Multiple Sensitivity Analyses Research Articles

Testing clinical selection criteria for intraoperative transoesophageal echocardiography in isolated coronary artery bypass graft surgery

BackgroundThere is a lack of evidence associating intraoperative transoesophageal echocardiography (TOE) use with improved outcomes among coronary artery bypass graft (CABG) surgery subpopulations. MethodsThis matched retrospective cohort study used a US private claims dataset to compare outcomes among different CABG surgery patient populations with vs without TOE. Statistical analyses involved exact matching on pre-selected subgroups (congestive heart failure, single vessel, and multivessel CABG) and used fine and propensity-score balanced techniques to conduct multiple matched comparisons and sensitivity analyses. ResultsOf 42 249 patients undergoing isolated CABG surgery, 24 919 (59.0%) received and 17 330 (41.0%) did not receive TOE. After matching, intraoperative TOE was significantly associated with a lower, 30-day mortality: 2.63% vs 3.20% (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.71–0.92; P=0.002). In the subgroup matched comparisons, intraoperative TOE was significantly associated with a lower, 30-day mortality rate among those with congestive heart failure: 4.20% vs 5.26% (OR: 0.78; 95% CI: 0.66–0.94; P=0.007) and among those undergoing multivessel CABG with congestive heart failure: 4.23% vs 5.24% (OR: 0.80; 95% CI: 0.65–0.97; P=0.025), but not among those undergoing multivessel CABG without congestive heart failure: 1.83% vs 2.15% (OR: 0.85; 95% CI: 0.70–1.02; P=0.089, nor any of the remaining three subgroups. ConclusionsAmong US adults undergoing isolated CABG surgery, intraoperative TOE was associated with improved outcomes in patients with congestive heart failure (vs without) and among patients undergoing multivessel (vs single vessel) CABG. These findings support prioritised TOE allocation to these patient populations at centres with limited TOE capabilities.

Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis

BackgroundPrior investigations have indicated associations between Knee Osteoarthritis (KOA) and certain inflammatory cytokines, such as the interleukin series and tumor necrosis factor-alpha (TNFα). To further elaborate on these findings, our investigation utilizes Mendelian randomization to explore the causal relationships between KOA and 91 inflammatory cytokines.MethodsThis two-sample Mendelian randomization utilized genetic variations associated with KOA from a large, publicly accessible Genome-Wide Association Study (GWAS), comprising 2,227 cases and 454,121 controls of European descent. The genetic data for inflammatory cytokines were obtained from a GWAS summary involving 14,824 individuals of European ancestry. Causal relationships between exposures and outcomes were primarily investigated using the inverse variance weighted method. To enhance the robustness of the research results, other methods were combined to assist, such as weighted median, weighted model and so on. Multiple sensitivity analysis, including MR-Egger, MR-PRESSO and leave one out, was also carried out. These different analytical methods are used to enhance the validity and reliability of the final results.ResultsThe results of Mendelian randomization indicated that Adenosine Deaminase (ADA), Fibroblast Growth Factor 5(FGF5), and Hepatocyte growth factor (HFG) proteins are protective factors for KOA (IVWADA: OR = 0.862, 95% CI: 0.771–0.963, p = 0.008; IVWFGF5: OR = 0.850, 95% CI: 0.764–0.946, p = 0.003; IVWHFG: OR = 0.798, 95% CI: 0.642–0.991, p = 0.042), while Tumor necrosis factor (TNFα), Colony-stimulating factor 1(CSF1), and Tumor necrosis factor ligand superfamily member 12(TWEAK) proteins are risk factors for KOA. (IVWTNFα: OR = 1.319, 95% CI: 1.067–1.631, p = 0.011; IVWCSF1: OR = 1.389, 95% CI: 1.125–1.714, p = 0.002; IVWTWEAK: OR = 1.206, 95% CI: 1.016–1.431, p = 0.032).ConclusionThe six proteins identified in this study demonstrate a close association with the onset of KOA, offering valuable insights for future therapeutic interventions. These findings contribute to the growing understanding of KOA at the microscopic protein level, paving the way for potential targeted therapeutic approaches.

