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We tracked the effective reproduction number (R t ) of the predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on 1-11 November (when China's zero-COVID interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on 10-22 December and self-reported to have been test-positive since 1 November. After China's announcement of 20 measures to transition from zero-COVID, we estimated that R t increased to 3.44 (95% credible interval (CrI): 2.82-4.14) on 18 November and the infection incidence peaked on 11 December. We estimated that the cumulative infection attack rate (IAR; that is, proportion of the population infected since 1 November) in Beijing was 75.7% (95% CrI: 60.7-84.4) on 22 December 2022 and 92.3% (95% CrI: 91.4-93.1) on 31 January 2023. Surveillance programs should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings., (© 2022. The Author(s).)

On January 6, 2022, a cluster of COVID-19 cases* caused by the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, was detected in Hong Kong Special Administrative Region, China (Hong Kong), resulting in the territory's fifth wave of COVID-19 cases (1). This wave peaked on March 4, 2022, with 8,764 COVID-19 cases per million population (2), resulting in a total of 1,049,959 cases and 5,906 COVID-19-associated deaths reported to the Hong Kong Department of Health during January 6-March 21, 2022. † Throughout this period, the COVID-19 mortality rate in Hong Kong (37.7 per million population) was among the highest reported worldwide since the COVID-19 pandemic began (3). Publicly available data on age-specific vaccination coverage in Hong Kong with a 2-dose primary vaccination series (with either Sinovac-CoronaVac [Sinovac], an inactivated COVID-19 viral vaccine, recommended for persons aged ≥3 years or BNT162b2 [Pfizer-BioNTech], an mRNA vaccine, for persons aged ≥5 years), as of December 23, 2021, § , ¶ and COVID-19 mortality during January 6-March 21, 2022, were analyzed. By December 23, 2021, 67% of vaccine-eligible persons in Hong Kong had received ≥1 dose of a COVID-19 vaccine, 64% had received ≥2 doses, and 5% had received a booster dose. Among persons aged ≥60 years, these proportions were 52%, 49%, and 7%, respectively. Among those aged ≥60 years, vaccination coverage declined with age: 48% of persons aged 70-79 years had received ≥1 dose, 45% received ≥2 doses, and 7% had received a booster, and among those aged ≥80 years, 20%, 18%, and 2% had received ≥1 dose, ≥2 doses, and a booster dose, respectively. Among 5,906 COVID-19 deaths reported, 5,655 (96%) occurred in persons aged ≥60 years**; among these decedents, 3,970 (70%) were unvaccinated, 18% (1,023) had received 1 vaccine dose, and 12% (662) had received ≥2 doses. The overall rates of COVID-19-associated mortality among persons aged ≥60 years who were unvaccinated, who had received 1 COVID-19 vaccine dose, and who had received ≥2 vaccine doses were 10,076, 1,099, and 473 per million population, respectively; the risk for COVID-19-associated death among unvaccinated persons was 21.3 times that among recipients of 2-3 doses in this age group. The high overall mortality rate during the ongoing 2022 Hong Kong Omicron COVID-19 outbreak is being driven by deaths among unvaccinated persons aged ≥60 years. Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially among persons aged ≥60 years., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: The cost-effectiveness of mammography screening among Chinese women remains contentious. Here, we characterized breast cancer (BC) epidemiology in Hong Kong and evaluated the cost-effectiveness of personalized risk-based screening., Methods: We used the Hong Kong Breast Cancer Study (a case-control study with 3501 cases and 3610 controls) and Hong Kong Cancer Registry to develop a risk stratification model based on well-documented risk factors. We used the Shanghai Breast Cancer Study to validate the model. We considered risk-based programs with different screening age ranges and risk thresholds under which women were eligible to join if their remaining BC risk at the starting age exceeded the threshold., Results: The lifetime risk (15-99 years) of BC ranged from 1.8% to 26.6% with a mean of 6.8%. Biennial screening was most cost-effective when the starting age was 44 years, and screening from age 44 to 69 years would reduce breast cancer mortality by 25.4% (95% credible interval [CrI] = 20.5%-29.4%) for all risk strata. If the risk threshold for this screening program was 8.4% (the average remaining BC risk among US women at their recommended starting age of 50 years), the coverage was 25.8%, and the incremental cost-effectiveness ratio (ICER) was US$18 151 (95% CrI = $10 408-$27 663) per quality-of-life-year (QALY) compared with no screening. The ICER of universal screening was $34 953 (95% CrI = $22 820-$50 268) and $48 303 (95% CrI = $32 210-$68 000) per QALY compared with no screening and risk-based screening with 8.4% threshold, respectively., Conclusion: Organized BC screening in Chinese women should commence as risk-based programs. Outcome data (e.g., QALY loss because of false-positive mammograms) should be systemically collected for optimizing the risk threshold., (© The Author(s) 2021. Published by Oxford University Press.)

