TELAAH KRITIS JURNAL

A Comparison of Entecavir and Lamivudine

for HBeAg-Positive Chronic Hepatitis B

Pembimbing:
J. Eko Wahono, dr., Sp.S., M.Kes
Peserta Pendidikan Dokter Spesialis I:
Kelompok 9
No.
1.
2.
3.
4.
5.

Nama

NIM

Program Studi

FAKULTAS KEDOKTERAN UNAIR/RSUD Dr. SOETOMO

AGUSTUS 2016

I.

Pendahuluan.

II.

Pertanyaan Klinis.
Pada pasien Hepatitis B kronis HbE ag + dewasa apakah pengunaan entecavir memilki

efikasi yang lebih baik dibandingkan terapi antivirus lainnya?

III. Formulasi Pertanyaan Klinis dalam PICO Penelusuran Bukti.
Intervention/

Patient / Problem /
Population

Indicator/

Comparison

Pasien Hepatitis B

Index
Pemberian

Pemberian

kronis HbEAg positif

entecavir

antivirus lainnya

Outcome
Efikasi terapi

dewasa
IV.

Penyusunan Struktur Umum PICO untuk Penelusuran Bukti.

Struktur Umum Penelusuran Bukti:
(Patient Hepatitis B chronic AND adult AND Hb E Ag + AND entecavir OR
lamivudine AND efficacy)

V.

Bukti (Jurnal) Terbaik yang Diperoleh

Penulis : Ting-Tsung Chang, M.D., Robert G. Gish, M.D., Robert de Man, M.D.,
Adrian Gadano, M.D., Jose Sollano, M.D.,You-Chen Chao, M.D., Anna S. Lok, M.D.,
Kwang-Hyub Han, M.D., Zachary Goodman, M.D., Ph.D., Jin Zhu, Ph.D., Anne
Cross, Ph.D., Deborah DeHertogh, M.D., Richard Wilber, M.D., Richard Colonno,
Ph.D., and David Apelian, M.D., Ph.D., for the BEHoLD AI463022 Study Group*
Judul : A Comparison of Entecavir and Lamivudine for HBeAg-Positive Chronic
Hepatitis B
Nama & Tahun Jurnal : The new England journal of medicine vol. 354 no. 10

PICO
P
I
C

PertanyaanKlinis
Pasien Hepatitis B kronis

Jurnal yang Diperoleh

Pasien Hepatitis B kronis Hb E Ag + usia 16

HbE ag + dewasa

tahun atau lebih.

Pemberian entecavir 0,5 mg sekali sehari selama

Penggunaan entecavir
Penggunaan antivirus
lainnya

minimal 52 minggu.
Penggunaan Lamivudine 100 mg sekali sehari
selama minimal 52 minggu.
Primer: proporsi pasien dengan perbaikan
gambaran histologis, didefinisikan sebagai
perbaikan pada minimal 2 poin pada Knodell
necroinflammatory score dengan tanpa
perburukan Knodell fibrosis score pada minggu
48, elatif terhadap data awal.

Efikasi Terapi

Sekunder: pengurangan HBV DNA level pada

minggu 48 dibandingan data awal dan proporsi
pasien dengan undetectable HBV DNA,
penurunan skor fibrosis Ishak; hilangnya
HBeAg; Serokonversi HBeAg (hilangnya
HBeAg dan munculnya HBe antibody); dan
normalisasi serum alanine aminotransferase.

Relevansi PICO Pertanyaan Klinis dengan PICO Jurnal

VI.

Desain Penelitian, Fokusdan Worksheet yang digunakan untuk telaah kritis dari
Jurnal yang diperoleh.
Desain Penelitian
: Eksperimental
Fokus Jurnal
: Terapi
Worksheet yang digunakan pada telaah kritis : Terapi
VALIDITY
RAMMBO
1. Recruitment

Telaah Validity
Worksheet
Terapi
Apakah subjek
mewakili?

Jawabansesuai Worksheet
Ya,
(Methods, pg. 36-37 )
Study design and participants
We undertook a multicentre, pragmatic, double-blind,
placebo-controlled, parallel-group, randomised trial at
46 UK intensive-care units between December, 2006,
and March, 2010. Eligible participants were intubated
and mechanically ventilated adults aged 16 years and
older within 72 h of ARDS onset. Patients were identifi ed
and recruited by local investigators at each site. We
defi ned ARDS in accordance with the American
European Consensus criteria:14 a pressure of arterial
oxygen to fractional inspired oxygen concentration
(PaO2/FIO2) ratio of 200 mm Hg or less, bilateral
pulmonary infi ltrates consistent with oedema, and the
absence of clinically evident left atrial hypertension.
Exclusion criteria were pregnancy; current treatment with
intravenous -2 agonist or need for continuous,
regular, aerolised -2 agonists; current treatment with
-adrenergic antagonists; imminent withdrawal of
medical treatment; chronic liver disease, defi ned as
Child-Pugh grade C; and enrolment in another clinical
trial of an investigational medicinal product within the
previous 28 days.

2. Allocation

Apakah penempatan I & C diacak

dan
disembunyikan?
Sehingga
kelompokkelompok I & C
sebanding pada
awal percobaan?

Ya,

3. Maintenance

4. Measurement
Blinding
Outcome

Apakah kelompokkelompok
memperoleh
kointervensi yang
sama? Apakah ada
kecukupan tindak
lanjut?

