published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Public Health / Master / Master of Public Health

Background: Many western observational studies suggest moderate alcohol use is associated with better health including lower risk of cardiovascular diseases, diabetes and cognitive decline. However, the apparent benefit is susceptible to confounding by healthier attributes in moderate users. Randomized controlled trials of moderate alcohol use are infeasible. To assess the validity of these association for causal inference, I examined these associations in a setting (Southern China) with a different social patterning of alcohol use from more commonly studied western populations and using a Mendelian randomization design. Objectives: This thesis utilized two large Southern Chinese cohorts, the Guangzhou Biobank Cohort Study (GBCS) (n=30,499) and the Elderly Health Centre (EHC) Cohort (n=64,353) to examine sex-specific association of moderate alcohol use with cognitive function using observational designs. I also examined systematic differences between alcohol users and the credibility of alcohol-metabolizing genes as instruments for Mendelian randomization in GBCS. Mendelian randomization was used to examine the effect of alcohol use on cognitive function and cardiovascular risk factors and morbidity among men in GBCS. Methods: I used multivariable linear regression to examine the adjusted association of alcohol use categories (never, occasional, social weekly (EHC only), moderate, heavy and former) with cognitive function, measured by delayed 10-word recall test (phases 1-3 of GBCS), Mini-Mental State Examination (phase 3 of GBCS) and Abbreviated Mental Test (EHC), stratified by sex and age. I used multinomial logistic regression to examine the sex-specific systematic difference by alcohol category in GBCS. I used multivariable linear regression to examine the genetic association of ALDH2 with different cardiovascular risk factors and morbidities, cognitive outcomes and liver enzymes and to assess if alcohol phenotypes mediated any apparent genetic association in men. I used 2 stage least squares (2SLS) regression to examine the association of alcohol units (10g ethanol/day) with cognitive function and cardiovascular risk factors (blood pressure, lipids and fasting glucose) and morbidities (self reported cardiovascular disease and ischemic heart disease) in men in GBCS. Results: Occasional alcohol use, rather than moderate alcohol use, was consistently associated with higher cognitive function in both studies. Systematic differences among alcohol users were present. Occasional alcohol users had better health attributes while moderate users had slightly poorer attributes compared to never users. Aldehyde dehydrogenase 2 (ALDH2) was a credible instrument for Mendelian randomization. From Mendelian randomization, low to moderate alcohol use was not associated with cognitive function in men. However, it was positively associated with HDL cholesterol and diastolic blood pressure but not with fasting glucose or cardiovascular morbidity in men. Conclusions: Moderate alcohol use was not associated with cognitive function, suggesting that previous positive studies could be confounded by better health attributes in moderate users. The lack of association of alcohol use with cardiovascular morbidity despite raising HDL cholesterol is consistent with non-observational studies showing the non-causal role of HDL cholesterol in cardiovascular disease. These may suggest the apparent cardioprotection of alcohol is confounded although it remains possible that cardioprotection is population-specific via pathways other than HDL cholesterol, which require further investigations. / published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Background: With the increasing public health concern over the alcohol related health burden and mortality globally, the World Health Organization (WHO) has listed alcohol use as the top three risk factors in Non-Communicable Disease (NCD) and the alcohol related mortality and morbidity could be avoided through early intervention and prevention. The Department of Health (DH) of Hong Kong Special Administration Region (HKSAR) has declared the alcohol epidemic was alarming with the increasing in prevalence of alcohol use and binge drinking especially among young people with the westernization of Hong Kong society. In combating local alcohol use epidemic, DH has put priority to reform health care sector system and to ensure that the local health care system is responsive to the local alcohol use problem. Brief intervention (BI) was found to be effective in dealing with at-risk alcohol use especially in primary health care settings in the various past systematic reviews. However, most reviews mainly focus on physician-led BI while the role of nurse in BI delivery in alcohol drinking had not been under great attention. The effectiveness of nurse-led BI to at-risk drinking has not been fully examined as compared with physician-led interventions in the past reviews. Evaluation of treatment components in terms of intensity, treatment components and service settings may also shed light to public health policy makers in development of local model of BI in dealing with drinking problem in the Chinese population. Objective: To investigate the effectiveness of physician-led or nurse-led BI on quantity of alcohol consumption, number of drinking days, number of binge drinking episode and health care utilization. The potentially effective treatment intensity, treatments components and setting of intervention were also investigated. Methods: All the studies published from 1990 to 2012 in MEDLINE, would be evaluated on the effectiveness of BI delivered by physicians and/or nurses to adult at-risk drinkers in primary health care settings, were searched and identified using a combination of keywords. Results: A total of 13 randomized controlled trials out of 134 articles from MEDLINE were included in this systematic review. The included studies used different outcome measurements to compare the effectiveness of BI by physicians and/or nurses in treating at-risk drinking. Similar demographics and clinical characteristics of the subjects between the intervention and control groups were reported. The studies were from 5 countries. The age range of subjects was from 14 to 75 years old. Majority of subjects drank beyond the recommended limits defined by Alcohol Abuse and Alcoholism (NIAA), United State (US). Through there were discrepancies among the results generated in the included studies on the effectiveness of physician-led and/ or nurse-led BI, the benefits of nurse-led BI in treatment of at-risk drinking cannot be dispelled and could be considered as an alternative or supplement to the physician-led BI in busy primary health care setting today. BI with at least two 5-15 minute sessions was found to be more effective than very BI with one 5-minute session only. High quality BI with all five essential treatment components (information giving, advice, goal setting, assistance and follow up) were found to be more effective than partially included treatment. BI were found effective in dealing at risk alcohol use in all General Out Patient Clinic (GOPC) while the effectiveness of BI on alcohol drinking in Special Out Patient Clinic (SOPC) needs further research to warrant the result. Conclusion: Based on this systematic review, the potential effects of nurse-led BI remain unclear in comparison with physician-led BI for at-risk drinkers. More researches on the effectiveness of BI by nurse and its cost-effectiveness as well as BI delivered by different primary health care personnel in treating at-risk alcohol drinking with long study period, especially in the Chinese population, is needed to provide further evidence on the development of local BI in local primary health care settings. / published_or_final_version / Medicine / Master / Master of Public Health

