined inhaled administration of verapamil and a first-line rifamycin antibiotic will further improve the treatment efficacy. An inhalable dry powder consisting of amorphous verapamil and crystalline rifapentine with l-leucine as an excipient was produced by spray drying. The in vitro aerosol characteristic of the powder, its microbiological activity and stability were assessed. When the powder was dispersed by an Osmohaler, the total fine particle fraction (FPFtotal, wt % of particles in aerosol <5 μm) of verapamil and rifapentine was 77.4 ± 1.1% and 71.5 ± 2.0%, respectively. The combination drug formulation showed a minimum inhibitory concentration (MIC90) similar to that of rifapentine alone when tested against both M. tb H37Ra and M. tb H37Rv strains. Importantly, the combination resulted in increased killing of M. tb H37Ra within the infected macrophage cells compared to either verapamil or rifapentine alone. In assessing cellular toxicity, the combination exhibited an acceptable half maximal inhibitory concentration (IC50) values (62.5 μg/mL) on both human monocytic (THP-1) and lung alveolar basal epithelial (A549) cell lines. Finally, the powder was stable after 3 months storage in 0% relative humidity at 20 ± 3 °C.
Publisher: AMPCo
Date: 10-12-2018
DOI: 10.5694/MJA18.00755
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IMMUNI.2017.07.018
Abstract: The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.
Publisher: Wiley
Date: 21-07-2019
DOI: 10.1111/ANAE.14779
Abstract: The primary aim of this study was to identify, describe and compare the content of existing difficult airway management algorithms. Secondly, we aimed to describe the literature reporting the implementation of these algorithms. A directed search across three databases (MEDLINE, Embase and Scopus) was performed. All articles were screened for relevance to the research aims and according to pre-determined exclusion criteria. We identified 38 published airway management algorithms. Our results show that most facemask employ a four-step process as represented by a flow chart, with progression from tracheal intubation, facemask ventilation and supraglottic airway device use, to a rescue emergency surgical airway. The identified algorithms are overwhelmingly similar, yet many use differing terminology. The frequency of algorithm publication has increased recently, yet adherence and implementation outcome data remain limited. Our results highlight the lack of a single algorithm that is universally endorsed, recognised and applicable to all difficult airway management situations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-06-2022
DOI: 10.1097/CCM.0000000000005118
Abstract: To evaluate the functional outcome and health-related quality of life of in-hospital cardiac arrest survivors at 6 and 12 months. A longitudinal cohort study. Seven metropolitan hospitals in Australia. Data were collected for hospitalized adults (≥ 18 yr) who experienced in-hospital cardiac arrest, defined as “a period of unresponsiveness, with no observed respiratory effort and the commencement of external cardiac compressions.” None. Prior to hospital discharge, patients were approached for consent to participate in 6-month and 12-month telephone interviews. Outcomes included the modified Rankin Scale, Barthel Index, Euro-Quality of Life 5 Dimension 5 Level, return to work and hospital readmissions. Forty-eight patients (80%) consented to follow-up interviews. The mean age of participants was 67.2 (± 15.3) years, and 33 of 48 (68.8%) were male. Good functional outcome (modified Rankin Scale score ≤ 3) was reported by 31 of 37 participants (83.8%) at 6 months and 30 of 33 (90.9%) at 12 months. The median Euro-Quality of Life-5D index value was 0.73 (0.33–0.84) at 6 months and 0.76 (0.47–0.88) at 12 months. The median Euro-Quality of Life-Visual Analogue Scale score at 6 months was 70 (55–80) and 75 (50–87.5) at 12 months. Problems in all Euro-Quality of Life-5D-5 L dimension were reported frequently at both time points. Hospital readmission was reported by 23 of 37 patients (62.2%) at 6 months and 16 of 33 (48.5%) at 12 months. Less than half of previously working participants had returned to work by 12 months. The majority of in-hospital cardiac arrest survivors had a good functional outcome and health-related quality of life at 6 months, and this was largely unchanged at 12 months. Despite this, many reported problems with mobility, self-care, usual activities, pain, and anxiety/depression. Return to work rates was low, and hospital readmissions were common.
