Background: Human papillomavirus (HPV) DNA test is more sensitive and can detect more high-grade cervical intraepithelial lesions than cytology test in cervical cancer screening. There are studies confirming HPV test being more effective in cervical cancer screening by detecting the persistence of HPV infection that could lead to cancer. However, the costs associated with a HPV test is higher than a cytology test. Moreover, HPV test is less specific which could subject more women to further triage tests or unnecessary invasive diagnostic procedures. Therefore healthcare costs could possibly increase if primary HPV screening is to be adopted. Study objective: The aim of the study is to systematically review the cost-effectiveness of primary HPV testing in cervical cancer screening Method: Electronic search was performed in three biomedical databases (PubMed, Medline, Cochrane Library) and one economic evaluation database to identify relevant studies. Studies were selected according to the explicit inclusion and exclusion criteria defined. Only those studies carried out in high-income countries were included so that result could be better applied to Hong Kong. Results: A total of 19 studies were included in this systematic review. Cytology-only method is generally not cost-effective. To be cost-effective, it has to be performed in a longer screening interval which would reduce not only the screening costs but also a reduction in the health outcomes. Among the different options in HPV-based primary screening, HPV testing with cytology triage is the most cost-effective strategy in many of the studies. Combined HPV/cytology co-screening could achieve the biggest health benefit but is also most costly. HPV-based screening is more cost-effective for those >30 years of age and is usually less cost-effective if applied to young women. From the result in sensitivity analysis, HPV-based screening is sensitive to an increase in the costs of the HPV test, a low HPV test sensitivity and a low screening compliance rate. Conclusion: Primary HPV screening is cost-effective and generally performs better than cytology screening. The result of this systematic review guides the future direction of developing an optimal cervical screening strategy in Hong Kong. Local context has to be considered when examining the cost-effectiveness of primary HPV testing for cervical screening. Good quality local epidemiological data on HPV infection and cervical cancer and screening would be required to aid future research on the application of HPV test for cervical cancer screening in Hong Kong. / published_or_final_version / Public Health / Master / Master of Public Health

Objective The main objective is to evaluate the current diabetic retinopathy (DR) screening by optometrists under Risk Assessment and Management Programme (RAMP) in general outpatient clinics (GOPC), and to compare it to conventional screening by clinical examination. The secondary objective is to predict the prevalence of DR and maculopathy (DMac) in the study cohort, and identify risk factors especially the role of nephropathy. Methodology Ophthalmologist’s re-grading of the digital fundus photos previously screened by optometrists according to RAMP protocol was used as the gold standard to evaluate the current screening programme. Accuracy of optometrist screening was calculated by percentage of agreement and Kappa coefficient. Fundus photo grading by ophthalmologist and optometrist was compared to clinical examination findings in eye clinics. Sensitivities and specificities were calculated, and plotted on ROC curve for comparison of the two methods of screening. Prevalences of DR and DMac were estimated from the gold standard grading, and their correlation with other factors also screened by RAMP was identified using chi-square test and logistic regression. Results There was an overall over-grading of disease by optometrists. The overall inter-observer agreement in diagnosis was 81.2%, and the overall kappa coefficient was 0.65 (p<0.001), which reached substantial strength of agreement. Use of mydriatics reduced the percentage of ungradable photos by at least 4 times. The overall agreement of clinical examination with ophthalmologist-photo-grading was 69.2%, and that with optometrist was 60.9%, and the respective Kappa coefficients were 0.31 (p<0.001) and 0.25 (p<0.001). The areas under curve (AUC) on ROC curve were larger for optometrist photo screening (DR=0.85 and DMac=0.80) than clinical examination (DR=0.52 and DMac=0.54). The prevalences of DR and DMac were 19.4% and 3.3% respectively. Duration of DM was the only common significant predictor of referable DR and DMac by chi-square test. 15-year of disease significantly increased the risk of more advanced DR and DMac. Nephropathy was only significant for DR but not DMac. Moderate renal dysfunction as indicated by decreased excretory glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and presence of macroalbuminuria significantly worsened DR staging, by over 5 times (p=0.02). Family history of diabetes mellitus (DM), on the other hand, increased the risk of DMac only, by 5 times (p=0.01). Conclusion The current optometrists’ screening is reasonably valid and reliable, although there is room for improvement. None-the-less, the higher false-positive rates than false-negative rates for referable disease suggests that it is safer than otherwise. It is a better method than clinical examination. Duration of DM and presence of nephropathy, especially macroalbuminuria which predates decrease in eGFR, and family history of DM can predict more advanced DR and/or DMac development. / published_or_final_version / Public Health / Master / Master of Public Health

