UMMiSITI MALAYSIA SABAH

Transcription

SURVIVAL ANAL YSIS OF DIABETIC PATIENTS IN QUEEN ELIZABETH
HOSPITAL, KOTA KINABALU
WONG YEW LEONG
Ytlll-u.) II" .. \/"\1 ~
UMMiSITI MALAYSIA SABAH
THIS DISSERTATION IS SUBMITTED AS PART OF THE PRE-REQUIREMENT TO
BE CONFERRED THE DEGREE IN BACHELOR OF SCIENCE IN MA THEMA TICS
WITH ECONOMICS
PROGRAMME MA THEMA TICS WITH ECONOMICS
SCHOOL OF SCIENCE AND TECHNOLOGY
UNIVERSITY MALAYSIA SABAH
APRIL 2007
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Malaysia Sabah dcng'~n syarat-syarnt kegunaan scpctti berikut
I. Tesis adalab bakmilik Universiti Malay,tia Sabah.
2. ~ell'ustakaan Universiti Malaysia SAbah dibenarkan membuat salinan untuk tujuan pengajian sabaja.
3. PCll'ustakaan dibcnarkao membuat s:dilu.n tcsis ini scbagai bahan pcrtukaran antara institusi pengajian
tinggi.
4. ""Sila tandakan ( I )
(Mcngandungi maldumat yang berdaIjah keselamatan. atau
kepcnti!lgan Malaysia scpecti yang tetmaktub di dalam
AKTA:RAliSIA RASMI t912)
SULIT
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TERHAD
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TIDAK TER1{AD
(Mengandungi maldumat TERHAD yang tclah ditentukan
oleh organisasilbadan di maoa penyclidikan dijalankan)
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Jika tcsis ini SULIT atau TERHAD. sill! lampirkan sura! daripada pihak bcrIcua.worganisasi
herken3..al\ dengan menyatakan sekaJi scbab dan tcmpoh I~is ini pcrlu dilccbskan scbagai SULIT
dan TERHAD.
@ Tcsis dimaksudkan scbagai tcsis bagi Iju..ah Doktor Falsa!:.&h dan Sasjana secara penyelidil:an, i!.t3U
discltasi bag; pcncajian sccara kclja kUrnJs dan pcnyelidik.an. atau Laporan Projck Sarjana Muda
(LPSM).
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ii
DECLARATION
I declared that this dissertation is my original work except for the quotations and
summary that has been cited in the reference.
20 April 2007
WONG YEW LEONG
(HS 2004-1813)
iii
CERTIFIED BY
Signature
1.
SUPERVISOR
(pN. sm RAHAYU BT. MOHD HASHIM)
2.
EXAMINER 1
(pN. SURIANI BT. HASSAN)
3.
DEAN
)~~'1-
(ASSOCIATE PROF. DR. SHARIFF AK OMANG)
_---'~
_ _ _ __
UMS
UNIVERSITI MALAYSIA SABAH
IV
ACKNOWLEDGEMENT
First and foremost, I would like to express my deepest gratitude to my supervisor,
Pn. Siti Rahayu for her guidance and time in helping me to fInish up the dissertation on
time. She has given lots of suggestions and guidance regarding the running of the analysis.
She also mentioned what are the essential items that are needed in each section so that I
would not miss out any important information. Next, I would also express my thanks to
my friends especially Ai Chang, Nick and Yee Chi for their support. They have also
given me suggestions. We have spent time discussing the appropriate infonnation needed
from the fIrst chapter to the end. Next, I would like to thank the staffs in Queen Elizabeth
Hospital especially Mr. Dominique and Mr. Abdul Rahman for their dedication and time
in fulfIlling my needs for this dissertation. They were patience in answering all my
questions. Not forgetting my family for their uncountable moral supports. I would not
forget their dedication and involvement although they are getting nothing from their
contributions.
