IMPACT ASSESSMENT OF PHARMACEUTICAL CARE INTERVENTION ON

NEWLY DIAGNOSED DIABETES MELLITUS PATIENTS IN A TERTIARY

CARE HOSPITAL OF A SUB METROPOLITAN CITY OF WESTERN NEPAL

by

DINESH KUMAR UPADHYAY

Thesis submitted in fulfilment of the requirements for thedegree of Doctor of Philosophy

October 2013

ii

DEDICATION

I DEDICATE THE PRESENT STUDY TO THOSE

PEOPLE WHO HAVE LOST THEIR LOVED ONES

DUE TO DIABETES

iii

ACKNOWLEDGEMENTS

In recognition of my doctoral research I am in debt to my GOD, the almighty, the most

gracious, the most merciful, my constant guide, friend and source of strength who gave

me courage, will, determination, and wisdom to complete this ardent task. I thank HIM

for giving me the most wonderful supportive family members; the opportunity to work

with some of the most highly qualified and respected professionals, the most excellent

working environment, and the best of friends.

I would like to express my sincere gratitude and bottomless appreciation to my

beloved supervisor Dr. Mohamed Izham Mohamed Ibrahim, Professor of Social and

Administrative Pharmacy and Associate Dean for Research and Graduate Studies

Affairs, College of Pharmacy, Qatar University, Doha Qatar (who was formerly

Professor of Social and Administrative Pharmacy and Deputy Dean of Research and

Postgraduate Studies at the School of Pharmaceutical Sciences, Universiti Sains

Malaysia, Penang, Malaysia) for supervising me to carry out this research work as well

as fulfilling the role of a teacher, guide, counsellor, advisor, and a mentor. His constant

and steady support, which often goes beyond academics, helped me a lot in learning the

research methodology and conducting the research in a better way. As a human being I

perceived him a very clever, intelligent and an embodiment of patience. This work

would not have been possible without his guidance and encouragement throughout the

study. I belief, I was very fortunate being his student and got the opportunity to learn

about the real meaning of research.

I am profoundly grateful to my clinical supervisor Dr. Vijay M. Alurkar,

Professor and Head, Department of Medicine, Manipal College of Medical Sciences and

iv

Manipal Teaching Hospital, Pokhara, Nepal for his excellent guidance during my course

of data collection in the hospital. I am also thankful to him for giving me opportunity to

deal the diabetes patients, counsel, and educate them regarding their disease under his

close supervision. My heartfelt thanks to Professor Dr. Pranaya Mishra, who was

formerly Associate Professor at the Department of Pharmacology, Manipal College of

Medical Sciences (MCOMS), Pokhara, Nepal and presently working as Professor and

Course Director at Department of Pharmacology, Saba University School of Medicine,

Saba, Netherlands-Antilles for co-supervising me in conducting this research work and

helping me in translation of questionnaire and different educational materials into

Nepali. His task-oriented approach, constructive comments and ‘one work at a time’

strategy helped me very much throughout my research.

My sincere thanks to Dr. Archana Saha, Professor and Head, Department of

Pharmacology for her administrative support and help in conducting the study and

permitting me leave whenever required. I acknowledge the services of Dr. Brij Mohan

Nagpal, Deans of the MCOMS for permitting me to execute the study in the hospital. I

am also thankful to all the members of Ethics and Research Committee, Manipal

College of Medical Sciences for approving the research study and permitted me to

conduct the study in the hospital. I also acknowledge the direct and indirect contribution

of my pharmacy staffs in conducting my research work in the hospital. My sincere thank

goes to all the medical and paramedical staffs of Manipal Teaching Hospital for their

contribution in my work. My sincere thank goes to Mr. Ghanshyam Adhikari for his

assistance to me in drafting the Nepali version of questionnaire and other study tools. I

would like to acknowledge the sincere contribution of all the members who were

involved in Linguistic Validation process of ADDQoL questionnaire.

v

I would also like to express my sincere appreciation to Dr. Azmi Ahmad Hassali

Associate Professor, Department of Social and Administrative Pharmacy and Deputy

Dean, Student Affairs & Networking, School of Pharmaceutical Sciences, and Dr. Asrul

Akmal Shafie, Associate Professor and Chairperson, Department of Social and

Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains

Malaysia, Penang, Malaysia for their encouragement and support time to time whenever

I needed during my course of thesis writing. I never felt that I am away from my home

because of their friendly and caring nature and always kept me enthusiastic.

My special thank goes to Professor Clare Bradley, Health Psychology Research,

Department of Psychology, Royal Holloway, University of London, Engham, Surrey,

UK for her continuous support and guidance in conducting Linguistic Validation of

Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire into Nepali

language and permitted me to use ADDQoL questionnaire in my research study. I would

like to thank all my friends and well-wishers for giving me moral support and inputs

during my entire journey of research study. I am also grateful for the services and

support I received from non-academic staffs in the Discipline of Social and

Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains

Malaysia, Penang, Malaysia. I am very thankful to Eli Lilly Company for providing the

free sample of insulin pen (Brand: Humapen) for diabetes patients whenever needed. I

offer my heartfelt thanks to all the diabetes patients who actively participated in the

study and shared their valuable time and information. This project was not possible

without their support and contribution. Last but not least, I am thankful to my parents,

brothers and sisters for whom no words can express my gratitude for the constant

encouragement, moral support and prayers.

vi

TABLE OF CONTENTS

Title Page

DEDICATION Ii

ACKNOWLEDGEMENTS iii

TABLE OF CONTENTS vi

LIST OF TABLES xvii

LIST OF FIGURES xxi

LIST OF APPENDICES xxiii

ABBREVIATIONS xxiv

ABSTRAK xxvi

ABSTRACT xxix

CHAPTER 1 – GENERAL INTRODUCTION

1.1 Introduction 1

1.1.1 Background of diabetes mellitus 1

1.2 Epidemiology of diabetes mellitus 4

1.2.1 Global scenario of diabetes mellitus 4

1.2.2 Prevalence of diabetes mellitus in Nepal 5

1.3 Impact of diabetes mellitus and its complications 6

1.4 Concept of pharmaceutical care vs. Medication therapeuticmanagement 8

1.5 Concept of pharmaceutical care in Nepal 11

1.6 Pharmaceutical care and its importance in diabetes mellitusmanagement 12

1.7 Problem statement 13

1.8 Rationale of the study and its importance 15

1.9 Contribution of the study findings 17

vii

1.10 Study objectives 18

1.10.1 General objective 18

1.10.2 Specific objectives 18

1.11 Thesis overview 20

CHAPTER 2 - LITERATURE REVIEW AND RESEARCHCONCEPTUAL FRAMEWORK

2.1 Definition of diabetes mellitus 22

2.2 Classification of diabetes mellitus 22

2.3 Clinical presentation of diabetes mellitus 24

2.4 Diagnosis of diabetes mellitus 24

2.5 Complications of diabetes mellitus 25

2.6 Management of diabetes mellitus 27

2.6.1 Non-pharmacological treatment 27

2.6.2 Pharmacological treatment 28

2.7 Literature review related to knowledge, attitude and practice ofdiabetes mellitus patients 29

2.7.1 Studies from the developed countries 30

2.7.2 Studies from the developing countries 33

2.8 Literature review related to health-related quality of life of diabetesmellitus patients 40

2.8.1 Studies from the developed countries 41

2.8.2 Studies from the developing countries 44

2.9 Literature review related to medication adherence and metaboliccontrol (i.e. glycaemic and blood pressure control ) of diabetesmellitus patients

47

2.9.1 Concept of medication adherence 47

2.9.2 Methods to measure medication adherence 50

2.9.3 Studies from the developed countries 53

viii

2.9.4 Studies from the developing countries 55

2.10 Literature review related to direct healthcare costs of diabetesmellitus patients 57

2.10.1 Studies from the developed countries 57

2.10.2 Studies from the developing countries 58

2.11 Literature review related to diabetes mellitus patients’ satisfactionto provided healthcare services 59

2.11.1 Studies from the developed countries 60

2.11.2 Studies from the developing countries 61

2.12 Conceptual framework of the research study 63

2.13 Research questions 65

2.14 Research hypotheses 65

2.15 Conclusion 66

CHAPTER 3 – GENERAL METHODOLOGY

3.1 Study design 69

3.2 Study location and time frame 74

3.3 Ethical approval from hospital for undertaking the study 75

3.4 Consent from study patients 75

3.5 Study population and sample size 75

3.5.1 Inclusion criteria 77

3.5.2 Exclusion criteria 77

3.6 Development of study tools and design of the questionnaire 78

3.6.1 Consent form 78

3.6.2 Socio-demography form 78

3.6.3 Lab investigation documentation form 79

3.6.4 Direct healthcare costs documentation form 79

ix

3.6.5 Medication documentation form 79

3.6.6 Diabetes information booklet 80

3.6.7 Diabetes complication chart 80

3.6.8 Diabetic food chart 80

3.6.9 Medication envelope 81

3.6.10 Insulin pen and insulin syringe 81

3.6.11 Glucometer 81

3.6.12 Diabetic kit 82

3.6.12 (a) Glass tubings 82

3.6.12 (b) Chart of human anatomy with circulatory system 83

3.6.12.(c) Daily medication calendar 83

3.6.12.(d) Calendar of antidiabetic medicines 84

3.6.13 Formulation of Knowledge, Attitude and Practice````````questionnaire 84

3.6.13 (a) Scoring method for Knowledge, Attitude and``````````````````Practice questionnaire 86