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/CH18206
Abstract: Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in the antitubercular compound 2-(decylsulfonyl)acetamide to a thioamide using Lawesson’s reagent to study its activity against a range of microorganisms. This derivative (8) had significantly diminished activity against tuberculosis but slightly better activity than the parent compound against the Gram positive species Staphylococcus aureus. This activity against a second major pathogen is remarkable considering the structural simplicity of these compounds.
Publisher: Frontiers Media SA
Date: 2017
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.DCI.2018.07.022
Abstract: Host lipid metabolism is an important target for subversion by pathogenic mycobacteria such as Mycobacterium tuberculosis. The appearance of foam cells within the granuloma are well-characterised effects of chronic tuberculosis. The zebrafish-Mycobacterium marinum infection model recapitulates many aspects of human-M. tuberculosis infection and is used as a model to investigate the structural components of the mycobacterial granuloma. Here, we demonstrate that the zebrafish-M. marinum granuloma contains foam cells and that the transdifferentiation of macrophages into foam cells is driven by the mycobacterial ESX1 pathogenicity locus. This report demonstrates conservation of an important aspect of mycobacterial infection across species.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.VACCINE.2018.03.037
Abstract: Tuberculosis (TB) infection affects a quarter of the global population resulting in a large burden of TB disease and mortality. The long-term control of TB requires vaccines with greater efficacy and durability than the current Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary immunization may increase and prolong immunity at the site of Mycobacterium tuberculosis infection. We have investigated recombinant influenza A viruses (rIAVs) expressing the p25 CD4
Publisher: American Chemical Society (ACS)
Date: 15-12-2016
DOI: 10.1021/ACS.MOLPHARMACEUT.6B00905
Abstract: Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles. The rifapentine powder was delivered to BALB/c mice by intratracheal insufflation at a dose of 20 mg/kg. The inflammatory response in the lungs and bronchoalveolar lavage (BAL) was examined at 12 h, 24 h, and 7 days post-treatment by flow cytometry and histopathology. At 12 and 24 h post-treatment, there was a significant influx of neutrophils into the lungs, and this returned to normal by day 7. A significant recruitment of macrophages occurred in the BAL at 24 h. Consistent with these findings, histopathological analysis demonstrated pulmonary vascular congestion and significant macrophage recruitment at 12 and 24 h post-treatment. In conclusion, the pulmonary delivery of crystalline rifapentine caused a transient neutrophil-associated inflammatory response in the lungs that resolved over 7 days. This observation may limit pulmonary delivery of rifapentine to once a week at a dose of 20 mg/kg or less. The effectiveness of weekly dosing with inhalable rifapentine will be assessed in murine Mycobacterium tuberculosis infection.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2017
DOI: 10.1007/S11095-017-2213-4
Abstract: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. Phage D29 lysate was lified to a titer of 11.8 ± 0.3 log Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2020
DOI: 10.1200/JCO.19.03117
Abstract: To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. Patients recruited between 2002 and 2015 with stage 4 disease 1 year or stage 4/4S with MYCN lification 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome. A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) ± SE (0.40 ± 0.01) and overall survival (OS 0.45 ± 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 ± 0.03 5-year OS, 0.37 ± 0.03 P .001 and P = .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 ± 0.01) compared with IME (0.30 ± 0.02 P .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 ± 0.02 v 0.39 ± 0.04 P = .038) CILP was 0.14 ± 0.01 after CME and 0.27 ± 0.03 after IME ( P .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy ( P = .030 and P = .038). In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/NCOMMS14414
Abstract: Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis , the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.
