Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

Endothelium-derived microparticles from chronically thromboembolic pulmonary hypertensive patients facilitate endothelial angiogenesis.

BACKGROUND: Increased circulating levels of endoglin(+) endothelial microparticles (EMPs) have been identified in several cardiovascular disorders, related to severity. Endoglin is an auxilary receptor for transforming growth factor ß (TGF-ß) important in the regulation of vascular structure. RESULTS: We quantified the number of microparticles in plasma of six patients with chronic thromboembolic pulmonary hypertension (CTEPH) and age- and sex-matched pulmonary embolic (PE) and healthy controls and investigated the role of microparticle endoglin in the regulation of pulmonary endothelial function in vitro. Results show significantly increased levels of endoglin(+) EMPs in CTEPH plasma, compared to healthy and disease controls. Co-culture of human pulmonary endothelial cells with CTEPH microparticles increased intracellular levels of endoglin and enhanced TGF-ß-induced angiogenesis and Smad1,5,8 phosphorylation in cells, without affecting BMPRII expression. In an in vitro model, we generated endothelium-derived MPs with enforced membrane localization of endoglin. Co-culture of these MPs with endothelial cells increased cellular endoglin content, improved cell survival and stimulated angiogenesis in a manner similar to the effects induced by overexpressed protein. CONCLUSIONS: Increased generation of endoglin(+) EMPs in CTEPH is likely to represent a protective mechanism supporting endothelial cell survival and angiogenesis, set to counteract the effects of vascular occlusion and endothelial damage.

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.

Aberrant chloride intracellular channel 4 expression contributes to endothelial dysfunction in pulmonary arterial hypertension.

BACKGROUND: Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions of patients with pulmonary arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension. METHODS AND RESULTS: CLIC4 protein expression was increased in plasma and blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension and in the pulmonary vascular endothelium of 3 rat models of pulmonary hypertension. CLIC4 gene deletion markedly attenuated the development of chronic hypoxia-induced pulmonary hypertension in mice. Adenoviral overexpression of CLIC4 in cultured human pulmonary artery endothelial cells compromised pulmonary endothelial barrier function and enhanced their survival and angiogenic capacity, whereas CLIC4 shRNA had an inhibitory effect. Similarly, inhibition of CLIC4 expression in blood-derived endothelial cells from patients with idiopathic pulmonary arterial hypertension attenuated the abnormal angiogenic behavior that characterizes these cells. The mechanism of CLIC4 effects involves p65-mediated activation of nuclear factor-κB, followed by stabilization of hypoxia-inducible factor-1α and increased downstream production of vascular endothelial growth factor and endothelin-1. CONCLUSION: Increased CLIC4 expression is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension.

Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension.

RATIONALE: MicroRNAs (miRNAs or miRs) are implicated in the pathogenesis of various cardiovascular diseases, including pulmonary arterial hypertension (PAH). OBJECTIVES: We sought to measure changes in plasma levels of miRNAs in patients with PAH and relate them to the severity of the disease. METHODS: A microarray screen was performed on total plasma RNA from eight patients with PAH and eight healthy control subjects. Quantitative polymerase chain reaction confirmed reduced miR-150 concentrations and was then used to measure miR-150 levels in (1) two separate cohorts of patients with PAH, from London (n = 145) and Sheffield (n = 30), respectively; (2) circulating microvesicles and blood cells; and (3) lungs from a monocrotaline rat model. MEASUREMENTS AND MAIN RESULTS: Fifty-eight miRNAs showed differences in plasma concentration and miR-150 the largest down-regulation in PAH. Receiver-operator-characteristic analysis showed both raw and normalized plasma miR-150 levels correlated with 2-year survival (P < 0.01) in patients with PAH. Cox regression analysis confirmed miR-150 levels as a significant predictor of survival. Age, baseline cardiac index, World Health Organization functional class, 6-minute walk distance, disease duration, and red cell distribution width also predicted survival. Entering these covariates in a multivariable model verified plasma miR-150 levels as an independent predictor of survival in PAH (hazard ratio, 0.533; P = 0.010). miR-150 levels also predicted survival in a second, independent PAH cohort. miR-150 levels were significantly reduced in circulating microvesicles from patients with PAH and the lungs of the monocrotaline rat. CONCLUSIONS: Reduced circulating miR-150 levels are associated with poor survival in PAH.

