Objective: To systematically review the effect of self-management education on diabetic control in type 2 diabetes Research design and methods: PubMed was searched for English-language articles published between 2010 and 2013. All the studies were original articles selected manually and used randomized control trials generating results of self-management education in people with type 2 diabetes referring to diabetic control. Relevant data were divided and tabulated into factors of population characteristics, interventions and outcomes. Interventions were classified into three sections as collaborative information intervention, lifestyle intervention, and skills teaching intervention based on the patterns of education. Outcomes were categorized into glycemic control, cardiovascular disease (CVD) risk factors and nephropathy risk factors. Results: A total of 24 studies were identified of initial 41 articles for this review. Effects of self-management education on glycemic control were demonstrated to be positive both in short-term (<10 months) and long-term (>10 months) follow-up, but more positive effects in short-term follow-up. The same effectiveness happens to CVD risk factors, including lipids, weight and blood pressure. On the other hand, with short-term follow-up, teaching skills intervention of self-management education is more effective than collaborative information intervention and lifestyle intervention on reducing glycemic control and CVD risk factors. Also with long-term follow-up, teaching skills intervention of self-management education had more effectiveness than collaborative information intervention and lifestyle intervention on reducing glycemic control. However, few studies including CVD risk factors in the long-term follow-up, so it is difficult to evaluate the effectiveness of on CVD risk factors with long-term follow-up. Conclusions: Evidences supports the positive effectiveness of self-management education with collaborative information intervention, lifestyle intervention and skills teaching intervention among type 2 diabetes patients on diabetic control, in both short-term follow-up and long-term follow-up, but short-term follow-up is more effective than long-term follow-up. Further research is needed to develop self-management interventions to maintain long-term follow-up effects on glycemic control, CVD risk factors and other diabetes complications. / published_or_final_version / Public Health / Master / Master of Public Health

Background: Ulcerative colitis (UC) occurs in remissions and relapses and requires frequent outpatient follow-ups for management by specialists. These visits may not always coincide with the need for attention leading to unnecessary outpatient visits, nonattendances, inadequate monitoring, patient dissatisfaction and increased costs. Self management and shared decision making with health professionals may help overcome such challenges. Use of printed patient education interventions as a self management technique in UC has been discussed in this review. Objectives: To determine the impacts and implications of printed patient education interventions on patient empowerment, improved patient care, decreased healthcare use without burden on primary care and its impact on saving costs. The applicability of such an intervention in context of Hong Kong will also be discussed. Methods: PubMed and ProQuest Health and Medicine Databases, and Google scholar search engine were searched for original studies reporting results of randomized controlled trials (RCTs) of use of printed patient education interventions in management of inflammatory bowel disease and ulcerative colitis. There was no limit put on publication dates. Results: Four RCTs were finalized for review. The studies named primary and secondary outcomes, some of which were common to more than one study, and included process evaluations. Knowledge of UC was evaluated as an outcome in two studies, quality of life in four, health related anxiety and depression in two, patient satisfaction in two, medication adherence in one, relapses experienced in one and healthcare use in three. Knowledge and patient satisfaction was found to significantly improve in two studies. Statistically significant reduction was found in healthcare use in 2 RCTs with one also reporting fewer visits to outpatient department and primary care. Results were statistically insignificant for quality of life, medication adherence, relapse length, reporting of relapses and health related anxiety and depression in different studies though further study of their long-term effects is warranted to be better demonstrate their potential benefits. Conclusion: The presently proposed printed materials used in the studies appear to produce modest benefits in self management of UC. As the idea of self management evolves with time, we would need to define the optimal format of printed intervention and ways for continuous reinforcement in patients, as, currently, UC management is a lifelong process. / published_or_final_version / Public Health / Master / Master of Public Health

