Evaluating Pilot Implementation of 'PenCS Flu Topbar' App in Medical Practices to Improve National Immunisation Program-Funded Seasonal Influenza Vaccination in Central Queensland, Australia.

BACKGROUND: The 'PenCS Flu Topbar' app was deployed in Central Queensland (CQ), Australia, medical practices through a pilot programme in March 2021. METHODS: We evaluated the app's user experience and examined whether the introduction of 'PenCS Flu Topbar' in medical practices could improve the coverage of NIP-funded influenza vaccinations. We conducted a mixed-method study including a qualitative analysis of in-depth interviews with key end-users and a quantitative analysis of influenza vaccine administrative data. RESULTS: 'PenCS Flu Topbar' app users reported positive experiences identifying patients eligible for NIP-funded seasonal influenza vaccination. A total of 3606 NIP-funded influenza vaccinations was administered in the eight intervention practices, 14% higher than the eight control practices. NIP-funded vaccination coverage within practices was significantly higher in the intervention practices (31.2%) than in the control practices (27.3%) (absolute difference: 3.9%; 95% CI: 2.9%-5.0%; p < 0.001). The coverage was substantially higher in Aboriginal and Torres Strait Islander people aged more than 6 months, pregnant women and children aged 6 months to less than 5 years for the practices where the app was introduced when compared to control practices: incidence rate ratio (IRR) 2.4 (95% CI: 1.8-3.2), IRR 2.7 (95% CI: 1.8-4.2) and IRR 2.3 (1.8-2.9) times higher, respectively. CONCLUSIONS: Our evaluation indicated that the 'PenCS Flu Topbar' app is useful for identifying the patients eligible for NIP-funded influenza vaccination and is likely to increase NIP-funded influenza vaccine coverage in the eligible populations. Future impact evaluation including a greater number of practices and a wider geographical area is essential.

P2X7 receptor knockout does not alter renal function or prevent angiotensin II-induced kidney injury in F344 rats.

P2X7 receptors mediate immune and endothelial cell responses to extracellular ATP. Acute pharmacological blockade increases renal blood flow and filtration rate, suggesting that receptor activation promotes tonic vasoconstriction. P2X7 expression is increased in kidney disease and blockade/knockout is renoprotective. We generated a P2X7 knockout rat on F344 background, hypothesising enhanced renal blood flow and protection from angiotensin-II-induced renal injury. CRISPR/Cas9 introduced an early stop codon into exon 2 of P2rx7, abolishing P2X7 protein in kidney and reducing P2rx7 mRNA abundance by ~ 60% in bone-marrow derived macrophages. The M1 polarisation response to lipopolysaccharide was unaffected but P2X7 receptor knockout suppressed ATP-induced IL-1ß release. In male knockout rats, acetylcholine-induced dilation of the renal artery ex vivo was diminished but not the response to nitroprusside. Renal function in male and female knockout rats was not different from wild-type. Finally, in male rats infused with angiotensin-II for 6 weeks, P2X7 knockout did not reduce albuminuria, tubular injury, renal macrophage accrual, and renal perivascular fibrosis. Contrary to our hypothesis, global P2X7 knockout had no impact on in vivo renal hemodynamics. Our study does not indicate a major role for P2X7 receptor activation in renal vascular injury.

Epigenetic modulators link mitochondrial redox homeostasis to cardiac function in a sex-dependent manner.

While excessive production of reactive oxygen species (ROS) is a characteristic hallmark of numerous diseases, clinical approaches that ameliorate oxidative stress have been unsuccessful. Here, utilizing multi-omics, we demonstrate that in cardiomyocytes, mitochondrial isocitrate dehydrogenase (IDH2) constitutes a major antioxidative defense mechanism. Paradoxically reduced expression of IDH2 associated with ventricular eccentric hypertrophy is counterbalanced by an increase in the enzyme activity. We unveil redox-dependent sex dimorphism, and extensive mutual regulation of the antioxidative activities of IDH2 and NRF2 by a feedforward network that involves 2-oxoglutarate and L-2-hydroxyglutarate and mediated in part through unconventional hydroxy-methylation of cytosine residues present in introns. Consequently, conditional targeting of ROS in a murine model of heart failure improves cardiac function in sex- and phenotype-dependent manners. Together, these insights may explain why previous attempts to treat heart failure with antioxidants have been unsuccessful and open new approaches to personalizing and, thereby, improving such treatment.