Finally, I would also like to express my deepest gratitude to all the other
anonymous members whose names I can't remember for their contributions to this
dissertation. Without the help and guidance of all those involved, this dissertation might
not have been completed.
v
ANALISIS MANDIRI PESAKIT DIABETES DI HOSPITAL QUEEN
ELIZABETH, KOTA KINABALU
ABSTRAK
Diabetes merupakan salah satu penyumbang utama terhadap kematian yang melibatkan
penyakit bukan sahaja di Malaysia malahan di seluruh dunia. Oleh yang demikian, adalah
penting sekiranya aliran ataupun golongan umur utama yang menghidapi penyakit ini
dapat ditentukan agar pihak yang berwajib dapat melaksanakan usaha bagi menurunkan
kadar kematian penyakit ini. Objektifutama kajian ini dilakukan adalah untuk melakukan
analisis kemandirian bagi menentukan kadar kemandirian pesakit diabetes di Sabah,
menentukan aliran kemandirian pesakit diabetes, menghitung fungsi mandiri, fungsi
ketumpatan dan fungsi hazard melalui jadual sifir usia dan menentukan samada wujudnya
perbezaan 'secara bererti antara jantina, etnik dan kategori umur yang menghidapi
penyakit ini dengan menggunakan ujian log-rank. Data pesakit telah diarnbil dari Hospital
Queen Elizabeth (QEH), Kota Kinabalu, Sabah. Pembolehubah yang diperlukan dalam
kajian ini adalah, jantina, umur, jangka hayat kemandirian dan etnik. Fungsi kemandirian,
fungsi ketumpatan dan fungsi hazard digunakan. Plot penganggar Kaplan-Meier
diplotkan sebagai sokongan bagi penentuan kadar kemandirian bagi pesakit diabetes di
Sabah. Didapati bahawa fungsi mandiri pesakit diabetes adalah tinggi manakala
kebarangkalian ketumpatan dan kadar hazard adalah rendah.
Keputusan juga
menunjukkan bahawa tiada wujudnya perbezaan secara hererti antara jantina, etnik dan
kategori umur. Ini hermakna bahawa semua orang mempunyai risiko yang sarna
menghidapi penyakit ini tanpa mengira jantina ataupun etnik.
vi
ABSTRACT
Diabetes has been known as one of the major contribution of mortality not only in
Malaysia but also around the world. Hence, it is important if the trend or the major groups
suffered by this disease can be determined so that they can benefit through efforts by
major parties to lower the risk of death. The objectives of this research are to conduct a
survival analysis to detennine the survival rate of diabetic patients, to determine the trend
of survival in diabetic patients, to compute survival function, density function and hazard
function from life table and to determine whether significance difference exists among
genders, ethnics and ages by using log-rank test. The data was collected from Queen
Elizabeth Hospital (QEH). The variables included in this study are gender, age, time of
survival and ethnics. Survival function, density function and hazard function were used.
Log-rank test was also perfonned in this dissertation to compare between two factors to
determine whether significant difference existed in the variables or not. Kaplan-Meier
estimator plot was also plotted to determine the survival pattern of the patients with
diabetes in Sabah. It showed that the survival function of diabetic patients was high while
the density probability and hazard rate was low in Sabah. The result also showed there
was no significance difference existed among genders, ethnics and ages. This implied that
all of them had the same risk in being diagnosed with this disease regardless of genders
and ethnics.
