Average Effect Research Articles

Is chronic kidney disease predictive of coronary artery bypass grafting after acute coronary syndrome? A systematic review and meta-analysis

Abstract Background Coronary artery bypass grafting (CABG) provides superior long-term outcomes to percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease. People with chronic kidney disease (CKD) are at increased risk of multi-vessel coronary artery disease, and experience greater morbidity and mortality following acute coronary syndrome (ACS). Purpose To determine whether CKD affects choice of revascularisation strategy after ACS. Methods We searched EMBASE, MEDLINE, SCOPUS, CENTRAL and the NIHR’s website of funded studies to identify articles referring to ACS and invasive coronary management in high-income countries over the past 12 years until 29th September 2023. Full text articles were included if data on rates of CABG were reported in people with and without CKD who were revascularised following ACS. CKD was defined as one or more recording of an estimated glomerular filtration rate (eGFR) <60mls/min/1.73m2, however proxies for this were accepted. Risk of bias was assessed via ROBINS-E. Random effect meta-analyses estimated the odds ratios for CKD and CABG, stratified by ACS type and receipt of dialysis. Certainty of evidence was assessed according to GRADE. Results Initial searches generated 15,138 articles, of which 13 observational studies were included in this review (8,021,743 participants). Amongst people revascularised following ACS, those with CKD were more likely to receive CABG than those without kidney disease (OR for the average exposure effect 1.47 (95% CI 1.30-1.66)). The likelihood of CABG in people with CKD receiving dialysis and those with CKD not receiving dialysis were similar as the 95% confidence intervals demonstrate (ORs 1.25 (95% CI 1.00-1.57) and 1.41 (1.19-1.67) respectively). The effect of CKD on increased likelihood of CABG appeared greater following ST-elevation myocardial infarction (STEMI) than non-ST elevation ACS (NSTE-ACS) (OR 1.53 (95% CI 1.27-1.83) versus 1.10 (0.98-1.25) respectively, p=0.003). Certainty of the evidence was low for receipt of CABG in people with CKD not receiving dialysis, and moderate for all other outcomes. Conclusion In high-income countries, CKD is associated with increased receipt of CABG amongst people revascularised following ACS. This finding is likely explained by the greater prevalence of multi-vessel coronary artery disease in this population. It is however unclear why the association between CKD and receipt of CABG is stronger in those with STEMI compared to NSTE-ACS, and whether this accurately reflects differential need between the two groups.Figure 1Figure 2

Performance and safety of complex percutaneous coronary intervention in centres without on-site cardiac surgery: a multi-centre australian registry study.

Abstract Background Performing complex percutaneous coronary intervention (PCI) procedures in hospitals with no on-site cardiac surgery (NOSCS) remains controversial due to a lack of contemporary data and guideline support. Methods Victorian Cardiac Outcomes Registry data was analysed including all PCI cases in the state of Victoria, Australia, from 2014 to 2022. Patients were stratified by PCI at sites with on-site cardiac surgery (OSCS) or NOSCS. Complex PCI was defined as PCI to unprotected left main, bifurcation lesions, rotational atherectomy or intravascular lithotripsy use, severe left ventricular systolic dysfunction, chronic total occlusion, or vein graft PCI. The primary outcome was composite MACCE comprising all-cause mortality, stroke, non-fatal MI, emergency CABG, unplanned revascularisation, definite stent thrombosis and major bleeding (BARC 3 & 5) at 30-days. Risk ratio for average treatment effect in the NOSCS cohort was estimated using inverse probability treatment weighting. Results 94,268 total PCI procedures (32.6% NOSCS) were analysed, including 12,459 complex PCI cases (28.7% NOSCS). Patients from NOSCS were younger (65.0 vs 67.4, p<0.001), less likely to have had previous PCI (29.5% vs 34.5%, p<0.001) or CABG (4.6% vs 8.0% p<0.001) and presented more frequently with acute coronary syndromes (NSTEMI [32.0% vs 28.0%, p<0.001; STEMI [23.3% vs 15.2%], p<0.001). A propensity weighted sample of 30,850 OSCS patients and 30,692 NOSCS patients demonstrated no difference in adjusted 30-day MACCE (risk ratio 0.93, 95% CI 0.87-1.01, p=0.051) for all PCI procedures. In a propensity-weighted subgroup of 3,638 OSCS and 3,576 NOSCS patients who underwent complex PCI, there was also no difference in adjusted 30-day MACCE (risk ratio 0.97, 95%CI 0.86-1.09, p=0.60). Unadjusted rates of CABG at 30-days were very low (0.1 vs 0.1%, p=1.00). Conclusion Patients undergoing PCI and complex PCI at NOSCS centres had comparable 30-day outcomes to those treated at OSCS centres. Newer percutaneous therapies such as intravascular lithotripsy and percutaneous left ventricular assist devices may further improve safety and efficacy of high-risk PCI in NOSCS centres as operator experience increases. Increasing PCI and complex PCI capabilities at NOSCS is likely to increase equitable treatment access for more patients.

