MV-based relative electron density estimation (iMREDe) for MR-LINAC dose calculation.

BACKGROUND: MR-LINAC systems have been increasingly utilized for real-time imaging in adaptive treatments worldwide. Challenges in MR representation of air cavities and subsequent estimation of electron density maps impede planning efficiency and may lead to dose calculation uncertainties. PURPOSE: To demonstrate the generation of accurate electron density maps using the primary MV beam with a flat-panel imager. METHODS: The ViewRay MRIdian MR-LINAC system was modeled digitally for Monte Carlo simulations. Iron shimming, the magnetic field, and the proposed flat panel detector were included in the model. The effect of the magnetic field on the detector response was investigated. Acquisition of projections over 360 degrees was simulated for digital phantoms of the Catphan 505 phantom and a patient treated for Head and Neck cancer. Shim patterns on the projections were removed and detector noise linearity was assessed. Electron density maps were generated for the digital patient phantom using the flat-panel detector and compared with actual treatment planning CT generated electron density maps of the same patient. RESULTS: The effect of the magnetic field on the detector point-spread function (PSF) was found to be substantial for field strengths above 50 mT. Shims correction in the projection images using air normalization and in-painting effectively removed reconstruction artifacts without affecting noise linearity. The relative difference between reconstructed electron density maps from the proposed method and electron density maps generated from the treatment planning CT was 11% on average along all slices included in the iMREDe reconstruction. CONCLUSIONS: The proposed iMREDe technique demonstrated the feasibility of generating accurate electron densities for the ViewRay MRIdian MR-LINAC system with a flat-panel imager and the primary MV beam. This work is a step towards reducing the time and effort required for adaptive radiotherapy in the current ViewRay MR-LINAC systems.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia. METHODS: A microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort's ranges of ages. RESULTS: Sixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective. CONCLUSIONS: HCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

COVID-19 in Vietnam and Its Impact on Road Trauma: Retrospective Study Based on National Data.

BACKGROUND: Despite significant improvement in the last decade, road trauma remains a substantial contributor to deaths in Vietnam. The COVID-19 pandemic necessitated public health measures that had an unforeseen benefit on road trauma in high-income countries. We investigate if this reduction was also seen in a low- to middle-income country like Vietnam. OBJECTIVE: Our aim was to investigate how the COVID-19 pandemic and the government policies implemented in response to it impacted road trauma fatalities in Vietnam. We also compared this impact to other government policies related to road trauma implemented in the preceding 14 years (2007-2020). METHODS: COVID-19 data were extracted from the Vietnamese Ministry of Health database. Road traffic deaths from 2007 to 2021 were derived from the Vietnamese General Statistical Office. We used Stata software (version 17; StataCorp) for statistical analysis. Poisson regression modeling was used to estimate trends in road fatality rates based on annual national mortality data for the 2007-2021 period. The actual change in road traffic mortality in 2021 was compared with calculated figures to demonstrate the effect of COVID-19 on road trauma fatalities. We also compared this impact to other government policies that aimed to reduce traffic-related fatalities from 2007 to 2020. RESULTS: Between 2007 and 2020, the number of annual road traffic deaths decreased by more than 50%, from 15.3 to 7 per 100,000 population, resulting in an average reduction of 5.4% per annum. We estimated that the road traffic mortality rate declined by 12.1% (95% CI 8.9-15.3%) in 2021 relative to this trend. The actual number of road trauma deaths fell by 16.4%. This reduction was largely seen from August to October 2021 when lockdown and social distancing measures were in force. CONCLUSIONS: In 2021, the road traffic-related death reduction in Vietnam was 3 times greater than the trend seen in the preceding 14 years. The public health response to the COVID-19 pandemic in Vietnam was associated with a third of this reduction. It can thus be concluded that government policies implemented to address the COVID-19 pandemic resulted in a 4.3% decrease in road traffic deaths in 2021. This has been observed in high-income countries, but we have demonstrated this for the first time in a low- and middle-income country.

Survival of primary liver cancer for people from culturally and linguistically diverse backgrounds in Australia.

