Instrumental Variable Analysis Research Articles

Perioperative outcomes of esophagectomy after doublet versus docetaxel‐based triplet neoadjuvant chemotherapy in older patients: A nationwide inpatient database study in Japan

AbstractBackgroundAlthough docetaxel‐based triplet neoadjuvant chemotherapy has yielded promising results for locally advanced esophageal cancer, there are concerns that the triplet regimen can increase perioperative adverse events in older patients. This retrospective study assessed the perioperative outcomes following doublet or docetaxel‐based triplet chemotherapy and esophagectomy in older patients.MethodsThe data of patients aged 70–79 years who received cisplatin and 5‐fluorouracil (CF) or docetaxel, cisplatin, and 5‐fluorouracil (DCF) before esophagectomy were extracted from a nationwide Japanese inpatient database (April 2012–March 2022). The primary outcomes were major and respiratory complications. The secondary outcomes included anastomotic leakage, 30‐day unplanned readmission, and 30‐ and 90‐day mortality. Analyses were conducted using overlap propensity score weighting, propensity score matching, and instrumental variable methods to adjust for potential confounders.ResultsOf 5229 eligible patients, 3457 (66%) and 1772 (34%) patients received neoadjuvant CF and DCF, respectively. Major and respiratory complications occurred in 5229 (40%) and 1388 (27%) patients, respectively. After overlap weighting, DCF was not associated with a higher frequency of major (odds ratio 0.99 [95% confidence interval 0.87–1.12]) and respiratory complications (odds ratio 1.04 [0.90–1.19]) compared with CF. The frequencies of anastomotic leakage, 30‐day unplanned readmission, and 30‐ and 90‐day mortality did not differ between the groups. Propensity score matching and instrumental variable analyses yielded similar results.ConclusionsNeoadjuvant DCF was not associated with a higher frequency of perioperative adverse events compared with CF after esophagectomy in patients aged 70–79 years.

Effectiveness of Oral Prophylactic Antibiotics for Diagnostic Bronchoscopy: A Nationwide Database Study.

Although the guidelines generally omit routine antibiotic prophylaxis for diagnostic bronchoscopy, this recommendation is primarily based on studies with relatively small sample sizes conducted at single institutions. Moreover, the applicability of recent technical and procedural advancements to these guidelines remains uncertain. To evaluate whether oral prophylactic antibiotic administration for diagnostic bronchoscopy reduces post-bronchoscopy infections among non-infectious diseases in the current setting. Using the Diagnosis Procedure Combination database, a national inpatient database in Japan, we identified patients who underwent diagnostic bronchoscopy with or without oral prophylactic antibiotics between April, 2020 and March, 2022. We employed the propensity score-stabilized inverse probability of treatment weighting and instrumental variable analyses to compare post-bronchoscopy infections between the groups. Stratified analyses were also conducted based on patient profiles and antibiotic types. A total of 68,660 eligible patients were divided into prophylaxis (N=10,426) and no prophylaxis (N=58,234) groups. Post-bronchoscopy infections were observed in 612 patients (0.89%). The stabilized inverse probability of treatment weighting analysis showed that the prophylactic group was significantly associated with a decrease in post-bronchoscopy infections (odds ratio, 0.60; 95% confidence interval, 0.45 to 0.80). The instrumental variable analysis showed similar results (odds ratio, 0.50; 95% confidence interval, 0.34-0.74). Oral antibiotic prophylaxis was associated with reduction in post-bronchoscopy infection in patients who were older than 70 years, underwent bronchoscopy for malignancy, underwent biopsy or bronchoalveolar lavage, or received aminopenicillin or fluoroquinolone for prophylaxis. Our findings suggest a potential role for prophylactic antibiotics in reducing post-bronchoscopy infections among non-infectious cases. While prophylactic antibiotics may help prevent these infections, their use should be carefully considered in relation to individual patient profiles and the specific antibiotics being administered.