Incidence and risk of autoimmune disease in patients with a previous diagnosis of myocarditis - a nationwide Danish register-based cohort study

Abstract Introduction Myocarditis is a severe condition with an acute onset characterized by myocardial inflammation. The aetiology is heterogenous ranging from viral infections to autoimmune diseases (AD). However, it is currently unknown if patients with a first-time diagnosis of myocarditis are at higher risk of developing an autoimmune disease (AD) at a later stage. Purpose To estimate the risk of developing AD in patients with a first-time diagnosis of myocarditis during 20 years of follow-up. Methods Data source and study design: Nationwide register-based cohort study using data from Danish national administrative registers containing data on ICD-10 codes of diagnoses, prescription of pharmaceuticals, as well as date of birth and death on all Danish citizens. Study population: All Danish patients with a diagnosis of myocarditis from 2002-2020. Patients with previous diagnosis of AD were excluded. A control population without a diagnosis of myocarditis nor AD was sex and aged matched 1:5. Endpoints: Receiving a diagnosis of AD out of 35 recognized AD, and all-cause mortality. Statistics: Cumulative incidence of AD diagnosis was calculated by use of Aalen-Johansen estimation and all-cause mortality rate by Kaplan-Meier estimation. Hazard ratio (HR) by multivariate Cox regression modelling, standardized to sex, age, and comorbidities. Standardized relative (RR) and absolute (AR) risk derived from Cox regression by estimated Average Treatment Effect. Continuous variables are presented as median [1st quartile, 3rd quartile]. Results Study population: Myocarditis cohort: n=2,684. Control cohort: n=13,420. Median follow-up time: 9.5 years [5.4, 14.6]. Median age: 46 years [28, 67]. 69.5 % were of male sex. Comorbidities including hypertension, heart failure, and ischemic heart disease were significantly more common in patients with myocarditis. Autoimmune disease: At 20 years of follow-up, the cumulative incidence of AD diagnosis was 14.1% in the myocarditis cohort, and 5.8% in the control cohort. Adjusted HR for AD diagnosis in myocarditis vs. control cohorts was 2.65 (95% CI 2.19-3.17). Adjusted RR at 1 and 20 years of follow-up was 2.26 (95% CI 2.13-3.11) and 2.47 (95% CI 2.03-2.90), respectively. Figure 1 (left) shows AR of developing an AD at 20 years of follow-up, stratified by sex and age group. Mortality: Kaplan-Meier all-cause mortality was 40.5% in the myocarditis cohort, and 28.5% in the control cohort. Adjusted HR: 1.84 (95% CI 1.67-2.03). Adjusted RR at 1 and 20 years of follow-up: 1.77 (95% CI 1.60-1.93) and 1.31 (95% CI 1.25-1.36), respectively. Figure 1 (right) shows stratified AR of all-cause mortality at 20 years of follow-up. Conclusions Patients with a diagnosis of myocarditis had a significantly higher risk of developing AD in addition to significantly higher all-cause mortality compared to patients without previous myocarditis diagnosis. These findings suggest underlying and subsequent AD should be considered in patients with myocarditis.20-year AR of AD and all-cause mortalityICD-10 codes of AD investigated

Guidelines to practice in hospitals at home: penicillin infusion pumps in erysipelas treatment

