Community-based access to oral antiviral treatments for COVID-19 in Australia.

BACKGROUND: The availability of oral antivirals for SARS-CoV-2 infection reduces the risk of severe, acute illness in people at higher risk for death and hospitalisation. OBJECTIVE: The process for antiviral prescription and dispensing in Australia is outlined using nationwide data. DISCUSSION: Australia has focused on providing rapid access to antivirals to high-risk people in the community via general practices and community pharmacies. Although the introduction of oral antiviral treatments is an important part of the response to the COVID-19 pandemic, vaccination remains the most effective way of mitigating the risk of developing severe complications of COVID-19, including hospitalisation and death.

Electrical Conductivity of Additively Manufactured Copper and Silver for Electrical Winding Applications.

Efficient and power-dense electrical machines are critical in driving the next generation of green energy technologies for many industries including automotive, aerospace and energy. However, one of the primary requirements to enable this is the fabrication of compact custom windings with optimised materials and geometries. Electrical machine windings rely on highly electrically conductive materials, and therefore, the Additive Manufacturing (AM) of custom copper (Cu) and silver (Ag) windings offers opportunities to simultaneously improve efficiency through optimised materials, custom geometries and topology and thermal management through integrated cooling strategies. Laser Powder Bed Fusion (L-PBF) is the most mature AM technology for metals, however, laser processing highly reflective and conductive metals such as Cu and Ag is highly challenging due to insufficient energy absorption. In this regard, this study details the 400 W L-PBF processing of high-purity Cu, Ag and Cu-Ag alloys and the resultant electrical conductivity performance. Six Cu and Ag material variants are investigated in four comparative studies characterising the influence of material composition, powder recoating, laser exposure and electropolishing. The highest density and electrical conductivity achieved was 88% and 73% IACS, respectively. To aid in the application of electrical insulation coatings, electropolishing parameters are established to improve surface roughness. Finally, proof-of-concept electrical machine coils are fabricated, highlighting the potential for 400 W L-PBF processing of Cu and Ag, extending the current state of the art.

Social Disconnection and Psychological Distress in Canadian Men During the COVID-19 Pandemic.

The COVID-19 pandemic has significantly challenged many men's mental health. Efforts to control the spread of the virus have led to increasing social disconnection, fueling concerns about its long-term effects on men's mental health, and more specifically their experience of psychological distress. Social disconnection, psychological distress, and the relationship between them have yet to be formally explored in a Canadian male sample during the COVID-19 pandemic. The present study examined whether reduced social connection among men was associated with increased anxiety and depressive symptoms (psychological distress) and whether this association was moderated by living alone. The sample consisted of 434 help-seeking Canadian men who completed standardized measures. Analyses controlled for the potentially confounding effects of age and fear of COVID-19. Findings revealed that less social connection was associated with increased psychological distress. This association was not moderated by living alone, nor was living alone directly associated with psychological distress. Younger age and fear of COVID-19 were each independently associated with psychological distress. Socially disconnected men were more likely to experience anxiety and depressive symptoms, suggesting the need for interventions focussed on men's social connectedness, social support, and belongingness to help reduce some COVID-19-induced mental health risks.

Feasibility of pulse oximetry after water immersion.

OBJECTIVE: This study aimed to determine if pulse oximetry could reliably be used after immersion in water, and if so, which of the finger, earlobe or nose most reliably produced a functional waveform. METHOD: Pulse oximetry data was recorded from the ear, nose and finger before and after 30 min of immersion in water. The primary outcome was the ability to measure pulse oximetry at any of the sites. RESULTS: A total of 119 participants were enrolled (with a median age of 16 years, 55% male). A useful pulse oximetry waveform was obtained after immersion from at least one of the measurement sites in 118 (99.2%) participants. Waveforms were usable after immersion in 96% of participants at the nostril, compared to 92% at the finger, and 41% at the ear lobe. The likelihood of success at the ear was significantly lower than either the finger or the nose (41% vs 92% and 96% respectively, p < 0.0001 for both comparisons). The finger and nostril were similar. Oxygen saturations were not significantly different after immersion at the nostril (100% vs 100%, p = 0.537) and finger (100% vs 100%, p = 0.032) sites but were different at the ear (100% vs 96%, p < 0.0001). CONCLUSION: This study demonstrates that pulse oximetry is feasible and reliable in a large cohort of participants who have been immersed in water for 30 min. The results support the nostril as the most reliable location. Only pulse oximeters registered for clinical use should be employed for patient care.

