Development and Validation of Medical Decision Tools in Detection and Treatment of Abdominal

311 Pages·2017·11.16 MB·English

by  Manar Khashram

Development and Validation of Medical
Decision Tools in Detection and Treatment of
Abdominal Aortic Aneurysm

Dr. Manar Khashram

A thesis submitted for the degree of Doctor of Philosophy
University of Otago, Christchurch, New Zealand
December 2016

In memory of Professor Philip J Walker
(8 December 1957 - 31 December 2014)
A true surgeon, academic and mentor
This work was initially stimulated by a 79-year-old man who presented to
hospital with a ruptured abdominal aortic aneurysm. He was in profound
shock, was not able to be retrieved and died after 1 hour of hospital
presentation. On assessing his available radiological imaging performed 6
years ago, an undiagnosed 3.3cm infrarenal abdominal aortic aneurysm was
seen.
Potentially, his aneurysm could have been treated prior to his demise.
Abdominal aortic aneurysm (AAA) is a permanent dilatation of the infrarenal
segment of the abdominal aorta which can be fatal if the aneurysm ruptures.
Ruptured AAA is the second leading cause of global surgical mortality, and
prophylactic AAA repair can decrease mortality by a tenfold if surgery is
performed as an elective procedure. While screening and repair of AAA could
potentially reduce AAA-related mortality, selecting patients that are likely to
benefit from repair remains a complex medical decision process which has
been compounded by an improved life expectancy of the general population,
minimal invasive treatment methods and the increased prevalence of AAA in
the elderly.
The overall aim of this thesis was to improve detection and management of
AAA and to develop a predictive decision tool that can assist in clinical
management. This thesis has been conducted, to shed some light into issues
highlighted above using New Zealand and international data. The format of
this thesis was categorized into three main domains: First, the prevalence of
AAA and the influence of aortic size on late survival was documented in a
large cohort of individuals undergoing CT colonography for gastrointestinal
symptoms in Canterbury, New Zealand; Second, a systematic review and
meta-analysis of prognostic factors that might influence late survival
following AAA repair were performed, and the national clinical and
administrative AAA repair databases were interrogated to provide
epidemiological and outcome data; Third, the factors identified from this
review were applied into developing a discrete event-simulation model to
predict survival following AAA repair. The model developed has been
externally validated against existing national databases of patients
undergoing AAA repair and it appears sufficiently accurate to predict five-
year survival. The results and conclusions presented throughout this thesis
fill some of the gap in AAA knowledge, and such predictive decision-making
tools might help improve AAA management.
I would like to thank Professor Justin Roake and Associate Professor Gregory
Jones for the invaluable supervision and mentorship they provided during
this thesis. I would also like to express my gratitude to the Foundation for
Surgery- New Zealand Research Scholarship and the University of Otago for
funding this research project. A special thank you goes to Department of
Surgery, particularly Morwenna Malcolm, for the administrative support,
and for the analytical team at the Ministry of Health for providing national
data throughout the research period.
There were several researchers that I collaborated with in this work and
without whom this project would not be completed: Jonathan Williman, Phil
Hider, Ian Thomson, Peter Sandiford, Suzanne Pitama and Giorgi
Kvizhinadze, and four medical students: Anshuman Gupta, Mohamud
Osman, Michaela Mullen and Heidi Chen.
The automated data-entry for model validation in Chapter 6 was built with
the help of my Excel-guru brother Ziad- thank you for the endless hours
advising on data problems across continents.
To my parents for the continuous encouragement, and my wife Rasha- I am
not sure I could have done this without your support.
To the “vascular and friends” weekly running sessions during the last year of
the thesis that kept me sane and focused.
Last but not least, to those patients with an AAA whose data was used to
generate this work, in the hope that your experiences might help the lives of
others.
Preface .................................................................................................................... ii
Abstract ................................................................................................................. iii
Acknowledgements ............................................................................................ iv
Table of Contents ................................................................................................. v
List of Figures ..................................................................................................... xiii
List of Tables ...................................................................................................... xvi
List of Abbreviations ........................................................................................ xix
List of Publications ............................................................................................ xx
Chapter 1: Approaches to Detection and Management of Abdominal
Aortic Aneurysms ................................................................................................ 1
1.1 Introduction to AAA ...................................................................................................... 1
1.2 Abdominal Aortic Aneurysm .................................................................................... 2
1.2.1 Definition ................................................................................................................... 2
1.2.2 Risks for developing AAA .................................................................................. 2
1.2.3 AAA presentation .................................................................................................. 2
1.2.4 Prevalence of AAA ................................................................................................. 4
1.2.5 The burden of AAA on health systems ........................................................ 6
1.3 Natural History of AAA ................................................................................................ 7
1.3.1 Risks of small AAA expansion ......................................................................... 7
1.3.2 Risks of AAA rupture ........................................................................................... 8
1.4 Measurement and Detection .................................................................................... 9
1.4.1 Variations in methods of measurement ..................................................... 9
1.4.2 Detection of AAA by serendipity or screening ..................................... 11
1.5 Management of Established Asymptomatic AAA ........................................ 12
1.5.1 Surveillance of small AAA .............................................................................. 12
1.5.2 AAA repair of small AAA (<5.5cm) ............................................................ 13
1.5.3 AAA repair of large AAA (>5.5cm) ............................................................. 14
1.5.4 Long-term results ............................................................................................... 18
1.5.5 Cost estimates of AAA repair ........................................................................ 18
1.5.6 Long-term survival following AAA repair .............................................. 20
1.5.7 Factors influencing late survival ................................................................. 20
1.5.8 AAA-related death .............................................................................................. 21
1.5.9 Quality of life after repair ................................................................................ 22
1.6 Screening for AAA ....................................................................................................... 22
1.6.1 History of screening ........................................................................................... 22
1.6.2 AAA screening trials .......................................................................................... 22
1.6.3 Established screening programmes ........................................................... 24
1.6.4 Cost effectiveness of AAA screening .......................................................... 25
1.6.5 Reasons for lack of screening ........................................................................ 26
1.7 Challenges ....................................................................................................................... 26
1.7.1 Women and AAA disease ................................................................................. 26
1.7.2 AAA in the elderly ............................................................................................... 27
1.7.3 Targeted screening............................................................................................. 28
1.7.4 Barriers to AAA screening .............................................................................. 29
1.7.5 Who to target for AAA screening?............................................................... 29
1.8 New Zealand Specific AAA Data ............................................................................ 30