Purpose: To investigate the prevalence, associations, and causes of visual impairment and blindness in the adult population of Hong Kong., Methods: This cross-sectional population-based study included 2018 (870, 43% male) randomly selected adults with a mean age 52 ± 16 years (range 18-90 years) in Hong Kong. Each participant underwent comprehensive ophthalmic examinations. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) of each eye was recorded. Prevalence of visual impairment and blindness was calculated using both World Health Organization (WHO) and United States (US) definitions, based on BCVA and PVA., Results: Visual acuity measurements were available for 1952 (96.8%) participants. The prevalence of visual impairment, based on BCVA value, using WHO and US definition, was 1.0 ± 0.1% and 2.7 ± 0.4%, respectively. The prevalence of visual impairment, based on PVA value, was 5.1 ± 0.5% and 14.0 ± 0.8%, using WHO and US definition, respectively. Multivariate analysis demonstrated the presence of visual impairment (PVA, WHO definition) increased significantly with older age (odds ratio 1.039, P < .001) and thinner central cornea thickness (odds ratio 0.994, P = .014), but not significantly associated with other socioeconomic, systemic or ocular parameters after adjusting for age and central corneal thickness. Under-correction of refractive error was the most common reason for presenting visual impairment. Causes of impaired BCVA were cataract (37%), age-related macular degeneration (26%), diabetic macular edema (11%), glaucoma (11%), epiretinal membrane (5%), and unknown (11%)., Conclusion: The prevalence of visual impairment in Hong Kong increased significantly with older age and thinner central corneal thickness. The major causes for impairment were under-correction of refractive error, cataract, and age-related macular degeneration.

Background: Owing to rapidly raising property prices, living with parents is the most common living arrangement among young adults in urban areas. Studies for "full nest syndrome" or "boomerang children" have demonstrated that moving back in with parents was associated with more depressive symptoms. On the other hand, studies have suggested that living with parents was not associated with mental health in several countries where inter-generational households could potentially provide more social support among household members. We examined whether delayed residential independence might adversely impact mental health of young adults., Methods: The cross-sectional study was conducted from 2009 to 2011 in Hong Kong SAR, China - a highly urbanized city with the least affordable housing in the world. The analytic samples were 3612 young adults. Outcomes of interest were depressive symptoms and mental well-being., Results: Co-residence with parents under self headship was associated with young adults' fewer depressive symptoms (β = -0.157, 95% confidence interval [CI] = -0.311 to -0.003) and better mental well-being (β = 1.342, 95% CI = 0.522 to 2.162)., Limitations: This is susceptible to reverse causation, whereby young adults with poorer mental health may be more likely to stay or move back into their parental home., Conclusions: Our findings showed that young adults co-residing with parents as the household head were associated with fewer depressive symptoms and better mental well-being compared to living with parents under their parental headship., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies of novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have reported varying estimates of epidemiological parameters, including serial interval distributions-i.e., the time between illness onset in successive cases in a transmission chain-and reproduction numbers. By compiling a line-list database of transmission pairs in mainland China, we show that mean serial intervals of COVID-19 shortened substantially from 7.8 to 2.6 days within a month (9 January to 13 February 2020). This change was driven by enhanced nonpharmaceutical interventions, particularly case isolation. We also show that using real-time estimation of serial intervals allowing for variation over time provides more accurate estimates of reproduction numbers than using conventionally fixed serial interval distributions. These findings could improve our ability to assess transmission dynamics, forecast future incidence, and estimate the impact of control measures., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-2 1 . This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection 2 . Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Background: When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China., Methods: We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic., Findings: From Jan 15 to March 3, 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. We estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7·1 times (95% credible interval [CrI] 4·8-10·9) from version 1 to 2, 2·8 times (1·9-4·2) from version 2 to 4, and 4·2 times (2·6-7·3) from version 4 to 5. If the fifth version of the case definition had been applied throughout the outbreak with sufficient testing capacity, we estimated that by Feb 20, 2020, there would have been 232 000 (95% CrI 161 000-359 000) confirmed cases in China as opposed to the 55 508 confirmed cases reported., Interpretation: The case definition was initially narrow and was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan, China, or other known cases. These changes should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias., Funding: Health and Medical Research Fund, Hong Kong., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: As of March 18, 2020, 13 415 confirmed cases and 120 deaths related to coronavirus disease 2019 (COVID-19) in mainland China, outside Hubei province-the epicentre of the outbreak-had been reported. Since late January, massive public health interventions have been implemented nationwide to contain the outbreak. We provide an impact assessment of the transmissibility and severity of COVID-19 during the first wave in mainland Chinese locations outside Hubei., Methods: We estimated the instantaneous reproduction number (R t ) of COVID-19 in Beijing, Shanghai, Shenzhen, Wenzhou, and the ten Chinese provinces that had the highest number of confirmed COVID-19 cases; and the confirmed case-fatality risk (cCFR) in Beijing, Shanghai, Shenzhen, and Wenzhou, and all 31 Chinese provinces. We used a susceptible-infectious-recovered model to show the potential effects of relaxing containment measures after the first wave of infection, in anticipation of a possible second wave., Findings: In all selected cities and provinces, the R t decreased substantially since Jan 23, when control measures were implemented, and have since remained below 1. The cCFR outside Hubei was 0·98% (95% CI 0·82-1·16), which was almost five times lower than that in Hubei (5·91%, 5·73-6·09). Relaxing the interventions (resulting in R t >1) when the epidemic size was still small would increase the cumulative case count exponentially as a function of relaxation duration, even if aggressive interventions could subsequently push disease prevalence back to the baseline level., Interpretation: The first wave of COVID-19 outside of Hubei has abated because of aggressive non-pharmaceutical interventions. However, given the substantial risk of viral reintroduction, particularly from overseas importation, close monitoring of R t and cCFR is needed to inform strategies against a potential second wave to achieve an optimal balance between health and economic protection., Funding: Health and Medical Research Fund, Hong Kong, China., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP., Methods: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number., Results: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9)., Conclusions: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions., Methods: We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23-24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI)., Findings: In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47-2·86) and that 75 815 individuals (95% CrI 37 304-130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8-7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227-805), 113 (57-193), 98 (49-168), 111 (56-191), and 80 (40-139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1-2 weeks., Interpretation: Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally., Funding: Health and Medical Research Fund (Hong Kong, China)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9-32%).