Surgical Approach and Variation in Long-Term Survival Following Colorectal Cancer Surgery Using Instrumental Variable Analysis

Objective: The study aimed to determine whether increased use of minimally invasive surgical approaches, compared with open, improves long-term survival after colon and rectal cancer resections. Background: Existing prospective and observational data comparing surgical approach for colon and rectal cancer are limited by selection bias, necessitating better approaches for causal inference to understand the relationship between surgical approach and long-term survival. Methods: We included colon and rectal cancer patients who underwent colon or rectal resection from the American College of Surgeons National Cancer Database between 2011 and 2018. Using an instrumental variable (IV) approach, we accounted for measured and unmeasured differences between patients undergoing colon or rectal cancer resection based on operative approach – robotic, laparoscopic, or open. The IV used in this study was rate of robotic-assisted colon and rectal cancer surgery within 81 different hospital regions based on US Census region and rurality during the 12 months before each patient’s operation. Proportional hazard modeling was used to estimate risk-adjusted mortality rates. Results: There were 326,406 colon and 96,979 rectal cancer patients included in this study. The risk-adjusted 5-year cumulative incidence of mortality for colon and rectal cancer was highest for patients who underwent open approaches (35.73 [95% confidence interval {CI}: 35.37–36.1] and 39.27 [95% CI: 28.44–30.13], respectively), compared with lower mortality for those undergoing laparoscopic (28.91 [95% CI: 28.55–29.27] and 22.93 [95% CI: 22.11–23.78], respectively) and robotic approaches (26.39 [95% CI: 24.51–28.42] and 19.77 [95% CI: 17.32–22.43], respectively). Growth in utilization of minimally invasive approaches outpaced improvements in long-term survival. Conclusions: Patients undergoing minimally invasive surgical approaches for colon and rectal cancer had improved long-term survival. However, long-term survival changes did not correlate with the large expansion of minimally invasive approaches, which suggests that growing these approaches is not a viable strategy to improve long-term patient outcomes.

Exploring the influence of medical staffing and birth volume on observed-to-expected cesarean deliveries: a panel data analysis of integrated obstetric and gynecological departments in Germany.

Cesarean deliveries account for approximately one-third of all births in Germany, prompting ongoing discussions on cesarean section rates and their connection to medical staffing and birth volume. In Germany, the majority of departments integrate obstetric and gynecological care within a single department. The analysis utilized quality reports from German hospitals spanning 2015 to 2019. The outcome variable was the annual risk-adjusted cesarean section ratio-a metric comparing expected to observed cesarean sections. Explanatory variables included annual counts of physicians, midwives, and births. To account for case number-related staffing variations, full-time equivalent midwife and physician staff positions were normalized by the number of deliveries. Uni- and multivariate panel models were applied, complemented by multiple instrument variable analyses, including two-stage least square and generalized method of moments models. Incorporating data from 509 integrated obstetric departments and 2089 observations, representing 2,335,839 deliveries with 720,795 cesarean sections (over 60% of all inpatient births in Germany), multivariate model with fixed effects revealed a statistically significant positive association between the number of physicians per birth and the risk-adjusted cesarean section ratio (0.004, p = 0.004). Two-stage least square instrument variable analysis (0.020, p < 0.001) and a system GMM estimator models (0.004, p < 0.001) validated these results, providing compelling evidence for a causal relationship. The study established a robust connection between the number of physicians per birth and the risk-adjusted cesarean section ratio in integrated obstetric and gynecological departments in Germany. While the cause of the effect remains unclear, one possible explanation is a lack of specialization within these departments due to the combined provision of both obstetric and gynecological care.

Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses.

This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period. Cardiovascular disease (myocardial infarction or stroke) was identified based on information regarding diagnosis, medical procedures, and drug codes. Facility-level prescription preference for romosozumab was used as an instrumental variable, defined as the proportion of romosozumab prescribed at the patient's facility within 90days prior to the index date. Of the 59 694 included prescriptions, 8808 were for romosozumab and 50 886 were for bisphosphonates. The mean age in the romosozumab group was higher than that in the bisphosphonates group (80.5 vs. 78.2years, respectively), and most patients were females (85.3 vs. 80.2%, respectively). The incidence of cardiovascular disease within 1year of prescription was 12.3 per 100 person-years for romosozumab versus 11.4 for bisphosphonates (unadjusted incidence rate ratio: 1.08, 95% confidence interval: 1.00-1.18). An instrumental variable analysis using the two-stage residual inclusion method yielded a hazard ratio of 1.30 (95% confidence interval: 0.88-1.90) for romosozumab compared with bisphosphonates over 1year. Although possibly underpowered, this study showed that no definitive evidence of increased cardiovascular risk associated with romosozumab use compared with bisphosphonates was observed in patients with osteoporosis. These findings should be further validated by larger pharmacoepidemiological studies to alleviate clinicians' concerns about romosozumab's safety.

