1,721,679 research outputs found
Treatment of infective endophthalmitis by intravitreal drugs
No full textpublished_or_final_versionabstractMedicineDoctoralDoctor of Philosoph
New factors that affect adrenomedullin expression
No full textADM is a 52-amino acid peptide which carries out multiple biological functions in cardiovascular system such as vasodilation and hypotension, and is a prognostic marker for cardiovascular diseases. Recent studies show that its plasma level is elevated in diabetes, however the reason and significance for such an increase has not been understood. Recent research has proposed that inflammation and oxidative stress both contribute to the pathogenesis of diabetes. If ADM is a marker in diabetes, it is possible that ADM is regulated by these two mechanisms, and so this project aims to investigate how these mechanisms could affect ADM expression.
Recent studies have demonstrated that advanced glycation endproducts (AGEs) could lead to development of various diabetic complications. AGEs are formed as intermediate product in the non-enzymatic glycation of reducing sugars. Formation of these products is stimulated by hyperglycemia and oxidative stress, which could also induce ADM expression. Hence one of the studies investigated the direct effect of AGEs on ADM expression in an in vitro model. A rat macrophage cell line NR8383 was used to investigate the dose-response and time-point responses of macrophage cells in expressing ADM stimulated by AGEs. 6 hours of AGEs treatment resulted in no significant effect on ADM gene expression. The gene expression increased in all time points in which the change was at maximum after 1 hour of AGE treatment compared with other time points (P<0.05). However the time-dependent effect on ADM gene expression was insignificant compared with controls. How oxidative stress could lead to increased ADM expression deserves further investigation.
ADM plays a role in inflammation that it could influence IL-6 and adiponectin expressions. This project also investigated whether IL-6 and adiponectin could affect ADM levels on the opposite. The associations between IL6 and adiponectin single nucleotide polymorphisms (SNPs) with plasma ADM levels were studied using a cohort of 476 subjects from the Cardiovascular Risk Factor Prevalence Study (CRISPS). Specific tagging SNPs were genotyped for the 476 subjects. Significant associations were identified for the IL6 SNP rs17147230 and adiponectin SNP rs182052 with plasma ADM levels in additive model (β=-0.096, P=0.034, and β=0.104, P=0.023 respectively adjusting for age and sex). The associations remained significant after adjusting for various covariates (P<0.05). Genotypic model shows that the minor alleles of rs17147230 and rs182052 resulted in 12.8% decrease and 17.7% increase in plasma ADM levels. These findings show that ADM level could be regulated by IL-6 which is an inflammatory cytokine, and adiponectin which is a protective peptide in inflammation. Reducing inflammation could lower ADM level and adiponectin might be a therapeutic candidate.published_or_final_versionMedicineMasterMaster of Philosoph
Metabolic syndrome: its prevalence and association with urotensin II
No full textpublished_or_final_versionabstractMedicineMasterMaster of Philosoph
Medication safety in hospitals : medication errors and interventions to improve the medication use process
No full textMedication errors are an unnecessary threat to patient safety. The aim of this study was to assess the epidemiology of medication errors and to assess the effectiveness of interventions intended to avoid medication errors in a tertiary-care hospital in Hong Kong.
The epidemiology of medication errors included the study of the pattern of interception of medication errors and the study of technology-related medication errors using medication incidents reported during years 2006–2010. 34.1% of all medication errors that were reported in the study hospital were not intercepted and 92.4% of all drug administration errors reached the patient. 17.1% of all reported medication errors were technology-related and, most were due to human interaction with technology.
The effects of a bar-code assisted medication administration (BCMA) system when used without the support of computerised prescribing (stand-alone), on its users and the dispensing process was studied using direct observations, questionnaires (Likert scale) and interviews. It was found that this system increased the number of dispensing steps from 5 to 8 and dispensing time by 1.9 times. Potential dispensing errors also increased (P<0.001). The perceived usefulness of the technology decreased among pharmacy staff (P=0.008) after implementation and they (N=16) felt that the system offered less benefit to the dispensing process (8/16) without the support of computerised prescribing. Nurses (N=10) felt that the stand-alone BCMA system was useful in improving the accuracy of drug administration (8/10).
