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1.  Responses to Threat of Influenza A(H7N9) and Support for Live Poultry Markets, Hong Kong, 2013 
Emerging Infectious Diseases  2014;20(5):882-886.
We conducted a population survey in Hong Kong to gauge psychological and behavioral responses to the threat of influenza A(H7N9) and support for closure of live poultry markets. We found low anxiety and low levels of exposure to live poultry but mixed support for permanent closure of the markets.
PMCID: PMC4012820  PMID: 24750988
avian influenza A(H7N9); influenza; viruses; Hong Kong; public health; behavioral response; psychological response; community; H7N9; survey; respiratory infections; live poultry markets; poultry; birds
2.  Infection Fatality Risk of the Pandemic A(H1N1)2009 Virus in Hong Kong 
American Journal of Epidemiology  2013;177(8):834-840.
One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60–69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.
PMCID: PMC3658096  PMID: 23459950
death; human influenza; severity
3.  The Contribution of Social Behaviour to the Transmission of Influenza A in a Human Population 
PLoS Pathogens  2014;10(6):e1004206.
Variability in the risk of transmission for respiratory pathogens can result from several factors, including the intrinsic properties of the pathogen, the immune state of the host and the host's behaviour. It has been proposed that self-reported social mixing patterns can explain the behavioural component of this variability, with simulated intervention studies based on these data used routinely to inform public health policy. However, in the absence of robust studies with biological endpoints for individuals, it is unclear how age and social behaviour contribute to infection risk. To examine how the structure and nature of social contacts influenced infection risk over the course of a single epidemic, we designed a flexible disease modelling framework: the population was divided into a series of increasingly detailed age and social contact classes, with the transmissibility of each age-contact class determined by the average contacts of that class. Fitting the models to serologically confirmed infection data from the 2009 Hong Kong influenza A/H1N1p pandemic, we found that an individual's risk of infection was influenced strongly by the average reported social mixing behaviour of their age group, rather than by their personal reported contacts. We also identified the resolution of social mixing that shaped transmission: epidemic dynamics were driven by intense contacts between children, a post-childhood drop in risky contacts and a subsequent rise in contacts for individuals aged 35–50. Our results demonstrate that self-reported social contact surveys can account for age-associated heterogeneity in the transmission of a respiratory pathogen in humans, and show robustly how these individual-level behaviours manifest themselves through assortative age groups. Our results suggest it is possible to profile the social structure of different populations and to use these aggregated data to predict their inherent transmission potential.
Author Summary
For infections such as influenza, there are several aspects to the transmission process, including the properties of the pathogen itself, the host immune system and host behaviour. Although it has been proposed that self-reported social mixing patterns can be used to explain the behavioural component of infection – and mathematical modelling studies based on reported social contacts are used routinely to inform health policy – it is not clear how these contacts contribute to individual- and group-level infection risk. By analysing the relationship between social contacts and infection patterns during the 2009 Hong Kong influenza pandemic, we show that infection risk was strongly influenced by the average reported social mixing behaviour of an individual's age group, rather than by their personal reported contacts. We also demonstrate how social contact surveys can be combined with mathematical models to create useful tools with which to study respiratory infections in humans. This should make it possible to predict how the impact of interventions will vary from one population to the next based on their contacts and, potentially, to explain differences in infection attack rates between groups with different mixing behaviours.
PMCID: PMC4072802  PMID: 24968312
4.  Comparative Epidemiology of Pandemic and Seasonal Influenza A in Households 
The New England journal of medicine  2010;362(23):2175-2184.
There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings.
We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses.
Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness.
Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.
PMCID: PMC4070281  PMID: 20558368
5.  The Serial Intervals of Seasonal and Pandemic Influenza Viruses in Households in Bangkok, Thailand 
American Journal of Epidemiology  2013;177(12):1443-1451.
The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11–14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.
PMCID: PMC3676150  PMID: 23629874
human; influenza; Thailand
6.  Influenza Vaccine Effectiveness in the Community and the Household 
We examined influenza vaccine effectiveness in preventing community- and household-acquired influenza. Estimates were lower than those demonstrated in other observational studies carried out the same season, with unexpected findings of lower effectiveness with repeated vaccination and no protection with household exposure.
