published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

published_or_final_version / Microbiology / Master / Master of Medical Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

Risk is a crucial concept in healthcare communication. This is attested to by a large body of research on risk communication in psychology, sociology, and, more recently, discourse analysis. This previous research has primarily focused on how healthcare providers manage risk talk, whereas patients’ risk talk has received little attention. Where it has been researched, it has been presented in an oversimplified way, namely that the patients have been reported to perceive their risk in a simplified, ‘all-or-nothing manner’. Using theme-oriented discourse analysis (Roberts and Sarangi, 2005), this study challenges this simplified perception by examining patients’ risk talk in prenatal screening for Down syndrome. The data for this study comprises 14 video-recorded consultations collected in one prenatal hospital in Hong Kong. The particular focus of the study is on patients who have received a ‘positive’ result from the initial screening for Down syndrome that has put them in a high-risk group by increasing their probability of having a baby with Down syndrome. In these consultations patients are informed about further testing to confirm the diagnosis. To examine the patients’ risk talk, the transcripts of the interactions have been coded along the lines of structural, thematic and interactional maps (Roberts and Sarangi, 2005) to note down risk talk by patients, what is it concerned with and the interactional dynamics of how it is managed. The analysis suggests that patients’ risk talk concerns three types of risks, namely the “risk of occurrence” (that is the probability of having a child with Down Syndrome) the “risk of knowing” (that is dealing with the knowledge about having a child with Down Syndrome) and what has been referred to in this study as the “risk of not knowing” (that is not finding out about the condition due to the uncertainty surrounding the tests). In contrast to the findings in the previous studies, the patients in the data actively initiate risk talk by raising clarification questions and talking about their concerns. The analysis has revealed the differences in how different types of risk talk are constructed by the patients. These differences are discussed in regards to the phases of the consultation in which risk talk occurs and whether risk talk is aimed at eliciting further information or making a decision about pursuing further testing. The analysis has also noted that risk communication is a joint activity involving the patients and the healthcare providers. In addressing patients’ risk talk the healthcare providers in the data take on an indirect approach, thereby avoiding influencing the patients’ decision-making and managing the uncertainty surrounding prenatal screening. The analysis has also pointed out that the patients’ socioeconomic and cultural backgrounds have a crucial impact on how risk talk is constructed by the patients. / published_or_final_version / Linguistics / Master / Master of Philosophy

Chronic obstructive pulmonary disease (COPD) is one of the world’s most common chronic diseases, and consists of chronic bronchitis that involves chronic inflammation of the bronchi, or emphysema that involves destruction of lung alveoli. In COPD patients, the airways become narrowed, and the airflow is irreversibly obstructed. This leads to a limitation of the flow of air to and from the lungs, causing shortness of breath (dyspnea), as well as abnormal inflammatory response in the lung. Nowadays, COPD is often under-diagnosed, as spirometry was not performed until patient has significant symptoms of dyspnea, cough and sputum production. At that stage, the COPD patients may have reached an advanced stage with considerable loss of lung function. Thus, biomarkers are of great interest for research and clinical purposes in COPD, especially for early diagnosis of COPD. In this study, the relationship between plasma levels of different biomarkers, including monocyte chemoattractant protein-1 (MCP)-1 (a primary chemoattractant biomarker), matrix metalloproteinase nine (MMP)-9, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) (injury and repair biomarkers), and growth differentiation factor 15 (GDF)-15 (a novel biomarker), in 29 healthy ever-smokers and 116 COPD patients was investigated using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We also investigated the correlations between these biomarkers and lung function. There were significant increases in plasma MCP-1, MMP-9, HGF and GDF-15 in COPD patients compared to healthy smokers. Among ever-smokers with or without COPD, plasma MCP-1, MMP-9 and HGF levels were inversely correlated with force expiratory volume in one second![FEV1 (% predicted)] after adjustment for age, smoking status and packyears smoked. Correlation was also found between plasma MCP-1 and HGF, plasma MMP-9 and HGF or GDF-15, plasma HGF and GDF-15 after adjustment for age, smoking status and pack-years smoked. Further multiple linear regression analyses demonstrated that plasma MMP-9 level increased with the COPD GOLD stages. In conclusion, our findings suggest that MMP-9 might be as an important biomarker for COPD initiation and progression. As this study provides only evidence of association rather than of causation, prospective studies are required to assess biological significance of these associations between the plasma biomarkers. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Methicillin-resistant Staphylococcus aureus (MRSA) is an important and common pathogen causing community- and healthcare-associated infection. Culture methods were used for identification of MRSA for a long period of time, however it spends a lot of time on incubation and 1 to 2 days is needed to obtain the identification and antibiogram. Molecular tests were developed in the past decades and different genes were used. In this study a Staphylococcus aureus-specific gene, sau gene was designed and accompanied with mecA gene to detect the presence of MRSA in 322 nasal swabs from Tuen Mun Hospital. To evaluate the performance of in-house RT-PCR, samples were run in parallel with LightCycler? MRSA Advanced test and BBLTM CHROMagar? MRSA. 75 (23%) of samples were MRSA positive. The sensitivities and specificities of in-house RT-PCR and LightCycler? MRSA Advanced test were 76.7%/ 89.2% and 87.8%/ 96.6% respectively. The mean processing time for a batch of 32 samples by CHROMagar, in-house RT-PCR and LightCycler? MRSA Advanced test were 48.9 hours, 134.4 mins and 149.8 mins. In-house RT-PCR showed comparable performance and short turnaround time. sau gene can be used with mecA gene for the detection of MRSA in nasal swab. / published_or_final_version / Medicine / Master / Master of Medical Sciences

