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1.
BMC Bioinformatics ; 21(Suppl 14): 368, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998690

RESUMO

BACKGROUND: Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. RESULTS: We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide variations or the copy number variations, differentially expressed genes and those in active subnetworks to construct a prognosis signature. Cox proportional hazards model with Lasso penalty and LOOCV was used to identify best gene signature among different gene categories. We determined a 12-gene signature (BCHE, CCNA1, CYP24A1, DEPTOR, MASP2, MGLL, MYO1A, PODXL2, RAPGEF3, SGK2, TNNI2, ZBTB16) for prognostic risk prediction based on overall survival time of the patients with lung adenocarcinoma. The patients in both training and test data were clustered into high-risk and low-risk groups by using risk scores of the patients calculated based on selected gene signature. The overall survival probability of these risk groups was highly significantly different for both training and test datasets. CONCLUSIONS: This 12-gene signature could predict the prognostic risk of the patients with lung adenocarcinoma in TCGA and they are potential predictors for the survival-based risk clustering of the patients with lung adenocarcinoma. These genes can be used to cluster patients based on molecular nature and the best candidates of drugs for the patient clusters can be proposed. These genes also have a high potential for targeted cancer therapy of patients with lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/patologia , Genômica/métodos , Neoplasias Pulmonares/patologia , Transcriptoma , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Área Sob a Curva , Análise por Conglomerados , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas/genética , Curva ROC , Fatores de Risco , Taxa de Sobrevida
2.
BMJ Open ; 10(8): e039455, 2020 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-32868368

RESUMO

INTRODUCTION: The outbreak of the SARS-CoV-2 virus causing COVID-19, declared a global pandemic by the WHO, is a novel infection with a high rate of morbidity and mortality. In South Africa, 55 421 cases have been confirmed as of 10 June 2020, with most cases in the Western Cape Province. Coronavirus leaves us in a position of uncertainty regarding the best clinical approach to successfully manage the expected high number of severely ill patients with COVID-19. This presents a unique opportunity to gather data to inform best practices in clinical approach and public health interventions to control COVID-19 locally. Furthermore, this pandemic challenges our resolve due to the high burden of HIV and tuberculosis (TB) in our country as data are scarce. This study endeavours to determine the clinical presentation, severity and prognosis of patients with COVID-19 admitted to our hospital. METHODS AND ANALYSIS: The study will use multiple approaches taking into account the evolving nature of the COVID-19 pandemic. Prospective observational design to describe specific patterns of risk predictors of poor outcomes among patients with severe COVID-19 admitted to Tygerberg Hospital. Data will be collected from medical records of patients with severe COVID-19 admitted at Tygerberg Hospital. Using the Cox proportional hazards model, we will investigate the association between the survival time of patients with COVID-19 in relation to one or more of the predictor variables including HIV and TB. ETHICS AND DISSEMINATION: The research team obtained ethical approval from the Health Research Ethics Committee of the Faculty of Medicine and Health Sciences, Stellenbosch University and Research Committee of the Tygerberg Hospital. All procedures for the ethical conduct of scientific investigation will be adhered to by the research team. The findings will be disseminated in clinical seminars, scientific forums and conferences targeting clinical care providers and policy-makers.


Assuntos
Infecções por Coronavirus , Hospitalização , Hospitais , Pandemias , Pneumonia Viral , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Surtos de Doenças , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Registros Médicos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Saúde Pública , Projetos de Pesquisa , África do Sul/epidemiologia , Sobreviventes , Tuberculose/complicações
3.
BMC Med ; 18(1): 274, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892742

