Mendelian randomization: causal inference leveraging genetic data.

Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for the presence of unmeasured confounders. MR has been widely applied to unresolved questions in epidemiology, making use of summary statistics from genome-wide association studies on an increasing number of human traits. However, an understanding of essential concepts is necessary for the appropriate application and interpretation of MR. This review aims to provide a non-technical overview of MR and demonstrate its relevance to psychiatric research. We begin with the origins of MR and the reasons for its recent expansion, followed by an overview of its statistical methodology. We then describe the limitations of MR, and how these are being addressed by recent methodological advances. We showcase the practical use of MR in psychiatry through three illustrative examples - the connection between cannabis use and psychosis, the link between intelligence and schizophrenia, and the search for modifiable risk factors for depression. The review concludes with a discussion of the prospects of MR, focusing on the integration of multi-omics data and its extension to delineating complex causal networks.

Improved nonparametric penalized maximum likelihood estimation for arbitrarily censored survival data.

Nonparametric maximum likelihood estimation encompasses a group of classic methods to estimate distribution-associated functions from potentially censored and truncated data, with extensive applications in survival analysis. These methods, including the Kaplan-Meier estimator and Turnbull's method, often result in overfitting, especially when the sample size is small. We propose an improvement to these methods by applying kernel smoothing to their raw estimates, based on a BIC-type loss function that balances the trade-off between optimizing model fit and controlling model complexity. In the context of a longitudinal study with repeated observations, we detail our proposed smoothing procedure and optimization algorithm. With extensive simulation studies over multiple realistic scenarios, we demonstrate that our smoothing-based procedure provides better overall accuracy in both survival function estimation and individual-level time-to-event prediction (imputation) by reducing overfitting. Our smoothing procedure decreases the bias (discrepancy between the estimated and true simulated survival function) using interval-censored data by up to 48% compared to the raw un-smoothed estimate, with similar improvements of up to 34% and 23% in within-sample and out-of-sample prediction, respectively. Our smoothing algorithm also demonstrates significant overall improvement across all three metrics when compared to a popular semiparametric B-splines estimation method. Finally, we apply our method to real data on censored breast cancer diagnosis, which similarly shows improvement when compared to empirical survival estimates from uncensored data. We provide an R package, SISE, for implementing our penalized likelihood method.

The importance of air quality for underground spaces: An international survey of public attitudes.

Space is a resource that is constantly being depleted, especially in mega-cities. Underground workspaces (UGS) are increasingly being included in urban plans and have emerged as an essential component of vertical cities. While progress had been made on the engineering aspects associated with the development of high-quality UGS, public attitudes toward UGS as work environments (ie, the public's design concerns with UGS) are relatively unknown. Here, we present the first large-scale study examining preferences and attitudes toward UGS, surveying close to 2000 participants from four cities in three continents (Singapore, Shanghai, London, and Montreal). Contrary to previous beliefs, air quality (and not lack of windows) is the major concern of prospective occupants. Windows, temperature, and lighting emerged as additional important building performance aspects for UGS. Early adopters (ie, individuals more willing to accept UGS and thus more likely to be the first occupants) across all cities prioritized air quality. Present results suggest that (perceived) air quality is a key building performance aspect for UGS that needs to be communicated to prospective occupants as this will improve their attitudes and views toward UGS. This study highlights the importance of indoor air quality for the public.

Associations of perceived indoor environmental quality with stress in the workplace.

Indoor environmental quality (IEQ) is a general indicator of the quality of conditions inside a building. We investigated associations of perceived IEQ including air quality, thermal comfort, noise, and light quality with stress at work and the extent to which workplace location modifies these associations. We recruited 464 full-time workers from four companies in Singapore. Data on socio-demographic characteristics, lifestyle/health-related factors, and workplace factors were collected through self-administered questionnaires. Perceived IEQ satisfaction scores of all four factors were collected using the validated OFFICAIR questionnaire. We fitted a logistic regression model to assess associations between each perceived IEQ score and stress at work, adjusting for potential confounders. The odds ratio for stress at work associated with a 1-unit increase in perceived air quality score was 0.88 (0.82-0.94), 0.89 (0.82-0.97) for thermal comfort, 0.93 (0.87-0.98) for noise, and 0.88 (0.82-0.94) for light quality. Significant associations were found in office and control rooms for all four perceived IEQ, except for thermal comfort in office rooms. Higher satisfaction levels of perceived air quality, thermal comfort, noise, and lighting, were significantly associated with a reduction in stress at work. Our findings could potentially provide a useful tool for environmental health impact assessment for buildings.

Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination.

BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level.

The influence of pre-existing health conditions on short-term mortality risks of temperature: Evidence from a prospective Chinese elderly cohort in Hong Kong.

BACKGROUND: Both cold and hot temperatures are associated with adverse health outcomes. Less is known about the role of pre-existing medical conditions to confer individual's susceptibility to temperature extremes. METHODS: We studied 66,820 subjects aged ≥65 who were enrolled and interviewed in all the 18 Elderly Health Centers of Department of Health, Hong Kong from 1998 to 2001, and followed up for 10-13 years. The distributed lag nonlinear model (DLNM) combined with a nested case-control study design was applied to estimate the nonlinear and delayed effects of cold or hot temperature on all natural mortality among subjects with different pre-existing diseases. RESULTS: The relative risk of all natural mortality associated with a decrease of temperature from 25th percentile (19.5°C) to 1st percentile (11.3°C) over 0-21 lag days for participants who reported to have an active disease at the baseline was 2.21 (95% confidence interval (CI): 1.19, 4.10) for diabetes mellitus (DM), 1.59 (1.12, 2.26) for circulatory system diseases (CSD), and 1.23 (0.53, 2.84) for chronic obstructive pulmonary disease (COPD), whereas 1.04 (0.59, 1.85) for non-disease group (NDG). Compared with NDG, elders with COPD had excess risk of mortality associated with thermal stress attributable to hot temperature, while elders with DM and CSD were vulnerable to both hot and cold temperatures. CONCLUSIONS: Elders with pre-existing health conditions were more vulnerable to excess mortality risk to hot and/or cold temperature. Preventative measures should target on elders with chronic health problems.

The smoke-free legislation in Hong Kong: its impact on mortality.

OBJECTIVES: To examine trends in deaths for conditions associated with secondhand smoke exposure over the years prior to and following the implementation of a smoke-free policy in Hong Kong. DESIGN: Time-series study. SETTING: Death registration data from Hong Kong Special Administrative Region (SAR) Government Census and Statistics Department. PARTICIPANTS: All deaths registered from 1 January 2001 to 31 December 2011. MAIN OUTCOME MEASURES: Deaths for conditions associated with passive smoking include cardiovascular disease (CVD), respiratory disease and other causes. RESULTS: There was a decline in the annual proportional change for ischaemic heart disease (IHD), acute myocardial infarction (AMI) and CVD mortality in the year after the intervention for all ages and those aged 65 years or older. There were also clear declines in the cool season peaks for these three conditions in the first postintervention year. There was a further drop in the cool season peak for AMI among all ages in the year after the exemptions ceased. No declines in annual proportional change or changes in seasonal peaks of mortality were found for any of the control conditions. CONCLUSIONS: The findings in this study add to the evidence base, as summarised in the Surgeon General's report, extending the impact of effective smoke-free legislation to those aged 65 years or older and to cerebrovascular events in younger age groups. They also reinforced the need for comprehensive, enforced and effective smoke-free laws if the full extent of the health gains are to be achieved.

Who is more vulnerable to death from extremely cold temperatures? A case-only approach in Hong Kong with a temperate climate.

The short-term effects of ambient cold temperature on mortality have been well documented in the literature worldwide. However, less is known about which subpopulations are more vulnerable to death related to extreme cold. We aimed to examine the personal characteristics and underlying causes of death that modified the association between extreme cold and mortality in a case-only approach. Individual information of 197,680 deaths of natural causes, daily temperature, and air pollution concentrations in cool season (November-April) during 2002-2011 in Hong Kong were collected. Extreme cold was defined as those days with preceding week with a daily maximum temperature at or less than the 1st percentile of its distribution. Logistic regression models were used to estimate the effects of modification, further controlling for age, seasonal pattern, and air pollution. Sensitivity analyses were conducted by using the 5th percentile as cutoff point to define the extreme cold. Subjects with age of 85 and older were more vulnerable to extreme cold, with an odds ratio (OR) of 1.33 (95 % confidence interval (CI), 1.22-1.45). The greater risk of extreme cold-related mortality was observed for total cardiorespiratory diseases and several specific causes including hypertensive diseases, stroke, congestive heart failure, chronic obstructive pulmonary disease (COPD), and pneumonia. Hypertensive diseases exhibited the greatest vulnerability to extreme cold exposure, with an OR of 1.37 (95 % CI, 1.13-1.65). Sensitivity analyses showed the robustness of these effect modifications. This evidence on which subpopulations are vulnerable to the adverse effects of extreme cold is important to inform public health measures to minimize those effects.

