Genetically predicted 17beta-estradiol, cognitive function and depressive symptoms in women: A Mendelian randomization in the Guangzhou Biobank Cohort Study

© 2016.Objective: The role of estrogen in cognitive function and depressive symptoms is controversial due to discrepancies between results from randomized controlled trials (RCT) and observational studies. Mendelian randomization analysis may provide further insights concerning the role of estrogen in these outcomes as it assesses the effect of lifelong endogenous exposure but is less vulnerable to confounding than observational studies. Method: We used separate sample instrumental variable analysis to estimate the association of log 17β estradiol with cognitive function (Delayed 10 word recall, and Mini Mental State Examination (MMSE)) and depressive symptoms (Geriatric Depression Scale (GDS)) in older Chinese women of the Guangzhou Biobank Cohort Study (GBCS, n = 3086). The estimate was derived based on the Wald estimator, the ratio of the association of genetic determinants (rs1008805 and rs2175898) of log 17β-estradiol with cognitive function and depressive symptoms in GBCS and the association of log 17β-estradiol with genetic determinants in the sample of young women in Hong Kong (n = 236). Results: Genetically predicted 17β-estradiol was not associated with delayed 10-word recall (0.42 words per log increase in 17β-estradiol (pmol/L), 95% confidence interval (CI) -. 0.49 to 1.34) MMSE (0.39 per log increase in 17β-estradiol (pmol/L), 95% CI -. 0.87 to 1.65) or GDS (0.24 per log increase in 17β-estradiol (pmol/L), 95% CI -. 0.57 to 1.05). Conclusion: These results were largely consistent with evidence from RCTs and did not show any beneficial effect of estrogen on cognitive function and depressive symptoms. However, larger Mendelian randomization analyses are needed to identify any minor effects.postprin

Age at menarche and cardiovascular risk factors using Mendelian randomization in the Guangzhou Biobank Cohort Study

Observational studies show earlier age at menarche associated with higher risk of cardiovascular disease although these studies could be confounded by childhood obesity or childhood socioeconomic position. We tested the hypothesis that earlier age at menarche is associated with poorer cardiovascular risk factors using a Mendelian randomization design. We conducted a Mendelian randomization study in a large Southern Chinese cohort, the Guangzhou Biobank Cohort Study (n = 12,279), to clarify the causal role of menarche in cardiovascular disease risk factors including blood pressure, lipids, fasting glucose, adiposity and type 2 diabetes. A genetic allele score was obtained from single nucleotide polymorphisms associated with age at menarche using stepwise regression and with cross validation. Estimates of the association of age at menarche with cardiovascular disease risk factors were obtained using two stage least squares regression. Height was included as a positive control outcome. The F-statistic for the allele score (rs17268785, rs1859345, rs2090409, rs4452860 and rs4946651) was 19.9. Older age at menarche was associated with lower glucose (− 0.39 mmol/L per year older menarche, 95% confidence interval (CI) − 0.78 to − 0.001) but not clearly with any other cardiovascular risk factors. Older age at menarche was also associated with taller height. Age at menarche did not appear to affect cardiovascular disease risk factors except for glucose in an inverse manner. However, these results need to be confirmed in larger Mendelian randomization studies

Area Median Income and Metropolitan Versus Nonmetropolitan Location of Care for Acute Coronary Syndromes: A Complex Interaction of Social Determinants

Background: Metropolitan versus nonmetropolitan status and area median income may independently affect care for and outcomes of acute coronary syndromes. We sought to determine whether location of care modifies the association among area income, receipt of cardiac catheterization, and mortality following an acute coronary syndrome in a universal health care system. Methods and Results: We studied a cohort of 14 012 acute coronary syndrome patients admitted to cardiology services between April 18, 2004, and December 31, 2011, in southern Alberta, Canada. We used multivariable logistic regression to determine the odds of cardiac catheterization within 1 day and 7 days of admission and the odds of 30‐day and 1‐year mortality according to area median household income quintile for patients presenting at metropolitan and nonmetropolitan hospitals. In models adjusting for area income, patients who presented at nonmetropolitan facilities had lower adjusted odds of receiving cardiac catheterization within 1 day of admission (odds ratio 0.22, 95% CI 0.11–0.46, P<0.001). Among nonmetropolitan patients, when examined by socioeconomic status, each incremental decrease in income quintile was associated with 10% lower adjusted odds of receiving cardiac catheterization within 7 days (P<0.001) and 24% higher adjusted odds of 30‐day mortality (P=0.008) but no significant difference for 1‐year mortality (P=0.12). There were no differences in adjusted mortality among metropolitan patients. Conclusion: Within a universal health care system, the association among area income and receipt of cardiac catheterization and 30‐day mortality differed depending on the location of initial medical care for acute coronary syndromes. Care protocols are required to improve access to care and outcomes in patients from low‐income nonmetropolitan communities