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. Old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, whether frailty, a common geriatric syndrome of reduced reserve to stressors, is associated with poor prognosis among older COVID-19 patients is unknown. The aim of our study is to investigate the association between frailty and severe disease among COVID-19 patients aged ≥ 60 years. METHODS: A prospective cohort study of 114 hospitalized older patients (≥ 60 years) with confirmed COVID-19 pneumonia was conducted between 7 February 2020 and 6 April 2020. Epidemiological, demographic, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. All patients were assessed for frailty on admission using the FRAIL scale, in which five components are included: fatigue, resistance, ambulation, illnesses, and loss of weight. The outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards models to identify the unadjusted and adjusted associations between frailty and severe illness. The significant variables in univariable analysis were included in the adjusted model. RESULTS: Of 114 patients, (median age, 67 years; interquartile range = 64-75 years; 57 [50%] men), 39 (34.2%), 39 (34.2%), and 36 (31.6%) were non-frail, pre-frail, and frail, respectively. During the 60 days of follow-up, 43 severe diseases occurred including eight deaths. Four of 39 (10.3%) non-frail patients, 15 of 39 (38.5%) pre-frail patients, and 24 of 36 (66.7%) frail patients progressed to severe disease. After adjustment of age, sex, body mass index, haemoglobin, white blood count, lymphocyte count, albumin, CD8+ count, D-dimer, and C-reactive protein, frailty (HR = 7.47, 95% CI 1.73-32.34, P = 0.007) and pre-frailty (HR = 5.01, 95% CI 1.16-21.61, P = 0.03) were associated with a higher hazard of severe disease than the non-frail. CONCLUSIONS: Frailty, assessed by the FRAIL scale, was associated with a higher risk of developing severe disease among older COVID-19 patients. Our findings suggested that the use of a clinician friendly assessment of frailty could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.


Assuntos
Infecções por Coronavirus , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/virologia , Avaliação Geriátrica/métodos , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
4.
Yonsei Med J ; 61(9): 805-815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882765

RESUMO

PURPOSE: We explored the role of parental social class in preterm birth (PTB) and low birth weight (LBW) in association with child mortality in Korea. MATERIALS AND METHODS: A total of 7,302,732 births in Korea between 1995 and 2007 were used for designing the national retrospective cohort study. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine the risk of child death after adjusting for covariates. RESULTS: Parental social class was associated with adverse birth outcomes and child mortality in Korea. Parental social class increased the strength of the relationship of adverse birth outcomes with child mortality. Child mortality was higher among PTB and LBW infants from parents with a lower social class than normal births from parents with a higher social class. In particular, the disparity in child mortality according to parental social class was greater for LBW and PTB than intrauterine growth retardation births. When one of the parents had a middle-school education or lower, the disparity in child mortality due to adverse birth outcomes was large regardless of the other spouse's educational status. Inactive economic status for the father, as well as an occupation in manual labor by the mother, increased the risk of child mortality. CONCLUSION: Strong relationships for social inequalities and adverse birth outcomes with inequalities in child mortality in South Korea were found in this study. Tackling social inequalities, as well as reducing adverse birth outcomes, are needed to reduce the disparities in child mortality in South Korea.


Assuntos
Mortalidade da Criança , Nascimento Prematuro/epidemiologia , Classe Social , Adulto , Criança , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos
5.
Anticancer Res ; 40(9): 5237-5243, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878812

RESUMO

BACKGROUND/AIM: Adult T-cell leukemia/lymphoma (ATLL) is a relatively refractory CD4-positive peripheral T-cell lymphoma. VCAP-AMP-VECP (mLSG15) is one of the standard chemotherapeutic regimens for patients with aggressive ATLL. Mogamulizumab (moga), a monoclonal antibody for C-C chemokine receptor 4 antigen expressed on the cell surface, has recently been poised for use as monotherapy and in combination with chemotherapy. However, to date, a significant survival benefit has not been obtained with the combination of moga + mLSG15 therapy. PATIENTS AND METHODS: We retrospectively analyzed 77 patients diagnosed with aggressive ATLL. Of them, 22 were treated with moga + a chemotherapy regimen comprised of etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone (EPOCH), 16 with moga + mLSG15, and 39 with chemotherapy alone. RESULTS: A risk reduction of approximately 30% was obtained with moga + EPOCH compared with moga + mLSG15. CONCLUSION: The addition of moga to chemotherapy did not result in a survival benefit compared with chemotherapy alone. However, a statistically significant overall survival benefit was observed in patients with moga-induced skin disorders.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
7.
BMJ Open ; 10(9): e038976, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32948572