Abstract Background Hospitals at home are increasingly offering outpatient parenteral antimicrobial therapy (OPAT) in an attempt to reduce costly inpatient care, but these settings favor broad-spectrum antibiotics that require less frequent dosing than penicillin. Benzyl penicillin could be delivered via continuous infusion pumps (eCIP), but studies on their safety and efficacy in OPAT are scarce, and it remains unclear how much the availability of eCIPs increases penicillin use in real-life settings. Methods We examined 462 electronic healthcare records of erysipelas patients treated between January 2018 and January 2022 in a large Finnish OPAT clinic. Average marginal effects from logistic models were estimated to assess how the introduction of eCIPs in December 2020 affected penicillin use, and to compare clinical outcomes between patients with and without eCIPs. Results Introduction of eCIPs increased the predicted probability of penicillin treatment by 36.0 percentage points (95% confidence interval 25.5-46.5). During eCIP implementation, patients who received an eCIP had 73.1 (58.0-88.2) percentage points higher probability than patients without an eCIP to receive penicillin treatment. They also had about 20 percentage points higher probability to be cured at the time of discharge and three months after it. Patient and nurse satisfaction regarding eCIPs was very high. Conclusions Benzyl penicillin eCIP treatment is effective and safe, and substantially increases the use of penicillin instead of broad-spectrum antibiotics. To reduce the risk of antimicrobial resistance, eCIPs could increasingly be promoted for use in OPAT clinics, and there should be adequate education and support in their implementation. Key messages • Continuous infusion of benzyl penicillin via elastomeric infusors substantially decreases broad-spectrum antibiotic use among erysipelas patients treated at home. • When erysipelas patients can be treated with outpatient parenteral antibiotic therapy, the use of elastomeric benzyl penicillin infusors is safe and effective and should thus be increasingly promoted.

High-sensitivity troponin T and risk of stroke in persons with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity troponin (hsTn) concentrations are associated with the risk of recurrent ischemic events and death from any cause. Higher hsTn levels may suggest greater infarct size and possibly, a more pronounced risk of non-coronary atherosclerotic events. Purpose To examine the association between single and serial hsTnT levels and the risk of incident stroke in individuals presenting with suspected acute coronary syndrome. Methods In this Danish nationwide registry-based study, we identified individuals without a history of stroke who presented for myocardial infarction, unstable angina, suspected myocardial infarction, or chest pain from 2013 through 2019, and who underwent serial hsTnT (Roche Diagnostics, Rotkreuz, Switzerland; 99th percentile upper reference limit: 13.5 ng/l) measurements 1-7 hours apart. Subjects were stratified according to their hsTnT level pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnT level change (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-16 ng/l, 17-68 ng/l, >=69 ng/l). The standardized risk of stroke was computed using multivariable logistic regression with average treatment effect modeling. Results The final study sample consisted of 26867 persons, of whom 10407 (38.7%) were diagnosed with myocardial infarction, 1404 (5.2%) with unstable angina, and 15056 (56.0%) with suspected myocardial infarction or chest pain. Median age was 64.3 years, and 40.1% were women. The prevalences of known cardiovascular disease were as follows: coronary artery disease, 20.2%; prior coronary revascularization, 8.4%; heart failure, 6.4%; and atrial fibrillation, 8.9%. At 30 days, 69 individuals had been diagnosed with a stroke, and an additional 185 individuals were diagnosed from days 31 through 365. The standardized risk of stroke at 30 days was <=0.31% in all main groups and did not meaningfully differ from each other. The risk remained low between days 31-365 (<=0,79%), with no significant between-group difference. The magnitude of hsTnT change within each group did not affect stroke risk, nor did hsTnT quartile based on the first measurement. Conclusions Persons with suspected acute coronary syndrome had a very low overall risk of incident stroke. Single or serial hsTnT levels at presentation did not seem helpful in identifying individuals at an increased risk of stroke.

The impact of intimate partner violence on adverse birth outcomes in 20 sub-Saharan African countries: propensity score matching analysis

