Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity.

To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαß repertoires and promiscuous αß-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαß diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.

Identification of an Optimized Receptor-Binding Domain Subunit Vaccine against SARS-CoV-2.

Current vaccine efforts to combat SARS-CoV-2 are focused on the whole spike protein administered as mRNA, viral vector, or protein subunit. However, the SARS-CoV-2 receptor-binding domain (RBD) is the immunodominant portion of the spike protein, accounting for 90% of serum neutralizing activity. In this study, we constructed several versions of RBD and together with aluminum hydroxide or DDA (dimethyldioctadecylammonium bromide)/TDB (d-(+)-trehalose 6,6'-dibehenate) adjuvant evaluated immunogenicity in mice. We generated human angiotensin-converting enzyme 2 knock-in mice to evaluate vaccine efficacy in vivo following viral challenge. We found that 1) subdomain (SD)1 was essential for the RBD to elicit maximal immunogenicity; 2) RBDSD1 produced in mammalian HEK cells elicited better immunogenicity than did protein produced in insect or yeast cells; 3) RBDSD1 combined with the CD4 Th1 adjuvant DDA/TDB produced higher neutralizing Ab responses and stronger CD4 T cell responses than did aluminum hydroxide; 4) addition of monomeric human Fc receptor to RBDSD1 (RBDSD1Fc) significantly enhanced immunogenicity and neutralizing Ab titers; 5) the Beta version of RBDSD1Fc provided a broad range of cross-neutralization to multiple antigenic variants of concern, including Omicron; and 6) the Beta version of RBDSD1Fc with DDA/TDB provided complete protection against virus challenge in the knock-in mouse model. Thus, we have identified an optimized RBD-based subunit vaccine suitable for clinical trials.

Clinical utility of maternal TORCH screening in fetal growth restriction: A retrospective two-centre study.

OBJECTIVE: The aim of this study was to evaluate the indications for maternal TORCH (Toxoplasma gondii, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)) serology, with a focus on the yield in isolated fetal growth restriction (FGR). MATERIALS AND METHODS: A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. TORCH testing ordered for pregnancy losses and stillbirth was excluded. RESULTS: Medical records of 718 pregnancies were reviewed, representing 760 fetuses. Isolated FGR was the indication for TORCH screening in 71.2% of pregnancies. Screens ordered for isolated FGR were positive in 7.4% (95% CI 5.5-10.0%). There were 49 positive maternal immunoglobulin M (CMV = 34, Toxoplasma = 15). Two acute maternal infections during pregnancy were diagnosed (CMV = 1, Toxoplasma = 1), with both screens ordered to assess symptomatic maternal illness. There was one neonatal CMV infection, born to a woman with symptomatic primary CMV. No maternal or neonatal rubella or HSV infections were identified. We found a diagnostic yield of TORCH screening for isolated FGR of 0.0% (95% CI 0.00-0.8%). An estimated AUD$64 269.75 was expended on maternal TORCH screens in this study. CONCLUSION: Maternal TORCH testing for isolated FGR is of no diagnostic yield and should be abandoned.

The Who, What, When, and Where of Inpatient Direct Oral Penicillin Challenge-Implications for Health Services Implementation.

Inpatient direct oral challenge programs are increasingly deployed as part of antimicrobial stewardship initiatives to reduce the burden and impacts of penicillin allergy labels on antibiotic prescribing. Using data from a prospective, multicenter cohort inpatient penicillin allergy program, we identify the key targets for delabeling to aid health service implementation.

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID-19 in unvaccinated patients with acute disease. We found that circulating CD27neg CD45RA+ CX3CR1+ Vδ1effector cells expressing Granzymes (Gzms) were enriched in COVID-19 patients with acute disease. Moreover, higher frequencies of GzmB+ Vδ2+ T cells were observed in acute COVID-19 patients. SARS-CoV-2 infection did not alter the γδ T cell receptor repertoire of either Vδ1+ or Vδ2+ subsets. Our work demonstrates an association between effector populations of γδ T cells and acute COVID-19 in unvaccinated individuals.

