Individual Participant Data Meta-analysis Research Articles

Association of smoking with knee osteoarthritis structural defects and symptoms: an individual participant data meta-analysis

Prior meta-analyses have suggested a protective link between smoking and knee osteoarthritis (KOA), but they relied on aggregate data, potentially obscuring the true relationship. To address this limitation, we conducted an Individual Participant Data (IPD) meta-analysis using data from three large cohorts: the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Participants from 16 centers in the USA and Netherlands were categorized as current, former, or never smokers. We assessed six outcomes, three related to structural changes over 4–5 years of follow-up, and three related to changes in KOA symptoms over 2–2.5 years, 5 years, and 7–8 years of follow-up. First, the incidence of radiographic KOA was evaluated in 10,072 knees, defined as having a Kellgren-Lawrence grade ≥ 2 (‘radiographic KOA’) at follow-up but not at baseline. Second, the progression of radiographic KOA was evaluated in 5274 knees, defined as an increase in Kellgren–Lawrence grade between baseline and follow-up in knees that had radiographic KOA at baseline. Third, the incidence of symptomatic KOA was evaluated in 12,910 knees, defined as having radiographic KOA in addition to symptoms at follow-up but not at baseline. Fourth, fifth, and sixth, we investigated changes between baseline and all follow-ups in scores for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales of pain, disability, and stiffness (in 2640 knees). There were no differences between smoking groups in any of these six outcomes. Our study, leveraging data from three large cohorts and the advantages of IPD, finds no evidence that smoking offers any protection against KOA, refuting the notion that smoking may benefit joint health.

Changes in Cardiorespiratory Fitness Following Exercise Training Prescribed Relative to Traditional Intensity Anchors and Physiological Thresholds: A Systematic Review with Meta-analysis of Individual Participant Data.

It is unknown whether there are differences in maximal oxygen uptake ( O2max) response when prescribing intensity relative to traditional (TRAD) anchors or to physiological thresholds (THR). The present meta-analysis sought to compare: (a) mean change in O2max, (b) proportion of individuals increasing O2max beyond a minimum important difference (MID) and (c) response variability in O2max between TRAD and THR. Electronic databases were searched, yielding data for 1544 individuals from 42 studies. Two datasets were created, comprising studies with a control group ('controlled' studies), and without a control group ('non-controlled' studies). A Bayesian approach with multi-level distributional models was used to separately analyse O2max change scores from the two datasets and inferences were made using Bayes factors (BF). The MID was predefined as one metabolic equivalent (MET; 3.5 mLkg-1min-1). In controlled studies, mean O2max change was greater in the THR group compared with TRAD (4.1 versus 1.8 mLkg-1min-1, BF > 100), with 64% of individuals in the THR group experiencing an increase in O2max > MID, compared with 16% of individuals taking part in TRAD. Evidence indicated no difference in standard deviation of change between THR and TRAD (1.5 versus 1.7 mLkg-1min-1, BF = 0.55), and greater variation in exercise groups relative to non-exercising controls (1.9 versus 1.3 mLkg-1min-1, BF = 12.4). In non-controlled studies, mean O2max change was greater in the THR group versus the TRAD group (4.4 versus 3.4 mLkg-1min-1, BF = 35.1), with no difference in standard deviation of change (3.0 versus 3.2 mLkg-1min-1, BF = 0.41). Prescribing exercise intensity using THR approaches elicited superior mean changes in O2max and increased the likelihood of increasing O2max beyond the MID compared with TRAD. Researchers designing future exercise training studies should thus consider the use of THR approaches to prescribe exercise intensity where possible. Analysis comparing interventions with controls suggested the existence of intervention response heterogeneity; however, evidence was not obtained for a difference in response variability between THR and TRAD. Future primary research should be conducted with adequate power to investigate the scope of inter-individual differences in O2max trainability, and if meaningful, the causative factors.