Hepatocellular Carcinoma (HCC) the fifth most common cancer and the third leading cause of death among cancer worldwide. Curative treatments such as liver resection and liver transplantation are generally used in treating early-stage HCC patients. However, only 10% to 30% of HCC patients are eligible for the surgery, which is due to the asymptomatic characteristic of HCC, most HCC patients are diagnosed at late stage. Palliative treatment such as TAE, TACE and Sorafenib provide them options to maintain their quality of life and extend their survival. Nevertheless, current treatments provides limited benefits to them as efficacy remains unsatisfactory. Therefore, there is a great need to develop new palliative treatments and explore new agents for the treatment of HCC. The aim of this study is to investigate the efficacy of a new therapeutic agent, Ombrabulin, in the treatment of HCC. Angiogenesis in HCC has been well-studied for many years as many studies proved that angiogeneisis plays an important role in the progression and development of HCC. Angiogenesis can also affect the prognosis and efficacy of treatments in HCC. As a result, antiangiogenesis and vascular disrupting agents have become new target in the therapaies of HCC. Ombrabulin is a synthetic vascular disrupting agent, which can inhibit tubulin polymerization in endothelial cells, causing cytoskeleton disorganization in endothelial cells. Endothelial cells will then detach from the basement membrane and eventually lead to vascular shutdown. This study demonstrated for the first time that Ombrabulin could selectively inhibit human umbilical vein endothelial cell (HUVEC) growth in vitro; particularly the early-form of HUVEC, which represent immature endothelial cell in neovasculature. Furthermore, this study also demonstrated the antiangiogenic effect of Ombrabulin on endothelial cells. By F-actin staining, it was shown that Ombrabulin caused changes in HUVECs morphology, which supported that Ombrabulin could lead to distortion in cytoskeleton. In vivo study demonstrated the early effect and long term effect of Ombrabulin. For the first part of the in vivo study, Nude mice were treated with single-dose of Ombrabulin for one week. Hoechst 33342, anti-CD34 staining and PCNA staining were carried out to study the functional effect of Ombrabulin and the combination effect with Sorafenib in vivo. Mice treated with Ombrabulin resulted in decreased blood perfusion, microvessel density and tumor cell proliferation, and tumor necrosis was also observed. In the combination with Sorafenib, it did not show synergistic effect in both tumor cell proliferation and microvessel density. For the second part of the in vivo study, nod scid mice were treated with multiple doses of Ombrabulin for three weeks to study the long term effect of Ombrabulin. Mice treated with Ombrabulin resulted in significantly smaller tumor size, demonstrating its antitumor efficacy in HCC. Furthermore, combination treatment of Sorafenib and Ombrabulin in vivo could enhance the efficacy of the treatment of HCC. In conclusion, Ombrabulin has vascular disrupting and antitumor effects, which could efficiently suppress HCC tumor growth in vivo. These results suggest that Ombrabulin could be a promising vascular disrupting agent in treating HCC. Combination with sorafenib should be further explored in clinical studies to demonstrate the synergistic antitumor effects in HCC patients. / published_or_final_version / Surgery / Master / Master of Philosophy

Lymphomas are malignant diseases involving the lymphatic system. Arsenic trioxide (As2O3) is a current therapeutic agent for acute promyelocytic leukaemia (APL).APL cells are sensitive to As2O3, with As2O3directly targeting the PML-RARA protein that plays an important role in the oncogenesis of APL. In order to discover the potential of As2O3as a treatment of lymphoma, understanding of the molecular mechanism of As2O3in human lymphoma cells is essential. In this thesis, we showed that the MYC gene is a therapeutic target for As2O3in B-cell lymphomas and the CCND1 (cyclin D1) gene is another therapeutic target for As2O3in mantle cell lymphoma (MCL), a subtype of non-Hodgkin lymphoma (NHL). Both real-time RT-PCR and immunoblotting analysis showed that the expression levels of MYC in all B-cell lymphoma cell lines were down-regulated at both mRNA and protein level after As2O3treatment. The expression levels of MYC were also found to positively correlate with the arsenic sensitivity as measured by MTT assay. Hence, the higher the level of MYC expression, the higher the arsenic sensitivity of human B-cell lymphoma cell lines. Besides, the change of downstream genes after modulation of MYC expression level by As2O3 treatment was investigated. The expression level of CDKN1A and CDKN1B was increased after As2O3 treatment. Interestingly, the growth rate of MYC over-expressing lymphoma cell lines decreased significantly after As2O3treatment, while there was no significant decrease in colony formation assay in lymphoma cells without MYC over-expression. Immunoblotting analysis showed that As2O3could degrade the cyclin D1 protein in mantle cell lymphoma cell lines in a dose-dependent manner. Real-time RT-PCR analysis also showed that the mRNA level of CCND1gene was decreased after As2O3treatment. We also demonstrated that As2O3-induced cyclin D1 protein degradation was related to the proteasome pathway. The growth rate of MCL cell line decreased significantly after As2O3treatmentby using colony formation assay. Human water channel protein, aquaporin 9 (AQP9) has been demonstrated to facilitate the arsenic uptake in human leukaemia cells. In this thesis, we showed that the expression levels of AQP9were found to positively correlate with the arsenic sensitivity as measured by MTT assay in B-cell lymphoma cells. We also demonstrated that dexamethasone could up-regulate AQP9expressions at both mRNA and protein levels in human B-cell lymphoma cell lines. These results not only suggest that As2O3is a potential therapy for B-cell lymphomas, especially for those MYC-over-expressed B-cell lymphomas and MCL, but also indicate that MYC may act as a biomarker for predicting the clinical behaviour of B-cell lymphoma patients to the As2O3treatment.Moreover, dexamethasone pre-treatment may enhance the therapeutic effect of As2O3by up-regulating AQP9expression in B-cell lymphomas. / published_or_final_version / Medicine / Master / Master of Philosophy

Poor adherence to continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnoea (OSA) limits its therapeutic effectiveness and has a major impact on clinical outcomes. Effective education programme is important to enhance CPAP use. However, existing education programmes are either manpower or resource demanding and may not be feasible in clinical practice. Moreover, the Self-Efficacy Measure for Sleep Apnoea (SEMSA) has been widely adopted for assessing adherence-related cognitions on CPAP therapy in OSA patients, but it was not available for Chinese. The aims of this thesis are: (i) to perform linguistic and psychometric evaluation of a Chinese version of SEMSA (SEMSA-C); (ii) to examine the efficacy of brief motivational enhancement education programme in addition to standard care versus standard care only on improving adherence to CPAP treatment in patients with OSA. The SEMSA-C was obtained after the standard forward-backward translation process. A randomised controlled trial was then conducted on newly diagnosed OSA patients. Patients in the control group received standard care (SC) comprising advice on the importance of CPAP therapy and its care while those in the intervention group received SC plus motivational enhancement education programme (ME). ME focused to enhance subjects’ knowledge, motivation and self-efficacy to use CPAP, comprising one 45-minute session on the day after CPAP titration and one 10-minute telephone follow-up shortly after commencing CPAP treatment. Epworth Sleepiness Scale (ESS), SEMSA-C, and quality of life were assessed. CPAP usage data were downloaded at the completion of this 3-month study. The primary outcome was the CPAP adherence. Furthermore, 21 patients were randomly sampled at baseline and completed the SEMSA-C at one week. 100 patients (Men : Women, 84 : 16) with OSA indicated for CPAP treatment were recruited, with an average age of 52±10 years, and apnoea hypopnoea index (AHI) of 36.2±22 events/hour. Factor analysis of SEMSA-C identified three factors: risk perception, outcome expectancies and treatment self-efficacy. Their corresponding internal consistency was high with Cronbach’s alpha >0.88, which were larger than all correlations between subscales (Range: 0.14 to 0.58). The correlations between items and their hypothesized subscale (Range: 0.58 to 0.85) were generally higher than the correlations between items and their competing subscales (Range: -0.10 to 0.58). One-week test-retest intra-class correlation ranged from 0.70 to 0.82. CPAP adherence was associated with outcome expectancies and treatment self-efficacy at 3-month assessment. Furthermore, SEMSA-C demonstrated an improvement in self-efficacy (standardised response mean = 0.33, p = .044) but no significant changes were observed in the other two factors, after CPAP use. The 100 patients were followed for 3 months. The interventional effects maintained during the 3-month study period. There were a better CPAP use [higher daily CPAP usage of 2 hours/day (Cohen d = 1.33, p < .001), four-fold the number of subjects using CPAP for ≥ 70% of days with ≥ 4 hours per day (p < 0.001)], and greater improvements in ESS by 2.2 (p = 0.001) and treatment self-efficacy by 0.2 (p = 0.012) in the intervention group, relative to the control group. The traditional Chinese SEMSA-C possesses satisfactory psychometric properties. It is a reliable and responsive instrument to measure perceived risks, outcome expectancies and treatment self-efficacy in Chinese patients with OSA. Moreover, the newly developed brief motivational enhancement education programme in addition to standard care is effective in improving adherence to CPAP treatment, treatment self-efficacy and daytime sleepiness. / published_or_final_version / Nursing Studies / Doctoral / Doctor of Nursing

abstract / Civil Engineering / Doctoral / Doctor of Philosophy

