Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses.

Whole blood models are rapid and versatile for determining immune responses to inflammatory and infectious stimuli, but they have not been used for bacterial discrimination. Staphylococcus aureus, S. epidermidis and Escherichia coli are the most common causes of invasive disease, and rapid testing strategies utilising host responses remain elusive. Currently, immune responses can only discriminate between bacterial 'domains' (fungi, bacteria and viruses), and very few studies can use immune responses to discriminate bacteria at the species and strain level. Here, whole blood was used to investigate the relationship between host responses and bacterial strains. Results confirmed unique temporal profiles for the 10 parameters studied: IL-6, MIP-1α, MIP-3α, IL-10, resistin, phagocytosis, S100A8, S100A8/A9, C5a and TF3. Pairwise analysis confirmed that IL-6, resistin, phagocytosis, C5a and S100A8/A9 could be used in a discrimination scheme to identify to the strain level. Linear discriminant analysis (LDA) confirmed that (i) IL-6, MIP-3α and TF3 could predict genera with 95% accuracy; (ii) IL-6, phagocytosis, resistin and TF3 could predict species at 90% accuracy and (iii) phagocytosis, S100A8 and IL-10 predicted strain at 40% accuracy. These data are important because they confirm the proof of concept that host biomarker panels could be used to identify bacterial pathogens.

Diagnostic strategies in postpartum individuals with suspected venous thromboembolism: A scoping review.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased postpartum and contributes to important morbidity and mortality. While there have been advances in evaluating diagnostic algorithms for suspected VTE during pregnancy, there is limited data for postpartum individuals. OBJECTIVE: We conducted a scoping review to describe and evaluate diagnostic strategies used to investigate suspected VTE in postpartum individuals. METHODS: A comprehensive search strategy was conducted in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (January 1, 2000-September 30, 2022) to identify original articles that reported on diagnostic strategies in postpartum individuals with suspected VTE. We extracted demographics, clinical decision rules used, D-dimer and imaging completed, including test performance and VTE outcomes. RESULTS: A total of 13 studies conducted across 11 countries with separate postpartum data were included for 759 individuals with suspected PE (n = 634) or DVT (n = 125), including unpublished data (n = 251). Among those with suspected PE, computed tomography pulmonary angiography was conducted more commonly (n = 522) than ventilation-perfusion scans (n = 69), with PE positivity rates that ranged from 4 %-27.6 % and 0-50 % across studies, respectively. Among 131 postpartum individuals with suspected PE who had a D-dimer measured, only 4.6 % (6/131) had a negative D-dimer test. For postpartum individuals with suspected DVT, the most common diagnostic test was compression ultrasonography (positivity rate 12.2 %-18.6 %). There were limited retrospective data evaluating the clinical decision rules. CONCLUSIONS: There are heterogeneous approaches globally in the diagnosis of suspected postpartum VTE. Limited high-quality data available underscores the need for more robust evidence to inform clinical practice.

Health-system specialty pharmacist intervention types, acceptance, and associated actions for patients with multiple sclerosis.

PURPOSE: Health-system specialty pharmacy (HSSP) pharmacists play an integral role in the care of patients with multiple sclerosis (PwMS) by facilitating medication access, providing counseling, improving adherence, and decreasing provider workload. However, current literature detailing pharmacist interventions and their acceptance rates in this population is limited. The purpose of this study was to identify the types and acceptance rate of clinical interventions completed by pharmacists for PwMS. METHODS: To evaluate the acceptance rate of HSSP pharmacist interventions, we conducted a retrospective, multicenter, observational, descriptive study for the period from October 2019 to August 2022. Intervention types were categorized into reasons for intervention, recommendations from the pharmacists, and their acceptance rates. RESULTS: For 225 patients enrolled in HSSP services, 449 interventions were completed, with an average of 2.0 interventions per patient. Most interventions identified were associated with medication adherence (28.7%), medication regimen (27.6%), adverse drug reaction (ADR) (20.7%), and laboratory values (15.1%). The average adherence, defined by the proportion of days covered, was 94%. The most common recommendations were to continue therapy (14.9%), schedule laboratory tests (12.7%), and follow up with providers (11.8%). Recommendations had an acceptance rate of 85.3%, with 3.8% of recommendations declined and 10.9% requiring follow-up with providers. CONCLUSION: Pharmacists impact patient outcomes through the completion of clinical interventions that improve adherence, identify medication regimen problems, manage ADRs, and coordinate proper laboratory testing. Pharmacist recommendations were most often accepted for interventions related to medication regimen and ADRs. Proper identification and management of medication regimen concerns, as well as tolerability of medications, can positively impact adherence and improve overall patient outcomes.