Publisher: Wiley
Date: 06-2020
DOI: 10.1111/ANAE.15115
Abstract: The coronavirus disease 2019 pandemic has led to the manufacturing of novel devices to protect clinicians from the risk of transmission, including the aerosol box for use during tracheal intubation. We evaluated the impact of two aerosol boxes (an early‐generation box and a latest‐generation box) on intubations in patients with severe coronavirus disease 2019 with an in‐situ simulation crossover study. The simulated process complied with the Safe Airway Society coronavirus disease 2019 airway management guidelines. The primary outcome was intubation time secondary outcomes included first‐pass success and breaches to personal protective equipment. All intubations were performed by specialist (consultant) anaesthetists and video recorded. Twelve anaesthetists performed 36 intubations. Intubation time with no aerosol box was significantly shorter than with the early‐generation box (median (IQR [range]) 42.9 (32.9–46.9 [30.9–57.6])s vs. 82.1 (45.1–98.3 [30.8–180.0])s p = 0.002) and the latest‐generation box (52.4 (43.1–70.3 [35.7–169.2])s, p = 0.008). No intubations without a box took more than 1 min, whereas 14 (58%) intubations with a box took over 1 min and 4 (17%) took over 2 min (including one failure). Without an aerosol box, all anaesthetists obtained first‐pass success. With the early‐generation and latest‐generation boxes, 9 (75%) and 10 (83%) participants obtained first‐pass success, respectively. One breach of personal protective equipment occurred using the early‐generation box and seven breaches occurred using the latest‐generation box. Aerosol boxes may increase intubation times and therefore expose patients to the risk of hypoxia. They may cause damage to conventional personal protective equipment and therefore place clinicians at risk of infection. Further research is required before these devices can be considered safe for clinical use.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2018
Publisher: AMPCo
Date: 12-06-2019
DOI: 10.5694/MJA2.50238
Publisher: Oxford University Press (OUP)
Date: 25-05-2018
DOI: 10.1093/IJE/DYY078
Publisher: Public Library of Science (PLoS)
Date: 19-08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2022
Publisher: Public Library of Science (PLoS)
Date: 07-05-2021
DOI: 10.1371/JOURNAL.PONE.0251523
Abstract: This paper aimed to describe the airway practices of intensive care units (ICUs) in Australia and New Zealand specific to patients presenting with COVID-19 and to inform whether consistent clinical practice was achieved. Specific clinical airway guidelines were endorsed in March 2020 by the Australian and New Zealand Intensive Care Society (ANZICS) and College of Intensive Care Medicine (CICM). Prospective, structured questionnaire for all ICU directors in Australia and New Zealand was completed by 69 ICU directors after email invitation from ANZICS. The online questionnaire was accessible for three weeks during September 2020 and analysed by cloud-based software. Basic ICU demographics (private or public, metropolitan or rural) and location, purchasing, airway management practices, guideline uptake, checklist and cognitive aid use and staff training relevant to airway management during the COVID-19 pandemic were the main outcome measures. The 69 ICU directors reported significant simulation-based inter-professional airway training of staff (97%), and use of video laryngoscopy (94%), intubation checklists (94%), cognitive aids (83%) and PPE “spotters” (89%) during the airway management of patients with COVID-19. Tracheal intubation was almost always performed by a Specialist (97% of ICUs), who was more likely to be an intensivist than an anaesthetist (61% vs 36%). There was a more frequent adoption of specific airway guidelines for the management of COVID-19 patients in public ICUs (94% vs 71%) and reliance on specialist intensivists to perform intubations in private ICUs (92% vs 53%). There was a high uptake of a standardised approach to airway management in COVID-19 patients in ICUs in Australia and New Zealand, likely due to endorsement of national guidelines.