RESUMO

OBJECTIVE: Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. SETTING: A nested case-control design using confirmed case reports released from the news or the national/provincial/municipal health commissions of China between 18 December 2019 and 8 March 2020. PARTICIPANTS: Patients with confirmed SARS-CoV-2 infection, excluding asymptomatic patients, in mainland China outside of Hubei Province. OUTCOME MEASURES: Patient demographics, survival time and status, and history of comorbidities. METHOD: A total of 94 publicly reported deaths in locations outside of Hubei Province, mainland China, were included as cases. Each case was matched with up to three controls, based on gender and age ±1 year old (94 cases and 181 controls). The inverse probability-weighted Cox proportional hazard model was performed, controlling for age, gender and the early period of the outbreak. RESULTS: Of the 94 cases, the median age was 72.5 years old (IQR=16), and 59.6% were men, while in the control group the median age was 67 years old (IQR=22), and 64.6% were men. Adjusting for age, gender and the early period of the outbreak, poor health conditions were associated with a higher risk of COVID-19 mortality (HR of comorbidity score, 1.31 [95% CI 1.11 to 1.54]; p=0.001). The estimated mortality risk in patients with pre-existing coronary heart disease (CHD) was three times that of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old woman with no other comorbidities) was 0.53 (95% CI 0.34 to 0.82), while it was 0.85 (95% CI 0.79 to 0.91) for those without CHD. Older age was also associated with increased mortality risk: every 1-year increase in age was associated with a 4% increased risk of mortality (p<0.001). CONCLUSION: Extra care and early medical interventions are needed for patients with pre-existing comorbidities, especially CHD.


Assuntos
Doença das Coronárias/epidemiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Bronquite Crônica/epidemiologia , Estudos de Casos e Controles , Infarto Cerebral/epidemiologia , China/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Falência Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Renal/epidemiologia , Adulto Jovem
8.
Medicine (Baltimore) ; 99(38): e21840, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957308

RESUMO

BACKGROUND: The prognostic significance of preoperative prognostic nutritional index (PNI) in ovarian cancer (OC) is uncertain, and this study is aimed to clarify the prognostic significance. METHODS: We used 4 common databases for conducting a systematic review and meta-analysis, and eligible studies were included in the analysis. The association of preoperative PNI with overall survival (OS), progression-free survival (PFS), and clinicopathological parameters was analyzed. RESULTS: A total of 2050 patients with OC receiving the surgical treatment were analyzed in this study. Patients with low PNI tended to have a shorter OS (hazard ratio [HR] = 1.82, 95% CI = 1.30-2.55, P < .01) and PFS (HR = 1.91, 95% CI = 1.53-2.39, P < .01) compared with those with high PNI. Besides, low PNI was significantly associated with more advanced International Federation of Gynecology and Obstetrics stage (P < .01), the occurrence of ascites (P < .01), larger residual tumor (P < .01), insensitive to chemotherapy (P < .01), and higher CA125 (P < .01) compared with high PNI in OC. CONCLUSION: Low preoperative PNI is associated with shorter OS, shorter PFS, and worse clinicopathological parameters in OC. Low preoperative PNI is an unfavorable prognostic indicator of patients with OC.


Assuntos
Estado Nutricional/fisiologia , Neoplasias Ovarianas/mortalidade , Antígeno Ca-125/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/sangue , Prognóstico , Modelos de Riscos Proporcionais
9.
Medicine (Baltimore) ; 99(38): e22036, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957321

RESUMO

Studies about the effects of metabolically healthy obesity on cardiovascular disease (CVD) have yielded conflicting results. These heterogeneous results could be due to the limited usefulness of BMI in measuring general adiposity, as body mass index (BMI) does not accurately reflect body composition. This study aimed to evaluate the effect of body shape on CVD outcomes across different obesity phenotypes, and to provide an explanation for the heterogeneous effects of metabolically healthy obese (MHO) phenotype on CVD.We analyzed data from the Korean Genome and Epidemiology Study, a population-based cohort study conducted between 2001 and 2012. We divided the participants into 4 groups: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). To assess body shape, we calculated the z-score of the log-transformed a body shape index (LBSIZ). We computed Pearson correlation coefficients to examine the association of LBSIZ with muscle mass index, percentage of total fat mass (%Total FM), and percentage of abdominal fat mass (%Abdominal FM). We also used Cox proportional hazards regression to evaluate the effect of LBSIZ on CVD events according to the obesity phenotypes.A total of 9460 participants were assessed in this study. The incidence of CVD was 8.53 cases per 1000 person-year. LBSIZ showed strong positive correlation with %Total FM and %Abdominal FM, but negative correlation with muscle mass index. In Cox regression, MHO individuals did not show increased risk of CVD compared with MHNO individuals (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.96-1.73). However, MHO individuals in the 3rd (HR, 2.40; 95% CI, 1.28-4.51) and 4th (HR, 3.67; 95% CI, 1.99-6.74) quarters of LBSIZ showed significantly higher risk of CVD compared with MHNO individuals in the 1st quarter of LBSIZ. Moreover, LBSIZ showed a linear relationship with CVD among MHO individuals.While the MHO individuals showed similar CVD risk to the MHNO individuals, CVD risk increases with LBSIZ among the MHO individuals. LBSIZ appears to be a useful measure for CVD risk assessment in clinical practice and epidemiologic studies, especially for MHO patients.