Background: Lower birth weight is associated with diabetes although the underlying mechanisms are unclear. Muscle mass could be a modifiable link and hence a target of intervention. We assessed the associations of birth weight with muscle and fat mass observationally in a population with little socio-economic patterning of birth weight and using Mendelian randomization (MR) for validation., Methods: In the population-representative "Children of 1997" birth cohort (n = 8,327), we used multivariable linear regression to assess the adjusted associations of birth weight (kg) with muscle mass (kg) and body fat (%) at ~17.5 years. Genetically predicted birth weight (effect size) was applied to summary genetic associations with fat-free mass and fat mass (kg) from the UK Biobank (n = ~331,000) to obtain unconfounded estimates using inverse-variance weighting., Results: Observationally, birth weight was positively associated with muscle mass (3.29 kg per kg birth weight, 95% confidence interval (CI) 2.83 to 3.75) and body fat (1.09% per kg birth weight, 95% CI 0.54 to 1.65). Stronger associations with muscle mass were observed in boys than in girls (p for interaction 0.004). Using MR, birth weight was positively associated with fat-free mass (0.77 kg per birth weight z-score, 95% CI 0.22 to 1.33) and fat mass (0.58, 95% CI 0.01 to 1.15). No difference by sex was evident., Conclusion: Higher birth weight increasing muscle mass may be relevant to lower birth weight increasing the risk of diabetes and suggests post-natal muscle mass as a potential target of intervention., Competing Interests: The authors have declared that no competing interests exist.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects 6.0% of the global population. G6PD deficiency has been associated with lower risk of cardiovascular disease and higher risk of diabetes, which could be etiologically informative, but these relations are uncertain. To clarify, we assessed the associations of G6PD deficiency with serum metabolite profiles in late adolescence., Methods: In a nested case-control study of 50 G6PD-deficient late adolescents (~17.5 years) and 150 sex-matched non-G6PD-deficient controls from a Chinese birth cohort: "Children of 1997", we compared 80 serum metabolites analyzed by nuclear magnetic resonance spectrometry using adjusted linear regression with Bonferroni correction for testing 12 traits (p < 0.0042)., Results: G6PD-deficiency was inversely associated with serum levels of total cholesterol (-0.27 mmol, 95% confidence interval (CI) -0.46, -0.09, p = 0.004), free cholesterol (-0.08 mmol, 95% CI -0.13, -0.03, p = 0.003) and creatinine (-0.004 mmol, 95% CI -0.007, -0.001, p = 0.003), adjusted for sex and parental education. G6PD deficiency was not associated with fatty acids, amino acids, glucose or related metabolites, ketone bodies or glycoprotein., Conclusions: G6PD deficiency is associated with lower serum levels of cholesterol and creatinine, but not other serum metabolites. Whether such differences are transient or become more evident in adulthood warrant further investigations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Not commissioned; externally peer reviewed.

Background/objectives: Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy., Methods: In the prospective Chinese birth cohort "Children of 1997" (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2- < 8 years) and adolescence (8-16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life., Results: In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (-0.13, 95% confidence interval (CI) -0.22, -0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4)., Conclusions: In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

Background/objectives: In economically developed settings, household income is usually inversely associated with child and adolescent adiposity, but this association may not extend to migrants. Hong Kong is a unique developed setting to study how household income and adolescent adiposity vary by migrant status given many Hong Kong-born Chinese children were born to parents who migrated from neighboring provinces of Mainland China., Subjects/methods: We examined differences between the associations of absolute household income vs. relative household income on adolescent body mass index (BMI) z-score or overweight (including obesity) status using a linear or logistic model in a Chinese birth cohort (n = 5613, 68% follow-up). We focused on whether the associations differed by mother's or father's migrant status (birthplace)., Results: No association was found between absolute household income and BMI z-score among adolescents with either native or migrant mothers. However, the association of relative household income with BMI z-score varied by mother's migrant status (P-values for interaction <0.0005). In adolescents of native born mothers, greater relative household income deprivation was associated with higher BMI z-score (0.03 z-score per USD 128 difference in Yitzhaki index, 95% confidence interval (CI) 0.01 to 0.05). However, in adolescents of migrant mothers, greater relative household income deprivation was associated with lower BMI z-score (-0.05, 95% CI -0.09 to -0.01). Similar association of relative household income with overweight (including obesity) status was found in adolescents of native born mothers but not in adolescents of migrant mothers., Conclusions: Relative income (mediated by social comparisons with others in society) appears to be relevant to adolescent adiposity, but the association depends on the interplay between individual characteristics (migrant background) and societal context.