BACKGROUND: Survival for Primary Liver Cancer (PLC) has been investigated in Australia, but limited work has been conducted on the burden for people with different socioeconomic status, region of residence, causes of PLC, and culturally and linguistically diverse (CALD) backgrounds. This study aimed to cover this gap in the literature by investigating PLC survival with the aforementioned factors. METHODS: This study linked four administrative datasets: Victorian Cancer Registry, Admitted Episodes Dataset, Emergency Minimum Dataset, and Death Index. The cohort was all cases with a PLC notification within the Victorian Cancer Registry between 01/01/2008 and 01/01/2016. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test was used to compare the difference in survival between subgroups. The Cox proportional hazard model was used to explore factors associated with PLC survival. RESULTS: The 1-, 3- and 5-year survival rates were 50.0%, 28.1% and 20.6%, respectively, with a median survival of 12.0 months (95% confidence interval (CI): 11.0 - 12.9 months). Higher survival was associated with younger age, hepatocellular carcinoma, and higher socio-economic status. People born in Asian, African, and American regions had higher survival than those born in Australia and New Zealand. Cases with viral hepatitis as an identified aetiology had higher survival than those whose PLC was related to alcohol consumption (hazard ratio=1.52, 95% CI: 1.19 - 1.96), diabetes and fatty liver disease (hazard ratio=1.35, 95% CI: 1.08 - 1.68). CONCLUSION: Survival outcomes for people diagnosed with PLC were still poor and affected by many factors. Asian and African cases had better survival than Australian and New Zealand patients as PLC in Asian and African cases was mostly caused by viral hepatitis. Metropolitan areas were associated with a higher survival than rural areas, not only due to accessibility to surveillance and healthcare services but also because the majority of overseas-born patients reside in metropolitan areas.

Hospitalisation costs of primary liver cancer in Australia: evidence from a data-linkage study.

Objective This study aimed to estimate the public hospital costs associated with primary liver cancer (PLC) in the first and second years following the cancer diagnosis. Methods This study linked administrative datasets of patients diagnosed with PLC in Victoria, Australia, from January 2008 to December 2015. The health system perspective was adopted to estimate the direct healthcare costs associated with PLC, based on inpatient and emergency costs. Costs were estimated for the first 12 months and 12-24 months after the PLC diagnosis and expressed in 2017 Australian dollars (A$). The cost estimated was then extrapolated nationally. The linear mixed model with a Box-Cox transformation of the costs was used to explore the relationship between costs and patients' sociodemographic and clinical characteristics. Results For the first 12 months, the total and annual per-patient cost was A$211.4 million and A$63 664, respectively. Costs for the subsequent year were A$49.7 million and A$46 751, respectively. Regarding the cost extrapolation to Australia, the total cost was A$137 million for the first 12 months after notification and A$42.6 million for the period from 12 to 24 months. Higher costs per episode of care were mostly associated with older age, hepatocellular carcinoma type of PLC, metropolitan hospitals, and Asian birth region. Conclusion This study showed the public hospital admission and emergency costs associated with PLC and the substantial economic burden this cancer has placed on the Australian health system.

Trauma Care Training in Vietnam: Narrative Scoping Review.

BACKGROUND: The model of trauma in Vietnam has changed significantly over the last decade and requires reforming medical education to deal with new circumstances. Our aim is to evaluate this transition regarding the new target by analyzing trauma and the medical training system as a whole. OBJECTIVE: This study aimed to establish if medical training in the developing country of Vietnam has adapted to the new disease pattern of road trauma emerging in its economy. METHODS: A review was performed of Vietnamese medical school, Ministry of Health, and Ministry of Education and Training literature on trauma education. The review process and final review paper were prepared following the guidelines on scoping reviews and using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. RESULTS: The current trauma training at the undergraduate level is minimal and involves less than 5% of the total credit. At the postgraduate level, only the specialties of surgery and anesthesia have a significant and increasing trauma training component ranging from 8% to 22% in the content. Trauma training, which focuses on practical skills, accounts for 31% and 32% of the training time of orientation courses for young doctors in "basic surgery" and "basic anesthesia," respectively. Other relevant short course trainings, such as continuing medical education, in trauma are available, but they vary in topics, facilitators, participants, and formats. CONCLUSIONS: Medical training in Vietnam has not adapted to the new emerging disease pattern of road trauma. In the interim, the implementation of short courses, such as basic trauma life support and primary trauma care, can be considered as an appropriate method to compensate for the insufficient competency-related trauma care among health care workers while waiting for the effectiveness of medical training reformation.