Improved estimation of functional enrichment in SNP heritability using feasible generalized least squares.

Functional enrichment results typically implicate tissue or cell-type-specific biological pathways in disease pathogenesis and as therapeutic targets. We propose generalized linkage disequilibrium score regression (g-LDSC) that requires only genome-wide association studies (GWASs) summary-level data to estimate functional enrichment. The method adopts the same assumptions and regression model formulation as stratified linkage disequilibrium score regression (s-LDSC). Although s-LDSC only partially uses LD information, our method uses the whole LD matrix, which accounts for possible correlated error structure via a feasible generalized least-squares estimation. We demonstrate through simulation studies under various scenarios that g-LDSC provides more precise estimates of functional enrichment than s-LDSC, regardless of model misspecification. In an application to GWAS summary statistics of 15 traits from the UK Biobank, estimates of functional enrichment using g-LDSC were lower and more realistic than those obtained from s-LDSC. In addition, g-LDSC detected more significantly enriched functional annotations among 24 functional annotations for the 15 traits than s-LDSC (118 vs. 51).

Modulating Consciousness through Awareness Training Program and Its Impacts on Psychological Stress and Age-Related Gamma Waves.

Aging often leads to awareness decline and psychological stress. Meditation, a method of modulating consciousness, may help individuals improve overall awareness and increase emotional resilience toward stress. This study explored the potential influence of the Awareness Training Program (ATP), a form of consciousness modulation, on age-related brain wave changes and psychological stress in middle-aged adults. Eighty-five participants with mild stress were recruited and randomly assigned to ATP (45.00 ± 8.00 yr) or control (46.67 ± 7.80 yr) groups, matched by age and gender. Ten-minute resting-state EEG data, obtained while the participants' eyes were closed, were collected using a 128-channel EEG system (EGI). A strong positive Pearson correlation was found between fast-wave (beta wave, 12-25 Hz; gamma wave, 25-40 Hz) EEG and age. However, after the 7-week ATP intervention, this correlation became insignificant in the ATP group. Furthermore, there was a significant reduction in stress levels, as measured by the Chinese version of the 10 item Perceived Stress Scale (PSS-10), in the ATP group. These results suggest that ATP may help modulate age-related effects on fast brain waves, as evidenced by the reduced correlation magnitude between age and gamma waves, and lower psychological stress. This suggests that ATP, as a form of consciousness modulation, may improve stress resilience and modulate age-related gamma wave changes.

Obesity and influenza associated mortality: evidence from an elderly cohort in Hong Kong.

OBJECTIVE: Obesity was not identified as a risk factor for influenza until the recent 2009 H1N1 pandemic. Based on a cohort of 66,820 subjects aged 65 years and over with the follow-up period from July 1998 to December 2010 in Hong Kong, we assessed the modifying effect of obesity on mortality risks specifically attributable to influenza infections (termed as "influenza associated mortality risks"). METHODS: A Cox proportional model with time dependent covariates was adopted to assess the hazard ratio of mortality in each obesity group when influenza activity increased 10% in the community. RESULTS: Hazard ratio of influenza-associated all-cause mortality was 1.081 (95% confidence interval 1.013, 1.154), 1.047 (1.012, 1.084), 0.981 (0.936, 1.028), 1.018 (0.980, 1.058) and 1.062 (0.972, 1.162) in the underweight, normal, overweight, moderate obesity and severe obesity groups, respectively. A similar U shape pattern across the obesity groups was also observed in influenza associated mortality risks of respiratory diseases, pneumonia and influenza. This pattern was more evident among ever smokers, although the influenza effect estimates in each obesity group had overlapping confidence intervals. CONCLUSION: There is some but limited evidence to suggest that underweight and obesity were associated with higher mortality risks of influenza in old population.