3.6.13 (b) Validation of Knowledge, Attitude and Practice`````````````````` questionnaire 87

3.6.14 Formulation of Diabetes Patient Satisfaction questionnaire 87

3.6.14 (a) Scoring method for Diabetes Patient Satisfactionquestionnaire 88

3.6.14 (b) Validation of Diabetes Patient Satisfactionquestionnaire 88

3.6.15 Adaptation of Audit of Diabetes-Dependent Quality of Lifequestionnaire 89

3.6.15 (a) Scoring method for the Audit of Diabetes-Dependent````````````````` Quality of Life questionnaire 90

3.6.15 (b) Description of Linguistic Validation process for `` Audit of Diabetes-Dependent Quality of Life ` ` ``` questionnaire

91

x

3.7 Data collection and description of pharmaceutical care interventionamong diabetes mellitus patients 94

3.7.1 Intervention phase 95

3.7.2 Reinforcement phase 102

3.8 Data management and analysis 102

3.8.1 Sources of data 102

3.8.2 Data analysis 103

3.9 Statistical analysis 104

3.10 Pilot study 105

CHAPTER 4 - IMPACT ASSESSMENT OF PHARMACEUTICALCARE INTERVENTION ON THE KNOWLEDGE, ATTITUDE ANDPRACTICE OF NEWLY DIAGNOSED DIABETES MELLITUSPATIENTS IN A TERTIARY CARE HOSPITAL

4.1 Introduction 108

4.2 Study objectives 109

4.2.1 General objective 109

4.2.2 Specific objectives 110

4.3 Methodology 110

4.3.1 Study design 110

4.3.2 Study location and duration of the study 111

4.3.3 Study population and sample selection 111

4.3.4 Instrument used to assess knowledge, attitude and practice ofdiabetes mellitus patients 111

4.3.5 Educational intervention of diabetes patients throughpharmaceutical care 112

4.3.6 Method of data collection 112

4.3.7 Data analysis 112

4.4 Results 113

xi

4.4.1 Socio-demographic characteristics of study patients 113

4.4.2 Patients’ knowledge about diabetes and its management atbaseline and follow-ups 117

4.4.3 Patients’ knowledge scores about diabetes and itsmanagement at baseline and follow-ups 121

4.4.4 Patients’ attitude about diabetes management and its effect onpatients’ sexual life at baseline and follow-ups 123

4.4.5 Patients’ attitude scores about diabetes and its management atbaseline and follow-ups 127

4.4.6 Patients’ practice about diabetes management at baseline andfollow-ups 129

4.4.7 Patients’ practice scores about diabetes management atbaseline and follow-ups 133

4.4.8 KAP scores of control group, test 1 group and Test 2 grouppatients at baseline and follow-ups 135

4.4.9 Correlation of baseline knowledge, attitude and practice andKAP scores with patients’ age and monthly income 137

4.4.10 Gender-wise comparison of baseline knowledge, attitude,practice and KAP scores 138

4.4.11 Comparison of baseline knowledge, attitude, practice andKAP scores with patients’ education 138

4.4.12 Comparison of baseline knowledge, attitude, practice andKAP scores with patients’ occupation 140

4.4.13 Comparison of patients’ knowledge, attitude, practice andKAP scores at baseline, 3-months, 6-months, 9-months and12-months follow-ups within the test groups (Test 1 groupand Test 2 group)

142

4.4.14 Comparison of knowledge, attitude, practice and KAP scoresbetween Test 1 group and Test 2 group 145

4.4.15 Comparison of knowledge, attitude, practice and KAP scoresbetween Control group and Test 1 group 147

4.4.16 Comparison of knowledge, attitude, practice and KAP scoresbetween Control group and Test 2 group 149

xii

4.4.17 Relationship between knowledge and attitude (K-A),knowledge and practice (K-P), and attitude and practice (A-P) scores

151

4.5 Discussion 153

4.5.1 Patients’ knowledge, attitude and practice about diabetes andits management 154

4.5.1 (a) General knowledge about diabetes mellitus 156

4.5.1 (b) Knowledge about diabetes complications and its `` `````````preventive measures 159

4.5.1 (c) Patients’ attitude about diabetes and its management 162

4.5.1 (d) Patients’ practice about diabetes and its management 164

4.6 Conclusion 166

CHAPTER 5 - IMPACT ASSESSMENT OF PHARMACEUTICALCARE INTERVENTION ON HEALTH-RELATED QUALITY OFLIFE OF NEWLY DIAGNOSED DIABETES MELLITUS PATIENTSIN A TERTIARY CARE HOSPITAL

5.1 Introduction 167

5.2 Study objectives 168

5.2.1 General objective 168

5.2.2 Specific objectives 169

5.3 Methodology 169

5.3.1 Study design 170

5.3.2 Study site and duration of the study 170

5.3.3 Study population and sample selection 170

5.3.4 Instrument used to assess patients’ health-related quality of```````life 170

5.3.5 Pharmaceutical care intervention of diabetes mellitus patients 171

5.3.6 Method of data collection 171

5.3.7 Data analysis 171

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5.4 Results 172

5.4.1 General quality of life scores of the control group and testgroups (Test 1 group and Test 2 group) DM patients atbaseline and follow-ups

172

5.4.2 Impact scores, Importance scores and Weighted impact scores```````of control group and test groups (Test 1 group and Test 2```````group) DM patients at baseline and follow-ups

174

5.4.3 Average weighted impact scores (AWIS) of control group andtest groups (Test 1 group and Test 2 group) DM patients atbaseline and follow-ups

184

5.4.4 Association of patients’ baseline average weighted impactscores (AWIS) with patients’ age and monthly income 186

5.4.5 Comparison between patients’ gender and patients’ baselineaverage weighted impact scores (AWIS) 186

5.4.6 Comparison between patients’ education and patients’baseline average weighted impact scores (AWIS) 187

5.4.7 Comparison of patients’ average weighted impact scores(AWIS) at baseline, 3-months, 6-months, 9-months and 12-months follow-ups within test groups (Test 1 group and Test2 group)

188

5.4.8 Comparison of patients’ average weighted impact scores(AWIS) between Test 1 group and Test 2 group 190

5.4.9 Comparison of patients’ average weighted impact scores(AWIS) between Control group and Test 2 group 191

5.4.10 Comparison of patients’ average weighted impact scores(AWIS) between Control group and Test 1 group 192

5.5 Discussion 193

5.6 Conclusion 200

CHAPTER 6 - IMPACT ASSESSMENT OF PHARMACEUTICALCARE INTERVENTION ON MEDICATION ADHERENCE ANDCLINICAL OUTCOMES, DIRECT HEALTHCARE COSTS ANDSATISFACTION OF NEWLY DIAGNOSED DIABETES MELLITUSPATIENTS IN A TERTIARY CARE HOSPITAL

6.1 Introduction 202

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6.2 PART- 1: Impact of pharmacist-provided pharmaceutical care `````````intervention on medication adherence and clinical`````outcomes (i.e. glycaemic and blood pressure control) of`````newly diagnosed diabetes mellitus patients

206

6.2.1 General objective 206

6.2.2 Specific objectives 206

6.2.3 Methodology 207

6.2.3 (a) Medication counselling of diabetes mellitus patients 207

6.2.3 (b) Measurement of medication adherence by pill counts```````````method 209

6.2.3 (c) Method of data collection 212

6.2.3 (d) Data analysis 212

6.2.4 Results 212

6.2.4 (a) Patients’ medication adherence and clinical outcomes,and patients’ conversion rate at baseline and follow-ups

212

6.2.4 (b) Association of patients’ baseline medicationadherence with patients’ age and monthly income 217

6.2.4 (c) Comparison of patients’ baseline medicationadherence with patients’ gender, education andoccupation

217

6.2.4 (d) Comparison of patients’ medication adherence andclinical outcomes at baseline, 3-months, 6-months, 9-months and 12-months follow-ups within test groups(Test 1 group and Test 2 group)

219

6.2.4 (e) Comparison of patients’ medication adherence andclinical outcomes between T1G and T2G, CG andT1G, and CG and T2G

223

6.3 PART- 2: Impact of pharmacist-provided pharmaceutical careintervention on direct healthcare costs of newly diagnosed diabetesmellitus patients

225

6.3.1 General objective 225

6.3.2 Specific objectives 225

6.3.3 Methodology 226

xv

6.3.3 (a) Estimation of direct medical and non-medical costs ofdiabetes mellitus patients 226

6.3.3 (b) Method of data collection 228

6.3.3 (c) Data analysis 228

6.3.4 Results 229

6.3.4 (a) Geometric changes in direct medical and non-medical`````````````````costs of Control group, Test 1 group and Test 2 group`````````````````patients at baseline, 3-months, 6-months, 9-months`````````````````and 12-months follow-ups

229

6.3.4 (b) Direct healthcare costs (direct medical + non-medical`````````````````costs) of control group, Test 1 group and Test 2 group`````````````````patients at baseline and follow-ups

233

6.3.4 (c) Comparison of direct healthcare costs of patients at ``` ` ```` baseline, 3-months, 6-months, 9-months and 12-`````````````````months follow-ups within test groups (Test 1 group```````````````` and Test 2 group)

236

6.3.4 (d) Comparison of direct healthcare costs between test`````````````````groups (Test 1 group and Test 2 group), and control`````````````````group and test groups patients

238

6.4 PART- 3: Impact of pharmacist-provided pharmaceutical careintervention on satisfaction of newly diagnosed diabetes mellituspatients

