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1.
J Clin Lipidol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38908969

RESUMO

BACKGROUND: Current guidelines recommend the reporting of incidental CAC on non-EKG-gated CT scans of the chest. The finding of incidental moderate or severe CAC on non-cardiac non-contrast chest CT correlates with a CAC score ≥ 100 Agatston units, a guideline-based indication for a clinician-patient discussion regarding the initiation of statin therapy. In contemporary practice, whether the presence and severity of incidental CAC are routinely reported on such CT scans of the chest is unknown. METHODS: At a major university hospital, we collected a one-month convenience sample of 297 patients who had chest CT imaging for indications other than lung cancer screening (OICT) and 42 patients who underwent lung cancer chest CT screening (LSCT). We evaluated reporting patterns of incidental CAC in the body and impression of the reports as compared to the overreading of such studies by a board-certified CT chest radiologist. We hypothesized and demonstrated that there was underreporting of incidental CAC on these scans. We then undertook an initiative to educate reporting radiologists on the importance of reporting CAC and implemented a reporting template change to encourage routine reporting. Then we repeated another one-month sample (n= 363 for the OICT and n= 63 for the LSCT groups) to evaluate reporting patterns following our intervention. RESULTS: The presence of incidental moderate and severe CAC was systematically underreported in the OICT group (0 and 4.8 %) and the severity was never mentioned in the impression of reports. In the LSCT group, the presence of incidental moderate and severe CAC was also underreported (66.7 % and 75 %) and the severity of CAC was mentioned 50 % of the time in the impression of the reports. Following the initiation of an educational program and radiology reporting template change, there was a significant increase in reporting of moderate or severe CAC in the OICT group (0 vs. 80.0 %, p < 0.001) and (4.8 vs. 93.5 %, p < 0.001) respectively and a significant increase in the reporting of the severity of incidental CAC for those with severe CAC in the LSCT group (50 vs. 94.1 %, p=0.006). CONCLUSION: Despite guideline recommendations, Incidental CAC was underreported at a large academic center. We implemented a system that significantly improved reporting patterns of incidental CAC. Failure to report incidental CAC represents a missed opportunity to initiate preventive therapies. Hospital systems interested in improving the quality of their radiology reporting procedures should examine their practices to assure that CAC quantification is routinely performed.

2.
J Am Coll Cardiol ; 79(8): 819-836, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35210038

RESUMO

There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a) that are useful in understanding an individual's long-term ASCVD risk. The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, that have potential clinical utility, but whose best use remains uncertain. Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood.


Assuntos
Aterosclerose/diagnóstico , Aterosclerose/terapia , Fatores de Risco de Doenças Cardíacas , Aterosclerose/epidemiologia , Humanos , Fatores de Risco , Adulto Jovem
3.
J Am Coll Cardiol ; 78(16): 1573-1583, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34649694

RESUMO

BACKGROUND: There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis. OBJECTIVES: The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile. METHODS: We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors. RESULTS: Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors. CONCLUSIONS: Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Modelos Cardiovasculares , Medição de Risco , Calcificação Vascular/diagnóstico por imagem , Adulto , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
4.
Mayo Clin Proc ; 95(8): 1740-1749, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32646743

RESUMO

Allocation of statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in borderline- and intermediate-risk patients has traditionally been based on population-based global risk assessment and other clinical and laboratory characteristics. Patient-specific treatment decisions are needed to provide maximal benefit and avoid unnecessary treatment. Guideline-based lipid management proposes that coronary artery calcium scoring is reasonable to implement in patients with a 10-year risk of 5.0% to 19.9% (borderline to intermediate risk) by using the pooled cohort equations when the decision about whether to initiate statin therapy is uncertain. We report data from both observational studies and a large primary prevention randomized controlled trial that support the position that this decision is, in fact, uncertain in about half of such patients because of risk misclassification. Such misclassification can be largely avoided by more widespread implementation of coronary calcium scoring, which helps to identify those with coronary artery calcium scores of 0, a finding associated with a less than 5.0% 10-year probability of an ASCVD event. Deferral of statin therapy in such patients, in the absence of smoking, diabetes, or a family history of premature ASCVD, provides more individualized and appropriate care and avoids the expense and potential adverse effects of statin therapy in those with low potential for absolute risk reduction. A rationale is also provided for the importance of coronary artery calcium scoring in women 50 years and older, possibly in place of 1 screening mammogram in women at least 55 years of age to avoid incremental radiation exposure, on the basis of the substantially higher lifetime risk of morbidity and mortality from ASCVD than from breast cancer. In patients with borderline or intermediate ASCVD risk, coronary artery calcium scoring should be used, whenever possible, as an aid to rational statin allocation for the primary prevention of ASCVD.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária/métodos , Adulto , Idoso , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Tomada de Decisão Compartilhada , Feminino , Custos de Cuidados de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prevenção Primária/economia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Calcificação Vascular/diagnóstico
5.
J Clin Lipidol ; 14(4): 414-418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32505727

