Curso Medicina Baseada em Evidências

1. Abordagem da Literatura Médica
Universidade de Caxias do Sul
Prof. Petrônio Fagundes de Oliveira Fº
petronioliveira@gmail.com

2. ABORDAGEM DA LITERATURA
MÉDICA

3. Epidemiologia Clínica
Introdução
• Encontrar a melhor resposta para uma questão
clínica é quase como encontrar uma agulha no
palheiro.
• As informações essenciais estão misturadas com
uma grande quantidade de informações não
confiáveis.
• Desafio: separar o joio do trigo!
• GESTÃO DO CONHECIMENTO

4. Epidemiologia Clínica

5. Epidemiologia Clínica
Qual a informação confiável?

6. Epidemiologia Clínica
DVD I
N
T
E
R CD
N
E
T

7. Epidemiologia Clínica
• Embora o objetivo de leitura de publicações
científicas possa ser resumido à necessidade
de uma constante atualização, entender
como a literatura pode ser abordada é
fundamental.

8. Epidemiologia Clínica
• Três tipos de abordagens são possíveis:
1) Leitura de vigilância
2) Revisão exaustiva de um tema
3) Busca de solução para um problema específico

9. Epidemiologia Clínica
Leitura de Vigilância
• Serve para:
– Satisfazer a curiosidade científica
do médico acerca das novidades
– Adquirir uma cultura biomédica
geral mais ampla e atualizada
• Trata-se de uma leitura “corrida” dos
artigos e revistas.
― Triagem de artigos que serão lidos depois com mais
atenção.
― Triagem de artigos que serão lidos depois com mais
atenção
• É uma leitura menos comprometida.

10. Epidemiologia Clínica
Revisão exaustiva do tema
• A revisão exaustiva é muito mais dirigida.
• Geralmente, foca apenas um assunto e deve
abranger, esgotar toda a literatura científica relativa
a ele que possa ser encontrada.
• Ela é finita e concentrada no tempo.
• Em geral, direciona-se mais para objetivos de
caráter acadêmico.
– Monografias, dissertações, teses
– Livros

11. Epidemiologia Clínica
Busca de solução para um problema específico
• É abordagem que mais interessa à maioria dos
profissionais, pois resulta diretamente do
exercício profissional.
• Decorre dos questionamentos, dúvidas,
problemas e doenças trazidos pelos pacientes.
• A leitura deve ser atenta e cuidadosa, pois
destina-se a fundamentar cientificamente a
solução de um problema clínico.
• É a forma mais comum de
aprendizado contínuo - MBE

12. Epidemiologia Clínica
Fontes de informação bibliográfica
• Existem diversas formas de publicações:
• Artigos científicos originais
• Revisões da literatura
• Meta-análises
• Capítulos de livros
• Livros
Artigos Originais têm
maior probabilidade
de trazer novidades

13. Epidemiologia Clínica
• Os artigos originais são atraentes, mas
requerem mais atenção e cuidado.
• A maioria das novidades não trazem implicações
imediatas para a prática profissional.
• As revisões, as metanálises e os livros, em
geral, são bastante seguros, mas padecem
do fato de chegarem à publicação vários
anos após os artigos que lhe deram origem.
• Entretanto, devemos nos lembrar que este
envelhecimento pode representar amadurecimento com
conclusões mais sólidas.

14. O que ler?
Como ler?
ARTIGOS ORIGINAIS

15. Epidemiologia Clínica
O que ler?
• De um modo geral deve-se ler as novidades
com o objetivo de completar ou atualizar o
que o médico deve saber sobre os quatros
aspectos básicos da sua atuação profissional:

16. Epidemiologia Clínica
• O que há de novo quanto a etiologia (ou
fatores causais e de risco) de uma doença?
• Qual a validade do que há de novo nos
procedimentos diagnósticos (clínicos ou
laboratoriais) de uma doença?
• Quais as vantagens , os benefícios e os riscos de
um determinado tratamento, novo ou não?
• Quais os atuais perspectivas de evolução e de
prognóstico de um determinado paciente?

17. Epidemiologia Clínica
Como ler?
• A estratégia adequada implica em cinco
etapas bem definidas:
1) O que é preciso ler?
2) Qual a melhor evidência?
3) O que vale a pena ler?
4) Análise da qualidade do material selecionado
para a leitura.
5) Identificação das conclusões que têm
repercussão na prática médica.