Association of heavy menstrual bleeding with cardiovascular disease in US female hospitalizations

BackgroundHeavy menstrual bleeding (HMB) is a common menstrual disorder associated with multiple risk factors of cardiovascular disease (CVD) in women. In addition, HMB is often present with irregular menstruation (IM) which is a risk factor for CVD outcomes. However, the relationship between HMB and CVD outcomes is unexplored in the presence or absence of IM. We determined the association of HMB with multiple CVD outcomes using a nationally representative sample of female hospitalizations in the US.MethodsAll hospitalizations of females with HMB diagnosis and normal menstrual cycles from ages of 18 to 70 years were extracted from the National Inpatient Sample Database, 2017. The HMB was defined using the International Classification of Diseases (ICD)-10 for excessive and frequent menstruation bleeding and included any current or history of HMB diagnosis. Outcomes including major adverse cardiovascular events (MACE), coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF) or arrhythmia, myocardial infarction (MI), and diabetes (DM) were defined using ICD-10 codes. Adjusted logistic regression and prosperity scores-matched logistic regression analyses were conducted to summarize adjusted associations with an odds ratio (OR) and a 95% confidence interval (CI).ResultsAmong 2,430,851 hospitalizations, HMB was observed in 7762 (0.68%) females with age ≤ 40 years and 11,164 (0.86%) females with age > 40 years. Among hospitalizations with age ≤ 40 years, HMB was significantly associated with increased odds of CVD outcomes including MACE (OR = 1.61; 95% CI: 1.25, 2.08), CHD (OR = 1.72; 95% CI: 1.10, 2.71), stroke (OR = 1.95; 95% CI: 1.12, 3.40), HF (OR = 1.53; 95% CI: 1.15, 2.03), and AF/arrhythmia (OR = 1.84; 95% CI: 1.34, 2.54). These associations were confirmed in multiple sensitivity analyses. In contrast, HMB was not robustly associated with CVD events among hospitalizations of women with age > 40 years. HMB without IM was strongly associated with DM, HF, AF, and MACE outcomes while HMB with IM was strongly associated with CHD and AF outcomes in hospitalizations of young women.ConclusionsHMB is associated with CVD events among US hospitalizations of young women. A routine investigation and screening of menstrual disorders, especially HMB, is useful for CVD risk stratification and management in young women.

#1052 Associations of new-onset proteinuria during hospitalization with all-cause mortality and kidney outcome

Abstract Background and Aims Proteinuria has been routinely screened in hospitalized patients at admission, but the changes in urinary protein during hospitalization is usually neglected. The epidemiology and clinical implication of new-onset proteinuria during hospitalization remains unclear. We aim to examine the associations between new-onset proteinuria during hospitalization with all-cause mortality, cardiovascular mortality, and composite kidney outcomes after discharge. Method We conducted a multicenter cohort of hospitalized adults without proteinuria at admission and with at least one repeated urinary protein test before discharge from the China Renal Data System. New-onset proteinuria was defined as a change in the urine dipstick protein test from negative to 1+ or more during hospitalization. The primary outcome was all-cause mortality after discharge. Secondary outcomes included cardiovascular mortality and composite kidney outcomes of sustained new-onset eGFR<60 ml/min/1.73 m2, >40% decline in eGFR, maintain dialysis, kidney transplant, or end stage renal disease. The associations between new-onset proteinuria and study outcomes were assessed by Cox proportional hazard models. Results Among 219,669 inpatients with mean age of 54 years, new-onset proteinuria occurred in 7.3% of the study population during hospitalization. After a mean follow-up of 4.9 years, patients with new-onset proteinuria during hospitalization was significantly associated with increased risk of all-cause mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.07-1.25), cardiovascular deaths (HR 1.25; 95% CI, 1.07-1.46), and adverse kidney outcomes (HR 1.51; 95% CI, 1.14-2.01), compared to those without proteinuria. These associations were independent of the occurrence of AKI and remained consistent across subgroups and multiple sensitivity analyses, regardless of the severity and recovery status of new-onset proteinuria. Conclusion The presence of new-onset proteinuria during hospitalization demonstrated significant prognostic value and should be carefully monitored to improve patient care.

Embodied cognition comes of age: A processing advantage for action words is modulated by aging and the task.

