174 research outputs found
Real-world evidence of cardiovascular complications following COVID-19 vaccines
No full textThe vaccines were considered essential in lessening the severity of the disease and slowing the transmission of COVID-19 during the pandemic. Due to stringent enrolment requirements and a shorter follow-up, the safety evidence from randomised clinical trials of COVID-19 vaccines may not be sufficient, especially in the expedited programs. Therefore, it is important to conduct post-marketing safety surveillance with real-world data for a comprehensive understanding of vaccine safety profiles, especially for novel vaccines with mRNA platforms.
Cardiovascular diseases (CVD) have been identified as intriguing adverse complications due to the higher incidence observed after COVID-19 infection. Yet, safety evaluation on CVD events following COVID-19 vaccination remains limited. This thesis aims to estimate the relative risks of three CVD major complications, including thromboembolic events, haemorrhagic stroke, and carditis associated with the administration of mRNA (BNT162b2) and inactivated (CoronaVac) vaccines. Additionally, it compares the absolute risk of these events between the COVID-19 vaccines and infection.
This thesis utilised three real-world databases in Hong Kong to answer the above research questions: 1) electronic health records (EHR) for all government-subsidised public hospitals and clinics, 2) a database for the sole public mass COVID-19 vaccination program, and 3) a territory-wide COVID-19 infection recording system. The vaccine safety on CVDs was assessed using the Self-Controlled Case Series (SCCS) design. By facilitating within-individual comparison, this approach mitigates the influence of time-invariant confounding factors. However, the outcomes of interest in this thesis may violate the event-dependent exposure and event-dependent observation assumptions for a standard SCCS. To address this, a modified SCCS approach was adopted, and it identified a higher risk of haemorrhagic stroke and carditis following the BNT162b2 vaccine compared to referent windows. The CoronaVac vaccination does not carry a higher risk of these CVD complications. Importantly, the absolute risks following both vaccines were significantly lower than those observed after COVID-19 infection.
A further focus of the thesis is the younger population, which was found to have a higher risk of carditis following their second dose of BNT162b2. To address the above issue, the thesis explores the impact of an interval extending between the first and second doses of BNT162b2 on carditis risk and its effectiveness. Two nested case-control study designs were utilised, and it discovered that prolonging the BNT162b2 vaccine's interdose interval can lower the incidence of carditis in the younger while preserving protection against COVID-19 infections.
In summary, this thesis offers an in-depth analysis of the CVD safety profile of COVID-19 vaccinations in the Hong Kong population, including both the inactivated and mRNA platforms. Although a higher relative risk of CVD events was observed after mRNA vaccination, the absolute risk is lower after vaccination than infection. Adjusting the dosing schedule can help optimise the balance between safety and effectiveness among the younger. Besides, a modified SCCS is more appropriate for safety identification when assumption violations exist. This knowledge is vital for ensuring the safe and effective implementation of COVID-19 vaccination programs, ultimately contributing to the global efforts in combating the COVID-19 pandemic.published_or_final_versionPharmacology and PharmacyDoctoralDoctor of Philosoph
Dementia in observational studies using electronic health records : opportunities and challenges with pharmacoepidemiology
No full textDementia is a global health challenge that currently affects more than 50 million people internationally with increasing prevalence. Evidence to support safe medication use in people living with dementia and therapies that may reduce the risk its development can help to facilitate healthy ageing and address the growing dementia burden.
Studies of dementia face challenges such as requiring a long period of follow-up due to the gradual nature of its development, a lack of consistent dementia diagnosis definitions, and potential confounding bias when making comparisons between different groups of older people with different degrees of frailty and disease states. Although randomised controlled trials are the gold standard of investigating the effectiveness of interventions, their interpretation in studies of dementia are limited due to their restricted study samples in terms of size, age, and follow-up time. Therefore, alternative study types that can circumvent the weaknesses of clinical trials, such as observational studies, are crucial in bridging the knowledge gap in dementia research.
The aim of the thesis is to investigate several topics surrounding safe medication use related to dementia and highlight opportunities and challenges in using observational study designs within this disease area. The data used in the studies included in this thesis were electronic health records extracted from the population-wide database managed by the Hong Kong Hospital Authority. Two of the studies were collaboration projects with the addition of electronic health records from the United Kingdom, Sweden, and Australia.
Observational studies applying pharmacoepidemiologic methods were conducted in populations of people with dementia or with dementia as an outcome, with COVID-19 vaccines and antihypertensive drugs being medicines of interest. Studies included were an analysis of COVID-19 vaccine adverse events in people with dementia, multinational studies on prescribing trends of antihypertensive drugs in people with dementia and the association of the use of different antihypertensive drug classes and the risk of incident dementia, and the application of high-dimensional propensity scores as a method to mitigate confounding bias.
