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1.
Br J Cancer ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147670

RESUMO

BACKGROUND: Genome-wide association studies (GWASs) have enriched the fields of genomics and drug development. Adrenocortical carcinoma (ACC) is a rare cancer with a bimodal age distribution and inadequate treatment options. Paediatric ACC is frequently associated with TP53 mutations, with particularly high incidence in Southern Brazil due to the TP53 p.R337H (R337H) germline mutation. The heterogeneous risk among carriers suggests other genetic modifiers could exist. METHODS: We analysed clinical, genotype and gene expression data derived from paediatric ACC, R337H carriers, and adult ACC patients. We restricted our analyses to single nucleotide polymorphisms (SNPs) previously identified in GWASs to associate with disease or human traits. RESULTS: A SNP, rs971074, in the alcohol dehydrogenase 7 gene significantly and reproducibly associated with allelic differences in ACC age-of-onset in both cohorts. Patients homozygous for the minor allele were diagnosed up to 16 years earlier. This SNP resides in a gene involved in the retinoic acid (RA) pathway and patients with differing levels of RA pathway gene expression in their tumours associate with differential ACC progression. CONCLUSIONS: These results identify a novel genetic component to ACC development that resides in the retinoic acid pathway, thereby informing strategies to develop management, preventive and therapeutic treatments for ACC.

2.
Blood Cancer J ; 10(2): 16, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029705

RESUMO

Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal gene expression. Despite this knowledge, the specific gene expression alterations that contribute to the development of leukemia remain incompletely understood. Here, through characterization of transcriptional regulation by the RUNX1-ETO fusion protein, we have identified Ras-association domain family member 2 (RASSF2) as a critical gene that is aberrantly transcriptionally repressed in t(8;21)-associated AML. Re-expression of RASSF2 specifically inhibits t(8;21) AML development in multiple models. Through biochemical and functional studies, we demonstrate RASSF2-mediated functions to be dependent on interaction with Hippo kinases, MST1 and MST2, but independent of canonical Hippo pathway signaling. Using proximity-based biotin labeling we define the RASSF2-proximal proteome in leukemia cells and reveal association with Rac GTPase-related proteins, including an interaction with the guanine nucleotide exchange factor, DOCK2. Importantly, RASSF2 knockdown impairs Rac GTPase activation, and RASSF2 expression is broadly correlated with Rac-mediated signal transduction in AML patients. Together, these data reveal a previously unappreciated mechanistic link between RASSF2, Hippo kinases, and Rac activity with potentially broad functional consequences in leukemia.

3.
BMC Oral Health ; 20(1): 16, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964367

RESUMO

BACKGROUND: Oral Health Related Quality of Life (OHRQoL) measures play an important role in understanding subjective patient experiences in oral health care. The Oral Impact on Daily Performance (OIDP) scale is a validated OHRQoL tool that measures the impact and extent to which an individual's daily activities may be compromised by their oral health. It is commonly used to facilitate oral health service planning. The aim of this study was to modify and validate a Sinhalese version of the OIDP for use in Sri Lankan adolescents. METHODS: Stage I involved cultural adaptation of the tool through translation and modification. Stage II involved the exploring factor structure, validation and a reliability assessment. After translation and cultural adaptation, stage II was conducted among 220 secondary school students aged 15-19 in the Gampaha district, Sri Lanka. Participants completed the modified OIDP scale along with questions on self-reported perceived oral health problems and treatment need which were used to assesses the concurrent validity of the modified OIDP scale. Factorability was assessed by inspection of correlation matrix and Kaiser-Meyer-Olkin and Bartlett's Test of Sphericity tests as a measure of sampling adequacy. An exploratory factor analysis was carried out using Principal Component Analysis method and factors were rotated using the oblimin method. RESULTS: The Kaiser-Meyer-Olkin measure was 0.87 and Bartlett's test of Sphericity was significant (p < 0.001) Cronbach's alpha was calculated as 0.88, indicating a high level of internal consistency of the modified OIDP scale. The principal component analysis produced two factors with Eigen values ranging from 1.12 to 4.40, explaining 70.0% of total variance. Concurrent validity was satisfactory as the OIDP score increased when the adolescents' perceived oral health decreased. The final modified OIDP consists of eight self-reported items which assesses the impact severity of eight daily performances over past three months. Participant scores ranged from 0 to 24 out of a worst possible score of 40, and nearly 48% of the responders reported at least one impact during past three months. The most prevalent oral health impact related to chewing and enjoying foods, reported by 36.8% of respondents. CONCLUSION: This study suggests that the modified OIDP scale has promising psychometric properties and is appropriate for use among adolescents in Sri Lanka. Further research is required to test the validity of this tool in other cohorts.

