Background Better understanding of the demographic distribution of epilepsy and the prevalence of 'more specific forms of epilepsy' in community-based settings would improve our understanding of this disorder at the population level . Although we now have good estimates of epilepsy prevalence for most countries, we still lack knowledge on its demographic distribution by age, ethnicity, region, and socioeconomic status. In addition, no studies to date have reported the prevalence of epilepsy syndromes using patient interview outside a hospital setting. This thesis provides the first community-based estimates of the prevalence of the most common clinical group of epilepsies presumed to have a genetic basis - The Idiopathic Generalised Epilepsies (IGE) - by patient and witness interview. Methods This thesis has involved conducting five pieces of new research: (i) a series of reviews and analyses of descriptive data on epilepsy prevalence, particularly focusing on the critical methodological issues of ascertainment, diagnosis and classification of epilepsy for epidemiological purposes; (ii) the validation of a modified diagnostic epilepsy questionnaire adapted for administration in population studies; (iii) recruitment of a community-based cohort - The Tasmanian Epilepsy Register (TER) - through the Australian national prescription database; (iv) estimation of the overall prevalence and distribution of self-reported treated epilepsy in Tasmania by imputation methods; (v) estimation of the prevalence and distribution of IGE in Tasmania by telephone interviewing. Results My modified diagnostic questionnaire, administered by telephone interviewing and interpreted with standardized guidelines, demonstrated excellent agreement with an epilepsy specialist's clinical assessment in diagnosing the presence of epilepsy (K = 0.94), seizure-onset types (K = 0.84), simple or complex partial seizures (K=0. 87), any generalized non-convulsive seizure (K=0.82), and IGE (K = 0.82). A lthough stil l substantial, agreement was not as close for secondarily general ized seizures (K = 0.74), and generalized tonic-clonic seizures (K = 0.79). 7541 patients treated with antiepileptic drugs (AEDs) in the preceding year in Tasman ia were eligible for recruitment through the Australian national prescription database. After three mail contacts, 54.0% responded, with 43.6% who indicated treatment for epilepsy representing 86.0% of total possible epilepsy cases by imputation (n=2063) in Tasmania. 1180 agreed to participate in the TER, 90.0% of participants received their AEDs either exclusively from their general practitioner (70.9%) or in combination with a medical specialist (19.1%) in the preceding twelve months. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); this was: lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00); greater with increasing age (p< 0.001 ); similar in the three main geographical regions; and similar by categories of socioeconomic status based on postcode of residence. Following enrolment, 959/1083 (88.6%) eligible TER participants completed the diagnostic telephone interviewing, with partial epilepsy classified in two thirds, and generalised epilepsy in slightly more than one-fifth. IGE was observed in 20.3%, with tonic-clonic seizures (17.03%) and the absence epilepsies combined (11.01 %) being the most common IGE seizure types and syndromes respectively. The estimated prevalence of IGE was 0.89 per 1000; is highest between the ages of 20-39 years and in females, but was similar between Tasmanian regions and socio-economic groups. IGE prevalence beyond childhood related to refractory childhood or adolescent disease rather than olderonset cases, and was characterised by the presence of myoclonic and tonic-clonic seizures. Generalised seizures, but not IGE, were less prevalent in southern Tasmania. Conclusions Utilising the design approach described in this thesis may provide an alternative to neurological assessment, and when coupled with case ascertainment through prescription data, can provide a valid estimate of the prevalence of 'more specific forms of epilepsy' in countries with high access to health services. The observed pattern of high elderly epilepsy prevalence, is similar to patterns in recent studies in other developed countries, and has important implications for future planning of health services in these countries. IGE represents a considerable proportion of community-treated disease with important aetiological and prognostic determinants occurring at the seizure rather than syndrome level of classification.

