IMpleMenting Effective infection prevention and control in ReSidential aged carE (IMMERSE): protocol for a multi-level mixed methods implementation study.

BACKGROUND: Older people living in residential aged care facilities are at high risk of acquiring infections such as influenza, gastroenteritis, and more recently COVID-19. These infections are a major cause of morbidity and mortality among this cohort. Quality infection prevention and control practice in residential aged care is therefore imperative. Although appointment of a dedicated infection prevention and control (IPC) lead in every Australian residential aged care facility is now mandated, all people working in this setting have a role to play in IPC. The COVID-19 pandemic revealed inadequacies in IPC in this sector and highlighted the need for interventions to improve implementation of best practice. METHODS: Using mixed methods, this four-phase implementation study will use theory-informed approaches to: (1) assess residential aged care facilities' readiness for IPC practice change, (2) explore current practice using scenario-based assessments, (3) investigate barriers to best practice IPC, and (4) determine and evaluate feasible and locally tailored solutions to overcome the identified barriers. IPC leads will be upskilled and supported to operationalise the selected solutions. Staff working in residential aged care facilities, residents and their families will be recruited for participation in surveys and semi-structured interviews. Data will be analysed and triangulated at each phase, with findings informing the subsequent phases. Stakeholder groups at each facility and the IMMERSE project's Reference Group will contribute to the interpretation of findings at each phase of the project. DISCUSSION: This multi-site study will comprehensively explore infection prevention and control practices in residential aged care. It will inform and support locally appropriate evidence-based strategies for enhancing infection prevention and control practice.

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.

Presenting symptoms of COVID-19 and clinical outcomes in hospitalised older adults.

BACKGROUND: In July 2020, a COVID-19 outbreak was recognised in the geriatric wards at a subacute campus of the Royal Melbourne Hospital affecting patients and staff. Patients were also admitted to this site after diagnosis in residential care. AIMS: To describe the early symptoms and the outcomes of COVID-19 in older adults. METHODS: Patients diagnosed with COVID-19 at the facility in July or August 2020 were identified and their medical records were examined to identify symptoms present before and after their diagnosis and to determine their outcomes. RESULTS: Overall, 106 patients were identified as having COVID-19, with median age of 84.3 years (range 41-104 years); 64 were diagnosed as hospital inpatients after a median length of stay of 49 days, 31 were transferred from residential aged care facilities with a known diagnosis and 11 were diagnosed after discharge. There were 95 patients included in an analysis of symptom type and timing onset. Overall, 61 (64.2%) were asymptomatic at the time of diagnosis of COVID-19, having been diagnosed through screening initiated on site. Of these, 88.6% developed symptoms of COVID-19 within 14 days. The most common initial symptom type was respiratory, but there was wide variation in presentation, including fever, gastrointestinal and neurological symptoms, many initially not recognised as being due to COVID-19. Of 104 patients, 32 died within 30 days of diagnosis. CONCLUSIONS: COVID-19 diagnosis is challenging due to the variance in symptoms. In the context of an outbreak, asymptomatic screening can identify affected patients early in the disease course.

Incursions of Candida auris into Australia, 2018.

Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization. Phylogenetic analysis revealed putative transmission between 2 patients and suspected overseas acquisition in the others. Vigilant screening of at-risk patients is required.

The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases.

