實證醫學 病例討論報告
Evidence-Based Medicine
日期：2010.10.21
職級：實習醫學生Clerk 1
姓名：林佳霓、丁瑋甄、江家瑋、陳威任、
郭哲宏姚祺宇
Outline
Clinical scenario-臨床場景(無)
Asking-提出問題
Acquire- 搜尋資料
Appraisal-嚴格評讀
Apply-臨床應用(無)
Audit-自我評估
Asking-提出臨床問題
1.Background questions
(1)question
(2)answer
(3)apply
2.Foreground questions
(1)PICO
(2)search data
a. Summary
b. Synopses
c. Synthesis
Asking (提出臨床問題）
提出 background questions
Background question
Q1:What is the anatomy of fetal
membranes?
Q2:What is premature rupture of
membrances(PROM)?
Q3:What is the causes of PROM?
Q4:What is the risks of PROM?
Q5:How to approach?
Q1:What is the anatomy of fetal
membranes?
Amnion chorion
Layers of amnion chorion
Q2:What is premature rupture of
membrances(PROM)?
 Premature rupture of the membranes refers to
rupture of the fetal membranes (ie, amniorrhexis)
prior to the onset of labor or regular uterine
contractions.
 Once the membranes rupture, labor usually starts
within 12 to 24 hours. If labor doesn't begin
during this period, the situation is called
premature rupture of membranes (PROM).
 It can occur at term or prior to term, in which case
it is designated preterm premature rupture of the
membranes (PPROM).
Epidemiology
Pre-labour rupture of the membranes occurs in
6-19% of term pregnancies
Pre-term PROM in 2% of all pregnancies.
Presentation
Mother may give history of a 'popping
sensation' or a 'gush' with continuous watery
liquid draining thereafter. Their underwear or
pad may be damp.
Q3:What is the causes of PROM?
Infections of the uterus
Multiple births-(twins, triplets, etc)
In-competent cervix
Premature separation of the placenta
(placental abruption)
cord prolapse
malpresentation
Excess amniotic fluid (polyhydramnios)
Smoking
Certain procedures
Q4:What is the complicaions of
PROM?
 Subsequent studies have shown that risk
increases as time from rupture increases.
 chorioamnionitis and endometritis(higher
after12~16 hours)
 postpartum hemorrhage (higher after 8 hours)
 neonatal sepsis : the rate of neonatal sepsis
was 0.3 percent at 0 to 6 hours, 0.5 percent at 6
to 18 hours, 0.8 percent at 18 to 24 hours, and
1.1 percent after 24 hours
 fetal distress, fetal restriction deformities and
pulmonary hypoplasia, and fetal/neonatal
death.
Q5:How to approach?
 The initial evaluation of all pregnancies in which
PROM is suspected should include confirmation
of membrane rupture, confirmation of gestational
age, and assessment of fetal well-being.
 The diagnosis of PROM is based upon a
characteristic history (ie, leaking fluid per
vagina), physical examination (ie, visualization
of fluid flowing from the cervical os),
supplemented by laboratory tests in cases of
diagnostic uncertainty.
 Do not do a vaginal inspection as this will
increase the risk of ascending infection!
We suggest prompt delivery for women
with term or near term PROM. Labor is
induced, unless there are contraindications
to labor or vaginal delivery, in which case
cesarean delivery is performed.
Foreground Questions
Do doctors need to prescribe prophylactic
antibiotics when premature rupture of the
membrane(PROM) happens?
What is the prognosis to the newborn in
comparison with the mother?
PICO
P
I
C
O
PROM(premature rupture of
membrane)
Prophylaxis antibiotics
No prophylaxis
The rate of maternal and fetal
infection and the prognosis
Acquire-搜尋最有用的資料
先從已經過評讀的database開始找起
system->summaries-> synopses
->synthesesstudy
The "5S" levels of organisation of evidence from healthcare research
Brian Haynes, R Evid Based Med 2006;11:162-164
UpToDate
DynaMed
ACP PIER
BMJ Clinical Evidence
ACP journal club
Evidencebasedmedicine.com
Cochrane Library
BMJ Evidence Updates
Other Systemic reviews eg.
PubMed systemic reivew
PubMed
SUMsearch
TRIP
Google
Copyright ©2006 BMJ Publishing Group Ltd.
Detabase: Cochrane
Level:1a
Background
 Pre-term, pre-labour rupture of membranes
(pPROM) occur when
the amniotic sac ruptures before 37 weeks of
gestation (pre-term)
prior to the onset of labour (pre-labour)
 pPROM is associated with
about one-third of pre-term deliveries in high-income
countries
increased rates of neonatal and maternal infection.