An Australian COVID-19 respiratory care unit experience.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a heterogeneous presentation ranging from severe pneumonitis to asymptomatic infection. International studies have demonstrated the utility of respiratory care units (RCUs) to facilitate the delivery of non-invasive ventilation techniques to patients with COVID-19 pneumonitis. AIMS: This study aims to describe the patient characteristics, flow and outcomes of admissions to the Royal Melbourne Hospital (RMH) COVID-19 RCU (CRCU) during its initial period of operation. METHODS: Single-centre retrospective cohort study, all patients admitted to CRCU between 17 September and 10 December 2021 were included in this study. Patient demographics, including comorbidities and limitations of medical treatment, were analysed. Admission source and discharge destination were reviewed. Length of stay was recorded. Finally, in-hospital and CRCU mortality were analysed. RESULTS: Ninety-seven patients, comprising 111 admissions, occurred during the study period with median age of 65 years (48% female). Most patients were admitted from and discharged to the ward. Twenty patients died in hospital (21%), with age, 4C score, comorbidity and presence of obstructive lung disease predicting mortality (area under the curve (AUC) 0.85, P < 0.001). Mortality was significantly higher in those over 65 years of age compared to those under 65 (P < 0.001), or those deemed not for intubation compared to those for intubation (P = 0.0019). CONCLUSIONS: This study demonstrates the feasibility of operating a CRCU within an Australian tertiary healthcare setting.

The Psychological and Wellbeing Impacts of Quarantine on Frontline Workers during COVID-19 and Beyond.

OBJECTIVE: The current study investigated the experiences, wellbeing impacts, and coping strategies of frontline workers who participated in "Hotels for Heroes", an Australian voluntary hotel quarantine program during the COVID-19 pandemic. The program was open to those who were COVID-19 positive or exposed to COVID-19 as part of their profession. METHODS: Frontline workers who had stayed in voluntary quarantine between April 2020 and March 2021 were invited to participate in a voluntary, anonymous, cross-sectional online survey including both quantitative and qualitative responses. Complete responses were collected from 106 participants, which included data on sociodemographic and occupational characteristics, experiences of the Hotels for Heroes program, and validated mental health measures. RESULTS: Mental health problems were prevalent amongst frontline workers (e.g., moderate anxiety symptoms, severe depression symptoms, and greater than usual impact of fatigue). For some, quarantine appeared to be helpful for anxiety and burnout, but quarantine also appeared to impact anxiety, depression, and PTSD negatively, and longer stays in quarantine were associated with significantly higher coronavirus anxiety and fatigue impacts. The most widely received support in quarantine was from designated program staff; however, this was reportedly accessed by less than half of the participants. CONCLUSIONS: The current study points to specific aspects of mental health care that can be applied to participants of similar voluntary quarantine programs in the future. It seems necessary to screen for psychological needs at various stages of quarantine, and to allocate appropriate care and improve its accessibility, as many participants did not utilise the routine support offered. Support should especially target disease-related anxiety, symptoms of depression and trauma, and the impacts of fatigue. Future research is needed to clarify specific phases of need throughout quarantine programs, and the barriers for participants receiving mental health supports in these contexts.

Improving care for people with bronchiectasis: opportunities and challenges highlighted from service evaluation.

BACKGROUND: Bronchiectasis is a serious, debilitating condition warranting specialist care. AIMS: To determine if care provided in a tertiary hospital general respiratory clinic was guideline concordant and to validate the Bronchiectasis Severity Index (BSI) in the Australian context. METHODS: A single-centre ambispective study was conducted. The first stage involved a retrospective medical record audit between 1 January 2015 and 31 December 2016. All aspects of bronchiectasis management were reviewed. In the second prospective phase the cohort was followed for 4 years to determine survival and the validity of the BSI determined. RESULTS: A total of 145 patients was included, with mean age of 65 years (standard deviation = 16.6). The aetiology of bronchiectasis was explicitly documented for 58 (40%) patients, with potential causes identified in another 37 patients. Post-infectious aetiologies were described in 62 (43%) patients. Most patients had lung function testing (n = 142; 97%) and sputum culture results (n = 120; 83%). Long-term antibiotics were prescribed to 49 (34%) patients. Only patients culturing Pseudomonas spp. were prescribed inhaled antibiotics. Documentation regarding essential management recommendations was low, including airway clearance (46%), pneumococcal vaccination (27%) and written action plans (32%). Severe disease was common, with more than one-third (34-48%) having BSI scores >9. One-fifth (21%) of the cohort died during the 4-year follow-up period. The BSI was significantly associated with mortality risk (odds ratio 7.7; 95% confidence interval = 3.1-19.3; P < 0.001). CONCLUSION: Our cohort had a high proportion of patients with severe disease and significant mortality; some, but not all, aspects of recommended care were delivered.