Estimated health and economic impact of using high-dose influenza vaccine on respiratory and circulatory plus respiratory hospitalizations of older adults in Australia.

Background: Standard dose influenza vaccine provides moderate protection from infection, but with lower effectiveness among the elderly. High dose and adjuvanted vaccines (HD-TIV and aTIV) were developed to address this. This study aims to estimate the incremental health and economic impact of using HD-TIV (high dose trivalent vaccine) instead of aTIV (adjuvanted trivalent vaccine) on respiratory and circulatory plus respiratory hospitalizations of older people (≥65 years) in Australia. Methods: This is a modelling study comparing predicted hospitalization outcomes in people receiving HD-TIV or aTIV during an average influenza season in Australia. Hospitalization records of Australian adults ≥65 years of age from 01 April to 30 November during 15 influenza seasons (2002-2017 excluding 2009, which was a pandemic) were extracted from the Australian Institute of Health and Welfare [AIHW] and used to calculate hospitalisation rates during an average season. Relative vaccine effectiveness data for aTIV and HD-TIV were used to estimate morbidity burden related to influenza. Results: Between 2002 and 2017, the average respiratory hospitalization rate among older people during influenza season (April-November) was 3,445/100,000 population-seasons, with an average cost of AU$ 7,175 per admission. The average circulatory plus respiratory hospitalization rate among older Australian people during that time was 10,393/100,000 population-seasons, with an average cost of AU$ 7829 per admission. For older Australians, HD-TIV may avert an additional 6,315-9,410 respiratory admissions each year, with an incremental healthcare cost saving of AU$ 15.9-38.2 million per year compared to aTIV. Similar results were also noted for circulatory plus respiratory hospitalizations. Conclusions: From the modelled estimations, HD-TIV was associated with less economic burden and fewer respiratory, and circulatory plus respiratory hospitalizations than aTIV for older Australians.

Informing the design of a whole of life immunisation register for Australia.

INTRODUCTION: In 2016, Australia launched a whole life immunisation register, the Australian Immunisation Register (AIR), building on a universal childhood register established in 1997. Immunisation Information Systems are well established in Europe, the US and elsewhere. However, a national system covering immunisation across the lifespan, with complete capture of the population and satisfactory data quality, is rare. METHODS: A national workshop was convened in 2016 with key stakeholders from the government, new and existing vaccine users, and vaccine providers to review the ideal features of the AIR to ensure optimal effectiveness. This workshop focused on the functionality needed to identify population groups newly included in the register and support the achievement of high immunisation coverage in these groups eligible for National Immunisation Program vaccines. RESULTS: Key recommendations included the need for bidirectional data flow between the AIR and providers; systematic approaches to the capture and recording of accurate and complete data to ascertain important denominators for subpopulations, includingAboriginal and Torres Strait Islander status, medical risk factors, occupation, ethnicity, country of birth, and vaccines given during pregnancy; linkage with other government datasets including notifiable diseases; the capture of adverse events following immunisation; ease of access by patients, providers; and by researchers. CONCLUSIONS: Some recommendations from the workshop have informed the development and future utility of the AIR. Some recommendations from the workshop have been integrated into the current iteration of the AIR, which is more important than ever given the roll-out of COVID-19 vaccines. The accuracy and validity of data have subsequently improved through data entry controls, data integrity checks and reporting requirements. Access to AIR data for research remains protracted and costly, limitingresearch potential.

The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan.