Background
 Infection may be a cause of or result from
pPROM.
 Empiric antibiotic therapy following pPROM has
been demonstrated in high-income countries to
increase the time period between pPROM and
delivery
reduce the risks of maternal and neonatal infection.
 We reasoned that empiric antibiotic therapy
following pPROM may be an efficacious
intervention in low and middle income countries
(LMICs) as well.
Background
 the data support the use of antibiotics in pPROM
but counsel against the use of co-amoxiclav.
as this was associated with increased risk of neonatal
necrotizing enterocolitis.
Methods
 Searches
 We reviewed the 22 trials included in the
Cochrane review and abstracted data on the
outcomes of neonatal mortality, and the
incidence of severe morbidity relating to preterm delivery or infection:
necrotizing enterocolitis
intra-ventricular haemorrhage
respiratory distress syndrome (RDS)
confirmed sepsis.
Results
Results
Results
Results
Results
Results
Results
Results
 Studies in low and middle-income countries
 One trial in Mozambique - both the risk of death
(RR＝0.47) and risk of sepsis (RR＝0.17)
appeared lower in the treated arm.
 A trial in a middle-income setting (Turkey) - both
the risk of death (RR＝0.80) and the risk of
sepsis (RR＝0.43) appeared lower in the treated
arm.
 the trial in Chile - RDS (RR＝0.32), intraventricular haemorrhage (RR＝0.43) and early
onset sepsis (RR＝0.34) were all, less common
in the intervention arm.
Results
 The risks of a positive blood culture (9% vs
30%), RDS (25% vs 44%), necrotizing
enterocolitis (3% vs 11%) and intra-ventricular
haemorrhage (7% vs 12%) were all lower in
babies born to mothers who had received
antibiotics.
Discussion
 There is high-quality evidence that antibiotics for
pPROM reduce the risk of complications due to
prematurity and risk of neonatal infection in highincome settings. The evidence for a reduction in
neonatal mortality is less strong.
Discussion
 However, there is a dearth of data from lowincome countries, where newborns have less
access to other forms of care.
 In the absence of these other interventions, the
use of antibiotics for pPROM will certainly
prevent neonatal deaths by preventing RDS.
 Similarly, the prevention of sepsis cases through
the use of antibiotics for pPROM will certainly
prevent infection deaths.
Discussion
 There is evidence (P＝0.01) of a reduction in the
incidence of RDS (estimated reduction 12%,
95% CI 3–20%) with larger reductions in intraventricular haemorrhage (33%, 95% CI 8–51%,
P＝0.01) and necrotizing enterocolitis (24%,
95% CI 5–44%, P＝0.09).
Discussion
 RDS is the most common complication and has
the smallest effect estimate, so we propose that
antibiotics for pPROM can reduce deaths due to
complications of prematurity by 12% among
newborns born following pPROM.
 About one-third of pre-term deliveries are
associated with pPROM, so we propose an
affected fraction of 33% of all pre-term deaths.
 Thus, we estimate that increasing coverage with
antibiotics for pPROM might prevent 4% of all
pre-term deaths.
Discussion
 Our analysis suggests a 39% reduction in
incidence of neonatal sepsis with antibiotic
therapy for pPROM among newborns born
following pPROM.
 the proportion of pre-term births with pPROM
(assumed to be one-third).
 Thus, antibiotics for pPROM might reduce
sepsis deaths by about 8% overall (i.e. 39%
reduction among 20% of deaths).
Discussion
 Most data have been reassuring, with no
increased adverse sequelae following empiric
antibiotic therapy for pPROM.
 The ORACLE I trial, the single largest reported,
of nearly 5000 women with pPROM randomized
to either placebo or one of several antibiotic
regimens found neither increases in immediate
neonatal adverse sequelae related to antibiotics
nor differences in neurodevelopmental outcome
at 7 years of age.
Discussion
 However, in a related concurrent trial, empiric
antibiotic therapy for pre-term labour, without
rupture of membranes, was associated with an
increased risk of
neonatal necrotizing enterocolitis (associated with coamoxiclav)
subsequent neurodevelopmental functional
impairment (associated with erythromycin)
without any significant prolongation in pregnancy or
improvement in other neonatal comorbidities.
 The reasons for increases in neonatal morbidity
following antibiotic therapy in pre-term labour
remain speculative.
Conclusion
 we propose that, amongst births complicated by
pPROM, empiric antibiotic therapy could reduce
deaths due to complications of prematurity by
12% and deaths due to sepsis by 39%.