Avoiding the use of inappropriate abbreviations in prescriptions will help to reduce medication errors. Therefore the effectiveness of a ‘Do Not Use’ list (a list of error-prone abbreviations used in the study hospital) and attitudes of health care professionals on using abbreviations in prescriptions was studied using prescription review and questionnaires respectively. The use of abbreviations included in the ‘Do Not Use’ list decreased significantly (P<0.001) after its introduction but other unapproved abbreviations to denote drug names and instructions were commonly used. 96% of doctors, and all pharmacists and nurses, believed that avoiding inappropriate abbreviations will help to reduce medication errors.
The use of abbreviations in prescriptions and attitudes of pharmacists in the study hospital was compared with a different medical system to determine the appropriateness of developing a universal error-prone abbreviation list. It was found that the types and frequencies of using inappropriate abbreviations vary among different medical systems.
In conclusion, additional interventions such as technological interventions are needed to minimise drug administration errors, but proper planning and careful monitoring are needed to avoid unintended errors when using technologies. Implementing a stand-alone BCMA system aimed at reducing drug administration errors may affect the dispensing process. Therefore effects of a technology on all related processes need to be considered before implementation, and monitored after implementation. The introduction of a ‘Do Not Use’ list is effective in reducing inappropriate abbreviations in prescriptions and most health care professionals agree that avoiding inappropriate abbreviations may help to reduce medication errors. However, formulating in-house error-prone and standard abbreviation lists in hospitals, continuous updating of the lists and frequent reminders to prescribers are recommended.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Systematic review and meta-analyses on the optimal interventions to reduce adverse cardiovascular events for cardiovascular diseases and diabetes mellitus
No full textAtherosclerotic cardiovascular disease, hypertension, and diabetes mellitus are three leading causes of global morbidity and mortality that are closely associated with each other, as risk factors and coexisting complications. Reducing cardiovascular diseases in patients with hypertension and diabetes mellitus is as important as lowering blood pressure and blood glucose. However, the optimal treatment strategies for these diseases with maximum cardiovascular protection and minimum adverse events all remain unknown due to the limited or contradicted evidence. This thesis designed four studies aiming to fill the evidence gap with the latest evidence released and add more insights to current clinical guidelines.
Percutaneous coronary intervention with drug-eluting stents implantation has been widely used in the treatment of atherosclerotic cardiovascular disease. A certain period of dual antiplatelet therapy is needed to reduce thrombotic complications. The optimal duration of dual antiplatelet therapy and the optimal antiplatelet P2Y12 inhibitor involved are always debated. In the first and second studies, two systematic review and network meta-analyses were performed to compare the efficacy and safety of different durations of dual antiplatelet therapy and P2Y12 inhibitors used in the therapy (clopidogrel, ticagrelor, prasugrel, and cangrelor). Short-term dual antiplatelet therapy less than 12 months was shown to be non-inferior to 12-month and longer durations beyond 12 months in reducing ischaemic events and deaths while with fewer excessive bleeds, so was more favourable for most patients. Ticagrelor found with a better net efficacy and safety profile was preferred over the other newer P2Y12 inhibitors in combination with aspirin as dual antiplatelet therapy.
Antidiabetic drugs may have direct cardiovascular effects independent of their glucose-lowering effects. Among the latest second-line antidiabetic drug classes, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose co-transporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors, which drug class can provide the best cardiovascular protection for diabetic patients is unclear due to the absence of direct comparative trials. In the third study through systematic review and network meta-analysis, SGLT-2 inhibitors and GLP-1 RAs were proved to be superior to DPP-4 inhibitors in reducing cardiovascular events and deaths while SGLT-2 inhibitors were found to be more beneficial in reducing hospitalisation for heart failure and renal events.
The latest hypertension guidelines have recommended a lower blood pressure treatment goal with intensive blood pressure control. Uncertainties have been raised regarding the necessity and safety of more intensive blood pressure-lowering strategies. In the final study, a systolic blood pressure of <130 mmHg was demonstrated to reduce cardiovascular events more than the other blood pressure levels, which could be regarded as an appropriate treatment target for most hypertensive patients. More aggressive blood pressure lowering to <120 mmHg was associated with the lowest risk of stroke, which could be considered for patients who can tolerate the therapy to reduce stroke.