Assuntos
Composição Corporal/fisiologia , Doenças Cardiovasculares/epidemiologia , Obesidade Metabolicamente Benigna/epidemiologia , Obesidade Metabolicamente Benigna/patologia , Adiposidade , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Glicemia , Índice de Massa Corporal , Pesos e Medidas Corporais , Fumar Cigarros/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos
10.
JAMA Netw Open ; 3(9): e2022058, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32965501

RESUMO

Importance: Coronavirus disease 2019 (COVID-19) is an acute respiratory illness with a high rate of hospitalization and mortality. Biomarkers are urgently needed for patient risk stratification. Red blood cell distribution width (RDW), a component of complete blood counts that reflects cellular volume variation, has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases. Objective: To investigate whether an association between mortality risk and elevated RDW at hospital admission and during hospitalization exists in patients with COVID-19. Design, Setting, and Participants: This cohort study included adults diagnosed with SARS-CoV-2 infection and admitted to 1 of 4 hospitals in the Boston, Massachusetts area (Massachusetts General Hospital, Brigham and Women's Hospital, North Shore Medical Center, and Newton-Wellesley Hospital) between March 4, 2020, and April 28, 2020. Main Outcomes and Measures: The main outcome was patient survival during hospitalization. Measures included RDW at admission and during hospitalization, with an elevated RDW defined as greater than 14.5%. Relative risk (RR) of mortality was estimated by dividing the mortality of those with an elevated RDW by the mortality of those without an elevated RDW. Mortality hazard ratios (HRs) and 95% CIs were estimated using a Cox proportional hazards model. Results: A total of 1641 patients were included in the study (mean [SD] age, 62[18] years; 886 men [54%]; 740 White individuals [45%] and 497 Hispanic individuals [30%]; 276 nonsurvivors [17%]). Elevated RDW (>14.5%) was associated with an increased mortality risk in patients of all ages. The RR for the entire cohort was 2.73, with a mortality rate of 11% in patients with normal RDW (1173) and 31% in those with an elevated RDW (468). The RR in patients younger than 50 years was 5.25 (normal RDW, 1% [n = 341]; elevated RDW, 8% [n = 65]); 2.90 in the 50- to 59-year age group (normal RDW, 8% [n = 256]; elevated RDW, 24% [n = 63]); 3.96 in the 60- to 69-year age group (normal RDW, 8% [n = 226]; elevated RDW, 30% [104]); 1.45 in the 70- to 79-year age group (normal RDW, 23% [n = 182]; elevated RDW, 33% [n = 113]); and 1.59 in those ≥80 years (normal RDW, 29% [n = 168]; elevated RDW, 46% [n = 123]). RDW was associated with mortality risk in Cox proportional hazards models adjusted for age, D-dimer (dimerized plasmin fragment D) level, absolute lymphocyte count, and common comorbidities such as diabetes and hypertension (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW >14.5% vs ≤14.5%; P < .001). Patients whose RDW increased during hospitalization had higher mortality compared with those whose RDW did not change; for those with normal RDW, mortality increased from 6% to 24%, and for those with an elevated RDW at admission, mortality increased from 22% to 40%. Conclusions and Relevance: Elevated RDW at the time of hospital admission and an increase in RDW during hospitalization were associated with increased mortality risk for patients with COVID-19 who received treatment at 4 hospitals in a large academic medical center network.


Assuntos
Infecções por Coronavirus/mortalidade , Índices de Eritrócitos , Eritrócitos , Hospitalização , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Biomarcadores/sangue , Boston/epidemiologia , Coronavirus , Infecções por Coronavirus/sangue , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Admissão do Paciente , Pneumonia Viral/sangue , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Síndrome Respiratória Aguda Grave
11.
JAMA Netw Open ; 3(9): e2022310, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32965502