RESUMO

A classic finding in patients with familial hypercholesterolemia is the presence of markedly elevated levels of total and low-density lipoprotein cholesterol (LDL-C) with an LDL-C concentration of 190 mg/dL or greater. However, severe hypercholesterolemia is not inevitably present, and many patients who carry this diagnosis may have lower LDL-C levels. This case history describes a young woman whose mother and brother met clinical and genetic criteria for heterozygous familial hypercholesterolemia, but who had only a mild elevation in LDL-C, falling to <130 mg/dL after dietary intervention. Despite this finding, genetic testing revealed the presence of the same genetic variants as were noted in her mother and brother. In addition, a second genetic variant predisposing them to cholesterol gallstone formation was identified in all three family members. If genetic testing had not been performed, the diagnosis may have been missed or delayed, resulting in an increased risk for the vascular complications associated with familial hypercholesterolemia. This case supports the value of genetic testing of family members of those with familial hypercholesterolemia, even when LDL-C levels are not severely elevated.


Assuntos
Colesterol/sangue , Hiperlipoproteinemia Tipo II/sangue , Adulto , Feminino , Testes Genéticos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Linhagem
6.
J Clin Lipidol ; 13(3): 345-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31229021

RESUMO

In this NLA Roundtable four members of the writing committee join the Editor to discuss the process of developing the AHA/ACC/Multisociety Cholesterol Guidelines, which were unveiled in November 2018. They also provide personal insights on the finished product. Highlights include 1) the committee's decision to summarize 10 take-home messages providing rapid communication of key points, 2) emphasis on clinician -patient discussion, which may bring up issues specific to women or other population groups at risk, 3) personalizing risk with risk-enhancing factors such as LDL-C ≥ 160 mg/dl, metabolic syndrome, chronic kidney disease, pre-eclampsia, premature menopause, high risk ethnicity, inflammatory diseases, hypertriglyceridemia and in selected cases, Lp(a), hs-CRP and apoB; 4) using coronary artery calcium scoring when a risk decision is uncertain in intermediate risk patients 5) monitoring for goals of moderate or intensive LDL cholesterol reduction, 6) thresholds for adding nonstatin LDL-lowering therapy in those at very high risk or for heterozygous familial hypercholesterolemia and 7) cost value assessment for expensive treatment.


Assuntos
Colesterol/metabolismo , Guias como Assunto , Sociedades Médicas , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/metabolismo , Fatores de Risco
7.
J Am Coll Cardiol ; 70(14): 1785-1822, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-28886926

RESUMO

In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided.


Assuntos
Anticolesterolemiantes/farmacologia , Cardiologia/métodos , Doença da Artéria Coronariana/prevenção & controle , Ezetimiba/farmacologia , Hipercolesterolemia/tratamento farmacológico , Conduta do Tratamento Medicamentoso/organização & administração , Quimioprevenção/métodos , LDL-Colesterol/análise , Consenso , Inibidores Enzimáticos/farmacologia , Humanos , Hipercolesterolemia/diagnóstico , Sequestrantes/farmacologia , Estados Unidos
8.
J Clin Lipidol ; 10(1): 15-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26892119

RESUMO

Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1.


Assuntos
Cirurgia Bariátrica , Metabolismo dos Lipídeos , Obesidade/metabolismo , Obesidade/cirurgia , Sociedades Médicas , Tecido Adiposo/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Hormônios Gastrointestinais/metabolismo , Microbioma Gastrointestinal , Humanos , Obesidade/microbiologia , Obesidade/patologia , Estados Unidos
9.
J Clin Lipidol ; 10(1): 33-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26892120

RESUMO

Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1.


