Tugas Metodologi Penelitian

Cohort













Oleh :

G2A009077 G2A009103











FAKULTAS KEDOKTERAN
UNIVERSITAS DIPONEGORO
SEMARANG
2011

ABSTRACT


A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted
in a cohort of adult volunteers from two textile factories located in West Java, Indonesia.
Volunteers in the cohort were bled every three months and were actively followed for the
occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of
symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/
mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In
areas where no symptomatic cases were detected, the incidence of asymptomatic or mild
infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype
identified, but all four serotypes were detected among the cohort. Four cases of DHF and one
case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to
DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection,
followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of
a longitudinal cohort study of naturally acquired DF and DHF in adults.




Study Identification
Author : Kevin R.Porter, Charmagne G. Beckett, Herman Kosasih, Ratna Irsiana Tan,
Bachti Alisjahbana, Pandji Irani Fianza Rudiman, Susana Widjaja, Erlin Listiyaningsih,
Chairin Nisa Ma'roef, James L. McArdle, Ida Parwati, Primal Sudjana, Hadi Jusuf, Djoko
Yuwono, and Suharyono Wuryad
Title : EPIDEMIOLOGY OF DENGUE AND DENGUE HEMORRHAGIC FEVER IN A
COHORT OF ADULTS LIVING IN BANDUNG, WEST JAVA, INDONESIA
Year of Publication : 2005
Journal Title : The American Journal of Tropical Medicine and Hygiene
Page : 60 66



SECTION 1 : Internal validity
1.1 Q : The study addresses an appropriate and clearly focused question
A : In this study the criterion is Well-covered
S : The study is focused with Epidemiology of dengue and dengue hemorragic fever in The
PT Naintex textile factory in Cibeunying Kidul was enlisted to participate in the study. In
Acramanik (neighboring Ujung Berung), employees at the PT Grandtex factory were
recruited to participate. And thera are no study except that epidemiology.

1.2 Q : The two groups being studied are selected from source populations that are comparable
in all respects other than the factor under investigation
A : Ya. Kedua grup dalam penelitian ini berasal dari populasi yang kondisinya seimbang.
Kedua kelompok sampel adalah orang dewasa (18-45 tahun), karyawan dari dua pabrik
tekstil di jawa barat, indonesia. Dalam penelitian ini juga dijelaskan nama pabrik dan
lokasinya. Kegiatan dan kondisi lingkungan juga dijelaskan dengan baik. Pada awal
penelitian, kedua kelompok sampel sama sama mengikuti seminar, mengisi data pribadi,
data kesehatan,data demografi, dan informed consent. kemudian kedua kelompok sampel
sama sama diperiksa baik fisik maupun sampel darah.
S : The PT Naintex textile factory in Cibeunying Kidul was enlisted to participate in the
study. In Acramanik (neighboring Ujung Berung), employees at the PT Grandtex factory
were recruited to participate...The ages of the employees ranged from 18 to 66 years old,
with the majority (estimated at 90%) being 1845 years of age. The employees work six
days a week in three rotating shifts of eight hours. The shifts are rotated every two weeks.
The working hours for each shift are 6:00 AM to 2:00 PM, 2:00 PM to 10:00 PM, and
10:00 PM to 6:00 AM. These working hours result in all study participants having DEN
vector exposures both at work and at home. Fogging takes place at both companies on a
regular basis to reduce mosquito populations. Prior to enrollment, a series of seminars
was conducted to introduce the study to factory personnel and to answer any questions.
Consent forms were distributed for advanced reading prior to the start of enrollment.
Prior to entering into the study, the consent forms were completed and signed by each
volunteer.

All volunteers completed medical history questionnaires and demographic data forms.
Physical examinations were conducted on each volunteer and blood samples were
obtained for baseline routine laboratory tests that included a complete cell blood count
(CBC) with differential, electrolytes, liver enzymes, urinalysis, PT, PTT, protein, and
albumin. Baseline tourniquet tests were also performed on each volunteer.