RESUMO

Importance: Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment. Objective: To identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection. Design, Setting, and Participants: This longitudinal cohort study included 88 747 patients tested for SARS-CoV-2 nucleic acid by polymerase chain reaction between Feburary 28 and May 14, 2020, and followed up through June 22, 2020, in the Department of Veterans Affairs (VA) national health care system, including 10 131 patients (11.4%) who tested positive. Exposures: Sociodemographic characteristics, comorbid conditions, symptoms, and laboratory test results. Main Outcomes and Measures: Risk of hospitalization, mechanical ventilation, and death were estimated in time-to-event analyses using Cox proportional hazards models. Results: The 10 131 veterans with SARS-CoV-2 were predominantly male (9221 [91.0%]), with diverse race/ethnicity (5022 [49.6%] White, 4215 [41.6%] Black, and 944 [9.3%] Hispanic) and a mean (SD) age of 63.6 (16.2) years. Compared with patients who tested negative for SARS-CoV-2, those who tested positive had higher rates of 30-day hospitalization (30.4% vs 29.3%; adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.13), mechanical ventilation (6.7% vs 1.7%; aHR, 4.15; 95% CI, 3.74-4.61), and death (10.8% vs 2.4%; aHR, 4.44; 95% CI, 4.07-4.83). Among patients who tested positive for SARS-CoV-2, characteristics significantly associated with mortality included older age (eg, ≥80 years vs <50 years: aHR, 60.80; 95% CI, 29.67-124.61), high regional COVID-19 disease burden (eg, ≥700 vs <130 deaths per 1 million residents: aHR, 1.21; 95% CI, 1.02-1.45), higher Charlson comorbidity index score (eg, ≥5 vs 0: aHR, 1.93; 95% CI, 1.54-2.42), fever (aHR, 1.51; 95% CI, 1.32-1.72), dyspnea (aHR, 1.78; 95% CI, 1.53-2.07), and abnormalities in the certain blood tests, which exhibited dose-response associations with mortality, including aspartate aminotransferase (>89 U/L vs ≤25 U/L: aHR, 1.86; 95% CI, 1.35-2.57), creatinine (>3.80 mg/dL vs 0.98 mg/dL: aHR, 3.79; 95% CI, 2.62-5.48), and neutrophil to lymphocyte ratio (>12.70 vs ≤2.71: aHR, 2.88; 95% CI, 2.12-3.91). With the exception of geographic region, the same covariates were independently associated with mechanical ventilation along with Black race (aHR, 1.52; 95% CI, 1.25-1.85), male sex (aHR, 2.07; 95% CI, 1.30-3.32), diabetes (aHR, 1.40; 95% CI, 1.18-1.67), and hypertension (aHR, 1.30; 95% CI, 1.03-1.64). Notable characteristics that were not significantly associated with mortality in adjusted analyses included obesity (body mass index ≥35 vs 18.5-24.9: aHR, 0.97; 95% CI, 0.77-1.21), Black race (aHR, 1.04; 95% CI, 0.88-1.21), Hispanic ethnicity (aHR, 1.03; 95% CI, 0.79-1.35), chronic obstructive pulmonary disease (aHR, 1.02; 95% CI, 0.88-1.19), hypertension (aHR, 0.95; 95% CI, 0.81-1.12), and smoking (eg, current vs never: aHR, 0.87; 95% CI, 0.67-1.13). Most deaths in this cohort occurred in patients with age of 50 years or older (63.4%), male sex (12.3%), and Charlson Comorbidity Index score of at least 1 (11.1%). Conclusions and Relevance: In this national cohort of VA patients, most SARS-CoV-2 deaths were associated with older age, male sex, and comorbidity burden. Many factors previously reported to be associated with mortality in smaller studies were not confirmed, such as obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking.


Assuntos
Causas de Morte , Infecções por Coronavirus , Hospitalização , Pandemias , Pneumonia Viral , Respiração Artificial , Veteranos , Idoso , Betacoronavirus , Estudos de Coortes , Comorbidade , Coronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Dispneia/etiologia , Dispneia/terapia , Feminino , Febre/etiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Fatores de Risco , Síndrome Respiratória Aguda Grave , Índice de Gravidade de Doença , Estados Unidos , United States Department of Veterans Affairs
12.
Anticancer Res ; 40(10): 5853-5860, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988915

