Plasmablastic myeloma transformation of light-chain multiple myeloma.

Plasmablastic myeloma (PBM) is an uncommon and aggressive morphologic variant of multiple myeloma (MM). The neoplastic immature cells exhibit diverse morphology, posing a diagnostic challenge. The diagnostic criteria for PBM include the identification of ≥ 2% plasmablasts in the bone marrow aspirate. This case describes the incidental finding of a light-chain multiple myeloma (LCMM) transformed into PBM, a phenomenon not previously reported.

The Impact and Usability of the eRIC System in the ICU - A Qualitative Study.

The Intensive Care Unit (ICU) is an information-intense environment where more patient data points are recorded than in other wards. The electronic Record for Intensive Care (eRIC) is an ICU information system that integrates patient data every minute from multiple systems. Once implemented across New South Wales (NSW), eRIC will be one of the largest system-wide ICU clinical information systems in the world. This study explored experiences with the use of eRIC by ICU clinicians at an Australian metropolitan teaching hospital. Semi-structured, in-depth interviews relating to physician electronic test management processes were conducted with 11 ICU clinicians and one clinical information system manager was observed in their use of the system. The introduction of eRIC resulted in an additional patient record, which was perceived to hold implications for workflow and patient safety. Study findings are valuable for informing implementation as the rollout of eRIC continues.

Erythroid variant evolving from chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitors: a rare case report.

BACKGROUND: Chronic myeloid leukemia (CML) is characterized by the presence of BCR::ABL1 fusion gene resulting from a reciprocal translocation, t(9;22)(q34;q11.2), leading to prominent granulocytic proliferation. The majority of patients initially present in chronic phase (CP), which may progress to advanced CML with predominantly granulocytic phenotypes in the absence of proper treatment or response to tyrosine kinase inhibitors (TKIs). We present an exceptionally rare case in which an erythroid variant emerged from a CML patient resistant to multiple TKIs. This variant is characterized by the detection of t(9;22) BCR::ABL1 fusion in erythroid precursors at various maturation stages and the absence of granulocytic progenitor hyperplasia typically seen in classical CML. CASE PRESENTATION: A 33-year-old female with CP-CML had received multiple TKI therapies since her initial diagnosis in 2015. Due to intolerable side effects and inconsistent adherence, she exhibited an inadequate response and developed new-onset pancytopenia. Bone marrow (BM) biopsy specimen revealed a hypercellular marrow with significant erythroid hyperplasia (90% of marrow cellularity) and a reversed myeloid-to-erythroid (M: E) ratio of 1:10. Both erythroid and myeloid cells displayed progressive maturation without dysplasia or excess blasts. Chromosomal analysis identified t(9;22) (q34;q11.2) in 19 out of 20 metaphase cells. BCR::ABL1 fusion transcript (p210 isoform) was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). Notably, no additional pathogenic cytogenetic abnormalities or ABL1 kinase domain mutations were detected. Here, we report the first published case of an erythroid variant emerging in a CML patient resistant to multiple TKIs-a distinct entity from the erythroid blast crisis evolving from CML. CONCLUSION: The erythroid variant of CML is distinguished by the presence of t(9;22) (q34;q11.2) BCR::ABL1 in predominant erythroid precursors at different stages of maturation. In a myeloid neoplasm showing predominant erythroid hyperplasia without typical CML features, it is vital to correlate morphology and t(9;22) BCR::ABL1 cytogenetic testing for accurate diagnosis, and to prevent confusion with PEL transformation in CML.

Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow.

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead to the focal nature of atherosclerosis. Using a step flow chamber to investigate the effects of disturbed shear (DS) and pulsatile shear (PS) on ECs in the same flow channel, we conducted single-cell RNA sequencing analyses to explore the distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters and demonstrated that DS induces EC transition from atheroprotective to proatherogenic phenotypes. Using an automated cell type annotation algorithm (SingleR), we showed that DS promoted endothelial-to-mesenchymal transition (EndMT) by inducing the transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-ß) signaling, glycolysis, and fatty acid synthesis. Enolase 1 (ENO1), a key gene in glycolysis, was one of the top-ranked genes in the DS-induced EndMT cluster. Pseudotime trajectory analysis revealed that the kinetic expression of ENO1 was significantly associated with EndMT and that ENO1 silencing repressed the DS- and TGF-ß-induced EC inflammation and EndMT. Consistent with these findings, ENO1 was highly expressed in ECs at the inner curvature of the mouse aortic arch (which is exposed to DS) and atherosclerotic lesions, suggesting its proatherogenic role in vivo. In summary, we present a comprehensive single-cell atlas of ECs in response to different flow patterns within the same flow channel. Among the DS-regulated genes, ENO1 plays an important role in DS-induced EC inflammation and EndMT. These results provide insights into how hemodynamic forces regulate vascular endothelium in health and disease.