To clarify the causal role of age at menarche in depressive symptoms we conducted a Mendelian randomization study using a large Southern Chinese cohort (n = 12,233). A genetic allele score was derived using stepwise regression with cross validation. Older age at menarche was not associated with geriatric depression scale score. Our findings suggest that higher rates of depression in women are likely attributable to other factors which require investigation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: An intergenerational "mismatch," a transition from limited to plentiful living conditions over generations, may increase cardiovascular disease risks. In a migrant population within a homogenous culture, we tested the hypothesis that an intergenerational mismatch in childhood living condition is associated with higher body mass index (BMI) and blood pressure in childhood and adolescence., Methods: We used data from 6,965 native born Chinese in Hong Kong (participated in "Children of 1997" birth cohort) and migrant Chinese born elsewhere in China in 1997 (N = 9,845). We classified children into those with intergenerational mismatch (child migrants or first-generation migrants) or those without (second+-generation migrants). Generalized estimating equations were used to examine the associations of migration status (child migrants, first-generation migrants or second+-generation migrants) with age- and sex-specific BMI z-score at 8-15 years and age-, sex-, and height-specific blood pressure z-score at 11-13 years, adjusted for sex, month of birth, and age., Results: Compared with second+-generation migrants, first-generation migrants had higher diastolic blood pressure z-score (.04, 95% confidence interval (CI) .02, .06) and BMI z-score (.12, 95% CI .06, .18), whereas child migrants had higher diastolic blood pressure z-score (.03, 95% CI .01, .05) regardless of age at migration and higher BMI z-score if they had migrated in infancy (.17, 95% CI .11, .23)., Conclusion: Different relations for blood pressure and BMI suggest that intergenerational mismatch and proximal exposures may have different impacts on adiposity and blood pressure., (Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Observationally, lower birth weight is usually associated with poorer academic performance; whether this association is causal or the result of confounding is unknown. To investigate this question, we obtained an effect estimate, which can have a causal interpretation under specific assumptions, of birth weight on educational attainment using instrumental variable analysis based on single nucleotide polymorphisms determining birth weight combined with results from the Social Science Genetic Association Consortium study of 126,559 Caucasians. We similarly obtained an estimate of the effect of birth weight on academic performance in 4,067 adolescents from Hong Kong's (Chinese) Children of 1997 birth cohort (1997-2016), using twin status as an instrumental variable. Birth weight was not associated with years of schooling (per 100-g increase in birth weight, -0.006 years, 95% confidence interval (CI): -0.02, 0.01) or college completion (odds ratio = 1.00, 95% CI: 0.96, 1.03). Birth weight was also unrelated to academic performance in adolescents (per 100-g increase in birth weight, -0.004 grade, 95% CI: -0.04, 0.04) using instrumental variable analysis, although conventional regression gave a small positive association (0.02 higher grade, 95% CI: 0.01, 0.03). Observed associations of birth weight with academic performance may not be causal, suggesting that interventions should focus on the contextual factors generating this correlation., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Lower parental education is associated with higher adolescent blood pressure (BP). We examined the contribution of modifiable risk factors from infancy to adolescence that could potentially explain the link between parental education and SBP and DBP in the offspring., Methods: In a prospective Chinese birth cohort, 'Children of 1997' of 5604 adolescents (68% follow-up), we analyzed the relation between parental educational attainment and sex-specific, age-specific and height-specific BP z-scores at ∼13 years. Using mediation analysis, we examined the contribution of household income at birth (both absolute income and relative income deprivation), exposures during infancy (breastfeeding and early life second-hand smoking), lifestyles during childhood (diet, physical activity and screen-time), weight or BMI status during fetal, infancy, childhood and puberty, pubertal stage as well as parental BMI., Results: We found that adolescent BMI, but not birth weight or infant growth or childhood BMI, mediated the inverse association of parental education with adolescent SBP (proportion mediated: 24%), followed by maternal BMI (proportion mediated: 18%). Factors explaining the link between parental education and DBP were less clear. Absolute income, breastfeeding, childhood diet and physical activity, pubertal stage and paternal BMI did not mediate the association between parental education and adolescent BP., Conclusion: Low parental education is a risk factor for high SBP and, to a lesser extent, DBP in adolescents. Important mediators of this relation include adolescent and maternal body weight.