1.3 Q : The study indicates how many of the people asked to take part did so , in each of the
groups being studied
A : Well covered
S : Didalam penelitian diberikan jumlah partisipan dalam angka yang pasti.
"The PT Naintex textile factory in Cibeunying Kidul was enlisted to participate in the
study. In Acramanik (neighboring Ujung Berung), employees at the PT Grandtex factory
were recruited to participate. PT Naintex employs 1,500 people and PT Grandtex
employs 4,000 people."
Dapat dilihat bahwa PT Naintex dan PT Grandtex mencantumkan berapa banyak
karyawannya yang mengikuti studi penelitian tersebut

1.4 Q : The likelihood that some eligible subjects might have the outcome at the time of
enrollment is assessed and taken into account in the analysis
A : Not reported
S : penulis tidak mencantumkan hal tersebut. Karena merupakan studi epidemiologi,
'outcome', Yang pada penelitian ini berupa dengue fever dan dengue hemorrhagic fever,
walaupun didapatkan saat 'enrollment' tidak akan mempengaruhi hasil analisa.

1.5 Q : What precentage of individuals or cluster recruited into each arm of the study dropped
out before the study was completed?
A : There are 162 participants (6,4 percent) who were dropped out before the study was
compeleted.
S : A total of 162 participants dropped out of the study after enrollment, 78 from Naintex
and 84 from Grandtex. One hundred forty-five volunteers resigned from their jobs, nine
died of study-unrelated reasons, and eight declined further participation for undisclosed
reasons

1.6 Q : Comparison is made between full participants and those lost follow up , by exposure
status
A : Not reported
S : A total of 1,825 volunteers from Grandtex and 711 volunteers from Naintex were
recruited to participate in the study. A total of 162 participants dropped out of the study
after enrollment, 78 from Naintex and 84 from Grandtex. One hundred forty-five
volunteers resigned from their jobs, nine died of study-unrelated reasons, and eight
declined further participation for undisclosed reasons.
Tetapi perbandingan antara keduanya tidak dicantumkan (not reported)

1.7 Q : The outcomes are clearly defined
A : Well covered
S : Data yang ditemukan cukup jelas karena peneliti telah mengetahui angka insidensi
kejadian DF dan DHF pada orang dewasa di kota Bandung yang merupakan daerah
endemis DF dan DHF. Juga dalam penelitian tersebut menemukan beberapa valuable
reagents yang dapat digunakan untuk studi imunopatogenesis dari Dengue yang
kemungkinan berkorelasi tentang proteksi terhadap penyakit dan infeksi Dengue
There were 565 febrile episodes among the cohort, of which 475 were non-DEN cases
(84%), 51 were outpatient DEN cases (9%), and 39 were hospitalized DEN cases
(6.9%).
Figure 1 shows the geographic distribution of cases per district. Of the seven districts
with DEN cases and more than 50 volunteers, Arcamanik, Rancaekek, Kiarancondong,
and Ujung Berung had the highest incidences of DEN virus infection, with 1830 cases
per 1,000 person-years of follow-up (Table 2).
For the DHF cases, three were caused by DEN-3 virus and the virus causing the fourth
case was not identified (Table 3). The non-shock DHF cases all had pre-existing in vitro
neutralizing antibodies against all four serotypes prior to illness. The low titers seen
against some of the serotypes (including the infecting serotype) probably represent cross-
neutralization due to high titers against one or more of the other serotypes. The one DSS
case was due to a DEN-1 virus secondary infection, following a primary infection with
DEN-2 virus.
Study demonstrates the ability to define the incidence of DEN disease and infection in an
adult cohort living in an area where all four virus serotypes circulate. This area is
therefore a prime location to conduct Phase 2 and 3 efficacy trials of promising DEN
virus vaccine candidates. The study also resulted in the collection of valuable reagents
that can be used to study the immunopathogenesis of DEN and to further define
correlates of protection against DEN disease and infection.




