Interaction Test Research Articles

Short versus 1-Year Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: An Updated Systematic Review and Meta-Analysis

Current guidelines recommend dual antiplatelet therapy (DAPT) for 6 to 12 months post percutaneous coronary intervention (PCI), with recent trials assessing the safety and efficacy of shortening DAPT duration to ≤3 months. A systematic search of PubMed, Scopus, and Cochrane Central databases identified studies comparing short DAPT followed by P2Y12i monotherapy (78% ticagrelor) vs. standard 12-month DAPT in patients undergoing PCI with drug-eluting stent (DES). Nine randomized controlled trials, including 42,770 patients (short DAPT n=21,370, 49.96%) of whom 28,307 (66.18%) presented with acute coronary syndrome (ACS), were included. Short DAPT significantly reduced NACE (RR 0.78; 95%CI 0.67-0.91; p=0.001; I2=62%), major bleeding (RR 0.54; 95%CI 0.39-0.73; p<0.001; I2=63%) as well as any bleeding (RR 0.55; 95%CI 0.43-0.72; p<0.001; I2=77%)​​ at 12 months compared with 1-year DAPT. No significant differences were observed in MACCE, myocardial infarction, stroke, stent thrombosis, mortality, or revascularization. Ticagrelor monotherapy after short DAPT further reduced MACCE (RR 0.85, 95% CI 0.73-0.99, p=0.040; I²=22%), NACE (RR 0.74, 95% CI 0.61-0.89, p=0.001; I²=68%), and major bleeding (RR 0.56, 95% CI 0.40-0.78, p<0.001; I²=71%) compared with 1-year DAPT, however, the test for subgroup interaction (Pinteraction>0.05) for clopidogrel subgroup was not significant. P2Y12i monotherapy reduced the risk of NACE (RR 0.77; 95%CI 0.66-0.90; p=0.001; I2=52%, Pinteraction=0.58) and major bleeding (RR 0.44; 95%CI 0.35-0.55; p<0.001; I2=0%, Pinteraction<0.01) in the ACS cohort, but not in the CCS cohort. In conclusion, short DAPT for ≤3 months followed by P2Y12i monotherapy (particularly ticagrelor) was associated with decreased NACE and bleeding without differences in other outcomes and should be considered a favorable option in patients with either ACS or CCS following PCI with DES.

Association between perioperative platelet distribution width changes and postoperative acute kidney injury in patients with renal insufficiency: a retrospective study

BackgroundAcute kidney injury (AKI) is a major complication following cardiac surgery with a high incidence in those with existing kidney dysfunction. Platelet distribution width (PDW) reflects variability in platelet size and serves as an indicator of platelet activation. Recent investigations linked PDW changes to kidney pathology, suggesting its utility in identifying individuals at risk for AKI, thus necessitating exploration of its predictive value.MethodsPatients with preoperative renal dysfunction [15 ≤ estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2] who underwent cardiac surgery from January 2018 to December 2021 were retrospectively enrolled. PDW values were measured preoperatively and again upon admission to the ICU immediately after cardiac surgery, with the change in PDW (dPDW) defined as the difference between these two measurements. The primary outcome was postoperative AKI, defined base on the Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria. Multivariate regression models were performed to identify the association between dPDW and AKI and its potential trend. Restricted cubic spline analysis assessed non-linear associations between dPDW and AKI. The Youden index identified an optimal dPDW cut-off for AKI prediction. Subgroup analysis was performed to elucidate the consistency of these associations across the various subgroups.ResultsAKI occurred in 53.10% (513/966) of patients, accompanied by significant PDW increases in cases of AKI (P < 0.001). After adjusting confounders, dPDW was identified as a significant risk factor for AKI [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.02 ~ 1.16), P = 0.012]. Patients in the highest dPDW quartile (Q4) had a 195% higher AKI risk compared to those in the lowest quartile (Q1) (OR = 2.95, 95% CI:1.78 ∼ 4.90, P < 0.001). Trend analysis indicates that the risk of AKI increased with higher dPDW quartiles (P for trend < 0.001). Youden index showed that dRDW = 1.1 was identified as the optimal diagnostic cut-off value for AKI. Subgroup analyses and interaction tests showed a robust association between dPDW and AKI in all subgroups (P for interaction > 0.05).ConclusionsThis study underscored perioperative PDW changes as a significant predictor of postoperative AKI in patients with renal insufficiency, highlighting its potential in refining risk stratification and management strategies.Clinical trial numberNot applicable for this observational retrospective study.