Background: China accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010-2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6-71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China., Methods and Findings: We characterized the economic and health burden of EV71-associated HFMD (EV71-HFMD) in China using (i) the national surveillance database, (ii) virological surveillance records from all provinces, and (iii) a caregiver survey on the household costs and health utility loss for 1,787 laboratory-confirmed pediatric cases. Using a static model parameterized with these data, we estimated the effective vaccine cost (EVC, defined as cost/efficacy or simply the cost of a 100% efficacious vaccine) below which routine pediatric vaccination would be considered cost-effective. We performed the base-case analysis from the societal perspective with a willingness-to-pay threshold of one times the gross domestic product per capita (GDPpc) and an annual discount rate of 3%. We performed uncertainty analysis by (i) accounting for the uncertainty in the risk of EV71-HFMD due to missing laboratory data in the national database, (ii) excluding productivity loss of parents and caregivers, (iii) increasing the willingness-to-pay threshold to three times GDPpc, (iv) increasing the discount rate to 6%, and (v) accounting for the proportion of EV71-HFMD cases not registered by national surveillance. In each of these scenarios, we performed probabilistic sensitivity analysis to account for parametric uncertainty in our estimates of the risk of EV71-HFMD and the expected costs and health utility loss due to EV71-HFMD. Routine pediatric EV71 vaccination would be cost-saving if the all-inclusive EVC is below US$10.6 (95% CI US$9.7-US$11.5) and would remain cost-effective if EVC is below US$17.9 (95% CI US$16.9-US$18.8) in the base case, but these ceilings could be up to 66% higher if all the test-negative cases with missing laboratory data are EV71-HFMD. The EVC ceiling is (i) 10%-14% lower if productivity loss of parents/caregivers is excluded, (ii) 58%-84% higher if the willingness-to-pay threshold is increased to three times GDPpc, (iii) 14%-19% lower if the discount rate is increased to 6%, and (iv) 36% (95% CI 23%-50%) higher if the proportion of EV71-HFMD registered by national surveillance is the same as that observed in the three EV71 vaccine phase III trials. The validity of our results relies on the following assumptions: (i) self-reported hospital charges are a good proxy for the opportunity cost of care, (ii) the cost and health utility loss estimates based on laboratory-confirmed EV71-HFMD cases are representative of all EV71-HFMD cases, and (iii) the long-term average risk of EV71-HFMD in the future is similar to that registered by national surveillance during 2010-2013., Conclusions: Compared to no vaccination, routine pediatric EV71 vaccination would be very cost-effective in China if the cost of immunization (including all logistical, procurement, and administration costs needed to confer 5 y of vaccine protection) is below US$12.0-US$18.3, depending on the choice of vaccine among the three candidates. Given that the annual number of births in China has been around 16 million in recent years, the annual costs for routine pediatric EV71 vaccination at this cost range should not exceed US$192-US$293 million. Our results can be used to determine the optimal vaccine when the prices of the three vaccines are known.

Background: Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus., Methods and Findings: Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16., Conclusions: The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.

Introduction: Low early life socio-economic position is more strongly associated with adiposity among women than men. We examined whether the sex difference of social patterning in general and central adiposity exists before adulthood., Methods: In Hong Kong's "Children of 1997" birth cohort, we used multivariable regression to examine the association of parental education, a marker of early life socio-economic position, with body mass index (BMI) (n = 7252, 88% follow-up) and waist-height ratio (n = 5636, 68% follow-up), at 14 years., Results: Parental education of Grade 9 or below, compared to Grade 12 or above, was associated with higher waist-height ratio z-score particularly in girls (0.30, 95% confidence interval (CI) 0.19, 0.41) compared to boys (0.12, 95% CI 0.02, 0.22) (p for sex interaction = 0.02). Lower parental education was associated with greater BMI z-score in adolescents of locally born mothers, but not adolescents of migrant mothers, with no difference by sex., Conclusions: Different social patterning in different markers of adiposity may imply different sociological and biological mediating pathways. A stronger association between low early life socio-economic position and waist-height ratio in adolescent girls may indicate sex-specific influences of SEP related early life exposures on central adiposity.

Background: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China., Methodology: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey., Principal Findings: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey., Conclusion/significance: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets.

We assessed the effect of closing live poultry markets in China on influenza A(H7N9) virus detection and viability. Intensive sampling was carried out before, during, and after a 2-week citywide market closure; the markets were cleaned and disinfected at the beginning of the closure period. Swab samples were collected at different sites within the markets and tested for H7N9 by real-time reverse transcription PCR and culture. During the closure, H7N9 viral RNA detection and isolation rates in retail markets decreased by 79% (95% CI 64%-88%) and 92% (95% CI 58%-98%), respectively. However, viable H7N9 virus could be cultured from wastewater samples collected up to 2 days after the market closure began. Our findings indicates that poultry workers and the general population are constantly exposed to H7N9 virus at these markets and that market closure and disinfection rapidly reduces the amount of viable virus.

Background: The novel influenza A(H7N9) virus has caused 2013 spring and 2013-2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic., Methods: We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves. In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014. In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014. All responses were weighted by age and sex to the respective adult populations., Findings: Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%). In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey. One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness., Conclusions: Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic.

