Thesis outline

In brief, the structure of the thesis is as follows: Chapter 1: Introduction

This chapter summarises key topics related to thesis including the clinical manifestations of stroke, the occurrence of stroke, the measurement of outcomes after stroke, and a description of the healthcare system in Viet Nam and, in particular, the hospital in which the studies reported in this thesis were conducted.

Chapter 2: Methods

This chapter provides general information on the methods used in the surveillance study (Chapter 3) and the cohort study (Chapters 4-7). Specific information on each study are included in the relevant chapter.

Chapter 3: Hospital-based surveillance of stroke over 12 months at a tertiary teaching hospital in Ho Chi Minh City, Viet Nam.

This chapter describes a surveillance study of patients with stroke admitted to 115 People’s Hospital during a 12 month period to examine the age of stroke onset, type of stroke, severity of stroke at admission and 28-day case-fatality. The incidence density of hospital- admitted first-ever stroke in Ho Chi Minh City is present in this chapter. At the time of submission of this thesis, the content of this chapter had been submitted as a manuscript in consideration of publication in the International Journal of Stroke.

30 Chapter 4: Case-fatality and functional status three months after first-ever stroke in Viet Nam.

This chapter describes a follow-up of a cohort of 441 patients with first-ever stroke admitted to the Stroke Unit of 115 People’s Hospital in Ho Chi Minh City, Viet Nam, to examine the associations between study factors (demographic factors, socio-economic factors, health status before stroke onset, lifestyle risk factors, clinical status at admission) and severity of functional status at three months. At the time of submission of this thesis, the content of this chapter have been prepared as a manuscript for submission in

consideration of publication in the European Journal of Neurology Chapter 5: Costs of first-ever stroke in Viet Nam.

This chapter reports estimates of the direct medical, direct non-medical and indirect costs during hospitalisation from 437 members of the cohort of patients with first-ever stroke admitted to Stroke Unit of 115 People’s Hospital. At the time of submission of this thesis, the content of this chapter have been prepared as a manuscript for submission in

consideration of publication in the Value in Health journal.

Chapter 6: Health-related quality of life after stroke: reliability and validity of the Duke Health Profile for use in Viet Nam.

This chapter reports an investigation of the reliability and validity of measurements of HRQoL of stroke survivors at three months made with the Duke Health Profile. The sample for this study consists of 108 of the first 135 participants in the cohort of patients with first-ever stroke admitted to Stroke Unit at 115 People’s Hospital who had survived to three months, and 94 of their caregivers. At the time of submission this thesis, the content of this chapter is accepted for publication in the International Journal of Quality of Life Research [1].

Chapter 7: Health-related to quality of life among survivors three month after stroke. This chapter reports measurements three months after stroke onset made with the Duke Health Profile and the EuroQoL EQ-5D of the HRQoL of 376 stroke survivors in the cohort of stroke patients with first-ever stroke admitted to Stroke Unit at 115 People’s Hospital. At the time of submission this thesis, the contents of this chapter have been prepared as a manuscript for submission in consideration of publication in the Stroke Journal.

Chapter 8: Summary.

This chapter draws together the major findings and conclusions, summaries the contributions of the thesis, and presents recommendation for future research.

31

Chapter 2: Methods

2.1. Preface

The aims of this thesis were to investigate the occurrence, presentation, costs and three-month outcomes of stroke in Ho Chi Minh City, Viet Nam. The findings in respect of occurrence and presentation of stroke in this thesis were derived from hospital-based surveillance of patients with stroke who were admitted to 115 People’s Hospital during the period from 9th _December 2009 to 8th _{December 2010. To obtain information on costs related to stroke treatment in} hospital and on outcomes at three months, a cohort of patients with first-ever stroke was recruited and followed over a three month period in a study conducted from 1st February 2012 to 31st December 2012. This chapter provides information firstly on the surveillance study, and secondly on the cohort study. The data obtained using the methods outlined in this chapter will be analysed in subsequent chapters.

2.2. Surveillance of stroke

The author of this thesis supervised the data collection and data management at the study site, cleaned the data, undertook the data analysis and interpretation, and drafted the manuscript reporting the results that is included as Chapter 3 of this thesis.

Background

The hospital-based surveillance of stroke was conducted as part of a larger project funded by The Atlantic Philanthropies to organise systems for surveillance of non-communicable diseases in Viet Nam. This project was a joint undertaking of the Ministry of Health of the Socialist Republic of Viet Nam and its technical advisers, the Menzies Institute for Medical Research (previously named the Menzies Research Institute and, when this study commenced, the Menzies Centre for Population Health Research) and the WHO.

In respect of surveillance of stroke, major tertiary hospitals with stroke care in Ha Noi and Ho Chi Minh City were visited by Australian project leaders to identify potential sites based on certain selection criteria. These included the quality of systems for ascertainment of hospital admissions for stroke, facilities for the treatment of stroke, and the annual average number of admission for stroke. The sites chosen were 115 People’s Hospital, a major teaching hospital located in Ho Chi Minh City in the south of Viet Nam, and Bach Mai Hospital located in Ha Noi in the north of Viet Nam. This thesis presents findings of surveillance at 115 People’s Hospital in Ho Chi Minh City.

Study site

115 People’s Hospital was one of three tertiary hospitals (Cho Ray Hospital and Gia Dinh Hospital were the others) with stroke intensive care facilities in Ho Chi Minh City in 2007. At this hospital, the majority of stroke patients are admitted to the Stroke Unit of the

Cerebrovascular Disease Department after transfer from the Emergency Department. Small numbers of patients with very severe stroke were at that time admitted to the Intensive Care Unit (ICU) or the Cardiology Department. For this study, a system for capture of data within

32 each of these departments in the hospital had to be devised to ensure that ascertainment of patients with stroke was as complete as possible. After the completion of this study, an

Intensive Care Unit was established in 2012 for the treatment of severe stroke cases within the Cerebrovascular Disease Department.