1.8 Q : The assessment of outcome is made blind to exposure status.
A : Not reported
S : Prior to enrollment, a series of seminars was conducted to introduce the study to factory
personnel and to answer any questions. Consent forms were distributed for advanced
reading prior to the start of enrollment.Prior to entering into the study, the consent forms
were completed and signed by each volunteer. All volunteers completed medical history
questionnairesand demographic data forms. Physical examinations wereconducted on
each volunteer and blood samples were obtained
for baseline routine laboratory tests that included acomplete cell blood count (CBC) with
differential, electrolytes,liver enzymes, urinalysis, PT, PTT, protein, and
albumin.Baseline tourniquet tests were also performed on each volunteer. Peripheral
blood mononuclear cells (PBMCs) and plasma were obtained and stored for later
evaluation of baselineanti-DEN immune status. Volunteers were excluded from
participation if they were afflicted by, or had a history of, anemia (hemoglobin level < 8
g/dL), infection with human immunodeficiency virus, non-DEN-related bleeding
disorder,or any immunologic disorder. Active surveillance of the volunteer cohort
occurred whereby the factory personnel office would notify the study coordinator in the
event an employee volunteer failed to show up for work. Evaluation by the factory
physician was required for an employee to be officially excused from work. Upon
receiving notification of the absenteeism, the study coordinator would immediately
contact the volunteer by telephone to determine the reason for the absence. Within 24
hours of making phone contact, a medical evaluation was conducted and blood samples
were obtained. For volunteers not possessing a telephone, the study nurse or physician
visited his or her residence no later than 24 hours of absenteeism notification. The
detection of a febrile illness warranted a medical evaluation.

1.9 Q : Where blinding was not possible , there is some recognition that knowledge of exposure
status could have influenced the assessment of outcome
A : Adequately addressed
S : Semua hal yang akan di tinjau atau di teliti dilakukan secara baik dengan memanfaatkan
sampel yang ada. dari semua sampel yang tersedia dan memenuhi syarat untuk diteliti,
akan tetap diambil beberapa dari semuanya secara acak. hal ini sangat bermanfaat untuk
dapat memperkuat hasil penelitian sebab sampel yang dipilih dan dipakai merupakan
sampel acak dari relawan yang masuk kategori.

all the subjects are analysed in the groups to which randomly allocated ( often referred to
as intention to treat analysis )
1. Although samples were"collected from all volunteers", the "hemagglutination-
inhibition (HI) test was used to screen serum samples from 250 randomly" selected
volunteers not experiencing a DEN-related febrile illness to detect DEN seroconversion.
2. Asymptomatic DEN virus infection. To estimate the level of asymptomatic or mild
DEN virus infection among volunteers in the cohort, sera collected during the cohort
serosurvey from randomly selected individuals were screened by HI.
3. Each DEN virus infection episode was counted separately, regardless of whether it was
the same volunteer or not.

1.10 Q : The measure of assessment of exposure is reliable
A : Adequately addressed
S : A total of 1,825 volunteers from Grandtex and 711 volunteers from Naintex were
recruited to participate in the study. There were 1,198 men and 627 women from
Grandtex, and 303 men and 408 women from Naintex. The mean age of volunteers was
37.7 years old (range = 1864 years) at Grandtex and 33.1 years old (range = 1866
years) at Naintex. The majority of volunteers were either Javanese (1,144) or Sundanese
(1,288). A total of 162 participants dropped out of the study after enrollment, 78 from
Naintex and 84 from Grandtex. One hundred forty-five volunteers resigned from their
jobs, nine died of study-unrelated reasons, and eight declined further participation for
undisclosed reasons.

1.11 Q : Evidence from other sources is used to demonstrate that the method of outcome
assessment is valid and reliable?
A : Adequately addressed
S : For diagnosing DHF and DSS in hospitalized volunteers, the World Health
Organization (WHO) criteria were used. Acute serum samples obtained during the febrile
illness were assayed for DEN virus RNA by a nested RT-PCR. The method of Lanciotti
and others was used to assessed.

1.12 Q : Exposure level or prognostic factor is assessed
A : Not reported
S : Penelitian ini tidak menganalisis dan menilai faktor prognostik dari infeksi virus dengue
karena penelitian ini merupakan studi epidemiologi yang menganalisis insidensi DHF
pada orang dewas di suatu daerah yang endemis DEN Virus, yaitu bandung.
"A prospective cohort study of DEN was initiated in a DEN-endemic region of West Java
Indonesia to define the epidemiology of this disease in an adult population.

1.13 Q : The main potential confounder are identified and taken into account in the design and
analysis
A : Not reported
S : Confounding factors are not reported in this study.

