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.

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.

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.

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.

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.

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.

Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson's disease.

The recurrent 22q11.2 deletion is a genetic risk factor for early-onset Parkinson's disease. Adults with the associated 22q11.2 deletion syndrome (22q11.2DS) may exhibit phenotypes that could help identify those at highest risk and reveal disease trajectories. We investigated clinical and neuroimaging features relevant to Parkinson's disease in 26 adults: 13 with 22q11.2DS at genetic risk of Parkinson's disease (mean age = 41.5 years, standard deviation = 9.7), 12 healthy age and sex-matched controls, and a 22q11.2DS patient with l-DOPA-responsive early-onset Parkinson's disease. Neuroimaging included transcranial sonography and positron emission tomography using 11C-dihydrotetrabenazine (11C-DTBZ), a radioligand that binds to the presynaptic vesicular monoamine transporter. The 22q11.2DS group without Parkinson's disease demonstrated significant motor and olfactory deficits relative to controls. Eight (61.5%) were clinically classified with parkinsonism. Transcranial sonography showed a significantly larger mean area of substantia nigra echogenicity in the 22q11.2DS risk group compared with controls (P = 0.03). The 22q11.2DS patient with Parkinson's disease showed the expected pattern of severely reduced striatal 11C-DTBZ binding. The 22q11.2DS group without Parkinson's disease however showed significantly elevated striatal 11C-DTBZ binding relative to controls (∼33%; P < 0.01). Results were similar within the 22q11.2DS group for those with (n = 7) and without (n = 6) psychotic illness. These findings suggest that manifestations of parkinsonism and/or evolution to Parkinson's disease in this genetic at-risk population may include a hyperdopaminergic mechanism. Adequately powered longitudinal studies and animal models are needed to evaluate the relevance of the observed clinical and imaging phenotypes to Parkinson's disease and other disorders that are more prevalent in 22q11.2DS, such as schizophrenia.

Contribution of insula in Parkinson's disease: A quantitative meta-analysis study.

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect.

Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease.

OBJECTIVE: Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. METHODS: We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance. RESULTS: Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. INTERPRETATION: Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction.

National survey of risk factors for non-communicable disease in Vietnam: prevalence estimates and an assessment of their validity.

BACKGROUND: To estimate the prevalence of non-communicable disease (NCD) risk factors at a provincial level in Vietnam, and to assess whether the summary estimates allow reliable inferences to be drawn regarding regional differences in risk factors and associations 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. Data were analysed using complex survey methods. RESULTS: Differences by sex in mean years of schooling (males 8.26 ± 0.20, females 7.00 ± 0.18), proportions of current smokers (males 57.70 %, females 1.73 %), and binge-drinkers (males 25.11 %, females 0.63 %), and regional differences in diet, reflected the geographical and socio-cultural characteristics of the country. Provinces with a higher proportion of urban population had greater mean levels of BMI (r = 0.82), and lesser proportions of active people (r = -0.89). The associations between the summary estimates were generally plausible (e.g. physical activity and BMI, r = -0.80) but overstated, and with some anomalous findings due to characterisation of smoking and hypertension by STEPS protocols. CONCLUSIONS: This report provides an extensive description of the sex-specific and regional distribution of NCD risk factors in Vietnam and an account of some health-related consequences of industrialisation in its early stages. The STEPS protocols can be utilized to provide aggregate data for valid between-population comparisons, but with important caveats identified.

Uncovering the role of the insula in non-motor symptoms of Parkinson's disease.

Patients with Parkinson's disease experience a range of non-motor symptoms, including cognitive impairment, behavioural changes, somatosensory and autonomic disturbances. The insula, which was once thought to be primarily a limbic cortical structure, is now known to be highly involved in integrating somatosensory, autonomic and cognitive-affective information to guide behaviour. Thus, it acts as a central hub for processing relevant information related to the state of the body as well as cognitive and mood states. Despite these crucial functions, the insula has been largely overlooked as a potential key region in contributing to non-motor symptoms of Parkinson's disease. The insula is affected in Parkinson's disease by alpha-synuclein deposition, disruptions in normal neurotransmitter function, alterations in connectivity as well as metabolic and structural changes. Although research focusing on the role of the insula in Parkinson's disease is scarce, there is evidence from neuroimaging studies linking the insula to cognitive decline, behavioural abnormalities and somatosensory disturbances. Here, we review imaging studies that provide insight into the potential role of the insula in Parkinson's disease non-motor symptoms.

Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment.