Background. There is a recognized need to determine influenza vaccine effectiveness on an annual basis and a long history of studying respiratory illnesses in households.
Methods. We recruited 328 households with 1441 members, including 839 children, and followed them during the 2010–2011 influenza season. Specimens were collected from subjects with reported acute respiratory illnesses and tested by real-time reverse transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or an immunization registry. The effectiveness of 2010–2011 influenza vaccination in preventing laboratory-confirmed influenza was estimated using Cox proportional hazards models adjusted for age and presence of high-risk condition, and stratified by prior season (2009–2010) vaccination status.
Results. Influenza was identified in 78 (24%) households and 125 (9%) individuals; the infection risk was 8.5% in the vaccinated and 8.9% in the unvaccinated (P = .83). Adjusted vaccine effectiveness in preventing community-acquired influenza was 31% (95% confidence interval [CI], −7% to 55%). In vaccinated subjects with no evidence of prior season vaccination, significant protection (62% [95% CI, 17%–82%]) against community-acquired influenza was demonstrated. Substantially lower effectiveness was noted among subjects who were vaccinated in both the current and prior season. There was no evidence that vaccination prevented household transmission once influenza was introduced; adults were at particular risk despite vaccination.
Conclusions. Vaccine effectiveness estimates were lower than those demonstrated in other observational studies carried out during the same season. The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study.
PMCID: PMC3693492  PMID: 23413420
influenza; vaccine effectiveness; households with children
7.  The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong 
In recent years Hong Kong has invested in research infrastructure to appropriately respond to novel infectious disease epidemics. Research from Hong Kong made a strong contribution to the international response to the 2009 influenza A(H1N1) pandemic (pH1N1). Summarizing, describing and reviewing the Hong Kong's response to the 2009 pandemic, this article aimed to identify key elements of a real-time research response.
A systematic search in PubMed and EMBASE for research into the infection dynamics and natural history, impact or control of pH1N1 in Hong Kong. Eligible articles were analyzed according to their scope.
55 articles were included in the review. Transmissibility of pH1N1 was similar in Hong Kong to elsewhere, and only a small fraction of infections were associated with severe disease. School closures were effective in reducing pH1N1 transmission, oseltamivir was effective for treatment of severe cases while convalescent plasma therapy has the potential to mitigate future pandemics.
There was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing important information on the epidemiology of the novel virus with relevance internationally as well as locally. The scientific knowledge gained through these detailed studies of pH1N1 is now being used to revise and update pandemic plans. The experiences of the research response in Hong Kong could provide a template for the research response to future emerging and reemerging disease epidemics.
PMCID: PMC3705741  PMID: 22883352
8.  Population-Based Hospitalization Burden of Influenza A Virus Subtypes and Antigenic Drift Variants in Children in Hong Kong (2004–2011) 
PLoS ONE  2014;9(4):e92914.
We aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in Hong Kong.
The pediatric age-specific rates of influenza A hospitalization in Hong Kong for 2004–2011 which encompassed the emergence of H1N1pdm09 were extrapolated from admissions to 2 hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza A was detected by immunofluorescence, culture and/or PCR on nasopharyngeal aspirates.
Influenza A caused high rates of hospitalization in children with year to year fluctuations. The highest hospitalization burden was seen with H1N1pdm09 in 2009. Additional factors affecting hospitalization were the proportion of viral circulation among different subtypes, and antigenic drifts. Taking these into effect, an H3N2 dominated year was not always associated with more hospitalizations than a ‘seasonal’ H1N1 year. Hospitalization burden was higher in seasons when drifted viruses of H1N1 or H3N2 dominated. No hospitalization was documented in infants <6 months of age during years when an undrifted virus circulated (2006 for H1N1 and 2008 for H3N2) but significant hospitalization was observed with a drifted or shifted virus (2004, 2005, 2007 and 2010 for H3N2, and 2009 for H1N1pdm09).
We documented a consistently high pediatric hospitalization burden of influenza A. Knowledge of antigenic changes and their proportion of circulation aids in the interpretation of impact of the subtypes. Year-to-year variation in hospitalization rates in young infants appeared to correlate with antigenic variation, lending support to the role of protection from maternal antibodies.