18. Epidemiologia Clínica
1. O que é preciso ler?
• Saber previamente que informação se busca.
• Jamais fazer uma busca a esmo.
• Antes de iniciar a seleção das leituras é
necessário uma definição do tema a ser
abordado e quais as perguntas para as quais se
busca resposta.
• As questões devem ser colocadas por escrito, de
forma clara, delimitada, bem definida.

19. Epidemiologia Clínica
Exemplo
Origem da busca Tema e Pergunta de busca
• Lactentes sibilantes
cujos pais têm asma
– Tema de interesse
• Asma Brônquica
– Pergunta a ser
respondida
• Qual risco de asma em
lactentes sibilantes cujos
pais são asmáticos?

20. Epidemiologia Clínica
P Lactentes sibilantes filhos de pais asmáticos
I
C
O Asma no futuro

21. Epidemiologia Clínica
2. Qual a melhor evidência?
• Pesquisa, por exemplo,
no PubMed
• Ferramenta de pesquisa
gratuíta mantida pela
National Library of
Medicine, National
Institutes of Health
• Pode ser acessada no
endereço:
http://www.ncbi.nlm.nih.gov/PubMed/

22. Epidemiologia Clínica
Medline
• Selecionar termos do índice • Combinar os termos,
eletrônico, ou thesaurus. usando operadores
Thesaurus é constituído de lógicos:
MeSH (Medical Subject • OR, AND, WITH , NEAR
Headings). • NOT– elimina as palavras
• Pensar nos sinônimos digitas depois do NOT.
possíveis e nos termos • ( ) – parênteses são
relacionados que possam empregados para agrupar
ser utilizados. Podem ser partes da sintaxe, com o
usados os termos do MeSH objetivo de realizar
ou palavras textuais; pesquisas mais complexas

23. Epidemiologia Clínica
• Na busca, usa-se a língua • No exemplo anterior:
inglesa, evitando as • Buscar com a seguinte
palavras: about, the, of, a, frase : “Risco de asma em
in, as, if, why, never, lactentes sibilantes” ou,
before, is e it, pois os em inglês, “Risk of
mecanismos de busca as asthma in young children
ignoram. with recurrent wheezing”.
Desta frase, retiram-se as
palavras-chave: asthma
risk, recurrent wheezing e
young children. Busca-se
individualmente e depois
se combinam as buscas.

24. Epidemiologia Clínica
Para maiores informações:

25. Epidemiologia Clínica
3. O que vale a pena ler?
• A partir das questões definidas na primeira etapa
temos que selecionar o que vale a pena ler;
• Artigos cuja qualidade vale a pena avaliar,
investindo mais tempo na busca das
respostas.
• Analisar com cuidado na busca da resposta mais
válida que satisfaça a necessidade do paciente
que gerou a pergunta de partida.

26. Epidemiologia Clínica
No exemplo:
• Na busca, digitando a palavra asthma risk na janela de
busca do PubMed, limitado aos últimos 10 anos,
encontrou-se, em 01/04/2012, 10275 títulos.

27. Epidemiologia Clínica
No exemplo:
• Acrescentando outro limite relacionado às crianças menores
de dois anos de idade e utilizando a outra palavra-chave
recurrent wheezing encontrou-se em torno de 111 títulos.

28. Epidemiologia Clínica
Pediatr Pulmonol. 2010 Feb;45(2):149-56.
Prevalence and risk factors of wheeze in Dutch infants in their first year of life.
Visser CA, Garcia-Marcos L, Eggink J, Brand PL.
Source
Princess Amalia Children's Clinic, Isala Klinieken, Zwolle, the Netherlands.
Abstract
Factors operating in the first year of life are critical in determining the onset and persistence of wheezing in
preschool children. This study was designed to examine the prevalence and risk factors of wheeze in the first
year of life in Dutch infants. This was a population-based survey of 13-month-old infants visiting well baby
clinics for a scheduled immunization. Parents/caregivers completed a standardized validated questionnaire on
respiratory symptoms in the first year of life and putative risk factors. The independent influence of these
factors for wheeze was assessed by multiple logistic regression analysis. A total of 1,115 questionnaires were
completed. Wheeze ever (with a prevalence in the first year of life of 28.5%) was independently associated with
male gender, eczema, sibs with asthma, any allergic disease in the family, day care, damp housing, and
asphyxia. Recurrent wheeze (prevalence 14.5%) showed independent associations with eczema, sibs with
asthma, and day care. In addition to these factors, severe wheeze (prevalence 15.4%) was also associated with
premature rupture of membranes during birth, and with damp housing. Wheeze is common during the first
year of life, and places a major burden on families and the health care system. Factors associated with wheeze
are mainly related to markers of atopic susceptibility, and to exposure to infections. The strongest modifiable
risk factor for wheeze in the first year of life is home dampness. Interventions to reduce home dampness to
reduce wheeze in infancy should be examined.
(c) 2010 Wiley-Liss, Inc.