Assuntos
Cirurgia Bariátrica , Metabolismo dos Lipídeos , Obesidade/metabolismo , Obesidade/cirurgia , Sociedades Médicas , Tecido Adiposo/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Transporte Biológico , Colesterol/metabolismo , Sistema Endócrino/fisiopatologia , Microbioma Gastrointestinal , Humanos , Lipídeos/biossíntese , Obesidade/microbiologia , Obesidade/patologia , Estados Unidos
10.
J Clin Lipidol ; 9(2): 129-69, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25911072

RESUMO

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.


Assuntos
Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Apolipoproteínas B/sangue , Aterosclerose/sangue , Aterosclerose/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , LDL-Colesterol/sangue , Gerenciamento Clínico , Dislipidemias/sangue , Dislipidemias/patologia , Órgãos Governamentais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco
11.
AIDS ; 28(7): 969-77, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24691204

RESUMO

OBJECTIVE: To use multimodality imaging to explore the relationship of biomarkers of inflammation, T-cell activation and monocyte activation with coronary calcification and subclinical vascular disease in a population of HIV-infected patients on antiretroviral therapy (ART). DESIGN: Cross-sectional. METHODS: A panel of soluble and cellular biomarkers of inflammation and immune activation was measured in 147 HIV-infected adults on ART with HIV RNA less than 1000 copies/ml and low-density lipoprotein cholesterol (LDL-C) 130  mg/dl or less. We examined the relationship of biomarkers to coronary calcium (CAC) score and multiple ultrasound measures of subclinical vascular disease. RESULTS: Overall, median (interquartile range, IQR) age was 46 (40-53) years; three-quarters of participants were male and two-thirds African-American. Median 10-year Framingham risk score was 6%. Participants with CAC more than 0 were older, less likely to be African-American and had higher current and lower nadir CD4 T-cell counts. Most biomarkers were similar between those with and without CAC; however, soluble CD14 was independently associated with CAC after adjustment for traditional risk factors. Among those with a CAC score of zero, T-cell activation and systemic inflammation correlated with carotid intima-media thickness and brachial hyperemic velocity, respectively. Compared with normal participants and those with CAC only, participants with increasing degrees of subclinical vascular disease had higher levels of sCD14, hs-CRP and fibrinogen (all P<0.05). CONCLUSION: Soluble CD14 is independently associated with coronary artery calcification, and, among those with detectable calcium, predicts the extent of subclinical disease in other vascular beds. Future studies should investigate the utility of multimodality imaging to characterize vascular disease phenotypes in this population.


Assuntos
Calcinose , Doença das Coronárias/epidemiologia , Vasos Coronários/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Receptores de Lipopolissacarídeos/sangue , Adolescente , Adulto , Doenças Assintomáticas/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
J Digit Imaging ; 25(1): 129-36, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21557030

RESUMO

Cardiovascular disease is the leading cause of global mortality, yet its early detection remains a vexing problem of modern medicine. Although the computed tomography (CT) calcium score predicts cardiovascular risk, relatively high cost ($250-400) and radiation dose (1-3 mSv) limit its universal utility as a screening tool. Dual-energy digital subtraction radiography (DE; <$60, 0.07 mSv) enables detection of calcified structures with high sensitivity. In this pilot study, we examined DE radiography's ability to quantify coronary artery calcification (CAC). We identified 25 patients who underwent non-contrast CT and DE chest imaging performed within 12 months using documented CAC as the major inclusion criteria. A DE calcium score was developed based on pixel intensity multiplied by the area of the calcified plaque. DE scores were plotted against CT scores. Subsequently, a validation cohort of 14 additional patients was independently evaluated to confirm the accuracy and precision of CAC quantification, yielding a total of 39 subjects. Among all subjects (n = 39), the DE score demonstrated a correlation coefficient of 0.87 (p < 0.0001) when compared with the CT score. For the 13 patients with CT scores of <400, the correlation coefficient was -0.26. For the 26 patients with CT scores of ≥400, the correlation coefficient yielded 0.86. This pilot study demonstrates the feasibility of DE radiography to identify patients at the highest cardiovascular risk. DE radiography's accuracy at lower scores remains unclear. Further evaluation of DE radiography as an inexpensive and low-radiation imaging tool to diagnose cardiovascular disease appears warranted.


Assuntos
Angiografia Digital/métodos , Calcinose/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos de Casos e Controles , Angiografia Coronária/métodos , Doença da Artéria Coronariana/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não Paramétricas
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