4.
Differentiation ; 112: 58-66, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31954271

RESUMO

Despite significant effort devoted to developing new treatments and procedures, cardiac disease is still one of the leading causes of death in the world. The loss of myocytes due to ischemic injury remains a major therapeutic challenge. However, cell-based therapy to repair the injured heart has shown significant promise in basic and translation research and in clinical trials. Embryonic stem cells have been successfully used to improve cardiac outcomes. Unfortunately, treatment with these cells is complicated by ethical and legal issues. Recent progress in developing induced pluripotent stem cells (iPSCs) using non-viral vectors has made it possible to derive cardiomyocytes for therapy. This review will focus on these non-integration-based approaches for reprogramming and their therapeutic advantages for cardiovascular medicine.

5.
Cancer Res ; 80(4): 901-911, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31857292

RESUMO

Tumors are heterogeneous and composed of cells with different dissemination abilities. Despite significant effort, there is no universal biological marker that serves as a metric for metastatic potential of solid tumors. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Adhesion strength is heterogeneous even among cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups; when cultured under stromal conditions, this adhesion phenotype was stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Weakly adherent cells displayed increased migration in both two-dimensional and three-dimensional migration assays; this was maintained for several days in culture. Subpopulations did not show differences in expression of proteins involved in the focal adhesion complex but did exhibit intrinsic focal adhesion assembly as well as contractile differences that resulted from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity. In human breast tumors, expression of genes associated with the weakly adherent population resulted in worse progression-free and disease-free intervals. These data suggest that adhesion strength could potentially serve as a stable marker for migration and metastatic potential within a given tumor population and that the fraction of weakly adherent cells present within a tumor could act as a physical marker for metastatic potential. SIGNIFICANCE: Cancer cells exhibit heterogeneity in adhesivity, which can be used to predict metastatic potential.

6.
BMJ Open ; 9(11): e030955, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690607

RESUMO

OBJECTIVE: To quantitatively assess the factors associated with non-beneficial treatments (NBTs) in hospital admissions at the end of life. DESIGN: Retrospective multicentre cohort study. SETTING: Three large, metropolitan tertiary hospitals in Australia. PARTICIPANTS: 831 adult patients who died as inpatients following admission to the study hospitals over a 6-month period in 2012. MAIN OUTCOME MEASURES: Odds ratios (ORs) of NBT derived from logistic regression models. RESULTS: Overall, 103 (12.4%) admissions involved NBTs. Admissions that involved conflict within a patient's family (OR 8.9, 95% CI 4.1 to 18.9) or conflict within the medical team (OR 6.5, 95% CI 2.4 to 17.8) had the strongest associations with NBTs in the all subsets regression model. A positive association was observed in older patients, with each 10-year increment in age increasing the likelihood of NBT by approximately 50% (OR 1.5, 95% CI 1.2 to 1.9). There was also a statistically significant hospital effect. CONCLUSIONS: This paper presents the first statistical modelling results to assess the factors associated with NBT in hospital, beyond an intensive care setting. Our findings highlight potential areas for intervention to reduce the likelihood of NBTs.

7.
J Infect Prev ; 20(6): 266-273, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31762788

RESUMO

Background: Hospital-acquired infections (HAI) contribute to prolonged hospital stays and account for a substantial economic burden to healthcare systems. Middle-income countries (MICs) experience a greater burden of HAI than developed countries. Evidence on the cost-effectiveness of interventions to reduce HAI is required to inform decision-making in these settings. Aim: To synthesise the evidence on cost-effectiveness as related to HAI interventions in MICs and to assess the quality of this evidence. Methods: A systematic review of published literature on the cost-effectiveness of interventions to reduce the incidence of HAI in MICs between 2000 and 2018 was conducted. Results: Six studies met the pre-determined inclusion criteria. The studies were from three countries: Thailand; India; and Vietnam. The evidence suggests that interventions to reduce HAI are cost-effective and, in most cases, cost-saving to healthcare systems. The quality of the reporting varied across studies. Conclusions: The implementation of HAI prevention interventions appears to be a high value use of resources in MICs. There is a need for further cost-effectiveness analyses in a wider range of MICs in order to confirm these findings. Improved standardisation and quality of reporting is required.

