Quantifying Benefit-Risk Trade-Offs Toward Prophylactic Treatment Among Adult Patients With Hemophilia A in China: Discrete Choice Experiment Study.

BACKGROUND: Hemophilia A is a chronic condition that requires meticulous treatment and management. Patient preferences for prophylactic treatment can substantially influence adherence, outcomes, and quality of life, yet these preferences remain underexplored, particularly in China. OBJECTIVE: This study aimed to investigate the preferences for prophylactic treatment among Chinese adult patients with hemophilia A without inhibitors, considering clinical effectiveness, side effects, dosing mode, and dosing frequency. METHODS: A discrete choice experiment was used to elicit patient preferences for prophylactic treatment of hemophilia. The study was conducted across 7 provinces in China with socioeconomic and geographical diversity. Subgroup analysis was performed according to education level, geographic location, and treatment type, alongside the exploration of benefit-risk trade-offs. RESULTS: A total of 113 patients completed the discrete choice experiment questionnaire, and we included 102 responses for analysis based on predetermined exclusion criteria. The study found that patients prioritized reducing annual bleeding times and avoiding the risk of developing inhibitors over treatment process attributes. Subgroup analysis revealed that lower-educated patients and those from rural areas attached more importance to the dosing mode, likely due to barriers to self-administration. Patients demonstrated a clear understanding of benefit-risk trade-offs, exhibiting a willingness to accept an increased risk of developing inhibitors for improved clinical outcomes. CONCLUSIONS: This study provides valuable insights into the preferences of patients with hemophilia A for prophylactic treatment in China. Understanding these preferences can enhance shared decision-making between patients and clinicians, fostering personalized prophylactic treatment plans that may optimize adherence and improve clinical outcomes.

Causal effects of maternal exposure to PM2.5 during pregnancy on depression symptoms in adolescence: Identifying vulnerable windows and subpopulations in a national cohort study.

Few studies have examined the causal relationship between chronic exposure to air pollutants during pregnancy and depression in adolescent offspring. In addition, it has not been investigated whether exposure is most harmful to adolescents in certain populations and at certain stages of pregnancy. A total of 1975 adolescents from 1632 families from the China Family Panel Study, a representative national longitudinal cohort, were included in this study. We used high-resolution satellite retrieval data to assess the PM2.5 exposure of mothers during pregnancy. Specifically, we employed a two-stage instrumental variable model (IV-2SLS) within the counterfactual causal inference framework, and selected and validated appropriate instruments, thereby mitigating potentially biased results arising from bi-direction between dependent and independent variables. This approach allowed us to explore the causal relationship between maternal PM2.5 exposure during pregnancy and adolescent depression symptoms. The endogeneity of air pollution during pregnancy and the need for a causal model were suggested by the results of the model comparisons. Using the IV-2SLS model, we found that maternal exposure to PM2.5 during pregnancy exacerbates depressive symptoms in the offspring during adolescence (ß = 0.2, 95% CI: 0.05-0.34). We also found that exposure during the first trimester may cause greater harm. Adolescents with low household income, being male, irregular exercise habits, living in rural areas, and having mothers with poorer mental status may be more vulnerable. The findings suggest that maternal exposure to PM2.5 during pregnancy may have a negative impact on the depression symptoms of offspring in adolescence and that more attention should be paid to vulnerable populations and the window of vulnerability.

Identifying the causal effects of long-term exposure to PM2.5 and ground surface ozone on individual medical costs in China-evidence from a representative longitudinal nationwide cohort.

BACKGROUND: There is little evidence on whether PM2.5 and ground surface ozone have consistent effects on increased individual medical costs, and there is a lack of evidence on causality in developing countries. METHODS: This study utilized balanced panel data from 2014, 2016, and 2018 waves of the Chinese Family Panel Study. The Tobit model was developed within a counterfactual causal inference framework, combined with a correlated random effects and control function approach (Tobit-CRE-CF), to explore the causal relationship between long-term exposure to air pollution and medical costs. We also explored whether different air pollutants exhibit comparable effects. RESULTS: This study encompassed 8928 participants and assessed various benchmark models, highlighting the potential biases from failing to account for air pollution endogeneity or overlooking respondents without medical costs. Using the Tobit-CRE-CF model, significant effects of air pollutants on increased individual medical costs were identified. Specifically, margin effects for PM2.5 and ground-level ozone signifying that a unit increase in PM2.5 and ground-level ozone results in increased total medical costs of 199.144 and 75.145 RMB for individuals who incurred fees in the previous year, respectively. CONCLUSIONS: The results imply that long-term exposure to air pollutants contributes to increased medical costs for individuals, offering valuable insights for policymakers aiming to mitigate air pollution's consequences.

Assessing the causal effect of long-term exposure to air pollution on cognitive decline in middle-aged and older adults - Empirical evidence from a nationwide longitudinal cohort.

Air pollution remains a risk factor for the global burden of disease. Middle-aged and older people are more susceptible to air pollution because of their declining physical function and are more likely to develop diseases from long-term air pollution exposure. Studies of the effects of air pollution on cognitive function in middle-aged and older adults have been inconsistent. More representative and definitive evidence is needed. This study analysed data from the Chinese Family Panel Study, an ongoing nationwide prospective cohort study, collected in waves 2014, 2016 and 2018. Rigorously tested instrument was selected for analysis and participants' PM2.5 and instrument exposures were assessed using high-precision satellite data. The causal relationship between long-term exposure to air pollution and poor cognitive function in middle-aged and older adults was investigated using the Correlated Random Effects Control Function (CRE-CF) method within a quasi-experimental framework. This study included a total of 7042 participants aged 45 years or older. A comparison of CRE-CF with other models (OLS model, ordered probit model, and ordered probit-CRE model) demonstrated the necessity of using CRE-CF given the endogeneity of air pollution. The credibility and validity of the instrumental variable were verified. In the CRE-CF model, long-term exposure to PM2.5 was found to accelerate cognitive decline in middle-aged and older adults (coefficients of -0.159, -0.336 and -0.244 for the total cognitive, verbal and mathematical scores, respectively). Taken together, these results suggest that chronic exposure to ambient air pollution is associated with cognitive decline in middle-aged and older adults, which highlights the need for appropriate protective policies.

Long-term exposure of PM2.5 components on the adults' depressive symptoms in China - Evidence from a representative longitudinal nationwide cohort.

In recent years, there is growing evidence that long-term exposure to fine particulate matter (PM2.5) is associated with depressive symptoms. However, little is known about the individual effects of PM2.5 components, particularly in low-income and middle-income countries. We investigated the association between long-term exposure to major components of PM2.5 and worsening depressive symptoms in Chinese adults based on a large, long-term, nationally representative, population-based prospective cohort. Our data were derived from China Family Panel Study (CFPS) wave 2012, 2016 and 2018 and a long-term (2010-2019) high-resolution PM2.5 components dataset covering the whole China. We assessed respondents' depressive symptoms using standardized scales and applied advanced Fixed-effect ordered logit model (FE-ologit) to capture the ordinal nature of respondents' depressive symptoms and control for individual-specific and time-invariant effects to investigate their associations with PM2.5 components. We included 9503 respondents and the FE-ologit model results indicated that the odds ratio of increase per standard unit was 1.118 (95 % CI: 1.020, 1.225) for black carbon, 1.134 (95 % CI: 1.028, 1.252) for organic matter, 1.127 for ammonium (95 % CI: 1.011, 1.255), 1.107 for nitrate (95 % CI: 0.981, 1.248), and 1.117 for sulfate (95 % CI: 1.020, 1.224). Our study suggests that long-term exposure to PM2.5 components is significantly associated with worsening of depressive symptoms, and that different components may have different toxicity. Reducing PM2.5 emissions, especially the major sources of organic matter and ammonium, may reduce the burden of depressive symptoms in Chinese adults.

Causal effects of air pollution on mental health among Adults--An exploration of susceptible populations and the role of physical activity based on a longitudinal nationwide cohort in China.

Long-term exposure to air pollutants is likely to be associated with mental disorders, but relevant studies remain limited and inconsistent, and evidence to assess causality is particularly lacking, especially in developing countries. In addition, there are few studies on the role of physical activity in this relationship. We investigated the causal relationship between air pollutant exposure and mental health among Chinese adults and whether physical activity could play a positive role in this relationship. Using the balanced panel data for 2014 and 2016 from the China Family Panel Study, a representative Chinese national cohort study, we selected and validated appropriate instrumental variable to explore the causal relationship between air pollution and mental health and explored the moderating effect of physical activity using an instrumental variable fixed effects model (IVFE) in a counterfactual causal inference framework. PM2.5 and ground surface ozone were selected as proxies for different types of air pollutants and extended the interpretability by studying them for populations with different characteristics. A total of 21,944 participants were included in this study. In the IVFE model, we found that both PM2.5 and ground surface ozone significantly negatively affected mental health, and that habitual physical activity counteracted this negative effect regardless of different types of air pollution. We also found that the findings held for adults with different characteristics. The findings suggest that habitual physical activity may offset the deterioration of mental health in adults in developing countries due to air pollution, regardless of age, gender, income, and the presence of chronic diseases.

Reduction of inter-observer variability using MRI and CT fusion in delineating of primary tumor for radiotherapy in lung cancer with atelectasis.

Purpose: To compare the difference between magnetic resonance imaging (MRI) and computed tomography (CT) in delineating the target area of lung cancer with atelectasis. Method: A retrospective analysis was performed on 15 patients with lung cancer accompanied by atelectasis. All positioning images were transferred to Eclipse treatment planning systems (TPSs). Six MRI sequences (T1WI, T1WI+C, T1WI+C Delay, T1WI+C 10 minutes, T2WI, DWI) were registered with positioning CT. Five radiation oncologists delineated the tumor boundary to obtain the gross tumor volume (GTV). Conformity index (CI) and dice coefficient (DC) were used to measure differences among observers. Results: The differences in delineation mean volumes, CI, and DC among CT and MRIs were significant. Multiple comparisons were made between MRI sequences and CT. Among them, DWI, T2WI, and T1WI+C 10 minutes sequences were statistically significant with CT in mean volumes, DC, and CI. The mean volume of DWI, T2WI, and T1WI+C 10 minutes sequence in the target area is significantly smaller than that on the CT sequence, but the consistency is higher than that of CT sequences. Conclusions: The recognition of atelectasis by MRI was better than that by CT, which could reduce interobserver variability of primary tumor delineation in lung cancer with atelectasis. Among them, DWI, T2WI, T1WI+C 10 minutes may be a better choice to improve the GTV delineation of lung cancer patients with atelectasis.

Does long-term exposure to air pollution impair physical and mental health in the middle-aged and older adults? - A causal empirical analysis based on a longitudinal nationwide cohort in China.

The world is aging, posing a challenge to public health. Air pollution is increasingly recognized as an important environmental risk factor, with effects on both physical and mental health. Considering the vulnerability of older adults, they tend to have more prevalent comorbidities that may lead to broader consequences. However, evidence to comprehensively assess the causal effects of long-term air pollution exposure on the physical and mental health of older adults remains limited and inconsistent, especially in developing countries. The longitudinal data from the Chinese Family Panel Study (a representative Chinese national cohort study) for 2012, 2014, 2016, and 2018 were included in this study. The Correlated Random Effects Control Function method (CRE-CF) in a counterfactual causal inference framework was employed to explore the causal relationship between long-term exposure to air pollution and physical and mental health and self-rated health status in middle-aged and older adults, considering the ordered categorical nature of health outcomes. The appropriate instrumental variable was selected and validated. This study included 5846 participants aged >45 years in 2012. In the CRE-CF model for activities of daily living (ADLs, positively associated with physical health), subjective memory impairment (SMI, negatively associated with memory health) and self-rated health status in middle-age and older adults, the coefficient of PM2.5 is -0.069, 0.102, and 0.106 respectively, and all statistically significant at 5% level, which suggests that chronic exposure to air pollutants had significant negative effects on ADLs, SMI and self-rated health in middle-aged and older adults. The findings suggest that long-term exposure to air pollutants can impair the health of middle-aged and older adults across the board, including physical and mental health. In the context of an aging society, the findings of this study will provide tremendous implications for the authority to protect them from damage caused by long-term exposure to air pollutants.

Assessing the causal effects of long-term exposure to PM2.5 during pregnancy on cognitive function in the adolescence: Evidence from a nationwide cohort in China.

The effects of air pollution on adolescents need further consideration. Although there is evidence that maternal exposure to air pollution may affect the cognitive function of offspring, relevant studies remain limited and inconsistent, with a lack of studies assessing the causal effects and evidence from developing countries. Using data from Chinese Family Panel Studies, a representative Chinese nationwide cohort study, OLS combined with instrumental variable + two-stage least square (IV+2SLS) was used to explore the causal effects of exposure to PM2.5 concentrations during pregnancy on the cognitive function of offspring when they become adolescents. After detailed argumentation and multiple testing, Planetary Boundary Layer Height (PBLH) and Surface Pressure (SP) were selected as the instrumental variables for this study. One thousand five hundred fifty-five adolescents participated in this study, with a mean age of 13.3 years (sd = 2.3). There were 706 females (45.4%), the mean maternal PM2.5 exposure concentration was 64.9 µg/m3, and recorded a mean cognitive function score of 38.1 (sd = 9.4). The OLS results found that maternal exposure to air pollution increased cognitive function in offspring adolescents, corroborating the presence of endogeneity. Multi-domain knowledge, the results of the weak instrumental variable assessments of F-tests (F = 237 > 10) and Stock-yogo tests (minimum eigenvalue statistic = 153.16 > 16.38), and the results of the Hansen J overidentification test (p > 0.05) verified the plausibility and validity of the instrumental variables. The IV+2SLS results, following causal modeling, showed that PM2.5 exposure during pregnancy impairs the cognitive ability of offspring adolescents (ß = -0.040, p < 0.05). Robustness tests also validated the results. This study provides important policy implications for developing countries on protecting their adolescents and reminds parents that the protection of adolescents from air pollution should begin from conception.

Heterogeneous effects of hospital competition on inpatient expenses: an empirical analysis of diseases grouping basing on conditions' complexity and urgency.

BACKGROUND: Multiple pro-competition policies were implemented during the new round of healthcare reform in China. Differences in conditions' complexity and urgency across diseases associating with various degrees of information asymmetry and choice autonomy in the process of care provision, would lead to heterogeneous effects of competition on healthcare expenses. However, there are limited studies to explore it. This study aims to examine the heterogeneous effects of hospital competition on inpatient expenses basing on disease grouping according to conditions' complexity and urgency. METHODS: Collecting information from discharge data of inpatients and hospital administrative data of Sichuan province in China, we selected representative diseases. K-means clustering was used to group the selected diseases and Herfindahl-Hirschman Index (HHI) was calculated based on the predicted patient flow to measure the hospital competition. The log-linear multivariate regression model was used to examine the heterogeneous effects of hospital competition on inpatient expenses. RESULTS: We selected 19 representative diseases with significant burdens (more than 1.1 million hospitalizations). The selected diseases were divided into three groups, including diseases with highly complex conditions, diseases with urgent conditions, and diseases with less complex and less urgent conditions. For diseases with highly complex conditions and diseases with urgent conditions, the estimated coefficients of HHI are mixed in the direction and statistical significance in the identical regression model at the 5% level. For diseases with less complex and less urgent conditions, the coefficients of HHI are all positive, and almost all of them significant at the 5% level. CONCLUSIONS: We found heterogeneous effects of hospital competition on inpatient expenses across disease groups: hospital competition does not play an ideal role in reducing inpatient expenses for diseases with highly complex conditions and diseases with urgent conditions, but it has a significant effect in reducing inpatient expenses of diseases with less complex and less urgent conditions. Our study offers implications that the differences in condition's complexity and urgency among diseases would lead to different impacts of hospital competition, which would be given full consideration when designing the pro-competition policy in the healthcare delivery system to achieve the desired goal.

The Comparison Between Different Hospital Market Definition Approaches: An Empirical Analysis of 11 Representative Diseases in Sichuan Province, China.

Objective: This study aims to provide empirical evidence for the controversy about whether the inference is consistent if alternative hospital market definition methods are employed, and for which definition method is the best alternative to the predicted patient flow approach. Data sources: Collecting data from the discharge data of inpatients and hospital administrative data of Sichuan province in China in the fourth quarter of 2018. Study Design: We employed Herfindahl-Hirschman Index (HHI) as the proxy of market competition used as an example to measure the hospital market structure. Correlation coefficients of HHIs based on different definition methods were assessed. The corresponding coefficient of each HHI estimated in identical regression models was then compared. In addition, since the predicted patient flow method has been argued by the literature of its advantages compared with the previous approaches, we took the predicted patient flow as a reference to compare with the other approaches. Data Extraction Methods: We selected the common diseases with a significant burden, and 11 diseases were included (902,767 hospitalizations). Principal Findings: The correlation coefficients of HHIs based on different market definition methods are all significantly greater than 0, and the coefficients of HHIs are different in identical regression models. Taking the predicted patient flow approach as a reference, we found that the correlation coefficients between HHIs based on fixed radius and predicted patient flow approach is larger than others, and their parameter estimates are all consistent. Conclusion: Although the HHIs based on different definition methods are significantly and positively correlated, the inferences about the effectiveness of market structure would be inconsistent when alternative market definition methods are employed. The fixed radius would be the best alternative when researchers want to use the predicted patient flow method to define the hospital market but are hindered by the data limitations and computational complexity.

Hospital market competition and health technology diffusion: An empirical study of laparoscopic appendectomy in China.

The evidence about the role of hospital market competition on health technology diffusion in developing countries is scarce. In this study, we examined the association between hospital market competition and the diffusion of health technologies in China's healthcare system. Laparoscopic appendectomy, a minimally invasive surgery for patients with acute appendicitis, was selected as a representative of cost-effective health technology. The inpatient discharge dataset linked to the annually hospital administrative data and to the demographic and socioeconomic data were used. A total of 261,922 patients who were diagnosed with acute appendicitis and had received either open appendectomy or laparoscopic appendectomy at 820 hospitals in Sichuan, China between 2017 and 2019 were included in our analyses. Our outcome measure was the use of laparoscopic appendectomy during hospitalization. We accounted for the endogeneity of hospital competition measures using the Herfindahl-Hirschman Index calculated by predicted patient flows. Controlling for the observable patient, hospital and region characteristics, multivariate logistic regression was performed to model the association between hospital competition and the diffusion of laparoscopic appendectomy. The rapid diffusion of laparoscopic appendectomy over the study period and the substantial variation in use across regions and hospitals were observed. The regression results showed that laparoscopic appendectomy diffused faster in the markets where hospitals faced more competition. Our findings suggest that the diffusion of laparoscopic appendectomy is not only driven by medical factors but also nonmedical factors like hospital market competition. Our study provides new evidence on the association between market structure and technology diffusion in China's hospital market and offers the implications of appropriate technologies diffusion in health for policymakers.

Does hospital competition lead to medical equipment expansion? Evidence on the medical arms race.

With the implementation of a series of pro-competition policies in China, the hospital market competition has been intensified dramatically over the past decade. Based on previous literature, such competition is very much likely to bring about an upgoing trend in the promotion and expansion of medical facilities among hospitals as an essential strategy for attracting patients, which is known as Medical Arms Race (MAR). Comprehensive evaluations have been conducted by previous studies on the consequences of the MAR, which, however, merely provided inadequate empirical evidence on the relationship between hospital competition and MAR. Utilizing the variations in hospital competition across various regions and through different time periods in Sichuan Province as a prototype representative of the nationwide situation, a dynamic panel data model was established and adopted in this study for investigating whether intensified hospital competition had resulted in the expansion of medical facilities in China during the corresponding time period. The geopolitical boundaries and Herfindahl-Hirschman Index (HHI) were respectively employed to define the hospital market and measure the competition degree. We found that a 10% reduction in HHI is associated with an 8.79% increase in regional total costs of advanced medical equipment per capita, suggesting that hospital competition would lead to medical equipment expansion. Our results provide novel evidence on MAR which is particularly applicable for the healthcare system in China, providing suggestions for nationwide healthcare reform in order to mitigate potential negative outcomes induced by the implementation of pro-competition policies.

The association of hospital competition with inpatient costs of stroke: Evidence from China.

The main purpose of this article is to analyze the association between hospital competition and stroke inpatient costs. Stroke is selected as the representative of a class of diseases characterized by asymmetric information and lack of autonomy of service choice. A total of 98,061 observations are selected from a medical record dataset in the Sichuan Province. The fixed radius approach of 15 miles and Herfindahl-Hirschman Index (HHI) are employed to define the hospital market and measure the competition intensity, respectively. The log-linear multivariate regression model is used to analyze the association between competition and stroke inpatient costs. The results show that every 10% increase in competition (0.1 unit decrease of HHI value) associated with an average 2.38% decrease in stroke inpatient total costs. We also explore the relationship between competition and sub-group costs of stroke inpatient, finding that hospitals facing more competition incur lower treatment, drug, and consumable costs. Further analysis shows that for-profit, private, and low-level hospitals are more sensitive when facing changes in market competition degree. Our study offers empirical evidence to support the introduction of pro-competition in China's new round of national health reform and provide implications for other countries facing similar health care challenges.

The Effect of China's National Essential Medicine Policy on Health Expenses: Evidence From a National Study.

To increase use of medical service across the country, the Chinese government has tried to improve equity in health care access and reduce patients' medical expenses. For this purpose, the National Essential Medicine Policy (NEMP) was introduced in 2009 to mandate the distribution of medicines to health care facilities at a low cost and without profit. This study aims to evaluate the effect of the essential medicine policy on average per-visit expenses for outpatient and inpatient services. The annual national surveillance system data covering all the grassroots-level primary health care facilities (PHFs) in 2675 counties and 31 provinces in China during 2008 to 2012 were used in this study. The 4-level hierarchical random effects models were utilized to deal with possible dose-response effects of the policy and possible variations of such effects at the provincial, county, and facility levels. Our research findings suggest that the NEMP had positive effects in reducing both outpatient and inpatient expenses at grassroots level, and the policy effects tended to be greater as the exposure time increased. This study provides implications on reforming China's health system and its medicine cost control policies.