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1.
Nat Commun ; 12(1): 1226, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619257

RESUMO

The goal of the National Cancer Institute's (NCI's) Genomic Data Commons (GDC) is to provide the cancer research community with a data repository of uniformly processed genomic and associated clinical data that enables data sharing and collaborative analysis in the support of precision medicine. The initial GDC dataset include genomic, epigenomic, proteomic, clinical and other data from the NCI TCGA and TARGET programs. Data production for the GDC started in June, 2015 using an OpenStack-based private cloud. By June of 2016, the GDC had analyzed more than 50,000 raw sequencing data inputs, as well as multiple other data types. Using the latest human genome reference build GRCh38, the GDC generated a variety of data types from aligned reads to somatic mutations, gene expression, miRNA expression, DNA methylation status, and copy number variation. In this paper, we describe the pipelines and workflows used to process and harmonize the data in the GDC. The generated data, as well as the original input files from TCGA and TARGET, are available for download and exploratory analysis at the GDC Data Portal and Legacy Archive ( https://gdc.cancer.gov/ ).


Assuntos
Análise de Dados , Bases de Dados Genéticas , Genômica , Sequência de Bases , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , Regulação da Expressão Gênica , Genoma Humano , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Mutação/genética , National Cancer Institute (U.S.) , RNA-Seq , Reprodutibilidade dos Testes , Estados Unidos , Vírus/genética
3.
Cancer Discov ; 11(3): 524, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33483379

RESUMO

The federal spending bill enacted by the U.S. Congress in December for fiscal year 2021 totals $1.4 trillion, plus another $900 billion in emergency COVID-19 relief funding. The $1.4 trillion includes budget increases for the NIH, NCI, and FDA that help the agencies keep pace with inflation. Research advocates say more than $10 billion in emergency supplemental funds for the NIH is urgently needed to support medical research affected by the COVID-19 pandemic.


Assuntos
Pesquisa Biomédica/legislação & jurisprudência , Governo Federal , Política de Saúde , Neoplasias/terapia , Apoio à Pesquisa como Assunto , Pesquisa Biomédica/economia , /economia , Humanos , Oncologia/organização & administração , National Cancer Institute (U.S.)/economia , National Institutes of Health (U.S.)/economia , Neoplasias/economia , Sociedades Médicas , Estados Unidos , United States Food and Drug Administration/economia
5.
Health Commun ; 36(1): 89-97, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33225770

RESUMO

Seeking cancer information is recognized as an important, life-saving behavior under normal circumstances. However, given the significant impact of COVID-19 on society, the healthcare system, and individuals and their families, it is important to understand how the pandemic has affected cancer information needs in a crisis context and, in turn, how public health agencies have responded to meeting the information needs of various audiences. Using data from the National Cancer Institute's Cancer Information Service (CIS) - a long-standing, multi-channel resource for trusted cancer information in English and Spanish - this descriptive analysis explored differences in cancer information-seeking among cancer survivors, caregivers, tobacco users, and members of the general public during the onset and continuation of the COVID-19 pandemic (February - September 2020), specifically comparing interactions that involved a discussion of COVID-19 to those that did not. During the study period, COVID-19 discussions were more likely to involve survivors or caregivers compared to tobacco users and the general public. Specific patterns emerged across the four user types and their respective discussions of COVID-19 related to language of service, point of CIS access, stage on the cancer continuum, subject of interaction, cancer site discussed, and referrals provided by the CIS. These results provide insights that may help public health agencies deliver, prioritize, and tailor their messaging and response to specific audiences based on heightened health information needs during a crisis.


Assuntos
/epidemiologia , Informação de Saúde ao Consumidor/estatística & dados numéricos , Comportamento de Busca de Informação , National Cancer Institute (U.S.)/estatística & dados numéricos , Neoplasias/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Cuidadores/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Idioma , Estadiamento de Neoplasias , Pandemias , Encaminhamento e Consulta/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Estados Unidos/epidemiologia
6.
J Chromatogr A ; 1635: 461767, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33310281

