Telehealth in remote Australia : a supplementary tool or an alternative model of care replacing face-to-face consultations?

Background: The COVID-19 pandemic increased the use of telehealth consultations by telephone and video around the world. While telehealth can improve access to primary health care, there are significant gaps in our understanding about how, when and to what extent telehealth should be used. This paper explores the perspectives of health care staff on the key elements relating to the effective use of telehealth for patients living in remote Australia. Methods: Between February 2020 and October 2021, interviews and discussion groups were conducted with 248 clinic staff from 20 different remote communities across northern Australia. Interview coding followed an inductive approach. Thematic analysis was used to group codes into common themes. Results: Reduced need to travel for telehealth consultations was perceived to benefit both health providers and patients. Telehealth functioned best when there was a pre-established relationship between the patient and the health care provider and with patients who had good knowledge of their personal health, spoke English and had access to and familiarity with digital technology. On the other hand, telehealth was thought to be resource intensive, increasing remote clinic staff workload as most patients needed clinic staff to facilitate the telehealth session and complete background administrative work to support the consultation and an interpreter for translation services. Clinic staff universally emphasised that telehealth is a useful supplementary tool, and not a stand-alone service model replacing face-to-face interactions. Conclusion: Telehealth has the potential to improve access to healthcare in remote areas if complemented with adequate face-to-face services. Careful workforce planning is required while introducing telehealth into clinics that already face high staff shortages. Digital infrastructure with reliable internet connections with sufficient speed and latency need to be available at affordable prices in remote communities to make full use of telehealth consultations. Training and employment of local Aboriginal staff as digital navigators could ensure a culturally safe clinical environment for telehealth consultations and promote the effective use of telehealth services among community members

Rituximab Treatment in Hepatitis C Infection: An In Vitro Model to Study the Impact of B Cell Depletion on Virus Infectivity

Hepatitis C virus (HCV) infected patients with vasculitis are often treated with the B-cell-depleting anti-CD20 antibody rituximab. Treatment reduces the cryoglobulins that cause vasculitis, yet it also leads to a transient increase in liver enzymes and HCV genomic RNA in the periphery. The mechanism underlying the increased viral load is unclear and both direct and indirect roles have been proposed for B cells in HCV infection. We previously reported that HCV can associate with B cells and can trans-infect hepatocytes. We established an in vitro assay to study the effect(s) of rituximab on B cell-associated HCV infectivity. Rituximab-mediated lysis of B cells in vitro increases the level of infectious HCV released from B cells. Our results, using a model where virus does not replicate in B cells, recapitulate observations seen in patients and may explain in part the rapid increase in blood HCV RNA observed after rituximab treatment

MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure.

OBJECTIVE: Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response. DESIGN: Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotype, functional/transcriptomic profile and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease controls. The temporal evolution of macrophage MerTK expression and its impact on resolution was examined in APAP-induced acute liver injury using wild-type (WT) and Mer-deficient (Mer-/-) mice. SLPI effects on hepatic myeloid cells were determined in vitro and in vivo using APAP-treated WT mice. RESULTS: We demonstrate a significant expansion of resolution-like MerTK+HLA-DRhigh cells in circulatory and tissue compartments of patients with ALF. Compared with WT mice which show an increase of MerTK+MHCIIhigh macrophages during the resolution phase in ALF, APAP-treated Mer-/- mice exhibit persistent liver injury and inflammation, characterised by a decreased proportion of resident Kupffer cells and increased number of neutrophils. Both in vitro and in APAP-treated mice, SLPI reprogrammes myeloid cells towards resolution responses through induction of a MerTK+HLA-DRhigh phenotype which promotes neutrophil apoptosis and their subsequent clearance. CONCLUSIONS: We identify a hepatoprotective, MerTK+, macrophage phenotype that evolves during the resolution phase following ALF and represents a novel immunotherapeutic target to promote resolution responses following acute liver injury

The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in enzyme-linked immunosorbent assay (ELISA) and whole cell-binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations, which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, this study identifies fenofibrate as a potential therapeutic agent requiring an urgent clinical evaluation to treat SARS-CoV-2 infection

Failure mechanisms of landfills under dynamic loading

Seismic stability of above-ground landfills is an issue of extreme engineering interest, and the proper implementation of the corresponding analyses requires dealing with several uncertainties related mainly to the special features of such large-scale geostructures. This study aims at providing an insight into the role of these parameters on the development of the potential failure modes that may take place during a seismic event. Additionally, the different failure modes are compared with respect to their seismic instability potential. Furthermore, an insight is provided on phenomena related to the simultaneous generation of more than one failure surfaces within the landfill. This is examined by developing a simple model based on the Newmark's sliding-block approach. Results indicate that the circular surfaces may provide a more critical mode of failure than the base sliding. © 2008 ASCE