Discussing diabetes, palliative and end of life care: choosing the 'right' language.

BACKGROUND: Palliative care and advance care planning are important components of diabetes and other chronic disease management plans. Most people with diabetes do not have conversations about palliative/end of life (EOL) care or advance care directives; often because diabetes clinicians are reluctant to discuss these issues. Guidelines for conversations and decision aids can assist shared decision-making for both clinicians and patients. The aim was to co-design information with older people with diabetes, families and clinicians to facilitate conversations about palliative and EOL care and to identify the language (words) people with diabetes, families and diabetes clinicians use to discuss death and dying. METHODS: We co-designed and tailored the information with advisory groups: (I) older people with diabetes/families, (II) interdisciplinary expert clinicians and undertook a scoping literature review to identify relevant content. The penultimate versions were independently evaluated in focus groups and via written feedback from representative stakeholder clinicians, people with diabetes and international experts in communication, palliative care and diabetes. RESULTS: The information met design and language criteria: 62 people participated in focus groups (48 clinicians, 14 older people with diabetes and 4 family members). There were important differences between people with diabetes and diabetes clinicians concerning the words used to refer to death: 'the language of death'. Diabetes clinicians choose soft words/euphemisms such as 'passed away' and 'gone' and indicated they mirrored patient language. People with diabetes preferred clear language and indicated euphemisms were confusing and misleading. Diabetes clinicians, rarely encountered death in their practice and indicated they lacked education about how to discuss diabetes EOL care. CONCLUSIONS: Co-design with key end-users improved relevance to these groups. Diabetes clinicians prefer to use euphemisms for death and would benefit from education and strategies to help them initiate conversations about EOL diabetes care.

Ventilation management in Victorian intensive care unit patients without acute respiratory distress syndrome.

BACKGROUND: The setting of tidal volume (VT) during controlled mechanical ventilation (CMV) in critically ill patients without acute respiratory distress syndrome (ARDS) is likely important but currently unknown. We aimed to describe current CMV settings in intensive care units (ICUs) across Victoria. METHODS: We performed a multicentre, prospective, observational study. We collected clinical, ventilatory and arterial blood gas data twice daily for 7 days. We performed subgroup analysis by sex and assessment of arterial partial pressure of carbon dioxide (PaCO2) management where hypercapnia was potentially physiologically contraindicated. RESULTS: We recorded 453 observational sets in 123 patients across seven ICUs. The most commonly selected initial VT was 500 mL (33%), and this proportion did not differ according to sex (32% male, 34% female). Moreover, 38% of patients were exposed to initial VT per predicted body weight (VT-PBW) > 8.0 mL/kg. VT-PBW in this range were more likely to occur in females, those with a lower height, lower ideal body weight or in those for whom hypercapnia was potentially physiologically contraindicated. As a consequence, females were more frequently exposed to a lower PaCO2 and higher pH. CONCLUSIONS: In adults without ARDS undergoing CMV in Australian ICUs, the initial VT was a stereotypical 500 mL in one-third of participants, irrespective of sex. Moreover, around 40% of patients were exposed to an initial VT-PBW > 8.0 mL/kg. Finally, women were more likely to be exposed to a high VT and hyperventilation.

Tumor necrosis factor-α potentiates the effects of angiotensin II on subfornical organ neurons.