Objectives: In Western contexts nut consumption is associated with better health. We examined the associations of nut consumption with cardiovascular disease risk in the non-Western setting of Southern China., Methods: In the Guangzhou Biobank Cohort Study we used multivariable linear regression to examine the associations of baseline nut (mainly peanuts) consumption (none (n = 6688), <3 portions/week (n = 2596) and ≥3 portions/week (n = 2444)) with follow-up assessment of Framingham cardiovascular disease score (excluding smoking) and its components in older Chinese (≥50 years) (follow-up 57.8%)., Results: Nut consumption was not associated with Framingham score (≥3 portions/week compared to none: 0.02 95% confidence interval (CI) -0.11 to 0.15), systolic blood pressure (-0.66 mmHg 95% CI -1.94, 0.62), diastolic blood pressure (-0.69 mmHg 95% CI -1.44, 0.07), HDL-cholesterol (-0.01 mmol/L 95% CI -0.02, 0.005), LDL-cholesterol (-0.01 mmol/L 95% CI -0.05, 0.02) or fasting glucose (0.04 mmol/L 95% CI -0.02, 0.09), adjusted for baseline values, energy intake, age, sex, phase of recruitment, socio-economic position, lifestyle and baseline health status., Conclusions: Observations concerning the benefits of nut consumption may be contextually specific, perhaps depending on the type of nut consumed.

Western observational studies show that moderate alcohol use is associated with lower cardiovascular disease (CVD) risk, but these associations may be confounded by the healthier attributes of moderate users in these settings. Mendelian randomization analysis may help to ascertain the causal effect of moderate alcohol use on specific factors related to CVD and thereby clarify the role of alcohol. We used Mendelian randomization analysis with the aldehyde dehydrogenase 2 gene (ALDH2) as an instrumental variable to examine the association of alcohol units (10 g of ethanol) per day with heart rate-corrected QT interval and heart rate assessed from electrocardiogram among 4,588 older southern Chinese men in the Guangzhou Biobank Cohort Study (2003-2008). The F statistic was 77 for ALDH2 on alcohol use, suggesting little weak-instrument bias. Instrumental variable analysis showed that alcohol units were not associated with the corrected QT interval, with β = 1.04 (95% confidence interval: -0.61, 2.70) milliseconds, but they were associated with increased heart rate, with β = 0.98 (95% confidence interval: 0.04, 1.92) beat per minute. This study suggests that moderate alcohol use in men is not beneficial for heart function via QT interval or heart rate but could be detrimental. Future studies using specific cardiovascular outcomes may elucidate how alcohol affects different aspects of the cardiovascular system and, hence, the overall effects of alcohol on CVD can be estimated., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status., Method: Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (≥50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003-2006), and whether these differed by health status., Results: The association of fruit consumption with the Framingham score varied by health status (P-value<0.001), but not vegetable consumption (P-value 0.51). Fruit consumption was associated with a lower Framingham score (-0.04 per portions/day, 95% confidence interval (CI) -0.08 to -0.004) among participants in poor health, adjusted for age, sex, recruitment phase, socio-economic position and lifestyle. However, similarly adjusted, fruit consumption was associated with a higher Framingham score (0.05, 95% CI 0.02 to 0.09) among participants in good health, perhaps due to a positive association of fruit consumption with fasting glucose. Similarly adjusted, vegetable consumption was associated with a higher Framingham score (0.03, 95% CI 0.01 to 0.05) among all participants, with no difference by health status., Conclusion: This large study from a non-western setting found that fruit and vegetable consumption was barely associated with the Framingham score, or major CVD risk factors.

Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3-7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.

Objectives: Observationally, testosterone is negatively associated with systemic inflammation, but this association is open to both residual confounding and reverse causality. Large-scale randomized controlled trials (RCTs), assessing exogenous effects, are presently unavailable. We examined the association of endogenous testosterone with well-established systemic inflammatory markers (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive protein (hsCRP)) using a separate-sample Mendelian randomization analysis to minimize reverse causality., Methods: A genetic prediction rule for serum testosterone was developed in 289 young Chinese men with mean age of 21.0, using selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031). Multivariable linear regression was used to examine the association of genetically predicted serum testosterone with inflammatory markers among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study., Results: Genetically predicted testosterone was unrelated to white blood cell count (-0.01 109/L per nmol/L testosterone, 95% confidence interval (CI) -0.05 to 0.04), granulocyte count (-0.02 109/L, 95% CI -0.06 to 0.02), lymphocyte count (0.005 109/L, 95% CI -0.01 to 0.02) and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06)., Conclusion: Our findings did not corroborate any anti-inflammatory effects of testosterone or corresponding potentially protective effects of testosterone on chronic diseases resulting from reduced low-grade systemic inflammation.