Publisher: American Society for Microbiology
Date: 02-2018
DOI: 10.1128/AAC.01714-17
Abstract: Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery however, phage dry-powder administration to the lungs has not yet been explored. Powder formulations provide potential advantages over a liquid formulation, including easy storage, transport, and administration. The purpose of this study was to assess the bactericidal activities of phage dry-powder formulations against multidrug-resistant (MDR) strain Pseudomonas aeruginosa FADDI-PA001 in a mouse lung infection model. Phage PEV20 spray dried with lactose and leucine produced an inhalable powder at a concentration of 2 × 10 7 PFU/mg. P. aeruginosa lung infection was established by intratracheal administration of the bacterial suspension to neutropenic mice. At 2 h after the bacterial challenge, the infected mice were treated with 2 mg of the phage powder using a dry-powder insufflator. At 24 h after the phage treatment, the bacterial load in the lungs was decreased by 5.3 log 10 ( P 0.0005) in the phage-treated group compared with that in the nontreated group. Additionally, the phage concentration in the lungs was increased by 1 log 10 at 24 h in the treated group. These results demonstrate the feasibility of a pulmonary delivery of phage PEV20 dry-powder formulation for the treatment of lung infection caused by antibiotic-resistant P. aeruginosa .
Publisher: Wiley
Date: 16-09-2023
DOI: 10.1111/IMJ.15884
Abstract: Vaccination has been shown to be highly effective in preventing death and severe disease from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Currently, few studies have directly compared vaccinated and unvaccinated patients with severe COVID‐19 in the intensive care unit (ICU). To compare the clinical characteristics and outcomes of vaccine recipients and unvaccinated patients with SARS‐CoV‐2 infection admitted to the ICU in a nationwide setting. Data were extracted from the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection Australia, in 57 ICU during Delta and Omicron predominant periods of the COVID‐19 pandemic. The primary outcome was inhospital mortality. Secondary outcomes included duration of mechanical ventilation, ICU length of stay, hospital length of stay and ICU mortality. There were 2970 patients admitted to ICU across participating sites from 26 June 2021 to 8 February 2022 1134 (38.2%) patients were vaccine recipients, and 1836 (61.8%) patients were unvaccinated. Vaccine recipients were older, more comorbid and less likely to require organ support. Unadjusted inhospital mortality was greater in the vaccinated cohort. After adjusting for age, gender and comorbid status, no statistically significant association between inhospital or ICU mortality, and vaccination status, was apparent. We found COVID‐19 infection can cause severe disease and death in vaccine recipients, though comorbid status and older age were significant contributors to mortality. Organ support requirements and the number of deaths were highest in the unvaccinated cohort.
Publisher: SAGE Publications
Date: 11-2018
Publisher: SAGE Publications
Date: 07-2020
Abstract: An integrative review of the literature specific to leadership within the intensive care unit was planned to guide future research. Four databases were searched. Study selection was based on predetermined inclusion and exclusion criteria and a quality check was done. Data extraction and synthesis involved developing a preliminary thematic coding framework based on a s le of papers. The coding framework and all selected papers were entered into NVivo software. All papers were then coded to the previously identified themes. Themes were summarised and presented with illustrative quotes highlighting key findings. In total, 1102 relevant quotations were coded across the 28 included papers. Four themes pertaining to leadership were described and analysed: (a) leadership dimensions and discourses (b) leadership experiences (c) facilitators and/or barriers to leadership and (d) leadership outcomes. The literature was found to focus on leader behaviours, as well as the leader dimensions of role allocation, clinical and communication skills and traditional hierarchies. Positive behaviours mentioned included good decision-making, staying calm under pressure and being approachable. Leadership experiences (and outcomes) are typically reported to be positive. Personal in idual factors seem the biggest enablers and barriers to leadership within the intensive care unit. Training is considered to be a facilitator of leadership within the intensive care unit. This study highlights the current literature on leadership in intensive care medicine and provides a basis for future research on interventions to improve leadership in the intensive care unit.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ADDR.2016.05.011