RESUMO

Asymmetric-flow field-flow fractionation (AF4) has been recognized as an invaluable tool for the characterisation of particle size, polydispersity, drug loading and stability of nanopharmaceuticals. However, the application of robust and high quality standard operating procedures (SOPs) is critical for accurate measurements, especially as these complex drug nanoformulations are most often inherently polydisperse. In this review we describe a unique international collaboration that lead to the development of a robust SOP for the measurement of physical-chemical properties of nanopharmaceuticals by multi-detector AF4 (MD-AF4) involving two state of the art infrastructures in the field of nanomedicine, the European Union Nanomedicine Characterization Laboratory (EUNCL) and the National Cancer Institute-Nanotechnology Characterisation Laboratory (NCI-NCL). We present examples of how MD-AF4 has been used for the analysis of key quality attributes, such as particle size, shape, drug loading and stability of complex nanomedicine formulations. The results highlight that MD-AF4 is a very versatile analytical technique to obtain critical information on a material particle size distribution, polydispersity and qualitative information on drug loading. The ability to conduct analysis in complex physiological matrices is an additional very important advantage of MD-AF4 over many other analytical techniques used in the field for stability studies. Overall, the joint NCI-NCL/EUNCL experience demonstrates the ability to implement a powerful and highly complex analytical technique such as MD-AF4 to the demanding quality standards set by the regulatory authorities for the pre-clinical safety characterization of nanomedicines.


Assuntos
Fracionamento por Campo e Fluxo , Nanomedicina/métodos , Tamanho da Partícula , Composição de Medicamentos/normas , União Europeia , Humanos , Laboratórios/normas , Nanomedicina/normas , Nanotecnologia , National Cancer Institute (U.S.) , Preparações Farmacêuticas/normas , Estados Unidos
7.
BMC Med Inform Decis Mak ; 20(Suppl 10): 273, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33319703

RESUMO

BACKGROUND: The National Cancer Institute (NCI) Thesaurus provides reference terminology for NCI and other systems. Previously, we proposed a hybrid prototype utilizing lexical features and role definitions of concepts in non-lattice subgraphs to identify missing IS-A relations in the NCI Thesaurus. However, no domain expert evaluation was provided in our previous work. In this paper, we further enhance the hybrid approach by leveraging a novel lexical feature-roots of noun chunks within concept names. Formal evaluation of our enhanced approach is also performed. METHOD: We first compute all the non-lattice subgraphs in the NCI Thesaurus. We model each concept using its role definitions, words and roots of noun chunks within its concept name and its ancestor's names. Then we perform subsumption testing for candidate concept pairs in the non-lattice subgraphs to automatically detect potentially missing IS-A relations. Domain experts evaluated the validity of these relations. RESULTS: We applied our approach to 19.08d version of the NCI Thesaurus. A total of 55 potentially missing IS-A relations were identified by our approach and reviewed by domain experts. 29 out of 55 were confirmed as valid by domain experts and have been incorporated in the newer versions of the NCI Thesaurus. 7 out of 55 further revealed incorrect existing IS-A relations in the NCI Thesaurus. CONCLUSIONS: The results showed that our hybrid approach by leveraging lexical features and role definitions is effective in identifying potentially missing IS-A relations in the NCI Thesaurus.


Assuntos
Vocabulário Controlado , Humanos , National Cancer Institute (U.S.) , Estados Unidos
8.
Rev. colomb. cancerol ; 24(3): 113-123, jul.-set. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1144330

RESUMO

Resumen Objetivo: Realizar la traducción y adaptación transcultural del componente de síntomas gastrointestinales (SGI) de la escala CTCAE versión 4.02 en pacientes ambulatorios tratados con quimioterapia en el Instituto Nacional de Cancerología en Bogotá. Métodos: Se realizó una búsqueda manual en medios electrónicos de escalas en idioma inglés o español que evaluarán la presencia, frecuencia o intensidad de SGI en pacientes oncológicos. La selección de los ítems fue efectuada por consenso informal de un comité técnico, el cual verificó la concordancia entre los principales SGI descritos en la literatura y los incluidos en la escala, ya que estos podrían afectar el estado nutricional. Posteriormente, para la adaptación transcultural, se siguieron los pasos y recomendaciones del manual ISPOR y del grupo de calidad de vida EORTC. La prueba piloto se efectuó en 30 pacientes seleccionados por conveniencia, quienes cumplieron los criterios de inclusión. Resultados: El 52% eran hombres; la edad promedio fue de 54,2 años (+/- 15,3 años). Los cánceres más frecuentes fueron: colorrectal (28%), estómago (16%) y mama (12%). Los 14 SGI incluidos en la escala fueron experimentados por todos los pacientes, por lo cual se conservaron, y no se requirió adicionar ningún otro. El tiempo promedio de aplicación del instrumento fue de 5 minutos y el 90% de los participantes lo consideró adecuado. Conclusiones: Se generó un instrumento de 14 ítems para medir SGI en pacientes oncológicos ambulatorios sometidos a quimioterapia, el cual es de rápida aplicación y utiliza lenguaje de fácil comprensión para el paciente. Aunque todavía quedan por definir sus propiedades clinimétricas.


