TESIS
PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR , BETWEEN 2010-2015
STEFANIE JÜRGENS MD
PROGRAM PASCASARJANA UNIVERSITAS UDAYANA DENPASAR 2016
TESIS
PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR , BETWEEN 2010-2015
STEFANIE JÜRGENS MD NIM: 1492161037
PROGRAM MAGISTER PROGRAM STUDI ILUM KESEHATAN MASYARAKAT PROGRAM PASCASARJANA UNIVERSITAS UDAYANA DENPASAR 2016
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PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR , BETWEEN 2010-2015
Tesis untuk Memperoleh Gelar Magister Pada Program Magister, Program Studi Ilmu Kesehatan Masyarakat, Program Pascasarjana Universitas Udayana
Stefanie Jürgens M.D. NIM 1492161037
PROGRAM MAGISTER PROGRAM STUDI ILUM KESEHATAN MASYARAKAT PROGRAM PASCASARJANA UNIVERSITAS UDAYANA DENPASAR 2016
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Lembar Pengesahan HASIL PENELITIAN INI TELAH DISETUJUI PADA TANGGAL 26.05.2016
Pembinbing I Prof.Dr. dr. Tuti Parwati Merati Sp. PD NIP: 194812281979032001
Pembinbing II dr. Anak Agung Sagung Sawitri MPH NIP: 196809141999032001
Mengetahui Ketua Program Studi Ilmu Kesehatan Masyarakat Program Pascasarjana Universitas Udayana Prof. dr. Dewa Nyoman Wirawan, MPH NIP: 19481010197702001 Prof.Dr. dr. Tuti Parwati Merati Sp. PD NIP: 194812281979032001 iv
Tesis ini Telah Diuji pada Tanggal 21.06.2016
Panitia Penguji Tesis Berdasarkan SK Rektor Universitas Udayana, No: 1174/UN14.4/HK/2015, Tanggal …
Ketua
: Prof Dr. dr. Tuti Parwati Merati Sp. PD
Anggota : 1. dr. A.A. sagung Sawitri MPH 2. Prof. dr. D.N. Wirawan MPH 3. Dr. dr. Dyah Pradnyaparamita Duarsa MSi 4. dr. Pande Putu Januaraga M.Kes Dr.PH
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SURAT PERNYATAAN BEBAS PLAGIARISME
Nama
: Stefanie Juergens M.D.
NIM
: 1492161037
Pgrogram Studi: Magister Ilmu Kesehatan Masyarakat Judul Tesis
: Predictors of Lost to Follow up and Mortality in Children ≤ 12 years ols receiving Antiretroviral Therapy in Sangalh General Hospital, Denpasar , between 2010-2015
Dengan ini menyatakan bahwa karya ilmiah tesis ini bebas plagiat. Apabila di kemudian hari terbukti terdapat plagiat dalam karya ilmiah ini, maka saya bersedia menerima sanksi sesuai peraturan di Universitas Udayana dan peraturan perundang-undangan lain yang berlaku.
Denpasar, 21.06.2016
Stefanie Juergens M.D.
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Ucapan Terima Kasih
First I would like to say thanks to my first Supervisor Prof Dr. dr. Tuti Parwati Merati Sp. PD for guidance and her input on the thesis. Also I would like to thank my second supervisor dr. A.A. Sawitri, for her encouragement, guidance and support during the learning process, during this thesis but beyond. Next I would like to thank each member of the examination comity Prof. dr. D.N. Wirawan MPH, Dr. dr. Dyah Pradnyaparamita Duarsa MSi and dr. Pande Putu Januaraga M.Kes Dr.PH for their input and corrections of this thesis. Also I would like to thank the entire mentor Field Research Training Program (FRTP) for their guidance and support during this. Special thanks also to Dr. Ketut Dewi Kumara Wati, Sp. A(K) for her help and the patience to answer all my questions. Next I would like to thank my fellow FRTP colleges and friends as well as everybody from the MIKM batch VI. Finally I would like to thank my family, my husband and my kids, for their support and for always believing in me.
Thank you.
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ABSTRACT PREDICTORS OF LOST TO FOLLOW UP AND MORTALITY IN CHILDREN ≤ 12 YEARS OLD RECEIVING ANTIRETROVIRAL THERAPY IN SANGLAH GENERAL HOSPITAL, DENPASAR , BETWEEN 2010-2015
Background: LTFU and mortality in HIV positive children from ARV therapy is different and more complex compared to adults. Besides their clinical characteristics, children dependent on their caregivers. Also very little is known about predictors in children in Asia. Method: The study design was a retrospective cohort study using secondary data of 138 HIV positive children receiving ARV treatment in Sanglah General Hospital, Bali between January 2010 till December 2015. Kaplan-Meier analysis was used to describe incidence rate and median time to mortality and Cox Proportional Hazard Model was used to identify its predictors. Analyzed variables were socio-demographic characteristics, birth history, primary care giver and clinical characteristics. Result/ Discussion: The study found that socio-demographic characteristics, birth history and primary care giver can not be used as predictors for LTFU and or mortality, but rather clinical manifestations such as Malnutrition (adjusted HR= 3.265) and Anemia (adjusted HR= 5.996). Also the higher the WHO stage, when stating the ARV therapy, the higher the risk for LTFU and or mortality in this study. Hence it can be assumed that the majority, which are LTFU might have died, and therefore not returned to the hospital. The overall mean age when children start ARV therapy is 3.21 years indicating an early diagnostic response. On the other hand the majority of the children received breast milk during the first 6 month and 73.19% were born vaginally which might lead to the assumption of low HIV testing during ANC.