Abstract: Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 12-2017
Publisher: AMPCo
Date: 05-2020
DOI: 10.5694/MJA2.50598
Publisher: Wiley
Date: 21-09-2019
DOI: 10.1111/ANS.14800
Abstract: Post-operative acute kidney injury after cardiopulmonary bypass (AKI-CPB) for cardiac surgery is a frequent complication. It may require renal replacement therapy (RRT), which is associated with an increased morbidity and mortality. This review explores the efficacy of proposed pharmacological and non-surgical renal protective strategies. A comprehensive literature search was done using Ovid MEDLINE, Embase and Scopus databases. Keywords included were cardiopulmonary bypass, cardiac surgery, coronary artery bypass, renal protection and renal preservation. Eligible articles consisted of all studies on patients who had undergone cardiac surgery via CPB with an outcome of AKI and/or RRT reported. All studies underwent a quality check via the risk of bias tool. The three most researched interventions (based on number of randomized controlled trials and total patients analysed) and their renal outcomes were then analysed with Review Manager Software. Eighty-eight articles were extracted. A total of 26 management strategies for renal protection following CPB were identified. N-acetylcysteine (NAC), remote ischaemic preconditioning (RIPC) and the use of volatile anaesthetic agents (VAAs) were further analysed. NAC, RIPC and VAA had no statistically significant benefit in reducing either AKI-CPB or the need for RRT following CPB. NAC, RIPC and VAA were found to have no statistical significant benefit in reducing either AKI-CPB or the need for RRT following CPB. There remains clinical uncertainty with all currently proposed pharmacological and non-surgical renal protective strategies for CPB. Future research in this area should analyse the effects of combined interventions or specifically focus on 'at-risk' patients.
Publisher: American Chemical Society (ACS)
Date: 04-11-2017
DOI: 10.1021/ACS.JPROTEOME.6B00685
Abstract: Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of frontline alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M. tb infection. Infection promoted a dramatic regulation of the macrophage proteome. Most notably, significant infection-dependent down-regulation (4-26 fold) of 11 lysosomal exoglycosidases, e.g., β-galactosidase, β-hexosaminidases and α-/β-mannosidases, was observed. Relative weak infection-driven transcriptional regulation of these exoglycosidases and a stronger augmentation of the extracellular hexosaminidase activity demonstrated that the lysosome-centric changes may originate predominantly from infection-induced secretion of the lysosomal content. The macrophages showed heterogeneous N-glycan profiles and displayed significant up-regulation of complex-type glycosylation and concomitant down-regulation of paucimannosylation upon infection. Complementary intact N-glycopeptide analysis supported a subcellular-specific manipulation of the glycosylation machinery and altered glycosylation patterns of lysosomal N-glycoproteins within infected macrophages. Interestingly, the corresponding macrophage-derived MPs displayed unique N-glycome and proteome signatures supporting a preferential packaging from plasma membranes. The MPs were devoid of infection-dependent N-glycosylation signatures, but interestingly displayed increased levels of the glyco-initiating oligosaccharyltransferase complex and associated α-glucosidases that correlated with increased formation, N-glycan precursor levels and N-glycan density of infected MPs. In conclusion, this system-wide study provides new insight into the host- and pathogen-driven N-glycoproteome manipulation of macrophages in TB.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-05-2021
DOI: 10.1213/ANE.0000000000005583
Abstract: Emergency front-of-neck airway rescue is recommended in a can’t intubate, can’t oxygenate clinical scenario. Cannula cricothyroidotomy has been reported as having a high failure rate. Our primary aim was to estimate the angle of the trachea in relation to the horizontal axis in a simulated emergency front-of-neck airway rescue position. Our secondary aims were to estimate the optimal cannula angle of approach and evaluate the anatomical relationship of the cricothyroid membrane (CTM) to adjacent structures. We also assessed whether the CTM lies above or below the neck midpoint, a point equidistant from the suprasternal notch (SSN), and the chin surface landmarks. All measurements were compared between the male and female subjects. Subjects having elective computed tomography of their thorax were consented to have extension of the computed tomography to