Zinc fingers and homeoboxes (ZHX) proteins are heterodimeric transcriptional factors largely expressed at the cell membrane in podocytes in vivo. We found ZHX2-based heterodimers in podocytes, with ZHX2-ZHX1 predominantly at the cell membrane of the podocyte cell body, and ZHX2-ZHX3 at the slit diaphragm. In addition to changes in overall ZHX2 expression, there was increased podocyte nuclear ZHX3 and ZHX2 in patients with focal segmental glomerulosclerosis, and increased podocyte nuclear ZHX1 in patients with minimal change disease. Zhx2 deficient mice had increased podocyte ZHX1 and ZHX3 expression. Zhx2 deficient mice and podocyte specific Zhx2 overexpressing transgenic rats develop worse experimental focal segmental glomerulosclerosis than controls, with increased nuclear ZHX3 and ZHX2, respectively. By contrast, podocyte specific Zhx2 overexpressing transgenic rats develop lesser proteinuria during experimental minimal change disease due to peripheral sequestration of ZHX1 by ZHX2. Using co-immunoprecipitation, the interaction of ZHX2 with aminopeptidase A in the podocyte body cell membrane, and EPHRIN B1 in the slit diaphragm were noted to be central to upstream events in animal models of minimal change disease and focal segmental glomerulosclerosis, respectively. Mice deficient in Enpep, the gene for aminopeptidase A, and Efnb1, the gene for ephrin B1 developed worse albuminuria in glomerular disease models. Targeting aminopeptidase A in Zhx2 deficient mice with monoclonal antibodies induced albuminuria and upregulation of the minimal change disease mediator angiopoietin-like 4 through nuclear entry of ZHX1. Thus, podocyte ZHX2 imbalance is a critical factor in human glomerular disease, with minimal change disease disparities mediated mostly through ZHX1, and focal segmental glomerulosclerosis deviations through ZHX3 and ZHX2.

Podocyte-specific expression of Cre recombinase promotes glomerular basement membrane thickening.

Conditional gene targeting using Cre recombinase has offered a powerful tool to modify gene function precisely in defined cells/tissues and at specific times. However, in mammalian cells, Cre recombinase can be genotoxic. The importance of including Cre-expressing control mice to avoid misinterpretation and to maximize the validity of the experimental results has been increasingly recognized. While studying the role of podocytes in the pathogenesis of glomerular basement membrane (GBM) thickening, we used Cre recombinase driven by the podocyte-specific podocin promoter (NPHS2-Cre) to generate a conditional knockout. By conventional structural and functional measures (histology by periodic acid-Schiff staining, albuminuria, and plasma creatinine), we did not detect significant differences between NPHS2-Cre transgenic and wild-type control mice. However, surprisingly, the group that expressed Cre transgene alone developed signs of podocyte toxicity, including marked GBM thickening, loss of normal foot process morphology, and reduced Wilms tumor 1 expression. GBM thickening was characterized by altered expression of core structural protein laminin isoform α5ß2γ1. RNA sequencing analysis of extracted glomeruli identified 230 genes that were significant and differentially expressed (applying a q < 0.05-fold change ≥ ±2 cutoff) in NPHS2-Cre mice compared with wild-type control mice. Many biological processes were reflected in the RNA sequencing data, including regulation of the extracellular matrix and pathways related to apoptosis and cell death. This study highlights the importance of including the appropriate controls for potential Cre-mediated toxicity in conditional gene-targeting experiments. Indeed, omitting the Cre transgene control can result in critical errors during interpretation of experimental data.

Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases.

Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre-emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.

Creating a web-based digital photographic archive: one hospital library's experience.

BACKGROUND: Cedars-Sinai Medical Center is a nonprofit community hospital based in Los Angeles. Its history spans over 100 years, and its growth and development from the merging of 2 Jewish hospitals, Mount Sinai and Cedars of Lebanon, is also part of the history of Los Angeles. The medical library collects and maintains the hospital's photographic archive, to which retiring physicians, nurses, and an active Community Relations Department have donated photographs over the years. The collection was growing rapidly, it was impossible to display all the materials, and much of the collection was inaccessible to patrons. CASE PRESENTATION: The authors decided to make the photographic collection more accessible to medical staff and researchers by purchasing a web-based digital archival package, Omeka. We decided what material should be digitized by analyzing archival reference requests and considering the institution's plan to create a Timeline Wall documenting and celebrating the history of Cedars-Sinai. CONCLUSION: Within 8 months, we digitized and indexed over 500 photographs. The digital archive now allows patrons and researchers to access the history of the hospital and enables the library to process archival references more efficiently.

Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic?

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in the United States and is a major cause of cardiovascular disease and death. DN develops insidiously over a span of years before clinical manifestations, including microalbuminuria and declining glomerular filtration rate (GFR), are evident. During the clinically silent period, structural lesions develop, including glomerular basement membrane (GBM) thickening, mesangial expansion, and glomerulosclerosis. Once microalbuminuria is clinically apparent, structural lesions are often considerably advanced, and GFR decline may then proceed rapidly toward end-stage kidney disease. Given the current lack of sensitive biomarkers for detecting early DN, a shift in focus toward examining the cellular and molecular basis for the earliest structural change in DN, i.e., GBM thickening, may be warranted. Observed within one to two years following the onset of diabetes, GBM thickening precedes clinically evident albuminuria. In the mature glomerulus, the podocyte is likely key in modifying the GBM, synthesizing and assembling matrix components, both in physiological and pathological states. Podocytes also secrete matrix metalloproteinases, crucial mediators in extracellular matrix turnover. Studies have shown that the critical podocyte-GBM interface is disrupted in the diabetic milieu. Just as healthy podocytes are essential for maintaining the normal GBM structure and function, injured podocytes likely have a fundamental role in upsetting the balance between the GBM's synthetic and degradative pathways. This article will explore the biological significance of GBM thickening in DN by reviewing what is known about the GBM's formation, its maintenance during health, and its disruption in DN.

Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease.

A mixed methods study of the barriers and enablers in implementing antimicrobial stewardship programmes in Australian regional and rural hospitals.

OBJECTIVES: The Australian Commission on Safety and Quality in Health Care released recommendations for antimicrobial stewardship programmes to be established within all Australian healthcare facilities. However, implementation practices are not well defined. The aim of this study was to gain an understanding of factors affecting implementation of antimicrobial stewardship programmes within Australian regional and rural hospitals. METHODS: This study was designed whereby a preliminary quantitative process was used to contribute to a principally qualitative study. Site visits to regional and rural hospitals in Queensland, New South Wales, Victoria and South Australia were planned to assess factors impacting on implementation of antimicrobial stewardship. Subsequently researchers identified issues requiring further exploration with specific key informant interviews and focus group discussions. Data were collected between May and October 2012 and entered into Nvivo10, openly coded and analysed according to mixed methods data analysis principles. RESULTS: Regional and rural hospitals were not conducting many of the recommended activities and seven major themes emerged. The key barriers were perceived to be lack of access to education, resources and specialist support. The enablers were a flatter governance structure, greater sense of pride, desire for success and good internet and tele-health access. CONCLUSIONS: This study helps us to identify where efforts should be focused to facilitate the establishment of antimicrobial stewardship programmes in regional and rural hospitals, by describing the gaps and limitations of current programmes and the major issues currently being faced, providing recommendations to better guide activities that support regional and rural hospitals.

Measuring antimicrobial prescribing quality in Australian hospitals: development and evaluation of a national antimicrobial prescribing survey tool.

OBJECTIVES: Antimicrobial stewardship (AMS) programmes have been developed with the intention of reducing inappropriate and unnecessary use of antimicrobials, while improving the quality of patient care and locally helping prevent the development of antimicrobial resistance. An important aspect of AMS programmes is the qualitative assessment of prescribing through antimicrobial prescribing surveys (APS), which are able to provide information about the prescribing behaviour within institutions. Owing to lack of standardization of audit tools and the resources required, qualitative methods for the assessment of antimicrobial use are not often performed. The aim of this study was to design an audit tool that was appropriate for use in all Australian hospitals, suited to local user requirements and included an assessment of the overall appropriateness of the prescription. METHODS: In November 2011, a pilot APS was conducted across 32 hospitals to assess the usability and generalizability of a newly designed audit tool. Following participant feedback, this tool was revised to reflect the requirements of the respondents. A second pilot study was then performed in November 2012 across 85 hospitals. RESULTS: These surveys identified several areas that can be targets for quality improvement at a national level, including: documentation of indication; surgical prophylaxis prescribed for >24 h; compliance with prescribing guidelines; and the appropriateness of the prescription. CONCLUSIONS: By involving the end users in the design and evaluation, we have been able to provide a practical and relevant APS tool for quantitative and qualitative data collection in a wide range of Australian hospital settings.