Key words: LTFU, mortality, pediatric HIV, ARV, Bali, Asia
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ABSTAKT PREDIKTOR LOST TO FOLLOW UP DAN KEMATIAN PADA ANAKANAK ≤ 12 TAHUN, YANG MENERIMA ANTIRETROVIRAL TERAPI DI RUMAH SAKIT UMUM PUSAT, DENPASAR, PERIODE TAHUN 2010-2015
Latar belakang: LTFU pada anak HIV positif yang sedang dalam terapi ARV berbeda dan lebih kompleks dibandingkan dengan dewasa. Selain karakteristik klinis , pasien anak-anak tergantung pada pengasuh mereka. Terdapat sedikit informasi mengenai prediktor pada anak-anak untuk LTFU atau kematian di Asia Metode: Desain penelitian adalah penelitian kohort retrospektif dengan menggunakan data sekunder dari 138 anak-anak HIV positif yang menerima pengobatan ARV di Rumah Sakit Umum Sanglah, Bali antara Januari 2010 sampai Desember 2015. Analisis Kaplan-Meier digunakan untuk menggambarkan tingkat kejadian dan waktu median untuk kematian. Cox Proportional Hazard Model digunakan untuk mengidentifikasi prediktornya. Variabel yang dianalisa adalah karakteristik sosio-demografis pasien, riwayat persalinan, pengasuh, dan karakteristik klinis. Hasil / Diskusi: Studi ini menemukan bahwa variable karakteristik sosiodemografis, riwayat persalinan, dan pengasuh tidak dapat digunakan sebagai prediktor untuk LTFU dan kematian. Walaupun begitu manifestasi klinis seperti Malnutrisi (adjusted HR = 3,265) dan Anemia (adjusted HR = 5,996) dapat digunakan. Semakin tinggi stase terapi ARV menurut WHO semakin tinggi risiko untuk LTFU dan/atau kematian dalam penelitian ini. Maka dapat diasumsikan bahwa mayoritas pasien yang LTFU kemungkinan besar telah meninggal sehingga oleh karena itu tidak kembali ke rumah sakit. Keseluruhan rata-rata usia ketika anak-anak mulai terapi ARV adalah 3.2 tahun yang menunjukkan tindakan diagnostik yang cukup cepat. Di sisi lain sebagian besar anak-anak mendapatkan ASI selama 6 bulan pertama dan 73,19% lahir per vaginal yang dapat menyebabkan asumsi bahwa tes HIV rendah selama ANC.
Kata kunci: loss to follow up, kematian, HIV pada anak, ARV, Bali, Asia
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TABLE OF CONTENT FRONT COVER MAIN COVER PREREQUISITES DEGREE (PRASYARAT GELAR) ……………………………………………………… SUPERVISORS APPROVAL SHEET (LEMBAR PERSETUJUAN PEMBIMBING)…………………………. EXSAMINATION COMITTE (PENETAPAN PANITIA PENGUJI)………………………………….. NOTE OF THANKS (UCAPAN TERIMA KASIH)……………………………………....……… ABSTRACT………………………………………………………………… ABSTAKT ……………………………………………………………………. TABLE OF CONTENT……………………………………………….. LIST OF FIGURES …………………………………………………... LIST OF TABLES ……………………………………………………. LIST OF APPENDIX ………………………………………………. LIST OF ABBREVIATIONS………………………………………...
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CHAPTER I – FORWARD …………………………………………... 1.1 Background ……………………………………………. 1.2 Research Question …………………………………….. 1.3 Research Objectives …………………………………… 1.4 Relevance of study ……………………………………..
1 1 4 4 5
CHAPTER II- LITERATURE REVIEW …………………………….. 2.1 ARV Therapy in Children ……………………………. 2.2 Primary Care Giver …………………………………… 2.3 Predictors for LTFU and mortality …………………… 2.4 Predictors found which have influenced Program development …………………………………………..
6 6 7 8 11
CHAPTER III- CONCEPTUAL FRAMEWORK AND RESEARCH HYPOTHESIS …………………………………………………….. 3.1 Conceptual Framework ………………………………... 3.2 Research Hypothesis …………………………………..