Association Between Systemic Immune-Inflammation Index and CA125 in Older Women: Insights from a Cross-Sectional NHANES Study.

The Systemic Immune-Inflammation Index (SII) is a novel biomarker that has been implicated in the pathogenesis of various neoplastic and non-neoplastic diseases. This study aimed to evaluate the association between SII and the conventional tumor marker CA125 (Carbohydrate antigen 125) in a population of postmenopausal women. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES), focusing on postmenopausal women with available data on SII and CA125. The SII was calculated using the formula: platelet count × neutrophil count/lymphocyte count. To evaluate the relationship between the SII and cancer antigen 125 (CA125), we conducted multivariate regression analyses. The linear association between these variables was further explored by fitting a smoothed curve to examine nuances in their relationship. Additionally, subgroup analyses were performed based on age, age at menarche and menopause, and hormone replacement therapy status to assess the heterogeneity of the relationship between SII and CA125 between different demographic groups. A total of 741 postmenopausal women with a mean age of 72.0 (±8.24) years were included in this analysis. The results demonstrated a significant positive correlation between SII and CA125 levels (β = 0.01; 95% CI, 0.00-0.02, p = 0.0128). Subgroup analyses and interaction tests revealed that variables such as age, age at menarche and menopause, and hormone replacement therapy did not significantly modify this association (p > 0.05). This study demonstrated a positive correlation between SII and C125 in older female patients in the United States.

Associations of Dietary Intake of Vitamin B6 and Plasma Pyridoxal 5'-Phosphate Level With Depression in US Adults: Findings From NHANES 2005-2010.

Evidence regarding the associations of pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk is scarce. Accordingly, we investigated the aforementioned associations in US adults. This is a cross-sectional study that included data from two independent samples of 12,716 and 11,967 individuals (aged ≥20years) participating in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The associations of the pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk were examined through multivariable logistic regression. In addition, we determined dose-response associations by fitting restricted cubic splines to the data. In the multivariable model, the highest quarter of dietary intake of vitamin B6 was associated with a significantly lower risk of depression compared to the lowest quarter (OR=0.63, 95% CI: 0.50, 0.79, p< 0.001). Similarly, the highest quartile of plasma PLP levels was linked to a reduced risk of depression compared to the lowest quartile (OR=0.76, 95% CI: 0.62, 0.93, p<0.01). With increasing quartiles of dietary intake of vitamin B6 and plasma PLP levels, the risk of depression also decreased accordingly (all p for trend < 0.01). Furthermore, the correlation analysis revealed that for every 1-SD increase in the level of plasma lutein+zeaxanthin and dietary intake of vitamin B6, the risk of depression showed a decreasing trend (all p<0.01). The interaction test results indicated that the dietary consumption of vitamin B6 did not significantly interact with any of the stratification factors (all p for interaction >0.05). Moreover, no significant interaction was found between the amount of plasma PLP and any hierarchical factors (all p for interaction >0.05), except for gender-based subgroup analysis (p for interaction >0.05). The dose-response relationship results showed a linear decrease trend in the relationship between dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate with the risk of depression. Plasma PLP levels and dietary vitamin B6 intake in the highest quartiles are associated with a lower risk of depression. These findings support the promotion of a balanced diet rich in vitamin B6. However, future randomized controlled trials are necessary to confirm the effects of vitamin B6 supplementation on depression risk. We should aim for a healthy and balanced diet in terms of nutritional supplementation.

