RESUMO

Cancer genomics has evolved over the years from understanding the pathogenesis of cancer to screening the future possibilities of cancer occurrence. Understanding the genetic profile of tumors holds a prognostic as well as a predictive value in this era of therapeutic surveillance, molecular remission, and precision medicine. Identifying molecular markers in tumors is the current standard of approach, and requires an efficient combination of an accessible sample type and a profoundly sensitive technique. Liquid biopsy or cell-free DNA has evolved as a novel sample type with promising results in recent years. Although cell-free DNA has significant role in various cancer types, this review focuses on its application in Non-Hodgkin's Lymphoma. Beginning with the current concept and clinical relevance of minimal residual disease in Non-Hodgkin's lymphoma, we discuss the literature on circulating DNA and its evolving application in the realm of cutting-edge technology.

Assuntos

DNA Tumoral Circulante/sangue , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Citometria de Fluxo , Marcadores Genéticos , Técnicas de Genotipagem , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Linfoma/sangue , Linfoma/genética , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico por imagem , Mutação , Neoplasia Residual/sangue , Neoplasia Residual/genética , Neoplasia Residual/patologia , Reação em Cadeia da Polimerase/métodos , Tomografia por Emissão de Pósitrons , Medicina de Precisão , Prognóstico , Transcriptoma , Translocação Genética

RESUMO

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Doenças Cardiovasculares , Neoplasias/mortalidade

RESUMO

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Assuntos

Sistemas de Saúde , Doenças Cardiovasculares , Seguro Saúde , Diabetes Mellitus

RESUMO

To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing.METHODS:Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders.FINDINGS:Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities.CONCLUSION:Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

Assuntos

Marketing , Dispositivos para o Abandono do Uso de Tabaco , Publicidade de Produtos Derivados do Tabaco , Nicotiana

RESUMO

Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or centralobesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex anddependent on country and cultural context. We investigated the association between psychosocial factors and general andabdominal obesity in the Prospective Urban Rural Epidemiologic study.SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35–70 years from 628 urban andrural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education,anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression).RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body massindex ⩾ 30 kgm−2) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress,with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (Po0.0001 forboth). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stresswith age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted(adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99–1.10)). There was no relationship between ethnicityandsex-specific central obesity (adjusted PR 1.00 (0.97–1.02)). Stratification by region yielded inconsistent associations. Depressionwas weakly but independently linked to obesity (PR 1.08 (1.04–1.12)), and very marginally to abdominal obesity (PR 1.01(1.00–1.03)).

Assuntos

Diabetes Mellitus , Hipertensão , Obesidade

RESUMO

BACKGROUND:Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries.METHODS:The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally.FINDINGS:Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength...

Assuntos

Coração , Doenças Cardiovasculares

RESUMO

OBJECTIVE: The purpose of this study was to determine if the exotic venomous species, Pterois volitans (lionfish) had reached as far south as St Vincent in the Caribbean. This predatory marine fish has successfully invaded the waters of the Western Atlantic and the Caribbean. Such success as an exotic invasive species is rare for a predatory marine fish. It is possible that the fish are growing larger and spreading faster than anticipated, thanks to a lower burden of parasites and a paucity of natural predators in their new environment. But prior to this report, no sightings of this species this far south had been reported. METHODS: The authors conducted a search along with the help of local divers and fishermen in the waters of St Vincent. RESULTS: Approximately one year after the initiation of the search, a juvenile specimen was positively confirmed and captured off the southern coast of St Vincent. CONCLUSIONS: The exotic predatory and venomous red lionfish, Pterois volitans, has successfully invaded marine waters as far south as the Windward Islands. Fishermen in these regions should be aware of this venomous species in the region and physicians must be aware of how to manage stings from such animals.