Background: QT interval prolongation, a predictor of cardiac arrhythmias, and elevated heart rate are associated with higher risk of cardiovascular mortality. Observationally testosterone is associated with shorter corrected QT interval and slower heart rate; however, the evidence is open to residual confounding and reverse causality. We examined the association of testosterone with electrocardiogram (ECG) parameters using a separate-sample instrumental variable (SSIV) estimator., Methods: To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on a parsimonious set of single nuclear polymorphisms (rs10046, rs1008805 and rs1256031). Linear regression was used to examine the association of genetically predicted testosterone with QT interval, corrected QT interval [using the Framingham formula (QTf) and Bazett formula (QTb)] and heart rate in 4212 older (50+ years) Chinese men from the Guangzhou Biobank Cohort Study., Results: Predicted testosterone was not associated with QT interval [-0.08 ms per nmol/l testosterone, 95% confidence interval (CI) -0.81 to 0.65], QTf interval (0.40 ms per nmol/l testosterone, 95% CI -0.12 to 0.93) or heart rate (0.26 beats per minute per nmol/l testosterone, 95% CI -0.04 to 0.56), but was associated with longer QTb interval (0.66 ms per nmol/l testosterone, 95% CI 0.02 to 1.31)., Conclusions: Our findings do not corroborate observed protective associations of testosterone with QT interval or heart rate among men, but potentially suggest effects in the other direction. Replication in a larger sample is required., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: In developed western populations, longer legs are a biomarker of better childhood conditions and negatively associated with cardiovascular disease risk factors. These associations are less obvious in non-western settings. However, early life is also a key immune system development phase., Aim: To examine the associations of height, leg length, sitting height and leg length/sitting height ratio with inflammatory markers (white blood, lymphocyte and granulocyte cell counts and C-reactive protein (CRP)) in a developing population of southern China., Subjects and Methods: This study used multivariable linear regression to examine the adjusted associations in 30,499 Chinese (50+ years)., Results: Height z-score was associated with lower white blood, lymphocyte and granulocyte cell counts. Leg length z-score was associated with lower white blood, lymphocyte and granulocyte cell counts and CRP. Sitting height z-score was associated with lower white blood and granulocyte cell counts, but not with lymphocyte cell count or CRP. Leg length/sitting height ratio z-score was associated with lower white blood, lymphocyte and granulocyte cell counts and CRP., Conclusion: Factors enabling more early growth may also lead to changes in immunity that are associated with reduced CVD risk.

Background: Projections of future trends in cancer incidence and mortality are important for public health planning., Methods: By using 1976-2010 data in Hong Kong, we fitted Poisson age-period-cohort models and made projections for future breast cancer incidence and mortality to 2025., Results: Age-standardised breast cancer incidence (/mortality) is projected to increase (/decline) from 56.7 (/9.3) in 2011-2015 to 62.5 (/8.6) per 100,000 women in 2021-2025., Conclusions: The incidence pattern may relate to Hong Kong's socio-economic developmental history, while falling mortality trends are, most likely, due to improvements in survival from treatment advancement and improved health service delivery.

Assessing the severity of emerging infections is challenging because of potential biases in case ascertainment. The first human case of infection with influenza A(H7N9) virus was identified in China in March 2013; since then, the virus has caused two epidemic waves in the country. There were 134 laboratory-confirmed cases detected in the first epidemic wave from January to September 2013. In the second epidemic wave of human infections with avian influenza A(H7N9) virus in China from October 2013 to October 2014, we estimated that the risk of death among hospitalised cases of infection with influenza A(H7N9) virus was 48% (95% credibility interval: 42-54%), slightly higher than the corresponding risk in the first wave. Age-specific risks of death among hospitalised cases were also significantly higher in the second wave. Using data on symptomatic cases identified through national sentinel influenza-like illness surveillance, we estimated that the risk of death among symptomatic cases of infection with influenza A(H7N9) virus was 0.10% (95% credibility interval: 0.029-3.6%), which was similar to previous estimates for the first epidemic wave of human infections with influenza A(H7N9) virus in 2013. An increase in the risk of death among hospitalised cases in the second wave could be real because of changes in the virus, because of seasonal changes in host susceptibility to severe infection, or because of variation in treatment practices between hospitals, while the increase could be artefactual because of changes in ascertainment of cases in different areas at different times.

Objective: To formulate a new birthweight reference for different gestational ages in Guangzhou, southern China, and compare it with the currently used reference in China and the global reference., Design and Setting: All singleton live births of more than 26 weeks' gestational age recorded in the Guangzhou Perinatal Health Care and Delivery Surveillance System for the years 2009, 2010 and 2011 (n=510 837) were retrospectively included in the study. In addition, the study sample was supplemented by all singleton live births (n=3538) at gestational ages 26-33 weeks from 2007 and 2008. We used Gaussian mixture models and robust regression to exclude outliers of birth weight and then applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to generate smoothed percentile curves separately for gender and parity., Results: Of infants defined as small for gestational age (SGA) in the new reference, 15.3-47.7% (depending on gestational age) were considered appropriate for gestational age (AGA) by the currently used reference of China. Of the infants defined as SGA by the new reference, 9.2% with gestational ages 34-36 weeks and 14.3% with 37-41 weeks were considered AGA by the global reference. At the 50th centile line, the new reference curve was similar to that of the global reference for gestational ages 26-33 weeks and above the global reference for 34-40 weeks., Conclusions: The new birthweight reference based on birthweight data for neonates in Guangzhou, China, differs from the reference currently used in China and the global reference, and appears to be more relevant to the local population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013-14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.