Combinatorial transition testing in dynamically adaptive systems: Implementation and test oracle

Due to the large number of possible interactions and transitions among features in dynamically adaptive systems, testing such systems poses significant challenges. To verify that such systems behave correctly, combinatorial interaction testing (CIT) can create concise test suites covering all valid pairs of features of such systems. While CIT claims to find all errors caused by two features, it does not cover certain errors occurring only for specific transitions between features. To address this issue we study the technique of Combinatorial Transition Testing (CTT), which includes both generation and detection of what we call behavioural transition errors. From an initial generation algorithm that combines both interaction and transition coverage but lacks scalability, we propose an optimised version that enables CTT even for hundreds of features. From a valid test suite covering all transitions, we complete our testing approach with a test oracle that detects all behavioural transition errors without any prior knowledge of the system’s behaviour. After a comprehensive analysis over a large number of feature models, we conclude that size of CTT-generated test suites and test effort needed to use our test oracle are linearly correlated to CIT-generated ones and that CTT grows logarithmically in the number of features.

Association between Neutrophil-to-high-density lipoprotein-cholesterol ratio and gallstones: insights from the national health and nutrition examination survey (2017–2020)

BackgroundInflammatory responses and lipid metabolism make vital impacts on the development of gallstones. This study investigated the relationship between gallstone disease (GSD) and the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) in American patients with gallstones.MethodsThe data analyzed were sourced from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) and comprised of participants with complete data on GSD and NHR. The relationship between NHR and GSD was evaluated with weighted multivariable logistic regression analysis. Additionally, subset analyses, interaction tests, smoothed curve fitting, and threshold effect analyses were conducted.ResultsAmong the 7894 participants analyzed in this study, the prevalence of GSD was 10.98%, and the average NHR value was 3.41 ± 0.06. The fully adjusted multivariable logistic regression results demonstrated an obvious positive association between NHR and the likelihood of GSD (OR = 1.09, 95% CI: 1.01, 1.16; P = 0.0197). Consistency of this association was confirmed through subset analyses and interaction tests across various subgroups, including those categorized by smoking status and asthma. Furthermore, smoothed curve fitting and threshold effect analyses revealed a nonlinear relationship with a threshold of 2.86.ConclusionsNHR shows a positive relationship to an increased likelihood of GSD among Americans. It can act as an easy and cost-effective tool for the early detection and management of individuals at risk for GSD.

Association between stroke and relative fat mass: a cross-sectional study based on NHANES

BackgroundThis study was aimed at investigating the correlation between the occurrence of stroke and relative fat mass (RFM), a novel metric for determining total body fat.MethodsThis cross-sectional study employed the National Health and Nutrition Examination Survey (NHANES) dataset, which encompassed the years 2005 to 2018 to assess the independent relationship between RFM and stroke. Moreover, multinomial logistic regression, subgroup analysis, smooth curve fitting, and interaction testing were also used.ResultsThis study included 35,842 participants and 1,267 (3.53%) of them were diagnosed with stroke. Fully adjusted Models showed that RFM was positively associated with stroke (odds ratio [OR] = 1.02; 95% confidence interval [CI] = 1.01–1.03). The odds of having a stroke in quartile 4 were significantly elevated by 44%, compared to quartile 1 (OR = 1.44,95%CI:1.09–1.90). In addition, a subgroup analysis also demonstrated that age and BMI significantly impacted the association between RFM and stroke (P for interaction<0.01).ConclusionsElevated RFM is associated with increased odds of stroke, suggesting that RFM may have potential value in the prevention and management of stroke.