These identified optimal treatment strategies should always be tailored for different patients after considering their benefit-risk profile in clinical practice.published_or_final_versionMedicineDoctoralDoctor of Philosoph
The association between cardiometabolic diseases and several chronic diseases
No full textCardiovascular disease (CVD) is a significant contributor to morbidity and mortality. The prevalence of CVD remains a crucial concern, underscoring the imperative to improve the management of CVD as chronic diseases. Metabolic syndrome (MetS) is a medical condition that presents a combination of risk factors such as abdominal obesity, hypertension, dyslipidemia, and insulin resistance. This condition has been found to significantly impact the development and advancement of CVD and increase the risk of CVD mortality.
The prevalence of MetS using the updated data from the United States National Health and Nutrition Examination Survey (NHANES) was estimated. It could facilitate the prevention and management of CVD. This thesis included individuals who were eligible non-pregnant, aged 20 years or older, and possessed valid data on hypertension, arthritis, chronic obstructive pulmonary disease (COPD), human papillomavirus (HPV) infection, and denture use in each respective chapter. Logistic regression was applied to examine the relationship shown in chapters 3 to 6, while controlling for potential confounding variables such as demographics, socioeconomic factors, well-established modified risk factors, related diseases, and medications.
This study reveals a noteworthy escalation in the prevalence of MetS in the US from 2011 to the pre-pandemic of COVID-19 (2011-2018). The prevalence of MetS increased from 37.6% (95% CI, 34.0-41.4) in the year 2011-2012 to 41.8% (95% CI, 38.1-45.7) in the year 2017-2018.
The escalating prevalence of MetS bears noteworthy consequences for CVD. The presence of individual components of metabolic syndrome poses a risk for CVD. However, when these components co-occur in the context of MetS, the risk for cardiovascular diseases is significantly compounded. The prevention of MetS and CVD involves a comprehensive approach including lifestyle modifications, pharmacological interventions, multidisciplinary care, patient education, and self-management. However, some individuals still exhibit these conditions despite these efforts, suggesting the involvement of unconventional risk factors in their emergence.
The thesis indicated significant associations between hypertension and arthritis, encompassing both rheumatoid arthritis (RA) and osteoarthritis (OA), as well as COPD. This association was particularly pronounced among individuals under the age of 60.
In addition to arthritis and COPD, it was observed that HPV infection exhibited an association with CVD, independent of the HPV genotype. This association was particularly prominent among women of advanced age. The observed association was statistically significant in the cohort of women who did not receive the HPV vaccine, whereas no such association was found in the group of women who received the vaccine. The administration of HPV vaccine could potentially confer supplementary advantages in preventing CVD. Furthermore, this thesis also presented the utilisation of dentures exhibited a noteworthy association with CVD, particularly among those within the age range of 40-49 years.
The identification and management of unconventional chronic diseases such as COPD, arthritis, HPV infection, and denture in relation to CVD carry significant clinical significance. Through the incorporation of novel insights into these factors and their integration into clinical practice, healthcare providers can improve risk assessment, prevention strategies, and overall management of cardiovascular disease.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Leveraging genome-wide data to understand cardiovascular diseases and their risk factors
No full textCardiovascular diseases (CVD) refer to a group of diseases, such as coronary heart disease, that affect the heart and blood vessels. They contribute significantly to death and illness, resulting in financial costs for society and impacting quality of life. The risk factors for CVDs are multifactorial, and the key modifiable risk factors include elevated cholesterol and blood pressure, diabetes, smoking, diet, physical activity, and obesity. This thesis utilized recent genome-wide association data and methodological advancements to deepen the understanding of genetic factors impacting various non-communicable diseases, specifically focusing on cardiovascular diseases and their related risk factors.