PMCID: PMC4005733  PMID: 24786780
9.  School closures during the 2009 influenza pandemic: national and local experiences 
BMC Infectious Diseases  2014;14:207.
School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives.
Data were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden. A standard data collection form was developed and sent to all participants. The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data.
Our review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic. The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries. Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area.
The single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.
PMCID: PMC4021091  PMID: 24739814
10.  Heterogeneity in Viral Shedding Among Individuals With Medically Attended Influenza A Virus Infection 
The Journal of Infectious Diseases  2013;207(8):1281-1285.
Compared with the average transmissibility of human influenza A virus, much less attention has been paid to the potential variability in its transmissibility. We considered viral shedding as a proxy for infectiousness and explored the heterogeneity of infectiousness among patients with medically attended seasonal influenza A virus infection. The analysis revealed that viral shedding is more heterogeneous in children than in adults. The top 20% most infectious children and adults were estimated to be responsible for 89%–96% and 78%–82%, respectively, of the total infectiousness in each age group. Further investigation is required to correlate the substantial variations in viral shedding with heterogeneity in actual transmissibility.
PMCID: PMC3603536  PMID: 23382573
influenza; viral shedding; infectiousness
11.  Anxiety, worry and cognitive risk estimate in relation to protective behaviors during the 2009 influenza A/H1N1 pandemic in Hong Kong: ten cross-sectional surveys 
BMC Infectious Diseases  2014;14:169.
Few studies have investigated associations between psychological and behavioral indices throughout a major epidemic. This study was aimed to compare the strength of associations between different cognitive and affective measures of risk and self-reported protective behaviors in a series of ten cross-sectional surveys conducted throughout the first wave of influenza A/H1N1 pandemic.
All surveys were conducted using questionnaire-based telephone interviews, with random digit dialing to recruit adults from the general population. Measures of anxiety and worry (affective) and perceived risk (cognitive) regarding A/H1N1 were made in 10 serial surveys. Multivariate logistic regression models were used to estimate the cognitive/affective-behavioral associations in each survey while multilevel logistic models were conducted to estimate the average effects of each cognitive/affective measure on adoption of protective behaviors throughout the ten surveys.
Excepting state anxiety, other affective measures including “anticipated worry”, “experienced worry” and “current worry” specific to A/H1N1 risk were consistently and strongly associated with adoption of protective behaviors across different survey periods. However, the cognitive-behavioral associations were weaker and inconsistent across the ten surveys. Perceived A/H1N1 severity relative to SARS had stronger associations with adoption of protective behaviors in the late epidemic periods than in the early epidemic periods.
Risk-specific worries appear to be significantly associated with the adoption of protective behaviors at different epidemic stages, whereas cognitive measures may become more important in understanding people’s behavioral responses later in epidemics. Future epidemic-related psycho-behavioral research should include more affective-loaded measures of risk.
PMCID: PMC3986671  PMID: 24674239
Influenza pandemic; Affect; Perceived risk; Protective behavior; Chinese adults
13.  Excess Mortality Associated With Influenza A and B Virus in Hong Kong, 1998–2009 
The Journal of Infectious Diseases  2012;206(12):1862-1871.
Background. Although deaths associated with laboratory-confirmed influenza virus infections are rare, the excess mortality burden of influenza estimated from statistical models may more reliably quantify the impact of influenza in a population.
Methods. We applied age-specific multiple linear regression models to all-cause and cause-specific mortality rates in Hong Kong from 1998 through 2009. The differences between estimated mortality rates in the presence or absence of recorded influenza activity were used to estimate influenza-associated excess mortality.
Results. The annual influenza-associated all-cause excess mortality rate was 11.1 (95% confidence interval [CI], 7.2–14.6) per 100 000 person-years. We estimated an average of 751 (95% CI, 488–990) excess deaths associated with influenza annually from 1998 through 2009, with 95% of the excess deaths occurring in persons aged ≥65 years. Most of the influenza-associated excess deaths were from respiratory (53%) and cardiovascular (18%) causes. Influenza A(H3N2) epidemics were associated with more excess deaths than influenza A(H1N1) or B during the study period.