The impact of COVID-19 on sign language assessment

This study investigated through an online survey how sign language practitioners changed their sign language assessment practices during the COVID-19 pandemic. The survey consisted of five sections and 29 questions overall. It was provided in written English and German as well as in International Sign and was administered online between October 2021 and December 2022. Twenty sign language testing professionals from a wide variety of countries participated in the survey. The results indicate a sharp increase of online testing during the pandemic, a decrease in the testing of sign language interaction and reception, a decline in the variety of testing purposes with a stronger focus on assessment for learning, and a shift to the use of more online tools such as video conferencing. Additionally, the results show that the home set-up of test takers, including reliable internet connection and access to appropriate hardware, are essential for online sign language testing. Sign language testing professionals reported different measures that were introduced to minimize cheating, such as live video monitoring during sign language exams or the implementation of proctoring software. The paper finishes with recommendations for future sign language assessment.

A worldwide test of the predictive validity of ideal partner preference matching.

Ideal partner preferences (i.e., ratings of the desirability of attributes like attractiveness or intelligence) are the source of numerous foundational findings in the interdisciplinary literature on human mating. Recently, research on the predictive validity of ideal partner preference matching (i.e., Do people positively evaluate partners who match vs. mismatch their ideals?) has become mired in several problems. First, articles exhibit discrepant analytic and reporting practices. Second, different findings emerge across laboratories worldwide, perhaps because they sample different relationship contexts and/or populations. This registered report-partnered with the Psychological Science Accelerator-uses a highly powered design (N = 10,358) across 43 countries and 22 languages to estimate preference-matching effect sizes. The most rigorous tests revealed significant preference-matching effects in the whole sample and for partnered and single participants separately. The "corrected pattern metric" that collapses across 35 traits revealed a zero-order effect of β = .19 and an effect of β = .11 when included alongside a normative preference-matching metric. Specific traits in the "level metric" (interaction) tests revealed very small (average β = .04) effects. Effect sizes were similar for partnered participants who reported ideals before entering a relationship, and there was no consistent evidence that individual differences moderated any effects. Comparisons between stated and revealed preferences shed light on gender differences and similarities: For attractiveness, men's and (especially) women's stated preferences underestimated revealed preferences (i.e., they thought attractiveness was less important than it actually was). For earning potential, men's stated preferences underestimated-and women's stated preferences overestimated-revealed preferences. Implications for the literature on human mating are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association of METS-IR index with psoriasis in US adults: a cross-sectional study.

Psoriasis is linked to insulin resistance (IR). Nevertheless, the applicability of the METS-IR index, a new IR evaluation tool, for evaluating changes in insulin sensitivity in psoriasis populations is currently unknown. This study aimed to investigate the relationship between the METS-IR index and psoriasis in a US adult population. This cross-sectional study utilized data from adults aged 20 to 80 years from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning 2003-2006 and 2009-2014. The associations between the METS-IR index and psoriasis were examined using multivariate logistic regression and smoothed curve fitting. Subgroup analyses and interaction tests were conducted to verify the stability of the association within the population. This study included 5,966 participants, of whom 182 had psoriasis. In the fully adjusted model, the METS-IR index was positively associated with psoriasis, showing a 1.7% increase in psoriasis prevalence for each one-unit increase in the METS-IR index (Model 2: OR 1.017, 95% CI 1.006-1.028). Participants in the highest quartile group were 91.9% more likely to develop psoriasis compared to those in the lowest quartile group (OR = 1.919, 95% CI 1.180-3.118). Smooth curve fitting revealed a nonlinear association between the METS-IR index and psoriasis, with an inflection point of 41.675. This positive association was more pronounced in females, non-obese individuals, those with light alcohol consumption, comorbid coronary heart disease and hyperlipidemia, non-hypertensive and non-diabetic individuals. The results of the study suggest that higher METS-IR scores are associated with an increased likelihood of psoriasis among U.S. adults. The METS-IR index is specifically recommended as a clinical indicator for the management and treatment of psoriasis in women, non-obese individuals, light alcohol consumers, individuals with comorbid coronary artery disease andhyperlipidemia, non-hypertensive and non-diabetic individuals. However, Considering the many known and unknown covariates that may be associated with psoriasis and influence theresults of the study, we remain cautious about the results obtained and look forward to the addition of subsequent studies.