What works in prison? Revisiting reintegration programs in Mexico

This paper explores the classic questions of whether social reintegration programs are successful and, if so, which correctional program yields better results. We seek to respond to these questions with information gathered from the most recent national incarcerated population survey in Mexico, based on the imprisoned persons’ perspectives regarding their expectations for social reintegration and prison reentry. The empirical strategy consisted of two steps: identifying the characteristics of programs considered useful for social reintegration and exploring the association between perceptions of these tools and expectations for prison reentry. A propensity score matching analysis and the estimation of two classification methods were implemented, while an instrumental variables analysis was used for the latter. Results show that incarcerated persons perceive those programs aimed at providing them with work skills and furthering their education to be more helpful. These are also associated with a decreased expectation of prison reentry.

Do Co‐Opted Boards Lead to Managerial Obfuscation? Evidence From the 10‐K Report Readability

ABSTRACTThis paper examines the relationship between board co‐option and managerial obfuscation captured through linguistic complexity of 10‐K reports. Using 7912 US firm‐year observations from 2003 to 2018, we find that firms with a higher proportion of co‐opted directors obfuscate the readability of the 10‐K reports. The findings are robust across various variable definitions, sample specifications and remain significant after addressing endogeneity concerns through multiple approaches, including lead‐lag regression, entropy balancing, instrumental variable analysis, the system GMM, and difference‐in‐difference estimations. Further analysis reveals that our main finding is driven by firms with weak internal (i.e., those with high CEO power and low board meeting attendance) and external (i.e., those with low institutional ownership and less analyst following) monitoring. The paper provides useful policy insights and implications for investors, regulators, and policymakers.

Risk of Suicide Among Patients With Major Physical Disorders Considering Comorbidities of Mental Disorders: An Instrumental Variable Analysis

Suicide is an important health concern. Excepting cancer, the association between physical disorders and suicidal risk is comparatively less explored. Instrumental variable analysis has been suggested as a powerful technique to deal with possible bias caused by unmeasured confounders in observational research. This population-based study set out to assess the suicidal risk of patients with major physical disorders by employing the instrumental variable analysis. Data were retrieved from the National Health Insurance Research Database and the Death Certification Registry in Taiwan (years 2010–2018). The Cox proportional hazards model with an instrumental variable estimator was performed, adjusting for comorbidities of mental disorders and other covariates. Analytical results showed that compared to their counterparts, patients with major physical disorders had an elevated risk of death by suicide within one year and three years after diagnosis of physical illness. Only did epilepsy not demonstrate a statistically significant impact on the risk of suicide.

On the Statistical Analysis of Experiments With Manipulation Checks

Psychologists are often interested in the effect of an internal state, such as ego depletion, that cannot be directly assigned in an experiment. Instead, they assign participants to a manipulation intended to produce this state and use manipulation checks to assess the manipulation’s effectiveness. In this article, I discuss statistical analyses for experiments in which researchers are primarily interested in the average treatment effect (ATE) of the target internal state rather than that of the manipulation. Often, researchers estimate the association of the manipulation itself with the dependent variable, but this intention-to-treat (ITT) estimator is typically biased for the ATE of the target state, and the bias could be either toward the null (conservative) or away from the null. I discuss the fairly stringent assumptions under which this estimator is conservative. Given this, I argue against the status-quo practice of interpreting the ITT estimate as the effect of the target state without any explicit discussion of whether these assumptions hold. Under a somewhat weaker version of the same assumptions, one can alternatively use instrumental-variables (IVs) analysis to directly estimate the effect of the target state. IVs analysis complements ITT analysis by directly addressing the central question of interest. As a running example, I consider a multisite replication study on the ego-depletion effect, in which the manipulation’s partial effectiveness led to criticism and several reanalyses that arrived at varying conclusions. I use IVs analysis to directly account for the manipulation’s partial effectiveness; this corroborated the replication authors’ reported null results.