241

6.4.1 General objective 241

6.4.2 Specific objectives 241

6.4.3 Methodology 241

6.4.3 (a) Instruments used to evaluate patients’ satisfaction 242

6.4.3 (b) Method of data collection 242

6.4.3 (c) Data analysis 242

6.4.4 Results 243

6.4.4 (a) Patients’ satisfaction with pharmacist andpharmaceutical care intervention at baseline andfollow-ups

243

6.4.4 (b) Patients’ satisfaction scores at baseline, 3-months, 6-months, 9-months and 12-months follow-ups 249

xvi

6.4.4 (c) Association of patients’ baseline satisfaction scoreswith patients’ age and monthly income 251

6.4.4 (d) Comparison of patients’ baseline satisfaction scoreswith patients’ gender and education 251

6.4.4 (e) Comparison of patients’ satisfaction scores atbaseline, 3-months, 6-months, 9-months and 12-months follow-ups within test groups (Test 1 groupand Test 2 group)

252

6.4.4 (f) Comparison of patients’ satisfaction scores betweenTest 1 group and Test 2 group 254

6.4.4 (g) Comparison of patients’ satisfaction scores betweenControl group and Test 2 group 255

6.4.4 (h) Comparison of patients’ satisfaction scores betweenControl group and Test 1 group 256

6.5 Discussion 257

6.5.1 Patients’ medication adherence and clinical outcomes 258

6.5.2 Direct healthcare costs of diabetes mellitus patients 268

6.5.3 Patients’ satisfaction with pharmacist and provided care 272

6.6 Conclusion 277

CHAPTER 7 - THESIS CONCLUSION

7.1 Summary of the study 280

7.2 Limitations of the study 281

7.3 Recommendations 283

7.4 Future research 284

7.5 Conclusion 285

REFERENCES 289

APPENDICES 320

xvii

LIST OF TABLES

Table No Title Page

3.1 Distribution chart of intervention and reinforcementprogramme in Control group, Test 1 group and Test 2 groupdiabetes mellitus patients

95

4.1 Socio-demographic characteristics of study patients 114

4.2 Patients’ knowledge about diabetes and its management atbaseline and follow-ups 119

4.3 Patients’ knowledge scores about diabetes and itsmanagement at baseline and follow-ups 122

4.4 Patients’ attitude about diabetes management and its effecton patients’ sexual life at baseline and follow-ups 124

4.5 Patients’ attitude scores about diabetes and its managementat baseline and follow-ups 128

4.6 Patients’ practice about diabetes management at baselineand follow-ups 130

4.7 Patients’ practice scores about diabetes management atbaseline and follow-ups 134

4.8 KAP scores of Control group, Test 1 group and Test 2 grouppatients at baseline and follow-ups 136

4.9 Correlation of baseline knowledge, attitude and practice andKAP scores with patients’ age and monthly income 137

4.10 Comparison of baseline knowledge, attitude, practice andKAP scores with patients’ gender 138

4.11 Comparison of baseline knowledge, attitude, practice andKAP scores with patients’ education 139

4.12 Comparison of baseline knowledge, attitude, practice andKAP scores with patients’ occupation 141

4.13 Comparison of patients’ knowledge, attitude, practice andKAP scores at baseline, 3-months, 6-months, 9-months and12-months follow-ups within test groups (Test 1 group andTest 2 group)

144

xviii

4.14 Comparison of knowledge, attitude, practice and KAPscores between Test 1 group and Test 2 group

146

4.15 Comparison of knowledge, attitude, practice and KAP scorebetween Control group and Test 1 group 148

4.16 Comparison of knowledge, attitude, practice and KAP scorebetween Control group and Test 2 group 150

4.17 Correlation between K-A, K-P and A-P scores of patients 152

5.1 General quality of life scores of control group and testgroups (Test 1 group and Test 2 group) diabetes mellituspatients at baseline and follow-ups

173

5.2 Impact scores, Importance scores and Weighted impactscores of Control group, Test 1 group and Test 2 grouppatients at baseline

176

5.2 (a) Impact scores, Importance scores and Weighted impactscores of Control group patients at 3-months, 6-months, 9-months and 12-months follow-ups

178

5.2 (b) Impact scores, Importance scores and Weighted impactscores of Test 1 group patients at 3-months, 6-months, 9-months and 12-months follow-ups

180

5.2 (c) Impact scores, Importance scores and Weighted impactscores of Test 2 group patients at 3-months, 6-months, 9-months and 12-months follow-ups

182

5.3 Average weight impact scores (AWIS) of control group andtest groups (Test 1 group and Test 2 group) patients atbaseline and follow-ups

185

5.4 Association of patients’ baseline average weighted impactscores (AWIS) with patients’ age and monthly income 186

5.5 Comparison between patients’ gender and patients’ baselineaverage weighted impact scores (AWIS) 187

5.6 Comparison between patients’ education and patients’baseline average weighted impact scores (AWIS) 187

5.7 Comparison of patients’ average weighted impact scores(AWIS) at baseline, 3-month, 6-month, 9-month and 12-month follow-ups within test groups (Test 1 group and Test2 group)

188

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5.8 Comparison of patients’ average weighted impact scores(AWIS) between Test 1 group and Test 2 group 190

5.9 Comparison of patients’ average weighted impact scores(AWIS) between Control group and Test 2 group 191

5.10 Comparison of patients’ average weighted impact scoresbetween Control group and Test 1 group 192

6.1 Conversion rate of diabetes mellitus patients at baseline andfollow-ups 216

6.2 Association of patients’ baseline medication adherence withpatients’ age and monthly income 217

6.3 Comparison of patients’ baseline medication adherence withpatients’ gender, education and occupation 218

6.4 Comparison of patients’ medication adherence and clinicaloutcomes at baseline, 3-months, 6-months, 9-months and12-months follow-ups within test groups (Test 1 group andTest 2 group)

220

6.5 Geometric changes in direct medical and non-medical costsof Control group, Test 1 group and Test 2 group patients atbaseline and follow-ups

231

6.6 Total direct healthcare cost (direct medical and non-medicalcosts) of control group and test groups patients at baseline,3-months, 6- months, 9-months and 12-months follow-ups

235

6.7 Direct healthcare costs comparison of patients at baseline, 3-months, 6-months, 9-months and 12-months follow-upswithin test groups (Test 1 group and Test 2 group)

237

6.8 Differences in direct healthcare costs of patients in both thetest groups over time 238

6.9 Comparison of direct healthcare costs between test groups(Test 1 group and Test 2 group) and control group and testgroups patients

240

6.10 Patients’ satisfaction with pharmacist and pharmaceuticalcare intervention at baseline and follow-ups 245

xx

6.11 Patients’ satisfaction scores at baseline, 3-months, 6-months,9-months and 12-months follow-ups 250

6.12 Association of patients’ baseline satisfaction scores withpatients’ age and monthly income 251

6.13 Comparison of baseline patients’ satisfaction scores withpatients’ gender and education 252

6.14 Comparison of patients’ satisfaction scores at baseline, 3-months, 6-months, 9-months and 12-months follow-upswithin test groups (Test 1 group and Test 2 group) 253

6.15 Comparison of patients’ satisfaction scores between Test 1group and Test 2 group 255

6.16 Comparison of patients’ satisfaction scores between Controlgroup and Test 2 group 256

6.17 Comparison of patients’ satisfaction scores between Controlgroup and Test 1 group

257

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LIST OF FIGURES

Figure No Title Page

1.1 Vision of the overall research 19

2.1 Conceptual framework representing problems encounteredin diabetes management and the provided means ofintervention for better patient outcome

64

3.1 Flow chart of study design 72

3.2 Flow chart of pharmaceutical care intervention 73

3.3 Location of Kaski district in the map of Nepal 74

4.1 Comparison of mean knowledge scores of Control group,Test 1 group and Test 2 group DM patients at baseline, 3-months, 6-months, 9-months, and 12-months follow-ups

122

4.2 Comparison of mean attitude scores of Control group, Test1 group and Test 2 group DM patients at baseline, 3-months, 6- months, 9-months and 12-months follow-ups

128

4.3 Comparison of mean practice scores of Control group, Test1 group and Test 2 group DM patients at baseline, 3-months, 6-months, 9-months and 12-months follow-ups

134

4.4 Comparison of overall mean KAP scores of Control group,Test 1 group and Test 2 group DM patients at baseline, 3-months, 6-months, 9-months and 12-months follow-ups

136

5.1 Average weight impact scores (AWIS) of control groupand test groups (Test 1 group and Test 2 group) DMpatients at baseline and follow-ups

185

6.1 Medication adherence of Control group, Test 1 group andTest 2 group DM patients at baseline and follow-ups 215

6.2 Fasting blood glucose (FBG) of Control group, Test 1group and Test 2 group DM patients at baseline andfollow-ups

215

6.3 Post prandial blood glucose (PPBG) of Control group, Test1 group and Test 2 group DM patients at baseline andfollow-ups

215

6.4 Glycated haemoglobin (HbA1c) of Control group, Test 1 215

xxii

group and Test 2 group DM patients at baseline andfollow-ups

6.5 Systolic blood pressure (SBP) of Control group, Test 1group and Test 2 group DM patients at baseline andfollow-ups

216

6.6 Diastolic blood pressure (DBP) of Control group, Test 1group and Test 2 group DM patients at baseline andfollow-ups

216

6.7 Direct healthcare costs (in Nepali rupees) of control groupand test groups DM patients at baseline, 3-months, 6-months, 9-months and 12-months follow-ups