Change in disease burden associated with influenza and air pollutants during the COVID-19 pandemic in Hong Kong.

Objectives: This study aimed to estimate the variation in disease burden associated with air pollutants and other respiratory viruses during the COVID-19 pandemic. Methods: We adopted a machine learning approach to calculate the excess mortality attributable to air pollutants and influenza, during the pre-pandemic and pandemic period. Results: In the first 2 years of the COVID-19 pandemic, there were 8762 (95% confidence interval, 7503-9993), and 12,496 (11,718-13,332) excess all-cause deaths in Hong Kong. These figures correspond to 117.4 and 167.9 per 100,000 population, and 12.6% and 8.5% of total deaths in 2020 and 2021, respectively. Compared to the period before the pandemic, excess deaths from all-causes, cardiovascular and respiratory diseases, pneumonia and influenza attributable to influenza A and B significantly decreased in all age groups. However, excess deaths associated with ozone increased in all age-disease categories, while the relative change of nitrogen dioxide (NO2) and particular matters less than 10 µm (PM10) associated burden showed a varied pattern. Conclusions: A notable shift in disease burden attributable to influenza and air pollutants was observed in the pandemic period, suggesting that both direct and indirect impacts shall be considered when assessing the global and regional burden of the COVID-19 pandemic.

Hand Hygiene Education Components Among First-Year Nursing Students: A Cluster Randomized Clinical Trial.

Importance: Few studies have directly and objectively measured the individual and combined effects of multifaceted hand hygiene education programs. Objective: To evaluate the individual and combined immediate effects of an instructional video and hand scan images on handwashing quality, decontamination, and knowledge improvement. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in June to July 2023 among first-year nursing students at a university in Hong Kong. The study used an intention-to-treat analysis. Intervention: Hand hygiene education sessions featuring an instructional video, hand scan images, or both. Main Outcomes and Measures: The primary outcome was the change in residue from fluorescent lotion remaining on participants' hands after handwashing before and after the intervention. The secondary outcomes included handwashing quality and knowledge of hand hygiene. Results: A total of 270 of 280 students (mean [SD] age, 19 [1] years; 182 [67.4%] female) participated in the trial (96.4% participation rate). Participants were randomized to a control group (66 participants), hand scan image group (68 participants), instructional video group (67 participants), and hand scan image with instructional video group (69 participants). All intervention groups had greater reductions in residue after the intervention compared with the control group, although none reached statistical significance (hand scan image group: 3.9 [95% CI, 2.0-5.8] percentage points; instructional video group: 4.8 [95% CI, 2.9-6.7] percentage points; hand scan image with instructional video: 3.5 [95% CI, 1.6-5.4] percentage points; control group: 3.2 [95% CI, 1.3-5.2] percentage points). The instructional video group showed a significant improvement in their handwashing performance, with a higher percentage of participants correctly performing all 7 steps compared with the control group (22.4% [95% CI, 13.1% to 31.6%] vs 1.5% [-7.9% to 10.9%]; P < .001). Hand scan images revealed that wrists, fingertips, and finger webs were the most commonly ignored areas in handwashing. Conclusions and Relevance: In this cluster randomized clinical trial of an education program for hand hygiene, a handwashing instructional video and hand scan images did not enhance the level of decontamination. The intervention group had improved handwashing techniques compared with the control group, a secondary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT05872581.

An AI-empowered indoor digital contact tracing system for COVID-19 outbreaks in residential care homes.