Ya,

Apakah subjek dan

penilai disamarkan
terhadap perlakuan
yang diterima dan/
atau apakah
pengukurannya
objektif?

Ya

All analyses were based on intention-to-treat analyses.

We compared the primary outcome and other dichot omous
outcomes using RRs and 95% CIs. We compared
continuous outcomes with mean diff erences and their
95% CIs. We analysed 28-day mortality with survival
analysis, and by comparison of the two groups with hazard
ratios and 95% CIs and the KaplanMeier curve. All
reported p values are two-sided and were not adjusted for
multiple comparisons. We used prespecifi ed sub group
analyses to investigate the eff ects of age, severity of
hypoxaemia at study entry, cause (direct vs indirect causes
of ARDS), and the APACHE II mortality risk, on the eff ect
of salbutamol. All subgroup analyses used interaction tests;
we either calculated the ratio of RRs between the
subgroups,
or used interaction terms in logistic regression models. We
did a post-hoc analysis for the main causes of death as
recorded on the death certifi cates of participants who died
within 28 days of randomisation.

Randomisation and masking

Study drug packs were prepared by Bilcare Global
Clinical Supplies (Europe; Powys, UK). The active and
placebo drug components of the infusions were
packaged identically into numbered treatment packs,
each containing 5 mL of either salbutamol sulphate BP
(1 mg/mL
in a sterile isotonic solution, GlaxoSmithKline,
Middlesex, UK) or placebo (09% sterile sodium
chloride). We used a computer-generated randomisation
sequence with a block size of eight. Patients
were randomly assigned in a 1:1 ratio by a centralised
24 h telephone or web-based randomisation service
(Uni versity of Aberdeen, UK). Randomisation was
minimised by centre, PaO2/FIO2 ratio (50, 5199, or
100 mm Hg), and age (<64, 6584, 85 years).
Participants, care providers, and investigators were
masked to group assignment.

IMPORTANCY
TelaahImportancy
Worksheet
Terapi
Apakahkemaknaanstatistik&ke
maknaanklinisdarihasilpeneliti
antergambardenganbaik?

Jawabansesuai Worksheet

Ya,
(Abstract(Result), pg. 35 )
The patients (61.79.9 yearsold, 163 males) who
underwent successful stenting were randomized to
aspirin and cilostazol (group I, n=141,61.29.6
years old) vs aspirin and clopidogrel (group II,
n=139, 62.010.0 years old) after 1 month of
aspirin,cilostazol, and clopidogrel combination
treatment. There were no significant differences in
baseline characteristicsof the groups. The type of
DES implanted did not differ between the groups.
There were no differences inangiographic and
procedural characteristics of the groups. Major
adverse cardiac events, including acute andsubacute stent thrombosis within 1 month, did not
occur in either group. Cases of angiographic late
stent thrombosiswere 1 (0.9%) in group I and 1
(0.8%) in group II. Follow-up coronary
angiography was performed in 237patients
(84.6%). Mean follow-up duration was 7.1
months. The rate of angiographic restenosis (stent
plus 5-mmborders) was 9 (8.0%) in group I and 20
(16.1%) in group II, p=0.041). The minimal
luminal diameter at followupperiod in group I was
2.550.63 mm compared with 2.410.83 mm in
group II (p=NS).
Pengukuranapa yang
KejadianRestenosis :
EER
: 0.08
digunakandanseberapadampak
CER
: 0,161
perlakuannya?
RR
: 0,422
(EER.CER,RRR,ARR,danNNT
ARR
: 0,081
?)
RRR
: 50%
NNT
: 12
Mungkinkahdampakterjadikare TidakKebetulan,
p = 0,041
nakebetulan?
CI 95%
P-value?
Interval kepercayaan (CI)?
(Statistical Analysis, pg. 37)
Continuous variables are shown as
meanstandard deviation and categorical variables
as proportions. Continuous variables were
compared by unpaired t-test or analysis of
variance as appropriate. Categorical variables
were compared by chi-square. All data was

analyzed by intention-to-treat. A p value <0.05

was considered to be significant.

APPLICABILITY
No
1.
2.

3.

4.

5.

6.

Telaah Applicability
Apakah PICO jurnal yang diperolehsesuai PICO

Jawaban
Ya

pertanyaanklinis?

Ya

Apakahpasienandacukupmiripdenganpasiendalampenelitian?
Apakahintervensi/Indicator/indeksdalampenelitianinidapatditerap
kanuntukmanajemenpasien di lingkungananda?
Karenaobat yang digunakandalaminterversisudahtersedia

di

hanyabelumdimasukkandalam guideline
Apakahoutcomes penelitianinipentingbagipasienanda?
Karenadapatmenurunkaninsiden restenosis
Akankahpotensimanfaatlebihbesar/ Indicator /
potensimerugikanbilaintervensi/Indicator/indeksinidiaplikasikan
padapasienanda?
Karenadapatmenurunkaninsiden restenosis
Apakahhasilpenelitianinidapatdiintegrasikandengannilainilaisertaharapanpasienanda?
Karenahalinidapatmenurunkankebutuhanuntuk

Ya
Indonesia
Ya

Ya

Ya

stenting

ulangpadapasien post DES

VII.

Kesimpulan
1. Penelitian yang dilaporkan dalam jurnal tersebut VALID
2. IMPORTANCY dalam penelitian tersebut tergambar dalam jurnal.
3. Hasil penelitian yang dilaporkan dalam jurnal tersebut bersifatAPPLICABLE
untuk pasien.