BACKGROUND: Endothelin A receptor antagonists (ETARA) slow chronic kidney disease (CKD) progression but their use is limited due to fluid retention and associated clinical risks. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) cause osmotic diuresis and improve clinical outcomes in CKD and heart failure. We hypothesized that co-administration of the SGLT2i dapagliflozin with the ETARA zibotentan would mitigate the fluid retention risk using hematocrit (Hct) and bodyweight as proxies for fluid retention. METHODS: Experiments were performed in 4% salt fed WKY rats. First, we determined the effect of zibotentan (30, 100 or 300 mg/kg/day) on Hct and bodyweight. Second, we assessed the effect of zibotentan (30 or 100 mg/kg/day) alone or in combination with dapagliflozin (3 mg/kg/day) on Hct and bodyweight. RESULTS: Hct at Day 7 was lower in zibotentan versus vehicle groups [zibotentan 30 mg/kg/day, 43% (standard error 1); 100 mg/kg/day, 42% (1); and 300 mg/kg/day, 42% (1); vs vehicle, 46% (1); P < .05], while bodyweight was numerically higher in all zibotentan groups compared with vehicle. Combining zibotentan with dapagliflozin for 7 days prevented the change in Hct [zibotentan 100 mg/kg/day and dapagliflozin, 45% (1); vs vehicle 46% (1); P = .44] and prevented the zibotentan-driven increase in bodyweight (zibotentan 100 mg/kg/day + dapagliflozin 3 mg/kg/day = -3.65 g baseline corrected bodyweight change; P = .15). CONCLUSIONS: Combining ETARA with SGLT2i prevents ETARA-induced fluid retention, supporting clinical studies to assess the efficacy and safety of combining zibotentan and dapagliflozin in individuals with CKD.

Selecting the right therapeutic target for kidney disease.

Kidney disease is a complex disease with several different etiologies and underlying associated pathophysiology. This is reflected by the lack of effective treatment therapies in chronic kidney disease (CKD) that stop disease progression. However, novel strategies, recent scientific breakthroughs, and technological advances have revealed new possibilities for finding novel disease drivers in CKD. This review describes some of the latest advances in the field and brings them together in a more holistic framework as applied to identification and validation of disease drivers in CKD. It uses high-resolution 'patient-centric' omics data sets, advanced in silico tools (systems biology, connectivity mapping, and machine learning) and 'state-of-the-art' experimental systems (complex 3D systems in vitro, CRISPR gene editing, and various model biological systems in vivo). Application of such a framework is expected to increase the likelihood of successful identification of novel drug candidates based on strong human target validation and a better scientific understanding of underlying mechanisms.

The role of chronic disease in the disparity of influenza incidence and severity between indigenous and non-indigenous Australian peoples during the 2009 influenza pandemic.

BACKGROUND: The 2009 H1N1 influenza pandemic (influenza A(H1N1)pdm09) disproportionately impacted Indigenous peoples. Indigenous Australians are also affected by a health gap in chronic disease prevalence. We hypothesised that the disparity in influenza incidence and severity was accounted for by higher chronic disease prevalence. METHODS: We analysed influenza data from Western Australia, South Australia, the Northern Territory, and Queensland. We calculated population prevalence of chronic diseases in Indigenous and non-Indigenous Australian populations using nationally-collected health survey data. We compared influenza case notifications, hospitalisations, intensive care admissions, and deaths reported amongst the total population of Indigenous and non-Indigenous Australians ≥ 15 years. We accessed age-specific influenza data reported to the Australian Department of Health during the 2009 'swine flu' pandemic, stratified by Indigenous status and the presence of one of five chronic conditions: chronic lower respiratory conditions, diabetes mellitus, obesity, renal disease, and cardiac disease. We calculated age-standardised Indigenous: non-Indigenous rate ratios and confidence intervals. FINDINGS: Chronic diseases were more prevalent in Indigenous Australians. Rates of influenza diagnoses were higher in Indigenous Australians and more frequent across all indices of severity. In those with chronic conditions, Indigenous: non-Indigenous influenza notification rate ratios were no lower than in the total population; in many instances they were higher. Rate ratios remained above 1·0 at all levels of severity. However, once infected (reflected in notifications), there was no evidence of a further increase in risk of severe outcomes (hospitalisations, ICU admissions, deaths) amongst Indigenous Australians compared to non-Indigenous Australians with a chronic disease. INTERPRETATION: Higher rates of influenza infection was observed amongst those Indigenous compared to non-Indigenous Australians, and this difference was preserved amongst those with a chronic condition. However, there was no further increase in prevalence of more severe influenza outcomes amongst Indigenous Australians with a chronic condition. This suggests that the prevalence of chronic disease, rather than Indigenous status, affected influenza severity. Other factors may be important, including presence of multiple morbidities, as well as social and cultural determinants of health.