include their neck. A preliminary radiation dose and risk assessment deemed the additional radiation to be of very low risk (level IIa). Subjects were positioned supinely on the computed tomography table. Standard neck extension was achieved by placing a pillow under the scapulae and a rolled towel under the neck to simulate emergency front-of-neck airway rescue positioning. Fifty-two subjects were included in this study: 31 men and 21 women. The mean angle of the trachea in relation to the horizontal axis was 25.5° (95% confidence interval [CI], 21.8–29.1) in men and 14.0° (95% CI, 11.5–16.5) in women. The mean minimum angles required for hypothetical cannula cricothyroidotomy for men and women were 55.2° (95% CI, 51.8–58.7) and 50.5° (95% CI, 45.4–55.6), respectively. The CTM was located lower in the neck in men compared to women. The CTM was located below the neck midpoint in 30 of 30 (100%) male subjects and 11 of 20 (55%) female subjects ( P .001). The trachea angulates posteriorly in a simulated emergency front-of-neck airway rescue position in supine subjects and to a greater degree in men compared to women ( P .001). The minimum angle required for hypothetical cannula cricothyroidotomy was ° in the majority (75%) of subjects studied. A steeper cannula angle of approach may be more reliable and warrants further clinical study. If airway anatomy is indistinct and performing a vertical scalpel cricothyroidotomy, consideration should be given to performing this incision lower in the neck in men compared to women.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1038/S41385-018-0065-9
Abstract: The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (T
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: SAGE Publications
Date: 07-2021
DOI: 10.1177/0310057X211024691
Abstract: The use of high flow nasal oxygen in the care of COVID-19-positive adult patients remains an area of contention. Early guidelines have discouraged the use of high flow nasal oxygen therapy in this setting due to the risk of viral spread to healthcare workers. However, there is the need to balance the relative risks of increased aerosol generation and virus transmission to healthcare workers against the role high flow nasal oxygen has in reducing hypoxaemia when managing the airway in high-risk patients during intubation or sedation procedures. The authors of this article undertook a narrative review to present results from several recent papers. Surrogate outcome studies suggest that the risk of high flow nasal oxygen in dispersing aerosol-sized particles is probably not as great as first perceived. Smoke laser-visualisation experiments and particle counter studies suggest that the generation and dispersion of bio-aerosols via high flow nasal oxygen with flow rates up to 60 l/min is similar to standard oxygen therapies. The risk appears to be similar to oxygen supplementation via a Hudson mask at 15 l/min and significantly less than low flow nasal prong oxygen 1–5 l/min, nasal continuous positive airway pressure with ill-fitting masks, bilevel positive airway pressure, or from a coughing patient. However, given the limited safety data, we recommend a cautious approach. For intubation in the COVID-positive or suspected COVID-positive patient we support the use of high flow nasal oxygen to extend time to desaturation in the at-risk groups, which include the morbidly obese, those with predicted difficult airways and patients with significant hypoxaemia, ensuring well-fitted high flow nasal oxygen prongs with staff wearing full personal protective equipment. For sedation cases, we support the use of high flow nasal oxygen when there is an elevated risk of hypoxaemia (e.g. bariatric endoscopy or prone-positioned procedures), but recommend securing the airway with a cuffed endotracheal tube for the longer duration procedures when theatre staff remain in close proximity to the upper airway, or considering the use of a surgical mask to reduce the risk of exhaled particle dispersion.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Springer Science and Business Media LLC
Date: 17-08-2017
DOI: 10.1038/S41598-017-09119-Y
Abstract: There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis . Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis . The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis -infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4 + T cells (IFN-γ + TNF + IL-2 + ). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (Advax CpG ), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/Advax CpG resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2 - specific CD4 + T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/Advax CpG is a strong candidate for further preclinical evaluation for progression to human trials.