 Taking account of the proportion of births
affected by pPROM and the proportion of sepsis
deaths that may occur in pre-term babies in lowincome settings, these effects translate into a
4% reduction in all deaths due to complications
of prematurity and an 8% reduction in all deaths
due to neonatal sepsis.
Antibiotics for prelabour rupture
of membranes at or near term
Flenady V, King J.
Centre for Clinical Studies-Women's and Children's Health, Women's and Children's
Health Service, Mater Hospital, Raymond Tce, South Brisbane, Queensland,
Australia. vflenady@mater.org.au
Database：Cochrane
Level：1a
BACKGROUND:
Prelabour rupture of the membranes at or
near term (term PROM) increases the risk
of infection for the woman and her baby.
The routine use of antibiotics for women at
the time of term PROM may reduce this
risk.
bacterial resistance and the risk of
maternal anaphylaxis with antibiotic use
OBJECTIVES
To assess the effects of antibiotics
administered prophylactically to women
with prelabour rupture of the membranes
at 36 weeks or beyond, on maternal, fetal
and neonatal outcomes.
Methods
SELECTION CRITERIA
All randomised trials which compared
outcomes for women and infants when
antibiotics were administered
prophylactically for prelabour rupture of
the membranes at or near term, with
outcomes for controls (placebo or no
treatment)
Types of participants
Women with spontaneous rupture of the
fetal membranes prior to the onset of
regular uterine contractions at gestational
age 36
weeks or beyond
Types of interventions
Any antibiotics, administered as
prophylaxis, by any route, to women at
gestational age 36 weeks or beyond, with
prelabour rupture
of the membranes.
Types of outcome measures
Maternal outcomes:
















suspected or proven chorioamnionitis
endometritis;
caesarean section;
operative delivery;
internal fetal monitoring;
epidural analgesia;
post partum haemorrhage;
post partum pyrexia;
post partum septicaemia;
wound infection;
adverse drug reactions;
post partum antibiotic usage;
breastfeeding on discharge from hospital;
length of hospital stay;
fetal death;
fetal death unrelated to congenital abnormality.
Types of outcome measures
Neonatal outcomes:
 neonatal early onset sepsis (definite and probable);
 neonatal sepsis (definite and probable);
 neonatal meningitis;
 neonatal pneumonia;
 Apgar score < 7 at five minutes;
 admission to neonatal special care nursery;
 admission to neonatal intensive care nursery;
 use of antibiotics;
 use of mechanical ventilation;
 length of hospital stay;
 neonatal death;
 neonatal death unrelated to congenital abnormality;
 perinatal mortality;
 perinatal mortality unrelated to congenital abnormality
SEARCH STRATEGY
Cochrane Pregnancy and Childbirth
Group's specialised register of controlled
trials (October 2001),
the Cochrane Controlled Trials Register
(The Cochrane Library, Issue 4, 2001),
MEDLINE (1965 to 2001).
experts and cross referencing relevant
material
DATA COLLECTION AND
ANALYSIS
Meta-analysis
using relative risk (RR), risk difference (RD)
and number needed to treat (NNT) (where
appropriate) for categorical data, and
mean difference (MD) for variables
measured on a continuous scale.
All results are presented with 95%
confidence intervals (CI).
RESULT
two trials, 838 women
The use of antibiotics resulted in a
statistically significant reduction in
maternal infectious morbidity
(chorioamnionitis or endometritis): RR
0.43 (95% CI 0.23, 0.82), RD -4% (95% CI
-7%, -1%), NNT 25 (95% CI 14 -100).
No statistically significant differences were
shown for outcomes of neonatal morbidity.
CONCLUSIONS
No clear practice recommendations can
be drawn from the results of this review on
this clinically important question, related to
a paucity of reliable data.
Further well designed randomised
controlled trials are needed to assess the
effects of routine use of maternal
antibiotics for women with prelabour
rupture of the membranes at or near term
Database：PubMed
Level：2b
Background
 It is commonly supposed that premature rupture of
the membranes followed by a long interval before
delivery increases the risk of neonatal infection.
 However, the degree of risk to the infant from
premature rupture of the membranes has never
been satisfactorily assessed, and even if it were
established, there is no clear evidence from
controlled trials that prophylactic antibiotics are
useful in this situation.
Aim of the study
To access whether the use of antibiotics to
the infants deliveried after PROM is
necessary
Method – types of studies
• Quasi-randomized trials comparing the
use of antibiotics with none use of the
antibiotics to infants deliveried after
PROM.