Background Better understanding of the demographic distribution of epilepsy and the prevalence of 'more specific forms of epilepsy' in community-based settings would improve our understanding of this disorder at the population level . Although we now have good estimates of epilepsy prevalence for most countries, we still lack knowledge on its demographic distribution by age, ethnicity, region, and socioeconomic status. In addition, no studies to date have reported the prevalence of epilepsy syndromes using patient interview outside a hospital setting. This thesis provides the first community-based estimates of the prevalence of the most common clinical group of epilepsies presumed to have a genetic basis - The Idiopathic Generalised Epilepsies (IGE) - by patient and witness interview. Methods This thesis has involved conducting five pieces of new research: (i) a series of reviews and analyses of descriptive data on epilepsy prevalence, particularly focusing on the critical methodological issues of ascertainment, diagnosis and classification of epilepsy for epidemiological purposes; (ii) the validation of a modified diagnostic epilepsy questionnaire adapted for administration in population studies; (iii) recruitment of a community-based cohort - The Tasmanian Epilepsy Register (TER) - through the Australian national prescription database; (iv) estimation of the overall prevalence and distribution of self-reported treated epilepsy in Tasmania by imputation methods; (v) estimation of the prevalence and distribution of IGE in Tasmania by telephone interviewing. Results My modified diagnostic questionnaire, administered by telephone interviewing and interpreted with standardized guidelines, demonstrated excellent agreement with an epilepsy specialist's clinical assessment in diagnosing the presence of epilepsy (K = 0.94), seizure-onset types (K = 0.84), simple or complex partial seizures (K=0. 87), any generalized non-convulsive seizure (K=0.82), and IGE (K = 0.82). A lthough stil l substantial, agreement was not as close for secondarily general ized seizures (K = 0.74), and generalized tonic-clonic seizures (K = 0.79). 7541 patients treated with antiepileptic drugs (AEDs) in the preceding year in Tasman ia were eligible for recruitment through the Australian national prescription database. After three mail contacts, 54.0% responded, with 43.6% who indicated treatment for epilepsy representing 86.0% of total possible epilepsy cases by imputation (n=2063) in Tasmania. 1180 agreed to participate in the TER, 90.0% of participants received their AEDs either exclusively from their general practitioner (70.9%) or in combination with a medical specialist (19.1%) in the preceding twelve months. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); this was: lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00); greater with increasing age (p< 0.001 ); similar in the three main geographical regions; and similar by categories of socioeconomic status based on postcode of residence. Following enrolment, 959/1083 (88.6%) eligible TER participants completed the diagnostic telephone interviewing, with partial epilepsy classified in two thirds, and generalised epilepsy in slightly more than one-fifth. IGE was observed in 20.3%, with tonic-clonic seizures (17.03%) and the absence epilepsies combined (11.01 %) being the most common IGE seizure types and syndromes respectively. The estimated prevalence of IGE was 0.89 per 1000; is highest between the ages of 20-39 years and in females, but was similar between Tasmanian regions and socio-economic groups. IGE prevalence beyond childhood related to refractory childhood or adolescent disease rather than olderonset cases, and was characterised by the presence of myoclonic and tonic-clonic seizures. Generalised seizures, but not IGE, were less prevalent in southern Tasmania. Conclusions Utilising the design approach described in this thesis may provide an alternative to neurological assessment, and when coupled with case ascertainment through prescription data, can provide a valid estimate of the prevalence of 'more specific forms of epilepsy' in countries with high access to health services. The observed pattern of high elderly epilepsy prevalence, is similar to patterns in recent studies in other developed countries, and has important implications for future planning of health services in these countries. IGE represents a considerable proportion of community-treated disease with important aetiological and prognostic determinants occurring at the seizure rather than syndrome level of classification.