BackgroundIntimate partner violence (IPV) is a significant public health problem, with serious consequences on women's physical, mental, sexual, and reproductive health, as well as birth outcomes. Women who encounter IPV are more likely to experience adverse birth outcomes such as low birth weight, premature delivery, and stillbirth. Although numerous studies are exploring the association between IPV and adverse birth outcomes, they merely used classical models and could not control for potential confounders. The purpose of this study was to ascertain whether there was a causation between IPV and adverse birth outcomes in sub-Saharan Africa (SSA) using a quasi-experimental statistical technique [i.e., propensity score matching (PSM) analysis].MethodThis study used the most recent (2015–22) Demographic and Health Survey (DHS) data from 20 SSA countries. A total weighted sample of 13,727 women was included in this study. IPV (i.e., sexual, physical, emotional, and at least one form of IPV) was the exposure/treatment variable and adverse birth outcomes (preterm delivery, low birth weight, stillbirth, and macrosomia) were the outcome variables of this study. PSM was employed to estimate the impact of IPV on adverse birth outcomes.ResultsThe average treatment effects (ATE) of sexual, physical, emotional, and at least one form of IPV were 0.031, 0.046, 0.084, and 0.025, respectively. Sexual, physical, emotional, and at least one form of IPV increased adverse birth outcomes by 3.1%, 4.6%, 8.4%, and 2.5%, respectively. Findings from the average treatment effect on treated (ATT) showed that women who experienced sexual, physical, emotional, and at least one form of IPV had an increased risk of adverse birth outcomes by 3.6%, 3.7%, 3.3%, and 3.0%, respectively, among treated groups.ConclusionThis study demonstrates a causal relationship between IPV and adverse birth outcomes in SSA countries, indicating a need for programs and effective interventions to mitigate the impact of IPV during pregnancy to reduce related adverse pregnancy outcomes. Furthermore, we suggest further research that investigates the causal effect of IPV on adverse birth outcomes by incorporating additional proximal variables not observed in this study.

Ethnic disparity in the care and management of non-ST-segment elevation myocardial infarction and its impact on short-term and long-term survival: a long-term study of a national registry

Abstract Background Previous examination of data from the United Kingdom indicates no apparent ethnic disparity in the treatment of patients hospitalised with non-ST-segment elevation myocardial infarction (NSTEMI). However, it remains uncertain whether this lack of disparity results in similar long-term survival outcomes among ethnic minority groups, particularly those with multiple underlying risk factors for coronary artery disease, when compared to White patients. Purpose To assess the impact of quality of care on short-term and long-term survival among NSTEMI patients while examining disparities based on ethnicity. Methods We analysed records of 252,964 individuals diagnosed with NSTEMI from the Myocardial Ischaemia National Audit Project database spanning 2005 to 2019, alongside Office of National Statistics data for mortality. Among them, 233,158 were identified as White patients, while 19,806 were categorised as belonging to ethnic minority groups (Asian, Black, and mixed ethnicity). Propensity score matching was used to compare average treatment effects between cohorts while survival was compared using Cox regression model. Results Ethnic minorities were younger (median age in years) (66 vs. 73, P < 0.001), predominantly male (70% vs. 63%, P < 0.001), and exhibited a higher prevalence of cardiovascular risk factors such as diabetes (52% vs. 24%, P < 0.001), hypertension (67% vs. 54%, P < 0.001), hypercholesterolemia (49% vs. 34%, P < 0.001), and chronic renal dysfunction (13% vs. 8%, P < 0.001). Ethnic minorities more frequently underwent invasive coronary angiography (80% vs. 68%, P < 0.001), percutaneous coronary intervention (53% vs. 44%, P < 0.001), and coronary artery bypass grafting (5% vs. 4%, P < 0.001). After conducting propensity score matching, both cohorts had no significant differences in in-hospital all-cause mortality [odds ratio (OR) 1.13, confidence interval (CI) 0.89 – 1.43; P = 0.268], cardiac mortality (OR 1.20, CI 0.89 – 1.54; P = 0.209), one-year mortality (OR 1.01, CI 0.89 – 1.13; P = 0.893) and major adverse cardiovascular events (OR 1.21, CI 0.95 – 1.48; P = 0.108). However, upon conducting a five-year survival analysis, ethnic minorities had better survival rates than their White counterparts (Hazard ratio (HR) 0.89, CI 0.86-0.92; P < 0.001). Conclusions Despite ethnic minorities being at a higher risk for coronary artery disease, our findings indicate that they experience better five-year survival rates than White patients. This suggests equitable access to care and potentially a more aggressive treatment approach in this relatively young patient cohort.

