AULA 1 – 08/02/2011

no dt T1 (Sandra)

1 8/02 Apresentação disciplinaIntrodução Epidemiologia AnalíticaExercic individual

2 15/02 COORTE

3 22/02 PUBMED

4 1/03 ARTIGO

5 15/03 SOBREVIDA

6 22/03 ARTIGO

7 29/03 CASO-CONTROLE

8 5/04 ARTIGO

9 12/04 REVISÃO 1

10 19/04 PROVA 1

11 26/04 ECR

12 3/05 ARTIGO

13 10/05 METANÁLISE

14 17/05 ARTIGO

15 24/05 DIAGNOSTICO

16 31/05 APRESENTAÇÃO ARTIGOS

17 7/06 APRESENTAÇÃO ARTIGOS

18 14/06 APRESENTAÇÃO ARTIGOS

19 21/06 REVISÃO 2

20 21/06 Prova

22 05/07 V.S.

Epidemiologia analíticaAVALIAÇÃO DA DISCIPLINA

• São 20 encontros (13 temáticos, 3 apresentações de artigos, 2 aulas de revisão e 2 provas). A reprovação por falta se dará se houver mais de 4 faltas.

• A avaliação da disciplina será a média aritmética de quatro notas:

• A cada aula haverá dois exercícios individuais, um feito em casa e outro feito em aula. Será computada a média dos dois e calculada a média geral dos 13 encontros temáticos.

• Apresentação de artigos por grupos de 8 a 9 alunos.• Prova 1 • Prova 2

Epidemiologia Analítica

• Qual a relação da epidemiologia analítica (epi3) com a Bioestatística (epi 1) e a Epidemiologia Descritiva (epi 2)?

• Qual a aplicação na prática médica?

• Qual a relação com a construção e aquisição do conhecimento científico?

Relacionando ......

De onde vem esta afirmativa?

Lendo o resumo

• Vyas H, Field D, Milner AD, Hopkin IE. Determinants of the first inspiratory volume and functional residual capacity at birth.Pediatr Pulmonol. 1986;2(4):189-93.

• • We have investigated the pattern of pressure and volume changes that occur in vaginally

delivered, full-term infants during the onset of spontaneous respiration. Within a few seconds of delivery of the head, simultaneous measurements were made of stomach and esophageal pressure changes together with volume changes determined at the mouth. Values obtained for volume were very similar, but pressure changes were of a greater magnitude than previously reported. A significant correlation has been shown between first inspiratory volume and functional residual capacity (FRC) at the end of the first breath (p less than 0.004). No significant relationship was found between first inspiratory pressure and FRC. However, using a calculated index of inspiratory pressure and time ("inspiratory effort"), a significant relationship of this to FRC was observed (p less than 0.02).

Relacionando...

Relacionando ......

De onde vem esta afirmativa?

• The successful transition from intrauterine to extrauterine life is dependent upon significant physiologic changes that occur at birth. In almost all infants (90 percent), these changes are successfully completed at delivery without requiring any special assistance. However, about 10 percent of infants will need some intervention, and 1 percent will require extensive resuscitative measures at birth [1].

Lendo as referências bibliográficas...

Que fonte é esta?

APGAR

Escore de Apgar

Pinheiro JM.The Apgar cycle: a new view of a familiar scoring system. Arch Dis Child Fetal Neonatal Ed. 2009;94(1):F70-2.

American Academy of Pediatrics; The Apgar score. Adv Neonatal Care. 2006;6(4):220-3.

Cuidados com o recém-nascido

Cuidados com o recém-nascido

De onde vem esta afirmativa?• Mullany LC, Darmstadt GL, Khatry SK, Katz J, LeClerq SC, Shrestha S, Adhikari R, Tielsch

JM• Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and

neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet. 2006;367(9514):910-8.