Background: The world is facing an ageing population. Physical inactivity is considered as the fourth leading risk factor for non-communicable diseases. Walking is recognized as an affordable exercise to elderly people. However there is rarely any systematic review conducted to examine the effect of walking on quality of life of elderly people Objective: This systematic review of randomized controlled trials is to examine the effect of walking on quality of life (QoL) of older people. Methods: Articles were searched through Medline and Ovid by using keywords of “elderly people”, “aged, 50 or more”, “old people”, “elderly”, “the aged”, “walk”, “walking”, “QoL” and “quality of life”. PICO criteria were used for the criteria in selecting articles for this review. CONSORT 2010 checklist was used to assess the quality of included studies. Results and Discussion: 8 articles out of 237 articles from Medline and 883 articles from Ovid were included in this systematic review after applying the inclusion and exclusion criteria. Studies were from 4 different countries. Average age of the subjects was above 60. Subjects were randomized to intervention (walking) and control groups. Outcome measures were QoL indicators. There was significant improvement in various QoL dimensions while other studies have results of either no significant difference between intervention and control groups, or results favoring the control group. Subjects’ adherence was high in the initial phase, yet it was doubtful whether subjects could maintain the habit without the assistance of experimenter and the assisting measures. Conclusions: From this systematic review, the effect of walking on quality of life on elderly people is still unclear. More large scale research works, especially randomized controlled trials are needed to examine the effect of walking on elderly people. / published_or_final_version / Public Health / Master / Master of Public Health

The current obesity epidemic has intensified research on lifestyle interventions aimed at combating obesity and associated cardiovascular (CV) and metabolic risk. This clustering of risk factors with obesity is known as the “Metabolic Syndrome” (MS). There is now a large body of evidence detailing the ability of omega-3 fatty acids (n-3 FA) and regular moderate exercise to independently ameliorate several CV risk factors; however the combination of these interventions may be a more effective strategy in reducing CV risk than either treatment alone. This thesis describes the independent and combined effects of supplementation with docosahexaenoic acid (DHA) rich fish oil, and regular moderate exercise, on CV, metabolic and inflammatory biomarkers. Sedentary, overweight volunteers (BMI > 25kg/m2) with mild hypertension (140/90 – 160/100mmHg), elevated plasma triglycerides (TAG) (>1.6mmol/L) or elevated total cholesterol (TC) (>5.5mmol/L) were recruited in three cohorts for a 12-week intervention trial. Subjects were randomised to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (placebo), sunflower oil and exercise. Subjects consumed 6 g/day of DHA-rich fish oil (26% DHA, 6% EPA; ~1.9g n-3 FA) or sunflower oil. The exercise groups walked 3 days/wk for 45 min, at 75% age-predicted maximal heart rate (HR). Outcome measures were assessed and compared across each intervention group at Weeks 0, 6 and 12, with the exception of body composition, heart rate variability (HRV) and immune functions, which were assessed at Weeks 0 and 12 only. Apart from the consumption of allocated capsules, all subjects were instructed to maintain their normal diet during the study. If not asked to exercise as part of the intervention subjects were also instructed to maintain their normal level of physical activity. Supplementation with DHA rich fish oil resulted in substantial increases in total long chain n-3 FA and DHA levels in erythrocyte membranes, accompanied by reduction of TAG, increase of high-density lipoprotein (HDL) cholesterol and reduction of superoxide production by stimulated neutrophils. Both the increase in HDL and the decrease in superoxide production were correlated with the change in erythrocyte DHA. Endothelium dependent arterial vasodilation (assessed by flow-mediated dilatation, FMD), HRV and HR response to exercise were also improved in subjects supplemented with the DHA-rich fish oil. Regular moderate intensity exercise, either alone or in addition to the DHA-rich fish oil supplementation, had no effect on these parameters, although it improved the compliance of small resistance arteries. Interestingly, however, both DHA-rich fish oil and regular exercise reduced body fat and these effects were additive when the interventions were combined. The change in fat mass was accompanied by an increase in fat oxidation during exercise, as measured by the respiratory exchange ratio. For the population as a whole, reductions in total and abdominal fat mass were associated with reductions in blood pressure. In summary, this study is the first to evaluate the metabolic and CV benefits that can be achieved by combining n-3 FA supplementation from fish oil and regular aerobic exercise in overweight/obese adults. While this combination did not produce any synergistic effects, several independent benefits were attained. The high compliance rate (>85%) within this study indicates that this intervention is well tolerated and may therefore be sustainable in the longer term. Future research should evaluate the mechanisms underlying the n-3 FA - mediated improvements in body composition. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1283720 / Thesis (PhD) -- School of Molecular and Biomedical Science, 2007