Sex differences in total cholesterol of Vietnamese adults.

BACKGROUND: The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. METHODS: Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. RESULTS: Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. CONCLUSION: There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.

A Systematic Review and Narrative Synthesis of Health Economic Evaluations of Hepatocellular Carcinoma Screening Strategies.

OBJECTIVES: Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data. METHODS: We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies. RESULTS: The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial. CONCLUSIONS: Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.

Extra-striatal dopamine in Parkinson's disease with rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) is a common condition found in more than 50% of the patients with Parkinson's disease (PD). Molecular imaging shows that PD with RBD (PD-RBD+) have lower striatal dopamine transporter activity within the caudate and putamen relative to PD without RBD (PD-RBD-). However, the characterization of the extra-striatal dopamine within the mesocortical and mesolimbic pathways remains unknown. We aim to elucidate this with PET imaging in 15 PD-RBD+ and 15 PD-RBD- patients, while having 15 age-matched healthy controls (HC). Each participant underwent a single PET scan with [11 C]FLB-457 to detect the D2 receptor availability within the extra-striatal regions of interest (ROI), including the prefrontal, temporal, and limbic areas. [11 C]FLB-457 retention was expressed as the nondisplaceable binding potential. Our results reveal that relative to HC, PD-RBD+ and PD-RBD- patients have lower levels of D2 receptor availability within the uncus parahippocampus, superior, lateral, and inferior temporal cortex. PD-RBD+ showed steep decline in D2 receptors within the left uncus parahippocampus with increasing disease severity, but this was not observed for PD-RBD- patients. Findings imply that extra-striatal dopaminergic system may play a role in contributing to symptomatic progress in PD patients with RBD. However, validation with more advanced PD patients are needed.

The Interdependence of Blood Pressure and Glucose in Vietnam.

INTRODUCTION: Modelling of associations of systolic blood pressure (BP) and blood glucose (BG) with their explanatory factors in separate regressions treats them as having independent biological mechanisms. This can lead to statistical inferences that are unreliable because the substantial overlap in their etiologic and disease mechanisms is ignored. AIM: This study aimed to examine the relationship of systolic blood pressure (BP) and blood glucose (BG) with measures of obesity and central fat distribution and other factors whilst taking account of the inter-dependence between them. METHODS: Participants (n = 14706, 53.5 % females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. RESULTS: Structural modelling identified direct effects for BG (men P = 0.000, women P = 0.029), age (men P = 0.000, women P = 0.000) and body mass index (BMI) (men P = 0.000, women P = 0.000) in the estimation of systolic BP, and for systolic BP (men P = 0.036, women P = 0.000) and waist circumference (WC) (men P = 0.032, women P = 0.009) in the estimation of BG. There were indirect effects of age, cholesterol, physical activity and tobacco smoking via their influence on WC and BMI. The errors in estimation of systolic BP and BG were correlated (men P = 0.000, women P = 0.004), the stability indices (men 0.466, women 0.495) showed the non-recursive models were stable, and the proportion of variance explained was mid-range (men 0.553, women 0.579). CONCLUSION: This study provided statistical evidence of a feedback loop between systolic BP and BG. BMI and WC were confirmed to be their primary explanatory factors. Saturated fat intake and physical activity were identified as possible targets of intervention for overweight and obesity, and indirectly for reducing systolic BP and BG. Harmful/hazardous alcohol intake was identified as a target of intervention for systolic BP.

Graph theory analysis of the dopamine D2 receptor network in Parkinson's disease patients with cognitive decline.

Cognitive decline in Parkinson's disease (PD) is a common sequela of the disorder that has a large impact on patient well-being. Its physiological etiology, however, remains elusive. Our study used graph theory analysis to investigate the large-scale topological patterns of the extrastriatal dopamine D2 receptor network. We used positron emission tomography with [11 C]FLB-457 to measure the binding potential of cortical dopamine D2 receptors in two networks: the meso-cortical dopamine network and the meso-limbic dopamine network. We also investigated the application of partial volume effect correction (PVEC) in conjunction with graph theory analysis. Three groups were investigated in this study divided according to their cognitive status as measured by the Montreal Cognitive Assessment score, with a score ≤25 considered cognitively impaired: (a) healthy controls (n = 13, 11 female), (b) cognitively unimpaired PD patients (PD-CU, n = 13, 5 female), and (c) PD patients with mild cognitive impairment (PD-MCI, n = 17, 4 female). In the meso-cortical network, we observed increased small-worldness, normalized clustering, and local efficiency in the PD-CU group compared to the PD-MCI group, as well as a hub shift in the PD-MCI group. Compensatory reorganization of the meso-cortical dopamine D2 receptor network may be responsible for some of the cognitive preservation observed in PD-CU. These results were found without PVEC applied and PVEC proved detrimental to the graph theory analysis. Overall, our findings demonstrate how graph theory analysis can be used to detect subtle changes in the brain that would otherwise be missed by regional comparisons of receptor density.

The Interaction Between Neuroinflammation and ß-Amyloid in Cognitive Decline in Parkinson's Disease.

Activated microglia have been reported to play an important role in Parkinson's disease (PD). A more rapid cognitive decline has been associated with deposits of ß-amyloid. In this study, the aim was to evaluate the role of brain ß-amyloid and its relationship with activated microglia in PD patients with normal and impaired cognition. We studied 17 PD patients with normal cognition (PDn), 12 PD patients with mild cognitive impairment (PD-MCI), and 12 healthy controls (HCs) with [11C] Pittsburgh compound B (PIB) to assess the impact of ß-amyloid deposition in the brain on microglial activation evaluated using the translocator protein 18-kDa (TSPO) radioligand [18F]-FEPPA. [11C] PIB distribution volume ratio was measured in cortical and subcortical regions. [18F]-FEPPA total distribution volume values were compared for each brain region between groups to evaluate the effect of PIB positivity while adjusting for the TSPO rs6971 polymorphism. Factorial analysis of variance revealed a significant main effect of PIB positivity in the frontal lobe (F(1, 34) = 7.1, p = 0.012). Besides the frontal (p = 0.006) and temporal lobe (p = 0.001), the striatum (p = 0.018), the precuneus (p = 0.019), and the dorsolateral prefrontal cortex (p = 0.010) showed significant group × PIB positivity interaction effects. In these regions, PD-MCIs had significantly higher FEPPA VT if PIB-positive. Our results indicate an interaction between amyloid-ß deposition and microglial activation in PD. Further investigations are necessary to evaluate if amyloid deposits cause neuroinflammation and further neurodegeneration or if increased microglia activation develops as a protective response.

Network Patterns of Beta-Amyloid Deposition in Parkinson's Disease.

Beta-amyloid (Aß) in the brain is a key pathological feature of certain neurodegenerative diseases. Recent studies using graph theory have shown that Aß brain networks are of pathological significance in Alzheimer's disease (AD). However, the characteristics of Aß brain networks in Parkinson's disease (PD) are unknown. In the present study using positron emission tomography (PET) with [11C]-Pittsburgh compound B (PiB), we applied a graph theory-based analysis to assess the topological properties of Aß brain network in PD patients with and without Aß burden (PiB-positive and PiB-negative, respectively) and healthy controls with Aß burden. We found that the PD PiB-positive group demonstrated significantly lower value in global efficiency and modularity compared with PD PiB-negative group. The less robust modular structure indicates the tendency of having increased inter-modular connections than intra-modular connectivity (i.e., reduced segregation). Results of hub organization showed that relative to PD PiB-negative group, different hubs were identified in the PiB-positive group, which were located mainly within the default mode network. Overall, our findings suggest disturbances in Aß topological organization characterized by abnormal network integration and segregation in PD patients with Aß burden. The stronger inter-modular connectivity observed in the PD PiB-positive group may suggest the spreading pattern of Aß between modules in those PD patients with elevated PiB burden, thus providing insight into the beta-amyloidopathy of PD.

Decreased pallidal vesicular monoamine transporter type 2 availability in Parkinson's disease: The contribution of the nigropallidal pathway.