• BACKGROUND: Omphalitis contributes to neonatal morbidity and mortality in developing countries. Umbilical cord cleansing with antiseptics might reduce infection and mortality risk, but has not been rigorously investigated. METHODS: In our community-based, cluster-randomised trial, 413 communities in Sarlahi, Nepal, were randomly assigned to one of three cord-care regimens. 4934 infants were assigned to 4.0% chlorhexidine, 5107 to cleansing with soap and water, and 5082 to dry cord care. In intervention clusters, the newborn cord was cleansed in the home on days 1-4, 6, 8, and 10. In all clusters, the cord was examined for signs of infection (pus, redness, or swelling) on these visits and in follow-up visits on days 12, 14, 21, and 28. Incidence of omphalitis was defined under three sign-based algorithms, with increasing severity. Infant vital status was recorded for 28 completed days. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. Analysis was by intention-to-treat. This trial is registered with , number NCT00109616. FINDINGS: Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group. Severe omphalitis in chlorhexidine clusters was reduced by 75% (incidence rate ratio 0.25, 95% CI 0.12-0.53; 13 infections/4839 neonatal periods) compared with dry cord-care clusters (52/4930). Neonatal mortality was 24% lower in the chlorhexidine group (relative risk 0.76 [95% CI 0.55-1.04]) than in the dry cord care group. In infants enrolled within the first 24 h, mortality was significantly reduced by 34% in the chlorhexidine group (0.66 [0.46-0.95]). Soap and water did not reduce infection or mortality risk. INTERPRETATION: Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality.

Principais conclusões: relacionado epi1, epi2 e epi3

Cuidado com o RN: uso de vitamina K na sala de parto – de onde vem esta afirmativa?

Lendo a referência

Puckett RM, Offringa M.Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev. 2000;(4):CD002776.

BACKGROUND: Vitamin K deficiency can cause bleeding in an infant in the first weeks of life. This is known as Hemorrhagic Disease of the Newborn (HDN). HDN is divided into three categories: early, classic and late HDN. Early HDN occurs within 24 hours post partum and falls outside the scope of this review. Classic HDN occurs on days one to seven; common bleeding sites are gastrointestinal, cutaneous, nasal and from a circumcision. Late HDN occurs from week 2-12; the most common bleeding sites are intracranial, cutaneous, and gastrointestinal. Vitamin K is commonly given prophylactically after birth for the prevention of HDN, but the preferred route is uncertain.

OBJECTIVES: To review the evidence from randomized trials in order to determine the effectiveness of vitamin K prophylaxis in the prevention of classic and late HDN. Main questions are: Is one dose of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN? Is there a significant difference between the oral route and the intramuscular route in preventing classic and late HDN? Are multiple oral doses of vitamin K, given after birth, able to significantly reduce the incidence of classic and late HDN?

SELECTION CRITERIA: All trials using random or quasi-random patient allocation, in which methods of vitamin K prophylaxis in infants were compared to each other, placebo or no treatment, were included.

DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author and were analysed with the standard methods of the Cochrane Collaboration and its Neonatal Review Group, using relative risk, risk difference and weighted mean difference.

MAIN RESULTS: Two eligible randomized trials, each comparing a single dose of intramuscular vitamin K with placebo or nothing, assessed effect on clinical bleeding. One dose of vitamin K reduced clinical bleeding at 1-7 days, including bleeding after circumcision, and improved biochemical indices of coagulation status. Eleven additional eligible randomized trials compared either a single oral dose of vitamin K with placebo or nothing, a single oral with a single intramuscular dose of vitamin K, or three oral doses with a single intramuscular dose. None of these trials assessed clinical bleeding. Oral vitamin K improved biochemical indices of coagulation status at 1-7 days. There was no evidence of a difference between the oral and intramuscular route in effects on biochemical indices of coagulation status. A single oral compared with a single intramuscular dose resulted in lower plasma vitamin K levels at two weeks and one month, whereas a 3-dose oral schedule resulted in higher plasma vitamin K levels at two weeks and at two months than did a single intramuscular dose.

• REVIEWER'S CONCLUSIONS: A single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN.

Que fonte é esta?