Interaction between the systemic immune-inflammation index and trouble sleeping in nonalcoholic fatty liver disease: a cross-sectional study of the NHANES 2005–2018 data

BackgroundThe systemic immune-inflammation index (SII) and trouble sleeping are independent risk factors for nonalcoholic fatty liver disease (NAFLD). Nevertheless, studies investigating the combined effects of the SII and troubled sleeping on NAFLD are lacking. In this study, we investigated the independent relationships and interactions between trouble sleeping and the SII among patients with NAFLD.MethodsData from seven survey cycles of the National Health and Nutrition Examination Survey (NHANES) (2005–2018) were analyzed. The SII was obtained by counting platelets, neutrophils, and lymphocytes. NAFLD was diagnosed using the US fatty liver index. Trouble sleeping was diagnosed using a sleep disorder questionnaire. The correlation between trouble sleeping and the SII in NAFLD was investigated using multiple regression analysis, subgroup stratification, interaction tests, and restricted cubic spline, and the presence or absence of additive or multiplicative interactions was determined. Additionally, mediation analyses were performed to explore the role of the SII in mediating the effects of trouble sleeping on NAFLD.ResultsThe survey included 10 963 participants. Multivariate logistic regression revealed that SII (OR: 1.21, 95% CI 1.08–1.35) and trouble sleeping (OR: 1.24, 95% CI 1.05–1.47) were positively correlated with NAFLD. For NAFLD, an additive but not multiplicative interaction was noted between the SII and trouble sleeping. The SII partially mediated the association between trouble sleeping and NAFLD, accounting for approximately 3.11% of the total effect (95% CI 0.01–0.05).ConclusionThe SII and trouble sleeping were independently correlated with NAFLD risk. Furthermore, a combined effect may exist between SII and trouble sleeping, which increases the risk of NAFLD.

Exploring the adhesion properties of extracellular vesicles for functional assays.

The "stickiness" of extracellular vesicles (EVs) can pose challenges for EV processing and storage, but adhesive properties may also be exploited to immobilize EVs directly on surfaces for various measurement techniques, including super-resolution microscopy. Direct adhesion to surfaces may allow examination of broader populations of EVs than molecular affinity approaches, which can also involve specialized, expensive affinity reagents. Here, we report on the interaction of EVs with borosilicate glass and quartz coverslips and on the effects of pre-coating coverslips with poly-L-lysine (PLL), a reagent commonly used to facilitate interactions between negatively charged surfaces of cells and amorphous surfaces. Additionally, we compared two mounting media conditions for super-resolution microscopy (SRM) imaging and used immobilized EVs for a B-cell interaction test. Our findings suggest that borosilicate glass coverslips immobilize EVs better than quartz glass coverslips. We also found that PLL is not strictly required for EV retention but contributes to the uniform distribution of EVs on borosilicate glass coverslips. Overall, these findings suggest that standard lab materials like borosilicate glass coverslips, with or without PLL, can be effectively used for the immobilization of EVs in specific imaging techniques.

Association of cardiometabolic index with sleep quality in adults: a population‑based study

