Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients. METHODS: We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to December 2020) for trials evaluating the effects of PAH therapies on CW. The coefficient of determination between the RR for CW and mortality was assessed by regression analysis. The frequency of occurrence, RR reduction, and importance to patients of the CW components were assessed. RESULTS: We included 35 independent cohorts (9450 patients). PAH therapies significantly reduced CW events (RR, 0.64 [95% CI, 0.55-0.73]), including PAH-related hospitalizations (RR, 0.61 [95% CI, 0.47-0.79]), treatment escalation (RR, 0.57 [95% CI, 0.38-0.84]) and symptomatic progression (RR, 0.58 [95% CI, 0.48-0.69]), and modestly reduced all-cause mortality when incorporating deaths occurring after a primary CW-defining event (RR, 0.860 [95% CI, 0.742-0.997]). However, the effects of PAH-specific therapies on CW only modestly correlated with their effects on mortality (R2trial, 0.35 [95% CI, 0.10-0.59]; P<0.0001), and the gradient in the treatment effect across component end points was large in the majority of trials. The weighted proportions of CW-defining events were hospitalization (33.5%) and symptomatic progression (32.3%), whereas death (6.7%), treatment escalation (5.6%), and transplantation/atrioseptostomy (0.2%) were infrequent. CW events were driven by the occurrence of events of major (49%) and mild-to-moderate (37%) importance to patients, with 14% of the events valued as critical. CONCLUSIONS: PAH therapies significantly reduced CW events, but study-level CW is not a surrogate for mortality in PAH trials. Moreover, components of CW largely vary in frequency, response to therapy, and importance to patients and are thus not interchangeable. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42020178949.

An Assessment of Annual Mortality Attributable to Ambient PM2.5 in Bangkok, Thailand.

Multiple studies indicate that PM2.5 is the most deleterious air pollutant for which there are ambient air quality standards. Daily concentrations of PM2.5 in Bangkok, Thailand, continuously exceed the World Health Organization (WHO) and the Thai National Ambient Air Quality Standards (NAAQSs). Bangkok has only recently begun to measure concentrations of PM2.5. To overcome this paucity of data, daily PM2.5/PM10 ratios were generated over the period 2012-2018 to interpolate missing values. Concentration-response coefficients (ß values) for PM2.5 versus non-accidental, cardiopulmonary, and lung cancer mortalities were derived from the literature. Values were also estimated and were found to be comparable to those reported in the literature for a Chinese population, but considerably lower than those reported in the literature from the United States. These findings strongly suggest that specific regional ß values should be used to accurately quantify the number of premature deaths attributable to PM2.5 in Asian populations. Health burden analysis using the Environmental Benefits Mapping and Analysis Program (BenMAP) showed that PM2.5 concentration in Bangkok contributes to 4240 non-accidental, 1317 cardiopulmonary, and 370 lung cancer mortalities annually. Further analysis showed that the attainment of PM2.5 levels to the NAAQSs and WHO guideline would reduce annual premature mortality in Bangkok by 33%and 75%, respectively.

Framework for life cycle sustainability assessment of municipal solid waste management systems with an application to a case study in Thailand.

At present, there are many environmental, economic and social problems associated with poor municipal solid waste (MSW) management in Thailand. The development of sustainable solid waste management systems is a crucial aspect and should be based on an integrated approach. Therefore, an integrated system was designed for Nonthaburi Municipality incorporating recycling, anaerobic digestion, incineration and landfill technologies. In order to assess sustainability, a clear methodology was developed via life cycle thinking and a set of endpoint composite indicators has been proposed considering the most critical ultimate damages/effects of MSW management on the environment, the economy and society. The results showed that the appropriate integration of technologies offers important prospects with regards to socio-economic and environmental aspects, contributing, therefore, to improved sustainability for the overall MSW management system. The methodology and the proposed indicators would be useful in strategic planning, including decision- and policy-making with respect to the development of appropriate sustainable MSW management systems.

Ozone and its potential control strategy for Chon Buri city, Thailand.

UNLABELLED: This work studies O3 pollution for Chon Buri city in the eastern region of Thailand, where O3 has become an increased and serious concern in the last decade. It includes emission estimation and photochemical box modeling in support of investigating the underlying nature of O3 formation over the city and the roles of precursors emitted from sources. The year 2006 was considered and two single-day episodes (January 29 and February 14) were chosen for simulations. It was found that, in the city, the industrial sector is the largest emissions contributor for every O3 precursor (i.e., NO(x), non-methane volatile organic compounds or NMVOC, and CO), followed by on-road mobile group. Fugitive NMVOC is relatively large, emitted mainly from oil refineries and tank farms. Simulated results acceptably agree with observations for daily maximum O3 level in both episodes and evidently indicate the VOC-sensitive regime for O3 formation. This regime is also substantiated by morning NMVOC/NO(x) ratios observed in the city. The corresponding O3 isopleth diagrams suggest NMVOC control alone to lower elevated O3. In seeking a potential O3 control strategy for the city, a combination of brute-force sensitivity tests, an experimental design, statistical modeling, and cost optimization was employed. A number of emission subgroups were found to significantly contribute to O3 formation, based on the February 14 episode, for example, oil refinery (fugitive), tank farm (fugitive), passenger car (gasoline), and motorcycle (gasoline). But the cost-effective strategy suggests control only on the first two subgroups to meet the standard. The cost of implementing the strategy was estimated and found to be small (only 0.2%) compared to the gross provincial product generated by the entire province where the city is located within. These findings could be useful as a needed guideline to support O3 management for the city. IMPLICATIONS: Elevated O3 in the urban and industrial city of Chon Buri needs better understanding of the problem and technical guidelines for its management. With a city-specific emission inventory and air quality modeling, O3 formation was found to be VOC sensitive, and a cost-effective control strategy developed highlights fugitive emissions from the industrial sector to be controlled.