Objectives: The causal role of some cardiovascular risk factors, such as HDL cholesterol, has been increasingly challenged and attention is returning to all elements of Virchow's triad, i.e., hypercoagulability (including viscosity) as well as endothelial function and blood flow. We examined the life course origins of coagulability., Methods: We used multivariable linear regression to assess whether childhood influences, proxied by height and its components, were associated with hematocrit (Hct), hemoglobin (HGB), and other hematological parameters in 28,595 older Chinese adults (mean age = 61.8 years) from the Guangzhou Biobank Cohort Study., Results: Adjusted for age, sex, and recruitment phase, leg length was negatively associated with platelets (PLT) (-0.83 × 10(9) /l per centimeter (cm), 95% confidence interval (CI) -1.01 to -0.65). Sitting height and height were positively associated with Hct (0.05% per cm, 95% CI 0.04-0.07 for sitting height; 0.02% per cm, 95% CI 0.01-0.02 for height), HGB (0.21 g/l per cm, 95% CI 0.17-0.25; 0.07 g/l per cm, 95% CI 0.04-0.09) and negatively associated with PLT (-1.2 × 10(9) /l per cm, 95% CI -1.4 to -1.0; -0.83 × 10(9) /l per cm, 95% CI -0.95 to -0.70). Further adjustment for potential confounders did little to change the estimates., Conclusions: For the first time we provide anthropometric evidence for the different roles of prepubertal and pubertal influences in relation to Hct and HGB. Whether factors that promote leg growth but reduce growth of sitting height may help to prevent cardiovascular events, via effects on hypercoagulability or viscosity, overall or in specific subgroups, remains to be determined., (© 2014 Wiley Periodicals, Inc.)

Background: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance., Methods: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping., Results: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96., Conclusions: A simple decision rule based on data readily obtainable in the setting of patients' first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement.

Purpose: In Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function., Methods: We examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1 second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression., Results: ALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1 second -1.52%, 95% confidence interval [CI], -2.52% to -0.51% for one inactive allele and -2.05%, 95% CI, -3.85% to -0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity -1.25%, 95% CI -2.15% to -0.35% and -1.65%, 95% CI, -3.25% to -0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders., Conclusions: Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: With China's rapid economic growth in the past few decades, there is currently an emerging focus on happiness. Cross-cultural validity studies have indicated that the four-item Subjective Happiness Scale (SHS) has high internal consistency and stable reliability. However, the psychometric characteristics of the SHS in broader Chinese community samples are unknown., Purpose: We evaluated the factor structure and psychometric properties of the SHS in the Hong Kong general population., Methods: The Chinese SHS was derived using forward-backward translation. Of the Cantonese-speaking participants aged ≥15 years, 2,635 were randomly selected from the random sample component of the FAMILY Cohort, a territory-wide cohort study in Hong Kong. In addition to the SHS, a single-item overall happiness scale, the Patient Health Questionnaire-9 (PHQ-9), the Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) scale, and the Medical Outcomes Study 12-item short-form version 2 (SF-12) mental and physical health scales were administered., Results: Exploratory and confirmatory factor analyses supported a single factor with high loadings for the four SHS items. Multiple group analyses indicated factor invariance across sex and age groups. Cronbach's alpha was 0.82, and 2-week test-retest reliability (n = 191) was 0.70. The SHS correlated significantly with single-item overall happiness (Spearman's rho [ρ] = 0.57), Family APGAR (ρ = 0.26), PHQ-9 (ρ = -0.34), and mental health-related quality of life (ρ = 0.40) but showed a lower correlation with physical health (ρ = 0.15). A regression model that included the PHQ-9 and Family APGAR scores explained 37% of the variance in SF-12 mental health scores; adding the SHS raised the variance explained to 41 %., Conclusions: Our results support the reliability and validity of the SHS as a relevant component in the measurement battery for mental well-being in a Chinese general population.

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.

Background: Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance., Methods: We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype., Findings: The surveillance registry included 7,200,092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010-12), of which 267,942 (3·7%) were laboratory confirmed and 2457 (0·03%) were fatal. Incidence and mortality were highest in children aged 12-23 months (38·2 cases per 1000 person-years and 1·5 deaths per 100,000 person-years in 2012). Median duration from onset to diagnosis was 1·5 days (IQR 0·5-2·5) and median duration from onset to death was 3·5 days (2·5-4·5). The absolute number of patients with cardiopulmonary or neurological complications was 82,486 (case-severity rate 1·1%), and 2457 of 82486 patients with severe disease died (fatality rate 3·0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September-October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3-19%, respectively)., Interpretation: This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions., Funding: China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme and Wellcome Trust, Harvard Center for Communicable Disease Dynamics, and Health and Medical Research Fund, Government of Hong Kong Special Administrative Region., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections., Methods: We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population., Results: The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24-17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154)., Conclusions: The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.

Background: Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and Nanjing--where most human cases of infection have occurred--live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus., Methods: We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods., Findings: 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93-100%) in Shanghai, by 99% (92-100%) in Hangzhou, by 97% (68-100%) in Huzhou, and by 97% (81-100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4-5·7)., Interpretation: LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed., Funding: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)