Publisher: American Thoracic Society
Date: 15-08-2022
Publisher: American Association for Cancer Research (AACR)
Date: 07-2018
DOI: 10.1158/1078-0432.CCR-17-2257
Abstract: Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses, however, occur in less than half of those treated, and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate antitumor immune response. Patients and Methods: We performed multiparameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti–PD-1 therapy. Results: Increased numbers of CD69+CD103+ tumor-resident CD8+ T cells were associated with improved melanoma-specific survival in immunotherapy-naïve melanoma patients. Local IL15 expression levels strongly correlated with these tumor-resident T-cell numbers. The expression of several immune checkpoints including PD-1 and LAG3 was highly enriched in this subset, and these cells significantly expanded early during anti–PD-1 immunotherapy. Conclusions: Tumor-resident CD8+ T-cell numbers are more prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are likely to initiate response to anti–PD-1 and anti–LAG-3 treatments. We propose that the immune profile of these cells prior to treatment could inform strategies for immune checkpoint blockade. Clin Cancer Res 24(13) 3036–45. ©2018 AACR.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.IJID.2018.06.013
Abstract: Patients completing treatment for tuberculosis (TB) in high-prevalence settings face a risk of developing recurrent disease. This has important consequences for public health, given its association with drug resistance and a poor prognosis. Previous research has implicated in idual factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug resistant disease as risk factors for recurrence. However, little is known about how these factors co-act to produce recurrent disease. Furthermore, perhaps factors related to the index disease means higher burden/low resource settings may be more prone to recurrent disease that could be preventable. We conducted a case-control study nested within a cohort of consecutively enrolled adults who were being treated for smear positive pulmonary TB in 70 randomly selected district clinics in Vietnam. Cases were patients with recurrent TB, identified by follow-up from the parent cohort study. Controls were selected from the cohort by random s ling. Information on demographic, clinical and disease-related characteristics was obtained by interview. Treatment information was extracted from clinic registries. Logistic regression, with stepwise selection, was used to develop a fully adjusted model for the odds of recurrence of TB. We recruited 10,964 patients between October 2010 and July 2013. Median follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with recurrence were identified as cases and 630 other patients were randomly selected as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB (adjusted odds ratio 79.6 95% CI: 25.1-252.0), self-reported prior TB therapy (aOR=2.5 95% CI: 1.7-3.5), and incomplete adherence (aOR=1.9 95% CI 1.1-3.1). Index disease treatment history is a leading determinant of relapse among patients with TB in Vietnam. Further research is required to identify interventions that will reduce the risk of recurrent disease and enhance its early detection within high-risk populations.
Publisher: American Medical Association (AMA)
Date: 23-03-2021
Publisher: Elsevier BV
Date: 04-2017
Publisher: The American Association of Immunologists
Date: 09-2017
Abstract: Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation however, its role in immunity to M. tuberculosis is unknown. To address this, we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lungs after 2 wk. However, this early control of infection was not maintained, and by 8 wk postinfection sanroque mice demonstrated an increased bacterial burden and dysregulated inflammation in the lungs. As the inflammation in the lungs of the sanroque mice could have been influenced by emerging autoimmune conditions that are characteristic of the mice aging, the function of Roquin was examined in immune cell subsets in the absence of autoimmune complications. M. bovis bacillus Calmette–Guérin-primed sanroque T cells transferred into Rag1−/− mice provided equivalent protection in the spleen and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4+ TCR transgenic) wild-type spleen cells into sanroque.Rag1−/− mice actually led to enhanced protection with reduced bacterial load, decreased chemokine expression, and reduced inflammation in the lungs compared with transfers into Rag1−/− mice expressing intact Roquin. These studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of M. tuberculosis infection.