Trialling of systems organisation and piloting of the survey was undertaken from September 2008 to August 2009. This included assessment of and improvements to methods of

ascertainment of stroke admissions in the hospital, instruction and guidance in questionnaire administration, testing of follow-up processes, and training in data entry procedures. A study to examine the reliability of stroke diagnosis and recognition of neurological signs and symptoms of stroke by local physicians was conducted in the study hospital during that period. The performance of these tasks by local physicians was compared with that of an Australian specialist (Dr Velandai Srikanth) [295].

Subjects

During the 12-month period from 9th December 2009 to 8th December 2010, patients

admitted with a diagnosis of stroke to the Emergency Department, ICU, the Stroke Unit of the Cerebrovascular Diseases Department, or the Cardiology Department were ascertained for possible recruitment in this study. The patients were considered for inclusion if they had been assessed by a neurologist in the ICU or Cerebrovascular Disease Department as having symptoms and signs of stroke. Confirmation by diagnostic neuro-imaging techniques – computerized tomography (CT) or magnetic resonance imaging (MRI) – was available for almost all cases. Exclusion criteria were transient ischemic attack (TIA) defined as focal neurologic symptoms lasting less than 24 hours, or discharge within 24 hours from the

hospital. Ascertainment and recruitment of cases is believed to be high (greater than 90%) but this cannot be confirmed because the denominator number of eligible cases was not able to be quantified.

Study tools

This study was conducted using the Step 1 (events in hospital) protocol of “The WHO

STEPwise approach to stroke surveillance (STEPS-Stroke)” survey methodology [98]. This is a standardized protocol developed by the WHO. The full protocol comprises three steps: Step 1 (events in hospital) for identifying cases of stroke admitted to hospital, Step 2 (fatal events) for identifying fatal stroke cases in the community, and Step 3 (non-fatal events) for

identifying non-fatal stroke cases in the community. Details of this protocol were provided in the previous Chapter.

Two primary data collection instruments were developed. The first was the stroke log form (Appendix 2A), a simple record of stroke admissions to each department. This form captured name, age, sex, type of stroke, hospital record number and whether the patient was transferred between departments. The second was a brief questionnaire to capture essential information on demographic details, type of stroke, signs and symptoms of stroke onset, risk factors, disability and vital status 28 days post-stroke (Appendix 2B). These were developed in several iterations in conjunction with the clinicians involved, and with translation in Vietnamese and back-translation to check accuracy.

33 Study factors

Clinical presentation of stroke

Signs and symptoms of stroke

Stroke signs including impaired consciousness, definite brainstem signs, limb weakness, face weakness, loss of sensation, visual field deficit, neglect, aphasia/dysphasia, apraxia and ataxic gait were assessed and recorded by neurologists. Symptoms of stroke including dizziness, headache, blurred vision, double vision, slurred speech, difficulty swallowing, confusion and seizures were recorded by neurologists from self-report of patients or their caregivers.

Risk factors

Vascular risk factors for stroke including atrial fibrillation, current smoking status, diabetes, hyperlipidaemia, hypertension and valvular heart disease were assessed by the treating physician.

Type of stroke

Type of stroke including ischaemic stroke (IS), intra-cerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH) was determined by neurologists using diagnostic neuro- imaging (CT or MRI).

First-ever stroke

The first-ever stroke was defined as a stroke occurring for the first time during a patient’s lifetime. Previous stroke was determined by a neurologist using all available information including hospital records, neuroimaging results and self- or family-member report. Outcome factors

Case-fatality at 28 days

Deaths due to stroke occurring in hospital and during the 28 days post-stroke onset were ascertained by telephone interview of the stroke patient or a family member to allow calculation of 28-day case fatality.

Functional status at admission

Functional status of stroke patients at admission, or soon thereafter, was assessed on the modified Rankin Scale (mRS) by a neurologist. The mRS scores are a grading of disability in six levels [122] ranging from 0 (normal) to 6 (death). For further details of this instrument, refer to section 3 of Introduction.

Hospital-admitted incidence density

The incidence density of hospital-admitted stroke was estimated from the number of patients with a first-ever stroke who were Ho Chi Minh City residents and had provided a residential address that could be geocoded to a ward of Ho Chi Minh City, and with the total of the populations of those wards as the denominator. The population data were provided by the General Statistics Office from Census data for 2010.

34 Data collection

The log form (Appendix 2A) was filled in by nurses or physicians working in each

department. The questionnaire (Appendix 2B) was completed by a treating physician in the Stroke Unit (one of 14 physicians) or ICU (one of two physicians). The treating neurologist assessed functional status of patients at admission using the mRS. Research nurses in the Stroke Unit contacted patients or their caregivers by telephone 28 days post-stroke to collect data on vital status, and entered data into the database.

Data management

Hard copies of the log forms and questionnaires were collected weekly from the sites and stored in locked filling cabinets in the Cerebrovascular Disease Department, 115 People’s Hospital. EpiData was used as a database to store data entered from the log forms and questionnaires. Data entry was conducted by research nurses. The data file was sent fortnightly to the Menzies Institute for Medical Research where it was checked for

inconsistencies and potential errors, and with results communicated to the site for action or verification where necessary.

When all data entry was completed, data cleaning – particularly to identify duplicate records (of which there were around 10,000), to identify missing data and to replace with complete data where possible, and to correct errors – was undertaken at the Menzies Institute for Medical Research by the author of this thesis.