RESUMO

BACKGROUND/AIM: The optimal treatment sequencing for asymptomatic de novo metastatic rectal cancer is unclear. The aim of this study was to investigate the role of upfront radiotherapy, with or without chemotherapy on risk for local complications, in patients with asymptomatic advanced metastatic rectal cancer treated with palliative intention. PATIENTS AND METHODS: All patients with de novo metastatic rectal cancer diagnosed between January 2008 and December 2017 in two healthcare regions in Sweden (Örebro län, Sörmland) were identified and data were extracted from electronic medical records. Patients were divided into 3 groups based on treatment sequence: upfront radiotherapy, upfront chemotherapy, and only palliative surgery. RESULTS: In total, 102 patients were included in the study cohort, 30 patients in upfront radiotherapy group, 54 in upfront chemotherapy, and 18 in only palliative surgery group. Patients with only upfront CT [odds ratio (OR)= 5.10; 95% confidence interval (CI)=1.24-20.91, p=0.024] had a higher risk to suffer from a local complication compared to those who received upfront radiotherapy. Cause-specific Cox regression analysis among patients who received oncological therapy revealed that female patients [cause-specific hazard ratio (csHR)=3.61; 95% confidence interval (CI)=1.67-7.81] and upfront chemotherapy [csHR=1.85; 95% CI=1.11-3.77] were associated with increased cumulative incidence of local complication over time, whereas primary surgery with ostomy or stent with lower risk [csHR=0.45; 95% CI=0.21-0.99]. CONCLUSION: Patients who received upfront radiotherapy, with or without chemotherapy, had fewer local complications due to primary tumor compared to patients who only received chemotherapy. This could indicate that radiotherapy to the primary tumor could be discussed with the patients as a first treatment option for asymptomatic metastatic rectal cancer to prevent local complications later during the disease.


Assuntos
Doenças Assintomáticas/terapia , Doenças Raras/radioterapia , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas/epidemiologia , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Masculino , Oncologia/tendências , Pessoa de Meia-Idade , Cuidados Paliativos , Modelos de Riscos Proporcionais , Doenças Raras/tratamento farmacológico , Doenças Raras/patologia , Doenças Raras/cirurgia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Suécia/epidemiologia
13.
Environ Health Prev Med ; 25(1): 46, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873231

RESUMO

BACKGROUND: Preventing the need for long-term care (LTC) by identifying physical function risk factors are important to decrease the LTC burden. The objective of this study was to investigate whether grip strength and/or walking speed, which are components of the frailty definition, are associated with LTC in community-dwelling older and oldest people. METHODS: The participants were 1098 community-dwelling older and oldest people who had not received LTC at the baseline. The endpoint was receiving LTC after the baseline survey. The independent variables were grip strength and walking speed, and participants were divided into two groups based on these variables. The confounding factors were age, sex, the Japanese version of the Montreal Cognitive Assessment (MoCA-J), hypertension, diabetes mellitus, stroke, joint diseases, living alone, body mass index, and serum albumin. We calculated the hazard ratio of receiving LTC using the Cox proportional hazard model. RESULTS: Among the 1098 participants, 107 (9.7%) newly received LTC during the follow-up. Regarding the physical function, only slow walking speed was significantly correlated with LTC after adjusting for all confounding factors except the MoCA-J score (HR = 1.74, 95% CI = 1.10-2.75, P = .018). However, slow walking speed was still a risk factor for LTC after adjusting for the MoCA-J score and other confounding factors (HR = 1.64, 95% CI = 1.03-2.60, P = .037). CONCLUSIONS: The findings from this study may contribute to a better understanding of slow walking speed as a factor related to LTC, which might be a criterion for disability prevention and could serve as an outcome measure for physical function in older people.


Assuntos
Exercício Físico , Vida Independente/estatística & dados numéricos , Assistência de Longa Duração/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Modelos de Riscos Proporcionais
14.
Epidemiol Infect ; 148: e198, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892789

RESUMO

This study aimed to analyse the survival of patients admitted to Brazilian hospitals due to the COVID-19 and estimate prognostic factors. This is a retrospective, multicentre cohort study, based on data from 46 285 hospitalisations for COVID-19 in Brazil. Survival functions were calculated using the Kaplan-Meier's method. The log-rank test compared the survival functions for each variable and from that, hazard ratios (HRs) were calculated, and the proportional hazard model was used in Cox multiple regression. The smallest survival curves were the ones for patients at the age of 68 years or more, black/mixed race, illiterate, living in the countryside, dyspnoea, respiratory distress, influenza-like outbreak, O2 saturation <95%, X-ray change, length of stay in the intensive care unit (ICU), invasive ventilatory support, previous heart disease, pneumopathy, diabetes, Down's syndrome, neurological disease and kidney disease. Better survival was observed in the influenza-like outbreak and in an asthmatic patient. The multiple model for increased risk of death when they were admitted to the ICU HR 1.28, diabetes HR 1.17, neurological disease HR 1.34, kidney disease HR 1.11, heart disease HR 1.14, black or mixed race of HR 1.50, asthma HR 0.71 and pneumopathy HR 1.12. This reinforces the importance of socio-demographic and clinical factors as a prognosis for death.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Idoso , Brasil/epidemiologia , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(4): 475-482, 2020 Apr 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895141