234

6.8 Comparison of mean satisfaction scores of Control group,Test 1 group and Test 2 group DM patients at baseline, 3-months, 6-months, 9-months and 12-month follow-ups

250

xxiii

LIST OF APPENDICES

Appendix No Title Page1 Informed consent 320

2 Socio-demography form 322

3 Lab investigation form 324

4 Direct healthcare costs documentation form 325

5 Medication documentation form 327

6 Diabetes information booklet 328

7 Diabetes complication chart 329

8 Diabetic food chart 330

9 Medication envelope 331

10 Insulin pen and insulin syringe 332

11 Glucometer 333

12 Diabetic kit 334

12 (a) Glass tubings 334

12 (b) Chart of human anatomy with circulatory system 334

12 (c) Daily medication calendar 335

12 (d) Calendar of antidiabetic medicines 336

13 Knowledge, Attitude and Practice Questionnaire related todiabetes and its management 337

14 Diabetes Patient Satisfaction Questionnaire 345

15 Audit of Diabetes-Dependent Quality of Life Questionnaire 347

16 Agreement letter to use of ADDQoL 19 354

17 Ethics approval letter 355

18 Patient responses to individual knowledge question relatedto diabetes and its management 356

19 Medication adherence and clinical outcomes of patients atthe baseline and follow-ups 374

19 (a)Differences in medication adherence and clinical outcomesof patients in both the test groups (Test 1 group and Test 2group) over time

377

19 (b)Comparison of patients’ medication adherence and clinicaloutcomes between T1G and T2G, CG and T1G and CG andT2G

378

20 List of publications related to thesis 380

xxiv

LIST OF ABBREVIATIONS

12M Twelve month

3M Three month

6M Six month

9M Nine month

ADA American Diabetes Association

ADDQoL Audit of Diabetes-Dependent Quality of Life

A-Score Attitude score

AWIS Average Weighted Impact Scores

BL Baseline

BMI Body Mass Index

BT Backward Translator

CD Cognitive Debriefing

CG Control group

DAFNE Dose Adjustment for Normal Eating

DBP Diastolic Blood Pressure

DDP Daily Dietary Plan

DHCs Direct Healthcare Costs

DIMS Diabetes Impact Measurement Scale

DKA Diabetic Ketoacidosis

DM Diabetes Mellitus

DMC Daily Medication Calendar

DPSQ Diabetes Patient Satisfaction Questionnaire

F/U Follow-up

FBG Fasting Blood Glucose

FT Forward Translator

GDM Gestational Diabetes Mellitus

GQoL General Quality of Life

HbA1c Glycated Haemoglobin

HCPs Health Care Professionals

HRQoL Health-Related Quality of Life

IDDM Insulin Dependent Diabetes Mellitus

xxv

IDF International Diabetes Federation

IGT Impaired Glucose Tolerance

IQR Inter-quartile Range

KAP Knowledge, Attitude and Practice

JNC Joint National Committee

KAP-Scores Knowledge, Attitude and Practice scores

K-Score Knowledge score

LV Linguistic Validation

MCC Medication Counselling Centre

MODY Maturity Onset Diabetes in Youth

NDA Nepal Diabetes Association

NDI Nurse Directed Intervention

NIDDM Non Insulin Dependent Diabetes Mellitus

NKHC Non-Ketotic Hyperosmolar Coma

NRs Nepali Rupees

OBRA Omnibus Reconciliation Act

OHAs Oral Hypoglycaemic Agents

PC Pharmaceutical care

PCI Pharmaceutical Care Intervention

PCP Pharmaceutical Care Program

PPBG Post Prandial Blood Glucose

P-Score Practice score

QoL Quality of Life

RBG Random Blood Glucose

SBP Systolic Blood Pressure

SMBG Self Monitoring Blood Glucose

SPSS Statistical Package for Social Sciences

T1G Test 1 group

T2G Test 2 group

VLCD Very Low Calorie Diet

WHO World Health Organization

WIS Weighted Impact Scores

xxvi

PENILAIAN IMPAK PENJAGAAN FARMASEUTIKAL KE ATAS PESAKIT

DIABETES MELLITUS YANG BARU DIDIAGNOS DI HOSPITAL

PENJAGAAN TERTIAR DI BANDAR SUB METROPOLITAN NEPAL BARAT

ABSTRAK

Status sosioekonomi yang buruk dan kekurangan pengetahuan adalah kekangan utama

yang perlu ditangani dalam pengurusan penyakit diabetes terutama dalam negara miskin.

Oleh itu, satu kajian klinikal kawalan rawak telah dilaksanakan dalam 5 fasa dengan

objektif untuk menilai impak intervensi penjagaan farmaseutikal ke atas tahap

pengetahuan, sikap dan praktis (KAP), kualiti hidup berkaitan kesihatan (HRQoL),

kepatuhan pengambilan ubat dan hasil akhir klinikal, kos penjagaan kesihatan langsung

dan kepuasan pesakit diabetes mellitus yang baru didiagnos di hospital penjagaan tertiar.

Satu sampel pesakit seramai 162 orang telah dipilih dari Julai 2010 sehingga Disember

2010 dan dirawak dengan cara 1:1:1 dalam tiga kumpulan selari: kumpulan kawalan (n=

54), kumpulan ujian 1 (n= 54) dan kumpulan ujian 2 (n= 54). Intervensi telah dijalankan

menggunakan bahan dan alat pendidikan yang direka khas. Ujian Kruskal-Wallis, Mann-

Whitney U, Friedman and Wilcoxon signed rank (p≤0.05) telah digunakan untuk

mencari perbezaan manakala ujian korelasi Spearman (p≤0.05) telah digunakan untuk

mencari hubungkait antara pembolehubah bersandar dan tak bersandar. Umur,

pendapatan bulanan, jantina, pendidikan dan pekerjaan pesakit didapati berkaitan secara

signifikan dengan skor pengetahuan, sikap dan praktis tentang diabetes dan

pengurusannya. Skor HRQoL dan kepuasan didapati berkaitan secara negatif dengan

umur mereka manakala umur, pendidikan dan pekerjaan pesakit adalah faktor peramal

yang signifikan bagi kepatuhan pengambilan ubat. Pada tahap asas, pesakit mempunyai

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pengetahuan dan praktis yang buruk tetapi secara relatif mempunyai sikap yang lebih

baik tentang diabetes dan mereka menganggap kualiti hidup masa sekarang adalah

buruk. Kepatuhan pesakit terhadap pengambilan ubat adalah baik tetapi kawalan

glisemik adalah buruk. Hasil kajian juga menunjukkan kos penjagaan kesihatan

langsung total adalah berpunca terutama daripada kos perubatan langsung dan pesakit

kurang berpuas hati dengan penjagaan farmaseutikal pada tahap asas. Analisis ukuran

berulangan menunjukkan penambahbaikan yang signifikan dalam skor pengetahuan,

sikap, praktis dan KAP total, HRQoL, kepatuhan pengambilan ubat dan hasil akhir

klinikal, kos penjagaan kesihatan langsung dan kepuasan pesakit pada setiap susulan

(p<0.001) selepas intervensi. Berbanding dengan kumpulan kawalan, pesakit dalam

kedua-dua kumpulan ujian menunjukkan tahap yang tinggi bagi pengetahuan [skor min

±sd (Kumpulan Kawalan (CG): 5.58±1.81; Kumpulan Ujian 1 (T1G): 13.18±1.57 dan

Kumpulan Ujian 1 (T2G): 15.59±.72)], sikap positif [skor min ±sd (CG: 10.86±1.66;

T1G: 13.04±1.37 dan T2G: 13.76±1.40)] dan praktis yang baik [skor min ±sd (CG:

6.86±1.08; T1G: 8.00±1.05 dan T2G: 9.47±.98)] pada susulan keempat, dan HRQoL

mereka bertambah baik secara konsisten dengan peningkatan besar pada susulan

keempat berbanding dengan tahap asas [skor median (CG: -3.16 berbanding -2.50; T1G:

-2.56 berbanding -2.61 dan T2G: -2.26 berbanding -2.30)], dan oleh itu memperbaiki

kualiti hidup umum mereka. Begitu juga, kepatuhan terhadap ubat [kepatuhan min ±sd

(T1G: 96.53±1.04%; T2G: 97.68±.74% dan CG: 85.02±3.46%)] dan kawalan glisemik

[median FBG, PPBG dan HbA1c (CG: 155, 186 dan 7.40%; T1G: 122, 148 dan 6.90%,

dan T2G: 119, 145 dan 6.40%, masing-masing)] telah diperbaiki secara konsisten dalam

kedua-dua kumpulan ujian dengan kepatuhan dan kawalan glisemik yang maksimum

pada susulan keempat. Walau bagaimanapun, terdapat penurunan kos penjagaan

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kesihatan langsung yang agak besar bagi pesakit dalam kedua-dua kumpulan ujian

sepanjang susulan dengan penurunan yang besar pada susulan keempat [kos median

dalam matawang Nepali (CG: 1851.50; T1G: 1020.00 dan T2G: 900.00); 1 USD = 73.38

Nepali rupees], dan mereka lebih berpuas hati dengan program penjagaan farmaseutikal

dengan skor kepuasan yang lebih tinggi pada susulan keempat [skor median (CG: 47.74;

T1G: 68 dan T2G: 73)]. Oleh itu intervensi penjagaan farmaseutikal menunjukkan hasil

akhir yang positif bagi pesakit diabetes dari segi penambahbaikan pengetahuan, sikap

dan praktis, HRQoL, kepatuhan terhadap pengambilan ubat dan hasil akhir klinikal,

kepuasan dan pengurangan kos penjaagaan kesihatan langsung.

xxix

IMPACT ASSESSMENT OF PHARMACEUTICAL CARE INTERVENTION ON

NEWLY DIAGNOSED DIABETES MELLITUS PATIENTS IN A TERTIARY

CARE HOSPITAL OF A SUB METROPOLITAN CITY OF WESTERN NEPAL

ABSTRACT

Poor socioeconomic status and lack of knowledge regarding disease are the major

hurdles to be addressed in management of the disease. Therefore, a randomised control

trial (RCT) study was conducted in five phases with the objectives of evaluating the

impact of pharmaceutical care intervention on knowledge, attitude and practice (KAP),

health-related quality of life (HRQoL), medication adherence and clinical outcomes,

direct healthcare costs and satisfaction of newly diagnosed diabetes mellitus patients in a

tertiary care hospital. A sample size of 162 patients was selected over 6-months duration

(from July 2010 to December 2010) and randomization was done by 1:1:1 in three

parallel groups: control group (n= 54), test 1 group (n= 54) and Test 2 group (n= 54).