Diagnostic imaging for suspected pulmonary embolism during pregnancy and postpartum: A comparative radiation dose study.

INTRODUCTION: To compare the radiation dose exposure and diagnostic efficiency of computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion imaging (V/Q) for clinically suspected pulmonary embolism (PE) in pregnant and postpartum women in a tertiary hospital setting. METHODS: A retrospective cohort study of 473 pregnant and postpartum women referred for CTPA or V/Q for clinically suspected PE between January 2013 and December 2018 at a tertiary hospital. Maternal effective radiation dose, breast-absorbed radiation dose and fetal-absorbed dose estimates were calculated. Diagnostic yield was evaluated from radiological findings. RESULTS: Computed tomographic pulmonary angiography (CTPA) was more commonly used for the imaging of suspected PE in pregnant and postpartum populations (51.9% vs. 48.1% and 77.1% vs. 22.9%, respectively). CTPA was associated with higher maternal effective and breast-absorbed doses (maternal effective CTPA 4.7 (±2.9) mSv (millisievert), V/Q 1.7(±0.8) mSv (mean difference 2.93 mSv P < 0.001), and breast-absorbed CTPA 8.0 (±5.2) mGy (milligray), V/Q 0.3 (±0.1) (mean difference 7.67 mGy P < 0.001), respectively). Fetal radiation dose exposure was low. The incidence of positive PE was 5.5%. Indeterminate rates of CTPA and V/Q were 3.0% and 5.5% (P = 0.176), respectively. CONCLUSIONS: Compared to V/Q, CTPA is associated with higher maternal and breast radiation dose; however, modern CT scanners achieve lower radiation doses than historically described. Fetal radiation dose was comparably low. The diagnostic yield of the imaging modalities in pregnant and postpartum women is similar. Revision of guidelines should occur with the advances in CT technology.

Bronchiectasis.

BACKGROUND: Bronchiectasis is a common chronic lung disease that is prevalent in the Australian community and is a significant disease burden in the Australian Aboriginal community. It significantly affects quality of life and increases healthcare costs; however, it is poorly reported and documented. OBJECTIVE: The aim of this article is to provide a comprehensive summary of the important features to recognise in bronchiectasis and an updated guide to the management of bronchiectasis. DISCUSSION: Bronchiectasis is an obstructive lung disease that is often associated with various underlying conditions that can occur as a result of infectious insult or impaired host defence. The main features of bronchiectasis are dilated airways with increased sputum production, recurrent exacerbations and impaired quality of life. Management is aimed at investigating and managing secondary causes with a focus on sputum clearance, reduction in exacerbations and improvement of quality of life.

ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial.

BACKGROUND: SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. METHODS: ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. DISCUSSION: This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12620000445976) and ClinicalTrials.gov (NCT04483960).

COVID-19 infection and the broader impacts of the pandemic on healthcare workers.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease or COVID-19 pandemic is associated with more than 230 million cases and has challenged healthcare systems globally. Many healthcare workers (HCWs) have acquired the infection, often through their workplace, with a significant number dying. The epidemiology of COVID-19 infection in HCWs continues to be explored, with manifold exposure risks identified, leading to COVID-19 being recognised as an occupational disease for HCWs. The physical illness due to COVID-19 in HCWs is similar to the general population, with some HCWs experiencing a long-term illness, which may impact their ability to return to work. HCWs have also been affected by the immense workplace and psychosocial disruption caused by the pandemic. The impacts on the psychological well-being of HCWs globally have been profound, with high prevalence estimates for mental health symptoms, including emotional exhaustion. Globally, governments, healthcare organisations and employers have key responsibilities, including: to be better prepared for crises with comprehensive disaster response management plans, and to protect and preserve the health workforce from the physical and psychological impacts of the pandemic. While prioritising HCWs in vaccine rollouts globally has been critical, managing exposures and outbreaks occurring in healthcare settings remains challenging and continues to lead to substantial disruption to the health workforce. Safeguarding healthcare workforces during crises is critical as we move forward on the new path of 'COVID normal'.

COVID-19 pandemic 2020: a tertiary Melbourne hospital's experience.