Altered Circulating microRNAs in Patients with Diabetic Neuropathy and Corneal Nerve Loss: A Pilot Study.

An alteration in circulating miRNAs may have important diagnostic and therapeutic relevance in diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) underwent an assessment of neuropathic symptoms using Douleur Neuropathique 4 (DN4), the vibration perception threshold (VPT) using a Neurothesiometer, sudomotor function using the Sudoscan, corneal nerve morphology using corneal confocal microscopy (CCM) and circulating miRNAs using high-throughput miRNA expression profiling. Patients with T2DM, with (n = 9) and without (n = 7) significant corneal nerve loss were comparable in age, gender, diabetes duration, BMI, HbA1c, eGFR, blood pressure, and lipid profile. The VPT was significantly higher (p < 0.05), and electrochemical skin conductance (p < 0.05), corneal nerve fiber density (p = 0.001), corneal nerve branch density (p = 0.013), and corneal nerve fiber length (p < 0.001) were significantly lower in T2DM patients with corneal nerve loss compared to those without corneal nerve loss. Following a q-PCR-based analysis of total plasma microRNAs, we found that miR-92b-3p (p = 0.008) was significantly downregulated, while miR-22-3p (p = 0.0001) was significantly upregulated in T2DM patients with corneal nerve loss. A network analysis revealed that these miRNAs regulate axonal guidance and neuroinflammation genes. These data support the need for more extensive studies to better understand the role of dysregulated miRNAs' in diabetic neuropathy.

Modelling the influenza disease burden in people aged 50-64 and ≥65 years in Australia.

BACKGROUND: Estimation of influenza disease burden is necessary to monitor the impact of intervention programmes. This study aims to estimate the attributable fraction of respiratory and circulatory disease due to influenza among Australian adults 50-64 and ≥65 years of age. METHODS: A semi-parametric generalised-additive model was used to estimate annual and average rate of influenza-attributable hospitalisation and death per 100,000 population under the principal diagnosis of influenza/pneumonia, respiratory, circulatory and myocardial infarction (MI) from 2001 through 2017. RESULTS: Over the study period, seasonal influenza accounted for an estimated annual average respiratory hospitalisation rate of 78.9 (95%CI: 76.3, 81.4) and 287.5 (95%CI: 279.8, 295.3) per 100,000 population in adults aged 50-64 and ≥65 years, respectively. The corresponding respiratory mortality rates were 0.9 (95%CI: 0.7, 1.2) and 18.2 (95%CI: 16.9, 19.4) per 100,000 population. The 2017 season had the highest influenza-attributable respiratory hospitalisations in both age groups, and respiratory complications were estimated approximately 2.5 times higher than the average annual estimate in adults aged ≥65 years in 2017. For mortality, on average, influenza attributed 1,080 circulatory and 361 MI deaths in adults aged ≥65 years per year. Influenza accounted for 1% and 2.8% of total MI deaths in adults aged 50-64 and ≥65 years, respectively. CONCLUSION: Rates of cardiorespiratory morbidity and mortality were high in older adults, whilst the younger age group contributed a lower disease burden. Extension of influenza vaccination programme beyond the targeted population could be an alternative strategy to reduce the burden of influenza.