1.9 Academic Papers .......................................................................................................... 31
1.10 Structure of Thesis ................................................................................................... 33
Chapter 2: The Use of CT Colonography to Determine the Prevalence
of AAA ................................................................................................................... 35
2.1 Overview .......................................................................................................................... 35
2.2 Contribution ................................................................................................................... 36
2.3 Publication ...................................................................................................................... 36
2.4 Background .................................................................................................................... 36
2.4.1 Surrogate screening with CT colonography ........................................... 37
2.4.2 Selection process ................................................................................................. 37
2.4.3 CTC and AAA detection .................................................................................... 37
2.5 Objectives ........................................................................................................................ 38
2.6 Methods ............................................................................................................................ 38
2.6.1 Measurements ...................................................................................................... 39
2.6.2 Patient data collection ...................................................................................... 41
2.6.3 Validation of AAA measurement with CTC and USS........................... 41
2.6.4 Statistical analysis .............................................................................................. 41
2.7 Results .............................................................................................................................. 42
2.7.1 Patient Demographics ...................................................................................... 44
2.7.2 AAA prevalence ................................................................................................... 46
2.7.3 Predictors for AAA presence......................................................................... 47
2.7.4 Location of patients undergoing CTC ....................................................... 48
2.7.5 Fate of patients with a native AAA ............................................................. 49
2.7.6 Late survival of the population .................................................................... 49
2.7.7 CTC versus US measurement study ........................................................... 51
2.8 Discussion ....................................................................................................................... 52
2.8.1 AAA NZ prevalence ............................................................................................ 53
2.8.2 Combining all AAA prevalence studies from NZ ................................. 53
2.8.3 International AAA prevalence ...................................................................... 55
2.8.4 The impact of CTC on AAA detection ........................................................ 56
2.8.5 Other potential advantages from the CTC .............................................. 57
2.9 Limitations ..................................................................................................................... 58
2.9.1 Population studied............................................................................................. 58
2.9.2 Measurement differences ............................................................................... 59
2.9.3 Retrospective nature ........................................................................................ 59
2.10 Conclusions ................................................................................................................. 59
2.11 Further Work ............................................................................................................. 60
Chapter 3: The Definition of Abdominal Aortic Aneurysm: Predictors
for Developing AAA and Effects on Long-Term Survival ......................... 61
3.1 Overview ......................................................................................................................... 61
3.2 Contribution .................................................................................................................. 62
3.3 Publications ................................................................................................................... 62
3.4 Background .................................................................................................................... 62
3.4.1 The “normal” aorta and definition of AAA ............................................. 62
3.4.2 Aortic diameter and influence on survival ............................................. 64
3.5 Objectives ....................................................................................................................... 64
3.6 Methods ........................................................................................................................... 65
3.6.1 Study population ................................................................................................ 65
3.6.2 Aortic measurements ....................................................................................... 65
3.6.3 Definitions ............................................................................................................. 66
3.6.4 Data acquisition of aortic diameters in Māori ....................................... 67
3.6.5 Statistical analysis .............................................................................................. 68
3.7 Results ............................................................................................................................... 69
3.7.1 Aortic diameters .................................................................................................. 70
3.7.2 Infrarenal aortic diameters ............................................................................ 72
3.7.3 Influence of age and sex on infrarenal aortic diameters .................. 73
3.7.4 Sub-group analysis of Māori Aortic Diameters..................................... 74
3.8 Predictors of a larger aorta ..................................................................................... 79
3.8.1 Predicting the presence of AAA.................................................................... 81
3.8.2 Aortic size index and effect on survival ................................................... 83
3.8.3 Adjusted effect of infrarenal aortic diameter on survival ............... 85
3.8.4 Validity of CT measurements (Inter-observer error)........................ 86
3.9 Discussion ....................................................................................................................... 88
3.10 Limitations ................................................................................................................... 92
3.11 Conclusions .................................................................................................................. 94
3.12 Future Work ................................................................................................................ 94
Chapter 4: Determinants of Late Survival Following AAA Repair: A
Systematic Review & Meta-Analysis ............................................................. 95
4.1 Overview .......................................................................................................................... 95
4.2 Contribution ................................................................................................................... 95
4.3 Publications .................................................................................................................... 96
4.4 Background .................................................................................................................... 96
4.5 Objectives ........................................................................................................................ 97
4.6 Methods ............................................................................................................................ 97
4.6.1 Search strategy ..................................................................................................... 97
4.6.2 Inclusion and exclusion selection criteria ............................................... 98
4.6.3 Study selection ..................................................................................................... 99
4.6.4 Data extraction and quality assessment .................................................. 99
4.6.5 Statistical analysis .............................................................................................. 99
4.7 Results ............................................................................................................................ 100
4.7.1 Demographical factors .................................................................................. 105
4.7.2 Clinical assessments/investigations ....................................................... 107
4.7.3 Comorbidities & risk factors ....................................................................... 108