Changes in general practice use and costs with COVID-19 and telehealth initiatives: analysis of Australian whole-population linked data.

BACKGROUND: In response to the COVID-19 pandemic, general practice in Australia underwent a rapid transition, including the roll-out of population-wide telehealth, with uncertain impacts on GP use and costs. AIM: To describe how use and costs of GP services changed in 2020 - following the COVID-19 pandemic and introduction of telehealth - compared with 2019, and how this varied across population subgroups. DESIGN AND SETTING: Linked-data analysis of whole-population data for Australia. METHOD: Multi-Agency Data Integration Project data for ∼19 million individuals from the 2016 census were linked to Medicare data for 2019-2020. Regression models were used to compare age- and sex-adjusted GP use and out-of-pocket costs over time, overall, and by sociodemographic characteristics. RESULTS: Of the population, 85.5% visited a GP in Q2-Q4 2020, compared with 89.5% in the same period of 2019. The mean number of face-to-face GP services per quarter declined, while telehealth services increased; overall use of GP services in Q4 2020 was similar to, or higher than, that of Q4 2019 for most groups. The proportion of total GP services by telehealth stabilised at 23.5% in Q4 2020. However, individuals aged 3-14 years, ≥70 years, and those with limited English proficiency used fewer GP services in 2020 compared with 2019, with a lower proportion by telehealth, compared with the rest of the population. Mean out-of-pocket costs per service were lower across all subgroups in 2020 compared with 2019. CONCLUSION: The introduction of widespread telehealth maintained the use of GP services during the COVID-19 pandemic and minimised out-of-pocket costs, but not for all population subgroups.

Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target.

Cofilin signaling in hemin-induced microglial activation and inflammation.

Intracerebral hemorrhage (ICH) is the most severe form of stroke and is further exacerbated by the secondary injury involving inflammatory response due to the activation of microglia. This secondary injury is partly due to the toxic effects of hemin, an endogenous breakdown product of hemoglobin. Cofilin, an actin depolymerizing factor, controls actin dynamics and has been previously shown to be involved in mediating neuronal cell death in ischemic conditions and during bacterial lipopolysaccharide induced microglial activation. There are limited studies regarding the deleterious effects of extremely high concentrations of hemin released during ICH and its effects on microglia and subsequent cofilin response. Therefore, investigations were conducted to study the effects of hemin on microglial activation induced inflammation and the critical role of cofilin in mediating the response. We observed that hemin treated microglia had a concentration dependent increase in cofilin expression and NO production. There were increased levels of iNOS, TNF-α, HO1, Nrf2, Wfs-1, XBP-1 and spliced XBP-1 observed in response to hemin treatment and the signaling was found to be partly mediated by cofilin. Acute hemin treatment did not evoke Ca2+ signaling and long-term treatment of hemin also resulted in the failure of microglial response to acetylcholine-evoked Ca2+ signaling. Knockdown of cofilin by siRNA also reduced acetylcholine-evoked Ca2+ signaling. These studies demonstrate that cofilin signaling is important in hemin-induced inflammation, oxidative stress, ER stress, microglial migration, and the ability to evoke Ca2+ signaling. Therefore, cofilin inhibition could be a potential therapy in brain injuries triggered by hemin toxicity in conditions like ICH.

Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population.

BACKGROUND: CYP1A1, CYP2A6 and CHRNA5 are biologically plausible genes as risk factors for lung cancer but no studies have been reported in the Bangladeshi population. METHODS: We conducted this study to determine the prevalence and role of CYP1A1, CYP2A6 and CHRNA5 polymorphisms together with tobacco smoking in the development of lung cancer in Bangladesh. A case-control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants of the CYP1A1 gene-rs4646903, rs1048943 and rs1799814; 2 variants of CYP2A6 (CYP2A6*1B1, CYP2A6*4) and 1 variant of CHRNA5 (rs16969968) using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. RESULTS: Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI) using unconditional logistic regression models adjusting for age, sex and smoking. A significantly elevated lung cancer risk was associated with heterozygous, mutant and combined heterozygous plus mutant variants of CYP1A1 rs4646903. A significant association was also found for heterozygous and heterozygous plus mutant variants of rs1048943 which was in linkage disequilibrium with rs4646903. The risk of lung cancer was decreased significantly in individuals carrying at least one CYP2A6 deletion (CYP2A6*4) allele. No association with lung cancer risk was found for CHRNA5 rs16969968. When stratified by smoking, the effects of CYP1A1 and CYP2A6 polymorphisms on lung cancer susceptibility were found to be significant only in heavy smokers who had smoked 40 pack years or more (54% of all cases) but no associations were seen for lighter smokers. No association was also found with any polymorphism in the non-smokers in this study. CONCLUSIONS: Our results indicate that the CYP1A1*2B allele (rs4646903 and rs1048943) is associated with an increased lung cancer risk and CYP2A6*4 is associated with a decreased lung cancer risk in the study population.