8.
PLoS Biol ; 17(11): e3000434, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31765370

RESUMO

G protein-coupled receptors (GPCRs) are the most widely targeted gene family for Food and Drug Administration (FDA)-approved drugs. To assess possible roles for GPCRs in cancer, we analyzed The Cancer Genome Atlas (TCGA) data for mRNA expression, mutations, and copy number variation (CNV) in 20 categories and 45 subtypes of solid tumors and quantified differential expression (DE) of GPCRs by comparing tumors against normal tissue from the Gene Tissue Expression Project (GTEx) database. GPCRs are overrepresented among coding genes with elevated expression in solid tumors. This analysis reveals that most tumor types differentially express >50 GPCRs, including many targets for approved drugs, hitherto largely unrecognized as targets of interest in cancer. GPCR mRNA signatures characterize specific tumor types and correlate with expression of cancer-related pathways. Tumor GPCR mRNA signatures have prognostic relevance for survival and correlate with expression of numerous cancer-related genes and pathways. GPCR expression in tumors is largely independent of staging, grading, metastasis, and/or driver mutations. GPCRs expressed in cancer cell lines largely parallel GPCR expression in tumors. Certain GPCRs are frequently mutated and appear to be hotspots, serving as bellwethers of accumulated genomic damage. CNV of GPCRs is common but does not generally correlate with mRNA expression. Our results suggest a previously underappreciated role for GPCRs in cancer, perhaps as functional oncogenes, biomarkers, surface antigens, and pharmacological targets.

9.
Implement Sci ; 14(1): 78, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399105

RESUMO

BACKGROUND: Advanced physiotherapist-led services have been embedded in specialist orthopaedic and neurosurgical outpatient departments across Queensland, Australia, to ameliorate capacity constraints. Simulation modelling has been used to inform the optimal scale and professional mix of services required to match patient demand. The context and the value of simulation modelling in service planning remain unclear. We aimed to examine the adoption, context and costs of using simulation modelling recommendations to inform service planning. METHODS: Using an implementation science approach, we undertook a prospective, qualitative evaluation to assess the use of discrete event simulation modelling recommendations for service re-design and to explore stakeholder perspectives about the role of simulation modelling in service planning. Five orthopaedic and neurosurgical services in Queensland, Australia, were selected to maximise variation in implementation effectiveness. We used the consolidated framework for implementation research (CFIR) to guide the facilitation and analysis of the stakeholder focus group discussions. We conducted a prospective costing analysis in each service to estimate the costs associated with using simulation modelling to inform service planning. RESULTS: Four of the five services demonstrated adoption by inclusion of modelling recommendations into proposals for service re-design. Four CFIR constructs distinguished and two CFIR constructs did not distinguish between high versus mixed implementation effectiveness. We identified additional constructs that did not map onto CFIR. The mean cost of implementation was AU$34,553 per site (standard deviation = AU$737). CONCLUSIONS: To our knowledge, this is the first time the context of implementing simulation modelling recommendations in a health care setting, using a validated framework, has been examined. Our findings may provide valuable insights to increase the uptake of healthcare modelling recommendations in service planning.


Assuntos
Assistência Ambulatorial/normas , Assistência à Saúde/normas , Ciência da Implementação , Modelos Organizacionais , Neurocirurgia/normas , Ortopedia/normas , Pacientes Ambulatoriais , Técnicas de Planejamento , Melhoria de Qualidade , Grupos Focais , Necessidades e Demandas de Serviços de Saúde , Humanos , Pesquisa Qualitativa , Queensland
10.
BMC Health Serv Res ; 19(1): 608, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464609

RESUMO

BACKGROUND: Demand for gastrointestinal endoscopy in Australia is increasing as a result of the expanding national bowel cancer screening program and a growing, ageing population. More services are required to meet demand and ensure patients are seen within clinically recommended timeframes. METHODS: A discrete event simulation model was developed to project endoscopy waiting list outcomes for two large metropolitan health services encompassing 8 public hospitals in Australia. The model applied routinely collected health service data to forecast the impacts of future endoscopic demand over 5 years and to identify the level of service activity required to address patient waiting times and meet key policy targets. The approach incorporated evidence from the literature to produce estimates of cost-effectiveness by showing longer term costs and Quality Adjusted Life Years (QALYs) associated with service expansion. RESULTS: The modelling revealed that doing nothing would lead to the number of patients waiting longer than clinically recommended doubling across each health service within 5 years. A 38% overall increase in the number of monthly procedures available was required to meet and maintain a target of 95-98% of patients being seen within clinically recommended timeframes to the year 2021. This was projected to cost the funder approximately $140 million in additional activity over a 5 year period. Due to improved patient outcomes associated with timely intervention, it was estimated that the increased activity would generate over 22,000 additional QALYs across the two health services. This translated to an incremental cost-effectiveness ratio of $6467 and $5974 per QALY for each health service respectively. CONCLUSIONS: Discrete event simulation modelling provided a rational, data based approach that allowed decision makers to quantify the future demand for endoscopy services and identify cost-effective strategies to meet community needs.