Abstract Objective: To carry out the translation and transcultural adaptation of the gastrointestinal symptoms component (GIS) of the CTCAE, scale version 4.02, in outpatient patients treated with chemotherapy at the National Cancer Institute, Bogotá (Colombia). Methods: It was performed a manual search of scales on electronic media, in English or Spanish languages, which will evaluate the presence and intensity of GIS in oncological patients. The selection of the items was made by an informal consensus of a technical committee, which verified the concordance between the main GIS described in the literature and those included in the scale, all of which could affect the nutritional status. For transcultural adaptation, there were followed the steps and recommendations of the ISPOR Handbook, as well as those of the EORTC quality of life group. The pilot test was conducted in 30 patients selected for convenience, who met the inclusion criteria. Results: 52% were men; the average age was 54.2 years (+/-15.3 years). The most frequent cancers were: colorectal (28%), stomach (16%) and breast (12%). The 14 GIS included in the scale were experienced by all patients, so they were retained, and no other addition was required. The average time of application of the instrument was 5 minutes, and 90% of the participants considered it appropriate. Conclusions: A 14-item instrument was generated to measure GIS in cancer patients who undergo outpatient chemotherapy, which is of fast application and uses a language that is easily understood by patients. Its clinimetrics properties remain to be defined.


Assuntos
Humanos , Pacientes Ambulatoriais , Estômago , Neoplasias , Pacientes , Consenso , Compreensão , National Cancer Institute (U.S.) , Oncologia
9.
PLoS One ; 15(8): e0236021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745082

RESUMO

BACKGROUND: The National Lung Screening Trial (NLST) demonstrated that annual screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. Nonetheless, the leading cause of mortality in the study was from cardiovascular diseases. PURPOSE: To determine whether the used machine learning automatic algorithms assessing coronary calcium score (CCS), level of liver steatosis and emphysema percentage in the lungs are good predictors of cardiovascular disease (CVD) mortality and incidence when applied on low dose CT scans. MATERIALS AND METHODS: Three fully automated machine learning algorithms were used to assess CCS, level of liver steatosis and emphysema percentage in the lung. The algorithms were used on low-dose computed tomography scans acquired from 12,332 participants in NLST. RESULTS: In a multivariate analysis, association between the three algorithm scores and CVD mortality have shown an OR of 1.72 (p = 0.003), 2.62 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively, and an OR of 1.12 (p = 0.044) for level of liver steatosis. Similar results were shown for the incidence of CVD, OR of 1.96 (p < 0.0001), 4.94 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively. Also, emphysema percentage demonstrated an OR of 0.89 (p < 0.0001). Similar results are shown for univariate analyses of the algorithms. CONCLUSION: The three automated machine learning algorithms could help physicians to assess the incidence and risk of CVD mortality in this specific population. Application of these algorithms to existing LDCT scans can provide valuable health care information and assist in future research.


Assuntos
Doenças Cardiovasculares/mortalidade , Aprendizado de Máquina , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Ensaios Clínicos Fase III como Assunto , Vasos Coronários/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Enfisema/diagnóstico , Enfisema/epidemiologia , Enfisema/etiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia
10.
Clin Cancer Res ; 26(16): 4198-4200, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32503806

RESUMO

The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat (1). Patients with cancer are one of the most vulnerable populations. During this pandemic, clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine, and decrease required data collection. Going forward, the oncology research community must use the lessons learned to focus on redesigning studies to ensure that critical scientific questions are answered safely while expanding access and increasing partnerships with community physicians. These changes will accelerate clinical progress while protecting our patients.