The Cardiometabolic Index (CMI) represents an innovative metric that encompasses abdominal obesity and lipid levels, offering a comprehensive assessment of cardiometabolic health. It is derived through the multiplication of the waist-to-height ratio by the triglyceride-to-high-density lipoprotein cholesterol ratio. Although obesity and blood lipid levels are known factors affecting sleep quality, the direct correlation between CMI and sleep quality has yet to be elucidated. This study uses NHANES data to explore the potential correlation between CMI and sleep quality. Our research employed a cross-sectional design, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2014. CMI was used as the exposure variable, with sleep quality assessed through three self-reported measures: trouble sleeping, sleep disorders, and sleep duration. We employed multivariate logistic regression models and linear regression model as well as subgroup analyses to explore the independent relationship between CMI and sleep quality. Additionally, interaction tests were conducted to examine differences across various subgroups. The study included 4298 participants, comprising 2134 males and 2164 females. There was a positive correlation between CMI and trouble sleeping (OR = 1.63, 95% CI 1.28–2.08) and sleep disorders (OR = 1.96, 95% CI 1.43–2.67), while there was a negative correlation between CMI and sleep duration (β = − 0.17, 95% CI − 0.31 to − 0.03), indicating that a higher CMI was associated with shorter sleep duration. Subgroup analyses and interaction tests revealed a consistently positive association between CMI and sleep difficulty across various populations, including gender, age, hypertension, diabetes, and cardiovascular disease history. However, the relationship between CMI and sleep disorders was more prominent among participants aged 50 and above. In American adults, a higher CMI is linked to an increased prevalence of sleep disturbances. In clinical practice, CMI can be considered as a supplementary factor in the assessment and management of sleep problems. Our study also provided new insights for improving sleep quality.

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (&amp;lt;25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value &amp;lt;0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI &amp;lt;25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI &amp;lt;25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI &amp;lt;25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Effect of tranexamic acid in vascular surgery- a sub-study of the POISE-3 randomized clinical trial

Abstract Background/Introduction In the POISE-3 trial involving patients undergoing noncardiac surgery, tranexamic acid (TXA) reduced the incidence of the composite outcome of life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days. Bleeding is a major issue in vascular surgery. However, TXA use may be limited due to concerns about its safety in this high-risk population. With 1,399 participants in POISE-3 undergoing vascular surgery, this is the largest trial assessing TXA's efficacy in this population. Purpose In this post hoc subgroup analysis, we aimed to investigate the interaction between surgery type (vascular/non-vascular) and the effects of TXA vs placebo on bleeding and cardiovascular (CV) safety outcomes in the POISE-3 population. Methods: Eligible patients were ≥45 years, undergoing inpatient noncardiac surgery, and at risk for bleeding and CV complications. Patients were randomised (1:1) to TXA 1 gm IV bolus at start and end of surgery (total 2 gm) or placebo. We used Cox proportional hazards models incorporating tests for interaction to analyse time to the first occurrence of the composite bleeding outcome, and the CV safety outcome (composite of myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism) at 30 days. Estimates of hazard ratios (HR) with 95% confidence intervals (CI) were calculated for each subgroup with the interaction P value. Results 9,468 of 9535 (99.3%) POISE-3 patients are included in this analysis; 1399 of whom underwent vascular surgery (699 TXA, 700 placebo). Majority (89.8%) of the vascular surgeries were aorto-iliac, peripheral vascular and extracranial surgeries. In the vascular surgery group, 12.6% of patients receiving TXA experienced the composite bleeding outcome versus 14.7% with placebo (HR 0.85, 95% CI 0.64-1.13). For non-vascular surgery patients, these rates were 8.6% with TXA and 11.3% with placebo (HR 0.74, 95% CI 0.65-0.86), with an interaction P value of 0.42. In vascular surgery patients, the CV safety outcome occurred in 20.2% with TXA versus 18.1% with placebo (HR 1.12, 95% CI 0.88-1.42). In the non-vascular surgery group, both TXA and placebo arms showed a 13.1% incidence rate (HR 1.00, 95% CI 0.89-1.13), with an interaction P value of 0.43. Conclusion In vascular surgery patients, there were higher rates of bleeding and cardiovascular events compared to those undergoing non-vascular surgeries; however, there was no significant interaction between the effects of TXA and the type of surgery. The overall POISE-3 trial provides the best estimate of effect with TXA for all patients including those undergoing vascular surgery. The main limitation is that this subgroup analysis was not pre-specified.