Conclusions. Influenza was associated with a substantial number of excess deaths each year, mainly among the elderly, in Hong Kong in the past decade. The influenza-associated excess mortality rates were generally similar in Hong Kong and the United States.
PMCID: PMC3502382  PMID: 23045622
14.  Potential Use of School Absenteeism Record for Disease Surveillance in Developing Countries, Case Study in Rural Cambodia 
PLoS ONE  2013;8(10):e76859.
Disease surveillance allows prospective monitoring of patterns in disease incidence in the general community, specific institutions (e.g. hospitals, elderly care homes), and other important population subgroups. Surveillance activities are now routinely conducted in many developed countries and in certain easy-to-reach areas of the developing ones. However due to limited health resources, population in rural area that consisted of the most the vulnerable groups are not under surveillance. Cheaper alternative ways for disease surveillance were needed in resource-limited settings.
Methods and Findings
In this study, a syndromic surveillance system using disease specific absenteeism rates was established in 47 pre-schools with 1,417 students 3–6 y of age in a rural area of Kampot province, Cambodia. School absenteeism data were collected via short message service. Data collected between 1st January and 31st December 2012 was used for system evaluation for future potential use in larger scale. The system appeared to be feasible and acceptable in the rural study setting. Moderate correlation was found between rates of school absenteeism due to illness and the reference data on rates of attendance at health centers in persons <16 y (maximum cross-correlation coefficient = 0.231 at lag = −1 week).
School absenteeism data is pre-existing, easily accessible and requires minimum time and resources after initial development, and our results suggest that this system may be able to provide complementary data for disease surveillance, especially in resource limited settings where there is very little information on illnesses in the community and traditional surveillance systems are difficult to implement. An important next step is to validate the syndromic data with other forms of surveillance including laboratory data.
PMCID: PMC3796562  PMID: 24155907
15.  Influenza Transmission in a Cohort of Households with Children: 2010-2011 
PLoS ONE  2013;8(9):e75339.
Households play a major role in community spread of influenza and are potential targets for mitigation strategies.
We enrolled and followed 328 households with children during the 2010-2011 influenza season; this season was characterized by circulation of influenza A (H3N2), A (H1N1)pdm09 and type B viruses. Specimens were collected from subjects with acute respiratory illnesses and tested for influenza in real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays. Influenza cases were classified as community-acquired or household-acquired, and transmission parameters estimated.
Influenza was introduced to 78 (24%) households and transmission to exposed household members was documented in 23 households. Transmission was more likely in younger households (mean age <22 years) and those not reporting home humidification, but was not associated with household vaccination coverage. The secondary infection risk (overall 9.7%) was highest among young children (<9 years) and varied substantially by influenza type/subtype with the highest risk for influenza A (H3N2). The serial interval (overall 3.2 days) also varied by influenza type and was longest for influenza B. Duration of symptomatic illness was shorter in children compared with adults, and did not differ by influenza vaccination status.
Prospective study of households with children over a single influenza season identified differences in household transmission by influenza type/subtype, subject age, and home humidification, suggesting possible targets for interventions to reduce transmission.
PMCID: PMC3783407  PMID: 24086511
16.  Humoral Antibody Response after Receipt of Inactivated Seasonal Influenza Vaccinations one Year Apart in Children 
In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to subjects 6–15 years of age in two consecutive years. Receipt of TIV in year 2 induced seroprotection in most subjects. Among 39 children who received TIV in the second year, receipt of TIV in the first year was associated with lower antibody titer rises in the second year to seasonal influenza A(H1N1) and A(H3N2) strains for which the vaccine strains remained unchanged. Antibody response to a different influenza B strain in the second year was unaffected by receipt of TIV in the first year.
PMCID: PMC3422369  PMID: 22683675
vaccination; influenza; antibody response; children
17.  Moderate Alcohol Use and Cardiovascular Disease from Mendelian Randomization 
PLoS ONE  2013;8(7):e68054.
Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use.
We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study.
ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45).
Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.
PMCID: PMC3712994  PMID: 23874492
18.  Estimation of the serial interval of influenza 
Epidemiology (Cambridge, Mass.)  2009;20(3):344-347.