29. Epidemiologia Clínica
Allergol Immunopathol (Madr). 2007 Nov-Dec;35(6):228-31.
Risk factors of developing asthma in children with recurrent wheezing in the first
three years of life.
Cortés Alvarez N, Martín Mateos MA, Plaza Martín AM, Giner Muñoz MT, Piquer M, Sierra Martínez JI.
Source
Paediatric Allergy and Clinical Inmunology Section. Sant Joan de Déu Hospital-Clínic Hospital. University of
Barcelona. Spain. 33891nca@comb.es
Abstract
INTRODUCTION: Recurrent wheezing is a common problem during the first years of life, but it is still difficult to
identify which of these children may develop asthma in the future.
OBJECTIVES: To study risk factors of developing asthma in a group of patients with frequent wheezing during
the first three years of life.
MATERIAL AND METHODS: A prospective study was performed of a group of 60 patients, aged below three,
referred to our Hospital for recurrent wheezing. Age, sex, parental and personal history of atopy, clinical
features, laboratory tests, evolution and response to treatment were analyzed.
RESULTS: 60 patients were enrolled in study. Most of children were boys and have had the first episode of
wheezing after the 6 months of life. 63 % had personal history of atopy and 55 % parental history of allergy. The
group of atopic children had more wheezing exacerbations and worse evolution than the group of non atopic.
They also had more treatment necessities.
CONCLUSIONS: The identification of young children at high risk of developing asthma could permit an early
intervention before irreversible changes in the airway appeared.

30. Epidemiologia Clínica
J Pediatr. 2007 Oct;151(4):347-51, 351.e1-2. Epub 2007 Jul 12.
Breast-feeding duration and infant atopic manifestations, by maternal allergic
status, in the first 2 years of life (KOALA study).
Snijders BE, Thijs C, Dagnelie PC, Stelma FF, Mommers M, Kummeling I, Penders J, van Ree R, van den Brandt PA
.
Source Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.
BEP.Snijders@EPID.unimaas.nl
Abstract
OBJECTIVE: To investigate the potential effect of modification by maternal allergic status on the relationship
between breast-feeding duration and infant atopic manifestations in the first 2 years of life.
STUDY DESIGN: Data from 2705 infants of the KOALA Birth Cohort Study (The Netherlands) were analyzed. The
data were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months
postpartum. Total and specific immunoglobulin E measurements were performed on venous blood samples
collected during home visits at age 2 years. Relationships were analyzed using logistic regression analyses.
RESULTS: Longer duration of breast-feeding was associated with a lower risk for eczema in infants of mothers
without allergy or asthma (P(trend) = .01) and slightly lower risk in those of mothers with allergy but no asthma
(P(trend) = .14). There was no such association for asthmatic mothers (P(trend) = .87). Longer breast-feeding
duration decreased the risk of recurrent wheeze independent of maternal allergy (P(trend) = .02) or asthma
status (P(trend) = .06).
CONCLUSIONS:
Our findings show that the relationship between breast-feeding and infant eczema in the first 2 years of life is
modified by maternal allergic status. The protective effect of breast-feeding on recurrent wheeze may be
associated with protection against respiratory infections.