Review and Updates on Systemic Mastocytosis and Related Entities.

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.

The delivery of safe and effective test result communication, management and follow-up.

OBJECTIVES: This paper reports on a program of research funded by a National Health and Medical Research Council (NHRMC) partnership grant (2015-2021) entitled "Delivering safe and effective test result communication, management and follow-up". The project's objectives were to: 1) improve the effectiveness and safety of test-result management through the establishment of clear governance processes of communication, responsibility, and accountability; 2) harness health information technology to inform and monitor test-result management; and 3) enhance consumer contribution to the establishment of safe and effective test-result management systems. Type of program: The partnership project addressed its key objectives through: i) the development of a consumer-driven approach; ii) using diagnostic stewardship and digital health to enhance safety and quality; iii) identifying clinical workflows that can lead to timely and meaningful communication; and iv) contributing to the Royal College of Pathologists of Australasia and Australasian Association for Clinical Biochemistry and Laboratory Medicine's work on nationally harmonised alert thresholds for critical laboratory results. METHODS: The project employed a convergent mixed-methods approach using multistage studies across hospitals in South Eastern Sydney and Illawarra and Shoalhaven Local Health Districts. A consumer-centred approach, including patient reference groups and community forums, was used to identify mechanisms to enhance consumers' role in test-management governance processes and inform the direction of the research and interpretation of findings. Results and lessons learnt: The body of evidence generated by the project highlights the multilayered and interconnected components required to achieve safe and effective test results management. Addressing the significant patient safety risk associated with the failure to follow-up test results must include consideration of diagnostic clinical work tasks (involving multiple people across numerous clinical settings) and embrace patient-centred and digital health strategies for shared information and timely and meaningful communication.

Phthalates exposure and pubertal development in a 15-year follow-up birth cohort study in Taiwan.

Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored. Methods: We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years. Results: In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume. Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association.

Identifying Diagnostic Stewardship Mechanisms in the Electronic Test Result Management Process - Preliminary Findings from a Scoping Review.

Digital health can play a key role in diagnostic stewardship, which refers to the coordinated guidance and interventions to ensure the appropriate utilisation of diagnostic tests for therapeutic decision-making. Outcomes of test result management and the impacts of digital health are a result of the interaction between dimensions of a complex environment. This poster will present preliminary findings from a scoping review which identifies the stewardship mechanisms that facilitate safe and effective electronic management of test results.

Epitranscriptional Regulation: From the Perspectives of Cardiovascular Bioengineering.

The central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. As key intermediaries and modifiers, RNAs undergo various forms of modifications such as methylation, pseudouridylation, deamination, and hydroxylation. These modifications, termed epitranscriptional regulations, lead to functional changes in RNAs. Recent studies have demonstrated crucial roles for RNA modifications in gene translation, DNA damage response, and cell fate regulation. Epitranscriptional modifications play an essential role in development, mechanosensing, atherogenesis, and regeneration in the cardiovascular (CV) system, and their elucidation is critically important to understanding the molecular mechanisms underlying CV physiology and pathophysiology. This review aims at providing biomedical engineers with an overview of the epitranscriptome landscape, related key concepts, recent findings in epitranscriptional regulations, and tools for epitranscriptome analysis. The potential applications of this important field in biomedical engineering research are discussed.

WHIM Syndrome: First Reported Case in a Patient of African Ancestry.