Evaluating Harms Associated with Prolonged Antibiotic Duration of Therapy in Community Dwelling Older Adults: A Cohort Study using Instrumental Variable Analysis.

Shorter courses of antibiotic therapy are increasingly recommended to reduce antibiotic exposure. However quantifying the real-world impact of duration of therapy is hindered by bias common in observational studies. We aimed to evaluate the harms and benefits of longer versus shorter duration of therapy in older adults. This was a population-based cohort study using administrative health data from Ontario, Canada. We included outpatients aged 66 to 110 years who received a prescription for amoxicillin, cephalexin, and/or ciprofloxacin. Prescriptions were categorized as short (3-7 days) or long (8-14 days) duration. The primary outcome was a composite of antibiotic-related harms, including adverse reactions, Clostridioides difficile infection, and antibiotic resistance. The secondary outcome was a composite of safety measures including repeat antibiotic prescriptions, hospital visits and mortality. To reduce risk of bias, we used an instrumental variable analysis where the instrument was prescriber proportion of antibiotics that were long duration. Among 117,682 eligible patients, there was no difference in the primary harms outcome for patients receiving longer versus shorter courses of antibiotics (amoxicillin ORadj 0.99 (95%CI 0.84 to 1.15), cephalexin ORadj 1.11 (95%CI: 0.90 to 1.38), ciprofloxacin ORadj 0.94 (95%CI 0.74 to 1.20). Secondary safety outcomes were similar, with longer compared to shorter courses of antibiotic therapy (amoxicillin OR 1.01 (95%CI: 0.94 to 1.08), cephalexin OR 1.06 (95%CI 0.97 to 1.17), ciprofloxacin OR 0.99 (95%CI: 0.85 to 1.15)). In this instrumental variable analysis of community-dwelling older adults, longer antibiotic courses were not associated with an increased benefit or harm compared to shorter courses.

Causal Effect of Smoking and Cessation on Tooth Loss.

To estimate the causal effects of smoking and cessation on tooth loss using instrumental variable (IV) analysis. Data from the Behavioural Risk Factor Surveillance System (BRFSS), conducted from 1995 to 2006, 2008, 2010, and 2012 in 50 U.S. states and Washington DC, were merged with cigarette pack prices and smoking ban data from the CDC 'Tax Burden on Tobacco' and 'State Tobacco Activities Tracking and Evaluation' (STATE) System. Prices and bans served as IVs for ever smoking and cessation in a control function IV model for self-reported edentulism and loss of 6+ teeth. IV models were adjusted for age, sex, race/ethnicity, educational attainment, type 2 diabetes, state unemployment rates, state health expenditures, and state fixed effects. Ever smoking cigarettes increased the risk of edentulism by 2.6% (95% CI: 2.3%-2.8%) and the risk of loss of 6+ teeth by 10.7% (95% CI: 10.0%-11.3%). Smoking cessation reduced risks of edentulism and loss of 6+ teeth by 7.6% (95% CI: -7.8% to -742%) and 13.5% (95% CI: -13.7% to 13.3%), respectively. This study provides robust evidence that smoking increases tooth loss risk, while cessation significantly reduces it, emphasizing the oral health benefits of tobacco control policies.

A longitudinal analysis of the impact of multidimensional precarious employment on the mental health of men and women.

This study aimed to investigate the effect of precarious employment (PE) on the mental health of Australians. Building on previous research, we conceptualised PE as a multidimensional construct, accounted for gender differences in the associations, and our modelling strategy addressed the possibility of reverse causality bias. Data was pooled panel data from 15 waves (2005-2019) of the HILDA survey (n = 14,237). Using PCA, we created two multidimensional measures of PE: objective and subjective. Fixed effects (FE) regression models (attending to unmeasured time-invariant confounders) estimated the change in mental health associated with a change in PE, and instrumental variable (IV) analyses (addressing endogeneity bias) obtained an unbiased estimate of effect of subjective PE on mental health (with ordinary least squares (OLS) models as baseline). For both genders, FE models showed that objective and subjective multidimensional PE both had a strong negative association with mental health (stronger for subjective PE). IV analysis indicated OLS models overestimate the relationship between subjective PE and mental health for men but underestimate it for women, providing causal evidence that subjective PE is important for women's mental health. Overall, findings suggest that targeted PE policies have the potential to provide significant population mental health gains, particularly for working women.