31. Epidemiologia Clínica
Pediatrics. 2006 Jun;117(6):e1132-8.
Recurrent wheeze in early childhood and asthma among children at risk for atopy.
Ly NP, Gold DR, Weiss ST, Celedón JC.
Source Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
OBJECTIVES: Little is known about the natural history of wheezing disorders among children at risk for atopy. We
examined the relation between early wheeze and asthma at 7 years of age among children with parental history of
asthma or allergies followed from birth.
METHODS: Information on wheeze was collected bimonthly from birth to age 24 months and every 6 months thereafter.
Recurrent early wheeze was defined as > or =2 reports of wheezing in the first 3 years of life. Frequent early wheeze was
defined as > or =2 reports of wheezing per year in the first 3 years of life. At 7 years of age, asthma was defined as
physician-diagnosed asthma and wheezing in the previous year.
RESULTS: Of the 440 participating children, 223 (50.7%) had > or =1 report of wheeze before 3 years old, 111 (26.0%)
had recurrent early wheeze, and 12 (2.7%) had frequent early wheeze. Whereas only 31 (13.9%) of 223 children with >
or =1 report of wheeze developed asthma at 7 years of age, 24 (21.6%) of 111 children with recurrent early wheeze
developed asthma at 7 years of age. Among the 12 children with frequent early wheeze, 6 (50%) had asthma at 7 years
of age. After adjustment for other covariates, recurrent early wheeze in children at risk for atopy was associated with a
fourfold increase in the odds of asthma at 7 years of age, and frequent early wheeze was associated with an
approximately 12-fold increase in the odds of asthma at 7 years of age. Most (94%) of the children without frequent
early wheeze did not develop asthma at 7 years of age.
CONCLUSIONS: The absence of recurrent early wheeze indicates a very low risk of asthma at school age among children
with parental history of asthma or allergies. Early identification of children who will develop asthma at school age is
difficult, even in children at risk for atopy. However, children with parental history of asthma or allergies who have
frequent early wheeze, in particular, are at greatly increased risk of asthma and merit close clinical follow-up..

32. Epidemiologia Clínica
Chest. 2005 Feb;127(2):502-8.
Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness
at 10 years of age.
Arshad SH, Kurukulaaratchy RJ, Fenn M, Matthews S.
Source Department of Respiratory Medicine, University Hospital of North Staffordshire
STUDY OBJECTIVES: We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma,
and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these
conditions.
RESULTS: Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08;
95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR, 2.12; 95% CI 1.29 to 3.51), recurrent chest
infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76),
eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95%
CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal
asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest
infections at 1 year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to 8.18),
atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at 1 year of age (OR, 1.99; 95% CI,
1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95%
CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant.
CONCLUSIONS: Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and
recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age.
BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom
expression may differ from those predisposing the patient to BHR.

33. Epidemiologia Clínica
Pediatrics. 2004 Feb;113(2):345-50.
Does environment mediate earlier onset of the persistent childhood asthma
phenotype?
Kurukulaaratchy RJ, Matthews S, Arshad SH.
Source The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK.
OBJECTIVE: We investigated the role of environmental and hereditary factors in determining whether persistent
childhood wheezing phenotypes had an early or late onset.
METHODS: In a whole population birth cohort (n = 1456), children were seen at birth and at 1, 2, 4, and 10 years. At each
visit, information was collected prospectively regarding wheeze prevalence and used to classify subjects into wheezing
phenotypes. Information on genetic and environmental risk factors in early life was also obtained prospectively, and
skin-prick testing to common allergens was performed at 4 years.
RESULTS: Early-onset persistent wheezers (n = 125) had wheeze onset in the first 4 years, still present at age 10, whereas
late-onset persistent wheezers (n = 81) had wheeze onset after age 4 years that was still present at 10 years.
Multivariate logistic regression analysis identified independent significance only for inherited factors (parental asthma,
family history of rhinitis, eczema at 4 years, and atopic status at 4 years) in the development of late-onset persistent
wheeze. However, low social class at birth, recurrent chest infections at 2 years, and parental smoking at 2 years plus
inherited factors (eczema at 2 years; food allergy at 4 years; maternal asthma, sibling asthma, maternal urticaria, and
atopic status at 4 years) demonstrated independent significance for early-onset persistent wheeze.
CONCLUSION: Inheritance seems to be of prime significance in the cause of persistent childhood wheeze. Environmental
exposure in early life may combine with this tendency to produce an early onset of persistent wheeze. Absence of these
environmental factors might delay but not prevent the onset of wheeze in children with atopic heredity.