High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome

Abstract Background In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized. Purpose We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS. Methods Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-15 ng/l, 16-66 ng/l, >=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling. Results The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample. Conclusions In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure

A selective diesel vehicle ban’s impact on NO2 concentrations in Munich: a quasi-experimental study

Abstract Background The European Union’s current NO2 concentration limit of 40 μg/m³ is regularly exceeded in Munich, Germany. This limit is likely to be reduced towards the WHO recommended target of 10 μg/m³. In response, the city enacted a selective ban on older diesel vehicles, specifically those categorized as Euro 4 or older, within the current low-emission zone in February 2023. Our study examined how Munich’s selective ban on diesel vehicles impacted NO2 levels, concentrating on the six-month period after its introduction. Methods We employed a synthetic control approach in the primary analysis and a controlled interrupted time series approach in the secondary analysis. These quasi-experimental methods establish a ‘counterfactual’ no-intervention scenario, allowing for comparison with the actual observed scenario and estimation of the impact of the intervention. Historical data from monitoring stations within and outside the low-emission zone from 2014 to 2022 were utilized as controls, while potential confounders were considered. Results NO2 concentrations within Munich’s low-emission zone decreased across the study period. Effects of the selective diesel vehicle ban at monitoring stations within the low-emission zone were minimal, with wide confidence intervals indicating uncertainty. At Landshuter Allee, the average intervention effect was -2.67 μg/m3 (95%-CI = [-12.72; 7.38]), at Stachus it was -2.74 μg/m3 (95%-CI = [-9.91; 4.42]) and at Lothstrasse, it was -1.03 μg/m3 (95%-CI = [-7.75; 5.69]). The secondary analysis confirms these findings. Conclusions Munich’s selective diesel vehicle ban had limited effects in reducing NO2 concentrations. Factors such as its narrow focus on Euro 4 diesel vehicles, numerous exemptions, and unclear enforcement may explain this outcome. Comprehensive strategies and continuous monitoring and evaluation are crucial for effectively addressing urban air pollution and protecting public health. Key messages • Munich’s selective diesel vehicle ban had minimal effects on reducing NO2 levels, possibly due to its narrow scope, many exemptions, and unclear enforcement. • Current guidelines and court rulings signal the need for more effective solutions beyond selective bans, emphasizing the importance of well-designed interventions and rigorous evaluation.

Antidepressant medication before and after exiting paid work: a population-based study from Sweden

Abstract Background Exiting paid work can be linked to changes in mental health. However, antidepressant medication as an indicator of mental disorder has not been studied in a population that continues working longer. We aimed to explore trajectories of antidepressant medication before and after exiting paid work, among people in paid work at least until age 66. We then examined how sociodemographic factors and prior sickness absence and disability pension (SADP) were associated with such trajectories. Methods We included all people living in Sweden 2005-2020, aged 65-70 and in paid work 2010 based on income (N = 32,849, 39% women). All participants were in paid work at least 2005-2011, exited work during 2012-2015 and were not in paid work 2016-2020. We used register microdata for five years before and five years after exiting paid work and included a range of sociodemographic factors at the exit year as well as number of SADP days/year due to mental diagnosis (ICD-10) prior to work exit. We used group-based trajectory modelling to examine developmental patterns in antidepressant medication (ATC-code N06A) and average marginal effects to study factors that were associated with each trajectory. Results A majority, 89.5% did not have any antidepressant medication during the study period. Among those with such medication, two latent trajectories were identified: 94% had constant use and 6% increasing use. Having any SADP due to mental diagnoses before work exit was the most consistent determinant of belonging to the trajectories of increasing or of constant use of antidepressant medication, even after full adjustments. Older age at work exit was associated with a lower likelihood of belonging to increasing antidepressant medication trajectory. Conclusions Exit from paid work did not result in any major changes in the developmental patterns in antidepressant medication. Prior SADP was the most consistent determinant of antidepressant medication even after exit from paid work. Key messages • Most people working until aged 66 or older had no antidepressant use and among those who did, the use was stable. Only in a small group such medication increased, already before their work exit. • Sickness absence or disability pension days with mental diagnoses before work exit was associated with both increasing and constant antidepressant medication trajectories after the work exit.