Publisher: BMJ
Date: 20-11-2021
Publisher: SAGE Publications
Date: 09-2020
Abstract: The primary aim of this study was to evaluate the perceptions of Australian anaesthetists in relation to smartphone use within anaesthetic practice. In particular, we aimed to assess the frequency of smartphone use, the types and number of smartphone applications used, how reliant anaesthetists perceive themselves to be on smartphones and whether they perceive them to be a factor that aids or distracts from their practice. Secondly, we assessed whether there is an association between the type, frequency, reliance and perceptions of smartphone use and the years of experience as an anaesthetist. A 24-item questionnaire addressing these questions was created and distributed to an email list of credentialled anaesthetists in Melbourne, Australia. A total of 113 consultant anaesthetists who practise at 55 hospitals in Melbourne completed the questionnaire. Our results suggest that the majority of anaesthetists are using smartphones regularly in their practice. About 74% of respondents agreed that they rely on their smartphone for their work. We found that respondents were more likely to rely on smartphones and consider them to aid patient safety than to consider them a distraction. This phenomenon was particularly apparent in those who had been a consultant anaesthetist for less than three years. Furthermore, those who had been a consultant anaesthetist for less than three years were more likely to have more smartphone apps relating to anaesthetics, use them more often and rely on them to a greater degree. Our results highlight the ubiquitous and perceived useful nature of smartphones in anaesthetic practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-07-2020
Publisher: AMPCo
Date: 17-11-2019
DOI: 10.5694/MJA2.50416
Publisher: Public Library of Science (PLoS)
Date: 19-03-2018
Publisher: American Chemical Society (ACS)
Date: 07-02-2018
DOI: 10.1021/ACS.ORGLETT.7B03967
Abstract: The first total synthesis of the potent anti-mycobacterial cyclic depsipeptide natural product ecumicin is described. Synthesis was achieved via a solid-phase strategy, incorporating the synthetic non-proteinogenic amino acids N-methyl-4-methoxy-l-tryptophan and threo-β-hydroxy-l-phenylalanine into the growing linear peptide chain. The synthesis employed key on-resin esterification and dimethylation steps as well as a final macrolactamization between the unusual N-methyl-4-methoxy-l-tryptophan unit and a bulky N-methyl-l-valine residue. The synthetic natural product possessed potent antimycobacterial activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC
Publisher: Public Library of Science (PLoS)
Date: 20-10-2022
DOI: 10.1371/JOURNAL.PONE.0276420
Abstract: This study aimed to describe how video laryngoscopy is used outside the operating room within the hospital setting. Specifically, we aimed to summarise the evidence for the use of video laryngoscopy outside the operating room, and detail how it appears in current clinical practice guidelines. A literature search was conducted across two databases (MEDLINE and Embase), and all articles underwent screening for relevance to our aims and pre-determined exclusion criteria. Our results include 14 clinical practice guidelines, 12 interventional studies, 38 observational studies. Our results show that video laryngoscopy is likely to improve glottic view and decrease the incidence of oesophageal intubations however, it remains unclear as to how this contributes to first-pass success, overall intubation success and clinical outcomes such as mortality outside the operating room. Furthermore, our results indicate that the appearance of video laryngoscopy in clinical practice guidelines has increased in recent years, and particularly through the COVID-19 pandemic. Current COVID-19 airway management guidelines unanimously introduce video laryngoscopy as a first-line (rather than rescue) device.
Publisher: Springer Science and Business Media LLC
Date: 27-09-2016
DOI: 10.1208/S12248-016-9988-9
Abstract: The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 μm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer® with the same configuration (single pin and one-third air inlet) that accommodates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5-2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer® inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections.
Publisher: Public Library of Science (PLoS)
Date: 05-01-2016
Publisher: Elsevier BV
Date: 06-2018
Publisher: Wiley
Date: 12-09-2022
DOI: 10.1111/ANAE.15813
Abstract: The primary aim of this review was to identify, analyse and codify the prominence and nature of human factors and ergonomics within difficult airway management algorithms. A directed search across OVID Medline and PubMed databases was performed. All articles were screened for relevance to the research aims and according to predetermined exclusion criteria. We identified 26 published airway management algorithms. A coding framework was iteratively developed identifying human factors and ergonomic specific words and phrases based on the Systems Engineering Initiative for Patient Safety model. This framework was applied to the papers to delineate qualitative and quantitative results. Our results show that human factors are well represented within recent airway management guidelines. Human factors associated with work systems and processes featured more prominently than user and patient outcome measurement and adaption. Human factors are an evolving area in airway management and our results highlight that further considerations are necessary in further guideline development.
Location: Australia
Location: Australia
No related grants have been discovered for David Brewster.