Quantifying the burden of disease due to premature mortality in Hong Kong using standard expected years of life lost.

BACKGROUND: To complement available information on mortality in a population Standard Expected Years of Life Lost (SEYLL), an indicator of premature mortality, is increasingly used to calculate the mortality-associated disease burden. SEYLL consider the age at death and therefore allow a more accurate view on mortality patterns as compared to routinely used measures (e.g. death counts). This study provides a comprehensive assessment of disease and injury SEYLL for Hong Kong in 2010. METHODS: To estimate the SEYLL, life-expectancy at birth was set according to the 2004 Global Burden of Disease study at 82.5 and 80 years for females and males, respectively. Cause of death data for 2010 were corrected for misclassification of cardiovascular and cancer causes. In addition to the baseline estimates, scenario analyses were performed using alternative assumptions on life-expectancy (Hong Kong standard life-expectancy), time-discounting and age-weighting. To estimate a trend of premature mortality a time-series analysis from 2001 to 2010 was conducted. RESULTS: In 2010 524,706.5 years were lost due to premature death in Hong Kong with 58.3% of the SEYLL attributable to male deaths. The three overall leading single causes of SEYLL were "trachea, bronchus and lung cancers", "ischaemic heart disease" and "lower respiratory infections" together accounting for about 29% of the overall SEYLL. Further, self-inflicted injuries (5.6%; ranked 5) and liver cancer (4.9%; ranked 7) were identified as important causes not adequately captured by classical mortality measures. Scenario analyses highlighted that by using a 3% time-discount rate and non-uniform age-weights the SEYLL dropped by 51.6%. Using Hong Kong's standard life-expectancy values resulted in an overall increase of SEYLL by 10.8% as compared to the baseline SEYLL. Time-series analysis indicates an overall increase of SEYLL by 6.4%. In particular, group I (communicable, maternal, perinatal and nutritional) conditions showed highest increases with SEYLL-rates per 100,000 in 2010 being 1.4 times higher than 2001. CONCLUSIONS: The study stresses the mortality impact of diseases and injuries that occur in earlier stages of life and thus presents the SEYLL measure as a more sensitive indicator compared to classical mortality indicators. SEYLL provide useful additional information and supplement available death statistics.

Inhibitory dysfunction may cause prospective memory impairment in temporal lobe epilepsy (TLE) patients: an event-related potential study.

Introduction: Prospective memory (PM) is the ability to remember future intentions, and PM function is closely related to independence in daily life, particularly in patients with temporal lobe epilepsy (TLE). As PM involves various cognitive components of attention, working memory, inhibition and other executive functions, this study investigated how TLE may affect PM components and the underlying neural mechanisms. Methods: Sixty-four subjects were recruited, including 20 refractory TLE patients, 18 well-controlled TLE patients and 26 age-matched healthy controls. A set of neuropsychological tests was administered to assess specific brain functions. An event-related potential (ERP) task was used to further explore how PM and its components would be differentially affected in the two TLE types. Results: Our findings revealed that: (1) refractory TLE patients scored lower than the healthy controls in the digit span, Verbal Fluency Test and Symbol Digit Modalities Test; (2) refractory TLE patients exhibited impaired PM performance and reduced prospective positivity amplitudes over the frontal, central and parietal regions in ERP experiments when compared to the healthy controls; and (3) decreased P3 amplitudes in the nogo trials were observed over the frontal-central sites in refractory but not in well-controlled TLE patients. Discussion: To our knowledge, this is the first ERP study on PM that has specifically identified PM impairment in refractory but not in well-controlled TLE patients. Our finding of double dissociation in PM components suggests that inhibition dysfunction may be the main reason for PM deficit in refractory TLE patients. The present results have clinical implications for neuropsychological rehabilitation in TLE patients.

Assessing the impact of the 2018 tetanus guidelines on knowledge and practices of emergency physicians in trauma patients: a national survey study.