Construção do conhecimento científico

• Descrição dos fenômenos - Epidemiologia descritiva – frequências, características de eventos (biomédicos, clínicos, sociais)

• Epidemiologia analítica: buscando associações entre eventos

• Bioestatística: ferramenta para mensurar e avaliar probabilidades dos resultados encontrados

Como selecionar as melhores referências?

• Definindo a questão clínica

• Tipos de desenho epidemiológico

• Conceitos de causalidade

• Conceitos de evidência científica

Definindo a questão clínica Tópico Questão clínicaFrequência (cap 4)* Com que frequência a doença ocorre? Risco (cap 5 e 6) Quais os fatores associados à ocorrência da doença?

Qual a força desta associação?

Prognóstico (cap 7) Quais os fatores associados à evolução da doença?

Causalidade (cap 11) Posso garantir que os fatores associados são causais?

Tratamento (cap 8) A intervenção altera o curso da doença?

Qual a eficácia do tratamento?Prevenção (cap 9) A intervenção evita a ocorrência de doença?

Qual a eficácia da prevenção? Anormalidade/Diagnóstico (cap 3) O paciente tem ou não a doença?

Qual a acurácia do teste diagnóstico usado? Síntese da evidência (cap 12) Como identificar a melhor evidência sobre as

questões acima?

Qual a qualidade da evidência?

Como selecionar as melhores referências?

• Definindo a questão clínica

• Tipos de desenho epidemiológico

• Conceitos de causalidade

• Conceitos de evidência científica

Tipos de desenho epidemiológico

Posição do investigador Referência temporal

Denominações correntes

Observacional Transversal Inquérito, seccional

Longitudinal

Coorte

Caso-controle

Intervenção Longitudinal

Estudo experimental, ensaio clínico

Ensaio comunitário

Desenhos de estudoTransversal

Fator(exposição)

Doença(desfecho)

tempo

observador

Alanis MC, Goodnight WH, Hill EG, Robinson CJ, Villers MS, Johnson DD. Maternal super-obesity (body mass index > or = 50) and adverse

pregnancy outcomes. Acta Obstet Gynecol Scand. 2010;89(7):924-30.

• OBJECTIVE: To determine if pregnancy complications are increased in super-obese (a body mass index (BMI) of 50 or more) compared to other, less obese parturients.

• DESIGN: Cross-sectional study.• SETTING AND POPULATION: All 19,700 eligible women, including 425 (2.2%) super-obese women

with singleton births between 1996 and 2007 delivering at a tertiary referral center, identified using a perinatal research database.

• METHODS: Bivariate and trend analyses were used to assess the relation between super-obesity and various pregnancy complications compared to other well-established BMI categories. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression techniques.

• MAIN OUTCOME MEASURES: Outcomes for adjusted and unadjusted analyses were small-for-gestational age (SGA) birth, large-for-gestational age (LGA) birth, preeclampsia, gestational diabetes mellitus (GDM), fetal death, preterm birth, placental abruption, cesarean delivery, and Apgar scores < 7.

• RESULTS: Compared to all other obese and non-obese women, super-obese women had the highest rates of preeclampsia, GDM, LGA, and cesarean delivery (all p < 0.05 for trend test). Super-obesity was also associated with a 44% reduction in SGA compared to all other women (OR 0.55, 95% confidence interval (CI) 0.40- 0.76) and a 25% reduction compared to other, less obese women (OR 0.75, 95% CI 0.54-1.03). Super-obesity was positively associated with LGA, GDM, preeclampsia, cesarean delivery, and a 5-minute Apgar score < 7 compared to all other women after controlling for important confounders.

Desenhos de estudoCoorte

Fator/Terapia(exposição)

Doença/Cura(desfecho)

tempo

observador

Observacionais: coorte e sobrevidaExperimental: ensaio clínico randomizado

Tatishvili N, Gabunia M, Laliani N, Tatishvili S. Epidemiology of neurodevelopmental disorders in 2 years old Georgian children. Pilot study - population based

prospective study in a randomly chosen sample. Eur J Paediatr Neurol. 2010;14(3):247-52.