Natural language processing diagnosed behavioural disturbance phenotypes in the intensive care unit: characteristics, prevalence, trajectory, treatment, and outcomes.

BACKGROUND: Natural language processing (NLP) may help evaluate the characteristics, prevalence, trajectory, treatment, and outcomes of behavioural disturbance phenotypes in critically ill patients. METHODS: We obtained electronic clinical notes, demographic information, outcomes, and treatment data from three medical-surgical ICUs. Using NLP, we screened for behavioural disturbance phenotypes based on words suggestive of an agitated state, a non-agitated state, or a combination of both. RESULTS: We studied 2931 patients. Of these, 225 (7.7%) were NLP-Dx-BD positive for the agitated phenotype, 544 (18.6%) for the non-agitated phenotype and 667 (22.7%) for the combined phenotype. Patients with these phenotypes carried multiple clinical baseline differences. On time-dependent multivariable analysis to compensate for immortal time bias and after adjustment for key outcome predictors, agitated phenotype patients were more likely to receive antipsychotic medications (odds ratio [OR] 1.84, 1.35-2.51, p < 0.001) compared to non-agitated phenotype patients but not compared to combined phenotype patients (OR 1.27, 0.86-1.89, p = 0.229). Moreover, agitated phenotype patients were more likely to die than other phenotypes patients (OR 1.57, 1.10-2.25, p = 0.012 vs non-agitated phenotype; OR 4.61, 2.14-9.90, p < 0.001 vs. combined phenotype). This association was strongest in patients receiving mechanical ventilation when compared with the combined phenotype (OR 7.03, 2.07-23.79, p = 0.002). A similar increased risk was also seen for patients with the non-agitated phenotype compared with the combined phenotype (OR 6.10, 1.80-20.64, p = 0.004). CONCLUSIONS: NLP-Dx-BD screening enabled identification of three behavioural disturbance phenotypes with different characteristics, prevalence, trajectory, treatment, and outcome. Such phenotype identification appears relevant to prognostication and trial design.

Serological screening for cytomegalovirus during pregnancy: A systematic review of clinical practice guidelines and consensus statements.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide. cCMV can lead to severe long-term sequelae, including neurological impairment and developmental delay. We performed a systematic review of clinical practice guidelines containing recommendations concerning serological screening for CMV during pregnancy. METHOD: We performed a search of MEDLINE, Turning Research into Practice (TRIP) database and the grey literature for clinical practice guidelines or consensus statements published in the English language from Jan 2010 to June 2022. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations on CMV serological screening in pregnancy. RESULTS: Eleven guidelines and two consensus statements were included. None recommended universal serological screening for CMV in pregnant women; five recommended screening for high-risk women (those with frequent contact with young children). The overall quality of the guidelines varied; most were medium or low. CONCLUSIONS: Although clinical practice guidelines do not actively recommend routine serological screening in pregnancy, most did not meet standard processes for development and predated the emerging data on valaciclovir as a potential intervention. Existing recommendations are underpinned by limited, low-level evidence, exposing the lack of robust data in this area of practice. Further high-level evidence and methodologically robust guidelines are needed to guide clinical practice in this rapidly changing field.

Penicillin Allergy Delabeling Program: an exploratory economic evaluation in the Australian context.