RESUMO

BACKGROUNDMore than 80% of deaths from cardiovascular disease are estimated to occur inlow-income and middle-income countries, but the reasons are unknown.METHODSWe enrolled 156,424 persons from 628 urban and rural communities in 17 countries(3 high-income, 10 middle-income, and 4 low-income countries) and assessedtheir cardiovascular risk using the INTERHEART Risk Score, a validated score forquantifying risk-factor burden without the use of laboratory testing (with higherscores indicating greater risk-factor burden). Participants were followed for incidentcardiovascular disease and death for a mean of 4.1 years.RESULTSThe mean INTERHEART Risk Score was highest in high-income countries, intermediatein middle-income countries, and lowest in low-income countries (P<0.001).However, the rates of major cardiovascular events (death from cardiovascularcauses, myocardial infarction, stroke, or heart failure) were lower in high-incomecountries than in middle- and low-income countries (3.99 events per 1000 personyearsvs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Casefatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3%in high-, middle-, and low-income countries, respectively; P = 0.01). Urban communitieshad a higher risk-factor burden than rural communities but lower ratesof cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) andcase fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medicationsand revascularization procedures was significantly more common in high-incomecountries than in middle- or low-income countries (P<0.001).CONCLUSIONSAlthough the risk-factor burden was lowest in low-income countries, the rates ofmajor cardiovascular disease and death were substantially higher in low-incomecountries than in high-income countries. The high burden of risk factors in highincome...

Assuntos

Acidente Vascular Cerebral , Doenças Cardiovasculares , Infarto do Miocárdio

RESUMO

The relevance of loci associated with blood lipids recently identified in European populations in individuals of African ancestry is unknown. We tested association between lipid traits and 36 previously described single-nucleotide polymorphisms (SNPs) in 1,466 individuals of African ancestry from Spanish Town, Jamaica. For the same allele and effect direction as observed in individuals of European ancestry, SNPs at three loci (1p13, 2p21, and 19p13) showed statistically significant association (p < 0.05) with LDL, two loci (11q12 and 20q13) showed association with HDL cholesterol, and two loci (11q12 and 2p24) showed association with triglycerides. The most significant association was between a SNP at 1p13 and LDL cholesterol (p = 4.6 × 10(-8)). This SNP is in a linkage disequilibrium region containing four genes (CELSR2, PSRC1, MYBPHL, and SORT1) and was recently shown to relate to risk for myocardial infarction. Overall, the results of this study suggest that much of the genetic variation which influences blood lipids is shared across ethnic groups.

Assuntos

População Negra/genética , Loci Gênicos/genética , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único , População Branca/genética , Adulto , Idoso , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Jamaica/etnologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA

RESUMO

An insertion mutation within exon 12 of the factor XI gene has been described in Holstein cattle. This has opened the prospect for large-scale screening of cattle using the polymerase chain reaction (PCR) technique for the rapid identification of heterozygous animals. To facilitate such a screening process, the mutant and normal alleles of factor XI gene, represented by 244- and 320-bp PCR amplified fragments, were individually cloned in Escherichia coli using a multicopy plasmid cloning vehicle to generate pFXI-N and pFXI-M, respectively. The authenticity of the inserts was confirmed by nucleotide sequencing. A nested PCR method was developed, by which PCR amplicons generated from primers with annealing sites on the recombinant plasmids and by flanking the insert were used as templates for amplification of the diagnostic products using factor XI gene-specific primers. An equimolar mixture of both PCR amplicons, originating from pFXI-N and pFXI-M, constituted the carrier control while the individual amplicons were the affected and normal controls. The controls were used as references for in-gel comparison to screen a population of 307 cattle and 259 water buffaloes; the frequency of the mutant allele was found to be 0. No DNA size standards were required in this study. The simulated control DNA samples representing normal, carrier and affected cattle have the potential to help in large-scale screening of a cattle population for individuals that are carriers or affected by factor XI deficiency.

Assuntos

Doenças dos Bovinos/genética , Deficiência do Fator XI/veterinária , Triagem de Portadores Genéticos/métodos , Análise de Sequência de DNA/veterinária , Alelos , Animais , Sequência de Bases , Búfalos , Bovinos , Deficiência do Fator XI/genética , Genótipo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/veterinária