Method – types of participants
During the period January to September
1970 in Elsie Inglis Memorial Hospital.
Study series：100 infants born 24 hours
or more after the initial rupture of the
membranes.
Control series：100 infants delivered
within 24 hours of membrane rupture.
Method – types of intervention
The 200 infants on whom observations were made during
the trial were therefore allotted to one of 4 groups as
follows：
• Group A - infants delivered 24 hours or more after
rupture of the membranes but given no antibiotics.
 Group B - infants delivered 24 hours or more after
rupture of the membranes and given prophylactic
antibiotics.
 Group C - infants delivered 24 hours or more after
rupture of the membranes but considered to be at
particular risk and therefore given prophylactic
antibiotics.
 Group D - 100 control infants thought to be completely
well after normal deliveries and given no antibiotics.
The distribution of the cases is given in Table I.
The given antibiotics are ampicillin and cloxacillin
Risk
 Maternal factors - amnionitis
 Obstetric complications - caesarian
section, Ventouse or forceps delivery,
prolapsed cord, fetal distress.
 Pediatric complications (intra- or postpartum) - endotracheal intubation, low
Apgar at 5 minutes, umbilical
catheterization, subdural taps, clinical
evidence of infection.
Method - types of intervention
No
Yes
Yes
No
Method - types of outcome measures
Bacteriological investigations
Swabs of amnion, umbilicus, nasopharynx,
eyes, urine and feces specimens.
All cultures were incubated overnight at
37℃.
Neonatal clinical infections
Method - types of outcome measures
Bacteriological investigations
Swabs of amnion, umbilicus, nasopharynx,
eyes, urine and feces specimens.
All cultures were incubated overnight at
37℃.
Neonatal clinical infections
Result - Bacteriological investigations
 194 infants：no evidence of significant bacterial 'colonization'.
 6 cases：significant surface bacterial colonization had occurred
before or during delivery
Result - Neonatal infections
 Six incidents of infection were recorded, 3
occurring in the study series and 3 in the control
series.
No
Yes
Yes
No
Result - Neonatal infections
 In contrast, the incidence of clinical fungal infection (oral and
perianal candidiasis) was disturbingly high.
 receiving antibiotics：18%
 not receiving antibiotics：2%
Conclusion
 This study not only failed to confirm the place of
routine antibiotic prophylaxis but also illustrated
an undesirable effect of their use: 70% of cases
receiving antibiotics excreted fungi in the stools
on the fourth day of life, the growth of these
antibiotic-resistant yeasts being the sequel of
suppression of the normal bowel flora by the
broad spectrum antibiotics used.
 The administration of prophylactic antibiotics to
infants delivered after premature rupture of
membranes is unnecessary and potentially
dangerous.
EBM Conclusion
 Antibiotics for pre-term pre-labour rupture of
membranes: prevention of neonatal deaths due to
complications of pre-term birth and infection
 amongst births complicated by pPROM, empiric antibiotic therapy could reduce
deaths due to complications of prematurity by 12% and deaths due to sepsis by
39%.
 Antibiotics for prelabour rupture of membranes at or near
term
 No clear practice recommendations can be drawn from the results of this review
on this clinically important question, related to a paucity of reliable data.
 Premature rupture of membranes and effects of
prophylactic antibiotics
 The administration of prophylactic antibiotics to infants delivered after premature
rupture of membranes is unnecessary and potentially dangerous.
Appraisal -嚴格評讀
AAMPICOT
對找到的文章進行critical appraisal
The use of recombinant activated factor VII in obstetric
and gynecological hemorrhage (Review).
BJOG 2007;114:8-15. From
PubMed
證據等級
Grades of Recommendation
A
consistent level 1 studies
B
consistent level 2 or 3 studies or extrapolations from
level 1 studies
C
level 4 studies or extrapolations from level 2 or 3
studies
D
level 5 evidence or troublingly inconsistent or
inconclusive studies of any level
Answer
文獻試圖回答什麼問題？
Is activated factor VII effective in
reducing or stopping obstetric
and gynecological hemorrhage ?
Author
作者是誰，是否為這方面
的專家 -Yes.
是否回答我的問題？
-Yes.
有無利益衝突
-No conflict of interest
M Franchini, G Lippi, M Franchi
Method
RCT, cohort, case-control,
case series -case series
case report, expert opinion
Patient
是否隨機取樣
(randomization) -No
取樣是否具代表性
(representative) –Yes, though
the sample is not large enough.
Intervention
Comparison
是否有清楚的描述(Ascertain) -Yes.
是否實際可行 -Yes.
