Survival models for censored point processes

In studies of recurrent events, there can be a lot of information about a cohort over a period of time, but it may not be possible to extract as much information from the data as would be liked. This thesis considers data on individuals experiencing recurrent events, before and after they are randomised to treatment. The prerandomisation outcome is a period count, while the post-randomisation outcome is a survival time. Standard survival analysis may treat the pre-randomisation period count as a covariate, but it is proposed that point process models will give a more precise estimate of the treatment effect. A joint model is presented, based on a Poisson process with individual frailty. The pre-randomisation seizure counts are distributed as Poisson variables with rate depending on explanatory variables as well as a random frailty. The model for the post-randomisation survival times is the exponential distribution with the same individual seizure rate, modified by a multiplicative treatment effect. A conjugate mixing distribution (frailty) is used, and alternative mixing distributions are also discussed. The model is motivated by and illustrated on individual patient data from five randomised trials of two treatments for epilepsy. The data are presented, and the standard analyses are contrasted with the results of the joint model. This thesis also considers the relative efficiency of the joint model compared to other survival models. Finally, some extensions to the model are considered, including a more general non-conjugate mixing distribution, and alternative ways of including explanatory variables in the joint model

Survival models for censored point processes

In studies of recurrent events, there can be a lot of information about a cohort over a period of time, but it may not be possible to extract as much information from the data as would be liked. This thesis considers data on individuals experiencing recurrent events, before and after they are randomised to treatment. The prerandomisation outcome is a period count, while the post-randomisation outcome is a survival time. Standard survival analysis may treat the pre-randomisation period count as a covariate, but it is proposed that point process models will give a more precise estimate of the treatment effect. A joint model is presented, based on a Poisson process with individual frailty. The pre-randomisation seizure counts are distributed as Poisson variables with rate depending on explanatory variables as well as a random frailty. The model for the post-randomisation survival times is the exponential distribution with the same individual seizure rate, modified by a multiplicative treatment effect. A conjugate mixing distribution (frailty) is used, and alternative mixing distributions are also discussed. The model is motivated by and illustrated on individual patient data from five randomised trials of two treatments for epilepsy. The data are presented, and the standard analyses are contrasted with the results of the joint model. This thesis also considers the relative efficiency of the joint model compared to other survival models. Finally, some extensions to the model are considered, including a more general non-conjugate mixing distribution, and alternative ways of including explanatory variables in the joint model.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo

Hundreds of severe pediatric COVID-19 infections in Wuhan prior to the lockdown

Integrative Biolog

Epidemiology and risk factors for Carbapenemase-Producing Enterobacteriaceae carriage in the hospital: a population-based nested case-control study

Objective: This study aims to study the epidemiology of Carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. / Methods: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. / Results: From 1st January 2008 to 31st December 2019, 8,588 patients received CPE genotyping tests, and 2,353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics [Odds ratio:1.37 (1.22-1.53), p<.001] was found as an independent risk factor for carriage of CPE. / Conclusion: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE. / Summary: The incidence rate of Carbapenemase-producing Enterobacteriaceae is increasing in Hong Kong, with the predominant enzyme of class B carbapenemase. With multivariable conditional logistic regression, the previous use of any beta-lactam antibiotics was found as an independent risk factor for CPE carriage

Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study

Background: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. Methods: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8uC and 37.5uC) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). Findings: Using front of face ITIS for prediction of tympanic temperature $37.8uC, the area under the ROC curve was 0.86 (95$37.8uC at screening (95%CI 0 % to 12%); three had no influenza symptoms. Conclusion: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were no

The Impact of Pandemic Influenza H1N1 on Health-Related Quality of Life: A Prospective Population-Based Study

BACKGROUND: While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures. METHODS AND FINDINGS: Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths. A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, p  =  0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting). CONCLUSION: Given the global public health significance of influenza, it is remarkable that no previous prospective study of the QALY loss of influenza using standardised and well validated methods has been performed. Although the QALY loss was minor for individual patients, the estimated total burden of influenza over the pandemic was substantial when compared to other infectious diseases

Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization

BACKGROUND: Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services. METHODS: A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21-28 days for BNT162b2; 14-28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination. RESULTS: Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478-2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926-1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878-1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951-20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951-1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867-1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals. CONCLUSIONS: No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer's product information, until further studies support the benefits of delaying vaccination outweighing the risks