1.14 Q : Have confidence intervals been provided ?
A : No
S : Confidence Interval tidak diberikan pada penelitian ini.







SECTION 2 : Overall assessment of the study
2.1 Q : How well was the study done to minimise the risk of bias or confounding, and to
establish a causal relationship between exposure and effect? Code ++, + , or -
A : ++
S : it's very good because the volunteers were excluded from participation if they were
afflicted by, or had a history of, anemia (hemoglobin level < 8 g/dL), infection with
human immunodeficiency virus, non-DEN-related bleeding disorder, or any immunologic
disorder. Adult that have asymptomatic and mild DEN illness, blood samples were
obtained from the entire cohort every three months, adult that absenteeism the study
coordinator would immediately contact the volunteer by telephone to determine the
reason for the absence. Within 24 hours of making phone contact, a medical evaluation
was conducted and blood samples were obtained. For volunteers not possessing a
telephone, the study nurse or physician visited his or her residence no later than 24 hours
of absenteeism notification. The detection of a febrile illness warranted a medical
evaluation. Most of the volunteers who had febrile illnesses were identified through this
system, so all volunteers will identified if they have dengue fever or dengue hemorrhagic
fever.

2.2 Q : Taking into account clinical considerations, your evaluation of the methodology used,
and the statistical power of the study, are you certain that the overall effect is due to
exposure being investigated?
A : The statistical power of the study is strong enough , because they took the west java
area. Based on the number of cases reported as of September 1998, West Java is the
number 2 provinces recording the most adult ( 18 years old) DHF cases behind DKI
Jakarta.
S : The overall effect in this case (DHF disease) has been investigated deeply, from the
clinical consideration, we can see that the absentee rate due to illness averages seven per
day at Naintex and four per day at Grandtex. The ages of the employees ranged from 18
to 66 years old, with the majority (estimated at 90%) being 1845 years of age. The
employees work six days a week in three rotating shifts of eight hours. These working
hours result in all study participants having DEN vector exposures both at work and at
home, so its make a sense that they do this study based on the fact
the methodology they used,its been working well because their study demonstrates the
ability to define the incidence of DEN disease and infection in an adult, so their study
result can be accepted

2.3 Q : Are the result of this study directly applicable to the patient group targeted in this
guideline?
A : Yes
S : The study was conducted to define the epidemiology of dengue disease of adult
population in endemic region. And the patient group targeted is applicable because they
have the same qualification control as the purpose of the study


SECTION 3 : Description of the study (note : the following information is required for
evidence tables to facilitate cross study comparisons. Please complete all sections for
which information is available).
3.1 Q : do we know who the study was funded by?
A : academic institution
S : Financial support: This research was supported by the Military Infectious Diseases
Research Program and the Naval Medical Research Center for Work unit 62787A 870S

3.2 Q : How many centres are patient recruited from ?
A : 2 yaitu Dua yaitu PT.Naintex dan PT.Grandtex
S : The PT Naintex textile factory in Cibeunying Kidul was enlisted to participate in the
study. In Acramanik (neighboring Ujung Berung), employees at the PT Grandtex factory
were recruited to participate

3.4 Q : what is the social setting (is type of environment in which they live) of patients in the
study ?
A : Rural
S : PT Grandtex (Acramanik) and PT Naintex (Cibeunying Kidul) located in rural area.

3.5 Q : What criteria are use to decide who should be INCLUDED in the study?
A : In Arcamanik (neighboring Ujung Berung), employees at the PT Grandtex factory were
recruited to participate. PT Naintex employs 1,500 people and PT Grandtex employs
4,000 people. The absentee rate due to illness averages seven per day at Naintex and four
per day at Grandtex. The ages of the employees ranged from 18 to 66 years old, with the
majority (estimated at 90%) being 1845 years of age. The employees work six days a
week in three rotating shifts of eight hours. The shifts are rotated every two weeks. The
working hours for each shift are 6:00 am to 2:00 pm, 2:00 pm to 10:00 pm, and 10:00 pm
to 6:00 am.

3.6 Q : What a criteria are used to decide who should be EXCLUDED from the study
A : Kriteria eksklusi dari studi ini adalah :
a.populasi diluar pekerja PT Naintex dan Grantex
b. pegawai PT Naintex yang usianya di bawah 18 tahun atau di atas 45 tahun
c. pegawai yang tidak memiliki jam kerja 6 hari seminggu dengan 3 perputaran shift per 8
jam

3.7 Q : What risk factor is investigated in the study ?
A : Not covered

3.11 Q : How long were patients followed up for , during the study?
A : Mixed
S : Detection of asymptomatic or mild DEN virus infection.
To evaluate the cohort for the occurrence of asymptomatic and mild DEN illness, blood
samples were obtained from the entire cohort every three months.
to evaluate every three month but to follow up the patient 7 till 14 days.