The effects of hypothetical psychological interventions on alcohol use in European young adults

Abstract Background Low psychosocial well-being (PWB) and high emotion-driven impulsiveness (EDI) are associated with alcohol. Yet, it is unclear whether a hypothetical intervention targeting one or the other in adolescence might be more effective in reducing alcohol consumption (AC) in young adulthood. Therefore, we aimed to compare the separate causal effects of PWB and EDI in adolescence on AC in young adulthood. Methods We included 505 European young adults from the IDEFICS/I.Family cohort (mean age: 20.2 years; age range: 18.2-23.5 years) who did not drink alcohol at study entry. AC was operationalized as the amount of weekly consumed alcoholic beverages (mean: 4.2 drinks per week; range: 0.3-70 drinks per week). EDI was assessed using the negative urgency subscale from the UPPS-P Impulsive Behaviour Scale. PWB was assessed using the KINDLR Health-Related Quality of Life Questionnaire. Following the principles of target trial emulation, we estimated, separately, the average causal effects of PWB and EDI on AC accounting for relevant confounders and applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). We stratified the results by sex and parental education. Results If all adolescents, hypothetically, had high levels of PWB, compared to low levels, we estimated a decrease in the average amount of alcoholic beverages in young adulthood by 0.1 drinks per week [95%-confidence interval: -2.3; 2.1]. Furthermore, if all adolescents had low levels of EDI, compared to high levels, we estimated an increase in alcoholic beverages in young adulthood by 1.5 drinks per week [0.1; 2.9]. Different effects for sex and parental education groups were found. Conclusions Hypothetical interventions targeting PWB in adolescents were not found to have effects on reducing AC in young adulthood. Interventions targeting EDI, however, would lead to an increase in AC. This may be due to unmeasured confounding and the missing distinction between drinking motives. Key messages • We demonstrate that causal inference methods, compared to traditional ones, improve the robustness of estimated effect measures and address important sources of bias in European cohort data. • To inform public health interventions on reducing alcohol consumption, future research should investigate different drinking motives, e.g. alleviating negative emotions or enhancing positive emotions.

Early-life threat and deprivation: Are children similarly affected by exposure to each?

Extensive evidence documents negative consequences of adversity for children's development. Here, we extend such work by looking beyond average effects to consider variation in susceptibility to both threat and deprivation in terms of cognitive and social-emotional development, using an influence-statistic methodology. Data come from the ongoing Avon Longitudinal Study of Parents and Children (N = 14,541, 49.1% female, age range: 6 month to 12 year, race and ethnicity: 97.8% white, 0.4% black, and 0.6% other). With respect to anticipated associations of threat with problem behavior and of deprivation with cognition, results of this pre-registered research revealed that a roughly equal proportion of children proved to be susceptible in a domain-general manner (similarly influenced) and a domain-specific one (dissimilarly influenced). Implications for intervention are considered.

Impact of compliance with project requirements on projects value outcomes: Evaluation from TASAF-III beneficiaries’ perspectives in Tanzania

The study sought to evaluate the impact of compliance with projects requirements on projects value outcomes from Tanzania Social Action Fund (TASAF)-III beneficiaries’ perspectives in Tanzania. Specifically, the study evaluated the impact of compliance with project requirements on households’ relief from transitional income poverty (as a measure of projects value outcomes) in Tanzania. The study was a cross sectional design with multiple cases approach undertaken in twelve TASAF-III supported community economic development (CED) projects. Under multistage sampling procedure, the said CED projects, their six hosting districts and regions (Kilosa–Morogoro; Handeni–Tanga; Misungwi–Mwanza; Uyui–Tabora; Kibondo–Kigoma; and, Rungwe–Mbeya) were identified using stratified sampling. Simple random sampling enhanced to determine a sample of 480 households. Data were collected using research schedules and were descriptively and inferentially analyzed using STATA software. Propensity score matching (PSM), coupled with logistic model was considered the apt test statistic. The average treatment effect on the treated (ATT) observation results shown that, the mean differences in incomes [TZS. 7 794.30; t=0.61(t<2.00)] and spending [TZS 11 388.50; t=0.96 (t<2.00)] between the treated and control households’ are non-significant at t<2.00. This implied that, compliance with TASAF-III project requirements has no significant impact on households’ income poverty relief in Tanzania. Moreover, compliance with requirements does not necessarily lead to desired projects value outcomes—if requirements are not well defined. The study stresses on the selection of right projects’ requirements with positive outcomes rather than having a set of requirements which are non-predictive to the desired targets’ felt needs—when in compliance with.