Surgery-induced brain injury (SBI) refers to trauma caused by routine neurosurgical procedures that may result in post-operative complications and neurological deficits. Unlike accidental trauma, SBI is potentially subject to preemptive interventions at the time of surgery. SBI can cause bleeding, inflammation and the formation of tissue gaps. Conventional haemostatic techniques, though effective, are not necessarily conducive to healing. Inflammation and the absence of extracellular matrix in tissue gaps also hinder regeneration after SBI. This study investigated the applications of RADA16-I, a type I self-assembling peptide nanofibre scaffold (SAPNS), and mesenchymal stem cells (MSCs) in the treatment of SBI. Using animal SBI models, treatments were applied immediately and locally onto the operative fields, taking advantages of the haemostatic and cell-carrying properties of RADA16-I, the immune- modulatory effects of MSCs, and the earliest available therapeutic window for SBI. There were three objectives. Objective 1 was to compare RADA16-I with conventional haemostatic methods, including electrocautery and fibrin sealant, in their effects on the brain’s acute cellular inflammatory response. The hypothesis was that RADA16-I would cause the same or a lesser degree of inflammation. This study showed that RADA16-I was superior to electrocautery, and was noninferior to conventional topical haemostats. Objective 2 was to study the in vitro expansion of MSCs within RADA16-I in preparation for in vivo transplantation. The hypothesis was that the in vitro survival of MSCs would vary between different RADA16-I concentrations and culturing methods. This study showed that plating MSCs onto pre-buffered RADA16-I would protect the cells against RADA16-I’s intrinsic acidity and result in better initial survival. Subsequent integration with the RADA16-I hydrogel, however, was poor. Mixing the cells directly with RADA16-I caused initial cell loss but allowed better integration. RADA16-I at lower concentrations resulted in better survival but also more fragile hydrogels that were mechanically unfit for transplantation. Mixing MSCs with 0.5% RADA16-I for seven days represented a compromise between these competing factors. Objective 3 was to study the in vivo effects of a MSC-RADA16-I implant on tissue reactions after SBI. The hypothesis was that the combinatorial therapy would result in less cellular inflammatory response than MSC alone or RADA16-I alone. Implants of pre-buffered 0.5% RADA16-I hydrogel, with or without cells, were found to cause less inflammation than control. MSCs in free suspension resulted in significantly more pronounced inflammation than when carried in RADA16-I. Supplementing RADA16-I with MSCs, however, did not confer additional benefit over RADA16-I alone. The present study provided new preclinical evidence to support future clinical testing of RADA16-I as a novel surgical haemostat. It also demonstrated the feasibility of early intracerebral transplantation of RADA16-I hydrogel in the treatment of SBI. Whether RADA16-I and/or transplanted MSCs could modulate the brain’s inflammatory response after SBI require further investigations, which may include the search for the optimal ex vivo expansion technique and specifically tailored nanofibre scaffold. The translational applications of these findings would include the treatment of SBI over critical brain regions where trauma would cause severe functional deficits and where better healing would facilitate patient recovery. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Background Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS). In Hong Kong, the prevalence rates of MS is 4.8/100,000. First line disease modifying agent (DMA) type 1 interferon β (IFN-β) is the most commonly use therapy for relapsing and remitting MS(RRMS). Depending on the administration type and route of IFN-β, up to 80% of patients develop harmless binding antibody (BAb),which binds to IFN molecules but not necessary interfere its bioactivity. When IFN-β therapy continues, maturation of BAb response can lead to the formation of high affinity neutralizing antibody (NAb). About 45% of MS patients develop NAb against IFN-β in one year of IFN-β treatment. NAb shows a loss of IFN-β clinical effect by increasing MRI activity and disease progression. As the clinical effect of NAb is lagging behind the initial appearance of NAb in the body, it is suggested to develop a NAb assay to predict treatment failure and advice switching therapy for patients when NAb is present. Aim The aim of this study was: I. To develop and evaluate a qPCR-based method for the measurement of NAb to IFN-β in MS patient. II. To establish the normal reference range of NAb in Chinese population. III. To seek the possibility of using anti-IFN-β BAb assay and in vivo MxA gene expression assay as a screening test for NAb IV. To compare the performance between MxA induction qPCR, ELISA, WB assay and luciferase IFN-β reporter gene assay Materials and methods23Chinese RRMS patients who treated with IFN-β-1a therapy for a minimum of12 months were recruited in this study. Serum and PBMC were collected12 hours after the IFN-β-1a injection. MxA, IFNAR1 and IFNAR2 mRNA from PBMC were tested byin vivo MxA gene expression assay. NAb containing serum was tested by anti-IFN-β BAb assay, IFN-β reporter gene assay, in vitro MxA induction WB, ELISA and qPCR assay. In addition, blood samples from 3 Chinese volunteers without any known autoimmune disease history were collected to evaluate the baseline of NAb titer and MxA expression. Result The experimental condition of MxA induction qPCR assay was optimized by using 2.5×105A549 cells plating density, 10% FCS concentration,5 hours IFN-β stimulation time and GAPDH normalization. Assay accuracy was validated by reference anti-IFN-β antibody. Starting from 2.5 TRU, linear relationship could be observed (r2= 