Interventions were carried out with the used of specially designed educational materials

and tools. Descriptive and inferential statistics were performed in each part of the study.

Appropriate non-parametric tests such as Kruskal-Wallis, Mann-Whitney U, Friedman

and Wilcoxon signed rank tests (p≤0.05) have been used to find out the differences

while Spearman order correlation test (p≤0.05) was used to find out the association

among different dependent and independent variables. Patients’ age, monthly income,

gender, education and occupation were significantly associated with their knowledge,

attitude and practice scores about diabetes and its management. Patient’s HRQoL and

satisfaction scores were negatively associated with their age while age, education and

occupation of the patients were the significant predictor of patient’s medication

xxx

adherence. At baseline, patients had poor knowledge, practice but relatively better

attitude regarding diabetes and they perceived their present quality of life as ‘bad’. The

medication adherence of the patients was considerable but they had poor glycaemic

control. Total direct healthcare costs of patients were mainly attributable to direct

medical costs, and patients were ‘least satisfied’ with pharmaceutical care at baseline. A

repeated measure analysis showed significant improvement in knowledge, attitude,

practice and KAP scores, HRQoL, medication adherence and clinical outcomes, direct

healthcare costs and satisfaction of the patients in their each follow-up (p<0.001)

following intervention. Compared to control group, patients of both test groups showed

high degree of good knowledge [mean score±sd (CG: 5.58±1.81; T1G: 13.18±1.57 and

T2G: 15.59±.72)], positive attitude [mean score±sd (CG: 10.86±1.66; T1G: 13.04±1.37

and T2G: 13.76±1.40)] and good practices [means score±sd (CG: 6.86±1.08; T1G:

8.00±1.05 and T2G: 9.47±.98)] at fourth follow-ups, and their HRQoL consistently

improved with considerable improvement at the fourth follow-ups than baseline [median

score (CG: -3.16 vs. -2.50; T1G: -2.56 vs. -2.61 and T2G: -2.26 vs. -2.30)], and hence

improved their general quality of life. Similarly, medication adherence [mean

adherence±sd (T1G: 96.53±1.04%; T2G: 97.68±.74% and CG: 85.02±3.46%)] and

glycaemic control [median FBG, PPBG and HbA1c (CG: 155, 186 and 7.40%; T1G:

122, 148 and 6.90%, and T2G: 119, 145 and 6.40%, respectively)] were improved in

both test groups consistently with maximum adherence and glycaemic control at fourth

follow-ups. However, there were considerable reduction in total direct healthcare costs

of patients in both test groups throughout with high reduction at the fourth follow-ups

[median costs in Nepali rupees (CG: 1851.50; T1G: 1020.00 and T2G: 900.00); 1 USD

= 73.38 Nepali rupees], and they were more satisfied with pharmaceutical care program

xxxi

with greater satisfaction scores at fourth follow-ups [median score (CG: 47.74; T1G: 68

and T2G: 73)]. Thus, pharmaceutical care intervention showed positive outcomes for

diabetes mellitus patients in terms of improving their knowledge, attitude and practice,

HRQoL, medication adherence and clinical outcomes, satisfaction and minimizing their

direct healthcare costs.

1

CHAPTER 1

GENERAL INTRODUCTION

1.1 INTRODUCTION

1.1.1 Background of diabetes mellitus

Diabetes has been recognised as a devastating and deadly disease for more than 2000

years. It was one of the first diseases described in an Egyptian manuscript in 1500 BC

mentioning ‘too great emptying of the urine’. Around the same time, Indian physicians

also identified the disease and named it as ‘madhumeha’ or ‘honey urine’ and described

‘a mysterious disease causing thirst, enormous urine output and wasting away of the

body with flies and ants attracted to the urine of the people’ (Das & Shah, 2011). The

Greek Appollonius of Memphis first used the term ‘diabetes’ or ‘to pass through’ in

230 BC. The British surgeon John Rolle added the term ‘mellitus’ or ‘from honey’ to

diabetes in the late 1700s and separated the condition named diabetes insipidus, which

was also associated with frequent urination (MacCracken & Hoel, 1997).

Dr. Thomas Willis, a London-based physician, determined whether his patients

had diabetes or not by sampling their urine in the 17th century. According to him, if urine

had a sweet taste he would diagnose them with diabetes mellitus – "honeyed" diabetes.

This method of monitoring blood sugar became very popular and remained unchanged

until the 20th century. Different measures were tried in-between but effective treatment

was not developed until the early part of the 20th century. Sushruta, Arataeus and Willis

2

were the early pioneers in the treatment of diabetes. Greek physicians used to prescribe

exercise preferably on horseback to employ moderate friction and alleviate excess

urination. There were different forms of remedy suggested for the therapy of diabetes

including wine, overfeeding to compensate for loss of fluid weight, starvation diet,

potato therapy and oat cure in olden days (Das & Shah, 2011). In 1913, scientist Allen,

after three years of diabetes study, published a book named ‘Studies Concerning

Glycosuria and Diabetes’. This book encouraged scientists and doctors to develop

therapies for diabetes patients.

In recent decades, the medical profession has advanced drastically and new

technologies and medicines have been launched to treat heath-related problems, and to a

certain extent this profession has taken up the challenges, but still there are many

unresolved problems regarding patients' response towards therapy and better therapeutic

outcomes resulting poor patients’ satisfaction and high economic burden on them. These

problems may be due to low patient involvement in their therapy, low level of their

knowledge and awareness about their problem and sometimes poor healthcare facilities.

Such problems become more challenging mainly in chronic disease conditions that

require a long-term treatment strategy and special care and attention for the patient's

benefit and a better therapeutic result.

Diabetes mellitus (DM) is a chronic disease condition with a rapidly increased

prevalence and has become a serious healthcare challenge. At one time, this disease was

considered as a problem of high-income countries (Balabanova et al., 2009), but now it

is also growing rapidly even in low-income countries, mainly due to the change in

lifestyle pattern, urbanisation and intake of high dietary fats (Moodley & Rambiritch,

3

2007). Increased incidence of diabetes has not only produced a clinical burden but also a

social and economical burden (Kapur, 2007). Poor socioeconomic status and illiteracy

leading to a lack of knowledge about the disease are the major hurdles in management of

this disease (Mehta et al., 2006).

Diabetes mellitus is a heterogeneous disorder characterised by a varying degree

of insulin resistance and insulin deficiency, which leads to disturbances in glucose

homeostasis. It is commonly associated with prolonged ill-health and premature death.

Chronic hyperglycaemia may lead to long-term complications that affect several organ

systems and may lead to poor quality of life. These complications may cause disability

and deformities among various organs. The mortality rate in patients with DM may be

up to 4-5 times higher than in persons without the disease (Morgan et al., 2000).

Diabetes is also the leading cause of stroke, renal failure, blindness and leg amputation

in adults in developed countries (Centers for Disease Control and Prevention, 2011).

Patient knowledge of diabetes mellitus can assist in early detection of the disease

and reduce the incidence of complications. The management of diabetes and its

complications not only depends on drug therapy but also on physical exercise, controlled

diet and other lifestyle modifications. Unless education is imparted and awareness is

created among people, it is difficult to control the prevalence of diabetes. Diabetes

education and awareness and improving motivation for self-care not only enhance care

and reduce the burden of complication but also indirectly reduce the overall economic

cost of diabetes (Kapur, 2001). Comprehensive patient education about diabetes and

self-care skills is the cornerstone therapy for diabetes patients to attain tight glycaemic

control (Asha et al., 2004).

4

1.2 Epidemiology of diabetes mellitus

1.2.1 Global scenario of diabetes mellitus

Diabetes is a serious condition not only for the individual, but also for society as a

whole. Almost every country is under the burden of diabetes, which is considered a

major public health problem. Diabetes is a metabolic syndrome, which if left untreated

may lead to long-term life-threatening complications and premature death (Roglic et al.,

2005).

The prevalence of diabetes has increased globally over the past two decades.