Assessment of body composition in young adulthood and its associations to early changes in cardiovascular phenotypes: a cross-sectional study

Abstract Introduction Obesity in young adulthood is associated with various cardiovascular structural and functional changes, commonly used as markers of early subclinical cardiovascular disease. Whether these changes occur predominantly in relation to increased fat mass (FM) or are instead more closely related to simultaneous increases in underlying fat-free mass (FFM) that are known to occur in obesity, is incompletely understood. Purpose To investigate associations between both FM and FFM and a wide range of cardiac (left ventricular mass, LVM; end-diastolic volume, EDV; cardiac output, CO; stroke volume, SV), vascular (systolic blood pressure, SBP; diastolic blood pressure, DBP; mean arterial pressure, MAP; systemic vascular resistance, SVR) and autonomic (heart rate variability triangular index, HRVTI; baroreceptor reflex sensitivity, BRS) phenotypes commonly used to monitor the early evolution of subclinical CVD. Methods The study used data from extensive adipose and cardiovascular phenotyping of 408 healthy young adults (mean age 21 years) participating in a sub-study of the long-running ALSPAC birth cohort. We performed cross-sectional analysis using multiple imputation, multivariable linear regression and interaction testing to assess the association between both FM and FFM and cardiovascular phenotypes. Results Our study revealed that FFM resulted in a much greater increase in CO (difference in outcome per 1-SD difference in exposure β=0.58L/min, p&amp;lt;0.01, 95% CI=0.38, 0.77) than FM (β=0.20L/min, p=0.01, 95% CI=0.05, 0.36), following adjustment for both tissue types. FFM was also associated with an increase in LVM (β=19.1g, p&amp;lt;0.01, 95% CI=16.61, 21.58), EDV (β=22ml, p&amp;lt;0.01, 95% CI=18.18, 25.13) and SV (β=13ml, p&amp;lt;0.01, 95% CI=10.96, 15.75). FFM was also associated with improved autonomic and peripheral vascular function, including lower HR (β=-4bpm, p&amp;lt;0.01, 95% CI=-6.12, -1.95), higher HRVTI (β=2.1, p&amp;lt;0.01, 95% CI=0.72, 3.48) and lower SVR (β=-1.1, p&amp;lt;0.01, 95% CI=-2.12, -1.07), resulting in unchanged MAP despite elevations in CO. On the contrary, FM was not associated with LVM (β=-0.91g, p=0.35, 95% CI=-2.85, 1.02), and was associated with lower EDV (β=-4.62ml, p&amp;lt;0.01, 95% CI=-7.34, -1.88) and reduced autonomic function, as seen with HRVTI (β=-1.83, p&amp;lt;0.01, 95% CI=-3.02, -0.64) and BRS (β=-2.47, p=0.01, 95% CI=-4.27, -0.67). FM was also associated with increased HR (β=3.26bpm, p&amp;lt;0.01, 95% CI=1.57, 4.94) and increased SBP (β=2.14mmHg, p&amp;lt;0.01, 95% CI=1.01, 3.27) DBP (β=2.68mmHg, p&amp;lt;0.01, 95% CI=1.60, 3.77), and MAP (β=2.34mmHg, p&amp;lt;0.01, 95% CI=1.34, 3.34). Conclusion In young adults, changes in surrogate clinical markers of cardiac, vascular, and autonomic function commonly attributed solely to increases in fat mass should be interpreted with caution as they may be associated with underlying changes in FFM. Future work should focus on longitudinal studies of this cohort to confirm remodelling patterns based on these clinical markers.