Objectives To systematically review all studies HBV screening and vaccination health behaviour according to the Health Belief Model theoretical framework including perceived susceptibility, severity, barriers and benefits, cues to action and self-efficacy. Methodology The literature search used PUBMED, MEDLINE, CINAHL plus, Wan Fang database, and Chinese Journal Net with English and Chinese language. About 73 studies (PUBMED: 33 MEDLINE: 10, CINAHL plus: 3, Wan Fang database: 16, Chinese journal net: 11) in total were identified; after applying the inclusion and exclusion criteria, 11 studies met the criteria and in the final analysis. The target group included high infection rate groups (pregnant women, unprotected sexual behaviour, and immigrant group) and illness groups (chronic Hepatitis B and Hepatitis B virus carriers). Results and Discussion HBV screening and vaccination behaviour were determined by perceived the susceptibility, perceived severity, perceived barriers and benefits, and cues to action. The self-efficacy was seldom designed in the questionnaire of the reviewed articles. The Health belief model was a useful model for explaining HBV screening and vaccination behaviour. Screening- and vaccination-related beliefs of the screening and vaccination vary by high risk groups. From the review more attention to self-efficacy and perceived control may improve vaccination uptake. There were contrast results with the social economic characteristics, such as age, gender, income, in determining the HBV screening and vaccination behaviour. Conclusion and Implication As the policy maker, health care providers need to develop specific interventions paying attention to the different aspects of the Health Belief Model to improve the perceived of Hepatitis B virus. / published_or_final_version / Public Health / Master / Master of Public Health

Background: Abdominal aortic aneurysm (AAA) is a degenerative disease prevailing in men aged 65 years and above. Most AAA patients are asymptomatic until the disease develops to a very severe stage. Systematic screening could detect AAA in an early stage and early treatment is therefore provided to prevent AAA rupture and reduce AAA-related death. Ultrasonography is a recommended tool for AAA screening, which has been widely used in several western countries. Hong Kong currently has not introduced this screening programme yet. The present study attempts to investigate the health related quality of life (HRQOLO) of AAA patients in Hong Kong and then examine whether a systematic screening in elderly men in Hong Kong is cost effective compare with current practice (Non-screening strategy) Methods: Firstly, a questionnaire based study was conducted in a local university-affiliated vascular tertiary referral center targeting on AAA patients. Quality of life data was collected by a face-to-face interview using the Medical Outcomes Study Short-Form-36 Health Survey (SF-36). A controlled group was obtained from a large local population study matched by gender and age to the AAA group. The SF-36 scores were compared between the two groups; a stepwise multivariate regression analysis was conducted to show the association between the disease and the SF-36 scores. Secondly, a cost effectiveness analysis based on a Markov model was conducted to compare the screening strategy against non-screening practice. Incremental cost effectiveness ratios (ICER) was adopted as the rule of decision making. One-way sensitivity analysis and probabilistic analysis were performed to explore the uncertainty around the parameters. Results: 172 out of 252 patients participated the interview, among which 80% were aged 65 years or above, and 85% were males. Around 80% patients were detected incidentally. Comparing with the age and gender matched control group, AAA patients had an impaired HRQOL The disease adversely affected mental health summary of AAA patients. Under the discount rate of 3% on costs and effectiveness, the incremental costs of systematic screening against non-screening is HK$3,710.3; and the incremental life year gained and quality adjusted life year (QALY) gained are 0.024 and 0.014, respectively. The ICER is HK$ 151,070.1 per life year gained and HK$ 268,897.6 per QALY gained, which is cost effective under the threshold of one GDP per capita (HK$285,403) for one QALY gained. Conclusion: The economic evaluation based on the Markov model indicated systematic screening for AAA among elderly men in Hong Kong is cost effective. Government in Hong Kong should consider introducing the screening programme when resource is available. / published_or_final_version / Public Health / Master / Master of Philosophy

