Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design.

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).

Randomized evaluation of 5-month Ticagrelor monotherapy after 1-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with drug-coated balloons: REC-CAGEFREE II trial rationale and design.

BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.

Association between serum total bilirubin and diabetic kidney disease in US diabetic patients.

Background: Bilirubin has been widely reported to be a protective factor against diabetic kidney disease (DKD) in Asian populations. However, few large-sample analyses have been conducted in American populations. This study aimed to investigate the association between serum total bilirubin (STB) level and DKD in a US diabetic cohort. Methods: This cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Univariate and multivariate logistic regression analyses were performed to assess the association between STB level and DKD. Three models were conducted to control the potential confounding factors. Subgroup analysis was carried out for further validation. Results: Among the 5,355 participants, the median age [interquartile range (IQR)] was 62 [52-71] years; 2,836 (52.96%) were male, and 1,576 (29.43%) were diagnosed with DKD. In the entire cohort, no significant association between STB level and DKD was observed in any logistic regression models (p > 0.05). Subgroup analysis revealed that, in U.S. diabetic males, STB levels > 11.98 µmol/L were associated with a nearly 30% lower risk of DKD than STB levels ≤ 8.55 µmol/L. Additionally, a moderate STB level (8.56-11.98 µmol/L) was found associated with a nearly 25% lower risk of DKD in U.S. diabetic patients over 65 years old. Conclusion: The association of STB level with DKD may depict differences across diverse populations, among which the impact of race, sex, and age requires thorough consideration and relevant inferences should be interpreted cautiously.

Does the mainland China-Hong Kong exchange program change the views of local university students in Hong Kong on regional cooperation? A randomized control-group pre-test post-test experiment.

The Chinese central government has been running an intensive exchange program called the Mainland China-Hong Kong Ten Thousand Student Exchange Program since 2012 to support local Hong Kong university students' visits to mainland China, with the aim of promoting exchange and regional cooperation between Hong Kong and mainland China. However, little is known about local Hong Kong university students' views on regional cooperation and whether the program is effective in changing their views. Using a randomized experimental design, we find that most students hold positive views on regional cooperation between Hong Kong and mainland China, but a considerable percentage of students oppose integration with mainland China. We also find that the program is effective in positively changing students' views on certain aspects of regional cooperation related to the free trade zones and the Hong Kong-Zhuhai-Macau Bridge, but is not significantly effective on other aspects of regional cooperation. This study provides the first causal quantitative evidence regarding the impact of the mainland China-Hong Kong exchange program on local university students' views regarding regional cooperation. The findings help inform the public about the prospect of regional cooperation and offer policy implications on youth exchange between mainland China and Hong Kong.

Air pollution-induced health impacts and health economic losses in China driven by US demand exports.

Understanding how trade between regions or countries drives the transfer of air pollution has attracted considerable interest recently, but few studies have explored the various transfer pathways or evaluated economic losses due to the health impact of such air pollution. Here, we assess the air pollutant emissions and related health impacts and economic losses in China caused by export trade due to US demand by combining the linked multi-regional input-output (MRIO) model, GEOS-Chem model, integrated exposure-response model, and the willingness to pay method. We show that the air pollutant emissions embedded in China's export due to the US demand reached 5792.38 Kt in 2012 (2.48% of the total), which includes direct exports of intermediate (40.27%) and final (33.61%) products and indirect exports of intermediate products via domestic provinces (16.43%, domestic spillover) and other countries (9.69%, foreign spillover). The resulting increase in PM2.5 (<2.8 µg m-3) leads to additional 27,963 deaths in 30 provinces, with a higher death toll in coastal areas and the corresponding economic loss was higher in more developed regions and reached USD 2.08 billion. This study highlights the region-different air pollution and health impacts in China embedded in the US-demand trade, and provides a framework for the analysis of health and economic losses hidden in global trade, particularly between developing and developed countries.

Derivation and Validation of a Screening Model for Hypertrophic Cardiomyopathy Based on Electrocardiogram Features.

Background: Hypertrophic cardiomyopathy (HCM) is a widely distributed, but clinically heterogeneous genetic heart disease, affects approximately 20 million people worldwide. Nowadays, HCM is treatable with the advancement of medical interventions. However, due to occult clinical presentations and a lack of easy, inexpensive, and widely popularized screening approaches in the general population, 80-90% HCM patients are not clinically identifiable, which brings certain safety hazards could have been prevented. The majority HCM patients showed abnormal and diverse electrocardiogram (ECG) presentations, it is unclear which ECG parameters are the most efficient for HCM screening. Objective: We aimed to develop a pragmatic prediction model based on the most common ECG features to screen for HCM. Methods: Between April 1st and September 30th, 2020, 423 consecutive subjects from the International Cooperation Center for Hypertrophic Cardiomyopathy of Xijing Hospital [172 HCM patients, 251 participants without left ventricular hypertrophy (non-HCM)] were prospectively included in the training cohort. Between January 4th and February 30th, 2021, 163 participants from the same center were included in the temporal internal validation cohort (62 HCM patients, 101 non-HCM participants). External validation was performed using retrospectively collected ECG data from Xijing Hospital (3,232 HCM ECG samples from January 1st, 2000, to March 31st, 2020; 95,184 non-HCM ECG samples from January 1st to December 31st, 2020). The C-statistic was used to measure the discriminative ability of the model. Results: Among 30 ECG features examined, all except abnormal Q wave significantly differed between the HCM patients and non-HCM comparators. After several independent feature selection approaches and model evaluation, we included only two ECG features, T wave inversion (TWI) and the amplitude of S wave in lead V1 (SV1), in the HCM prediction model. The model showed a clearly useful discriminative performance (C-statistic > 0.75) in the training [C-statistic 0.857 (0.818-0.896)], and temporal validation cohorts [C-statistic 0.871 (0.812-0.930)]. In the external validation cohort, the C-statistic of the model was 0.833 [0.825-0.841]. A browser-based calculator was generated accordingly. Conclusion: The pragmatic model established using only TWI and SV1 may be helpful for predicting the probability of HCM and shows promise for use in population-based HCM screening.

A Framework for Characterizing the Multilateral and Directional Interaction Relationships Between PM Pollution at City Scale: A Case Study of 29 Cities in East China, South Korea and Japan.

Transboundary particulate matter (PM) pollution has become an increasingly significant public health issue around the world due to its impacts on human health. However, transboundary PM pollution is difficult to address because it usually travels across multiple urban jurisdictional boundaries with varying transportation directions at different times, therefore posing a challenge for urban managers to figure out who is potentially polluting whose air and how PM pollution in adjacent cities interact with each other. This study proposes a statistical analysis framework for characterizing directional interaction relationships between PM pollution in cities. Compared with chemical transport models (CTMs) and chemical composition analysis method, the proposed framework requires less data and less time, and is easy to implement and able to reveal directional interaction relationships between PM pollution in multiple cities in a quick and computationally inexpensive way. In order to demonstrate the application of the framework, this study applied the framework to analyze the interaction relationships between PM2.5 pollution in 29 cities in East China, South Korea and Japan using one year of hourly PM2.5 measurement data in 2018. The results show that the framework is able to reveal the significant multilateral and directional interaction relationships between PM2.5 pollution in the 29 cities in Northeast Asia. The analysis results of the case study show that the PM2.5 pollution in China, South Korea and Japan are linked with each other, and the interaction relationships are mutual. This study further evaluated the framework's validity by comparing the analysis results against the wind vector data, the back trajectory data, as well as the results extracted from existing literature that adopted CTMs to study the interaction relationships between PM pollution in Northeast Asia. The comparisons show that the analysis results produced by the framework are consistent with the wind vector data, the back trajectory data as well as the results using CTMs. The proposed framework provides an alternative for exploring transportation pathways and patterns of transboundary PM pollution between cities when CTMs and chemical composition analysis would be too demanding or impossible to implement.

A Randomized Comparison of the Healing Response Between the Firehawk Stent and the Xience Stent in Patients With ST-Segment Elevation Myocardial Infarction at 6 Months of Follow-Up (TARGET STEMI OCT China Trial): An Optical Coherence Tomography Study.

Background: The healing response of the Firehawk stent in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. Aim: We compared the vascular healing of a biodegradable polymer sirolimus-eluting stent (Firehawk) vs. a durable polymer everolimus-eluting stent (Xience) at 6 months after percutaneous coronary intervention (PCI) in patients with STEMI. Methods: In this prospective, multicenter, randomized, non-inferiority study, patients within 12 h of STEMI onset were randomized in a ratio of 1:1 to receive Firehawk or Xience stents. Optical coherence tomography (OCT) follow-up was performed 6 months after the index procedure and assessed frame by frame. The primary endpoint was the neointimal thickness (NIT) at 6 months evaluated by OCT. The safety endpoint was target lesion failure (TLF) at 12 months. Results: The Firehawk stent was non-inferior to the Xience stent in terms of the neointimal thickness (73.03 ± 33.30 µm vs. 78.96 ± 33.29 µm; absolute difference: -5.94 [one-sided 95% lower confidence bound: -23.09]; P non-inferiority < 0.001). No significant difference was observed between the Firehawk and Xience groups regarding the percentage of uncovered struts (0.55 [0.08, 1.32]% vs. 0.40 [0.21, 1.19]%, P = 0.804), the percentage of malapposed struts (0.17 [0.00, 1.52]% vs. 0.17 [0.00, 0.69]%, P = 0.662), and the healing score (1.56 [0.23, 5.74] vs. 2.12 [0.91, 3.81], P = 0.647). At 12 months, one patient in the Firehawk group experienced a clinically indicated target lesion revascularization. No other TLF events occurred in both groups. Independent risk factors of the NIT included body mass index, hyperlipidemia, B2/C lesions, thrombus G3-G5, thrombus aspiration, and postdilation pressure. Conclusion: In patients with STEMI, Firehawk was non-inferior to Xience in vascular healing at 6 months. Both stents exhibited nearly complete strut coverage, moderate neointimal formation, and minimal strut malapposition. Clinical Trial Number: NCT04150016.

Periprocedural Outcomes Associated With Use of a Left Atrial Appendage Occlusion Device in China.

Importance: Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation for patients with atrial fibrillation. However, the performance of LAAO among East Asian patients is unknown. Objective: To document the procedural success rate and configurations, major adverse event rates, and antithrombotic medication regimens during and after LAAO procedures among patients in China. Design, Setting, and Participants: In this cohort study, consecutive patients from 39 Chinese centers undergoing LAAO were prospectively enrolled between April 1, 2019, and October 31, 2020. Periprocedural and intraprocedural techniques and postprocedural medications were left to the surgeon's discretion. Data were analyzed from July 1 to November 1, 2021. Exposure: LAAO for patients with atrial fibrillation. Main Outcomes and Measures: The main outcomes were procedural success and complication rates periprocedure and major adverse event rates of death, stroke, systemic embolism, and bleeding events at 30 days postprocedure; the composite end point of death, stroke, and systemic embolism was also analyzed. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the associations of periprocedural techniques (types of anesthesia, intraprocedural imaging modalities, and combined ablation procedure) with 30-day adverse events. Results: Among 3096 enrolled participants, 1782 participants (57.6%) were men, and the mean (SD) age was 69 (9) years. Participants had a high risk of stroke (mean [SD] cardiovascular risk score, 4.0 [1.8]) and a moderate-to-high risk of bleeding (mean [SD] bleeding risk score, 2.4 [1.2]). A total of 1287 procedures (41.6%) were performed under local anesthesia, while 493 procedures (15.9%) used only fluoroscopy guidance. In 1297 procedures (41.9%), LAAO implantation was combined with radiofrequency ablation or cryoablation for atrial fibrillation. Procedural success was achieved in 3032 patients (97.9%). At 30-day follow-up, the rate of the composite end point of death, stroke, or systemic embolism was 0.52% (95% CI, 0.32%-0.84%), and the rate of any life-threatening or major bleeding was 1.23% (95% CI, 0.90%-1.68%). No significant associations were observed between the procedural success or 30-day adverse events and the types of anesthesia (general or local), intraprocedural imaging (transesophageal echocardiography, fluoroscopy, or intracardiac echocardiography), or whether a combined ablation procedure was performed or not. In centers performing at least 40 procedures per year, compared with those performing fewer than 40 procedures per year, procedural success was significantly higher (adjusted odd ratio [aOR], 1.97; 95% CI, 1.01-3.53; P = .02) and risk of life-threatening or major bleeding was significantly lower (aOR, 0.42; 95% CI, 0.21-0.87; P = .02). Conclusions and Relevance: These findings suggest that patients with a high risk of stroke and moderate to high risk of bleeding who underwent implantation of a LAAO device in Chinese centers had high rates of procedural success and low rates of short-term ischemic and bleeding events.

Export Expansion May Increase Adult Illness and Injury: A Quasi-Natural Experiment on China's Accession to the World Trade Organization.

Purpose: Exports can boost the economy, but may also cause harm to health through, for example, increased pollution and working hours. Although academic research extensively covers the impact of trade on health, few studies examine the mechanisms through which export expansion affects adult illness or injury within the past 4 weeks (illness/injury). Method: We utilized China's entry into the World Trade Organization (WTO) as a quasi-natural experiment to investigate the relationship between export expansion and adult illness/injury. We explored the possible mechanisms and the heterogeneity of these associations. Our methodology was based on the analysis of China's Health and Nutrition Survey data, Chinese Customs databases, and China's Statistical Yearbook. Results: Export expansion, induced by China's accession to the WTO, has a significantly positive effect on adult illness/injury [average effect (AE): 1.83%; 95% CI: 0.38-3.28%]. Our results remain robust following a series of robustness tests. Moreover, the effects of export expansion on adult illness/injury are more pronounced among urban residents (AE: 5.32%; 95% CI: 2.46-8.18%), women (AE: 2.68%; 95% CI: 0.57-4.80%), and higher-income groups (AE: 5.90%; 95% CI: 2.53-9.27%). Conclusions: We find a statistically significant and positive effect of export expansion on adult illness/injury.

Visualizing the intercity correlation of PM2.5 time series in the Beijing-Tianjin-Hebei region using ground-based air quality monitoring data.

The Beijing-Tianjin-Hebei area faces a severe fine particulate matter (PM2.5) problem. To date, considerable progress has been made toward understanding the PM2.5 problem, including spatial-temporal characterization, driving factors, and health effects. However, little research has been done on the dynamic interactions and relationships between PM2.5 concentrations in different cities in this area. To address the research gap, this study discovered a phenomenon of time-lagged intercity correlations of PM2.5 time series and proposed a visualization framework based on this phenomenon to visualize the interaction in PM2.5 concentrations between cities. The visualizations produced using the framework show that there are significant time-lagged correlations between the PM2.5 time series in different cities in this area. The visualizations also show that the correlations are more significant in colder months and between cities that are closer, and that there are seasonal changes in the temporal order of the correlated PM2.5 time series. Further analysis suggests that the time-lagged intercity correlations of PM2.5 time series are most likely due to synoptic meteorological variations. We argue that the visualizations demonstrate the interactions of air pollution between cities in the Beijing-Tianjin-Hebei area and the significant effect of synoptic meteorological conditions on PM2.5 pollution. The visualization framework could help determine the pathway of regional transportation of air pollution and may also be useful in delineating the area of interaction of PM2.5 pollution for impact analysis.

A framework for delineating the regional boundaries of PM2.5 pollution: A case study of China.

Fine particulate matter (PM2.5) pollution has been a major issue in many countries. Considerable studies have demonstrated that PM2.5 pollution is a regional issue, but little research has been done to investigate the regional extent of PM2.5 pollution or to define areas in which PM2.5 pollutants interact. To allow for a better understanding of the regional nature and spatial patterns of PM2.5 pollution, This study proposes a novel framework for delineating regional boundaries of PM2.5 pollution. The framework consists of four steps, including cross-correlation analysis, time-series clustering, generation of Voronoi polygons, and polygon smoothing using polynomial approximation with exponential kernel method. Using the framework, the regional PM2.5 boundaries for China are produced and the boundaries define areas where the monthly PM2.5 time series of any two cities show, on average, more than 50% similarity with each other. These areas demonstrate straightforwardly that PM2.5 pollution is not limited to a single city or a single province. We also found that the PM2.5 areas in China tend to be larger in cold months, but more fragmented in warm months, suggesting that, in cold months, the interactions between PM2.5 concentrations in adjacent cities are stronger than in warmer months. The proposed framework provides a tool to delineate PM2.5 boundaries and identify areas where PM2.5 pollutants interact. It can help define air pollution management zones and assess impacts related to PM2.5 pollution. It can also be used in analyses of other air pollutants.

Estimation of the PM2.5 health effects in China during 2000-2011.

Exposure to fine particulate matter (PM2.5) has been associated with mortality, but the extent of the adverse impacts differs across various regions. A quantitative estimation of health effects attributed to PM2.5 in China is urgently required, particularly because it has the largest population and high air pollution levels. Based on the remote sensing-derived PM2.5 and grid population data, we estimated the acute health effects of PM2.5 in China using an exposure-response function. The results suggest the following: (1) The proportion of the population exposed to high PM2.5 concentrations (>35 µg/m3) increased consistently from 2000 to 2011, and the population exposed to concentrations above the threshold defined by World Health Organization (WHO) (>10 µg/m3) rose from 1,191,191,943 to 1,290,562,965. (2) The number of deaths associated with PM2.5 exposure increased steadily from 107,608 in 2000 to 173,560 in 2010, with larger numbers in the eastern region. (3) PM2.5 health effects decreased in three pollution control scenarios estimated for 2017, i.e., the Air Pollution Prevention and Control Action Plan (APPCAP) scenario, the APPCAP under WHO IT-1 scenario (35 µg/m3), and the APPCAP under WHO IT-3 scenario (15 µg/m3), which indicates that pollution control can effectively reduce PM2.5 effects on mortality.

Temporal Patterns in Fine Particulate Matter Time Series in Beijing: A Calendar View.

Extremely high fine particulate matter (PM2.5) concentration has become synonymous to Beijing, the capital of China, posing critical challenges to its sustainable development and leading to major public health concerns. In order to formulate mitigation measures and policies, knowledge on PM2.5 variation patterns should be obtained. While previous studies are limited either because of availability of data, or because of problematic a priori assumptions that PM2.5 concentration follows subjective seasonal, monthly, or weekly patterns, our study aims to reveal the data on a daily basis through visualization rather than imposing subjective periodic patterns upon the data. To achieve this, we conduct two time-series cluster analyses on full-year PM2.5 data in Beijing in 2014, and provide an innovative calendar visualization of PM2.5 measurements throughout the year. Insights from the analysis on temporal variation of PM2.5 concentration show that there are three diurnal patterns and no weekly patterns; seasonal patterns exist but they do not follow a strict temporal division. These findings advance current understanding on temporal patterns in PM2.5 data and offer a different perspective which can help with policy formulation on PM2.5 mitigation.

Quality screening for air quality monitoring data in China.

Particulate matter data obtained from the national air quality monitoring network in China has become an essential and critical data source for many current and forthcoming studies as well as the formulation and implementation of air pollution regulatory policies on particulate matter (PM2.5 and PM10). However, the quality control of this data is dubitable and can affect many future studies and policies. This study identifies and elucidates two significant quality control issues with the data. They are PM2.5 levels exceeding concurrent co-located PM10 levels and the registration of same concentrations for consecutive hours at some stations. Future studies utilizing particulate matter data need to acknowledge and address these issues to ensure accurate and reliable results.