BACKGROUND: Internationally, clinical and economic advantages of low-risk penicillin delabelling have been explored, supporting changes to healthcare delivery systems where penicillin delabelling is embedded into inpatient usual care. AIMS: To determine if economic advantages of low-risk inpatient penicillin delabelling, described in the international literature, are realised in the Australian context. METHODS: This explorative economic evaluation had prospective patient data collection between January and August 2019, across two Australian health services. Part 1: determine the cost per effectively delabelled patient for Penicillin Allergy Delabeling Program inpatients (PADP cohort) compared with Outpatient Antibiotic Allergy Testing Service outpatients (OAATS cohort). Part 2: a cost analysis to compare hospital costs for inpatients with low-risk penicillin allergy who did (PADP cohort) and did not (usual care cohort) undergo PADP delabelling. RESULTS: Part 1: the PADP (n = 350) and OAATS (n = 27 patients, n = 36 individual visits) cohorts were comparable. In PADP, costs/proportion delabelled was $20.10/0.98, equating to $20.51 per effectively delabelled patient; in OAATS, it was $181.24/0.50, equating to $362. Compared with OAATS, PADP was associated with savings of $341.97 per effectively delabelled patient, indicating the outpatient testing was the dominated strategy, being more costly and less effective. Part 2: the PADP (n = 218) and usual care (n = 32) cohorts were comparable. Significantly favouring the delabelled PADP cohort, the mean difference per patient was -4.41 days (95% confidence interval: -7.64, -1.18) and -$9467.72 (95% confidence interval: -$15 419.98, -$3515.46). CONCLUSIONS: Consistent with international literature, delabelling low-risk penicillin allergies in the inpatient setting had economic advantages in the Australian context. Fully powered economic evaluations are urgently required to consolidate these findings.

Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context.

BACKGROUND: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. AIM: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. METHODS: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. RESULTS: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). CONCLUSIONS: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.

Estimating baseline creatinine to detect acute kidney injury in patients with chronic kidney disease.

BACKGROUND: Accurately estimating baseline kidney function is essential for diagnosing acute kidney injury (AKI) in patients with chronic kidney disease (CKD). We developed and evaluated novel equations to estimate baseline creatinine in patients with AKI on CKD. METHODS: We retrospectively analysed 5649 adults with AKI out of 11 254 CKD patients, dividing them evenly into derivation and validation groups. Using quantiles regression, we created equations to estimate baseline creatinine, considering historical creatinine values, months since measurement, age, and sex from the derivation dataset. We assessed performance against back-estimation equations and unadjusted historical creatinine values using the validation dataset. RESULTS: The optimal equation adjusted the most recent creatinine value for time since measurement and sex. Estimates closely matched the actual baseline at AKI onset, with median (95% confidence interval) differences of just 0.9% (-0.8% to 2.1%) and 0.6% (-1.6% to 3.9%) when the most recent value was within 6 months to 30 days and 2 years to 6 months before AKI onset, respectively. The equation improved AKI event reclassification by an additional 2.5% (2.0% to 3.0%) compared to the unadjusted most recent creatinine value and 7.3% (6.2% to 8.4%) compared to the CKD-EPI 2021 back-estimation equation. CONCLUSION: Creatinine levels drift in patients with CKD, causing false positives in AKI detection without adjustment. Our novel equation adjusts the most recent creatinine value for drift over time. It provides more accurate baseline creatinine estimation in patients with suspected AKI on CKD, which reduces false-positive AKI detection, improving patient care and management.

Use of a buprenorphine-based pain management protocol is associated with reduced opioid requirements and pain on swallowing in oral mucositis: a retrospective cohort study.

OBJECTIVE: The aim of this study is to ascertain the analgesic efficacy and total oral morphine equivalent daily dose (OMEDD) effect of a buprenorphine-based analgesic protocol in the treatment of severe Oral Mucositis (OM). DESIGN: This is a retrospective cohort study. SETTING: This study was done in a single Quaternary Referral Centre, Haematology Unit. SUBJECTS: Fifty-four stem cell transplant patients suffering at least grade 3 oral mucositis (OM), 24 prior to [Pr-I] and 30 subsequent to [Po-I] a buprenorphine-based OM analgesic protocol. METHODS: We analysed data from the above subjects with the primary outcome measure of difference in total OMEDDs from all opioid types and administration routes, and secondary outcome measures of area under the curve (AUC) of 11-point Numerical Rating Scale (NRS-11) pain assessments, sedation scores and respiratory rate. RESULTS: Post-protocol patients' total OMEDD requirements were significantly reduced [Pr-I: 1961 (1365)mg; Po-I: 928 (625)mg, p = 0.02], as were total NRS-11:hours AUC on swallowing [Pr-I: 54(24) score-hours; Po-I: 41(18) score-hours, p < 0.001]. There were no significant differences in objective measures of OM severity between groups (Number of Grade 3 or 4 OM severity assessments [mean (SD)] Pr-I: 5 (6.2); Po-I: 7 (5.1) or number of days Neutrophil count 0.0 or 0.1 × 109/L; Pr-I: 13 (5.4); Po-I: 15 (4.7)). 5 Pr-I and 4 Po-I patients required ketamine infusions, with 1 Pr-I patient also requiring IV lignocaine. CONCLUSIONS: Use of Buprenorphine via transdermal, sublingual and intravenous Patient Controlled Analgesia (PCA) delivery as part of an analgesic protocol for severe post stem cell transplant oral mucositis in adult patients appears to significantly reduce opioid requirements and pain on swallowing. Further randomised prospective work is required to confirm these associations.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