vii
TABLE OF CONTENTS
Page
DEC LARATION
ii
CERTIFIED BY
III
ACKNOWLEDGEMENT
iv
ABSTRAK
v
ABSTRACT
vi
TABLE OF CONTENTS
Vll
LIST OF TABLES
x
LIST OF FIGURES
xi
LIST OF ABBREVIATIONS
xiii
LIST OF SYMBOLS
xiv
CHAPTER 1 INTRODUCTION
1
1.1
Diabetes
2
1.1.1 The History of Diabetes
2
1.1.2 Type 1 Diabetes
4
1.1.3 Type 2 Diabetes
4
1.1.4 Gestational Diabetes
5
1.1.5 Main Complications of Diabetes
5
Current Issues
6
1.2.1 Diabetes in the World
8
1.2
viii
1.2.2 Diabetes in Asia
8
1.2.3 Diabetes in Malaysia
9
Survival Analysis
12
1.3.1 Life Table Analysis
13
1.3.2 Kaplan-Meier Estimator
13
1.3.3 Log-Rank Test
14
1.3.4 Cox Proportional Hazard Model
15
1.3.5 Censored Data
16
1.4
Objectives
17
1.5
Scope of Study
18
1.3
CHAPTER 2 LITERATURE REVIEW
19
2.1
Past Researches on Diabetes
19
2.2
Past Researches on Survival Analysis
25
CHAPTER 3 METHODOLOGY
29
3.1
Introduction
29
3.2
Variables of the Research
30
3.3
Data Source and Subject
30
3.4
Life Table
31
3.5
Survival Function
33
3.6
Density Function
36
3.7
Hazard Function
38
3.8
Kaplan-Meier Estimator
40
3.9
Log-Rank Test
41
UMS
ix
CHAPTER 4 RESULTS AND DATA ANALYSIS
45
4.1
Sample
45
4.2
Descriptive Analysis
45
4.3
Life Table
51
4.4
Survivorship Function
52
4.5
Density Function
57
4.6
Hazard Function
62
4.7
Kaplan-Meier Plot
66
4.8
Log-Rank Test
69
CHAPTER 5 DISCUSSION
81
5.1
Genders
81
5.2
Ethnics
83
5.3
Age
85
5.4
Survivorship Function
86
5.5
Density Function
88
5.6
Hazard Function
89
5.7
Log-Rank Test
90
CHAPTER 6 CONCLUSION AND SUGGESTIONS
92
LIST OF REFERENCES
94
APPENDICES
x
LIST OF TABLES
Page
Table Number
1.3
Adult obesity in 2002 and estimated level in 2010, expressed
as percent of people ~ 15 years of age with
1.4
10
BMI~30
Diabetes prevalence in people over 20 years of age in 2000 and predicted 11
for 2030 in countries with more than 100 million inhabitants
3.1
Variables of the research
30
4.19
Table showing the summary of deaths and censoring occurred according
70
to genders
4.21
The value of chi-square and its significance value for log-rank test
72
4.22
Computations of E/ and E2 of log-rank test
74
4.23
75
to ethnics
4.25
78
4.26
78
to categories of ages
4.27
79
5.1
Vital population statistics based on 1991 census of people living in Kota
84
Kinabalu
xi
LIST OF FIGURES
Figure Number
Page
1.1
The number of diabetic patients in 2010
7
1.2
The estimated number of diabetic patients in 2030
7
1.5
An example of Kaplan-Meier estimator plot
14
4.1
The number of female and male diabetic patients in QEH with 1
46
represents male and 2 represents female
4.2
The number of diabetic patients in QEH based on ethnics
47
4.3
The pie chart showing the number of diabetic patients admitted to QEH
48
based on percentage
4.4
The histogram above shows the number of patients that were registered
49
in QEH based on the age factor
4.5
The figure above shows the status of diabetic patients in QEH
50
4.6
Survival function of diabetic patients admitted to QEH, Kota Kinabalu
53
4.7
54
divided into male and female
4.8
55
divided into ethnics
4.9
56
divided into different categories of ages
4.10
Density function of diabetic patients admitted to QEH, Kota Kinabalu
57
Xli
4.11
59
divided into male and female patients
4.12
60
4.13
61
divided into categories of ages
4.14
Hazard rate of diabetic patients admitted to QEH, Kota Kinabalu
63
4.15
64
4.16
65
divided into ethnics
4.17
66
divided into categories of ages
4.18
Kaplan-Meier plot for the diabetic patients in QEH for year 2005
67
4.20
Log-rank plot for the factor of genders
71
4.24
Log-rank plot for the factor of ethnics
77
4.28
Log-rank plot for the factor of ages
80
Xlll
LIST OF ABBREVIATIONS
ADA
American Diabetes Association
BC
Before Christ
BMl
Body Mass Index
CDC
Centers for Disease Control
CHF
Congestive Heart Failure
CPHM
Cox Proportional Hazard Model
DCCT
Diabetes Control and Complication Trials
HRQoL