Background: Tetanus remains a significant public health issue in China, with the approach of anti-tetanus prophylaxis in the emergency department resulting in both overuse, particularly of human tetanus immune globulin (TIG), and underuse with the tetanus vaccine. This is largely due to the absence of updated guidelines on tetanus prophylaxis before 2018. Our study aimed to evaluate the effects of the 2018 Chinese tetanus guidelines on the knowledge and practices of emergency physicians about tetanus prevention in trauma patients. Methods: From November 2019 to April 2020, we conducted a web-based survey involving 499 emergency physicians. The survey included a questionnaire covering knowledge, attitudes, and practices related to tetanus. We assessed the influence of the 2018 tetanus guidelines on the knowledge and practices of emergency physicians related to tetanus prevention for patients with trauma using multiple regression analysis. Results: The survey results showed that only 45.3% of the participants had received formal training on tetanus immunization, despite 53.3% reporting the availability of tetanus vaccines at their institutions. Physicians typically prescribed tetanus antitoxin or human TIG instead of tetanus toxoid (TT) to treat injuries, regardless of the patient's TT vaccination history. Among the respondents, those who were aware of the 2018 tetanus guidelines had higher mean scores on the general knowledge, risk knowledge, and treatment knowledge scales, with increases of 6%, 13%, and 9%, respectively, compared to those who were unaware of the guidelines. Awareness of the 2018 tetanus guidelines was associated with a high level of knowledge, as indicated by the general knowledge score, recommendation knowledge score, and total knowledge score, after adjusting for the effects of all variables on the knowledge, attitudes, and practices of the participants. A high level of education was also associated with a high level of knowledge indicated by the recommendation knowledge score and total knowledge score. Conclusions: Our study highlights a substantial gap in the attitudes, knowledge, and practices of emergency physicians in China regarding tetanus immunization. The results suggest an urgent need to promote the Chinese Expert Consensus Guidelines on tetanus to improve emergency physicians' knowledge and competence in tetanus prophylaxis. The findings underscore the importance of enhancing physicians' awareness of the latest guidelines to ensure appropriate and effective treatment for patients with tetanus-prone injuries.

Short-term exposure to sulfur dioxide and daily mortality in 17 Chinese cities: the China air pollution and health effects study (CAPES).

Sulfur dioxide (SO(2)) is a major air pollutant and has significant impacts upon human health. Few multi-city studies in Asia have examined the acute health effects of SO(2). As part of the China Air Pollution and Health Effects Study (CAPES), this study aimed at investigating the short-term association between SO(2) and daily mortality in 17 Chinese cities. We applied two-stage Bayesian hierarchical models to obtain city-specific and national average estimates for SO(2). In each city, we used Poisson regression models incorporating natural spline smoothing functions to adjust for long-term and seasonal trend of mortality, as well as other time-varying covariates. We examined the associations by age, gender and education status. As a result, the combined analysis showed that an increase of 10 µg/m(3) of two-day moving averaged SO(2) was associated with 0.75% [95% posterior interval (PI), 0.47 to 1.02], 0.83% (0.95% PI, 0.47 to 1.19) and 1.25% (95% PI, 0.78 to 1.73) increase of total, cardiovascular and respiratory mortality, respectively. The effects of SO(2) appeared more evident among the elderly. These associations were generally independent of particles with aerodynamic diameter <10 µm (PM(10)) but did not persist after adjustment for nitrogen dioxide (NO(2)). In conclusions, this largest epidemiologic study of air pollution in China to date suggests that short-term exposure to SO(2) is associated with increased mortality risk; however, these associations may be attributable to SO(2) serving as a surrogate of other substances. Further studies are needed to tackle the independent health effect of SO(2).

Digital Biomarkers for Depression Screening With Wearable Devices: Cross-sectional Study With Machine Learning Modeling.