Academic orientation and alcohol-related harm among adolescents

BackgroundThis study aimed to examine the social gradient in self-reported alcohol-related harm (ARH) among young alcohol consumers by including a largely overlooked group of adolescents. We also explored the extent to which such a gradient could be attributed to differential exposure or differential vulnerability to risk factors.MethodCross-sectional survey of upper-secondary students (n = 2996) in Sweden. Negative binomial regressions estimated the relationship between academic orientation (higher education preparatory; HEP, vocational; VP and introductory; IP) and ARH. To assess the contribution of explanatory factors, we estimated models that included risk factors such as heavy episodic drinking (HED).ResultsA graded association was observed between academic orientation and ARH, with more ARH among students in IP (IRR = 1.79) and VP (IRR = 1.43) than in HEP. Adjustments for risk factors attenuated the estimates by approximately half, but there was still 14% more ARH in VP and 50% more in IP than in HEP. The additive interaction test indicated a positive and significant interaction for students in VP who engaged in HED, versus students in HEP, who did not.ConclusionThe findings suggest a negative gradient in the association between academic orientation and ARH, where the students in IP experienced the highest levels of ARH. While differential exposure and vulnerability to HED account for a significant proportion of the excess risk among VP students, HED seems to be less important relative to other risk factors among IP students. More research is needed to identify the mechanisms underlying the elevated levels of ARH among the most disadvantaged group—students enrolled in IP.

Discrete Choice Experiment on Financial Incentives for Engaging Young Adults in Vaping Cessation Programs

Introduction Contingency management involves rewarding individuals based on objective evidence of behavioral changes. This study explores preferences for financial incentives in vaping cessation programs. Methods A discrete choice experiment (DCE) was conducted among young adult current e-cigarette users aged 19-29. DCE attributes (and levels) included reward amount ($100, $300), reward schedule (consistent value, escalating value), reward procedure (gain-framed, loss-framed), vaping education modules (yes, no), text messaging support (yes, no), and cost ($30, $100). Participants were randomized into one of the four blocks, each containing four choice sets. Each choice set presented two hypothetical vaping cessation programs. Choice data (n × choice sets × alternative programs = 154 × 4 × 2 = 1,232 observations) were analyzed using generalized estimation equation models. Results Participants showed a preference for vaping cessation programs offering a higher reward amount (odds ratio [OR] = 11.5; 95% CI,7.0-19.2), gain-framed rewards for sustained abstinence (OR = 1.4; 95% CI,1.0-1.8), text messaging support (OR = 1.9; 95% CI,1.4-2.5), and a lower program cost (OR = 2.6; 95% CI,1.8-3.8). Interaction tests showed significant effects of the rewards procedure among daily e-cigarette users (adjusted OR [AOR] = 2.1; 95% CI,1.3-3.5), but not some-day users; and among those with no quit attempts in the past six months (AOR = 2.7; 95% CI,1.5-4.7), but not those with previous quit attempts. Female participants preferred text messaging support (AOR = 3.6; 95% CI,2.3-5.4), whereas male participants did not show this preference. Conclusion A multifaceted vaping cessation intervention augmented with financial incentives might improve participation and engagement among young adults. Future studies should investigate how these attributes can enhance program reach and vaping abstinence outcomes in real-world settings.

Association between weight-adjusted waist index with incident stroke in the elderly with hypertension: a cohort study

The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated. The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were carried out to investigate potential heterogeneities. Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up of 3.2 years, we found 547 new-onset stroke cases. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44–2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata. The study findings indicate that an elevated WWI is significantly related with a higher risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. To confirm these results and explore the causal mechanisms behind the observed correlation, more study is necessary.

Overcoming the "feast or famine" effect: improved interaction testing in genome-wide association studies.

Testing for interactions in GWAS can lead to insight into biological mechanisms, but poses greater challenges than ordinary genetic association GWAS. When testing for interaction in a GWAS setting with one fixed SNP or environmental variable, the standard test statistics may not have the expected statistical properties under the null hypothesis, which can lead to false detection of interaction, inconsistent results across studies, reduced power, and failure to replicate true signal. We propose the TINGA method to adjust the test statistics so that the null distribution of their p-values is closer to uniform. Through simulations and real data analysis, we illustrate the problems with the standard analysis and the improvement of our proposed method.