The need for pertussis vaccination among older adults and high-risk groups: a perspective from advanced economies of the Asia Pacific region.

Introduction: Influenza and pneumococcal vaccines are the most regularly prescribed vaccines amongst adults <65 years of age. Pertussis booster vaccines (available as combined diphtheria-tetanus-acellular pertussis, Tdap) uptake is relatively low in many countries in the Asia-Pacific region. Increasing Tdap vaccination is a strategy that may aid healthy aging.Areas Covered: Epidemiology data, including notification reports from 6 advanced economies in Asia (Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan) were reviewed to assess the pertussis disease burden and identify high-risk groups. Existing Tdap vaccination recommendations were reviewed. Current vaccination practices were discussed to benchmark and identify barriers and success factors for Tdap booster vaccination in older adults.Expert Opinion: The available evidence supports Tdap vaccination at an individual level for the prevention of pertussis, along with tetanus and diphtheria in those aged 65+ years, together with influenza and pneumococcal vaccination. Data gaps need to be filled to support the development of national/supranational recommendations for pertussis booster vaccination. Groups at higher risk of pertussis infection and its complications, including those with chronic obstructive pulmonary disease and asthma, could be considered as priority groups. Increasing disease awareness and establishing adult vaccination registries could improve vaccine coverage and promote healthy aging.

PLAIN LANGUAGE SUMMARYPertussis, also called whooping cough, is a common disease in adults. However, how it affects adults in some countries in the Asia-Pacific region is not well understood. In 2019, a panel of experts met to review the available information on adult cases of pertussis in Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan. Here, we present the outcomes of the meeting. Pertussis is increasingly reported in the Asia-Pacific region, including cases diagnosed in adults. The diagnosis may be missed in countries where awareness is still low and/or it is not tested routinely. The experts concluded that physicians should consider recommending pertussis vaccination to older adults (aged 65 or older) on an individual basis, as well as people with asthma or chronic obstructive pulmonary disease, who appear to be at higher risk of severe pertussis. Uptake of pertussis vaccination in adults could be improved by increasing awareness of the vaccines available and vaccination infrastructure for this age-group. Some of the measures proposed were as follows: improved access to vaccination; personalized reminders when vaccines are due; and more education about pertussis in adults for doctors, nursesnurses, and patients. The experts also proposed setting up adult vaccination registries for tracking and evaluation of vaccine uptake. This expert opinion might help the healthcare community build action plans to recognise the burden of the disease and increase rates of vaccination among adults. In addition, better data on the disease burden would help to generate awareness.

Estimating pertussis incidence in general practice using a large Australian primary care database.

BACKGROUND: While pertussis is notifiable in most countries, notifications typically underestimate the true pertussis burden. We explored the incidence of pertussis in general practice in Australia. METHODS: Using MedicineInsight, a large longitudinal electronic medical record database of general practice (primary care) encounters which includes >1.5 million patients, we first defined a cohort of active patients and then used free-text search algorithms to identify patients with pertussis-related encounters. We defined and identified pertussis-related encounters in four patient categories: pertussis-associated (category 1), potential pertussis (category 2), epidemiologically-linked pertussis (category 3), and symptoms consistent with pertussis (category 4). Incident pertussis-related encounter rates per 100,000 active patients were calculated from Jan 2008 to Aug 2015. RESULTS: Estimated mean annual pertussis incidence increased as definitions were expanded, from 94.3 (category 1 patients only) to 148.8 (categories 1+2+3 patients combined) per 100,000 active patients per year. Monthly time-series corresponding to the first three categories were highly correlated (Pearson's r > 90% for each pair), but each was poorly correlated with category 4. For categories 1+2+3, the highest incidence was among 0-4 and 5-9 year olds. Incidence was 30% higher in females than males (i.e. 184.5 vs 139.8 per 100,00 active patients for categories 1-3 patients combined). Pertussis-associated incidence (category 1) was similar to national pertussis notification rates. Categories 2 and 3 added 25% and 33%, respectively, on average relative to category 1 incidence. The estimated incidence from categories 1+2+3 together were on average 64% higher than national pertussis notification rates. CONCLUSION: We provide comprehensive estimates of pertussis-related incidence in general practice (primary care), well in excess of notified pertussis incidence in Australia. This highlights the utility of MedicineInsight data in providing a greater understanding of the burden of medically-attended pertussis infections.