No fever, no worries? A retrospective audit of bacteraemic patients in the emergency department.

BACKGROUND: Early identification and treatment of serious infections improve clinical outcomes. Previous studies have found that septic patients without fever are more likely to die than those with fever, due to delay in antibiotic administration. AIM: To determine whether antibiotic treatment and mortality differed in afebrile adult patients presenting to the emergency department (ED) with bacteraemia, compared with those with a history of fever. METHODS: Retrospective 6-month audit of all adult patients with positive blood cultures taken in the ED of a single tertiary hospital. Outcomes included the receipt of antibiotics within 4 and 24 h of ED arrival, in-hospital mortality and 30-day mortality. RESULTS: A total of 227 patients with clinically significant bacteraemia was identified, of which 38 (16.7%) were afebrile in the ED. There was no statistically significant difference in the proportion of afebrile or febrile patients receiving antibiotics within 4 h (44.7% vs 55.6%, P = 0.222) or 24 h (89.5% vs 95.2%, P = 0.163) of arrival at the ED. Inpatient mortality was not statistically different in the afebrile and febrile groups 15.8% vs 6.9%, P = 0.070), but 30-day mortality was higher among afebrile patients (27.6% vs 10.1%, P = 0.010). CONCLUSIONS: There was no significant difference in receipt of antibiotics within 4 h or 24 h ED arrival between the febrile and afebrile groups. However, afebrile patients experienced higher 30-day mortality. While most bacteraemic patients received antibiotics within 24 h, only half received antibiotics within 4 h, representing a key area for improvement.

Estimating baseline kidney function in hospitalized adults with acute kidney injury.

AIM: Baseline serum creatinine values are required to diagnose acute kidney injury but are often unavailable. We evaluated four conventional equations to estimate creatinine. We then developed and validated a new equation corrected by age and gender. METHODS: We retrospectively examined adults who, at first hospital admission, had available baseline creatinine data and developed acute kidney injury ≥24 h after admission. We split the study population: 50% (derivation) to develop a new linear equation and 50% (validation) to compare against conventional equations for bias, precision, and accuracy. We stratified analyses by age and gender. RESULTS: We studied 3139 hospitalized adults (58% male, median age 71). Conventional equations performed poorly in bias and accuracy in patients aged <60 or ≥75 (68% of the study population). The new linear equation had less bias and more accuracy. There were no clinically significant differences in precision. The median (95% confidence interval) difference in creatinine values estimated via the new equation minus measured baselines was 0.9 (-3.0, 5.9) and -0.5 (-7.0, 3.7) µmol/L in female patients 18-60 and 75-100, and -1.5 (-4.2, 2.2) and -7.8 (-12.7, -3.6) µmol/L in male patients 18-60 and 75-100, respectively. The new equation improved reclassification of KDIGO AKI stages compared to the MDRD II equation by 5.0%. CONCLUSION: Equations adjusted for age and gender are less biased and more accurate than unadjusted equations. Our new equation performed well in terms of bias, precision, accuracy, and reclassification.

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

BACKGROUND: Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients. METHODS: Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days). RESULTS: Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39-20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45-3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27-.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09-23.31]) and ß-lactam/ß-lactamase inhibitors (OR, 6.68 [95% CI, 3.94-11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36-.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26-.72]) in the delabeled group compared with the group who retained their allergy label. CONCLUSIONS: This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.