Estimates of the clinical-onset serial interval of human influenza infection (time between onset of symptoms in an index case and a secondary case) are used to inform public health policy and to construct mathematical models of influenza transmission. We estimate the serial interval of laboratory-confirmed influenza transmission in households.
Index cases were recruited after reporting to a primary healthcare center with symptoms. Members of their households were followed up with repeated home visits.
Assuming a Weibull model and accounting for selection bias inherent in our field study design, we used symptom-onset times from 14 pairs of infector/infectee to estimate a mean serial interval of 3.6 days (95% confidence interval = 2.9–4.3 days), with standard deviation 1.6 days.
The household serial interval of influenza may be longer than previously estimated. Studies of the complete serial interval, based on transmission in all community contexts, are a priority.
PMCID: PMC3057478  PMID: 19279492
19.  Household transmission of 2009 pandemic influenza A(H1N1): a systematic review and meta-analysis 
Epidemiology (Cambridge, Mass.)  2012;23(4):531-542.
During the 2009 influenza A(H1N1) pandemic, household transmission studies were implemented to understand better the characteristics of the transmission of the novel virus in a confined setting.
We conducted a systematic review and meta-analysis to assess and summarize the findings of these studies. We identified 27 articles, around half of which reported studies conducted in May and June 2009.
In 13 of the 27 studies (48%) that collected respiratory specimens from household contacts, point estimates of the risk of secondary infection ranged from 3 to 38%, with substantial heterogeneity. Meta-regression analyses revealed that a part of the heterogeneity reflected varying case ascertainment and study designs. The estimates of symptomatic secondary infection risk, based on 20 studies identifying febrile acute respiratory illness among household contacts, also showed substantial variability, with point estimates ranging from 4% to 37%.
Transmission of the 2009 pandemic virus in households appeared to vary in different countries and settings, with differences in estimates of the secondary infection risk also partly due to differences in study designs.
PMCID: PMC3367058  PMID: 22561117
20.  Aerosol transmission is an important mode of influenza A virus spread 
Nature communications  2013;4:1935.
Influenza A viruses are believed to spread between humans through contact, large respiratory droplets and small particle droplet nuclei (aerosols), but the relative importance of each of these modes of transmission is unclear. Volunteer studies suggest that infections via aerosol transmission may have a higher risk of febrile illness. Here we apply a mathematical model to data from randomized controlled trials of hand hygiene and surgical face masks in Hong Kong and Bangkok households. In these particular environments, inferences on the relative importance of modes of transmission are facilitated by information on the timing of secondary infections and apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We find that aerosol transmission accounts for approximately half of all transmission events. This implies that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households.
PMCID: PMC3682679  PMID: 23736803
21.  Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine 
We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.
PMCID: PMC3404712  PMID: 22423139
22.  Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials 
BMC Medicine  2013;11:108.
Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease.
A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60).
The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.
PMCID: PMC3648456  PMID: 23597181
Testosterone; Cardiovascular; Men; Trial
23.  Smoking, quitting and mortality in an elderly cohort of 56 000 Hong Kong Chinese 
Tobacco Control  2007;16(3):182-189.
Although the harms of smoking are well established, it is unclear how they extend into old age in the Chinese.
To examine the relationship of smoking with all‐cause and major cause‐specific mortality in elderly Chinese men and women, respectively, in Hong Kong.
Mortality by smoking status was examined in a prospective cohort study of 56 167 (18 749 men, 37 416 women) Chinese aged ⩾65 years enrolled from 1998 to 2000 at all the 18 elderly health centres of the Hong Kong Government Department of Health.