Health-related Quality of Life
IDDM
Insulin-dependent Diabetes Mellitus
NDFS
National Diabetes Fact Sheet
NHS
Nurses' Health Study
NIIDM
Non-insulin-dependent Diabetes Mellitus
OR
Odds ratio
PL
Product Limit
POAG
Primary Open-angle Glaucoma
QEH
Queen Elizabeth Hospital
RR
Rate Ratio
SMR
Standardized Mortality Ratio
SPSS
Statistical Packages for Social Sciences
UN
United Nations
WHO
World Health Organization
xiv
LIST OF SYMBOLS
%
Percentage
>
more than
>
more than or equal to
<
less than or equal to
<
less than
±
plus-minus sign
/
over
00
infinity
=
equal
At
delta t
At~O
limit as delta t approaches 0
f-
not equal to
I
chi-square
L
summation
(l
alpha
;::::
almost equal to
CHAPTERl
INTRODUCTION
Diabetes has been known as one of the major contribution of mortality not only in
Malaysia but also around the world. In America alone, according to the latest figure
released by Department of Health and Services under Centers for Disease Control (CDC)
in 2005, the total prevalence of diabetes by all ages were estimated at 20.8 million people
or around 7.0% of the total population in America. Although the percentage rate was
overall quite low, recent researches that were conducted in the past few years sensed that
the trend was growing continuously particularly in the 60 and above age category. Now,
about one in every four hundred to six hundred children and adolescents has Type 1
Diabetes and the people under the 60 and above age category accounted for 20.9010 of
total cases (National Diabetes Fact Sheet United States, 2005). In Malaysia, diabetes was
placed second behind heart disease for the total number of death. Detailed researches on
the mortality rate of diabetes have not been done thoroughly in Malaysia. Hence, it is
important if the trend or the major groups suffered by this disease can be determined so
that they can benefit through efforts by major parties to lower the risk of death. To do so,
2
estimation of mortality rates in diabetes in Malaysia need to be conducted by using
survival analysis techniques. Among them are Kaplan-Meier estimators, survival, density
and hazard function. By conducting these tests, the survival rates of patients suffering
from diabetes can be calculated.
1.1
Diabetes
Diabetes is a group of diseases marked by high level of glucose resulting from defects in
insulin production, insulin action or both. It can lead to serious complications and
premature death but steps to control the disease and lower the risk of complications do
exist. Diabetes was divided into two main different types of diabetes which are Type 1
and Type 2 Diabetes. The fonner was previously called insulin-dependent diabetes
mellitus (IDDM) or juvenile-onset diabetes while the latter was previously called noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes (National Diabetes
Fact Sheet United States, 2005).
1.1.1
The History of Diabetes
History of diabetes has begun since it was first discovered on papyrus by Ebers in Egypt,
1552 B.C. The first diabetes word was used was by Aretaeus of Cappadocia in the late
second century B.C. In 1869, Paul Langerhans, a Gennan medical student, announced in
a dissertation that the pancreas contains two systems of cells. One set secretes the normal
pancreatic juice; the function of the other was unknown. Several years later, these cells
3
were identified as the islets of Langerhans. History tributed Oskar Minkowski and Joseph
von Mering for their discovery that the pancreas played a major role in diabetes in the
year 1889. These Europeans discovered that when they took the pancreas out of animals,
they exhibited all the indicators associated with diabetes. At the beginning of the
twentieth century, Edward Sharpey-Schafer, a Scot, hypothesized that those suffering
from diabetes were lacking a substance that was made by the pancreas. He named this
chemical insulin.