Excessive weight can have a severe impact on health as well as creating a significant economic burden. Obesity is reaching epidemic proportions, but the mode of inheritance of obesity and its underlying complexity remains largely unresolved. Thus, the aim of this research project was to provide a further understanding of this condition in an Australian adolescent and adult population. Qualitative and quantitative differences in genetic and environmental influences affecting body mass index (BMI) in males and females, during development were examined. Structural equation models were fitted to longitudinal data collected at ages twelve, fourteen and sixteen from 470 monozygotic (MZ) twin pairs and 673 dizygotic (DZ) twin pairs. In addition, it is generally known that some genetic differences are only exposed in the presence of certain environmental stressors, such as the effects of parity and age on post-partum obesity. Therefore, models were fitted to data from 11, 915 female twins and their sisters from whom reproductive history was available in order to assess the changes in magnitude of genetic and environmental variation in female BMI due to these variables. To detect quantitative trait loci (QTLs) influencing adolescent BMI, up to 1133 highly polymorphic microsatellite markers were typed across the genome in a sub-sample of adolescent twins, their parents and siblings. Because gene mutations for some genetic disorders affecting body weight may manifest during childhood, univariate linkage analysis were applied to test for linkage between marker loci and BMI at twelve, fourteen and sixteen across the genome. Additionally, genes involved in pathways regulating body weight may operate differently in men and women. Therefore, a genome-wide linkage analysis allowing for sex difference in linkage patterns was performed in order to identify QTLs influencing BMI which may differ between adult males and females. Genetic factors contributed strongly to BMI in adolescent twins, accounting for approximately ninety percent of phenotypic variation at twelve, fourteen and sixteen years of age. In addition, the majority of this genetic variance was transmitted from age twelve to ages fourteen and sixteen. Sex differences in the size of genetic innovations at ages fourteen and sixteen suggest that the genetic variation in weight regulation is different in males and females. The presence of environmental influences in males and females may reflect the effects of lifestyle activities during adolescents such as severe exercise and diet regimes. Structural equation models exploring the effects of parity and age on female BMI revealed that genes become more important in the variation in BMI as parity increases. The ability to retain weight for lactation and support for foetal growth possibly reflects an evolutionary advantage in times when it was a necessary condition of survival. Unique environmental influences were also important in the variation female BMI across parity and age, possibly reflecting lifestyle factors and individual responses to social attitudes towards weight gain. Genome-wide linkage analysis in adolescent twins revealed strong evidence for linkage on chromosome 14q12-q13 at age fourteen (logarithm of odds (LOD) = 3.71, p = 0.000018) and suggestive linkage in the same region in sixteen year old twins (LOD = 2.46, p = 0.00038) which has been previously implicated in adiponectin in Northern Europeans. Chromosome 6p12 yielded a suggestive LOD = 2.95 (p = 0.00012) which harboured a known gene responsible for rebound weight gain. Evidence for replication (LOD = 1) at other areas of the genome was also observed, including 1, 4, 10, 11, 13 and 20, which have been previously associated with obesity in other studies, being LEPR, UCP1, OB10P, BMIQ3 and BMIQ6, respectively, although we did not have time to genotype these to test for association in our samples. The use of a genome-wide linkage analysis allowing for sex difference in linkage patterns identified areas on chromosome 8 and 20, providing us with evidence that some of the genes responsible for BMI may have different effects in adult men and women. Results revealed a suggestive linkage peak (-log10p = 3.13; equivalent to LOD = 2.19, p = 0.000741) at 12q24 (-log10p = 3.02; equivalent to LOD = 2.08, p = 0.000955), that has been implicated in weight in a wide range of populations and where non-insulin-dependent diabetes mellitus, a consequence of obesity, has also been mapped. We also identified many peaks near the threshold for replicating an existing finding (-log10p = 2; equivalent to LOD = 1.18, p = 0.01) in many areas across the genome that are within regions previously identified by other studies, as well as in locations that harbour genes known to influence weight regulation. Finally, the significances of these results are discussed and future directions are considered including association analysis on single nucleotide polymorphisms (SNPs) across six candidate genes: LEPR, GNβ3, UCP2, UCP3, FTO and INSIG2 which have previously been associated with obesity or BMI. We typed seventeen SNPs and performed analyses in a sample of 4494 MZ and DZ twins. Significant association was found for rs9939609 (A/T polymorphism) of the FTO gene. In our data, each additional copy of the rs9939609 A allele increased mean BMI by approximately 0.14kg/m2 in an apparent additive manner, comparable with recent published results from population-based studies in white European children and adults.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

Chronic heart failure (CHF) is defined as a complex clinical syndrome that is frequently, but not exclusively, characterised by objective evidence of an underlying structural abnormality or cardiac dysfunction. CHF affects up to 3% of the adult population and this rate is consistent throughout the developed world. In spite of the proven efficacy of treatments, there is a common theme of low implementation rates for recommended therapeutic guidelines. In Australia, where access to specialist CHF management is limited, the burden of care, for the 40% of CHF patients living outside capital cities falls predominantly onto community-based general practitioners (GPs). Unfortunately, there are diminishing numbers of GPs in rural and remote regions and this has created an apparent dual deficit in terms of equitable access to primary and specialist care for the CHF population living in these areas. The purpose of this research was to determine, in a series of themed studies, the population distribution, management and potential information technology solutions for CHF in rural and remote Australia. Appropriate methods were utilised for each study and included epidemiological studies, a quantitative analysis of a large practice audit, geo-mapping, a systematic review, a case study review and a qualitative analysis of participant feedback and clinical notes.

Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.

Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.

Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.