After a mean follow‐up of 4.1 years, 1848 male and 2035 female deaths occured among 54 214 subjects (96.5% successful follow‐up). At baseline, more men than women were current smokers (20.3% vs 4.0%) and former smokers (40.8% vs 7.9%). The adjusted RRs (95% CI) for all‐cause mortality in former and current smokers, compared with never smokers, were 1.39 (1.23 to 1.56) and 1.75 (1.53 to 2.00) in men and 1.43 (1.25 to 1.64) and 1.38 (1.14 to 1.68) in women, respectively. For current smokers, the RRs (95% CI) for all‐cause mortality were 1.59 (1.39 to 1.82), 1.72 (1.48 to 2.00) and 1.84 (1.43 to 2.35) for daily consumption of 1–9, 10–20 and >21 cigarettes, respectively (p for trend <0.001). RRs (95% CI) were 1.49 (1.30 to 1.72) and 2.20 (1.88 to 2.57) in former and current smokers for all deaths from cancer, and 1.24 (1.04 to 1.47) and 1.57 (1.28 to 1.94) for all cardiovascular deaths, respectively. Quitters had significantly lower risks of death than current smokers from all causes, lung cancer, all cancers, stroke and all cardiovascular diseases.
In old age, smoking continues to be a major cause of death, and quitting is beneficial. Smoking cessation is urgently needed in rapidly ageing populations in the East.
PMCID: PMC2598507  PMID: 17565138
24.  Age-Period-Cohort Projections of Ischaemic Heart Disease Mortality by Socio-Economic Position in a Rapidly Transitioning Chinese Population 
PLoS ONE  2013;8(4):e61495.
With economic development and population aging, ischaemic heart disease (IHD) is becoming a leading cause of mortality with widening inequalities in China. To forewarn the trends in China we projected IHD trends in the most economically developed part of China, i.e., Hong Kong.
Based on sex-specific IHD mortality rates from 1976 to 2005, we projected mortality rates by neighborhood-level socio-economic position (i.e., low- or high-income groups) to 2020 in Hong Kong using Poisson age-period-cohort models with autoregressive priors.
In the low-income group, age-standardized IHD mortality rates among women declined from 33.3 deaths in 1976–1980 to 19.7 per 100,000 in 2016–2020 (from 55.5 deaths to 34.2 per 100,000 among men). The rates in the high-income group were initially higher in both sexes, particularly among men, but this had reversed by the end of the study periods. The rates declined faster for the high-income group than for the low-income group in both sexes. The rates were projected to decline faster in the high-income group, such that by the end of the projection period the high-income group would have lower IHD mortality rates, particularly for women. Birth cohort effects varied with sex, with a marked upturn in IHD mortality around 1945, i.e., for the first generation of men to grow up in a more economically developed environment. There was no such upturn in women. Birth cohort effects were the main drivers of change in IHD mortality rates.
IHD mortality rates are declining in Hong Kong and are projected to continue to do so, even taking into account greater vulnerability for the first generation of men born into a more developed environment. At the same time social disparities in IHD have reversed and are widening, partly as a result of a cohort effect, with corresponding implications for prevention.
PMCID: PMC3623955  PMID: 23593484
25.  Potential use of multiple surveillance data in the forecast of hospital admissions 
This paper describes the potential use of multiple influenza surveillance data to forecast hospital admissions for respiratory diseases.
A sudden surge in hospital admissions in public hospital during influenza peak season has been a challenge to healthcare and manpower planning. In Hong Kong, the timing of influenza peak seasons are variable and early short-term indication of possible surge may facilitate preparedness which could be translated into strategies such as early discharge or reallocation of extra hospital beds. In this study we explore the potential use of multiple routinely collected syndromic data in the forecast of hospital admissions.
A multivariate dynamic linear time series model was fitted to multiple syndromic data including influenza-like illness (ILI) rates among networks of public and private general practitioners (GP), and school absenteeism rates, plus drop-in fever count data from designated flu clinics (DFC) that were created during the pandemic. The latent process derived from the model has been used as a measure of the influenza activity [1]. We compare the cross-correlations between estimated influenza level based on multiple surveillance data and GP ILI data, versus accident and emergency hospital admissions with principal diagnoses of respiratory diseases and pneumonia & influenza (P&I).
The estimated influenza activity has higher cross-correlation with respiratory and P&I admissions (ρ=0.66 and 0.73 respectively) compared to that of GP ILI rates (Table 1). Cross correlations drop distinctly after lag 2 for both estimated influenza activity and GP ILI rates.
The use of a multivariate method to integrate information from multiple sources of influenza surveillance data may have the potential to improve forecasting of admission surge of respiratory diseases.
PMCID: PMC3692818
influenza; surveillance; admission; respiratory

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