This study completed the analysis of mutational frequencies and clinicopathological patterns of six EGFR pathway-related genes (EGFR, HER2, HER4, KRAS, BRAF and MET) in 212 resected lung adenocarcinomas (AD) from 98 male and 114 female Chinese patients without prior chemotherapy or tyrosine kinase inhibitor (TKI) therapy. Genomic DNA and cDNA sequencing, quantitative PCR and fluorescence in-situ hybridization (FISH) were employed to investigate mutation and amplification status of the relevant genes. Overall, more than 75% of tumours were detected to harbour mutations or amplification in one of these six genes. The commonest mutation was found to involve EGFR, comprising 60.38% of cases, followed by KRAS (9.43%), HER2 (2.36%), MET (2.36%), BRAF (1.42%) and HER4 (0.47%). Four somatic mutations in MET exon 14 splicing region were found, leading to alternative splicing and a transcript lacking exon 14. Two of the MET mutant tumours and one MET wild-type tumour showed MET amplification of more than 3.5 fold increase in copy number. Mutations of EGFR were significantly more frequent in female (p = 0.0196), non-smokers (p < 0.001) and well differentiated tumours (p = 0.0209). KRAS mutations showed significant association with male (p = 0.0099) and smoking history (p = 0.0011). A novel HER2 D769Y mutation was found and HER2 mutations were associated with smokers (p = 0.0013) and poorly differentiated tumours (p = 0.0147). BRAF, MET mutations and MET amplification were not associated with clinicopathological factors. Mutations were mutually exclusive except for two cases with KRAS and HER4/BRAF. MET amplification was co-existent with MET mutations in two cases. MET amplification was found to negatively correlate with disease-free and cancer-specific survivals. The results suggested that MET amplification may contribute to disease progression and could be a therapeutic target in primary lung AD in Hong Kong Chinese patients. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Autism is a life-long neurodevelopmental condition. Autistic individuals have difficulties in communicative and social ability, and repetitive and stereotypic behavior. It has proposed that these symptoms are caused by underconnectivity in the autistic brain. Functional imaging studies have reported functional underconnectivity in autism. In this thesis, the structural connectivity of the autistic brain was studied. White matter contains axon fibers, which connect different cortical and subcortical brain regions. To measure the structural connectivity, Diffusion tensor imaging (DTI) was applied. Since water diffusion in axons inside the white matter is directional, by measuring the magnitude and direction of water diffusion in white matter, the structural integrity of white matter fibers could be estimated. In this thesis, the background of autism as a genetic, neurological and behavioral condition is outlined. The methods needed to acquire and analyze DTI data are illustrated. A meta-analysis on abnormalities found in autistic brain using DTI was conducted and the most consistently reported regions with DTI differences in autism compared to typically developing controls are described. The results of the metaanalysis were localized to white matter tracts likely to be involved, and the possible associations between anatomy and autistic behavioral features are discussed. Finally, a DTI tractography study was conducted in a sample but clinically representative sample of patients with ASD and eighteen major white matter tracts were explored. Underconnectivity in several tracts was identified. It is hoped that the findings reported here will enhance our understanding of widespread underconnectivity in autism. / published_or_final_version / Psychiatry / Master / Master of Philosophy