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The antimutagenic potency of wheat grain and berry extracts was studied in vitro against several heterocyclic amines (HCAs) using the Salmonella mutagenicity assay and the anticarcinogencity of wheat grain was studied in vivo using the rat colonic aberrant crypt focus assay. Wheat bran, which binds HCAs in vitro, as well as refined wheat and unrefined whole wheat, inhibited the mutagenic activities of 2-amino-3- methylimidazo [4, 5-f] quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) when they were co-incubated and the supernatant (minus grain) was added to the Salmonella mutagenicity assay. The water-soluble fraction alone from refined and unrefined wheat, but not bran, also inhibited these mutagens in vitro. In vivo, AIN- 93G diets containing refined wheat or unrefined wheat were examined for their ability to inhibit IQ-induced colonic aberrant crypt foci (ACF) in the F344 rat. A slight increase in the number of aberrant crypts/ACF (AC/ACF) was seen after 16 weeks in rats treated post-initiation with refined wheat (p<0.05), and fewer foci with 2 or 3 aberrant crypts (ACF-2) were found in rats given unrefined whole wheat post-initiation compared with animals treated with the same diet during the initiation phase (p<0.05). There was no significant difference in the profile of IQ urinary metabolites or excretion of promutagens 0-48 hours after carcinogen dosing, and grains had no effect on hepatic cytochrome P450 (CYP) 1A1, CYP1A2, aryl sulfotransferase, or N-acetyltransferase activities; however, a slightly higher UDP-glucuronosyl transferase activity was observed in rats fed unrefined wheat compared with refined wheat diets (p<0.05). Thus, despite their antimutagenic activities in vitro, only marginal effects were seen with refined and unrefined wheat in vivo with respect to induction of hepatic enzyme activities, carcinogen metabolism, or IQ-induced ACF in the rat colon. The fresh juice and extract of crandall black currant (Ribes aureum) were not mutagens in the Salmonella mutagenicity assay. Berry extract or fresh juice at levels to 50 ��l (22 mg berry) in a 500 ��l pre-incubation system significantly inhibited the mutagenicity of IQ, a mutagen from cooked meat, by 32% when rat liver S9 bioactivation system was present. One hundred ��l of crandall black currant extract gave 89% inhibition of IQ mutagenicity (p<0.05). However, the mutagenicity of 2-hydroxyamino-3-methylimidazo[4,5-f] quinoline (N-hydroxy- IQ), a direct-acting metabolite of IQ, was not affected. An in vitro fluorometric assay showed the activity of cytochrome P 450 (CYP) 1A1 and CYP 1A2 was decreased. Inhibition of CYP 1A2 activity may be an important mechanism of antimutagenicity of crandall black currant extract. Similar results were also observed with other berry samples. Key word: cereal grains, black currant, berry, aberrant crypt foci, heterocyclic amines, CYP1A1, CYP1A2, Salmonella mutagenicity assay. / Graduation date: 2003

published_or_final_version / Human Performance / Doctoral / Doctor of Philosophy

published_or_final_version / Pharmacology / Master / Master of Medical Sciences