RESUMO

OBJECTIVE: To explore the application and advantages of conditional inference forest in survival analysis. METHODS: We used simulated experiment and actual data to compare the predictive performance of 4 models, including Coxproportional hazards model, accelerated failure time model, random survival forest model and conditional inference forest model based on their Brier scores. RESULTS: Simulation experiment suggested that both of the two forest models had more accurate and robust predictive performance than the other two regression models. Conditional inference forest model was superior to the other models in analyzing time-to-event data with polytomous covariates, collinearity or interaction, especially for a large sample size and a high censoring rate. The results of actual data analysis demonstrated that conditional inference forest model had the best predictive performance among the 4 models. CONCLUSIONS: Compared with the commonly used survival analysis methods, conditional inference forest model performs better especially when the data contain polytomous covariates with collinearity and interaction.


Assuntos
Análise de Dados , Modelos de Riscos Proporcionais , Tamanho da Amostra , Análise de Sobrevida
16.
Int Heart J ; 61(5): 865-871, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921667

RESUMO

Bleeding complication has been considered as a serious problem in current percutaneous coronary interventions (PCI). Fortunately, several groups have already reported the effectiveness of protamine use just after PCI to immediately remove any arterial sheath. However, there is a concern that protamine reversal may increase non-occlusive thrombus and, in turn, lead to mid-term cardiovascular events such as target vessel revascularization (TVR) or stent thrombosis. Thus, the purpose of this study was to evaluate whether protamine use following elective PCI was associated with mid-term clinical outcomes. In total, 472 patients were included in this study; subsequently, they were divided into protamine group (n = 142) and non-protamine group (n = 330). The primary endpoint was the composite of ischemia-driven TVR and stent thrombosis. The median follow-up period was determined to be at 562 days. In total, 32 primary endpoints were observed during the study period, and the incidence of primary endpoints tended to be greater in the protamine group than in the non-protamine group (P = 0.056). However, the lesion length, the degree of calcification, and the prevalence of hemodialysis were significantly determined greater in the protamine group than in the non-protamine group. In the multivariate Cox proportional hazards model, the use of protamine (versus non-protamine: hazard ratio 0.542 and 95% confidence interval 0.217-1.355, P = 0.191) was deemed not to be associated with the primary endpoint after controlling legion length, calcification, and hemodialysis. In conclusion, immediate protamine use following elective PCI did not increase mid-term ischemia-driven TVR or stent thrombosis. However, immediate protamine use after PCI should be discussed further for the safety of the patient.


Assuntos
Estenose Coronária/cirurgia , Antagonistas de Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Protaminas/uso terapêutico , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Casos e Controles , Estenose Coronária/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Heparina/efeitos adversos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/estatística & dados numéricos , Complicações Pós-Operatórias/induzido quimicamente , Hemorragia Pós-Operatória/induzido quimicamente , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Stents , Trombose/induzido quimicamente , Calcificação Vascular/epidemiologia
17.
Int Heart J ; 61(5): 888-895, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921675

RESUMO

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.


Assuntos
Angina Instável/epidemiologia , Creatina Quinase/sangue , Insuficiência Cardíaca/epidemiologia , Mortalidade , Infarto do Miocárdio/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angina Instável/cirurgia , Causas de Morte , Feminino , Humanos , Japão/epidemiologia , Masculino , Revascularização Miocárdica/estatística & dados numéricos , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Prognóstico , Modelos de Riscos Proporcionais
18.
PLoS Med ; 17(9): e1003307, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931494