BACKGROUND: The COVID-19 pandemic has affected different parts of Australia in distinct ways across 2020 and 2021. In 2020, Melbourne was the epicentre of COVID-19. As one of the key tertiary centres caring for the patients affected by the outbreaks, the Royal Melbourne Hospital (RMH) managed the majority of the Victorian inpatient caseload. AIMS: To review the demographics, management and outcomes of patients with COVID-19 cared for by the RMH services in 2020. METHODS: A single health service retrospective cohort analysis of demographics, interventions and outcomes was conducted to characterise the RMH experience in 2020. RESULTS: From January to December 2020, 433 patients required admission more than 24 h. The demographics of affected patients and outcomes changed over the course of the study. Overall, 47% (203/433) required oxygen, most frequently (36%; 154/433) with low-flow devices (nasal prongs or hudson mask), and 11% (47/433) of patients required admission to intensive care. We recorded a 30-day mortality of 24% (104/433) mortality overall, rising to over 50% in patients aged over 80 years. CONCLUSIONS: The experience of this health service in 2020 demonstrated changing demographics over time, with associated differences in outcomes; notably marked mortality in older populations, frequent complications and limited inter-site transfer possible with mobilised resources.

COVID-19 and pregnancy: A review of clinical characteristics, obstetric outcomes and vertical transmission.

BACKGROUND: Since its emergence in December 2019, COVID-19 has spread to over 210 countries, with an estimated mortality rate of 3-4%. Little is understood about its effects during pregnancy. AIMS: To describe the current understanding of COVID-19 illness in pregnant women, to describe obstetric outcomes and to identify gaps in the existing knowledge. METHODS: Medline Ovid, EMBASE, World Health Organization COVID-19 research database and Cochrane COVID-19 in pregnancy spreadsheet were accessed on 18/4, 18/5 and 23/5 2020. Articles were screened via Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following were excluded: reviews, opinion pieces, guidelines, articles pertaining solely to other viruses, single case reports. RESULTS: Sixty articles were included in this review. Some pregnant participants may have been included in multiple publications, as admission dates overlap for reports from the same hospital. However, a total of 1287 confirmed SARS-CoV-2 positive pregnant cases are reported. Where universal testing was undertaken, asymptomatic infection occurred in 43.5-92% of cases. In the cohort studies, severe and critical COVID-19 illness rates approximated those of the non-pregnant population. Eight maternal deaths, six neonatal deaths, seven stillbirths and five miscarriages were reported. Nineteen neonates were SARS-CoV-2 positive, confirmed by reverse transcription polymerase chain reaction of nasopharyngeal swabs. [Correction added on 2 September 2020, after first online publication: the number of neonates indicated in the preceding sentence has been corrected from 'Thirteen' to 'Nineteen'.] CONCLUSIONS: Where universal screening was conducted, SARS-CoV-2 infection in pregnancy was often asymptomatic. Severe and critical disease rates approximate those in the general population. Vertical transmission is possible; however, it is unclear whether SARS-CoV-2 positive neonates were infected in utero, intrapartum or postpartum. Future work should assess risks of congenital syndromes and adverse perinatal outcomes where infection occurs in early and mid-pregnancy.

The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Investigation and diagnostic imaging of suspected pulmonary embolism during pregnancy and the puerperium: A review of the literature.

Pulmonary embolism (PE) is a leading cause of maternal mortality with women at increased risk of PE during pregnancy and the early postpartum period. Clinical assessment of suspected PE during pregnancy is challenging as signs and symptoms associated with PE overlap with physiological changes of pregnancy. Clinical tests and rules commonly used to assess pre-test probability of PE were historically not well validated in the pregnant population. The challenges of clinical assessment in the pregnant and postpartum population result in a lowered threshold for diagnostic imaging. Computed tomographic pulmonary angiography (CTPA) and nuclear medicine lung scintigraphy or ventilation/perfusion (V/Q) scans are the main types of diagnostic imaging for suspected PE. Both methods are associated with small levels of ionising radiation exposure to mother and foetus. Accuracy of the diagnostic imaging tests is paramount. Haemodynamic changes of pregnancy, including increased heart rate, increased blood volume and altered flow velocity in the pulmonary arteries, may influence the quality of imaging. This comprehensive review examines the literature and evidence for the investigation and diagnostic imaging of suspected pulmonary embolism during pregnancy with CTPA and V/Q. Clinical decision-making tools, biomarkers and diagnostic imaging during pregnancy and postpartum will be considered with a focus on diagnostic accuracy and yield, radiation dose exposure (maternal-foetal) and protocol modifications. Current practice guideline recommendations and recent literature on diagnostic pathways are also presented.