Background and Objectives: Pre-implantation Genetic Diagnosis (PGD) is an established alternative to prenatal diagnosis to select genetically disease-free embryos in vitro before they are transferred back to the mother, and it has gained acceptance for couples at risk of passing on monogenic diseases and chromosomal abnormalities around the world. More PGD cycles in conjunction with in vitro fertilization (IVF) have been offered to the Asian couples in Hong Kong who are carriers of genetic diseases or chromosomal abnormalities. This study evaluates the attitude and moral concerns towards PGD of the enrolled couples, and their knowledge of their underlying genetic conditions. Methods: This cross-sectional survey was carried out between June2013 and March 2014. All the couples enrolled in the PGD program at the Queen Mary Hospital were invited to join the study. Total 47 couples and 2 women, whose male partners declined to respond, were recruited. Self-reported structured questionnaires were completed by participating subjects. Statistical analysis was performed to study the attitude and concerns related to different PGD stages, genetic conditions, experience of past pregnancies and sex of the surveyed participants. Results and discussion: Ninety-six completed questionnaires were analysed with 36.5%from the Pre-PGD group, 31.2%from the PGD Treatment group and 32.5% from the Post-PGD group. There was a trend of increase in psychological stress and concerns related to the IVF/PGD related procedures when couples proceeded from the pre-PGD to the post-PGD stage. A good acceptability of PGD related procedures and similar moral value about the embryo fate, comparable to overseas studies, were observed, except we had a lower percentage of subjects (25%) who expressed no concern about repeated IVF cycles. The worries about the transfer of carrier embryos were high (33%)among couples who are thalassemia carriers. While 15% of the subjects disagreed with termination of pregnancy for a genetically confirmed abnormal IVF/PGD fetus,18% of the subjects could not decide at the time of the study. So counselling support to the couples when they face the above two difficult situations is important. We also found majority of the subjects (76%) optedto tell their children later about their conception. Support for parents to access counseling advice at their preferred time of disclosure is therefore worth considering. Regarding the knowledge of the couples on their underlying genetic conditions, most subjects (95%)knew their carrier status well. Most subjects (89%) with single gene disorder knew their recurrent risk of having an affected baby but only 32% could tell the inheritance pattern. Estimation of recurrent risk is more difficult for the group with balanced chromosomal translocation. Significance: This first study in Hong Kong on the Chinese couples enrolled in the PGD program highlights the specific concerns of the couples with different underlying genetic conditions at the different stages of PGD. The findings could serve as local reference to guide future studies and the development of PGD counseling services and follow-up for the couples seeking such intervention in the future. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

In cervical screening programmes, Papanicolaou test (Pap test) is the key screening tool. However Pap test is difficult to implement in low-resource region. Introduction of an economic, cost-effective and less skill demanding equipment is hence a potential direction of advance in cervical screening methodology. 　　Cervical carcinogenesis involves genetic instability which leads to chromosomal aneuploidy. Evaluation of aneuploidy may hence provide information for identifying cancer and precursor cells. An automated DNA-image-cytometry system (DNA-imager) capable of quantitating the DNA content of cells has recently been developed. 　　To evaluate the efficacy of DNA-imager in cervical cancer screening, a total of 483 residual ThinPrep liquid-based cytology (LBC) samples after diagnosis were retrieved and evaluated by the DNA-imager. The high risk human papillomavirus (HPV) status of the atypical squamous cells of undetermined significance (ASC-US) samples has been tested as a parallel study. According to established criteria, 423 out of the 483 samples were satisfactory for downstream analysis. The samples were designated “Normal”, “Suspicious” or “Abnormal” according to their DNA aneuploidy and proliferation activity. 　　Significantly more high grade lesion samples (HSIL and SCC) were designated as “Abnormal” by DNA-imager than were lower grade lesion samples (Negative, ASC-US, AGC, ASC-H, and LSIL) (94.19% vs 51.04%, p<0.0001). For detecting ≥HSIL, DNA-imager achieved high sensitivity and specificity (94.19% and 48.96%) using “Abnormal” as cut off. Adopting a more stringent definition of “Suspicious” or “Abnormal” would increase the sensitivity to 100% but decreased the specificity to 24.33%. 　　 　　Regarding ASC-US triage, DNA-imager achieved a sensitivity and specificity of 80.00% and 71.29% respectively when “Abnormal” was used as test positive to predict cases with ≥HSIL follow-up in the next two year. The sensitivity increased but the specificity decreased to 90.00% and 34.65% respectively if “Suspicious or above” was used as indicator of undesirable follow-up. HR-HPV test, on the other hand, was able to identify all cases with ≥HSIL upon follow-up (sensitivity = 100%) but the specificity was only 15.84%. Among these ASC-US sample, test positivity of the two tests showed poor concordance with each other (Cohen’s κ = 0.062 and 0.074 respectively for “Suspicious or above” or “Abnormal”, respectively). 　　Our findings suggested that DNA-imager may be a useful tool for automated primary screening of cervical cancer 3 / published_or_final_version / Pathology / Master / Master of Medical Sciences

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