Successful use of azithromycin for Escherichia coli-associated renal allograft malakoplakia: a report of two cases.

Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal approach to therapy includes antimicrobials with intracellular activity, reduction in immunosuppression, and debulking of lesions. Azithromycin has an intracellular mechanism of action and enhanced Gram-negative activity compared to other macrolides. Despite some in vitro data to support its use, there are no clinical breakpoints or epidemiological cut-off values for most Enterobacterales from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) or the Clinical and Laboratory Standards Institute (CLSI). We present two cases, previously unreported, of Escherichia coli associated renal allograft malakoplakia successfully treated with azithromycin.

Clinical manifestations of invasive meningococcal disease in Victoria with the emergence of serogroup W and serogroup Y Neisseria meningitidis.

BACKGROUND: Historically, Australian cases of invasive meningococcal disease (IMD) have been most frequently caused by Neisseria meningitidis serogroup B, but recently an increase in cases due to serogroup W (MenW) and serogroup Y (MenY) has occurred. AIM: To determine whether clinical manifestations of IMD have changed due to increased incidence of MenW and MenY. METHODS: We performed a retrospective review of IMD cases notified to the Department of Health and Human Services in Victoria, Australia. We compared the period between January 2013 and June 2015 (defined as P1) immediately before the increase in MenW and MenY was noted, with the equal time period of July 2015 to December 2017 (P2), when this increase was observed. RESULTS: IMD was notified more frequently in P2 than P1 (1.24 vs 0.53 per 100 000 person-years, P < 0.001). IMD cases in P2 were older (46 vs 19 years, P < 0.001), and more likely due to MenW (92/187, 49.2% vs 11/80, 13.8%, P < 0.001) or MenY (31/187, 16.6% vs 4/80, 5.0%, P = 0.01). IMD cases from P2 were more likely bacteraemic (151/187, 80.7% vs 55/80, 68.8%, P = 0.04), while meningitis (68/187, 36.4% vs 41/80, 51.3%, P = 0.03) and rash (65/181, 35.9% vs 45/78, 57.7%, P = 0.002) were less frequent. Intensive care unit admission rates and in-hospital mortality were unchanged. CONCLUSION: Alongside an increase in IMD in Victoria, the proliferation of cases of MenW and MenY occurred in older patients, and were more often identified through bacteraemia rather than meningitis or purpura fulminans. Clinicians should be aware of these changes to facilitate earlier identification and treatment of IMD.

Identifying patterns in unplanned hospital admissions during the COVID-19 pandemic: a single-centre retrospective study.

BACKGROUND: Countries with a high prevalence of COVID-19 have identified a reduction in crude hospital admission rates for non-COVID-19 conditions during the pandemic. There remains a paucity of such data from lower prevalence countries, including Australia. AIMS: To describe the patterns of unplanned hospital daily admission rates during the COVID-19 pandemic in a major Australian metropolitan hospital, with a focus on acute medical presentations including acute coronary syndrome (ACS), stroke and falls. METHODS: This single-centre retrospective analysis analysed hospital admission episodes between 1 March and 30 April 2020 (COVID-19-era) and compared this to a historical cohort during the same period between 2017 and 2019 (pre-COVID-19). Information collected included total admission rates and patient characteristics for ACS, stroke and falls patients. RESULTS: A total of 12 278 unplanned admissions was identified across the study period. The daily admission rate was lower in the COVID-19-era compared with pre-COVID-19 (46.59 vs 51.56 days, P < 0.001). There was also a reduced average daily admission rate for falls (7.79 vs 9.95 days, P < 0.001); however, similar admission rates for ACS (1.52 vs 1.49 days, P = 0.83) and stroke (1.56 vs 1.76 days, P = 0.33). CONCLUSIONS: Public health interventions have been effective in reducing domestic cases of COVID-19 in Australia. At our tertiary metropolitan hospital, we have observed a significant reduction in unplanned hospital admission rates during the COVID-19-era, particularly for falls. Public health messaging needs to focus on educating the public how to seek medical care safely and promptly in the context of the ongoing COVID-19 crisis.