Association of anaesthesia-directed sedation with unplanned discharge to a nursing home following non-ambulatory interventional radiology and endoscopic procedures: a retrospective cohort study.

Interventional radiology procedures and endoscopies are performed commonly worldwide, often necessitating pharmacological sedation to optimise patient comfort. It is unclear to what extent non-anaesthetists should provide procedural sedation. We studied adult patients who previously lived independently and underwent a non-ambulatory interventional radiology or gastroenterology procedure under anaesthetist-directed or non-anaesthetist-directed sedation at a large healthcare network. The primary outcomes were postprocedural adverse discharge to a nursing home and postprocedural duration of hospital stay. Among 22,868 patients included, 15,168 (66.3%) and 7700 (33.7%) underwent anaesthetist-directed sedation and non-anaesthetist-directed sedation, respectively. Of all patients receiving anaesthetist-directed sedation, 9.2% experienced adverse discharge to a nursing home compared with 21.3% undergoing non-anaesthetist-directed sedation. Anaesthetist-directed sedation was associated with reduced risk of adverse discharge to a nursing home (adjusted relative risk 0.54, 95%CI 0.45-0.63, p < 0.001, adjusted risk difference -4.6%, 95%CI -5.8 to -3.4, p < 0.001) and a shorter postprocedural duration of hospital stay (median (IQR [range]) 2 (1-6 [0-315]) days vs. 5 (2-12 [0-268]) days; adjusted model estimate 0.84, 95%CI 0.79-0.89, p < 0.001). The lower risk of adverse discharge to a nursing home and shorter duration of hospital stay in patients undergoing anaesthetist-directed sedation was reproduced in an instrumental variable analysis (adjusted risk difference -4.3%, 95%CI -8.4 to -0.1, p = 0.043; and -1.41 days, 95%CI -1.43 to -1.41 days, p < 0.001, respectively). Among patients undergoing anaesthetist-directed sedation the mean (SD) proportion of missing blood pressure measurements was lower (0.7 (4.9) % vs. 8.0 (14.6) %, p < 0.001), which mediated the effect of anaesthetist-directed sedation on adverse discharge. Among patients undergoing a non-ambulatory interventional radiology procedure or a gastrointestinal endoscopy, anaesthetist-directed sedation is associated with a reduced risk of adverse discharge to a nursing home and a shorter duration of hospital stay.

Exploring the influence of military experience directors on corporate governance: Evidence from Thai‐listed companies

AbstractDifferent board of directors (BODs) characteristics influence corporate strategy and performance. Essential attributes such as gender, education, and experience determine the preferences, opinions, and decisions to prioritize the strategy, which normally focuses on profitability. In 1997, during the Asian financial crisis, the Thai government and Thai firms adopted the sufficiency economy philosophy (SEP) approach to overcome financial catastrophes. This study explores the relationship between one distinct characteristic of the BOD, directors with direct and indirect military backgrounds, and the SEP performance. To minimize endogeneity and eliminate reverse causality, we apply a two‐stage least squares instrumental variable (2SLS‐IV) analysis. We find evidence supporting the upper echelons theory (UET), where the characteristics of the BOD, such as military experience, determine the organizational decision to enhance SEP performance.

The relationship between exercise habits and mental health among university students in China: a cross-sectional study based on instrumental variable analysis

BackgroundExercise habits significantly influence the mental health of university students. However, previous research has often neglected the endogeneity issues in this context, leading to biased estimates and limiting the ability to establish a clear causal relationship. This study aimed to address endogeneity issues and investigate the causal effect of exercise habits on the mental health of university students.MethodsThis cross-sectional study was conducted involving 1,120 university students from China. Data on demographic characteristics, exercise habits, and mental health were collected using both online and offline questionnaires. To evaluate the mental health benefits of exercise habits, we employed both the instrumental variable (IV) approach and ordinary least squares (OLS) regression.ResultsThe OLS estimates revealed a positive association between exercise habits and positive affect (β = 0.179, p < .001), life satisfaction (β = 0.134, p < .001), and self-actualization (β = 0.086, p < .001) among university students. The IV analysis indicated that exercise habits positively influenced positive affect (β = 0.263, p < .001), life satisfaction (β = 0.151, p = .006 < .01), and self-actualization (β = 0.102, p = .013 < .05). A comparison of the estimation results suggests that the OLS approach underestimates the mental health benefits of exercise habits.ConclusionsThis study provides preliminary causal evidence that exercise habits contribute to the promotion of mental health in university students. These findings offer valuable insights into potential preventive strategies for addressing mental health issues in this population through exercise interventions.