Outcome
是否有客觀雙盲的測量(MBO)
-No, data in literature are
derived from uncontrolled
studies
是否有統計學或臨床上的
意義？
-Yes, published data had
good responsive rate
Time
是否清楚描述研究取樣、操作、結果測量的時間點，追蹤
時間是否夠長 –Yes.
使用Work Sheet嚴格評讀
Diagnosis Worksheet
Are the results of this systematic review of therapy
valid?
 Is it a systematic review of randomised trials of the
treatment you’re interested in? Yes
 Does it include a methods section that describes?
 finding and including all the relevant trials?
 assessing their individual validity?
Yes
No
 Were the results consistent from study to study? Yes
Diagnosis Worksheet
Can you apply this valid, important evidence from a
systematic review in caring for your patient?
 Do these results apply to your patient? Yes
 Is your patient so different from those in the overview that its results
can’t help you? No, the situation corresponds with the study.
 How great would the potential benefit of therapy actually be for your
individual patient?
 pPROM:for baby -> prophylactic antibiotics are sugested
 PROM:for baby-> prophylactic antibiotics are unnecessary
Are your patient’s values and preferences satisfied by the
regimen and its consequences?
 Do your patient and you have a clear assessment of their values and
preferences? Can’t tell
 Are they met by this regimen and its consequences? Can’t tell
Diagnosis Worksheet
Should you believe apparent qualitative differences in
the efficacy of therapy in some subgroups of patients?
(Only if you can say “yes” to all of the following)
 Do they really make biologic and clinical sense? Nil
 Is the qualitative difference both clinically (beneficial for
some but useless or harmful for others) and statistically
significant? No, most of the results coincident with each
other.
 Was this difference hypothesised before the study began
(rather than the product of dredging the data), and has it
been confirmed in other, independent studies? Nil
 Was this one of just a few subgroup analyses carried out in
this study? Nil
Audit-自我評估
在「提出臨床問題」方面的自我評估
 我提出的問題是否具有臨床重要性？有，可減少醫療資源的浪費。
 我是否明確的陳述了我的問題？
 我的foreground question 是否可以清楚的寫成PICO？可以。
 我的background question是否包括what, when, how, who等字根？
有，但未全能概括。
 我是否清楚的知道自己問題的定位？（亦即可以定位自己的問題是屬
於診斷上的、治療上的、預後上的或流行病學上的），並據以提出問
題？知道，屬於預後上的。
 對於無法立刻回答的問題，我是否有任何方式將問題紀錄起來以備將
來有空時再找答案？有。
在「搜尋最佳證據」方面的自我評估




我是否已盡全力搜尋？是。
我是否知道我的問題的最佳證據來源？是。
我是否從大量的資料庫來搜尋答案？是。
我工作環境的軟硬體設備是否能支援我在遇到問題時進行立
即的搜尋？是，學校買的版權資源非常便利，但有些paper全
文仍無法取得。
 我是否在搜尋上愈來愈熟練了？是。
 我會使用「斷字」、布林邏輯、同義詞、MeSH term，限制
（limiters)等方法來搜尋？會。
 我的搜尋比起圖書館人員或其他對於提供病人最新最好醫療
有熱情的同事如何？還OK~
關於「嚴格評讀文獻」方面的自我評估





我是否盡全力做評讀了？盡力而為。
我是否了解Number need to treat 的意義？了解。
我是否了解Likelihood Ratios的意義？了解。
我是否了解worksheet每一項的意義？經查閱後大致了解意義。
評讀後，我是否做出了結論？是。
關於「應用到病人身上」的自我評估
 我是否將搜尋到的最佳證據應用到我的臨床工作中？是。
 我是否能將搜尋到的結論如NNT,LR用病人聽得懂的方式解釋
給病人聽？可以，但還無法解釋得很清楚。
 當搜尋到的最佳證據與實際臨床作為不同時，我如何解釋？
試著去分析差異所在，並向師長請教。
改變「醫療行為」的自我評估
當最佳證據顯示目前臨床策略需改變時，
我是否遭遇任何阻止改變的阻力？沒有，
尚未遭遇類似情境。
我是否因此搜尋結果而改變了原來的治療
策略？做了那些改變？尚須與師長學長姐
請教。
效率評估
這篇報告，我總共花了多少時間？共約15
個小時。(含找資料、評讀、討論、PPT製
作)
我是否覺得這個進行實證醫學的過程是值
得的？值得，疑問得到解答，也更熟悉
EBM的操作。
我還有那些問題或建議？評讀paper的方法
以及統計學相關數據分析不甚熟練。
Thanks for your attention!!