0.9873). The lower limit of quantification (LLOQ) was 0.02 LU/mL, the upper limit of quantification (ULOQ) was 16LU/mL and the limit of detection (LOD) was 0.002 LU/mL. The reproducibility of the assay was measured, the intra-and inter-assay imprecision(%CV)for high value were 5.95% and 7.17% respectively, while the intra-and inter-assay impression were8.31% and 15.95%respectively.Results of the qPCR-based method were concurring with that of luciferase IFN-β reporter gene assay. The upper limit of the NAb reference range in Chinese population was 40.3 TRU (n=3, 95% CI = 31.7-48.8). The performance observed in MxA induction ELISA assay swas unsatisfactory. The correlation of anti-IFN-β BAb assay and in vivoMxA gene expression assay results with NAb status indicated both tests were sensitive enough for NAb screening. Conclusion A normal range of NAb titer in Chinese population was established in this study. Anti-IFN-β BAb assay and in vivo MxA gene expression assay were proved suitable for NAb screening. The performance of the developed MxA induction qPCR assay was superior to MxA induction ELISA, WB assay and comparable to luciferase IFN-β reporter gene assay. By using MxA induction qPCR assay, actual efficacy of IFN-β therapy could be measured and monitored. Any treatment failure could be predicted earlier. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Malignant obstructive jaundice is always encountered in advanced stage. Malignancies include Distal Bile duct Carcinoma, Ampulla of Vater Carcinoma, and Pancreas Carcinoma are sometimes impossible to cure and resect. Therefore, palliative treatments are the only way to relieve the disease for the patients to have a better quality of life in their remaining life- span. Available palliative treatments include stenting and surgical bypass. In our analysis, metallic stenting and double bypass composing hepaticojejunostomy and gastrojejunostomy are studied as they can be considered as the two most efficient palliative methods so far that are widely used in Hong Kong in the management of malignant biliary obstruction. The treatment options depends on both the physicians and the patient. However, patients are often on the horns of a dilemma when they are allowed to choose these palliative treatments. This study hence aim to compare the cost-effectiveness of metallic stenting and surgical double bypass palliative treatment among five factors: 1) Number of hospital stay, 2) Re-admission rate, 3) Overall complication, 4) Change of bilirubin level and 5) Survival rate. A total of 40 patients data are being retrieved from the Queen Mary Hospital as 20 data are form the metallic stenting group, while the other 20 data are from surgical bypass. After collecting the data and finishing the study, it was found that apart from a longer hospital stay, the surgical bypass patient group would generally have a lower re-admission and complication rate. While the parameters include bilirubin change before and after the treatment and the survival rate are not significantly different, which indicated these two parameters may not be the determining factors when deciding the treatment choice. Based on the research outcome, surgical bypass may be a better choice of palliative treatment in the management of Malignant Biliary Obstruction that allows patients to obtain a better quality of life. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Introduction: Cognitive impairments occur frequently in stoke survivors, yet current conventional post-stroke care focuses mainly on motor function. Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are noninvasive brain stimulation techniques (NIBS) that are used in neurological rehabilitation. Its efficacy is well-established in motor recovery post-stroke, but research on its effects on the associated cognitive decline after stroke is fairly new. The aim of this review is to evaluate recent studies and provide a summary on the effects of NIBS on post-stroke cognitive decline. Methods: PubMed and CINAHL were searched using the keywords: “cerebrovascular accident”, “stroke”, “NIBS” or “noninvasive brain stimulation”, “tDCS” or “transcranial direct current stimulation”, and “TMS” or “transcranial magnetic stimulation”. PEDro system was used to assess the quality of the studies that passed the inclusion and exclusion criteria. Results: The initial search returned 1081 citations, among which 12 were included in this review. The mean PEDro score of the studies was 7.5 out of 10. The trials had a total of 176 participants with stroke. Lesion site was heterogeneous. Six trials investigated tDCS, and the other 6 investigated rTMS. The main outcome measures were grouped into 3 domains: memory, visuospatial, and attention. Both tDCS and rTMS resulted in significant changes in the visuospatial domain in terms of improving spatial neglect. The results on memory and attention are mixed, but tDCS shows more consistent results. Conclusion: NIBS is a safe and low-cost treatment that can improve cognitive decline post-stroke. However, the evidence is still lacking due to the small number of trials and sample sizes. More studies need to be conducted in order to establish a proper guideline for usage. Long term effects also need to be investigated. / published_or_final_version / Public Health / Master / Master of Public Health