The findings of these studies comprised of evidence supporting the safe use of COVID-19 vaccines in people with dementia, descriptions and analyses of antihypertensive prescribing practices, and head-to-head comparisons between the use of different antihypertensive drug classes and the risk of incident dementia. Angiotensin-II receptor blockers were found to have a reduced risk of incident dementia compared to angiotensin-converting enzyme inhibitors in a large, multinational cohort study setting with a relatively long follow-up of more than five years. The high-dimensional propensity score method was also successfully implemented using electronic health records in Hong Kong in a proof of concept study to improve confounding control between the antihypertensive class comparison groups in older people.
To build on the findings presented in this thesis, future studies are needed, such as studies aiming to elucidate the mechanisms of antihypertensives in dementia risk reduction, and advances in study methods to reliably evaluate the relationships between these medicines and dementia.published_or_final_versionPharmacology and PharmacyDoctoralDoctor of Philosoph
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Simulating longitudinal phase space in the SLC, from the damping rings to the final focus
No full textAt high currents the longitudinal phase space of the SLC beam is not simply described by gaussian distributions in both position and energy. The distorted ring beam, the curvature of the compressor rf, the limited energy aperture of the RTL, the wakefields in the linac, and the momentum compaction in the arc all contribute to some extent to a distortion of longitudinal phase space. In this paper we present simulation results that describe the phase space of the SLC beam, from the damping rings to the final focus area, and that include all these distorting effects. From bunch length measurements in the SLC it was discovered that the damping ring beam is lengthened and is clearly not gaussian. One author describes a potential well calculation for the ring bunch shape that agrees remarkably well with the measurements. These calculated shapes are the starting point for the simulations described in this paper. These initial distributions are propagated through the RTL, then the linac, and then the arcs. We will address questions of the bunch shape, beam tilt, beam loss, and tail population at the end of the RTL. Following this we discuss the energy spectrum at the end of the linac and the bunch shape when the beam reaches the final focus. Finally, in Appendix A we describe a method of measuring the bunch shape and the induced voltage in the SLC linac. 22 refs., 9 figs
Gemmeleg. Performance for the Feral Cello. Sound Music Computing Conference, Helsinki... 5 Jul 2017-8 Jul 2017
No full textGemmeleg by Laura Reid performed on the "Feral Cello" developed by Tom Davis at SLC Helsinki July 201
The association between oral fluoroquinolones and incident seizure event
No full textBACKGROUND: Fluoroquinolones are a class of antibiotics prescribed for various infections. Several case reports have indicated the potential association between the use of oral fluoroquinolones and the development of incident seizure event. OBJECTIVES: The objectives of this study were to: 1) investigate the association between the use of oral fluoroquinolones and the development of incident seizure event; 2) to estimate the crude absolute risk of developing incident seizure event whilst prescribed with oral fluoroquinolones. METHODS: A self-controlled case series study design was used to investigate the association. Patients were retrieved from an electronic patient record database called the Clinical Data Analysis and Reporting System in Hong Kong from the year of 2001 to 2013. Patients who had an incident seizure event and were prescribed with oral fluoroquinolones in the out-patients setting during the study period were included. Those with a history of post-traumatic or febrile convulsion were excluded. The rate of having incident seizure event during the exposure period was compared with the non-exposed period. Conditional Poisson regression was used to estimate the incidence rate ratio at a 5% significance level. A sensitivity analysis was conducted by excluding patients who died within 30 days after the incident seizure event. RESULTS: A total of 291,751 prescriptions of oral fluoroquinolones were identified among 166,325 patients. A total of 2,206 patients met the case definition and were included in the analysis. An incidence rate ratio of 0.89 (0.52, 1.53) was estimated. Fourteen cases of incident seizure event occurred during the exposure period. The crude absolute risk of having incident seizure event whilst prescribed with oral fluoroquinolones was approximately 4.8x10^-5 (2.9x10^-5, 8.1x10^-5). No statistically significant association was observed between the use of oral fluoroquinolones and the development of incident seizure event in the sensitivity analysis. CONCLUSIONS: This study does not support the association between the use of oral fluoroquinolones and the development of incident seizure event.link_to_subscribed_fulltex
Trends and uncertainties of mass-driven sea-level change in the satellite altimetry era
No full textOcean mass change is one of the main drivers of present-day sea-level change (SLC). Also known as barystatic SLC, ocean mass change is caused by the exchange of freshwater between the land and the ocean, such as melting of continental ice from glaciers and ice sheets, and variations in land water storage. While many studies have quantified the present-day barystatic contribution to global mean SLC, fewer works have looked into regional changes. This study provides an analysis of regional patterns of contemporary mass redistribution associated with barystatic SLC since 1993 (the satellite altimetry era), with a focus on the uncertainty budget. We consider three types of uncertainties: intrinsic (the uncertainty from the data/model itself), temporal (related to the temporal variability in the time series) and spatial–structural (related to the spatial distribution of the mass change sources). Regional patterns (fingerprints) of barystatic SLC are computed from a range of estimates of the individual freshwater sources and used to analyze the different types of uncertainty. Combining all contributions, we find that regional sea-level trends range from −0.4 to 3.3 mm yr−1 for 2003–2016 and from −0.3 to 2.6 mm yr−1 for 1993–2016, considering the 5–95th percentile