Assuntos
Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Oncologia/tendências , Neoplasias/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Controle de Infecções/normas , Oncologia/normas , National Cancer Institute (U.S.)/normas , National Cancer Institute (U.S.)/tendências , Segurança do Paciente/normas , Seleção de Pacientes , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Projetos de Pesquisa/normas , Projetos de Pesquisa/tendências , Telemedicina/normas , Telemedicina/tendências , Estados Unidos/epidemiologia
13.
J Med Internet Res ; 22(5): e16299, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32406865

RESUMO

BACKGROUND: Multiple types of mobile health (mHealth) technologies are available, such as smartphone health apps, fitness trackers, and digital medical devices. However, despite their availability, some individuals do not own, do not realize they own, or own but do not use these technologies. Others may use mHealth devices, but their use varies in tracking health, behaviors, and goals. Examining patterns of mHealth use at the population level can advance our understanding of technology use for health and behavioral tracking. Moreover, investigating sociodemographic and health-related correlates of these patterns can provide direction to researchers about how to target mHealth interventions for diverse audiences. OBJECTIVE: The aim of this study was to identify patterns of mHealth use for health and behavioral tracking in the US adult population and to characterize the population according to those patterns. METHODS: We combined data from the 2017 and 2018 National Cancer Institute Health Information National Trends Survey (N=6789) to characterize respondents according to 5 mutually exclusive reported patterns of mHealth use for health and behavioral tracking: (1) mHealth nonowners and nonusers report not owning or using devices to track health, behaviors, or goals; (2) supertrackers track health or behaviors and goals using a smartphone or tablet plus other devices (eg, Fitbit); (3) app trackers use only a smartphone or tablet; (4) device trackers use only nonsmartphone or nontablet devices and do not track goals; and (5) nontrackers report having smartphone or tablet health apps but do not track health, behaviors, or goals. RESULTS: Being in the mHealth nonowners and nonusers category (vs all mHealth owners and users) is associated with males, older age, lower income, and not being a health information seeker. Among mHealth owners and users, characteristics of device trackers and supertrackers were most distinctive. Compared with supertrackers, device trackers have higher odds of being male (odds ratio [OR] 2.22, 95% CI 1.55-3.19), older age (vs 18-34 years; 50-64 years: OR 2.83, 95% CI 1.52-5.30; 65+ years: OR 6.28, 95% CI 3.35-11.79), have an annual household income of US $20,000 to US $49,999 (vs US $75,000+: OR 2.31, 95% CI 1.36-3.91), and have a chronic condition (OR 1.69, 95% CI 1.14-2.49). Device trackers also have higher odds of not being health information seekers than supertrackers (OR 2.98, 95% CI 1.66-5.33). CONCLUSIONS: Findings revealed distinctive sociodemographic and health-related characteristics of the population by pattern of mHealth use, with notable contrasts between those who do and do not use devices to track goals. Several characteristics of individuals who track health or behaviors but not goals (device trackers) are similar to those of mHealth nonowners and nonusers. Our results suggest patterns of mHealth use may inform how to target mHealth interventions to enhance reach and facilitate healthy behaviors.


Assuntos
Comportamentos Relacionados com a Saúde/fisiologia , Neoplasias/epidemiologia , Telemedicina/estatística & dados numéricos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis/estatística & dados numéricos , National Cancer Institute (U.S.) , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
16.
Cancer Discov ; 10(6): 756, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32332087

RESUMO

As the COVID-19 pandemic stretches on, investigators are becoming increasingly concerned about longer-term effects on grants and funding for cancer research. Institutions and philanthropic organizations are especially likely to be hit hard by the economic crisis, with effects that will be particularly acute for early-career investigators.


Assuntos
Betacoronavirus , Pesquisa Biomédica/economia , Infecções por Coronavirus , Neoplasias , Pandemias , Pneumonia Viral , Infecções por Coronavirus/epidemiologia , Obtenção de Fundos , Humanos , National Cancer Institute (U.S.)/economia , Pneumonia Viral/epidemiologia , Pesquisadores , Apoio à Pesquisa como Assunto , Estados Unidos , Universidades/economia
17.
Adv Cancer Res ; 146: 219-226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32241390

RESUMO

National Cancer Institute (NCI) designated cancer centers are charged with reducing disparities, improving cancer-related health outcomes, and increasing clinical trial participation for the catchment area population. Succeeding in this endeavor requires a clear definition of each cancer center's geographic catchment area as well as the demographic characteristics of the populations residing in the catchment area. For this reason, the definition of the catchment area is now a required element of NCI grant applications. This primer provides detailed information related to the definition of cancer centers' catchment areas and provides a case example from the University of Texas MD Anderson Cancer Center to highlight best practice strategies for compiling and interpreting cancer health statistics for the catchment area.