When does adjusting covariate under randomization help? A comparative study on current practices

PurposeWe aim to thoroughly compare past and current methods that leverage baseline covariate information to estimate the average treatment effect (ATE) using data from of randomized clinical trials (RCTs). We especially focus on their performance, efficiency gain, and power.MethodsWe compared 6 different methods using extensive Monte-Carlo simulation studies: the unadjusted estimator, i.e., analysis of variance (ANOVA), the analysis of covariance (ANCOVA), the analysis of heterogeneous covariance (ANHECOVA), the inverse probability weighting (IPW), the augmented inverse probability weighting (AIPW), and the overlap weighting (OW) as well as the augmented overlap weighting (AOW) estimators. The performance of these methods is assessed using the relative bias (RB), the root mean square error (RMSE), the model-based standard error (SE) estimation, the coverage probability (CP), and the statistical power.ResultsEven with a well-executed randomization, adjusting for baseline covariates by an appropriate method can be a good practice. When the outcome model(s) used in a covariate-adjusted method is closer to the correctly specified model(s), the efficiency and power gained can be substantial. We also found that most covariate-adjusted methods can suffer from the high-dimensional curse, i.e., when the number of covariates is relatively high compared to the sample size, they can have poor performance (along with lower efficiency) in estimating ATE. Among the different methods we compared, the OW performs the best overall with smaller RMSEs and smaller model-based SEs, which also result in higher power when the true effect is non-zero. Furthermore, the OW is more robust when dealing with the high-dimensional issue.ConclusionTo effectively use covariate adjustment methods, understanding their nature is important for practical investigators. Our study shows that outcome model misspecification and high-dimension are two main burdens in a covariate adjustment method to gain higher efficiency and power. When these factors are appropriately considered, e.g., performing some variable selections if the data dimension is high before adjusting covariate, these methods are expected to be useful.

Self-Efficacy, Patient Activation, and the Burden of Inflammatory Bowel Disease on Patients' Daily Lives.

The effective management of inflammatory bowel disease (IBD) requires complex self-management behaviors. Both patient activation (the degree to which patients are willing and able to engage in care) and self-efficacy (one's confidence in performing certain behaviors) are thought to play an important role in chronic disease self-management, but patient activation is a broad concept that can be more difficult to precisely target than self-efficacy. We aimed to describe the relationship between patient activation, self-efficacy, and the burden of IBD on patients' daily lives. Patients with IBD were recruited from a single center to complete a survey including the Patient Activation Measure (PAM-13®), the IBD Self-Efficacy Scale (IBD-SES), and an IBD-specific patient-reported outcome measure. Using multivariable linear regression, we examined the relationship between IBD burden, self-efficacy, and patient activation, adjusting a priori for age, gender, IBD type, IBD medications, active corticosteroid use, anxiety, and depression. We performed a post-hoc mediation analysis to examine self-efficacy as a potential mediator in the relationship between patient activation and the burden of IBD on patient's daily lives. A total of 132 patients with IBD completed the survey (59% Crohn's disease, 41% ulcerative colitis, 52% female). Higher levels of patient activation and higher levels of self-efficacy were each associated with lower IBD burden (patient activation: ß = -1.9, p < 0.001, self-efficacy: ß = -2.6, p < 0.001). Post hoc mediation analysis confirmed that the relationship between patient activation and daily IBD burden was mediated by self-efficacy (Average Causal Mediation Effect = -1.00, p < 0.001, proportion mediated = 0.62, p < 0.001). The relationship between patient activation and IBD burden is highly mediated by self-efficacy, suggesting that self-efficacy could be a more precise target for intervention. Future studies could focus on targeting self-efficacy to build individuals' confidence in IBD self-management and testing of IBD-tailored self-management programs to ultimately improve disease outcomes.

The relationship between health literacy and healthy lifestyle behaviors: A meta-analysis.

Health literacy and healthy lifestyle behaviors are both pivotal elements for public health improvement. This meta-analysis aims to scrutinize studies investigating the nexus between health literacy and healthy lifestyle behaviors and to examine the correlation between health literacy and such behaviors. Studies conducted from 2013 to 2023 exploring the association between health literacy and healthy lifestyle behaviors, as well as the impact of gender and chronic disease status on health literacy, were included. The selection criteria for the meta-analysis involved a literature search utilizing databases such as PubMed, Google Academic, Web of Science, and the National Thesis Center. The keywords "health literacy" and "healthy lifestyle behaviors" were employed, identifying 206 studies. Subsequently, 53 studies meeting predetermined criteria were deemed suitable for inclusion in the meta-analysis. The analysis of the relationship between health literacy and healthy lifestyle behaviors revealed no publication bias. Despite heterogeneity among the studies, the correlation effect size was determined to be 0.278 using the random effect model. In the meta-analysis examining the effect of gender on health literacy, no publication bias was detected. Since there was heterogeneity among the studies, the average effect size was calculated as 0.078 according to the random effect model. Regarding the meta-analysis on the effect of chronic disease status on health literacy, no publication bias was observed, and due to homogeneity between the studies, the average effect size was determined to be -0.098 using the fixed effect model. A positive yet weak relationship was identified between health literacy and healthy lifestyle behaviors. Notably, gender was a significant sociodemographic factor affecting health literacy, with higher levels observed in women. Moreover, individuals without chronic diseases exhibited higher mean health literacy scores than those with chronic diseases.