Diabetes is accepted as the fourth- or fifth-leading cause of mortality among various

diseases worldwide (International Diabetes Federation, 2011). Worldwide, several

reports have been published on the prevalence of diabetes. In developed countries, the

age group over 65 reflects the highest prevalence for the disease whereas in the

developing world, greater prevalence occurs in the 45-64 years age-group (Wild et al.,

2004). Diabetes currently affects 150 million people around the world and this number is

expected to increase to 300 million by 2025 (King et al., 1998). The projected estimation

reported by World Health Organization (WHO) and International Diabetes Federation

(IDF) about the global prevalence of diabetes was 2.8% in 2000, and it would be

increased to 4.4% in 2030 (Wild et al., 2004), and 366 million in 2011 and it is expected

to be increased to 552 million by 2030 (International Diabetes Federation, 2011)

respectively. The five countries with the highest diabetes prevalence in 2010 were Nauru

(30.9%), United Arab Emirates (18.7%), Saudi Arabia (16.8%), Mauritius (16.2%) and

Bahrain (15.4%) (Shaw et al., 2010). The United State of America (USA) was the

5

leading country among developed nations accounting for 26.8 million diabetic adults in

2010 and it is expected to increase to 36 millions by 2030 (Shaw et al., 2010).

Developing countries will be hit the hardest by the growing diabetes epidemic.

Type 2 diabetes is more common in developing countries accounting for 90-95% of total

cases (Mohan et al., 2007). An aging population, a shift towards a more sedentary

lifestyle, increasing numbers of overweight and obese people, unhealthy diet and

growing urbanisation are possible factors contributing to this alarming increase of

diabetes prevalence (Amos et al., 1997; Zimmet et al., 2001). The incidence rate of

diabetes is much higher in developing countries (170%) compared to developed

countries (47%) (Zafar et al., 2011). Approximately 2-5% of adult populations located in

industrialised countries are affected by diabetes (Atak & Arslan, 2005). The prevalence

rate of diabetes is higher in the Asian nations. Approximately 50% of total global

diabetes populations are located in Asian countries including Indian, China and Nepal.

Among the top ten leading countries in terms of diabetes burden in the world, the top

five are Asian countries, in which India (87 million) and China (62.6 million) are

expected to be lead in terms of number of people with diabetes mellitus by 2030

(Cockram, 2000; Wild et al., 2004; Roglic et al., 2005; Mohan et al., 2007).

1.2.2 Prevalence of diabetes mellitus in Nepal

Nepal is located in between India and China. It is surrounded with hills and mountains

and is nearly 500 miles long and 110 miles wide with a population of 28 million

(Ministry of Health and Population, 2011). The country is divided into three

geographical areas, the flat ‘Terai planes’ in the south, the ‘Central hills’ and the ‘High

6

Himalayas’ in the north. This division has isolated the rural areas from the central areas

and has hindered the development of transportation, communication and health facilities.

In addition, about 90% of the population lives in rural areas (Singh, 2004).

The data suggest the percentage of diabetes dominancy in urban and rural areas

is 25.9% and 3.1% respectively (Singh & Bhattarai, 2003). According to the Nepal

Diabetes Association (NDA), approximately 15% of people more than 20-years old and

19% of people more than 40 years of age are affected with diabetes in urban areas

(Bhattarai & Singh, 2007). As per the WHO estimation, more than 436,000 people are

affected with diabetes in Nepal and the number is expected to increase to 1,328,000 by

2030 (Wild et al., 2004). The prevalence rate of type 2 diabetes mellitus and impaired

fasting glucose have been reported as being about 9.0% and 19.2% respectively from

one study conducted in a semi-urban population of Nepal (Ono et al., 2007). A recent

study from Nepal also expected the prevalence of diabetes to be increased by 17% in

2020 (Dulal & Karki, 2009). The reasons behind the high prevalence of DM in Nepal are

identified as low literacy, increased body weight due to intake of more fatty food, low

physical activity and change in lifestyle (Upadhyay et al., 2008; Maskey et al., 2011).

1.3 Impact of diabetes mellitus and its complications

Diabetes affects persons of all ages, sexes and races. The disease reduces both a person’s

health-related quality of life (HRQoL) and life expectancy and imposes a large

economic burden on their families, healthcare system and the nation. Diabetes is

associated with serious long-term effects, which could have a huge impact on the quality

of life of patients, especially when both micro-vascular and macro-vascular

7

complications are present. The risk factors for developing micro-vascular complications

include duration of diabetes, glycaemic control and hypertension. The strongest risk

factors for the development of macro-vascular complications include hypertension,

hyperlipidaemia, smoking and albuminuria. Micro-vascular complications affect the

small blood vessels and comprise of retinopathy, nephropathy and neuropathy. Macro-

vascular complications encompass cerebrovascular disease, ischaemic heart disease and

peripheral arterial disease (Marshall & Flyvbjerg, 2006). The risk for macro-vascular

diseases tend to manifest in people with type 2 diabetes more than those diagnosed with

type 1 diabetes, as hyperglycaemia contributes to the development of these

complications. There is evidence that has proved the relationship between the degree of

glycaemic control and the development of these complications (Klein & Klein, 1998;

Stratton et al., 2000; American Diabetes Association, 2002a; Nordwall et al., 2009;

Huang et al., 2011).

The incidence of mortality and disability due to diabetes is rising drastically all

over the world. People with diabetes have an increased risk of mortality and morbidity

compared with their non-diabetic counterparts. As pointed out by Mohan et al. in the

2009 the WHO report, there are about five times as many deaths indirectly attributable

to diabetes (Mohan & Pradeepa, 2009). The death rate of men living with diabetes is 1.9

times and for women 2.6 times more than men and women without diabetes respectively

(Lee et al., 2000). Premature mortality caused by diabetes results in an estimated 7 to 14

years of life lost compared to their non-diabetic counterparts (Narayan et al., 2003a;

Manuel & Schultz, 2004; Andrade, 2010). The majority of the diabetes-related deaths

are due to cardiovascular and cerebrovascular diseases and end-stage renal diseases

8

(Cusick et al., 2005). It is estimated that each year, approximately 3.8 million people die

from diabetes-related complications worldwide (International Diabetes Federation,

2006).

In addition to the morbidity and mortality, diabetes exerts a heavy economic

burden on the society. This burden is related to health-system costs incurred by society

in managing the disease, indirect costs resulting from productivity losses due to patient

disability and premature mortality, time spent by family members in seeking care of the

patient and intangible costs (psychological pain to the family and loved ones). It was

estimated that the total global cost to manage diabetes was USD 376 billion in 2010 and

it is expected to increase to USD 490 billion in 2030. Globally, 12% of the health

expenditure and USD 1330/person were anticipated to be spent on diabetes management

during the year 2010. This expenditure may fluctuate by region, age, gender and

country’s income. This data shows the huge impact on a nation’s economy. By looking

at these results, there is a need for urgent measures for better understanding of the

problem and novel strategies for prevention and treatment of the disease (Zhang et al.,

2010).

1.4 Concept of pharmaceutical care vs. Medication therapeutic management

Diabetes mellitus is spreading like a slow poison all over the world and causing

complications to the sufferer and affecting their quality of life and increasing the

economic burden. An individual suffering from type 2 DM is responsible for

himself/herself to a large extent since this disease is related to lifestyle and dietary

habits. However, development of type 1 diabetes mellitus is related with autoimmune

9

destruction of the pancreatic β-cells, due to which there is absolute deficiency of insulin

in the body. Quite often patients do not adhere with their pharmacological (medication)

and non-pharmacological (lifestyle modification, dietary habits and importance of

recommended physical activities) treatments that are required to achieve the desired

metabolic control and thus minimise the emergence of micro- and macro-vascular

complications. Such problems can be avoided by increasing medication-adherence and

adopting appropriate non-pharmacological measures, in which the pharmacist can play

an important role through a well-structured pharmaceutical care (PC) programme

(Machado-Alba et al., 2011).

Pharmaceutical care involves identifying, resolving and preventing drug-related

problems. It is well understood that the pharmacist deals with medicines all the time.

Pharmaceutical care was the first integrated philosophy of pharmacy practice to combine

the expertise of the pharmacist with influencing prescribing and evaluating the drug

regimen on one side and medication counselling on the other side to improve the

patients’ therapeutic outcomes, including quality of life. The role and contribution of the

pharmacist in the healthcare system to achieve therapeutic outcome was developed by

Hepler and Strand in 1990 (Hepler & Strand, 1990). According to them, ‘pharmaceutical

care practice involves direct interaction between the pharmacist and the patient, with

responsible provision of drug therapy in order to achieve definitive outcomes that

improve a patient’s quality of life and promote disease management’. These outcomes

are: (1) cure of disease; (2) eradication or decrease of patients’ symptomatology; (3)

arresting or slowing of disease process; or (4) preventing a disease or symptomatology

(Hepler & Strand, 1990). Later, the philosophy of Hepler and Strand was refined by

10

Cipolle et al. and they said that ‘it is a patient-centred practice’ (Cipolle et al., 2004). In

both these definitions, the emphasis is on the patient and the pharmacist’s responsibility

to ensure good quality of care to the patient and to achieve better patient outcomes. The

pharmacist’s role has evolved over the twentieth century from mainly being product

focused, preparing and dispensing drugs, into a more patient-orientated care provider,

and pharmaceutical care may be the target for the pharmacy profession worldwide.

Although, pharmaceutical care is delivered by many different healthcare professionals,

the pharmacists can be regarded as specialists in this practice as their focus is on

pharmacology and pharmacotherapy, important skills for providing pharmaceutical care.

Pharmaceutical care deals with the way people should receive and use

medications and instructions for the use of medicines. It also deals with the

responsibilities, medication surveillance, counselling and outcomes of care.