Background: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare, primary immunodeficiency syndrome characterized by warts, hypogammaglobulinemia, immunodeficiency, and characteristic bone marrow features of myelokathexis. The pathophysiology of WHIM syndrome is due to an autosomal dominant gain of function mutation in the CXCR4 chemokine receptor resulting in increased activity that impairs neutrophil migration from the bone marrow into the peripheral blood. This results in bone marrow distinctively crowded with mature neutrophils whose balance is shifted towards cellular senescence developing these characteristic, apoptotic nuclei termed myelokathexis. Despite the resultant severe neutropenia, the clinical syndrome is often mild and accompanied by a variety of associated abnormalities that we are just beginning to understand. Case Report. Diagnosis of WHIM syndrome is incredibly difficult due to phenotypic heterogeneity. To date, there are only about 105 documented cases in the scientific literature. Here, we describe the first case of WHIM syndrome documented in a patient of African ancestry. The patient in question was diagnosed at the age of 29 after a comprehensive work-up for incidental neutropenia discovered at a primary care appointment at our center in the United States. In hindsight, the patient had a history of recurrent infections, bronchiectasis, hearing loss, and VSD repair that could not be previously explained. Conclusions: Despite the challenge of timely diagnosis and the wide spectrum of clinical features that we are still discovering, WHIM syndrome tends to be a milder immunodeficiency that is highly manageable. As presented in this case, most patients respond well to G-CSF injections and newer treatments such as small-molecule CXCR4 antagonists.

Non-producer multiple myeloma presenting with acute hyperammonemic encephalopathy: case report.

BACKGROUND: Hyperammonemic encephalopathy (HE) is a rare and life-threatening complication of multiple myeloma, with underlying mechanisms that are not fully understood. In contrast to previously reported cases, most of which have been associated with IgG or IgA isotypes, we describe a patient with HE as the presenting symptom of non-producer multiple myeloma (NPMM). CASE PRESENTATION: A 60-year-old man developed lethargy that progressed into coma. He was found to have an elevated ammonia level, despite normal hepatic function. He was diagnosed with HE secondary to NPMM, demonstrating 80% plasma cells without light chain expression in the bone marrow and absence of a monoclonal protein in the serum or urine, including by matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX). Myeloma-directed therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone successfully reversed his HE. At clinical relapse, he received salvage chemotherapy followed by venetoclax therapy, leading to a short period of neurological recovery. CONCLUSIONS: This case demonstrates that HE can occur in a patient with NPMM and challenges the mechanism suggested by limited prior studies; i.e., that excess ammonia in multiple myeloma arises from degradation of M-proteins. We postulate that the neoplastic plasma cells in NPMM have amplified amino acid metabolism, despite lacking detectable intracellular or secreted immunoglobulins.

A framework for conducting policy-relevant primary care research: a COVID-19 case study in Australia.

The onset of the coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, and the ensuing implementation of response measures directly impacted the delivery of Australian primary care services. Understanding how these measures affected practice activity is important for gauging both their effectiveness and implications for future service planning. During the first 2years of the COVID-19 pandemic, a research project was undertaken to determine the impact of the pandemic on Australian general practice activity as a collaborative undertaking between researchers, general practitioners, data custodians, and five primary health networks from New South Wales and Victoria, Australia. The project methodology was based on an established research approach called action research, which involves participatory involvement from key stakeholders throughout the research process. The strength and success of the project's methodological approach stemmed from the synergistic interrelationship between the four key elements of: collaboration, repeated action research cycles (utilising electronic general practice data), engaged governance, and the production and dissemination of apposite knowledge outcomes. The project approach, knowledge outputs and lessons learned can be adapted to future research undertakings across any primary care setting and highlight the utility of action research and interdisciplinary research collaboration to produce knowledge directly relevant to clinical practice.

General practice perspective on the use of telehealth during the COVID-19 pandemic in Australia using an Action Research approach: a qualitative study.

OBJECTIVES: Telehealth has emerged as a viable and safe mode of care delivery in Australia during the COVID-19 pandemic. However, electronic general practice data reveal differences in uptake and consultation mode, which we hypothesise may be due to potential barriers impacting on quality of care. We aimed to identify the benefits and barriers of telehealth use in general practice, using an 'Action Research' approach involving general practitioners (GPs) and general practice stakeholders. DESIGN: Qualitative focus group performed within a broader Action Research methodology. SETTING: A focus group was held in August 2021, with general practice participants from Victoria, Australia. PARTICIPANTS: The study consisted of a purposive sample of 11 participants, including GPs (n=4), representatives from three primary health networks (n=4) and data custodian representatives (n=3) who were part of a project stakeholder group guided by an Action Research approach. METHODS: Semistructured interview questions were used to guide focus group discussions via videoconference, which were recorded and transcribed verbatim for analysis. The transcript was analysed using an inductive thematic approach. RESULTS: Emerging themes included evolution of telehealth, barriers to telehealth (privacy, eligibility, technology, quality of care, sociodemographic and residential aged care barriers) and benefits of telehealth (practice, quality of care, sociodemographic and residential aged care benefits). CONCLUSION: The findings highlight a range of barriers to telehealth that impact general practice, but also provide justification for the continuation and development of telehealth. These results provide important context to support data-driven population-based findings on telehealth uptake. They also highlight areas of quality improvement for the enhancement of telehealth as a valuable tool for routine general practice patient care.