34. Epidemiologia Clínica
Eur Respir J. 2003 Nov;22(5):767-71.
Predicting persistent disease among children who wheeze during early life.
Kurukulaaratchy RJ, Matthews S, Holgate ST, Arshad SH.
Source
The David Hide Asthma & Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK.
Abstract
This study sought to determine factors influencing the persistence of early life wheezing up to the age of 10 yrs
and to create a score identifying those with the highest risk of persistent disease. Children were seen at birth, 1,
2, 4 and 10 yrs in a whole population birth cohort study (n=1,456). Information was collected prospectively on
wheeze prevalence and subjects were classified into wheezing phenotypes. Early life genetic and environmental
risk factors were recorded and skin-prick testing (SPT) was performed at 4 yrs. Independently significant factors
for persisting wheeze were identified at logistic regression and used to create a score for persistence. Wheezing
persistence from the first 4 yrs to the age of 10 yrs occurred in 37% of early life wheezers. Independent
significance for persistence was associated with asthmatic family history, atopic SPT at 4 yrs and recurrent chest
infections at 2 yrs, whilst recurrent nasal symptoms at 1 yr conferred reduced risk. A cumulative risk score using
these factors identified wheezing persistence in 83% scoring 4 and transience in 80% scoring 0. Thus, a
combination of genetic predisposition, early life atopy and recurrent chest infections favours the persistence of
early life wheezing. Risk scores using such knowledge could provide prognostic guidance on the outcome of
early wheeze.

35. Epidemiologia Clínica
Artigo importante anterior à busca
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1403-6.
A clinical index to define risk of asthma in young children with recurrent wheezing.
Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD.
Source
Respiratory Sciences Center, University of Arizona, College of Medicine, Tucson, Arizona, USA.
Abstract
Because most cases of asthma begin during the first years of life, identification of young children at high risk of
developing the disease is an important public health priority. We used data from the Tucson Children's
Respiratory Study to develop two indices for the prediction of asthma. A stringent index included frequent
wheezing during the first 3 yr of life and either one major risk factor (parental history of asthma or eczema) or
two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). A loose index
required any wheezing during the first 3 yr of life plus the same combination of risk factors described
previously. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma
between ages 6 and 13 than children with a negative loose index. Risk of having subsequent asthma increased
to 4.3 to 9.8 times when a stringent index was used. We found that 59% of children with a positive loose index
and 76% of those with a positive stringent index had active asthma in at least one survey during the school
years. Over 95% of children with a negative stringent index never had active asthma between ages 6 and 13. We
conclude that the subsequent development of asthma can be predicted with reasonable accuracy using simple,
clinically based parameters.

36. Epidemiologia Clínica
4.Análise da qualidade do material selecionado
• Para analisar a literatura científica é
necessário:
– Ter objetivos bem claros
– Ter temas e perguntas bem definidos e
– Saber a que se destinam as publicações
selecionadas
– Saber analisar a metodologia e conhecer os
níveis de evidência científica

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• Todos os artigos têm algum grau de evidência
científica, mas nem sempre ela é totalmente
confiável.
• A força e a qualidade das evidências estão
relacionadas ao tipo de delineamento de estudo.

38. Epidemiologia Clínica
• Analisando a pesquisa encontraram-se apenas artigos
relevantes, provenientes, na sua maioria de estudos de
coorte.
• Atualmente, as várias organizações de saúde (OMS,
American College of Physicians, UptToDate, Cochrane
Collaboation), utilizam o Sistema GRADE (Grading of
Recommendations, Assessment, Development and
Evaluation) para emitir recomendações (BMJ
2008;336:924 ).
• Sistema GRADE: Uma proposta que combina a força da
recomendação e qualidade da evidência para orientar
quais condutas devem ser adotadas ou evitadas na
prática clínica.

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40. Epidemiologia Clínica
5. Identificação das conclusões que têm
repercussão na prática médica
• Aplicação dos resultados à duvida gerada pelo
atendimento do paciente.
• Baseado nas informações encontradas poder-se-ia
dizer, respondendo a angustia da mãe que existe,
nas condições da pergunta, risco maior do seu filho
vir a apresentar asma no futuro, com razoável nível
de evidência científica.

41. Epidemiologia Clínica
Melhoramos?