Vaccine coverage in children born to migrant mothers in Australia: A population-based cohort study.

BACKGROUND: Overall, infant immunisation coverage is currently >90% in Australia, but there are pockets of under-immunised children including children from migrant backgrounds. This study aimed to examine whether on-time vaccination coverage of diphtheria-tetanus-pertussis dose 3 (DTP3) for children born in Australia differed by mother's region of birth and if so, what factors were associated with these differences. METHODS: We conducted a population-based cohort study using linked data on perinatal, immunisation and birth records for 2 million children born in Western Australia and New South Wales between 1996 and 2012. We assessed on-time coverage of DTP3 (vaccination from 2 weeks prior to, and up until 30 days after, the due date) in children with mothers born overseas. Logistic regression models were developed to determine factors associated with on-time coverage for each maternal region of birth and all regions combined, adjusting for a range of demographic factors. Adjusted estimates of coverage were calculated for the different regions of birth. RESULTS: On-time DTP3 coverage was 76.2% in children of Australian born mothers, lower in children of mothers from Oceania (66.7%) and North America (68%), and higher in children born to mothers from South-East Asia (79.9%) and Southern Asia (79.3%). While most variables were consistently associated with lower coverage in all regions of birth, higher socioeconomic status and jurisdiction of birth showed varied results. Adjusted estimates of DTP3 coverage increased in children born to mothers from Australia (78.3%), Oceania (70.5%), Northern Africa (81.5%) and the Middle East (79.6%). DTP3 coverage decreased in children born to mothers from Europe and former USSR (74.6%), North-east Asia (75.2%), Southern Asia (76.7%), North America (65.5) and South/Central America and the Caribbean (73.2%). CONCLUSIONS: On-time vaccination rates differed by mother's region of birth. More research is needed to determine the main reasons for these remaining differences to improve vaccine uptake and also help guide policy and practice.

Why is influenza vaccine uptake so low among Aboriginal adults?

OBJECTIVES: Determine major barriers to, and facilitators of, influenza vaccination of Aboriginal adults, in order to improve coverage from the current level of 30%. METHODS: i) A focus group with 13 Aboriginal Immunisation Healthcare Workers; and ii) a cross-sectional survey of Aboriginal people aged ≥18 years at the 2017 New South Wales Koori Knockout (29 September-2 October). RESULTS: The focus group nominated poor identification of Aboriginality in general practice. Of 273 survey respondents, a substantial minority (30%) were unaware of their eligibility for free influenza vaccination. More than half (52%) believed the vaccine could cause influenza, 40% reported there were better ways than vaccination for avoiding infection and 30% said they would not have the vaccine if it was offered to them. Regarding health service access, few reported experiencing difficulty (17%), feeling uncomfortable (15%) or being discriminated against (8%), but 53% reported not receiving a reminder from a health professional. CONCLUSIONS: Misconceptions about influenza disease and vaccine among Aboriginal people and inadequate identification of Aboriginality in general practice appear to be the greatest barriers to vaccination, rather than health service access in general. Implications for public health: More active communication to and targeting of Aboriginal adults is required; this is even more urgent following the arrival of COVID-19.

Local endothelial DNA repair deficiency causes aging-resembling endothelial-specific dysfunction.