Pharmaceutical care can be achieved through the performance of a team of healthcare

professionals including the pharmacist, doctors, nurses and technicians. This facilitates

good communication between the different members of the healthcare team and

continuity of care (Hepler & Strand, 1990; Palaian et al., 2005; Hudson et al., 2007).

However, the concept of Medication therapy management (MTM) is a distinct

service or group of services that optimizes drug therapy with the intent of improved

therapeutic outcomes for individual patients. Medication therapy management includes

five core components: a medication therapy review (MTR), personal medication record

(PMR), medication-related action plan (MAP), intervention and/or referral, and

documentation and follow-up. During the MTM session, the pharmacist identifies

medication-related problem(s) and determines appropriate intervention(s) for resolution.

11

Often, the pharmacist collaborates with other health care professionals to resolve the

identified problem(s) (American Pharmacist Association and National Association of

Chain Drug Store Foundation, 2008).

1.5 Concept of pharmaceutical care in Nepal

It is evident that the pharmaceutical care concept is still in the theoretical stage in Nepal

and the practice is non-existent. A thorough literature survey showed that studies are

lacking in the area of pharmaceutical care in Nepal. In Nepal, pharmacists are still

considered as 'medicine sellers' to the public and they are more product oriented rather

than patient oriented (Khanal et al., 2010). Pharmacists are still not focused on their role

in patient care in the present healthcare system of Nepal. A review by Bhandari and

associates (2006) reported that pharmacists in the country were involved in providing

drug information and research work in few Nepali hospitals (Bhandari et al., 2006)

suggesting an emerging scope, although it is not substantial.

In the Nepalese context, pharmacists focus on the industrial sector or the

teaching profession, and then open their ‘medicine shops’ after finishing their pharmacy

education. Recently, in 2010, the pharmacy education system of Nepal put a step

forward in pharmacy education and started the Pharm.D program in Kathmandu

University with the objective of providing better knowledge and more recognition and

opportunity to the pharmacy graduates in the healthcare sector (Bhuvan et al., 2011). By

this program, the education system of Nepal has provided a clear understanding to the

pharmacists on their responsibilities as a healthcare professional and their contribution

as a pharmacist in patient care.

12

The present study also focused on the contribution of the pharmacist in patient

care through the pharmaceutical care program. This study may circulate the clear

concept of pharmaceutical care among the Nepali pharmacists and their role in patient

care so that they become more patient-focused at the hospital and community level.

1.6 Pharmaceutical care and its importance in diabetes mellitus management

The need for intensive diabetes mellitus management is the subject of discussion and

debate, and it is clear that intervention programs to improve diabetes care and outcomes

are important (Gæde et al., 2003; Krass et al., 2007; Wubben & Vivian, 2008). People

with diabetes stay in the hospital much longer than the non-diabetic subjects and

therefore it is a major concern for the healthcare system. The healthcare system may

adopt certain approaches to minimise the patient stay in the hospital by improving their

symptoms. It has been reported that the frequency of hospitalisation of diabetes patients

are 1.5 times more and on an average 2.8 days longer than their non-diabetic

counterparts (Koproski et al., 1997; Puig et al., 2007).

The pharmacist's role through pharmaceutical care has come up with some

definite outcomes in the form of improved clinical outcomes (significant glycaemic

control), improved patient satisfaction, improved cost management and reduced hospital

stay (Singhal et al., 2002; Davis et al., 2005; Scott et al., 2006; Krass et al., 2007;

Wubben & Vivian, 2008; Al Mazroui et al., 2009; Monte et al., 2009; Venkatesan et al.,

2012). Pharmacists are easily accessible to patients in comparison with other healthcare

professionals and therefore can provide better healthcare services to people with

diabetes. Diabetes patients who received monitoring by the pharmacist through the

13

pharmaceutical care program reduced glycated haemoglobin (HbA1c) level by an

average 1.9% in a six month period (Rothman et al., 2003). Similarly, people with

diabetes experience greater satisfaction with their care when they received proper

diabetes education, proper medication counselling and instruction on diet and exercise

from their pharmacists (Singhal et al., 2002; Cranor et al., 2003; Zanetti et al., 2007;

Sriram et al., 2011). A study reported that diabetic patients are able to reduce their

HbA1c level to 7% or below and decrease their unscheduled clinical visits if they are

provided proper physician supervision and systematic monitoring by the pharmacist

(Irons et al., 2002). Diabetes carries a huge medical cost for the patient and their family

members and decreases the productivity rate. Studies from different countries have

stated that a reduction in medical cost and an increase in their productivity rate can be

achieved by improving the patient’s symptoms and reducing the risk rate through a

structured pharmaceutical care program (Cranor et al., 2003; Garrett & Bluml, 2005).

1.7 Problem statement

Diabetes is an emerging health problem in Nepal. The number of people with diabetes is

increasing day by day. It is difficult to estimate exact number of diabetic patients due to

a lack of proper research and documentation in Nepal. Moreover, many diabetes patients

are not aware of their problem due to lack of knowledge and awareness (Mehta et al.,

2006; Upadhyay et al., 2008). They are also not getting effective and appropriate

treatment and advice due to lack of proper healthcare facilities. The second important

aspect is the dietary habit, which is unique in Nepal and they still have the old traditional

concept. Lack of proper knowledge about the disease and poor dietary education has

resulted in late detection of the disease by the patients, thus this has been a burning

14

problem. Therefore, looking at these aspects, the study has concluded the following

problems:

Past evidence suggests a lack of knowledge and awareness about diabetes among

the Nepali diabetic population and unavailability of systematic valid plans to cope with

such problems. Similarly, there has been a dearth of data and research to assess the

health-related quality of life (HRQoL) of diabetes patients and no research has been

done to date in Nepal to quantify HRQoL due to lack of a valid instrument to measure it

in the native language. In addition, there is no systematic approach in Nepal to increase

patient adherence to their medication, resulting in poor glycaemic control in diabetes

patients. Furthermore, to the best of my knowledge, there has been no focus on direct

health-care costs (direct medical and non-medical cost) from patients prospective and

there is a scarcity of valid research and data related to it in the country as well.

Added to the above issues, information is lacking to establish the association

between provided patient-care and patient satisfaction in diabetes management in the

Nepali healthcare system. Moreover, pharmacist involvement in patient care is still not

recognised in the Nepali healthcare system. In addition, the low literacy rate (age group

15+years, total literacy rate (%) 2008/09 was 56%) in the country (Ministry of

Education, 2010) still raises concerns over patient’s knowledge and acceptance of the

PC concept. Although, the existing scarcity of data, a quick reflection over the health

care situation and health seeking behaviours of the layman, raises much concern over the

‘health concern’ among the citizens. Since diabetes is a chronic condition and may not

present much of its symptoms at the initial stages one might have a poor ‘health

concern’ over the condition especially in a country where the vast majority of the

15

population is illiterate. In addition, one study established a relationship between

economic condition, educational status and health-seeking behaviour of Nepali citizens

(Subba, 2004). These entire observations make the necessity for need of in-depth study

in relevant domains of diabetes research.

1.8 Rationale of the study and its importance

The pharmaceutical care concept and the role of the pharmacist in patient care is mainly

popular in developed countries and several studies have been done in related areas

(Clifford et al., 2002; Strand et al., 2004; Clifford et al., 2005; Davis et al., 2005; Al

Mazroui et al., 2009; Correr et al., 2009; Neto et al., 2011). The total number

pharmacists registered with Nepal Pharmacy Council till year 2010 were 1690 among 28

million population of the country, with the pharmacist-to-public ration of 1:16,568

(Nepal Pharmacy Council, 2010). But the pharmacist involvement in patient care is still

not well recognized in developing countries like Nepal where the resources are limited

and pharmacist are still recognized as mere ‘drug seller’ (Palaian et al., 2005; Khanal et

al., 2010). No research has been done to date that has focused on the pharmacist's role in

patient care through a pharmaceutical care concept in healthcare services in Nepal. Due

to limited resources and increasing population, the health-related problems like

cardiovascular diseases, hypertension and diabetes have increased tremendously leading

to long-standing complications and more mortality and morbidity. The reasons may be

linked to low literacy, low knowledge and poor awareness about the disease condition in

patients. Lifestyle changes, obesity, poor dietary habits (intake of more fatty food) and

low physical activity are making these problems more aggressive and longer standing

(Mehta et al., 2006; Upadhyay et al., 2008; Maskey et al., 2011).

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Poor healthcare facilities combined with low knowledge and awareness in

patients causes more patient’s non-adherence to their medications leading to poor

therapeutic outcomes (Whitley et al., 2006; Al-Qazaz et al., 2011) and requiring more

hospital services. Together, this produces more economic burden on patients and their

family members. Such problems become more complex in chronic disease conditions

like diabetes where patients get overburdened with prescribed medication. Therefore, it

requires a bidirectional approach. First and foremost, the diabetes educational program

about the ways to prevent the disease should be organised on a large scale. Secondly, the

diabetes patients should get proper treatment, counselling and advice as per their need.

Early detection of DM can be helpful in managing the disease by exercise and controlled

diet, which directly affects the patient’s economic burden. Education and counselling

would be helpful for the patient to maintain their blood glucose level, which directly

affects the patient’s quality of life. Very little work has been done in Nepal so far in this

regard.