BACKGROUND: Depression is a prevalent mental disorder that is undiagnosed and untreated in half of all cases. Wearable activity trackers collect fine-grained sensor data characterizing the behavior and physiology of users (ie, digital biomarkers), which could be used for timely, unobtrusive, and scalable depression screening. OBJECTIVE: The aim of this study was to examine the predictive ability of digital biomarkers, based on sensor data from consumer-grade wearables, to detect risk of depression in a working population. METHODS: This was a cross-sectional study of 290 healthy working adults. Participants wore Fitbit Charge 2 devices for 14 consecutive days and completed a health survey, including screening for depressive symptoms using the 9-item Patient Health Questionnaire (PHQ-9), at baseline and 2 weeks later. We extracted a range of known and novel digital biomarkers characterizing physical activity, sleep patterns, and circadian rhythms from wearables using steps, heart rate, energy expenditure, and sleep data. Associations between severity of depressive symptoms and digital biomarkers were examined with Spearman correlation and multiple regression analyses adjusted for potential confounders, including sociodemographic characteristics, alcohol consumption, smoking, self-rated health, subjective sleep characteristics, and loneliness. Supervised machine learning with statistically selected digital biomarkers was used to predict risk of depression (ie, symptom severity and screening status). We used varying cutoff scores from an acceptable PHQ-9 score range to define the depression group and different subsamples for classification, while the set of statistically selected digital biomarkers remained the same. For the performance evaluation, we used k-fold cross-validation and obtained accuracy measures from the holdout folds. RESULTS: A total of 267 participants were included in the analysis. The mean age of the participants was 33 (SD 8.6, range 21-64) years. Out of 267 participants, there was a mild female bias displayed (n=170, 63.7%). The majority of the participants were Chinese (n=211, 79.0%), single (n=163, 61.0%), and had a university degree (n=238, 89.1%). We found that a greater severity of depressive symptoms was robustly associated with greater variation of nighttime heart rate between 2 AM and 4 AM and between 4 AM and 6 AM; it was also associated with lower regularity of weekday circadian rhythms based on steps and estimated with nonparametric measures of interdaily stability and autocorrelation as well as fewer steps-based daily peaks. Despite several reliable associations, our evidence showed limited ability of digital biomarkers to detect depression in the whole sample of working adults. However, in balanced and contrasted subsamples comprised of depressed and healthy participants with no risk of depression (ie, no or minimal depressive symptoms), the model achieved an accuracy of 80%, a sensitivity of 82%, and a specificity of 78% in detecting subjects at high risk of depression. CONCLUSIONS: Digital biomarkers that have been discovered and are based on behavioral and physiological data from consumer wearables could detect increased risk of depression and have the potential to assist in depression screening, yet current evidence shows limited predictive ability. Machine learning models combining these digital biomarkers could discriminate between individuals with a high risk of depression and individuals with no risk.

Effectiveness of a brief positive skills intervention to improve psychological adjustment in patients with end-stage kidney disease newly initiated on haemodialysis: protocol for a randomised controlled trial (HED-Start).

INTRODUCTION: Initiation onto haemodialysis is a critical transition that entails multiple psychosocial and behavioural demands that can compound mental health burden. Interventions guided by self-management and cognitive-behavioural therapy to improve distress have been variably effective yet are resource-intensive or delivered reactively. Interventions with a focus on positive affect for patients with end-stage kidney disease are lacking. This study will seek (1) to develop a positive life skills intervention (HED-Start) combining evidence and stakeholder/user involvement and (2) evaluate the effectiveness of HED-Start to facilitate positive life skills acquisition and improve symptoms of distress and adjustment in incident haemodialysis patients. METHODS AND ANALYSIS: This is a single/assessor-blinded randomised controlled trial (RCT) to compare HED-Start to usual care. In designing HED-Start, semistructured interviews, a codesign workshop and an internal pilot will be undertaken, followed by a two-arm parallel RCT to evaluate the effectiveness of HED-Start. A total of 148 incident HD patients will be randomised using a 1:2 ratio into usual care versus HED-Start to be delivered in groups by trained facilitators between January 2021 and September 2022. Anxiety and depression will be the primary outcomes; secondary outcomes will be positive and negative affect, quality of life, illness perceptions, self-efficacy, self-management skills, benefit finding and resilience. Assessments will be taken at 2 weeks prerandomisation (baseline) and 3 months postrandomisation (2 weeks post-HED-Start completion). Primary analyses will use an intention-to-treat approach and compare changes in outcomes from baseline to follow-up relative to the control group using mixed-effect models. ETHICS AND DISSEMINATION: Ethics approval was obtained from Nanyang Technological University Institutional Review Board (IRB-2019-01-010). Written informed consent will be obtained before any research activities. Trial results will be disseminated via publications in peer-reviewed journals and conference presentations and will inform revision(s) in renal health services to support the transition of new patients to haemodialysis. TRIAL REGISTRATION NUMBER: NCT04774770.