To date, the contribution of the nigropallidal pathway degeneration to Parkinson's disease (PD) motor symptoms has received little attention and is generally poorly understood in spite of solid evidence that the globus pallidus (GP) receives a dense neuronal projection from the substantia nigra. To explore the dopaminergic (DA) changes of the GP in PD, we measured the availability of vesicular monoamine transporter 2 (VMAT2) using [11C]DTBZ and positron emission tomography in 30 PD patients and 12 controls. PD patients were classified in two groups based on severity of disease. VMAT2 reduction was found to be significant in the external GP (GPe) regardless of the disease stage, while the internal GP (GPi) showed reduction only in more severe patients. Pallidal VMAT2 binding correlated with dopaminergic changes in the striatum, with the GPe showing a stronger association than GPi. Our findings showed DA terminals in the GPe and GPi may be differentially vulnerable in different stages of the disease, possibly playing a distinctive role in the development of motor complications with GPi DA deficiency contributing more to later-stage symptoms.

Genetic study of multimodal imaging Alzheimer's disease progression score implicates novel loci.

Identifying genetic risk factors underpinning different aspects of Alzheimer's disease has the potential to provide important insights into pathogenesis. Moving away from simple case-control definitions, there is considerable interest in using quantitative endophenotypes, such as those derived from imaging as outcome measures. Previous genome-wide association studies of imaging-derived biomarkers in sporadic late-onset Alzheimer's disease focused only on phenotypes derived from single imaging modalities. In contrast, we computed a novel multi-modal neuroimaging phenotype comprising cortical amyloid burden and bilateral hippocampal volume. Both imaging biomarkers were used as input to a disease progression modelling algorithm, which estimates the biomarkers' long-term evolution curves from population-based longitudinal data. Among other parameters, the algorithm computes the shift in time required to optimally align a subjects' biomarker trajectories with these population curves. This time shift serves as a disease progression score and it was used as a quantitative trait in a discovery genome-wide association study with n = 944 subjects from the Alzheimer's Disease Neuroimaging Initiative database diagnosed as Alzheimer's disease, mild cognitive impairment or healthy at the time of imaging. We identified a genome-wide significant locus implicating LCORL (rs6850306, chromosome 4; P = 1.03 × 10-8). The top variant rs6850306 was found to act as an expression quantitative trait locus for LCORL in brain tissue. The clinical role of rs6850306 in conversion from healthy ageing to mild cognitive impairment or Alzheimer's disease was further validated in an independent cohort comprising healthy, older subjects from the National Alzheimer's Coordinating Center database. Specifically, possession of a minor allele at rs6850306 was protective against conversion from mild cognitive impairment to Alzheimer's disease in the National Alzheimer's Coordinating Center cohort (hazard ratio = 0.593, 95% confidence interval = 0.387-0.907, n = 911, PBonf = 0.032), in keeping with the negative direction of effect reported in the genome-wide association study (ßdisease progression score = -0.07 ± 0.01). The implicated locus is linked to genes with known connections to Alzheimer's disease pathophysiology and other neurodegenerative diseases. Using multimodal imaging phenotypes in association studies may assist in unveiling the genetic drivers of the onset and progression of complex diseases.

The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam.

BACKGROUND: Waist circumference (WC) is an indicator of intra-abdominal adipose tissue, high levels of which confer an increased risk of cardiometabolic disease. Population data on WC should be more informative than data on body mass index (BMI), which is a general indicator of body size. This study aimed to evaluate the importance of WC relative to BMI in cross-sectional relationships with blood pressure (BP), glucose, and total cholesterol (TC) in the adult population of Vietnam. METHODS: The data were collected in a population-based survey conducted during 2009-10 using the "WHO STEPwise approach to surveillance of risk factors for non-communicable disease" (STEPS) methodology. The survey participants (n = 14 706 aged 25 to 64 years) were selected by multi-stage stratified cluster sampling from eight provinces representative of the eight geographical regions of Vietnam. All measurements were performed in accordance with the STEPS protocols. All analyses were performed using complex survey methods. RESULTS: The measurements of WC and BMI were highly correlated (men r = 0.80, women r = 0.77). For men, the strongest and predominant associations with BP, glucose, and TC were for WC or an index based on WC. For women, this was true for glucose but BMI was more important for BP and TC. WC or an index based on WC provided better discrimination than BMI of hypertension and elevated glucose, and of raised TC for men. Information on four new anthropometric indices did not improve model fit or subject discrimination. CONCLUSION: For BP/hypertension, glucose/elevated glucose, and TC/raised TC, WC was more informative than BMI for Vietnamese men, but both WC and BMI were important for Vietnamese women. Both WC and BMI need to be assessed for estimation of CVD risk in Vietnam.