In 1921, it was Frederick Grant Banting and Charles Herbert Best who continued
diabetes research. Their experiments showed that diabetes symptoms and risk factors
could be reduced by transferring pancreatic insulin from healthy dogs to diabetic dogs.
For this amazing discovery, Frederick Banting later received the Nobel Prize. Insulin
became widely available worldwide within a very short period of time.
Most the other major historical achievements of diabetes treatment had happened
during these years. In 1922, Leonard Thompson was the first person to be injected with
insulin in Toronto. In 1934, the first national diabetes association was formed, Diabetic
Association, in U.K. In 1970, the first glucose meter was developed. In 1983, first
biosynthetic human insulin was introduced. In 1993, Diabetes Control and Complications
Trial (DCCT) report was published. The DCCT results clearly demonstrate that intensive
therapy (more frequent doses and self-adjustment according to individual activity and
eating patterns) delays the onset and progression of long-term complications in
individuals with type 1 diabetes (Canadian Diabetes Association, 2006).
4
1.1.2
Type 1 Diabetes
IDDM developed when the body's immune system destroyed pancreatic beta cells, the
only cell in the body that makes the honnone insulin that regulated blood glucose. In
other word, it occurred when the body was unable to produce any insulin. To survive,
people with IDDM must have insulin injected or pumped. It usually strikes children and
young adults that accounted for 5% to 10% of total diagnosed cases of diabetes.
According to CDC, risk factors for Type 1 Diabetes may be autoimmune, genetic or
environmental. Several clinical trials of methods of the prevention of this disease are
currently in progress or are being planned since there is still no known way to prevent this
disease (National Diabetes Fact Sheet United States, 2005).
1.1.3
Type 2 Diabetes
Most of the diagnosed cases of diabetes were of Type 2 Diabetes which accounted for
about 90% to 95% of total cases. It usually begins as insulin resistance, a disorder in
which the cells do not use the insulin properly. As the need for insulin rises, the pancreas
gradually loses its ability to produce it. In other word, it means that the body was still
producing insulin but not enough. Type 2 Diabetes is associated with older age, obesity,
family history of diabetes, history of gestational diabetes, impaired glucose metabolism,
physical inactivity and raceiethnicity (National Diabetes Fact Sheet United States, 2005).
5
1.1.4
Gestational Diabetes
Another type of diabetes that occurred was called gestational diabetes which affected
women during pregnancy in which it was a form of glucose intolerance. It was also more
common among obese women and women with a family history of diabetes. During the
pregnancy period, they were required to be treated to normalize maternal blood glucose
level to avoid complications in the infant. It was said that about 5% to 10% of these
women would suffered from Type 2 Diabetes and another 20% to 50% of women with
gestational diabetes would have the chance of developing diabetes in the next 5 to 10
years. Since this research is only focusing on two main types of diabetes, further
discussion on the latter is not included (National Diabetes Fact Sheet United States,
2005).
1.1.5
Main Complications of Diabetes
Among the main complications of diabetes are heart disease and strokes (65% of deaths
in people with diabetes), high blood pressure (about 73%), blindness where diabetes is the
leading cause of new blind cases among adults aged 20 to 74 years old, kidney disease
(44% new cases), nervous system disease (60% to 70%), amputations (>60%), dental
disease, complication of pregnancy, biochemical imbalance and others. Type 1 and 2
Diabetes has different kinds of symptoms. In Type 1 Diabetes, the major symptoms are
frequent urination, unusual thirst, extreme hunger, unusual weight loss, extreme fatigue
and irritability. In Type 2 Diabetes, the major symptoms are any of the Type 1 Diabetes
6
symptoms, frequent infections, blurred vision, cutslbruises that are slow to heal,
tingling/numbness in the hands/feet and recurring gum, skin or bladder infections
(National Diabetes Fact Sheet United States, 2005).