Monocytes engineered with iSNAP inhibit human B-lymphoma progression.

Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47-SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well-known as the "Don't eat me" signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47-SIRPα axis to create iSNAP-M which activates pathways in engineered human monocytes (iSNAP-MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP-monocytes (iSNAP-MC). With PMA induction, the iSNAP-MC-derived macrophages (iSNAP-MΦ) showed upregelation in CD86 and CD80, but not CD206. TNFα expression and secretion were also increased in iSNAP-MΦ. Furthermore, the injection of iSNAP-MC into mice bearing human B-lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47-SIRPα axis, can be applied to suppress target tumors for cancer immunotherapy.

Telehealth utilisation in residential aged care facilities during the COVID-19 pandemic: A retrospective cohort study in Australian general practice.

INTRODUCTION: Our earlier analysis during the COVID-19 surges in 2020 showed a reduction in general practitioner (GP) in-person visits to residential aged care facilities (RACFs) and increased use of telehealth. This study assessed how sociodemographic characteristics affected telehealth utilisation. METHODS: This retrospective cohort consists of 27,980 RACF residents aged 65 years and over, identified from general practice electronic health records in Victoria and New South Wales during March 2020-August 2021. Residents' demographic characteristics, including age, sex, region, and pension status, were analysed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the associations with telehealth utilisation (telephone/video vs. in-person consultations) and with video versus telephone consultations, in mixed-effects multiple level regression models. RESULTS: Of 32,330 median monthly GP consultations among 21,987 residents identified in 2020, telehealth visits accounted for 17% of GP consultations, of which 93% were telephone consults. In 2021, of 32,229 median monthly GP consultations among 22,712 residents, telehealth visits accounted for 11% of GP consultations (97% by telephone). Pension holders (OR: 1.14; 95% CI: 1.10, 1.17) and those residing in rural areas (OR: 1.72; 95% CI: 1.57, 1.90) were more likely to use telehealth. However, residents in rural areas were less likely to use video than telephone in GP consultations (OR: 0.41; 95% CI: 0.29, 0.57). Results were similar in separate analyses for each COVID surge. DISCUSSION: Telephone was primarily used in telehealth consultations among pension holders and rural residents in RACFs. Along with the limited use of video in virtual care in rural RACFs, the digital divide may imply potential healthcare disparities in socially disadvantaged patients.

Investigating the association between blood transfusion and clinical outcomes in patients with acute coronary syndromes: a data linkage approach to Patient Blood Management.

BACKGROUND: The appropriateness of the use of blood transfusion in patients with acute coronary syndromes (ACS) remains contested. In general, studies addressing this issue were based on data from clinical trials, registries, or electronic medical records, and were conducted across different settings. Our study aimed to use a linked patient blood management data system from existing hospital databases to examine the association between blood transfusion and in-hospital mortality, length of stay (LOS) and readmission rates among patients with ACS, and to investigate this relationship at different haemoglobin (Hb) concentrations. MATERIALS AND METHODS: This was a retrospective observational study of patients admitted to participating hospitals between 1st January 2014 to 31st December 2017 with ACS recorded as primary diagnosis. Admission and nadir Hb concentrations were categorised as ≤100 g/L and >100 g/L. Generalised estimating equations were used to investigate the association between transfusion and clinical outcomes, while accounting for the correlation of multiple admissions from the same patients across hospitals over the study period. RESULTS: Of the 9,952 admissions included, blood transfusions occurred in 705 (7.1%). In unadjusted analyses, transfusion was associated with an increased risk of in-hospital mortality (OR: 2.97; 95% CI: 2.14-4.13) and an average LOS 3.55 (95% CI: 3.38-3.72) times longer. After adjusting for demographic and clinical factors, transfusion was associated with an increased risk of in-hospital mortality when Hb >100 g/L. Transfusion was not associated with the risk of readmission. DISCUSSION: The effect of transfusion on in-hospital mortality was largely dependent on the pre-transfusion Hb concentration. When Hb was >100 g/L transfusion was associated with increased mortality, whereas when Hb ≤100 g/L no association was observed.