12 12 12
CHAPTER IV – METHOD……… …………………………………. 4.1 Study Design ………………………………………….. 4.2 Place and Time of Research …………………………… 4.3 Study population ………………………………………. 4.3.1 Inclusion criteria ……………………………... 4.3.2 Exclusion criteria …………………………….. 4.4 Variables ……………………………………………….
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4.5
Data extraction and data collection ……………………. 4.5.1 Instrument ……………………………………. Data Processing ……………………………………….. Data Analysis …………………………………………. 4.7.1 Univariate Analysis ………………………….. 4.7.2 Bivariate Analysis ……………………………. 4.7.3 Multivariate Analysis ………………………… Ethical consideration …………………………………..
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CHAPTER V – RESULTS ………………………………………….. 5.1 Eligible Sample …….. ………………………………… 5.2 Characteristics of children …………………………… 5.2.1 Socio-demographic characteristics …………... 5.2.2 Birth History and PCG ………………………. 5.2.3 Clinical Presentation/Examinations…………. 5.3 Bivariate analysis …………………………………….. 5.3.1 Bivariate analysis of Socio-demographic characteristics ………………………………... 5.3.2 5.3.2 Bivariate analysis of Birth history and PCG characteristics ………………………….. 5.3.3 Bivariate analysis of Clinical Presentation/ Examination …………………………………. 5.4 Multivariate analysis …………………………………...
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CHAPTER VI – DISCUSSION ……………………………………… 6.1 Discussion …………………………………………….. 6.2 Weakness of the study …………………………………
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CHAPTER VII- CONCLUSION AND SUGGESTIONS …………… 7.1 Conclusion …………………………………………….. 7.2 Suggestion ……………………………………………..
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REFERENCE …………………………………………………………. APPENDIX …………………………………………………………
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4.6 4.7
4.8
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LIST OF FIGURES Figure 3.1 Figure 5.1 Figure 5.2 Figure 5.3 Figure 6
Conceptual Framework of predators of LTFU and/or mortality in children ≤ 12 years old receiving ARV therapy at Sanglah General Hospital between 2010 and 2015 Eligible Sample Number of children starting ARV Therapy per year 20102015 at Sanglah General Hospital Kaplan-Meier Survival Estimate Map of Bali districts
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LIST OF TABLES Table 5.1 Table 5.2 Table 5.3 Table 5.4 Table 5.5 Table 5.6 Table 5.7 Table 5.8 Table 5.9 Table 6
Socio-demographic characteristics of children receiving ARV therapy at Sanglah General Hospital between 20102015 Birth History of children and PCG characteristics receiving ARV therapy at Sanglah General Hospital between 20102015 Clinical Characteristics of the children Underlying Health Conditions in children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Bivariate analysis of Socio demographic characteristics of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Bivariate analysis of Birth history and PCG characteristics of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Bivariate analysis of WHO staging and laboratory results of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Bivariate analysis of OIs of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Multivariate analysis of predictors for LTFU and or death in children receiving ARV therapy at Sanglah General Hospital between 2010-2015 WHO classification of immunodeficiency HIV by CD4
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LIST OF APPENDIX Appendix 1 Appendix 2a Appendix 2b Appendix 2b Appendix 3 Appendix 4 Appendix 5 Appendix 6 Appendix 7 Appendix 8 Appendix 9 Appendix 10 Appendix 11
Appendix 12 Appendix 13
Data Extraction Sheet Life table (month) Life table (years) Survivor Function Starting Year of ARV therapy of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 List of Main Complain of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Reason for HIV testing in children Comparing WHO staging at first visit to when starting ART Type of OI in children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Bivariate analysis of OI OI in children receiving ARV therapy at Sanglah General Hospital between 2010-2015 WHO clinical staging of HIV disease in adults, adolescents and children Frequency of birth year of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Appendix 11: Birth process per birth year of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Breast -feeding per birth year of children receiving ARV therapy at Sanglah General Hospital between 2010-2015 Ethical clearance approval
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LIST OF ABBREVIATIONS AIDS
: Acquired Immune Deficiency Syndrome
ART
: Antiretroviral Therapy
ARV
: Antiretroviral
BMI
: Body Mass Index
CD4
: Cluster Difference 4
FTT
: Failure to thrive
HAART
: Highly Active Antiretroviral Therapy
HIV
: Human Immunodeficiency Virus
LTFU
: Loss to Follow Up
NRTI
: Nucleoside Reverse Transcriptase Inhibitor
NTB
: West Nusa Tenggara
NTT
: East Nusa Tenggara
PCG
: Primary Care Giver
PLWHA
: People Living With HIV/AIDS
PMTCT
: Prevention of Mother To Child Transmission
PPIA
: Pencegahan Penularan HIV dari Ibu ke Anak (= Prevention of Mother to Child transmission)
TB
:Tuberculosis
UNAIDS
: United Nation AIDS
WHO
: World Health Organization
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