Processing action words (e.g., fork, throw) engages neurocognitive motor representations, consistent with embodied cognition principles. Despite age-related neurocognitive changes that could affect action words, and a rapidly aging population, the impact of healthy aging on action-word processing is poorly understood. Previous research suggests that in lexical tasks demanding semantic access, such as picture naming, higher motor-relatedness can enhance performance (e.g., fork vs. pier)-particularly in older adults, perhaps due to the age-related relative sparing of motor-semantic circuitry, which can support action words. However, motor-relatedness was recently found to affect performance in younger but not older adults in lexical decision. We hypothesized this was due to decreased semantic access in this task, especially in older adults. Here we tested effects of motor-relatedness on 2,174 words in younger and older adults not only in lexical decision but also in reading aloud, in which semantic access is minimal. Mixed-effects regression, controlling for phonological, lexical, and semantic variables, yielded results consistent with our predictions. In lexical decision, younger adults were faster and more accurate at words with higher-motor relatedness, whereas older adults showed no motor-relatedness effects. In reading aloud, neither age group showed such effects. Multiple sensitivity analyses demonstrated that the patterns were robust. Altogether, whereas previous research indicates that in lexical tasks demanding semantic access, higher motor-relatedness can enhance performance, especially in older adults, evidence now suggests that such effects are attenuated with decreased semantic access, which in turn depends on the task as well as aging itself. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Circulating Levels of T-Cell Traits and the Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Amyotrophic lateral sclerosis (ALS) represents a rare and potentially fatal neurodegenerative disease. Diverse T-cell subsets could potentially exert diametrically opposite impacts upon ALS development. A two-sample Mendelian randomization (MR) analysis was performed to investigate the correlation between 244 T-cell subsets and ALS risk. Genetic instrumental variables were procured from a standard genome-wide association study (GWAS) that encompassed 244 T-cell subsets in 3757 individuals of European lineage. ALS-related data were collected from a GWAS comprising 20,806 ALS instances and 59,804 European control participants. Multiple sensitivity analyses were performed to verify the robustness of the significant results. Reverse MR analysis was used for delineating the effects of ALS on the characteristics of T-cells. After multiple comparison corrections, 24 out of the 244 subtypes demonstrated a potential association with ALS risk. Significantly, 75% of these associations encompassed the expression of the CD3 on diverse T-cell subtypes, revealing a highly consistent inverse relation to ALS risk. The proportion of T regulatory cells (Tregs) in CD4+ T cells and secreting Tregs in CD4+ T cells demonstrated negative associations with the risk of ALS. CCR7 expression on naive CD4+ T cells and CCR7 expression on naive CD8+ T cells showed positive associations with ALS risk. Certain T-cell subsets, particularly those identified by CD3 expression on terminally differentiated CD8+ T cells, proportions of Tregs, and CCR7 expression, indicated an association with ALS risk. These findings harmonize with and extend previous observational studies investigating the involvement of T lymphocyte subset-induced immunological processes in ALS.

Association of sarcopenia with the long-term risk of atrial fibrillation: A prospective cohort study.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Association between gut microbiota and central retinal artery occlusion: A two-sample Mendelian randomization study.

The gut microbiota might be closely related to central retinal artery occlusion (CRAO), but the causality has not been well defined. Two-sample Mendelian randomization (MR) study was used to reveal the potential causal effect between the gut microbiota and CRAO. Data for gut microbiota were obtained from the genome-wide association studies of the Dutch Microbiome Project (DMP) (n = 7738) and the MiBioGen consortium (n = 18,340), and data on CRAO were obtained from samples of FinnGen project (546 cases and 344,569 controls). Causalities of exposures and outcomes were explored mainly using the inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median (WM), simple mode, weighted mode, and MR Pleiotropy RESidual Sum and Outlier were simultaneously applied to validate the final results. We identified three microbial pathways (two risk factors/one protective factor) and seven microbial taxa (two risk factors/five protective factors) associated with CRAO in the DMP study. Based on the data from the MiBioGen consortium, we identified seven microbial taxa (two risk factors/five protective factors) associated with CRAO, including the Eubacterium genus, which was consistently identified as a risk factor in both the DMP and the MiBioGen consortium MR analyses. Our study implicates the potential causal effects of specific microbial taxa and pathways on CRAO, potentially providing new insights into the prevention and treatment of CRAO through specific gut microbial taxa and pathway. Since our conclusion is a hypothesis derived from secondary genome-wide association studies (GWAS) data analysis, further research is needed for confirmation.

A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases.

Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear. We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results. We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157). Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Demineralization effects on physicochemical and combustion characteristics of biomass: Insights into distributed kinetics, flue gas evolution, and slag formation

Biomass as the only carbon-bearing renewable energy has enormous potential to challenge the established energy structure dominated by fossil resources, and incineration technology is one of the most direct and efficient pathways for utilizing biomass resources, unfortunately enduring the inevitable sintering and slagging problems owing to the excessive alkali metals. Herein, we comparatively investigated the effects of five leaching solvents (water, acetic acid, wood vinegar, hydrochloric acid, and oxalic acid) on the physicochemical properties and ash-removal capabilities of wheat straw (WS) and rice husk (RH), with a view to achieving better performance in the subsequent combustion characteristics, kinetic examination, flue gas, and slag evolution. Results indicated with ionization ability increased (water < acetic acid < hydrochloric acid), the WS exhibited a strong demineralization performance (maximum 61.1%), further leading to a steep weight loss in its combustion characteristic curve at approximately 350 °C and a delayed peak temperature after the removal of alkali metal. Multiple distributed activation energy model and sensitivity analysis revealed that leaching pretreatment enhanced the activation energy (189–191.8 kJ mol−1) and optimized energy distribution at the preliminary stage of the combustion reaction. In addition, the absence of alkali metals suppressed the catalytic oxidation reaction in the flue gas, remarkably limiting the formation of CO2 but facilitating the release of CO and CH4. Meanwhile, a considerable optimal in biomass ash slagging, in which the initial temperature of the liquid phase slag for WS ash increased to 991 °C. Notably, HCl showed the strongest demineralization performance among the five leaching solvents during pretreatment, but the high-temperature slag content was still higher than that of acetic acid. Therefore, slagging performance is not only associated with the demineralization ability of leaching solvents, but also with ash composition.

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

Stasis imaging predicts the risk of cardioembolic events related to acute myocardial infarction

Introduction and objectivesIn the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging in predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. MethodsWe designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI, NCT02917213), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its ability to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. ResultsA total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. ConclusionsIn patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging.

Unraveling the genetic basis of the causal association between inflammatory cytokines and osteonecrosis.

Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis. Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results. The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034). This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.

Eosinophils and risk of ulcerative colitis in European population: Evidence from Mendelian randomization study.

Observational studies have indicated that peripheral blood eosinophil count is elevated in individuals diagnosed with ulcerative colitis (UC) and correlates with the disease activity of UC. However, this conclusion contradicts with findings from other studies. Therefore, we employed Mendelian randomization (MR) method to assess the genetic link between eosinophil count and UC. This MR study utilized summary data from genome-wide association studies (GWAS) on eosinophil count and UC. The main approach used for conducting MR analysis was the inverse variance weighted (IVW) method. Meta-analysis of the IVW results was performed alongside multiple sensitivity analyses to confirm the robustness of the MR analysis results. The IVW method unveiled a causal relationship between eosinophil count and UC (OR = 1.18, 95% CI: 1.04-1.33, p = .01) in the discovery cohort. This finding was further corroborated by the replication cohorts (OR = 1.16, 95% CI: 1.04-1.29, p = .01; OR = 1.12, 95% CI: 1.01-1.24, p = .03). The meta-analysis indicated that the overall odds ratio (OR) for all studies was 1.15 (common effect model, 95% CI: 1.08-1.23, p < .01). Sensitivity analysis suggested the absence of heterogeneity and horizontal pleiotropy in all MR analyses. Based on bidirectional two-sample MR analysis, there is an indication that elevated eosinophil count may increase the risk of UC. However, potential confounding factors cannot be ruled out, and further research is necessary to explore how eosinophils contribute to the onset and progression of UC.

How Do Developers Influence the Transaction Costs of China’s Prefabricated Housing Development Process? An Investigation through the Bayesian Belief Network Approach

The implementation of prefabricated housing (PH) has become prevalent in China recently due to its advantages in enhancing production and energy-saving efficiency within the construction system. However, stakeholders may not always fully realize the benefits of adopting PH due to the emergence of transaction costs (TCs) in the development process of such projects. This study investigated the strategies for developers to make rational choices for minimizing the TCs of the PH project considering their own attributes and external constraints. A Bayesian Belief Network model was applied as the analytical method, based on surveys conducted in China. A single sensitivity analysis indicated that developers influence the TCs of PH through the following three most impactful factors: prefabrication rate, PH experience, and contract payment method. Integrated strategies are recommended for developers in various situations based on a multiple sensitivity analysis. Developers facing challenges due to high prefabrication rates are advised to reduce the risks by procuring highly qualified general contractors and adopting unit-price contracts. For developers with limited PH experience, adopting the Engineering–Procurement–Construction procurement method is the most efficient way to reduce their TCs in the context of China’s PH market. This study contributes to the current body of knowledge concerning the effect of traders’ attributes and choices on TCs, expanding the application of TC theory and fulfilling the study on the determinants of TCs in construction management.