• Three hundred-forty-eight out of a regional population of 1272 newborn infants were randomly chosen and followed neurologically until age of two years to study the epidemiology of neurodevelopmental disorders, and to reveal the main factors influencing outcome. At the age of 24 months abnormal development was identified in 29 cases (8.5%) of children, comprising global developmental delay in five (1.5%), unclassified motor problems (hypotonia without ataxia) in four (1.2%), cerebral palsy in three (0.9%), behavioral/sleep disorders in 12 (3.5%) and epilepsy in five (1.5%). The most significant single risk factors for abnormal neurodevelopmental outcome were maternal age, chorioamnionitis, gestational age <37 weeks, pathological delivery, and a low (<5) Apgar score at 5min after birth. Coexistence of several risk factors increased the probability of an adverse outcome.

Estudo de coorte

Luna EJ, Moraes JC, Silveira L, Salinas HS. [Efficacy and safety of the Brazilian vaccine against hepatitis B in newborns].

Rev Saude Publica. 2009;43(6):1014-20.

• OBJECTIVE: To analyze the efficacy and safety of a recombinant Hepatitis B vaccine in newborns.

• METHODS: The study was carried out in a general hospital in the city of Guarulhos, Southeastern Brazil, between 2002 and 2005. The recombinant Hepatitis B vaccine from Instituto Butantan (VrHB-IB) was tested in two clinical trials. In both trials, newborns were randomly allocated to the experimental or control (reference vaccine) groups. Newborns were given three doses of vaccine, one up to 24 hours after birth and the other two 30 and 180 days later. In the first trial, 538 newborns completed the immunization protocol, and 486 in the second. Vaccines were considered equivalent when seroprotection difference was below 5%.

• RESULTS: Seroprotection in the first trial (anti-HBs > or = 10mUI/ml) was 92.5% (247/267) in the experimental group, compared to 98.5% (267/271) in the control (p = 0.001). With this result, VrHB-IB did not fulfill the pre-established criterion for equivalence. After increasing the concentration of antigen in the vaccine to 25 microg, seroprotection reached 100% in the experimental group and 99.2% in the control. No severe adverse effects were recorded.

• CONCLUSIONS: The reformulated VrHB-IB is considered equivalent to the reference vaccine, and its use is recommended in newborns.

Ensaio clínico randomizado

Desenhos de estudoCaso-Controle

Fator(exposição)

Doença(desfecho)

tempo

observador

Vukojević M, Soldo I, Granić D. Risk factors associated with

cerebral palsy in newborns. Coll Antropol. 2009;33 Suppl 2:199-201.• The aim of this study was to investigate the risk factors associated with cerebral

palsy (CP). For this purpose, a total of 55 newborns were investigated in the case control design study, with a total of 55 additional newborns that were matched to the cases. All patients were recruited in University Clinical Hospital Mostar and other institutions in the region between 1997-2005. The comparison of the Apgar score did not seem to show significant differences between cases and controls (odds ratio [OR] = 1.15, 95% confidence intervals [CI] 0.36-3.69). Hypoxia was more common in the CP group (36.3% vs. 5.4% in the control group; p < 0.001). Additionally, cases were more frequently exposed to the infections (p < 0.001), intracranial hemorrhage (p = 0.002), premature delivery, before the 28th gestation week ( p = 0.027), as well as the premature delivery during the 28-34 gestation week ( p = 0.001), and 34-38 gestation week ( p = 0.018). Accordingly, small birth weight was associated with cases more often than controls (p = 0.003). Bleeding during pregnancy was also more common in cases than controls (p = 0.032), while the breech presentation, emergency cesarean section, hydrocephalus, placenta disorders and pre-eclampsia were not associated with CP. The results suggest that CP cases were more commonly exposed to numerous risks, which all seem to contribute to the increased chances of PF. Traditional indicator, poor Apgar score was not found to be significantly associated with the CP.

Definindo a melhor evidência

• Conceitos de validade interna

• Conceitos de causalidade

• Tipo do desenho

• Diferentes propostas para classificar evidência