Assuntos
Endoscopia Gastrointestinal/estatística & dados numéricos , Planejamento em Saúde/métodos , Austrália , Análise Custo-Benefício , Tomada de Decisões , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/estatística & dados numéricos , Endoscopia Gastrointestinal/economia , Hospitais Públicos/economia , Hospitais Públicos/estatística & dados numéricos , Humanos , Neoplasias Intestinais/diagnóstico , Modelos Estatísticos , Anos de Vida Ajustados por Qualidade de Vida , Listas de Espera
11.
Hum Mutat ; 40(9): 1474-1485, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31260570

RESUMO

The CAGI-5 pericentriolar material 1 (PCM1) challenge aimed to predict the effect of 38 transgenic human missense mutations in the PCM1 protein implicated in schizophrenia. Participants were provided with 16 benign variants (negative controls), 10 hypomorphic, and 12 loss of function variants. Six groups participated and were asked to predict the probability of effect and standard deviation associated to each mutation. Here, we present the challenge assessment. Prediction performance was evaluated using different measures to conclude in a final ranking which highlights the strengths and weaknesses of each group. The results show a great variety of predictions where some methods performed significantly better than others. Benign variants played an important role as negative controls, highlighting predictors biased to identify disease phenotypes. The best predictor, Bromberg lab, used a neural-network-based method able to discriminate between neutral and non-neutral single nucleotide polymorphisms. The CAGI-5 PCM1 challenge allowed us to evaluate the state of the art techniques for interpreting the effect of novel variants for a difficult target protein.

13.
PLoS One ; 14(7): e0220209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31329651

RESUMO

OBJECTIVE: To estimate the productivity impacts of a policy intervention on the prevention of premature mortality due to obesity. METHODS: A simulation model of the Australian population over the period from 2003 to 2030 was developed to estimate productivity gains associated with premature deaths averted due to an obesity prevention intervention that applied a 10% tax on unhealthy foods. Outcome measures were the total working years gained, and the present value of lifetime income (PVLI) gained. Impacts were modelled over the period from 2003 to 2030. Costs are reported in 2018 Australian dollars and a 3% discount rate was applied to all future benefits. RESULTS: Premature deaths averted due to a junk food tax accounted for over 8,000 additional working years and a $307 million increase in PVLI. Deaths averted in men between the ages of 40 to 59, and deaths averted from ischaemic heart disease, were responsible for the largest gains. CONCLUSIONS: The productivity gains associated with a junk food tax are substantial, accounting for almost twice the value of the estimated savings to the health care system. The results we have presented provide evidence that the adoption of a societal perspective, when compared to a health sector perspective, provides a more comprehensive estimate of the cost-effectiveness of a junk food tax.


Assuntos
Análise Custo-Benefício , Dieta Hiperlipídica/economia , Fast Foods/economia , Mortalidade Prematura , Obesidade/epidemiologia , Impostos/estatística & dados numéricos , Adulto , Austrália , Feminino , Promoção da Saúde/economia , Promoção da Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/economia
14.
BMC Med Genomics ; 12(Suppl 6): 107, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345234

RESUMO

BACKGROUND: The major histocompatibility complex class I (MHC-I) molecule is a protein complex that displays intracellular peptides to T cells, allowing the immune system to recognize and destroy infected or cancerous cells. MHC-I is composed of a highly polymorphic HLA-encoded alpha chain that binds the peptide and a Beta-2-microglobulin (B2M) protein that acts as a stabilizing scaffold. HLA mutations have been implicated as a mechanism of immune evasion during tumorigenesis, and B2M is considered a tumor suppressor gene. However, the implications of somatic HLA and B2M mutations have not been fully explored in the context of antigen presentation via the MHC-I molecule during tumor development. To understand the effect that B2M and HLA MHC-I molecule mutations have on mutagenesis, we analyzed the accumulation of mutations in patients from The Cancer Genome Atlas according to their MHC-I molecule mutation status. RESULTS: Somatic B2M and HLA mutations in microsatellite stable tumors were associated with higher overall mutation burden and a larger fraction of HLA-binding neoantigens when compared to B2M and HLA wild type tumors. B2M and HLA mutations were highly enriched in patients with microsatellite instability. B2M mutations tended to occur relatively early during patients' respective tumor development, whereas HLA mutations were either early or late events. In addition, B2M and HLA mutated patients had higher levels of immune infiltration by natural killer and CD8+ T cells and higher levels of cytotoxicity. CONCLUSIONS: Our findings add to a growing body of evidence that somatic B2M and HLA mutations are a mechanism of immune evasion by demonstrating that such mutations are associated with a higher load of neoantigens that should be presented via MHC-I.