Real-world application of nirmatrelvir/ritonavir in hospitalized COVID-19 patients with onset of symptoms beyond 5days: a comparative study.

Physicians may administer Nirmatrelvir-ritonavir to patients who have been symptomatic for more than 5days. There is currently no clear evidence to support this approach. A real-world study was conducted to investigate the potential relationship between the administration of Nirmatrelvir-ritonavir and the rates of intubation or in-hospital mortality among COVID-19 patients who experienced symptoms for more than 5days. The end point was a composite event of intubation or in-hospital mortality. The outcomes between those patients who received Nirmatrelvir-ritonavir and those who did not were compared. A total of 847 patients were included in the analysis. Among them, 312 patients (36.84%) received Nirmatrelvir-ritonavir. Within the entire population, 86 patients (10.15%) experienced intubation or in-hospital mortality. The main analysis indicated that there was a significant association between the application of Nirmatrelvir-ritonavir and intubation or in-hospital mortality, with an odds ratio of 0.50 (95% confidence interval, 0.28 to 0.87; P = 0.0153) using inverse probability of treatment weighting. The finding was consistent with multiple sensitivity analyses. The application of Nirmatrelvir-ritonavir was associated with a significantly reduced risk of intubation or death in hospitalized COVID-19 patients who experienced symptoms for more than 5days as compared to those who did not receive the treatment.

Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor

BackgroundIn patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated.ObjectivesTo investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI.MethodsThis observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods.ResultsOne month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4–1.2] vs. 0.9 [0.6–2.3] mg/L, p &amp;lt; 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p &amp;lt; 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20–0.54], p &amp;lt; 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776).ConclusionIn ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT.Clinical trial registrationNCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Effects of Testosterone in Mediating the Relationship Between Daytime Napping and Osteoporosis in European Populations: A Mendelian Randomization Study.

We aimed to explore the causal effect of daytime napping on the risk of osteoporosis and the mediation role of testosterone in explaining this relationship. Summary data for Mendelian randomization (MR) analysis were obtained from the IEU OpenGWAS database. Univariable MR(UVMR) analysis and multiple sensitivity analyses were applied to explore the casual relationship between daytime napping and bone mineral density (BMD)/osteoporosis. We also conducted multivariable Mendelian randomization (MVMR) analysis to evaluate the correlation between testosterone-associated single-nucleotide variations and BMD/osteoporosis. Then, mediation analysis was performed to explore whether the association between daytime napping and BMD/osteoporosis was mediated via testosterone. Genetically predicted daytime napping was significantly associated with femoral neck BMD (β [95% CI]: 0.2573 [0.0487, 0.4660];P = 0.0156), lumbar spine BMD (β [95% CI]: 0.2526 [0.0211, 0.4840];P = 0.0324), and osteoporosis (OR [95% CI]: 0.5063 [0.2578, 0.9942];P = 0.0481). β and 95%CIs indicate the standard deviation (SD) unit of BMD increase per category increase in daytime napping. OR and 95%CIs represent the change in the odds ratio of osteoporosis per category increase in daytime napping. We observed a potentially causal effect of more frequent daytime nappingon higher BMD and a lower risk of osteoporosis. Daytime napping was causally associated with a higher level of bioavailable testosterone (β [95% CI]: 0.1397 [0.0619, 0.2175]; P = 0.0004). β and 95%CIs represent the change in the SD of testosterone per category increase in daytime napping. Furthermore, the causal effects of daytime napping on BMD/osteoporosis were partly mediated by bioavailable testosterone. Daytime napping can efficiently increase BMD and reduce the risk of osteoporosis, and testosterone plays a key mediating role in this process.

Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study

Background & aimsEvidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample. MethodsWe studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011–2016, with a five-year follow-up. We evaluated the association of total sugary drinks, carbonated beverages, vegetable juice, 100% fruit juice, sweetened coffee, black coffee, and green tea with subsequent depression. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD). Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios. ResultsIn total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index. ConclusionsTotal sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it.

To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study.

It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.