range across all grid points and depending on the choice of dataset. When all types of uncertainties from all contributions are combined, the total barystatic uncertainties regionally range from 0.6 to 1.3 mm yr−1 for 2003–2016 and from 0.4 to 0.8 mm yr−1 for 1993–2016, also depending on the dataset choice. We find that the temporal uncertainty dominates the budget, responsible on average for 65 % of the total uncertainty, followed by the spatial–structural and intrinsic uncertainties, which contribute on average 16 % and 18 %, respectively. The main source of uncertainty is the temporal uncertainty from the land water storage contribution, which is responsible for 35 %–60 % of the total uncertainty, depending on the region of interest. Another important contribution comes from the spatial–structural uncertainty from Antarctica and land water storage, which shows that different locations of mass change can lead to trend deviations larger than 20 %. As the barystatic SLC contribution and its uncertainty vary significantly from region to region, better insights into regional SLC are important for local management and adaptation planning.Physical and Space Geodes
Comparison between early and late stage lung cancer in relation to cost and mortality
No full textLung cancer (LC) is a life threatening disease associated with significant cost and high mortality. LC is diagnosed in either early stage or more frequently in late stage, the face of lung cancer. Objective: To make a comparison between early and late stage lung cancer (SLC) in relation to cost and mortality Methods: The study is a random effects data analysis of a historical dataset the Nationwide Inpatient Sample (NIS). The study is based on the time period 2002, 2006 and 2011. The primary outcomes of interest is cost (total cost per day) and mortality (died/did not die). Two replicates samples for the years 2002, 2006 and 2011 were taken. Demographic factors that influence cost and mortality were co-varied out of the analysis. Descriptive Statistical analysis and bivariate analysis were done for cost includes ANOVA and ANCOVA. A statistical analysis for mortality includes logistic regression. Cost and mortality for early versus late (SLC) were measured in isolation and after accounting for age, gender, race, socio-economic status, number of diagnoses, length of stay, and number of procedures.Results: In the three years, 3 samples of 2173, 13,032, and 15,771 including 3 replicate samples of 2060, 13,032 and 15,772 participated in the study. All significant relationships tested at an alpha level of (P<0.05). The cost for early (SLC) was higher compared to late (SLC) and is statistically significant. The number of procedures in part accounted for the difference. Late (SLC) had higher mortality compared to early (SLC) and is statistically significant. The number of diagnoses in part accounted for the difference. The study showed early (SLC) costs 14% more than late (SLC). Late stage is more deadly, however, the gap is surprisingly small at 30% or an odds ratio of 1.3 to 1.5 after adjusting for covariates. Conclusion: This study of HCUP data revealed that early (SLC) is more expensive than late (SLC). Additionally, the data revealed that mortality is higher in late (SLC) compared to early (SLC). Overall, these finding highlight the important role of Health Informatics in understanding the cost and mortality of early and late (SLC).Ph.D.Includes bibliographical referencesby Kathleen A. Hardin
Difference in ninth-grade student performance between small learning communities and traditional high school models, 2012
No full textThe purpose of this causal-comparative research study was to determine the extent to which ninth-grade student performances are impacted by the small learning community model. The urban high school of interest performed higher than the district in all accountability areas, and was comparable to the state in all areas except ninth-grade on track performance. Transforming this urban school district into small learning conmiunities was planned in order to address the needs of students with the ultimate goal of increasing the graduation rate and lowering the dropout rate. The urban school district being investigated in this study began the SLC transformation process with one school. That high school went from a comprehensive high school traditional model with a magnet program to the SLC model with four different academies. This one comprehensive school is phasing the SLC academies in by grade level. This affords the school the ability to make adjustments as the model is phased in during 4 years. The SLC model and traditional model of high school and the impact of the school model on ninth-grade student performance measures. It was proposed that the following variables were directly related to ninth-grade student achievement: number of absences; scores on the science, mathematics, and literature EOCTs; number of disciplinary referrals; GPA; and grade promotion. An investigation was also conducted to determine if there was a relationship between school model, gender, and student performance. Teacher perceptions are analyzed to determine their reflections on the processes for any correlations to the student outcomes. The study was designed to determine if those basic needs are met through the SLC model or the traditional school model. The Statistical Package for Social Sciences (SPSS) to analyze the data. Analyses of variance were used to compare six of the dependent variables between the two school models and for comparisons of these same variables among the four academies. The interviews were transcribed and coded to established dominant and emergent themes as it related to ninth-grade student achievement. Based on the findings, there were statistically no differences between the SLC and traditional school model for the ninth grade measures such as EOCT scores in mathematics, science, and English, grade point average and the number of disciplinary referrals. In addition, students enrolled in the traditional school model had significantly fewer absences, and there were a larger percentage of ninth grades students promoted in the traditional model than students who were enrolled in the SLC model. The researcher concludes that in year one of the implementation of the SLC model there was no significant impact on ninth grade student outcomes
A retrospective study of medical staff manpower and service demand in a Hong Kong Accident and Emergency Department
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