15.
Int J Evid Based Healthc ; 17(3): 157-163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31246696

RESUMO

BACKGROUND: Exposure to the rabies virus is fatal unless a patient is treated with a timely, accurate and complete administration of postexposure prophylaxis (PEP). The level of adherence to PEP guidelines by health service providers is therefore critical in providing high-quality care as well as preventing unnecessary costs. METHODS: We developed a simple user-friendly decision aid based on Sri Lankan national guidelines for the administration of PEP and trialed it over a 5-month period in three study settings. Pre and post levels of adherence to the national guidelines by service providers was measured in each setting. Changes to per patient cost for rabies medications and hospital admissions were also collected. RESULTS: A significant improvement in adherence to the guidelines was observed in two settings with a nonsignificant improvement observed in the third setting. We estimated a total cost saving of LKR 158 476 across the three sites, comprising LKR 14 418 in admissions cost savings and LKR 144 058 in medication savings. CONCLUSION: We conclude that the development of a decision aid for the administration of PEP is likely to be an effective and cost-saving intervention in the Sri Lankan setting. Further research is required to inform the generalizability of our findings.

16.
Science ; 364(6447): 1228-1229, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31249043
17.
J Cardiovasc Comput Tomogr ; 13(4): 203-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104941

RESUMO

BACKGROUND: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test. METHODS: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening. RESULTS: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals. CONCLUSION: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Testes Genéticos , Polimorfismo de Nucleotídeo Único , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Doença da Artéria Coronariana/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , Calcificação Vascular/etnologia
18.
BMC Bioinformatics ; 20(1): 265, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31132991

RESUMO

BACKGROUND: In standard high throughput sequencing analysis, genetic variants are not assigned to a homologous chromosome of origin. This process, called haplotype phasing, can reveal information important for understanding the relationship between genetic variants and biological phenotypes. For example, in genes that carry multiple heterozygous missense variants, phasing resolves whether one or both gene copies are altered. Here, we present a novel approach to phasing variants that takes advantage of unique properties of paired tumor:normal sequencing data from cancer studies. RESULTS: VAF phasing uses changes in variant allele frequency (VAF) between tumor and normal samples in regions of somatic chromosomal gain or loss to phase germline variants. We apply VAF phasing to 6180 samples from the Cancer Genome Atlas (TCGA) and demonstrate that our method is highly concordant with other standard phasing methods, and can phase an average of 33% more variants than other read-backed phasing methods. Using variant annotation tools designed to score gene haplotypes, we find a suggestive association between carrying multiple missense variants in a single copy of a cancer predisposition gene and earlier age of cancer diagnosis. CONCLUSIONS: VAF phasing exploits unique properties of tumor genomes to increase the number of germline variants that can be phased over standard read-backed methods in paired tumor:normal samples. Our phase-informed association testing results call attention to the need to develop more tools for assessing the joint effect of multiple genetic variants.


Assuntos
Variação Genética , Neoplasias/genética , Análise de Sequência de DNA , Sequência de Bases , Variações do Número de Cópias de DNA/genética , Frequência do Gene/genética , Predisposição Genética para Doença , Haplótipos/genética , Humanos
19.
Open Heart ; 6(1): e000939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997129

RESUMO

Background: Cardiovascular disease (CVD) is the single largest contributor to global mortality. Premature mortality due to CVD results in a loss of productivity, with associated economic and policy implications that are often overlooked. Methods: A human capital approach was adopted to project the long-term impacts of Australian CVD deaths in 2003 on labour force participation and the present value of lifetime income (PVLI) forgone. Impacts were modelled to the year 2030 and accounted for individual characteristics at the time of death including age, sex and socioeconomic status. Results: Premature deaths due to CVD in 2003 accounted for 51 659 working years and $2.69 billion in PVLI forgone when modelled to 2030 (95% CI $2.63 billion to $2.75 billion). The labour force impacts were highest for individuals aged between 35 and 64 at the time of death, and male deaths accounted for 87% of the total PVLI loss. The most costly disease type was ischaemic heart disease, followed by stroke and inflammatory heart disease. Deaths occurring in individuals residing in the most socioeconomically disadvantaged areas at the time of death had a disproportionately large impact on the total PVLI loss. Conclusions: This study quantifies the relative productivity costs of CVD mortality across a range of disease types and socioeconomic groups. The magnitude of these costs highlights the scope for investments in effective healthcare interventions to provide positive economic returns and may assist decision makers in allocating resources among competing priorities.

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