We previously identified genomic instability as a causative factor for vascular aging. In the present study, we determined which vascular aging outcomes are due to local endothelial DNA damage, which was accomplished by genetic removal of ERCC1 (excision repair cross-complementation group 1) DNA repair in mice (EC-knockout (EC-KO) mice). EC-KO showed a progressive decrease in microvascular dilation of the skin, increased microvascular leakage in the kidney, decreased lung perfusion, and increased aortic stiffness compared with wild-type (WT). EC-KO showed expression of DNA damage and potential senescence marker p21 exclusively in the endothelium, as demonstrated in aorta. Also the kidney showed p21-positive cells. Vasodilator responses measured in organ baths were decreased in aorta, iliac and coronary artery EC-KO compared with WT, of which coronary artery was the earliest to be affected. Nitric oxide-mediated endothelium-dependent vasodilation was abolished in aorta and coronary artery, whereas endothelium-derived hyperpolarization and responses to exogenous nitric oxide (NO) were intact. EC-KO showed increased superoxide production compared with WT, as measured in lung tissue, rich in endothelial cells (ECs). Arterial systolic blood pressure (BP) was increased at 3 months, but normal at 5 months, at which age cardiac output (CO) was decreased. Since no further signs of cardiac dysfunction were detected, this decrease might be an adaptation to prevent an increase in BP. In summary, a selective DNA repair defect in the endothelium produces features of age-related endothelial dysfunction, largely attributed to loss of endothelium-derived NO. Increased superoxide generation might contribute to the observed changes affecting end organ perfusion, as demonstrated in kidney and lung.

Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation.

GPR81 (G-protein-coupled receptor 81) is highly expressed in adipocytes, and activation by the endogenous ligand lactate inhibits lipolysis. GPR81 is also expressed in the heart, liver, and kidney, but roles in nonadipose tissues are poorly defined. GPR81 agonists, developed to improve blood lipid profile, might also provide insights into GPR81 physiology. Here, we assessed the blood pressure and renal hemodynamic responses to the GPR81 agonist, AZ'5538. In male wild-type mice, intravenous AZ'5538 infusion caused a rapid and sustained increase in systolic and diastolic blood pressure. Renal artery blood flow, intrarenal tissue perfusion, and glomerular filtration rate were all significantly reduced. AZ'5538 had no effect on blood pressure or renal hemodynamics in Gpr81-/- mice. Gpr81 mRNA was expressed in renal artery vascular smooth muscle, in the afferent arteriole, in glomerular and medullary perivascular cells, and in pericyte-like cells isolated from kidney. Intravenous AZ'5538 increased plasma ET-1 (endothelin 1), and pretreatment with BQ123 (endothelin-A receptor antagonist) prevented the pressor effects of GPR81 activation, whereas BQ788 (endothelin-B receptor antagonist) did not. Renal ischemia-reperfusion injury, which increases renal extracellular lactate, increased the renal expression of genes encoding ET-1, KIM-1 (Kidney Injury Molecule 1), collagen type 1-α1, TNF-α (tumor necrosis factor-α), and F4/80 in wild-type mice but not in Gpr81-/- mice. In summary, activation of GPR81 in vascular smooth muscle and perivascular cells regulates renal hemodynamics, mediated by release of the potent vasoconstrictor ET-1. This suggests that lactate may be a paracrine regulator of renal blood flow, particularly relevant when extracellular lactate is high as occurs during ischemic renal disease.

Pneumococcal vaccination uptake among patients aged 65 years or over in Australian general practice.

In Australia, pneumococcal vaccine is provided free to all adults aged ≥65 years and Indigenous people aged 15-65 years, and is subsidized for non-Indigenous adults <65 years of age with risk factors. This study aimed to explore pneumococcal vaccination uptake in older patients attending 550 Australian general practices from 2010-2017 by patient sociodemographics, presence of comorbidities and practice characteristics. Study 1: a cross-sectional analysis of 'active' patients aged ≥65 years in each year was performed to calculate annual pneumococcal vaccination uptake. Study 2: a cohort of 58,589 'every year' patients aged 60-65 years in 2010 was analyzed to identify the number of patients immunized during the study period. Logistic regression models assessed associations between vaccination, patient and practice characteristics. Annual pneumococcal vaccine uptake varied by patient's age (65-74 or ≥75 years), presence of comorbidities and regularity of practice visits (range 36% to 76%), and it declined slowly from 2011-2016 amongst all groups. Cohort analyses showed that 69% of those aged 60-65 years in 2010 had a recorded pneumococcal vaccination by 2017 (peak age of vaccination = 66 years), and vaccination was more likely among those with comorbidities, ex-smokers and frequent attenders to practices. Findings demonstrate that the NPS MedicineInsight database provides estimates of vaccination uptake consistent with past surveys, reproducible every year and at low cost. It has the advantage of additional clinical information compared to the Australian Immunization Register. Whilst vaccination uptake was adequate among 'every year' patients, interventions are needed to improve pneumococcal vaccination for all older Australians.

What isn't measured isn't done - eight years with no progress in Aboriginal and Torres Strait Islander adult influenza and pneumococcal vaccination.

OBJECTIVES: To describe and compare vaccination coverage for Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) adults in 2004-05 and 2012-13, including the impact of national vaccination funding initiatives. METHODS: National Aboriginal and Torres Strait Islander Health cross-sectional surveys - 2004-05 (n=5,757) and 2012-13 (n=5,482) - were compared. Self-reported influenza and pneumococcal vaccination coverage among Indigenous adults was analysed by age, remoteness, gender and risk factor status. RESULTS: Influenza vaccination coverage among Indigenous adults in 2004-05 and 2012-13 remained low. While coverage increased for those aged 18-49 years from 23% to 29%, it declined for those aged ≥65 years from 84% to 74%. For remote areas, influenza coverage among those aged 50-64 years declined from 76% to 66%. Pneumococcal vaccination coverage remained very low and declined across all age groups in 2004-05 and 2012-13 (50-64 years: 30% to 23%). For remote areas, pneumococcal coverage declined among those aged 50-64 years from 52% to 32%. CONCLUSIONS: Indigenous adult vaccination coverage for influenza and pneumococcal disease remains unacceptably low. Between 2004-05 and 2012-13, declines occurred in pneumococcal vaccination coverage across all age groups ≥18 years. Despite national funding of influenza vaccine in 2010, there was no increase in influenza coverage, except for the 18-49-year age group. Implications for public health: Current approaches to promote, deliver and monitor vaccination of Indigenous adults are inadequate.

Using general practice data to monitor influenza vaccination coverage in the medically at risk: a data linkage study.

OBJECTIVE: To examine the possibility of using data from a network of Australian General Practices (GPs) to estimate influenza vaccination coverage in Australians medically at risk. DESIGN: Data electronically extracted from a large national network of Australian GP clinics (MedicineInsight) was analysed for annual influenza vaccination coverage from 2008 to 2014. We compared the results with the 2009 and 2014 Adult Vaccination Survey. We adjusted for differences in the distribution of age, risk groups and provider types. SETTING: All states in Australia. PARTICIPANTS: GPs participating in MedicineInsight programme. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Annual vaccination coverage across risk groups as recorded in Adult Vaccination Survey in 2009 and 2014 were compared with vaccination coverage in MedicineInsight. The impact of National Immunisation Programme expansion of free vaccine in 2010 to cover patients aged <65 years with medical risk factors. RESULTS: The proportion of MedicineInsight patients aged ≥18 years and diagnosed with medical risk factors was higher in 2014 (33.2%), compared with the AVS in 2009 (25%). In 2009, influenza vaccination coverage estimates for those aged 18-64 years with medical risk factors was lower for MedicineInsight patients compared with the AVS (26% vs 36%). There was no evidence of any change in coverage between 2008 and 2014, despite the vaccine being available free of charge to this group from 2010. CONCLUSION: General practice databases have the potential to help fill the gap in vaccination coverage data in patients with medical risk factors.