The shared genetic architecture between periodontal diseases (PER) and glycemic traits were explored, including Type 2 diabetes (T2D), using genetic correlations, cross-phenotype association, expression-trait association, and functional analysis, such as pathway analysis. The findings revealed a genetic link between them, with a significant positive global genetic correlation. Through local genetic correlation analysis, several genomic regions were identified as shared between PER and glycemic traits or T2D. Additionally, 62 independent pleiotropic loci impacting both PER and glycemic traits were identified, including T2D. The
genetically predicted liability of Homeostasis Model Assessment of Beta-cell function adjusted for body mass index (BMI) was found to be causally associated with the risk of PER.
The shared genetic etiology between PER and blood lipid traits were investigated using similar approaches as Chapter 3. The study provided insights into the shared basis and novel biological mechanisms between them. A significant global genetic correlation was found between PER and blood lipid traits. Moreover, 58 independent pleiotropic loci were shared between PER and blood lipid traits. Two shared expression-trait associations were observed for total cholesterol or triglyceride and PER in coronary artery and cerebellar hemisphere tissues.
The causal relationship between two cardiovascular proteins, Galectin-3 (gal-3) and Suppression of Tumorigenicity 2 (ST2) Protein, and sleep traits and cardiometabolic traits were explored. The findings showed that genetically predicted gal-3 was significantly or suggestively causally associated with certain sleep traits. Reverse mendelian randomization (MR) analysis revealed significant or suggestive associations between genetically predicted gal-3 and triglyceride, fasting insulin, glycated hemoglobin (HbA1c) and Waist-to-Hip Ratio adjusted for BMI. Additionally, genetically predicted ST2 was found to be suggestively associated with sleep duration. In the reverse analysis, triglyceride and sleep duration were suggestively associated with genetically predicted ST2.
The causal association between amyotrophic lateral sclerosis (ALS) and 14 cardiovascular conditions were inspected using MR approaches. The results suggested a causal association between ALS and certain cardiovascular conditions and significant or suggestive associations between certain cardiovascular conditions and ALS. Multivariable MR analysis demonstrated
that myocardial infarction was significantly associated with the risk of ALS after controlling for low-density lipoprotein cholesterol.
In summary, my thesis applied recent genetic association statistical methods to investigate the genetic overlap between cardiovascular diseases or their risk factors and other complex traits. It provides a better insight into the biological mechanisms and genetic architecture underlying cardiovascular diseases and their risk factors. Further biological experiments are expected to consolidate these statistically and computationally supported results. (Word count: 498 words)published_or_final_versionMedicineMasterMaster of Philosoph
The changes in adrenomedullin levels and gene expression in a rat model of endotoxaemia
No full textpublished_or_final_versionabstracttocPhysiologyMasterMaster of Philosoph
Vitamin D status and its association with clinical outcomes in Hong Kong Chinese
No full textVitamin D is a human steroid and important to human health, but its optimal level is still controversial. Although evidence suggests that a low vitamin D level is linked to risk of cardiometabolic diseases, its association with stroke and diabetes remains inconclusive. The aim of this study was to evaluate the optimal level of serum 25-hydroxyvitmain D [25(OH)D] and its association with the risk of stroke and diabetes among Hong Kong Chinese. Association of metabolomic profiling with vitamin D was also performed to discover vitamin D-associated metabolites and possible health-related pathways. The prevalence of vitamin D deficiency among 5,276 Hong Kong Chinese participants of the Hong Kong Osteoporosis Study [HKOS] was 43.8% and the prevalence of insufficiency (<75nmol/L) or deficiency (<50nmol/L) was 90.1%. In fully adjusted three-phase segmented regression, the estimated first and second break-point of 25(OH)D was 27nmol/L (95% CI:24-30) and 47nmol/L (95% CI:37-56) respectively.