Background Routine voluntary HIV screening has been found to be cost-effective in regions with undiagnosed prevalence > 0.1%. However, a large proportion of infected patients are still unaware of their status and presenting to care late, leading to greater risk s for infection. As expanded ART has been shown to be highly effective in improving patient health and reducing HIV viral load, a strategy of expanded screening with earlier initiation of ART may be effective at reducing the numbers of new infections. Aim A systematic review was carried out with the aim of understanding what drives the cost-effectiveness of expanded HIV screening at low prevalence rates. A thorough investigation of sensitivity analysis was done to determine if low prevalent regions can implement screening at good value for cost and how money should be spent to maximize benefits. Methods An extensive literature review of studies published in English between 1996 and 2010 were identified from various electronic databases, included gray literature search and hand search. A qualitative assessment of the literature was undertaken. Results Results of the analysis found that expanded screening can be cost-effective at undiagnosed prevalence rates below that of current recommendations. Factors of linkage to care, and benefits of reduced secondary transmissions through reduced risk behaviors had the most impact on models. Screening while maximizing benefits due to linkage to care and secondary transmissions can may be appropriate for low prevalence regions such as Hong Kong, however further analysis would be necessary. / published_or_final_version / Public Health / Master / Master of Public Health

Inborn errors of metabolism (IEM) are under international spotlight because of the recent tremendous development in expanded newborn screening (NBS) and molecular genetics. IEM is a difficult subject involving more than 1,000 different disorders with protean clinical presentations and complicated diagnostic pathways. Cumulative incidence of IEM was reported up to 1 in 800. Patients can be affected in any ages. High clinical suspicion alone is not sufficient to reduce morbidities and mortalities. Notably, some IEM are amenable to treatment with promising outcome. Local data regarding the disease spectrum and incidences is largely lacking. Public awareness and readiness for expanded NBS is unknown. This renders difficulties in the consideration of expanded NBS in Hong Kong. In this study, laboratory data of classical IEM from 2005 to 2009 were retrospectively analyzed (Chapter 2). Local incidence was 1 in 4,122 and that of hyperphenylalaninemias was 1 in 29,542, similar to worldwide figures. Majority (69%) was amino acid disorders, 12% was organic acidemias and 19% was fatty acid oxidation defects. Most of these diseases are effectively amenable to treatment. Local cases including hyperphenylalaninemia, tyrosinemia type I, arginase deficiency, ornithine transcarbamylase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, tyrosine hydroxylase deficiency, thermolabile carnitine palmitoyltransferase II variants and adults IEM with X-linked adrenoleukodystrophy, cerebrotendinous xanthomatosis, familial transthyretin amyloidosis, Wilson disease and PANK2-associated young-onset Parkinsonism were described (Chapters 1.1.3 and 3). Electronic chemical pathology consultation service and dried blood spot metabolic screening were implemented (Chapter 4). There were 279 consultations and 158 screening in a 12-month period. Major referral reasons were developmental delay, neurological defects and unexplained biochemical abnormalities. The incidence in high risk screening was 1 in 158. A non-derivatized tandem mass spectrometry assay for amino acids and acylcarnitines was evaluated for its precision, accuracy and reference intervals (Chapter 5). The concordance rate was 100% in inter-laboratory comparison and external quality assurance programs. The method was proven to be accurate, rapid and affordable. It is suitable for large volume testing and emergency diagnostic needs. A feasibility study of a hospital-based expanded NBS service model was conducted on 360 newborns (Chapter 6). More than 90% of babies were older than 48 hours before discharge and were fit for blood collection. The service model consisted of parent education, consent, postnatal sample collection, technical analysis, clinical interpretation, reporting and follow-up actions. Questionnaire on the knowledge and attitude towards IEM and expanded NBS was surveyed on 172 parents to investigate the psychological, social and ethical aspects (Chapter 7). Here, 99.4% demanded more education on expanded NBS; 97.6% supported to implement the program; 97.7% supported population screening even though some diseases are incurable. Availability of treatment is not the most important pre-requisite for NBS; 93.9% accepted the possibility of false positive and false negative results. Acceptance towards expanded NBS among parents was high. Our data indicate that IEM is not uncommon in Hong Kong and it is indisputable for the introduction of a local expanded NBS program. Our data serve as groundwork for policy decision and further discussion on expanded NBS. / published_or_final_version / Pathology / Master / Doctor of Medicine