An AI-empowered indoor digital contact-tracing system was developed using a centralized architecture and advanced low-energy Bluetooth technologies for indoor positioning, with careful preservation of privacy and data security. We analyzed the contact pattern data from two RCHs and investigated a COVID-19 outbreak in one study site. To evaluate the effectiveness of the system in containing outbreaks with minimal contacts under quarantine, a simulation study was conducted to compare the impact of different quarantine strategies on outbreak containment within RCHs. The significant difference in contact hours between weekdays and weekends was observed for some pairs of RCH residents and staff during the two-week data collection period. No significant difference between secondary cases and uninfected contacts was observed in a COVID-19 outbreak in terms of their demographics and contact patterns. Simulation results based on the collected contact data indicated that a threshold of accumulative contact hours one or two days prior to diagnosis of the index case could dramatically increase the efficiency of outbreak containment within RCHs by targeted isolation of the close contacts. This study demonstrated the feasibility and efficiency of employing an AI-empowered system in indoor digital contact tracing of outbreaks in RCHs in the post-pandemic era.

Meta-analysis of adverse health effects due to air pollution in Chinese populations.

BACKGROUND: Pooled estimates of air pollution health effects are important drivers of environmental risk communications and political willingness. In China, there is a lack of review studies to provide such estimates for health impact assessments. METHODS: We systematically searched the MEDLINE database using keywords of 80 major Chinese cities in Mainland China, Hong Kong and Taiwan on 30 June 2012, yielding 350 abstracts with 48 non-duplicated reports either in English or Chinese after screening. We pooled the relative risks (RR) per 10 µg/m3 of particulate matter (PM10), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3). RESULTS: For short-term effects, the pooled RR (p<0.05) ranges were: 1.0031 (PM10) to 1.0140 (NO2) for all-cause mortality, 1.0034 (cardiopulmonary, PM10) to 1.0235 (influenza and pneumonia, SO2) for 9 specific-causes mortality, 1.0021 (cardiovascular, PM10) to 1.0162 (asthma, O3) for 5 specific-causes hospital admissions. For birth outcomes, the RR (p<0.05) ranged from 1.0051 (stillbirth, O3) to 1.1189 (preterm-birth, SO2) and for long-term effect on mortality from 1.0150 (respiratory, SO2) to 1.0297 (respiratory, NO2). Publication bias was absent (Egger test: p=0.326 to 0.624). Annual PM10 and NO2 concentrations were inversely associated with RR of mortality (p=0.017-0.028). CONCLUSIONS: Evidence on short-term effects of air pollution is consistent and sufficient for health impact assessment but that on long-term effects is still insufficient.

Mixed-mode Zentangle and Pastel Nagomi artwork for improving mental well-being in university students during COVID-19 pandemic - a randomized controlled feasibility trial.

Background: University students are identified as a high-risk group for mental health problems. Artworks have been found effective in enhancing individuals' mental well-being in different populations, but none have been conducted on university students. This study was to address this research gap to determine the feasibility and estimate the preliminary effects of Zentangle and Pastel Nagomi on the mental well-being of undergraduate students during the COVID-19 pandemic. Method: This was a 3-arm randomized controlled trial, with 33 undergraduates allocated to two 8-week artworks (Zentangle or Pastel Nagomi Art group) and a control group. Data were collected at baseline, and weeks 4, 6, 8, and 12. Focus group interviews were conducted at the 12-week follow-up. Results: The consent and attrition rates were 80.5 and 6.06%, respectively. The attendance rate ranged from 83.3 to 100%. Compared with the control group, the Pastel Nagomi art group had a significant improvement in retaining positive affect at week 6. This retention could be further observed at week 12. Moreover, the Zentangle group had a significant increase in positive affect at week 4, with better retention at week 12. In addition, the within-group analyses showed that the Pastel Nagomi art group had significantly decreased negative affect at weeks 6 and week 12; and the Zentangle group had significantly decreased depression at week 8. The qualitative findings suggested that the intervention resulted in the participants enjoying the artwork process, and being proud of their artwork and personal growth. Limitation: The study included an imbalance number of online vs. face-to-face sessions, and repeated measures may have affected the results. Conclusion: The study suggests that both artworks are effective in improving undergraduates' mental well-being and that it is feasible to conduct future large-scale studies (263 words).

Factors associated with hand washing effectiveness: an institution-based observational study.

BACKGROUND: Few studies have investigated how the effectiveness of hand washing in removing hand contaminants is influenced by the performance and duration of each step involved. We conducted an observational study by recruiting participants from a university campus, with the aim to comprehensively evaluate how performance, duration and demographic factors influence hand washing effectiveness. METHODS: A total of 744 videos were collected from 664 participants in July-October 2022 and independently evaluated by two infection control experts through labelling videos for correct and incorrect performance of each step. The individual hand washing effectiveness was determined by quantifying the percentage of residual fluorescent gel on the dorsum and palm areas of each participant's hands. A logistic regression analysis was conducted to identify factors that were significantly associated with better hand washing effectiveness. An exposure-response relationship was constructed to identify optimal durations for each step. Approximately 2300 hand images were processed using advanced normalization algorithms and overlaid to visualize the areas with more fluorescence residuals after hand washing. RESULTS: Step 3 (rub between fingers) was the most frequently omitted step and step 4 (rub the dorsum of fingers) was the most frequently incorrectly performed step. After adjustment for covariates, sex, performance of step 4 and step 7 (rub wrists), rubbing hands during rinsing, and rinsing time were significantly associated with hand washing effectiveness. The optimal overall hand washing time was 31 s from step 1 to step 7, and 28 s from step 1 to step 6, with each step ideally lasting 4-5 s, except step 3. The palms of both hands had less fluorescence residuals than the dorsums. The areas where residuals most likely appeared were wrists, followed by finger tips, finger webs and thumbs. CONCLUSIONS: Performance and duration of some hand washing steps, sex and rinsing time were associated with hand washing effectiveness. The optimal duration might be applied to all seven steps to achieve the best decontamination results. Further studies are needed to refine hand hygiene standards and enhance compliance.

The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling.

The hereditary spastic paraplegias (HSPs) are genetic conditions characterized by distal axonopathy of the longest corticospinal tract axons, and so their study provides an important opportunity to understand mechanisms involved in axonal maintenance and degeneration. A group of HSP genes encode proteins that localize to endosomes. One of these is NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) and we have shown recently that its Drosophila homologue spichthyin inhibits bone morphogenic protein (BMP) signalling, although the relevance of this finding to the mammalian protein was not known. We show here that mammalian NIPA1 is also an inhibitor of BMP signalling. NIPA1 physically interacts with the type II BMP receptor (BMPRII) and we demonstrate that this interaction does not require the cytoplasmic tail of BMPRII. We show that the mechanism by which NIPA1 inhibits BMP signalling involves downregulation of BMP receptors by promoting their endocytosis and lysosomal degradation. Disease-associated mutant versions of NIPA1 alter the trafficking of BMPRII and are less efficient at promoting BMPRII degradation than wild-type NIPA1. In addition, we demonstrate that two other members of the endosomal group of HSP proteins, spastin and spartin, are inhibitors of BMP signalling. Since BMP signalling is important for distal axonal function, we propose that dysregulation of BMP signalling could be a unifying pathological component in this endosomal group of HSPs, and perhaps of importance in other conditions in which distal axonal degeneration is found.

Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules.

To understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, spichthyin (Spict). Spict is found on early endosomes. Loss of Spict leads to upregulation of bone morphogenetic protein (BMP) signaling and expansion of the neuromuscular junction. BMP signaling is also necessary for a normal microtubule cytoskeleton and axonal transport; analysis of loss- and gain-of-function phenotypes indicate that Spict may antagonize this function of BMP signaling. Spict interacts with BMP receptors and promotes their internalization from the plasma membrane, implying that it inhibits BMP signaling by regulating BMP receptor traffic. This is the first demonstration of a role for a hereditary spastic paraplegia protein or ichthyin family member in a specific signaling pathway, and implies disease mechanisms for hereditary spastic paraplegia that involve dependence of the microtubule cytoskeleton on BMP signaling.

Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5.

The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome.

Factors Affecting Direct and Transfer Entrants' Active Coping and Satisfaction with the University.

Psychological wellbeing is vital to public health. University students are the future backbone of the society. Direct and transfer entrants might encounter different adjustment issues in their transition from secondary school or community college to university studies. However, worldwide, the factors affecting their active coping and satisfaction with the university are currently unknown. The purpose of this study was to address this gap. Nine-hundred-and-seventy-eight direct entrants and 841 transfer entrants, recruited by convenience sampling, completed a cross-sectional survey study in 2018. A valid and reliable Hong Kong modified Laanan-Transfer Student Questionnaire (HKML-TSQ) was used to collect data. Multiple methods of quantitative data analysis were employed, including factor analyses, test of model fit, t-tests, correlations, and linear regression. The results showed that the transfer entrants had relatively less desirable experiences in their adjusting processes than did the direct entrants. There was evidence of both common and different factors affecting the two groups' active coping and satisfaction with the university. Different stakeholders from community colleges, universities, and student bodies should work collaboratively to improve students' transitional experiences before, during and after admission to the university.

Differences in study workload stress and its associated factors between transfer students and freshmen entrants in an Asian higher education context.

Unlike the studies of freshmen entrants, the learning experiences of community college transfer (CCT) students in the receiving university is a topic that has only started to gain attention in recent decades. Little is known about the differences between CCT and freshmen entrants with regard to their study workload stress and its relationship with their perceptions of the teaching and learning environment, approaches to learning, self-efficacy and generic skills. The purpose of our study was to address this gap. This was a cross-sectional survey study conducted from April 2018 to November 2018 in a university in Hong Kong. The HowULearn questionnaire was adapted to local usage and validated for data collection. In total, 841 CCT students and 978 freshmen entrants completed the survey. The respondents were aged between 19 and 52 years (mean = 21.6, SD = 1.92), and 66.0% were women. The HowULearn questionnaire was determined by factor analyses to have eight factors. The reliabilities of the eight factors were found to be acceptable (Cronbach alphas = 0.709-0.918). The CCT students scored significantly higher than the freshmen entrants for perceived study workload stress and surface approaches to learning, but lower on teaching for understanding & encouraging learning, peer support, and self-efficacy beliefs. The surface approach to learning, deep & organized studying, alignment & constructive feedback, and generic skills were found to be predictors of study workload stress in both groups of students, and in the overall student data. This study has shown that CCT students and freshmen entrants differed with regard to their study workload stress and learning experiences. Our findings provide a message, both for educators in higher education and policy makers in the government-there is not a one-size-fits-all approach to different student populations when it comes to enhancing their learning experiences.

A novel method to construct an air quality index based on air pollution profiles.

BACKGROUND: Air quality indices based on the maximum of sub-indices of pollutants are easy to produce and help quantify the degree of air pollution. However, they discount the additive effects of multiple pollutants and are only sensitive to changes in highest sub-index. OBJECTIVES: We propose a simple and concise method to construct an air quality index that takes into account additive effects of multiple pollutants and evaluate the extent to which this index predicts health effects. MATERIALS AND METHODS: We obtained concentrations of four criteria pollutants: particulate matter with aerodynamic diameter ≤ 10µm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) and daily admissions to Hong Kong hospitals for cardiovascular and respiratory diseases for all ages and those 65 years or older for years 2001-2012. We derived sub-indices of the four criteria pollutants, calculated by normalizing pollutant concentrations to their respective short-term WHO Air Quality Guidelines (WHO AQG). We aggregated the sub-indices using the root-mean-power function with an optimal power to form an overall air quality index. The optimal power was determined by minimizing the sum of over- and under-estimated days. We then assessed associations between the pollution bands of the index and cardiovascular and respiratory admissions using a time-stratified case-crossover design adjusted for ambient temperature, relative humidity and influenza epidemics. Further, we conducted case-crossover analyses using the Hong Kong air quality data with the respective standards and classification of pollution bands of the China Air Quality Index (AQI), the United Kingdom Daily AQI (DAQI), and the United States Environmental Protection Agency (USEPA) AQI. RESULTS: The mean concentrations of PM10 and SO2 based on maximum 3-h mean exceeded the WHO AQG by 37% and 50%, respectively. We identified the combined condition of observed high-pollution days as either at least one pollutant > 1.5×WHO AQG or at least two pollutants > 1.0×WHO AQG to characterize the typical pollution profiles over the study period, which resulted in the optimal power=3.0. The distribution of days in different pollution bands of the index was: 5.8% for "Low" (0-50), 37.6% for "Moderate" (51-100), 31.1% for "High" (101-150), 14.7% for "Very High" (151-200), and 10.8% for "Serious" (201+). For cardiovascular and respiratory admissions, there were significant associations with the pollution bands of the index for all ages and those 65 years or older. The trends of increasing pollution bands in relation to increasing excess risks of cardiovascular and respiratory admissions were significant for the proposed index, the China AQI, the UK DAQI and the USEPA AQI (P value for test for linear trend < 0.0001), suggesting a dose-response relation. CONCLUSIONS: We have developed a simple and concise method to construct an air quality index that accounts for multiple pollutants to quantify air quality conditions for Hong Kong. Further developments are needed in order to support the extension of the method to other settings.

Long-term exposure to fine particulate matter air pollution and type 2 diabetes mellitus in elderly: A cohort study in Hong Kong.

BACKGROUND: Evidence for the link between long-term air pollution exposure and occurrence of diabetes is limited and the results are mixed. OBJECTIVES: We aimed to assess the association of long-term residential exposure to fine particulate matter (PM2.5) with the prevalence and incidence of type 2 diabetes mellitus (DM). METHODS: This is a prospective cohort study. We studied 61,447 participants of the Chinese Elderly Health Services cohort in Hong Kong enrolled 1998-2001 and followed participants without DM at baseline to 31 December 2010 to ascertain the first hospital admissions for type 2 DM. Yearly mean residential PM2.5 exposure was predicted based on satellite data. Logistic regression and time-varying Cox regression model were used to evaluate the prevalence and incidence risk of DM associated with PM2.5 while adjusting for potential individual and neighborhood confounders. RESULTS: There were 61,447 participants included in the study of prevalent DM, and in 53,905 participants without DM at baseline we studied incident type 2 DM. Over a mean follow-up of 9.8 years, we ascertained 806 incident cases of type 2 DM. After adjusting for potential confounders, the odds ratio (OR) for every interquartile range (3.2 µg/m3) increase of PM2.5 concentration was 1.06 (95% confidence interval (CI): 1.01-1.11) for prevalent DM, while the corresponding hazard ratio (HR) was 1.15 (95% CI: 1.05-1.25) for incident type 2 DM. CONCLUSIONS: Long-term exposure to high levels of PM2.5 may increase the risk of both prevalence and incidence of type 2 diabetes mellitus in Hong Kong elderly population.

Rationale and design of the randomized multicentre His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) trial.

AIMS: In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His-bundle pacing. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE-HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. METHODS AND RESULTS: This multicentre, double-blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His-bundle pacing and (ii) backup pacing only, using the non-His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B-type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His-bundle pacing. CONCLUSIONS: Hope-HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His-bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020.