Therefore, by conducting this study, we will understand better about diabetes

patients’ knowledge and awareness of their disease and its effect on their attitude and

practice. It also provides insight on the impact of diabetes on patient’s health-related

quality of life, medication adherence and clinical outcomes with emphasis of direct

healthcare costs and satisfaction level of patients.

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1.9 Contributions of the study findings

It was anticipated to have considerable contributions during beginning of the study.

Those anticipated outcomes of the study during initiation were helpful to establish the

importance of the pharmaceutical care concept in the healthcare system of Nepal where

previously no studies have addressed this concept. It was also anticipated that the

present study would be beneficial for the diabetes patients to improve their knowledge

and awareness, which will help them to improve their attitude and practice and hence

nourish their quality of life. The study will also provide a valid method to improve

therapeutic outcome and decrease economic burden. This study might also convey the

message to other healthcare professionals that the pharmacist is also an important

member of the healthcare team and can play a major role in patient care.

In addition, this study was expected to contribute to a better understanding of

future pharmacists about their role and place in the healthcare system and it may divert

their thinking to become more patient oriented. This study is an attempt to sensitise the

government and provide validated information to government officers and policy makers

so that they would have a better idea about the pharmacist's place in the healthcare

system and their role in patient care. The findings could also set up a good platform for

future researchers and provide a well-established module and primary data for further

research on a large scale. This study would develop the appropriate diabetic kit that can

be used to educate the patients (especially uneducated patients) about their disease

through live demonstrations for better understanding of the patients.

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1.10 Study objectives

Keeping the vision of the research study shown in Figure 1.1, the overall research

objectives are as follows:

1.10.1 General objective

The general objective of the research is to evaluate the impact of a pharmaceutical care

intervention targeted at newly diagnosed diabetes mellitus patients in terms of

knowledge, attitude, practice, health-related quality of life, medication adherence and

clinical outcomes, direct healthcare costs and patient’s satisfaction.

1.10.2 Specific objectives

The various specific objectives are as below:

1. To describe the demographic distribution of newly diagnosed diabetes mellitus

population with respect to their age, gender, ethnicity, education level and occupation.

2. To evaluate the impact of pharmaceutical care intervention provided by the

pharmacist in terms of knowledge, attitude and practice of patients about diabetes and its

management.

3. To quantify the impact of pharmaceutical care intervention provided by pharmacist in

terms of health-related quality of life outcomes of diabetes mellitus patients.

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Figure 1.1 Vision of the overall research

Improvespatient satisfaction

Betterhealth-relatedquality of life

Reductionin direct healthcare

costs

Reduce / prolongcomplications

Improvesglycaemic control

ImprovesSelf-care skills

Pharmaceutical care to diabetes patients

Motivation in patients

20

4. To evaluate the impact of pharmaceutical care intervention provided by pharmacist in

terms of medication adherence and clinical outcomes (i.e. glycaemia and blood pressure

control), direct healthcare costs and satisfaction of diabetes mellitus patients.

1.11 Thesis overview

This thesis consists of seven chapters including this chapter (general introduction).

Chapter 2 is related to a literature review and the conceptual framework. This chapter

gives brief information related to diabetes and its management followed by in-depth

reviews of literature related to individual study objectives with a suitable definition of

terms used wherever necessary. This chapter will be ending with the study's conceptual

framework, research questions and hypothesis with a brief conclusion about significant

gaps in diabetes care that need to be minimised with pharmacist intervention.

Chapter 3 will be basically discussing about general methodology used in present study.

This chapter will highlight the detail explanation about the methodology used in present

research study with description of different study tools and questionnaire formulation.

This chapter also talks about how the intervention and reinforcement program was

conducted for diabetes patients with a brief note on a pilot study conducted for

methodology and tools' validation.

Chapter 4 is about the impact assessment of pharmaceutical care intervention on the

knowledge, attitude and practice of newly diagnosed diabetes patients in tertiary care

hospital. This chapter includes a detailed analysis of diabetes patients’ knowledge,

attitude and practice (KAP) about diabetes and its management with emphasis of the

impact of the pharmacist-provided pharmaceutical care intervention on diabetes patients’

21

KAP. The chapter will be ending with detail discussion on study findings and

conclusion.

Chapter 5 describes the impact assessment of pharmaceutical care intervention on

health-related quality of life of newly diagnosed diabetes patients. This chapter provides

a detailed description and analysis of diabetes impact on general and overall health-

related quality of life of diabetes patients with emphasis on the impact of pharmaceutical

care intervention on health-related quality of life of diabetes patients. The chapter ends

with a discussion on the study findings and the conclusion.

Chapter 6 illustrates the impact assessment of pharmaceutical care intervention on

medication adherence and clinical outcomes, direct healthcare costs and satisfaction of

newly diagnosed diabetes patients. This chapter focuses initially on the pattern of

medication adherence and clinical outcomes of diabetes patients, assessment of direct

healthcare costs of patients and their satisfaction with an emphasis on the pharmacist

intervention on these outcomes. The chapter ends with a detailed discussion on findings

related to patients’ medication adherence and clinical outcomes, direct healthcare costs

and satisfaction along with a brief conclusion.

Chapter 7 is the thesis conclusion and also the final chapter of this thesis. This chapter

starts with a summary of the study followed by study limitations along with a set of

recommendations. The chapter ends by highlighting suitable future research and the

conclusion.

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CHAPTER 2

LITERATURE REVIEW AND RESEARCH CONCEPTUAL FRAMEWORK

2.1 Definition of Diabetes mellitus

Diabetes mellitus (DM) represents a group of metabolic disorders and is characterized

by an increase in blood glucose level termed as ‘hyperglycaemia’. It is associated with

abnormalities in carbohydrate, fat and protein metabolism that results due to defects in

insulin secretion, insulin action or a combination of both. Several pathogenic factors are

responsible for abnormality in insulin secretion and insulin action, which range from

autoimmune destruction of pancreatic β-cells to abnormalities that result in resistance to

insulin action (World Health Organization & International Diabetes Federation, 2006;

American Diabetes Association, 2012).

2.2 Classification of diabetes mellitus

Based on the aetiology, most cases of DM falls into two category ‘Type 1 diabetes

mellitus’ and ‘Type 2 diabetes mellitus’. Apart from this gestational diabetes mellitus

(GDM) and diabetes due to drugs (Drug induced diabetes mellitus) and secondary to

other disease conditions related with pancreas like acute and chronic pancreatitis etc.,

are also rarely seen (American Diabetes Association, 2002b).

In case of Type 1 DM, there is absolute deficiency of insulin due to immune-

mediated destruction of the pancreatic β-cells. This type of diabetes is common in

children and adolescents and can be managed with combination of pharmacological and

23

non-pharmacological agents like insulin, diet and exercise (Franz et al., 2004).

Autoimmune destruction of the β-cells is due to multiple genetic predispositions

and environmental factors and are still not well defined (Åkerblom & Knip, 1998;

Visalli et al., 2003; Majeed & Mea, 2011). The patients with type 1 diabetes mellitus

require exogenous administration of insulin throughout their life for survival (American

Diabetes Association, 2012).

Type 2 DM is most common type of diabetes and mainly found in 90-95% of all

diabetes cases (American Diabetes Association, 2007). This type of diabetes is also

known as ‘non insulin dependent diabetes mellitus’ (NIDDM) or ‘maturity onset

diabetes in youth’ (MODY). Type 2 DM occur due to impaired insulin secretion and

insulin resistance of target tissues, mainly liver and skeletal muscles. Type 2 DM

patients are in general at an increased risk of developing macro-vascular and micro-

vascular complications (Triplitt et al., 2005; American Diabetes Association, 2012).

These days large number of people at younger age group is developing type 2 DM due

to obesity and sedentary lifestyle (Hu, 2003). It is known that about 80% of type 2 DM

are preventable by following a healthy lifestyle, physical activity, maintaining ideal

body weight and proper nutritional supplements (International Diabetes Federation,

2009).

Gestational diabetes mellitus (GDM) refers to the detection of glucose

intolerance first time during pregnancy. Insulin resistance during pregnancy is mainly

due to certain metabolic changes which increases insulin requirement and may lead to

hyperglycaemia or impaired glucose tolerance (IGT). Most of the time women revert

back to normal glucose tolerance after post-partum with a substantial risk (30-60%) of

24

developing DM in later phase of the life (Centers for Disease Control and Prevention,

2011).

2.3 Clinical presentation of diabetes mellitus

Type 1 DM individuals are more often thin and prone to develop diabetic ketoacidosis

(DKA) due to insulin crisis, or under condition of severe stress with an excess of insulin

counter regulatory hormones. About 20-40% of patients with type 1 DM present with

diabetic ketoacidosis after several days of polyuria, polydipsia, fatigue, abdominal pain

and often with weight loss (Atkinson & Eisenbarth, 2001; Al Magamsi & Habib, 2004;

American Diabetes Association, 2007; Razavi, 2010). Commonly, patients of type 2 DM

may present with or without diabetes symptoms even though they carry the

complications indicating that they have diabetes since several years. Type 2 DM patients

may present with lethargy, polyuria, nocturia and polydipsia at diagnosis, and at times

associated with weight loss (Triplitt et al., 2005).

2.4 Diagnosis of diabetes mellitus

Normally the diagnosis of diabetes is performed only when the patient shows one or

more usual symptoms of diabetes. Early diagnosis can render better management of

diabetes and thus delaying the long term complications. The level of blood sugar is

measured in venous blood sample. The diagnosis of diabetes is performed on the basis of

the criteria given by American Diabetes Association (American Diabetes Association,

2007).