Ten years survival benefit and appropriateness of surgical versus percutaneous revascularization in synergy between percutaneous coronary intervention with taxus and cardiac surgery randomized trial.

Average treatment effects from randomized trials do not reflect the heterogeneity of an individual's response to treatment. This study evaluates the appropriate proportions of patients for coronary artery bypass grafting, or percutaneous intervention based on the predicted/observed ratio of 10-year all-cause mortality in the SYNTAX population. The study included 1800 randomized patients and 1275 patients in the nested percutaneous (n = 198) or surgical (n = 1077) registries. The primary end-point was 10-year all-cause mortality. The SYNTAX score II-2020 was validated internally in the randomized cohort and externally in the registry cohort. Proportions of patients with survival benefits from coronary artery bypass grafting or percutaneous intervention were determined using SYNTAX score II-2020. Ten-year mortality was 23.8% for coronary artery bypass grafting 28.6% for percutaneous intervention in the randomized cohort, 27.6% for coronary artery bypass grafting, and 55.4% for percutaneous intervention in the registries. In the coronary artery bypass grafting registry, the SYNTAX score II-2020 predicted 10-year mortality with helpful calibration and discrimination (C-index : 0.70, intercept : 0.00, slope : 0.76). The proportion of patients deriving a predicted survival benefit from coronary artery bypass grafting over percutaneous intervention was 82.4% (2143/2602) and 17.7% (459/2602) for the entire SYNTAX trial population; translating into a 4.7 to 1 appropriate ratio of treatment allocation to coronary artery bypass grafting and percutaneous intervention. Choosing a revascularization modality should depend on an individual's long-term prognosis rather than average treatment effects. Additionally, patients should be informed about their predicted prognosis. Registered on clinicaltrial.govSYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050);SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

PENGEMBANGAN E-COMIC BERBASIS PROBLEM BASED LEARNING (PBL) MATERI SISTEM EKSKRESI MANUSIA UNTUK MENINGKATKAN HASIL BELAJAR SISWA

This research was conducted because E-comic learning media based on Problem Based Learning material on the human excretory system was not yet available at Lolowau 2 State Junior High School and student learning outcomes did not meet the Minimum Completeness Criteria. The research applied is development research (Development Research) with the four D model. The results of the research obtained an average validity test score of 89.52%, practicality test by teachers 3.50 while students 3.57 and an average effectiveness test score 90.14 so it can be concluded that E-comic learning media can be applied in the learning process of human excretory system material in class Vlll.

Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. Adult patients presenting to the emergency department with severe sepsis or septic shock. EGDT vs. usual care. A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

The application of Bayesian method in estimating heterogeneity of treatment effect

It is well recognized that the benefit of medical interventions may not be distributed evenly in the target population due to patient heterogeneity, and conclusions based on traditional randomized clinical trials do not apply to everyone. Considering the increasing cost of randomized trials and difficulties in recruiting patients, there is an urgent need to develop analytical methods to estimate treatment effects in subgroups. In particular, due to limited sample sizes of subgroups, standard analysis tends to yield wide confidence intervals for the treatment effect, which are often uninformative. In this article, the superiority of the empirical Bayes estimate of the conditional average treatment effect is demonstrated by using a linear regression model to specifically represent treatment-covariate interactions. To obtain more accurate prior distributions and posterior estimates of treatment effects in subgroups, we utilize the covariate-dependent precision parameter across subgroups. Based on subgroup data obtained from clinical trials, the covariate-dependent precision parameter is used to assess the similarity of treatment effects across subgroups, which is an approach to obtain more reasonable prior information. To verify the validity of the empirical Bayes method, we evaluate it by a real clinical trial comparing insulin and metformin.