The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in cortico-striatal circuitry. Our aim was to investigate both striatal and cortical dopaminergic changes in patients with Parkinson's disease with mild cognitive impairment, who represent a vulnerable group for the development of dementia. We hypothesized severe striatal dopamine denervation in the associative (i.e. cognitive) region and cortical D2 receptor abnormalities in the salience and executive networks in Parkinson's disease with mild cognitive impairment compared with cognitively normal patients with Parkinson's disease and healthy control subjects. We used positron emission tomography imaging with dopaminergic ligands (11)C-dihydrotetrabenazine, to investigate striatal dopamine neuron integrity in the associative subdivision and (11)C-FLB 457, to investigate cortical D2 receptor availability in patients with Parkinson's disease (55-80 years of age) with mild cognitive impairment (n = 11), cognitively normal patients with Parkinson's disease (n = 11) and age-matched healthy control subjects (n = 14). Subjects were administered a neuropsychological test battery to assess cognitive status and determine the relationship between dopaminergic changes and cognitive performance. We found that patients with mild cognitive impairment had severe striatal dopamine depletion in the associative (i.e. cognitive) subdivision as well as reduced D2 receptor availability in the bilateral insula, a key cognitive hub, compared to cognitively normal patients and healthy subjects after controlling for age, disease severity and daily dopaminergic medication intake. Associative striatal dopamine depletion was predictive of D2 receptor loss in the insula of patients with Parkinson's disease with mild cognitive impairment, demonstrating interrelated striatal and cortical changes. Insular D2 levels also predicted executive abilities in these patients as measured using a composite executive z-score obtained from neuropsychological testing. Furthermore we assessed cortical thickness to ensure that D2 receptor changes were not confounded by brain atrophy. There was no difference between groups in cortical thickness in the insula, or any other cortical region of interest. These findings suggest that striatal dopamine denervation combined with insular D2 receptor loss underlie mild cognitive impairment in Parkinson's disease and in particular decline in executive function. Furthermore, these findings suggest a crucial and direct role for dopaminergic modulation in the insula in facilitating cognitive function.

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.

Using the Kirkpatrick Model to Evaluate the Effect of a Primary Trauma Care Course on Health Care Workers' Knowledge, Attitude, and Practice in Two Vietnamese Local Hospitals: Prospective Intervention Study.

Background: The Primary Trauma Care (PTC) course was originally developed to instruct health care workers in the management of patients with severe injuries in low- and middle-income countries (LMICs) with limited medical resources. PTC has now been taught for more than 25 years. Many studies have demonstrated that the 2-day PTC workshop is useful and informative to frontline health staff and has helped improve knowledge and confidence in trauma management; however, there is little evidence of the effect of the course on changes in clinical practice. The Kirkpatrick model (KM) and the knowledge, attitude, and practice (KAP) model are effective methods to evaluate this question. Objective: The aim of this study was to investigate how the 2-day PTC course impacts the satisfaction, knowledge, and skills of health care workers in 2 Vietnamese hospitals using a conceptual framework incorporating the KAP model and the 4-level KM as evaluation tools. Methods: The PTC course was delivered over 2 days in the emergency departments (EDs) of Thanh Hoa and Ninh Binh hospitals in February and March 2022, respectively. This study followed a prospective pre- and postintervention design. We used validated instruments to assess the participants' satisfaction, knowledge, and skills before, immediately after, and 6 months after course delivery. The Fisher exact test and the Wilcoxon matched-pairs signed rank test were used to compare the percentages and mean scores at the pretest, posttest, and 6-month postcourse follow-up time points among course participants. Results: A total of 80 health care staff members attended the 2-day PTC course and nearly 100% of the participants were satisfied with the course. At level 2 of the KM (knowledge), the scores on multiple-choice questions and the confidence matrix improved significantly from 60% to 77% and from 59% to 71%, respectively (P<.001), and these improvements were seen in both subgroups (nurses and doctors). The focus of level 3 was on practice, demonstrating a significant incremental change, with scenarios checklist points increasing from a mean of 5.9 (SD 1.9) to 9.0 (SD 0.9) and bedside clinical checklist points increasing from a mean of 5 (SD 1.5) to 8.3 (SD 0.8) (both P<.001). At the 6-month follow-up, the scores for multiple-choice questions, the confidence matrix, and scenarios checklist all remained unchanged, except for the multiple-choice question score in the nurse subgroup (P=.005). Conclusions: The PTC course undertaken in 2 local hospitals in Vietnam was successful in demonstrating improvements at 3 levels of the KM for ED health care staff. The improvements in the confidence matrix and scenarios checklist were maintained for at least 6 months after the course. PTC courses should be effective in providing and sustaining improvement in knowledge and trauma care practice in other LMICs such as Vietnam.

Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease.

The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [(11) C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [(11) C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [(11) C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [(11) C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.

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.