Assuntos
Pesquisa Biomédica/normas , Área Programática de Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/terapia , Participação do Paciente/estatística & dados numéricos , Pesquisa Biomédica/organização & administração , Humanos , National Cancer Institute (U.S.) , Estados Unidos
18.
Radiat Res ; 193(5): 425-434, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32216707

RESUMO

While radiosensitizing chemotherapy has improved survival for several types of cancer, current chemoradiation regimens remain ineffective for many patients and have substantial toxicities. Given the strong need for the development of novel radiosensitizers to further improve patient outcomes, the Radiation Research Program (RRP) and the Small Business Innovation Research (SBIR) in the National Cancer Institute (NCI) issued a Request for Proposals (RFP) through the NCI SBIR Development Center's contracts pathway. We sought to determine the research outcomes for the NCI SBIR Development Center's funded proposals for the development of radiosensitizers. We identified SBIR-funded contracts and grants for the development of radiosensitizers from 2009 to 2018 using the National Institutes of Health (NIH) Reporter database. Research outcomes of the NCI SBIR Development Center-funded proposals were determined using a comprehensive internet search. We searched PubMed, clinicaltrials.gov, company websites and google.com for research articles, abstracts and posters, clinical trials, press releases and other news, related to progress in the development of funded radiosensitizers. To protect the intellectual property of the investigators and small businesses, all information obtained and reported is publicly available. The SBIR Program has funded four contracts and 11 grants for the development of novel radiosensitizers. Two companies have received phase IIb bridge awards. Overall, 50% of companies (6/12) have successfully advanced their investigational drugs into prospective clinical trials in cancer patients, and all but one company are investigating their drug in combination with radiation therapy as described in the NCI SBIR Development Center proposal. To date, only one company has initiated a randomized trial of standard of care with or without their radiosensitizer. In conclusion, the NCI SBIR Development Center has funded the development of novel radiosensitizers leading to clinical trials of novel drugs in combination with radiation therapy. Continued follow-up is needed to determine if any of these novel radiosensitizers produce improved tumor control and/or overall survival.


Assuntos
Descoberta de Drogas/métodos , National Cancer Institute (U.S.) , Radiossensibilizantes , Pesquisa , Empresa de Pequeno Porte , Estados Unidos
19.
Eur J Cancer ; 129: 15-22, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114365

RESUMO

AIM: In 1999, a cooperative tripartite cancer research and training agreement was signed between Ireland (IE), Northern Ireland (NI) and the United States (US) National Cancer Institute, giving rise to the All-Ireland Cancer Consortium (AICC). We wished to consider if AICC increased the amount/impact of cancer research on the island of Ireland and what effect this enhanced research activity had on cancer services and cancer outcomes. METHODS: As comparator, we chose the city regions of Copenhagen and Lund & Malmö, whose physical connection was greatly improved following construction of bridges between Denmark and Sweden around the time AICC was established. We analysed cancer research outputs from all four geographical regions in the Web of Science (1988-2017), with a particular focus on citations and journal impact factors. We evaluated disability-adjusted life years (DALYs) as an indicator of change in health status. RESULTS: Research outputs increased in all four regions, but more in IE/NI than in the Scandinavian cities, while collaboration between IE and NI and both the US and the Rest of Europe increased even more substantially. Citation scores also showed a greater improvement for IE and NI. Journal citation impact factors indicated that IE/NI papers were increasingly being published in more highly cited journals. Research-enabled cancer service provision improved on the island of Ireland, with concomitant increases in cancer survival. CONCLUSION: The AICC collaborative agreement delivered significant additionality on the island of Ireland, promoting transnational cooperation, enhancing cancer research activity, and underpinning improved cancer services and better cancer outcomes.


Assuntos
Pesquisa Biomédica/organização & administração , Efeitos Psicossociais da Doença , Cooperação Internacional , Oncologia/organização & administração , Neoplasias/epidemiologia , Pesquisa Biomédica/estatística & dados numéricos , Dinamarca/epidemiologia , Nível de Saúde , Humanos , Incidência , Irlanda/epidemiologia , Fator de Impacto de Revistas , Oncologia/estatística & dados numéricos , National Cancer Institute (U.S.)/organização & administração , Neoplasias/diagnóstico , Neoplasias/terapia , Irlanda do Norte/epidemiologia , Editoração/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Suécia/epidemiologia , Estados Unidos
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