Identifying the mechanisms that contribute to safe and effective electronic test result management systems- a multisite qualitative study.

OBJECTIVE: Suboptimal design of health information technology (IT) systems can lead to the introduction of errors in the diagnostic process. We aimed to identify mechanisms that can affect the safety and effectiveness of these systems in hospital settings thus contributing to the building of an explicit and replicable understanding of the variables that can affect the functioning of IT systems. MATERIALS AND METHODS: This qualitative study drew from observations and semistructured interviews from a purposive sample of 46 participants (26 emergency department and 20 laboratory and medical imaging staff) across 3 Australian hospitals. Iterative, inductive coding of the data led to the development of higher-level themes based on relationships between codes. RESULTS: Two overarching themes emerged: (1) usability and safety of the electronic test result management system; and (2) system redesign considerations about who is meant to follow up, when and how. The usability and safety of digital systems and the way these systems deal with accountability processes are triggered by mechanisms that are contextually dependent. DISCUSSION: Our findings highlighted the multitransactional nature of the test result management process involving numerous healthcare professionals across different settings. This communication requires integration of the systems utilized by different departments and transparency of the test result follow-up process to facilitate clear lines of responsibility and accountability. CONCLUSION: Identifying mechanisms that shape the functionality and sustainability of electronic result management can offer a valuable appreciation of key elements that need to be accounted for, and the circumstances in which they need to operate effectively.

Diagnostic Informatics-The Role of Digital Health in Diagnostic Stewardship and the Achievement of Excellence, Safety, and Value.

Diagnostic investigations (pathology laboratory and medical imaging) aim to: increase certainty of the presence or absence of disease by supporting the process of differential diagnosis; support clinical management; and monitor a patient's trajectory (e. g., disease progression or response to treatment). Digital health can be defined as the collection, storage, retrieval, transmission, and utilization of data, information, and knowledge to support healthcare. Digital health has become an essential component of the diagnostic process, helping to facilitate the accuracy and timeliness of information transfer and enhance the effectiveness of decision-making processes. Digital health is also important to diagnostic stewardship, which involves coordinated guidance and interventions to ensure the appropriate utilization of diagnostic tests for therapeutic decision-making. Diagnostic stewardship and informatics are thus important in efforts to establish shared decision-making. This is because they contribute to the establishment of shared information platforms (enabling patients to read, comment on, and share in decisions about their care) based on timely and meaningful communication. This paper will outline key diagnostic informatics and stewardship initiatives across three interrelated fields: (1) diagnostic error and the establishment of outcomes-based diagnostic research; (2) the safety and effectiveness of test result management and follow-up; and (3) digitally enhanced decision support systems.

COVID-19: protocol for observational studies utilizing near real-time electronic Australian general practice data to promote effective care and best-practice policy-a design thinking approach.

BACKGROUND: Health systems around the world have been forced to make choices about how to prioritize care, manage infection control and maintain reserve capacity for future disease outbreaks. Primary healthcare has moved into the front line as COVID-19 testing transitions from hospitals to multiple providers, where tracking testing behaviours can be fragmented and delayed. Pooled general practice data are a valuable resource which can be used to inform population and individual care decision-making. This project aims to examine the feasibility of using near real-time electronic general practice data to promote effective care and best-practice policy. METHODS: The project will utilize a design thinking approach involving all collaborators (primary health networks [PHNs], general practices, consumer groups, researchers, and digital health developers, pathology professionals) to enhance the development of meaningful and translational project outcomes. The project will be based on a series of observational studies utilizing near real-time electronic general practice data from a secure and comprehensive digital health platform [POpulation Level Analysis and Reporting (POLAR) general practice data warehouse]. The study will be carried out over 1.5 years (July 2020-December 2021) using data from over 450 general practices within three Victorian PHNs and Gippsland PHN, Eastern Melbourne PHN and South Eastern Melbourne PHN, supplemented by data from consenting general practices from two PHNs in New South Wales, Central and Eastern Sydney PHN and South Western Sydney PHN. DISCUSSION: The project will be developed using a design thinking approach, leading to the building of a meaningful near real-time COVID-19 geospatial reporting framework and dashboard for decision-makers at community, state and nationwide levels, to identify and monitor emerging trends and the impact of interventions/policy decisions. This will integrate timely evidence about the impact of the COVID-19 pandemic related to its diagnosis and treatment, and its impact across clinical, population and general practice levels.