Time-Resolved Transposon Insertion Sequencing Reveals Genome-Wide Fitness Dynamics during Infection

ABSTRACT Transposon insertion sequencing (TIS) is a powerful high-throughput genetic technique that is transforming functional genomics in prokaryotes, because it enables genome-wide mapping of the determinants of fitness. However, current approaches for analyzing TIS data assume that selective pressures are constant over time and thus do not yield information regarding changes in the genetic requirements for growth in dynamic environments (e.g., during infection). Here, we describe structured analysis of TIS data collected as a time series, termed pattern analysis of conditional essentiality (PACE). From a temporal series of TIS data, PACE derives a quantitative assessment of each mutant’s fitness over the course of an experiment and identifies mutants with related fitness profiles. In so doing, PACE circumvents major limitations of existing methodologies, specifically the need for artificial effect size thresholds and enumeration of bacterial population expansion. We used PACE to analyze TIS samples of Edwardsiella piscicida (a fish pathogen) collected over a 2-week infection period from a natural host (the flatfish turbot). PACE uncovered more genes that affect E. piscicida’s fitness in vivo than were detected using a cutoff at a terminal sampling point, and it identified subpopulations of mutants with distinct fitness profiles, one of which informed the design of new live vaccine candidates. Overall, PACE enables efficient mining of time series TIS data and enhances the power and sensitivity of TIS-based analyses

Herpes zoster related hospitalization after inactivated (CoronaVac) and mRNA (BNT162b2) SARS-CoV-2 vaccination: A self-controlled case series and nested case-control study

BACKGROUND: Stimulation of immunity by vaccination may elicit adverse events. There is currently inconclusive evidence on the relationship between herpes zoster related hospitalization and COVID-19 vaccination. This study aimed to evaluate the effect of inactivated virus (CoronaVac, Sinovac) and mRNA (BNT162b2, BioNTech/Fosun Pharma) COVID-19 vaccine on the risk of herpes zoster related hospitalization. METHODS: Self-controlled case series (SCCS) analysis was conducted using the data from the electronic health records in Hospital Authority and COVID-19 vaccination records in the Department of Health in Hong Kong. We conducted the SCCS analysis including patients with a first primary diagnosis of herpes zoster in the hospital inpatient setting between February 23 and July 31, 2021. A confirmatory analysis by nested case-control method was also conducted. Each herpes zoster case was randomly matched with ten controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression and logistic regression models were used to assess the potential excess rates of herpes zoster after vaccination. FINDINGS: From February 23 to July 31, 2021, a total of 16 and 27 patients were identified with a first primary hospital diagnosis of herpes zoster within 28 days after CoronaVac and BNT162b2 vaccinations. The incidence of herpes zoster was 7.9 (95% Confidence interval [CI]: 5.2–11.5) for CoronaVac and 7.1 (95% CI: 4.1–11.5) for BNT162b2 per 1,000,000 doses administered. In SCCS analysis, CoronaVac vaccination was associated with significantly higher risk of herpes zoster within 14 days after first dose (adjusted incidence rate ratio [aIRR]=2.67, 95% CI: 1.08–6.59) but not in other periods afterwards compared to the baseline period. Regarding BNT162b2 vaccination, a significantly increased risk of herpes zoster was observed after first dose up to 14 days after second dose (0-13 days after first dose: aIRR=5.23, 95% CI: 1.61–17.03; 14–27 days after first dose: aIRR=5.82, 95% CI: 1.62–20.91; 0-13 days after second dose: aIRR=5.14, 95% CI: 1.29–20.47). Using these relative rates, we estimated that there has been an excess of approximately 5 and 7 cases of hospitalization as a result of herpes zoster after every 1,000,000 doses of CoronaVac and BNT162b2 vaccination, respectively. The findings in the nested case control analysis showed similar results. INTERPRETATION: We identified an increased risk of herpes zoster related hospitalization after CoronaVac and BNT162b2 vaccinations. However, the absolute risks of such adverse event after CoronaVac and BNT162b2 vaccinations were very low. In locations where COVID-19 is prevalent, the protective effects on COVID-19 from vaccinations will greatly outweigh the potential side effects of vaccination. FUNDING: The project was funded by Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No.COVID19F01). FTTL (Francisco Tsz Tsun Lai) and ICKW (Ian Chi Kei Wong)’s posts were partly funded by D(2)4H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission

Understanding longevity in Hong Kong: a comparative study with long-living, high-income countries

Background Since 2013, Hong Kong has sustained the world’s highest life expectancy at birth—a key indicator of population health. The reasons behind this achievement remain poorly understood but are of great relevance to both rapidly developing and high-income regions. Here, we aim to compare factors behind Hong Kong’s survival advantage over long-living, high-income countries. Methods Life expectancy data from 1960–2020 were obtained for 18 high-income countries in the Organisation for Economic Co-operation and Development from the Human Mortality Database and for Hong Kong from Hong Kong’s Census and Statistics Department. Causes of death data from 1950–2016 were obtained from WHO’s Mortality Database. We used truncated cross-sectional average length of life (TCAL) to identify the contributions to survival differences based on 263 million deaths overall. As smoking is the leading cause of premature death, we also compared smoking-attributable mortality between Hong Kong and the high-income countries. Findings From 1979–2016, Hong Kong accumulated a substantial survival advantage over high-income countries, with a difference of 1·86 years (95% CI 1·83–1·89) for males and 2·50 years (2·47–2·53) for females. As mortality from infectious diseases declined, the main contributors to Hong Kong’s survival advantage were lower mortality from cardiovascular diseases for both males (TCAL difference 1·22 years, 95% CI 1·21–1·23) and females (1·19 years, 1·18–1·21), cancer for females (0·47 years, 0·45–0·48), and transport accidents for males (0·27 years, 0·27–0·28). Among high-income populations, Hong Kong recorded the lowest cardiovascular mortality and one of the lowest cancer mortalities in women. These findings were underpinned by the lowest absolute smoking-attributable mortality in high-income regions (39·7 per 100 000 in 2016, 95% CI 34·4–45·0). Reduced smoking-attributable mortality contributed to 50·5% (0·94 years, 0·93–0·95) of Hong Kong’s survival advantage over males in high-income countries and 34·8% (0·87 years, 0·87–0·88) of it in females. Interpretation Hong Kong’s leading longevity is the result of fewer diseases of poverty while suppressing the diseases of affluence. A unique combination of economic prosperity and low levels of smoking with development contributed to this achievement. As such, it offers a framework that could be replicated through deliberate policies in developing and developed populations globally.VC-R acknowledges support from the ARC (ARC DP210100401)

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case–control study

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose

Improving Decision-Making for Population Health in Nonhealth Sectors in Urban Environments: the Example of the Transportation Sector in Three Megacities—the 3-D Commission.

Noncommunicable diseases (NCDs) represent a significant global public health burden. As more countries experience both epidemiologic transition and increasing urbanization, it is clear that we need approaches to mitigate the growing burden of NCDs. Large and growing urban environments play an important role in shaping risk factors that influence NCDs, pointing to the ineluctable need to engage sectors beyond the health sector in these settings if we are to improve health. By way of one example, the transportation sector plays a critical role in building and sustaining health outcomes in urban environments in general and in megacities in particular. We conducted a qualitative comparative case study design. We compared Bus Rapid Transit (BRT) policies in 3 megacities-Lagos (Africa), Bogotá (South America), and Beijing (Asia). We examined the extent to which data on the social determinants of health, equity considerations, and multisectoral approaches were incorporated into local politics and the decision-making processes surrounding BRT. We found that all three megacities paid inadequate attention to health in their agenda-setting, despite having considerable healthy transportation policies in principle. BRT system policies have the opportunity to improve lifestyle choices for NCDs through a focus on safe, affordable, and effective forms of transportation. There are opportunities to improve decision-making for health by involving more available data for health, building on existing infrastructures, building stronger political leadership and commitments, and establishing formal frameworks to improve multisectoral collaborations within megacities. Future research will benefit from addressing the political and bureaucratic processes of using health data when designing public transportation services, the political and social obstacles involved, and the cross-national lessons that can be learned from other megacities