Association of ambient particulate matter with heart failure incidence and all-cause readmissions in Tasmania: an observational study.

OBJECTIVES: We sought to investigate the relationship between air quality and heart failure (HF) incidence and rehospitalisation to elucidate whether there is a threshold in this relationship and whether this relationship differs for HF incidence and rehospitalisation. METHODS: This retrospective observational study was performed in an Australian state-wide setting, where air pollution is mainly associated with wood-burning for winter heating. Data included all 1246 patients with a first-ever HF hospitalisation and their 3011 subsequent all-cause readmissions during 2009-2012. Daily particulate matter <2.5 µm (PM2.5), temperature, relative humidity and influenza infection were recorded. Poisson regression was used, with adjustment for time trend, public and school holiday and day of week. RESULTS: Tasmania has excellent air quality (median PM2.5=2.9 µg/m3 (IQR: 1.8-6.0)). Greater HF incidences and readmissions occurred in winter than in other seasons (p<0.001). PM2.5 was detrimentally associated with HF incidence (risk ratio (RR)=1.29 (1.15-1.42)) and weakly so with readmission (RR=1.07 (1.02-1.17)), with 1 day time lag. In multivariable analyses, PM2.5 significantly predicted HF incidence (RR=1.12 (1.01-1.24)) but not readmission (RR=0.96 (0.89-1.04)). HF incidence was similarly low when PM <4 µg/m3 and only started to rise when PM2.5≥4 µg/m3. Stratified analyses showed that PM2.5 was associated with readmissions among patients not taking beta-blockers but not among those taking beta-blockers (pinteraction=0.011). CONCLUSIONS: PM2.5 predicted HF incidence, independent of other environmental factors. A possible threshold of PM2.5=4 µg/m3 is far below the daily Australian national standard of 25 µg/m3. Our data suggest that beta-blockers might play a role in preventing adverse association between air pollution and patients with HF.

A variant in PPP4R3A protects against alzheimer-related metabolic decline.

OBJECTIVES: A reduction in glucose metabolism in the posterior cingulate cortex (PCC) predicts conversion to Alzheimer's disease (AD) and tracks disease progression, signifying its importance in AD. We aimed to use decline in PCC glucose metabolism as a proxy for the development and progression of AD to discover common genetic variants associated with disease vulnerability. METHODS: We performed a genome-wide association study (GWAS) of decline in PCC fludeoxyglucose F 18 ([18 F] FDG) positron emission tomography measured in Alzheimer's Disease Neuroimaging Initiative participants (n = 606). We then performed follow-up analyses to assess the impact of significant single-nucleotide polymorphisms (SNPs) on disease risk and longitudinal cognitive performance in a large independent data set (n = 870). Last, we assessed whether significant SNP influence gene expression using two RNA sequencing data sets (n = 210 and n = 159). RESULTS: We demonstrate a novel genome-wide significant association between rs2273647-T in the gene, PPP4R3A, and reduced [18 F] FDG decline (p = 4.44 × 10-8 ). In a follow-up analysis using an independent data set, we demonstrate a protective effect of this variant against risk of conversion to MCI or AD (p = 0.038) and against cognitive decline in individuals who develop dementia (p = 3.41 × 10-15 ). Furthermore, this variant is associated with altered gene expression in peripheral blood and altered PPPP4R3A transcript expression in temporal cortex, suggesting a role at the molecular level. INTERPRETATIONS: PPP4R3A is a gene involved in AD risk and progression. Given the protective effect of this variant, PPP4R3A should be further investigated as a gene of interest in neurodegenerative diseases and as a potential target for AD therapies. Ann Neurol 2017;82:900-911.