In multivariable Cox-proportional hazard regression in 3,458 HKOS participants aged <45 years, the lower quintiles of 25(OH)D were significantly associated with higher risk of incident stroke compared with the highest quintile (Quintile 1: Hazard Radio [HR], 1.78; 95% CI, 1.16-2.74 and quintile 4: HR, 1.61; 95% CI, 1.07-2.43). A similar association was observed irrespective of gender and specifically for ischemic stroke, but not hemorrhagic stroke. In penalized regression spline plot, the relationship between vitamin D and risk of stroke was a reverse J-shape, showing the lowest HR at 25(OH)D 70 to 80nmol/L. For the relationship between 25(OH)D and incident diabetes among 4,342 HKOS participants aged 20 years or older (1,395 men, 2,947 women; mean age ± standard deviation [SD]: 54.3±16.5 years), fully-adjusted Cox-proportional hazard regression showed no significant difference in the risk of incident diabetes between the lowest and highest quintile of 25(OH)D. The interaction term between 25(OH)D and serum calcium did not affect the risk of incident diabetes significantly (p=0.700).
Identification of the metabolomic profiling associated with 25(OH)D was evaluated using multivariable linear regression in discovery stage using the HKOS baseline cohort 1 of 315 participants (aged 20 years or above; 93 men, 224 women; mean age ± SD: 48.1±15.8 years) and in the discovery stage using the HKOS follow-up cohort 2 of 275 participants (aged 20 years or above; 12 men, 263 women; mean age ± SD: 56.2±9.6 years). In meta-analysis of data from these two cohorts, 13 metabolites were highly correlated with 25(OH)D, and most were lipid in nature. Docosahexaenoylcarnitine and eicosapentaenoylcholine had the highest correlation, with effect estimate of 0.2554 (p=9.60 x10-9) and 0.1682 (p=4.94x10-7) respectively.
In conclusion, the optimal level of vitamin D was estimated to be 47nmol/L for general bone health among Hong Kong Chinese. 25(OH)D was associated with incident ischemic stroke but not with incident diabetes. In metabolomics, a high majority of vitamin D-associated metabolites were lipid in nature, suggesting that lipid metabolism may be related to the role of vitamin D in possible health outcomes.published_or_final_versionPharmacology and PharmacyDoctoralDoctor of Philosoph
Gout : its epidemiology and therapeutic effect of urate-lowering agent
No full textGout is chronic inflammatory arthritis characterised by monosodium urate crystal
deposition in peripheral joints. The global prevalence of gout is increasing except
Taiwan and the United States. However, there was no updated epidemiological data of
gout as well as the utilisation of urate-lowering agent in Hong Kong and the United
States (US). The risk factor of gout is essential. The association between high blood
lead level and gout has been shown in previous studies. However, the toxicity effect
of lead at low blood lead level was inconclusive. The association between gout and
depression was inconclusive. Whether the use of urate-lowering agent would increase
depression was not investigated. Therefore, this thesis aimed to study the
epidemiology of gout in Hong Kong and the US, risk factor analysis of urate control,3
toxicity effect of lead at low exposure level as well as the effect of urate control on
depression.
The Clinical Data Analysis and Report System was used to study the epidemiology of gout in Hong Kong in 2006-2017. Patients who used the service in a public hospital in Hong Kong in 2005 were included in this study. Patients who died before 2006 were
excluded. The incidence and prevalence of gout are increasing in Hong Kong.
However, the management of gout is suboptimal. Only one in four patients prescribed urate-lowering agents. Adult participants in the US National Health Nutrition and Examination Survey 2007-2016 were included to study the prevalence of gout, utilisation of urate-lowering agents, the association between blood lead level and gout as well as the association between urate control and depression. Gout was defined as self-reported gout. Urate-lowering agent prescription was defined using a pill bottle review. Serum urate level >6 mg/dL was used to define treatment failure. There was no significant increase in the prevalence of gout. However, the utilisation of urate-lowering agent was suboptimal. One in three patients with gout prescribed ULT. Stage 2-5 chronic kidney disease and thiazide diuretics prescription were the predictors of treatment failure. Blood lead level was associated with increased prevalence of gout. Gout was associated with an increased prevalence of depression. The use of uratelowering agent was not associated with increased depression.
Given that the incidence and prevalence of gout increased over the past eleven years in Hong Kong, the control for the risk factors, including lead exposure is important.
The suboptimal control of urate-lowering agent should be promoted for better management of gout. Patients should be screened for depression.published_or_final_versionMedicineDoctoralDoctor of Philosoph
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