Implementing antimicrobial stewardship in the Australian private hospital system: a qualitative study.

OBJECTIVE: To explore organisational factors and barriers contributing to limited uptake of antimicrobial stewardship (AMS) in Australian private hospitals and to determine solutions for AMS implementation. METHODS: A qualitative study using a series of focus group discussions was conducted in a large private hospital making use of a semistructured interview guide to facilitate discussion among clinical and non-clinical stakeholders. A thematic analysis using five sequential components that mapped and interpreted emergent themes surrounding AMS implementation was undertaken by a multidisciplinary team of researchers. RESULTS: Analysis revealed that autonomy of consultant specialists was perceived as being of greater significance in private hospitals compared with public hospitals. Use of an expert team providing antimicrobial prescribing advice and education without intruding on existing patient-specialist relationships was proposed by participants as an acceptable method of introducing AMS in private hospitals. There was more opportunity for nursing and pharmacist involvement, as well as empowering patients. Opportunities were identified for the hospital executive to market an AMS service as a feature that promoted excellence in patient care. CONCLUSIONS: Provision of advice from experts, championing by clinical leaders, marketing by hospital executives and involving nurses, pharmacists and patients should be considered during implementation of AMS in private hospitals.

Health literacy in patients with chronic hepatitis B attending a tertiary hospital in Melbourne: a questionnaire based survey.

BACKGROUND: Current estimates suggest over 218,000 individuals in Australia are chronically infected with hepatitis B virus. The majority of these people are migrants and refugees born in hepatitis B endemic countries, where attitudes towards health, levels of education, and English proficiency can be a barrier to accessing the Australian health care system, and best managing chronic hepatitis B. This study aimed to assess the knowledge of transmission and consequences of chronic hepatitis B among these patients. METHOD: A prospective study was conducted between May and August 2012. Patients with chronic hepatitis B were recruited from three Royal Melbourne Hospital outpatient clinics. Two questionnaires were administered. Questionnaire 1, completed during observation of a prospective participants' consultation, documented information given to the patient by their clinician. After the consultation, Questionnaire 2 was administered to assess patient demographics, and overall knowledge of the effect, transmission and treatment of hepatitis B. RESULTS: 55 participants were recruited. 93% of them were born overseas, 17% used an interpreter, and the average time since diagnosis was 9.7 years.Results from Questionnaire 1 showed that the clinician rarely discussed many concepts. Questionnaire 2 exposed considerable gaps in hepatitis B knowledge. Few participants reported a risk of cirrhosis (11%) or liver cancer (18%). There was a high awareness of transmission routes, with 89% correctly identifying sexual transmission, 93% infected blood, and 85% perinatal transmission. However, 25% of participants believed hepatitis B could be spread by sharing food, and over 50% by kissing and via mosquitoes. A knowledge score out of 12 was assessed for each participant. The average score was 7.5. Multivariate analysis found higher knowledge scores among those with a family member also diagnosed with chronic hepatitis B and those routinely seeing the same clinician (p = 0.009 and p = 0.002, respectively). CONCLUSION: This is the largest Australian study assessing knowledge and understanding of the effect, transmission, and treatment of hepatitis B among chronically infected individuals. The findings highlight the knowledge gaps and misconceptions held by these patients, and the need to expand education and support initiatives.

Antimicrobial stewardship in residential aged care facilities: need and readiness assessment.