RESUMO

BACKGROUND: Hypertension, together with obesity, is a leading cause of mortality and disability. Whilst metabolic surgery offers remission of several metabolic comorbidities, the effect for patients with hypertension remains controversial. The objective of the present study was to evaluate the effect of metabolic surgery on cardiovascular events and mortality on patients with morbid obesity (body mass index [BMI] ≥ 35 kg/m2) and hypertension. METHODS AND FINDINGS: We conducted a matched cohort study of 11,863 patients with morbid obesity and pharmacologically treated hypertension operated on with metabolic surgery and a matched non-operated-on control group of 26,199 subjects with hypertension (matched by age, sex, and area of residence) of varied matching ratios from 1:1 to 1:9, using data from the Scandinavian Obesity Surgery Register (SOReg), the Swedish National Patient Registers (NPR) for in-hospital and outpatient care, the Swedish Prescribed Drug Register, and Statistics Sweden. The main outcome was major adverse cardiovascular event (MACE), defined as first occurrence of acute coronary syndrome (ACS) event, cerebrovascular event, fatal cardiovascular event, or unattended sudden cardiac death. The mean age in the study group was 52.1 ± 7.46 years, with 65.8% being women (n = 7,810), and mean BMI was 41.9 ± 5.43 kg/m2. MACEs occurred in 379 operated-on patients (3.2%) and 1,125 subjects in the control group (4.5%). After adjustment for duration of hypertension, comorbidities, and education, a reduction in risk was seen in the metabolic surgery group (adjusted hazard ratio [HR] 0.73, 95% confidence intervals [CIs] 0.64-0.84, P < 0.001). The surgery group had lower risk for ACS events (adjusted HR 0.52, 95% CI 0.41-0.66, P < 0.001) and a tendency towards lower risk for cerebrovascular events (adjusted HR 0.81, 95% CI 0.63-1.01, P = 0.060) compared with controls. The main limitations with the study were the lack of information on BMI and history of smoking in the control group and the nonrandomised study design. CONCLUSION: Metabolic surgery on patients with morbid obesity and pharmacologically treated hypertension was associated with lower risk for MACEs and all-cause mortality compared with age- and sex-matched controls with hypertension from the general population.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Hipertensão/metabolismo , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/tendências , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Hipertensão/cirurgia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/mortalidade , Modelos de Riscos Proporcionais , Fatores de Risco , Suécia/epidemiologia
19.
PLoS Med ; 17(9): e1003331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941436

RESUMO

BACKGROUND: It is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality. METHODS AND FINDINGS: Our longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997-2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6-8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson's weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96-1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48-1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16-1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone. CONCLUSIONS: These findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.


Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea/psicologia , Idoso , Índice de Massa Corporal , Causas de Morte , Estudos de Coortes , Dieta Saudável , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Sobrepeso , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Suécia
20.
PLoS Med ; 17(9): e1003332, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960883

RESUMO

BACKGROUND: Whether a healthy lifestyle impacts longevity in the presence of multimorbidity is unclear. We investigated the associations between healthy lifestyle and life expectancy in people with and without multimorbidity. METHODS AND FINDINGS: A total of 480,940 middle-aged adults (median age of 58 years [range 38-73], 46% male, 95% white) were analysed in the UK Biobank; this longitudinal study collected data between 2006 and 2010, and participants were followed up until 2016. We extracted 36 chronic conditions and defined multimorbidity as 2 or more conditions. Four lifestyle factors, based on national guidelines, were used: leisure-time physical activity, smoking, diet, and alcohol consumption. A combined weighted score was developed and grouped participants into 4 categories: very unhealthy, unhealthy, healthy, and very healthy. Survival models were applied to predict life expectancy, adjusting for ethnicity, working status, deprivation, body mass index, and sedentary time. A total of 93,746 (19.5%) participants had multimorbidity. During a mean follow-up of 7 (range 2-9) years, 11,006 deaths occurred. At 45 years, in men with multimorbidity an unhealthy score was associated with a gain of 1.5 (95% confidence interval [CI] -0.3 to 3.3; P = 0.102) additional life years compared to very unhealthy score, though the association was not significant, whilst a healthy score was significantly associated with a gain of 4.5 (3.3 to 5.7; P < 0.001) life years and a very healthy score with 6.3 (5.0 to 7.7; P < 0.001) years. Corresponding estimates in women were 3.5 (95% CI 0.7 to 6.3; P = 0.016), 6.4 (4.8 to 7.9; P < 0.001), and 7.6 (6.0 to 9.2; P < 0.001) years. Results were consistent in those without multimorbidity and in several sensitivity analyses. For individual lifestyle factors, no current smoking was associated with the largest survival benefit. The main limitations were that we could not explore the consistency of our results using a more restrictive definition of multimorbidity including only cardiometabolic conditions, and participants were not representative of the UK as a whole. CONCLUSIONS: In this analysis of data from the UK Biobank, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others.


Assuntos
Estilo de Vida Saudável/fisiologia , Expectativa de Vida/tendências , Multimorbidade/tendências , Idoso , Bancos de Espécimes Biológicos , Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Causas de Morte , Doença Crônica/mortalidade , Estudos de Coortes , Dieta , Dieta Saudável , Feminino , Nível de Saúde , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Sobrepeso , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Reino Unido
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