Daily visibility and mortality: assessment of health benefits from improved visibility in Hong Kong.

Visibility in Hong Kong has deteriorated significantly over 40 years with visibility below 8km in the absence of fog, mist, or precipitation, increasing from 6.6 days in 1968 to 54.1 days in 2007. We assessed the short-term mortality effects of daily loss of visibility. During 1996-2006, we obtained mortality data for non-accidental and cardiorespiratory causes, visibility recorded as visual range in kilometers, temperature, and relative humidity from an urban observatory, and concentrations of four criteria pollutants. A generalized additive Poisson regression model with penalized cubic regression splines was fitted to control for time variant covariates. For non-accidental mortality, an interquartile range (IQR) of 6.5km decrease in visibility at lag0-1 days was associated with an excess risk (ER%) [95% CI] of 1.13 [0.49, 1.76] for all ages and 1.37 [0.65, 2.09] for ages 65 years and over; for cardiovascular mortality of 1.31 [0.13, 2.49] for all ages, and 1.72 [0.44, 3.00] for ages 65 years and over; and for respiratory mortality of 1.92 [0.49, 3.35] for all ages and 1.76 [0.28, 3.25] for ages 65 years and over. The estimated ER% for daily mortality derived from both visibility and air pollutant data were comparable in terms of magnitude, lag pattern, and exposure-response relationships especially when using particulate matter with aerodynamic diameter < or = 10 microm to predict the mortality associated with visibility. Visibility provides a useful proxy for the assessment of environmental health risks from ambient air pollutants and a valid approach for the assessment of the public health impacts of air pollution and the benefits of air quality improvement measures in developing countries where pollutant monitoring data are scarce.

Part 4. Interaction between air pollution and respiratory viruses: time-series study of daily mortality and hospital admissions in Hong Kong.