1.2
Current Issues
As cited in the National Diabetes Fact Sheet (NDFS) from the Centers of Disease Control
(CDC), diabetes was the sixth major killer for mortality in term of health related field in
America in 2005 (Centers of Disease Control, 2006). Not only that, diabetes has not only
been identified as major health problem in the Western countries alone, it was also at the
forefront of the current epidemic of diabetes in Asia Pacific region too (Cockram, 2000).
According to that research, the prevalence rate of Type 1 and 2 Diabetes was on the rise
and that included Malaysia with an estimated of about 50 million of diabetic sufferers just
in China and India alone in 2025. According to World Health Organization (WHO), the
numbers of diabetic patients in Malaysia would tripled in 2030 with estimated patients of
about 2,479,000 from the 942,000 in 2000 (King, 2006). The main concern is the
increasing trend for Type 2 Diabetes particularly in young people. In children and
adolescents in some part of Asia Pacific region, Type 2 Diabetes now outnumbered Type
1 Diabetes by a ratio of 4:1. It was found that the diabetes was caused by many factors
such as the physical activities, lifestyle, diet and others. Now, most of the nations from
East to West are currently holding lots of international conferences and seminars on how
to curb this epidemic from rising. Listed below were the figures for the numbers of
diabetic patients in 2000 and the estimated numbers of diabetic patients in 2030. In the
7
India, 6 was for developed countries, 7 was for America and 8 was for other developing
countries which includes Malaysia. The value in the chart was in millions of people.
The Number of Diabetic Patients In 2000
87.78
9.82
Figure 1.1- The number of diabetic patients in 2000 (Yach et ai, 2006)
The &tIm.tad Number of Diabetic Patlants In
2030
200.2
Figure 1.2-The estimated number of diabetic patients in 2030 (Yach et ai, 2006)
8
1.2.1
Diabetes in the World
Diabetes was considered as one of the main global health issues in the world and the trend
of diabetic sufferer was currently showing a significant increase. According to Health
Department, the estimated number of people with diabetes will increase from 151 million
people in 2000 to about 221 million people in 2010. An increase of 70 million people was
equivalent to an increase of 46% within 10 years of time frame. Prediction compiled by
Dr Hillary King of the World Health Organization (WHO) indicated that this figure will
rise to 300 millions by the year 2025 (King, 2006).
1.2.2 Diabetes in Asia
In Asia, India and China were the countries with the highest rate of prevalence of
diabetes. These countries would be expected to continue their domination as the nation
that has the highest rate of prevalence of diabetes in 2025. Although the rate of increase
of diabetic patients in China was quite moderate, contributing 38 million of diabetic
patients from the world population, it was the other way round in India. It will contribute
about 58 million of diabetic patients from the population in term of diabetes prevalence.
The increase in term of prevalence of Type 2 Diabetes among children and young
teenagers in Japan were said to be related with obesity factor and historical roots. The
scenario happened in Hong Kong was due to changes in lifestyle, physical activity and
excessive intake of food that have high calories (Yach et ai, 2006).
UMS
UNIV£RSITI MALAYSIA SABAH
9
1.2.3
Diabetes in Malaysia
Malaysia was classified as the fourth nation with the highest prevalence rate of diabetes
patients in Asia According to International Diabetes Institute. the number of diabetes
patients in Malaysia was expected to raise from 800.000 patients in 2002 to 1.3 million
patients in 2010. A National Survey that was conducted in 2000 also showed that the
prevalence of diabetes exceeds 7% of the adult population. Meanwhile. (Yach et al. 2006)
reported that overweight and obesity was long has been regarded as the main driver of
diabetes. In Malaysia. the percentage of obese males and females with body mass index
(BMI) > 30 was 1.6 and 6.8 respectively in 2002. This figure will rise to 1.7 and 11.0 in
2010 respectively. The table below showed the rate of adult obesity in 2002 and estimated
level in 2010 for selected countries.
UMS
94
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UNIVERSITI MALAYSIA SA BAH
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UMMiSITI MALAYSIA SABAH

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