Evaluating the Policy Implications of Renewable Portfolio Standards on Grid Reliability in the United States: An Instrumental Variable Quantile Analysis

This paper investigates the influence of Renewable Portfolio Standards (RPSs) on the reliability of grids while considering key indicators, including the System Average Interruption Duration Index (SAIDI), System Average Interruption Frequency Index (SAIFI), and Customer Average Interruption Duration Index (CAIDI), both without and with the inclusion of Major Event Days (MEDs). The study adopted the instrumental variable quantile regression (IVQR) method for estimation purposes. The first-stage 2SLS results confirm the robustness and validity of the instruments used, including the Democrats’ Participation Rate, Real Average Household Income, and Renewable Energy Capacity, which show strong relevance and satisfy the conditions of homogeneity. Our findings demonstrated that the adoption of RPS policies has significantly decreased the interruption of power in all of the considered quantiles. The impact is more potent in states facing more severe reliability challenges. The results proved the important role of the policies of RPSs in improving the stability of grids in the context of states having relatively poor reliability. In summary, the obtained findings demonstrate significant insights related to the policies of renewable energy in the resilience of infrastructure. Finally, the findings suggest that the government authorities should promote the RPS as a tool for enhancing the performance of grids in different states.

Maternal Hypertension and Fecundability: A Population-Based Cohort Study.

The association of hypertension and blood pressure control with fecundability among women is not yet elucidated. The purpose of this study was to evaluate the hypothesis that maternal preconception hypertension would be associated with reduced fecundability and that blood pressure control could reduce excess risk. Using the National Free Preconception Checkup Projects in Guangdong Province, China, 1422 couples whose female partners had been diagnosed with hypertension and 997 703 reference couples whose female partners were without hypertension were included in this prospective cohort study. Fecundability was measured by time to pregnancy (TTP) and infertility (TTP >12 months). Compared with women without hypertension, those with controlled hypertension (time ratio, 1.47 [95% CI, 1.24-1.73]) or uncontrolled hypertension (time ratio, 1.59 [95% CI, 1.34-1.90]) were associated with prolonged TTP and increased risk of infertility (relative risk, 1.19 [95% CI, 1.09-1.31]; relative risk, 1.24 [95% CI, 1.14-1.34]). However, using instrumental variable analyses, there was no significant association between blood pressure control and TTP (time ratio, 0.68 [95% CI, 0.34-1.36]; P=0.270) or infertility (relative risk, 0.97 [95% CI, 0.70-1.34]; P=0.849) among women with hypertension. These results were consistent in the propensity score matching and inverse probability of treatment weighting analyses. Maternal hypertension, with or without controlled blood pressure, was independently associated with prolonged TTP and an increased risk of infertility. These findings may provide insights for the implementation of preconception hypertension screening and the design of future trials.

The relationship between amyloid‐β, plasma/brain GFAP, and neocortical tau: a Mendelian randomization study