BACKGROUND: Populations in Asia are not only at risk of harm to their health through environmental degradation as a result of worsening pollution problems but also constantly threatened by recurring and emerging influenza epidemics and. pandemics. Situated in the area with the world's fastest growing economy and close to hypothetical epicenters of influenza transmission, Hong Kong offers a special opportunity for testing environmental management and public health surveillance in the region. In the Public Health and Air Pollution in Asia (PAPA*) project, the Hong Kong research team assessed the health effects of air pollution and influenza as well as the interaction between them. The team also assessed disparities in the health effects of air pollution between relatively deprived and more affluent areas in Hong Kong. The aim was to provide answers to outstanding research questions relating to the short-term effects of air pollution on mortality and hospital admissions; the health effects of influenza with a view to validating different measures of influenza activity according to virologic data; the confounding effects of influenza on estimates of the health effects of air pollution; the modifying effects of influenza on the health effects of air pollution; and the modifying effects of neighborhood social deprivation on the health effects of air pollution. DATA: Data on mortality and hospital admissions for all natural causes, as well as the subcategories of cardiovascular diseases (CVD) and respiratory diseases (RD), were derived from the Hong Kong Census and Statistics Department and the Hospital Authority. Daily concentrations of nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter with an aerodynamic diameter < or = 10 pm (PM10); and ozone (O3) were derived from eight monitoring stations with hourly data that were at least 75% complete during the study period. Three measures of influenza and respiratory syncytial virus (RSV) activity were derived from positive isolates of specimens in the virology laboratory of Queen Mary Hospital (QMH), the main clinical teaching center at The University of Hong Kong and part of the Hong Kong Hospital Authority network of teaching hospitals: influenza intensity (defined as the weekly proportion of positive isolates of influenza in the total number of specimens received for diagnostic tests); the presence of influenza epidemic (defined as a period when the weekly frequency of these positive isolates is > or = 4% of the annual total number of positive isolates [i.e., twice the expected mean value] in two or more consecutive weeks); and influenza predominance (defined as a period of influenza epidemic when the weekly frequency of RSV was less than 2% for two or more consecutive weeks). The weekly proportion of positive isolates of RSV in total specimens was determined in the same way as for influenza intensity. A social deprivation index (SDI) was defined by taking the average of the proportions of households or persons with the following six characteristics in each geographic area using the census statistics: unemployment; household income < U.S. $250 per month; no schooling at all; never-married status; one-person household; and subtenancy. A Poisson regression with quasi-likelihood to account for overdispersion was used to develop core models for daily health outcomes, with a natural spline smoothing function to filter out seasonal patterns and long-term trends in this time-series study of daily mortality and hospital admissions, and with adjustment for days of the week, temperature, and relative humidity (RH). Air pollutant concentration values were entered into the core model to assess the health effects of specific pollutants. The possible confounding effects of influenza were assessed by observing changes in magnitude of the effect estimate when each influenza measurement was entered into the model; and interactions between air pollution and influenza were assessed by entering the terms for the product of the air pollutant concentration and a measurement of influenza activity into the model. A Poisson regression analysis was performed to assess the effects of air pollution in each area belonging to low, middle, or high social deprivation strata according to the tertiles of the SDI. The differences in air pollution effects were tested by a case-only approach. RESULTS The excess risk (ER) estimates for the short-term effects of air pollution on mortality and hospitalization for broad categories of disease were greater in those 65 years and older than in the all-ages group and were consistent with other studies. The biggest health impacts were seen at the extremes of the age range. The three measures employed for influenza activity based on virologic data-one based on a proportion and the other two using frequencies of positive influenza isolates-were found to produce consistent health impact estimates, in terms of statistical significance. In general, we found that adjustment for influenza activity in air pollution health effect estimations took account of relatively small confounding effects. However, we conclude that it is worthwhile to make the adjustment in a sensitivity analysis and to obtain the best possible range of effect estimates from the data, especially for respiratory hospitalization. Interestingly, interaction effects were found between influenza activity and air pollution in the estimated risks for hospitalization for RD, particularly for 03. These results could be explained in terms of the detrimental effects of both influenza viruses and air pollutants, which may be synergistic or competing with each other, though the mechanism is still unknown. The results deserve further study and the attention of both public health policy makers and virologists in considering prevention strategies. IMPLICATIONS In Hong Kong, where air pollution may pose more of a health threat than in North American and Western European cities, the effects of air pollution also interact with influenza and with residence in socially deprived areas, potentially leading to additional harm. Asian governments should be aware of the combined risks to the health of the population when considering environmental protection and management in the context of economic, urban, and infrastructure development. This is the first study in Asia to examine the interactions between air pollution, influenza, and social deprivation from an epidemiologic perspective. The biologic mechanisms are still unclear, and further research is needed.

Acute effects of air pollution on all-cause mortality: a natural experiment from haze control measures in Chiang Mai Province, Thailand.

BACKGROUND: Serious haze episodes have been a seasonal event in Chiang Mai province for more than a decade. In 2008, local government agencies introduced comprehensive measures to control haze and limit its impacts on public health. This study assessed the acute effects of ambient air pollutants on all-cause mortality before and after the introduction of those haze control measures. METHODS: We obtained daily mortality counts and data on mass concentrations of particulate matter <10 micron in aerodynamic diameter (PM10), gaseous pollutants (SO2, NO2, O3, and CO), and meteorology in Chiang Mai Province between January 2002 and December 2016. We analyzed the data using a case-crossover approach adjusting for temperature, relative humidity, seasonality, and day-of-week. We assessed change in the excess risks of all-cause mortality associated with an increase in interquartile range (IQR) of pollutant concentration before and after control measures came into force. RESULTS: We found decreased PM10 levels and markedly reduced excess risks of daily mortality associated with an IQR increase in PM10 concentrations in the years after haze-control measures were implemented (2009-2016). We found mixed results for gaseous pollutants: SO2 showed no significant change in excess risk of daily mortality throughout the study period, while NO2 and CO showed significant excess risks only in the period 2012-2016, and 8-h maximum O3 showed a decrease in excess risk despite an increase in its atmospheric levels after the introduction of haze control measures in 2008. CONCLUSIONS: The findings indicate that the government haze control measures first introduced in Chiang Mai province in 2008 have successfully reduced episodic PM10 concentrations, which has led to a decrease in short-term all-cause mortality.