BACKGROUND: Information about the feasibility, barriers and facilitators of antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has been scant. Exploring the prevailing perceptions and attitudes of key healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS in the RACF setting is imperative to guide AMS interventions. METHODS: Semi-structured interviews and focus groups were conducted with key RACF healthcare providers until saturation of themes occurred. Participants were recruited using purposive and snowball sampling. The framework approach was applied for data analysis. RESULTS: A total of 40 nurses, 15 general practitioners (GPs) and 6 pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions of current antibiotic prescribing behaviour, perceptions of antibiotic resistance, attitude towards and understanding of AMS, perceived barriers to and facilitators of AMS implementation, and feasible AMS interventions. A higher proportion of GPs and pharmacists compared with nurses felt there was over-prescribing of antibiotics in the RACF setting. Antibiotic resistance was generally perceived as an issue for infection control rather than impacting clinical decisions. All key stakeholders were supportive of AMS implementation in RACFs; however, they recognized barriers related to workload and logistical issues. A range of practical AMS interventions were identified, with nursing-based education, aged-care specific antibiotic guidelines and regular antibiotic surveillance deemed most useful and feasible. CONCLUSIONS: Areas of antibiotic over-prescribing have been identified from different healthcare providers' perspectives. However, concern about the clinical impact of antibiotic resistance was generally lacking. Importantly, information gathered about feasibility, barriers and facilitators of various AMS interventions will provide important insights to guide development of AMS programs in the RACF setting.

Antibiotic prescribing practice in residential aged care facilities--health care providers' perspectives.

OBJECTIVE: To explore organisational workflow and workplace culture influencing antibiotic prescribing behaviour from the perspective of key health care providers working in residential aged care facilities (RACFs). DESIGN, SETTING AND PARTICIPANTS: Qualitative approach using semistructured interviews, focus groups and onsite observation between 8 January 2013 and 2 July 2013. Nursing staff, general practitioners and pharmacists servicing residents at 12 high-level care RACFs in Victoria were recruited. MAIN OUTCOME MEASURES: Emergent themes on antibiotic prescribing practices in RACFs. RESULTS: Sixty-one participants (40 nurses, 15 GPs and six pharmacists) participated. Factors influencing antibiotic prescribing practice have been divided into workflow-related and culture-related factors. Five major themes emerged among workflow-related factors: logistical challenges with provision of medical care, pharmacy support, nurse-driven infection management, institutional policies and guidelines, and external expertise and diagnostic facilities. Lack of onsite medical and pharmacy staff led to nursing staff adopting significant roles in infection management. However, numerous barriers hindered optimal antibiotic prescribing, especially inexperienced staff, lack of training of nurses in antibiotic use and lack of institutional infection management guidelines. With regard to culture-related factors, pressure from family to prescribe and institutional use of advance care directives were identified as important influences on antibiotic prescribing practices. CONCLUSIONS: Workflow- and culture-related barriers to optimal antibiotic prescribing were identified. This study has provided important insights to guide antimicrobial stewardship interventions in the RACF setting, particularly highlighting the role of nurses.

Daily COVID-19 employee attestations at a large quaternary hospital in Melbourne, Australia - Limitations and lessons learnt.

BACKGROUND: As one of the many measures to limit the potentially infectious persons entering healthcare settings, the Victorian Department of Health (DH) introduced a daily attestation between 2020 and 2022. Upon entry to a health service, employees were required to confirm they were free from symptoms related to COVID-19 and did not have contact with a confirmed COVID-19 case in the previous 7-14 days. METHODS: We performed a retrospective analysis of employee attestations and SARS-CoV-2 tests performed between 1/6/2021 and 14/2/2022 at the main campus of the Royal Melbourne Hospital. RESULTS: We found the proportion of SARS-CoV-2 positive employees identified through workplace attestation was low (1.3%). Most SARS-CoV-2 positive employees analysed in this study (94%) were asymptomatic. DISCUSSION: Although the proportion of SARS-CoV-2 positive employees identified was low, attestations may have deterred unwell employees from presenting to work. Proactively monitoring employee attestations, such as measuring and reporting the number of symptomatic attestations, may make this a more useful tool.