AbstractBackgroundPlasma glial fibrillary acidic protein (GFAP) is associated with amyloid‐β (Aβ) and tau, but their causal relationships remain unclear. We used Mendelian randomization (MR; using genetic causal anchors to avoid reverse causation) to clarify the causal relationship between plasma/brain GFAP, Aβ, and tau.MethodsStudy participants are from two independent datasets: the Harvard Aging Brain Study (HABS) and the Religious Orders Study/the Rush Memory and Aging Project (ROSMAP) (Table 1). From HABS, we used baseline plasma GFAP (MSD platform) and Aβ (PiB PET cortical composite with partial volume correction [PVC]) and longitudinal inferior temporal (IT) tau (FTP PET SUVR with PVC) data. From ROSMAP, we used post‐mortem frontal cortex GFAP expression (RNA‐Seq) and midfrontal Aβ and tau burden (immunohistochemistry). We used linear regressions to assess the relationship between APOE ε4, GFAP, and Aβ. For MR, we performed instrumental variable (IV) analyses using APOE ε4 as the instrument. In HABS, we used linear mixed effect models to assess baseline GFAP ‐ longitudinal IT tau association. In ROSMAP, we assessed the cross‐sectional GFAP ‐ tau association (linear regression). All variables were standardized, and all models were adjusted for age and sex.ResultIn HABS, APOE ε4 carriers had higher baseline plasma GFAP (n=324, β=0.32, p=0.0025), but this association attenuated after adjusting for Aβ (p=0.42). MR suggested the causal effect of Aβ on plasma GFAP (2SLS β=0.40, p=0.0018). Baseline plasma GFAP predicted longitudinal increase in IT tau (n=187, β=0.051, p=1.9×10‐4); this association attenuated after adjusting baseline Aβ and its time‐interaction (p=0.16). We observed consistent results in ROSMAP: APOE ε4 carriers had higher frontal GFAP expression (n=609, β=0.26, p=0.0051), but this association attenuated after adjusting for Aβ (p=0.11). MR supported the causal effect of Aβ on brain GFAP (2SLS β=0.39, p=0.0085). The frontal GFAP– tau association (β=0.10, p=0.012) weakened after controlling for Aβ (p=0.50).ConclusionOur study leveraging APOE ε4 as a genetic causal anchor supports that Aβ is at the causal upstream of increased brain GFAP gene expression and elevated plasma GFAP (Figure 1A). By contrast, the neocortical tau – GFAP association is likely confounded by Aβ (Figure 1B‐C).

Extreme Weather, agricultural insurance and farmer's climate adaptation technologies adoption in China

We explore how farmers adjust their climate adaptation behaviors and participation in agricultural insurance in response to extreme weather events. A random effects model is constructed to clarify the relationships between extreme weather events, agricultural insurance and climate adaptation technologies (CAT). Using survey data from 622 farmers in China, Probit models and instrumental variable analysis show that extreme weather events significantly increase farmers' adoption of CAT and their participation in agricultural insurance. Furthermore, agricultural insurance significantly promotes farmers' adoption of CAT. Agricultural insurance influences the adoption of CAT through both substitutive and complementary effects, the complementary effects are more pronounced. Therefore, we recommended the continued promotion of CAT and agricultural insurance to strengthen farmers' resilience to extreme weather events.

Association of Observation Stays with Clinical Outcomes and Costs in Medicare: An Instrumental Variable Analysis.

Observation stays in Medicare have grown over the last 15years, yet limited research exists on how observation may impact outcomes for older adults. To examine the relationship of an observation stay with 30-day hospital returns, total acute care days post-discharge, mortality, and out-of-pocket costs, compared to an inpatient admission. Retrospective cohort study using instrumental variable analysis. A 20% sample of US Medicare beneficiaries admitted to acute care with a length of stay < 5days between 2009 and 2019. Observation stay vs inpatient admission. Unplanned hospital return within 30days, total 30-day post-discharge acute care days, 30-day mortality, and 30-day acute care out-of-pocket spending. A total of 3,958,377 hospitalizations met study criteria, of which 1,656,631 (42%) were observation stays and 2,301,746 (58%) were inpatient admissions. Compared to inpatient admissions, observation stays were associated with a 4.39 percentage point (95% confidence interval [CI] 3.56%, 5.22%) higher rate of 30-day unplanned hospital returns, but no difference in total 30-day post-discharge acute care days (difference - 0.02days; 95% CI - 0.08, 0.03), no difference in 30-day mortality (difference 0.20 percentage points; 95% CI 0.00, 0.40), and lower 30-day out-of-pocket costs (difference - $552; 95% CI - $561, - $542). Among Medicare beneficiaries hospitalized for fewer than 5days, observation stay was associated with higher rates of 30-day unplanned hospital returns compared to inpatient admission. However, we simultaneously observed lower out-of-pocket costs among those hospitalized under an observation stay. The mixed results suggest that additional research and engagement with relevant parties is needed to optimize observation stay policy.