Inflammation is thought to play a fundamental role in the pathophysiology of hypertension and heart failure, although the mechanisms for this remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), influence the subfornical organ (SFO) to modulate sympathetic activity and blood pressure. The pressor effects of TNF-α in the SFO are partially mediated by angiotensin II (ANG II) receptor type 1 (AT1R), and TNF-α is known to potentiate ANG II-induced hypertension. However, the cellular mechanism of the interaction between TNF-α and ANG II/AT1R signaling remains unknown. In the present study, we performed Ca2+ imaging on dissociated SFO neurons in vitro from male Sprague-Dawley rats to determine whether TNF-α modulates ANG II-induced increases in intracellular Ca2+ in SFO neurons. We first established that a proportion of SFO neurons respond to ANG II, an effect that required AT1R signaling and extracellular Ca2+. We then tested the hypothesis that TNF-α may modulate the effects of ANG II on SFO neurons by examining the effects of TNF-α treatment on the ANG II-induced rise in intracellular Ca2+. We discovered that TNF-α potentiated the ANG II-induced rise in intracellular Ca2+, an effect that was dependent on the duration of TNF-α treatment. Finally, we determined that this potentiation of ANG II-induced Ca2+ activity relied on tetrodotoxin-sensitive voltage-gated Na+ (vgNa+) channels. These data suggest that the potentiation of ANG II/AT1R activity by TNF-α in SFO neurons results from the previously demonstrated ability of this cytokine to modulate the activation threshold of vgNa+ currents.

The proinflammatory cytokine tumor necrosis factor-α excites subfornical organ neurons.

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α-/- mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects.NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by modulating the voltage-gated transient Na+ current. This provides critical new information regarding the specific pathological mechanisms through which inflammation and TNF-α in particular may result in the development of hypertension.

Fewer hospitalizations for chronic obstructive pulmonary disease in communities with smoke-free public policies.

OBJECTIVES: We determined the impact of smoke-free municipal public policies on hospitalizations for chronic obstructive pulmonary disease (COPD). METHODS: We conducted a secondary analysis of hospital discharges with a primary diagnosis of COPD in Kentucky between July 1, 2003, and June 30, 2011 using Poisson regression. We compared the hospitalization rates of regions with and without smoke-free laws, adjusting for personal and population covariates, seasonality, secular trends over time, and geographic region. RESULTS: Controlling for covariates such as sex, age, length of stay, race/ethnicity, education, income, and urban-rural status, among others, we found that those living in a community with a comprehensive smoke-free law or regulation were 22% less likely to experience hospitalizations for COPD than those living in a community with a moderate-weak law or no law. Those living in a community with an established law were 21% less likely to be hospitalized for COPD than those with newer laws or no laws. CONCLUSIONS: Strong smoke-free public policies may provide protection against COPD hospitalizations, particularly after 12 months, with the potential to save lives and decrease health care costs.

Cutaneous extramedullary hemopoiesis in chronic myeloproliferative and myelodysplastic disorders.

Cutaneous extramedullary hemopoiesis (EMH) is a rare complication of chronic myeloproliferative and myelodysplastic disorders. Chronic idiopathic myelofibrosis (CIMF) is the most common underlying condition. To date, fewer than 30 cases have been reported in the literature and there has been significant confusion with regard to the proposed pathogenesis. In this article, we describe two additional cases of cutaneous EMH associated with chronic myeloid diseases and review the literature with the aim of clarifying the underlying pathogenesis of this unusual clinical condition. The diagnosis of cutaneous EMH in both patients with chronic myeloid diseases was made histopathologically, with immunohistochemistry confirming the presence of differentiating hemopoietic cells associated with dermal components. Cutaneous EMH in chronic myeloid diseases occurs as a result of migration of abnormal neoplastic hemopoietic precursor cells into the skin (in effect, metastasis) and subsequent differentiation along divergent myeloid cell lineages. The diagnosis should be considered in any patient with chronic myeloproliferative or myelodysplastic disease who develops a skin rash.

Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial.

BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response. METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens. Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks. Analyses were by intention to treat. FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo. Most improvement occurred in the first 6 weeks. Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7). Benzoyl peroxide was the most cost-effective treatment. Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance. INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance.