Improved life expectancy for Indigenous and non-Indigenous people in the Northern Territory, 1999-2018: overall and by underlying cause of death.

OBJECTIVES: To provide updated estimates of life expectancy at birth for Indigenous and non-Indigenous people in the Northern Territory, 1999-2018; to quantify the contributions of changes in life years lost to disease-specific causes of death to overall changes in life expectancy. DESIGN, SETTING, PARTICIPANTS: Analysis of Australian Coordinating Registry data on underlying and nine multiple causes of death (ICD-10) for deaths in the NT, by age, sex, and Indigenous status, 1 January 1999 - 31 December 2018. MAIN OUTCOME MEASURES: Life expectancy at birth by year and 5-year period, by Indigenous status and sex; change in life expectancy by year and 5-year period, by Indigenous status and sex; contributions in changes in life years lost to leading underlying causes of death, by 5-year period, Indigenous status and sex. RESULTS: Life expectancy for Indigenous men increased from 56.6 years in 1999 to 65.6 years in 2018 (change, 9.0 years; 95% CI, 7.9-10.0 years) and from 64.8 to 69.7 years for Indigenous women (4.9 years; 95% CI, 3.2-6.7 years); for non-Indigenous men, it increased from 77.4 to 81.0 years (3.6 years; 95% CI, 2.8-4.4 years), and from 84.3 to 85.1 years for non-Indigenous women (0.8 years; 95% CI, -0.4 to 1.9 years). Increased life expectancy for Indigenous men was primarily linked with fewer years of life lost to cancer (23% of overall change), unintentional injuries (18%), and cardiovascular disease (17%), and for Indigenous women with fewer life years lost to cancer (24%), intentional injuries (17%), and kidney disease (14%). During 1999-2018, the difference in life expectancy between Indigenous and non-Indigenous people declined by 26% for men (from 20.8 to 15.4 years) and by 21% for women (from 19.5 to 15.4 years). CONCLUSIONS: Life expectancy improved markedly during 1999-2018 for Indigenous people in the NT, particularly with respect to fewer years of life lost to cancer, injuries, and chronic disease. The smaller gains in life expectancy for non-Indigenous people were linked with improved survival for those with cancer and neurological conditions.

Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis.

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.

Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.

The Role of Formyl Peptide Receptor 1 Gene Polymorphisms in Human Colorectal Cancer.

Formyl peptide receptor 1 (FPR1) belongs to G protein-coupled receptors expressed mainly in phagocytic leukocytes. The gene encoding FPR1 is highly polymorphic and related to inflammation. In this study, we investigated the single nucleotide polymorphisms (SNPs) of Fpr1 in human colorectal cancer (CRC), and analyzed the association of Fpr1 SNPs with clinicopathological parameters and some specific diagnostic markers of CRC. Although the allele and genotype frequencies of Fpr1 SNPs in CRC tissues were not significantly different from that in whole blood cells derived from healthy Chinese subjects. Significant associations were observed between genotypes of c.289C>A and distant metastasis (P=0.001), and between genotypes of c.306T>C and tumor size (P=0.016). Genotypes of c.546C>A was closer to tumor size and lymphatic invasion (P=0.012 and P=0.043, respectively). Meanwhile, genotypes of c.1037C>A was related with tumor location and differentiation (P=0.000 and P=0.005, respectively). Besides, genotypes of c.576T>C>G was related with pathological type (P=0.000). Furthermore, several Fpr1 SNP positions including c.289 (C>A) and c.576 (G>C>T) were related to the expression of P53 (P=0.004 and P=0.008, respectively), and similar results were observed between other Fpr1 SNP positions and CEA, HER2 and Ki-67 (P<0.05). Our data demonstrate that Fpr1 SNPs may play the important role in the progression and metastasis of CRC.

Does delay in planned diabetes care influence outcomes for aboriginal Australians? A study of quality in health care.

BACKGROUND: To examine the association between delay in planned diabetes care and quality of outcomes. METHODS: A retrospective analysis of primary care and inpatient records for 2567 Aboriginal patients, with diabetes, living in 49 remote communities in the Northern Territory of Australia. Poisson regression was used to estimate the association between delay from diagnosis to documented diabetes care plan and three outcome measures: mean HbA1c level, most recent blood pressure and number of diabetes-related hospital admissions. RESULTS: Compared with no delay (< 60 days), patients with delay had increased risk of elevated mean HbA1c: 60 days to < 2 years, incidence rate ratio (IRR), 1.2 (95% CI:1.07-1.39); 2 years to < 4 years, incidence rate ratio (IRR), 1.2 (95% CI:1.04-1.45); 4 years and over, incidence rate ratio (IRR), 1.3 (95% CI:1.12-1.52). There was no evidence of association between delay and optimal blood pressure control. Risk of diabetes-related admission increased with increased delay. Compared with no delay the IRRs for delay were: 60 days to < 2 years, 1.2 (95% CI:1.07-1.42); 2 to < 4 years, 1.3 (95% CI: 1.15-1.58): and 4 years and over, 2.6 (95% CI,2.28-3.08). CONCLUSION: The study found that a timely diabetes care plan was associated with better short-term blood glucose control and fewer diabetes-related admissions but not with improved blood pressure control. Delays may be a result of both patient and service-related factors.

The role of adenosine in up-regulation of p38 MAPK and ERK during limb ischemic preconditioning-induced brain ischemic tolerance.

Our previous studies have demonstrated that limb ischemic preconditioning (LIP) induced brain ischemic tolerance and up-regulated the expression of p38 MAPK and ERK in the hippocampal CA1 region in rats. The present study was undertaken to investigate the role of adenosine in brain protection and up-regulation of p38 MAPK and ERK induced by LIP. It was found that adenosine A1 receptor antagonist DPCPX dose-dependently inhibited the protective effect of LIP. The up-regulation of p38 MAPK and ERK induced by LIP could be blocked by DPCPX. Furthermore, we observed the effect of adenosine on the brain ischemia. The results showed that pre-administration of adenosine could partly mimic the neuroprotective effect on the brain, up-regulate the expression of p38 MAPK and ERK. Based on the above results, it can be concluded that adenosine participated in brain protection and up-regulation of the expression of p38 MAPK and ERK during the induction of brain ischemic tolerance after LIP.

Estimating the total prevalence and incidence of end-stage kidney disease among Aboriginal and non-Aboriginal populations in the Northern Territory of Australia, using multiple data sources.

BACKGROUND: Most estimates for End Stage Kidney Disease (ESKD) prevalence and incidence are based on renal replacement therapy (RRT) registers. However, not all people with ESKD will commence RRT and estimates based only on RRT registry data will underestimate the true burden of ESKD in the community. This study estimates the total number of Northern Territory (NT) residents with ESKD including: those receiving RRT, those diagnosed but not receiving RRT and an estimate of "undiagnosed" cases. METHODS: Four data sources were used to identify NT residents with a diagnosis of ESKD: public hospital admissions, Australia and New Zealand Dialysis and Transplant Registry registrations, death registrations and, for the Aboriginal population only, electronic primary care records. Three data sources contained information recorded between 1 July 2008 and 31 December 2013, death registration data extended to 31 December 2014 to capture 2013 prevalent cases. A capture-recapture method was used to estimate both diagnosed and undiagnosed cases by making use of probability patterns of overlapping multiple data sources. RESULTS: In 2013, the estimated ESKD prevalence in the NT Aboriginal population was 11.01 (95% confidence interval (CI) 10.24-11.78) per 1000, and 0.90 (95% CI 0.76-1.05) per 1000 in the NT non-Aboriginal population. The age-adjusted rates were 17.97 (95% CI 17.82-18.11) and 1.07 (95% CI 1.05-1.09) per 1000 in the NT Aboriginal and non-Aboriginal populations respectively. The proportion of individuals receiving RRT was 71.4% of Aboriginal and 75.5% of non-Aboriginal prevalent ESKD cases. The age-adjusted ESKD incidence was also greater for the Aboriginal (5.26 (95% CI 4.44-6.08) per 1000 population) than non-Aboriginal population (0.36 (95% CI 0.25-0.47) per 1000). CONCLUSION: This study provides comprehensive estimates of the burden of ESKD including those cases that are not identified in relevant health data sources. The results are important for informing strategies to reduce the total burden of ESKD and to manage the potential unmet demand, particularly from comparatively young Aboriginal patients who may be suitable for RRT but do not currently access the services for social, geographic or cultural reasons.

Establishing contemporary trends in hepatitis B sero-epidemiology in an Indigenous population.

BACKGROUND: Indigenous populations globally are disproportionately affected by chronic hepatitis B virus (HBV) infection however contemporary sero-prevalence data are often absent. In the Indigenous population of the Northern Territory (NT) of Australia the unique C4 sub-genotype of HBV universally circulates. There are no studies of the sero-prevalence, nor the impact of the vaccination program (which has a serotype mismatch compared to C4), at a population-wide level. METHODS: We examined all available HBV serology results obtained from the three main laboratories serving NT residents between 1991 and 2011. Data were linked with a NT government database to determine Indigenous status and the most recent test results for each individual were extracted as a cross-sectional database including 88,112 unique individuals. The primary aim was to obtain a contemporary estimate of HBsAg positivity for the NT by Indigenous status. RESULTS: Based on all tests from 2007-2011 (35,633 individuals), hepatitis B surface antigen (HBsAg) positivity was 3·40% (95%CI 3·19-3·61), being higher in Indigenous (6·08%[5·65%-6·53%]) than non-Indigenous (1·56%[1·38%-1·76%]) Australians, p<0·0001. Birth cohort analysis showed HBsAg positivity fell over time for Indigenous people, with this decrease commencing prior to universal infant vaccination (which commenced in 1990), with an ongoing but slower rate of decline since 1990, (0·23% decrease per year versus 0·17%). CONCLUSIONS: HBsAg positivity is high in the NT, particularly in the Indigenous population. HBsAg positivity has fallen over time but a substantial part of this decrease is due to factors other than the universal vaccination program.

The Expression of Formyl Peptide Receptor 1 is Correlated with Tumor Invasion of Human Colorectal Cancer.

Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant receptors expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected in several cancers but the functions of FPR1 in tumor invasion and metastasis is poorly understood. In this study, we investigated the expression of FPRs in primary human colorectal cancer (CRC) and analyzed the association of FPRs expression with clinicopathological parameters. The levels of FPRs mRNA, especially those of FPR1, were significantly higher in colorectal tumors than in distant normal tissues and adjacent non-tumor tissues. FPR1 mRNA expression was also associated with tumor serosal infiltration. FPR1 protein expression was both in the colorectal epitheliums and tumor infiltrating neutrophils/macrophages. Furthermore, the functions of FPR1 in tumor invasion and tissue repair were investigated using the CRC cell lines SW480 and HT29. Higher cell surface expression of FPR1 is associated with significantly increased migration in SW480 cells compared with HT29 cells that have less FPR1 membrane expression. Finally, genetic deletion of fpr1 increased the survival rate of the resulting knockout mice compared with wild type littermates in a mouse model of colitis-associated colorectal cancer. Our data demonstrate that FPR1 may play an important role in tumor cell invasion in CRC patients.

Progress in closing the gap in life expectancy at birth for Aboriginal people in the Northern Territory, 1967-2012.

OBJECTIVES: To compare long term changes in mortality and life expectancy at birth (LE) of Aboriginal people in the Northern Territory and of the overall Australian population; to determine the contributions of changes in mortality in specific age groups to changes in LE for each population. DESIGN, SETTING, PARTICIPANTS: Retrospective trend analysis of death and LE data for the NT Aboriginal and Australian populations, 1967-2012. MAIN OUTCOME MEASURES: LE estimates based on abridged life tables; mortality estimates (deaths per 100 000 population); and age decomposition of LE changes by sex and time period. RESULTS: Between 1967 and 2012, LE increased for both NT Aboriginal and all Australians; the difference in LE between the two populations declined by 4.6 years for females, but increased by one year for males. Between 1967-1971 and 1980-1984, LE of NT Aboriginal people increased rapidly, particularly through reduced infant mortality; from 1980-1984 to 1994-1998, there was little change; from 1994-1998 to 2008-2012, there were modest gains in older age groups. Decomposition by age group identified the persistent and substantial contribution of the 35-74-year age groups to the difference in LE between NT Aboriginal people and all Australians. CONCLUSIONS: Early gains in LE for NT Aboriginal people are consistent with improvements in nutrition, maternal and infant care, and infectious disease control. A rapid epidemiological transition followed, when LE gains in younger age groups plateaued and non-communicable diseases became more prevalent. Recent LE gains, across all adult age groups, are consistent with improved health service access and chronic disease management. If LE is to continue improving, socio-economic disadvantage and its associated risks must be reduced.

GLT-1 Upregulation as a Potential Therapeutic Target for Ischemic Brain Injury.

Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which plays an important role in many aspects of normal brain function such as neural development, motor functions, learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous system is mainly regulated by the uptake activity of excitatory amino acid transporters. Among the five excitatory amino acid transporters, glial glutamate transporter-1 (GLT-1) is responsible for 90% of total glutamate uptake. Thus, GLT-1 is essential for maintaining the appropriate level of extracellular glutamate, and then limiting excitotoxicity of glutamate in central nervous system. Therefore, the regulation of GLT-1 might be a potential therapeutic target for ischemic brain injury. This review summarizes recent advances including our findings in the methods or medicine that could protect neurons against brain ischemic injury via upregulation of GLT-1 and discuss the possible application of these strategies.

Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A.

BACKGROUND: Accumulation of hyperphosphorylated tau is a major neuropathological feature of tauopathies including Alzheimer's disease (AD). Serum amyloid A (SAA), an acute-phase protein with cytokine-like property, has been implicated in amyloid deposition. It remains unclear whether SAA affects tau hyperphosphorylation. METHODS: Potential involvement of SAA in tau hyperphosphorylation was examined using intracerebral injection of SAA, and in Saa3 (-/-) mice receiving systemic administration of lipopolysaccharide (LPS). Induced SAA expression and microglial activation were evaluated in these mice using real-time PCR and/or immunofluorescence staining. Cultured primary neuronal cells were treated with condition media (CM) from SAA-stimulated primary microglial cells. The alteration in tau hyperphosphorylation was determined using Western blotting. RESULTS: Saa3 is the predominant form of SAA proteins induced by LPS in the mouse brain that co-localizes with neurons. Overexpression of SAA by intracerebral injection attenuated tau hyperphosphorylation in the brain. Conversely, Saa3 deficiency enhanced tau phosphorylation induced by systemic LPS administration. Intracerebral injection of SAA also induced the activation of microglia in the brains. IL-10 released to CM from SAA-stimulated microglia attenuated tau hyperphosphorylation in cultured primary neurons. IL-10 neutralizing antibody reversed the effect of SAA in the attenuation of tau phosphorylation. CONCLUSIONS: LPS-induced expression of SAA proteins in the brain leads to the activation of microglia and release of IL-10, which in turn suppresses tau hyperphosphorylation in a mouse model of systemic inflammation.

Trends in hospital admissions involving suicidal behaviour in the Northern Territory, 2001-2013.

OBJECTIVE: To investigate trends in hospital admissions involving suicidal behaviour in the Northern Territory (NT) resident population over the period 2001-2013. METHODS: Estimates of age-standardised rates and average changes in the annual rate of hospital admissions involving suicidal behaviour were calculated by socio-demographic characteristics and types of suicidal behaviour. RESULTS: Overall rates for Indigenous admissions were 2.7 times higher than non-Indigenous admissions and had increased by almost twice as much. While male and female rates of admission were similar for both Indigenous and non-Indigenous residents, the average annual change in rates was greater for Indigenous females (13.4%) compared to males (8.8%) and for non-Indigenous males (7.7%) compared to females (5.2%). Younger and middle-aged Indigenous admissions experienced increasing rates of admissions, whilst trends were similar across age groups for non-Indigenous admissions. Admissions with a diagnosis of suicidal ideation increased the most across all groups. Trends in intentional self-harm admissions differed according to Indigenous status and sex. CONCLUSIONS: There have been substantial increases in hospital admissions involving suicidal behaviour in the NT, most markedly for Indigenous residents. Indigenous females and youth appear to be at increasing risk. The steep increase in suicidal ideation across all groups warrants further investigation.

Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease.

BACKGROUND: Pathological features of Alzheimer's disease (AD) include aggregation of amyloid beta (Aß) and tau protein. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been implicated in the toxicity of aggregated Aß. It remains unclear whether MIF affects hyperphosphorylation and aggregation of tau. METHODS: The effects of MIF deficiency in tau hyperphosphorylation were examined in Mif (-/-) mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ) and in APP/PS1 transgenic mice mated with Mif (-/-) mice. MIF expression and astrocyte activation were evaluated in ICV-STZ mice using immunofluorescence staining. Cultured primary astrocytes were treated with high glucose to mimic STZ function in vitro, and the condition medium (CM) was collected. The level of tau hyperphosphorylation in neurons treated with the astrocyte CM was determined using Western blotting. RESULTS: MIF deficiency attenuated tau hyperphosphorylation in mice. ICV injection of STZ increased astrocyte activation and MIF expression in the hippocampus. MIF deficiency attenuated astrocyte activation in ICV-STZ mice. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in cultured primary neurons, an effect absent from Mif (-/-) astrocytes and WT astrocytes treated with the MIF inhibitor ISO-1. ISO-1 had no direct effect on tau phosphorylation in cultured primary neurons. CONCLUSIONS: These results suggest that MIF deficiency is associated with reduced astrocyte activation and tau hyperphosphorylation in the mouse AD models tested. Inhibition of MIF and MIF-induced astrocyte activation may be useful in AD prevention and therapy.

Effects of Moderate Hyperventilation on Jugular Bulb Gases under Propofol or Isoflurane Anesthesia during Supratentorial Craniotomy.

BACKGROUND: The optimal ventilated status under total intravenous or inhalation anesthesia in neurosurgical patients with a supratentorial tumor has not been ascertained. The purpose of this study was to intraoperatively compare the effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2 ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP), and heart rate (HR) in patients with a supratentorial tumor under different anesthetic regimens. METHODS: Twenty adult patients suffered from supratentorial tumors were randomly assigned to receive a propofol infusion followed by isoflurane anesthesia after a 30-min stabilization period or isoflurane followed by propofol. The patients were randomized to one of the following two treatment sequences: hyperventilation followed by normoventilation or normoventilation followed by hyperventilation during isoflurane or propofol anesthesia, respectively. The ventilation and end-tidal CO 2 tension were maintained at a constant level for 20 min. Radial arterial and jugular bulb catheters were inserted for the blood gas sampling. At the end of each study period, we measured the change in the arterial and jugular bulb blood gases. RESULTS: The mean value of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or propofol anesthesia during hyperventilation compared with those during normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER: t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased, and the O 2 ER significantly increased under propofol anesthesia compared with those values under isoflurane anesthesia during moderate hyperventilation (SjO 2 : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no significant changes in the SjO 2 and the O 2 ER were observed under propofol compared with those values under isoflurane during normoventilation. CONCLUSIONS: Our results suggest that the optimal ventilated status under propofol or isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under propofol anesthesia should be cautiously performed in neurosurgery to maintain an improved balance between the cerebral oxygen supply and demand.

Impact of perinatal health and socio-demographic factors on school education outcomes: A population study of Indigenous and non-Indigenous children in the Northern Territory.

AIM: This study investigated the association between early-life risk factors and school education outcomes. METHODS: This is an historical cohort study of 7601 children (61% were Indigenous) born in the Northern Territory between 1999 and 2004. Information was linked, for each child on: perinatal health, student enrolment and National Assessment Program - Literacy and Numeracy (NAPLAN) Year 3 results. Logistic regression was used to estimate the association between selected risk factors and a NAPLAN result 'below' the national minimum standard (NMS) in reading and numeracy. RESULTS: Indigenous children had much higher odds, than non-Indigenous children, of a result below the NMS for both reading (odds ratio (OR): 8.58, 95% confidence interval (CI): 7.55-9.74) ) and numeracy (OR: 11.52, 95% CI: 9.94-13.35). When adjusted for all other variables, the increased odds were attenuated for both reading (OR: 2.89, 95% CI: 2.46-3.40) and numeracy (OR: 3.19, 95% CI: 2.65-3.84). Common risk factors for Indigenous and non-Indigenous children included higher birth order, maternal smoking in pregnancy and being a boy. There were gradients of decreasing risk with increasing education level of primary care giver and increasing maternal age. Among Indigenous children only, risks increased when living in remote areas, with younger age (<8 years) and low birthweight. CONCLUSIONS: The study highlights that many of the risk factors associated with poor education outcomes among Indigenous children are shared with the general population. The results inform a targeted, cross-agency response to address modifiable early-life risk factors for educational disadvantage. Data linkage, using existing administrative datasets, provides a useful addition to methods that identify priority areas for prevention and early intervention.

R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma.

OBJECTIVES: Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss. METHODS: A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26. RESULTS: A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel. CONCLUSION: Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.

Does relative remoteness affect chronic disease outcomes? Geographic variation in chronic disease mortality in Australia, 2002­2006.

OBJECTIVE: To examine the variation of chronic disease mortality by remoteness areas of Australia, including states and territories. METHODS: Australian Bureau of Statistics (ABS) death registration data, by Statistical Local Area (SLA), were used to identify chronic disease mortality by remoteness category for states and territories and Australia. The analysis used multiple cause of death for six common chronic diseases: diabetes, ischaemic heart disease, stroke, hypertension, chronic obstructive pulmonary disease and renal disease. ABS correspondence files were used to adjust the SLA level death records and population. RESULTS: The chronic disease mortality rate for Australian residents living in a very remote area (512 per 100,000 persons) was respectively 1.3, 1.4, 1.5, and 1.6 times higher than Remote, Outer Regional, Inner Regional and Major Cities categories. This pattern was consistent for the two age groups of 35­64 years and 65 years and over, all six chronic diseases and all states and territories except Victoria. CONCLUSION AND IMPLICATIONS: This study shows that chronic disease mortality increases with increasing relative remoteness. The results highlight the importance and opportunity to redress poorer health outcomes for rural and remote area populations. The study is limited by absence of reliable Indigenous identification in national death data.

Dementia prevalence and incidence among the Indigenous and non-Indigenous populations of the Northern Territory.

OBJECTIVE: To estimate the prevalence and incidence of dementia in Northern Territory Indigenous and non-Indigenous populations. DESIGN, SETTING AND PARTICIPANTS: Four data sources were used to identify clients with a diagnosis of dementia, from 1 January 2008 to 31 December 2011. The data sources included hospital admissions, aged care services, primary care and death registration. A capture-recapture method was used to estimate prevalence and incidence, including both diagnosed and unknown cases. MAIN OUTCOME MEASURES: Prevalence and incidence of dementia among the NT Indigenous and non-Indigenous populations. RESULTS: In 2011, the estimated prevalence in the NT Indigenous population aged 45 years and over was 3.7 per 100, and 1.1 per 100 in the corresponding NT non-Indigenous population. The age-adjusted prevalence for the NT Indigenous population was 6.5 per 100, compared with the NT non-Indigenous prevalence of 2.6 per 100, which was similar to the national rate. The prevalence rate ratios of NT Indigenous to NT non-Indigenous men and women, respectively, were: 6.5 and 5.5 for the 45-64-years age group, 4.0 and 4.1 for those aged 65-74 years and 2.1 and 1.9 for those aged 75 years and over. The age-adjusted incidence among the NT Indigenous population aged 45 years and over (27.3 per 1000 person-years) was higher than that among the NT non-Indigenous population (10.7 per 1000 person-years). CONCLUSION: The NT Indigenous population has a much higher prevalence and incidence of dementia and younger onset of disease compared with their non-Indigenous counterparts. The results highlight the urgent need for interventions to moderate the emerging impact of dementia in the Australian Indigenous population.