Susceptibility to online misinformation: A systematic meta-analysis of demographic and psychological factors

Nearly five billion people use and receive news through social media and there is widespread concern about the negative consequences of misinformation on social media (e.g., election interference, vaccine hesitancy). Despite a burgeoning body of research on misinformation, it remains largely unclear who is susceptible to misinformation and why. To address this, we conducted a systematic individual participant data meta-analysis covering 256,337 unique choices made by 11,561 US-based participants across 31 experiments. Our meta-analysis reveals the impact of key demographic and psychological factors on online misinformation veracity judgments. We also disentangle the ability to discern between true and false news (discrimination ability) from response bias, that is, the tendency to label news as either true (true-news bias) or false (false-news bias). Across all studies, participants were well above-chance accurate for both true (68.51%) and false (67.24%) news headlines. We find that older age, higher analytical thinking skills, and identifying as a Democrat are associated with higher discrimination ability. Additionally, older age and higher analytical thinking skills are associated with a false-news bias (caution). In contrast, ideological congruency (alignment of participants' ideology with news), motivated reflection (higher analytical thinking skills being associated with a greater congruency effect), and self-reported familiarity with news are associated with a true-news bias (naïvety). We also find that experiments on MTurk show higher discrimination ability than those on Lucid. Displaying sources alongside news headlines is associated with improved discrimination ability, with Republicans benefiting more from source display. Our results provide critical insights that can help inform the design of targeted interventions.

Comparative efficacy of interpersonal psychotherapy and antidepressant medication for adult depression: a systematic review and individual participant data meta-analysis.

Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.

Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool

Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates. To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates. This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled. For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population. The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes. This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.

Predictors of study dropout in cognitive-behavioural therapy with a trauma focus for post-traumatic stress disorder in adults: An individual participant data meta-analysis

BackgroundAvailable empirical evidence on participant-level factors associated with dropout from psychotherapies for post-traumatic stress disorder (PTSD) is both limited and inconclusive. More comprehensive understanding of the various factors that contribute...

Attachment relationship quality with mothers and fathers and child temperament: An individual participant data meta-analysis.

A growing body of research suggests that, compared with single parent-child attachment relationships, child developmental outcomes may be better understood by examining the configurations of child-mother and child-father attachment relationships (i.e., attachment networks). Moreover, some studies have demonstrated an above-chance level chance of concordance between the quality of child-mother and child-father attachment relationships, and child temperament has been offered as a plausible explanation for such concordance. To assess whether temperament plays a role in the development of different attachment network configurations, in this preregistered individual participant data meta-analysis we tested the degree to which the temperament dimension of negative emotionality predicts the number of secure, insecure-avoidant, insecure-resistant, and disorganized attachment relationships a child has with mother and father. Data included in the linear mixed effects analyses were collected from seven studies sampling 872 children (49% female; 83% White). Negative emotionality significantly predicted the number of secure (d = -0.12) and insecure-resistant (d = 0.11), but not insecure-avoidant (d = 0.04) or disorganized (d = 0.08) attachment relationships. Nonpreregistered exploratory analyses indicated higher negative emotionality in children with insecure-resistant attachment relationships with both parents compared to those with one or none (d = 0.19), suggesting that temperament plays a small yet significant role in child-mother/child-father insecure-resistant attachment relationships concordance. Taken together, results from this study prompt a more in-depth examination of the mechanism underlying the small yet significantly higher chance that children with increased negative emotionality have for developing multiple insecure-resistant attachment relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.

Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages. This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study. Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses. Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (-57.2 pmol/L [95% confidence interval, -69.4, -44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (-24.7 pmol/L [-29.1, -20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (-18.4 pmol/L [-27.6, -9.3]) and in men who formerly smoked (-5.7 pmol/L [-8.9, -2.6]), were in poor general health (-14.0 pmol/L [-20.1, -7.8]), and had diabetes (-19.6 pmol/L [-23.0, -16.3]), cardiovascular disease (-5.8 pmol/L [-8.3, -3.2]), or cancer (-19.2 pmol/L [-24.4, -14.1]). Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.

Blood pressure-lowering and risk of cancer: an individual participant-level data meta-analysis and mendelian randomisation studies

Abstract Background The current body of randomised evidence concerning the effect of blood pressure lowering on the risk of cancer remains limited. Purpose We leveraged the strengths of both randomised controlled trials (RCTs) and genomic information to examine this question. Methods Individual-level data from 314,016 participants from 42 RCTs were pooled to investigate the effect of blood pressure lowering on the risk of cancer through one-stage individual participant data (IPD) meta-analysis. The primary outcome was incident cancer, defined as the first occurrence of any cancer diagnosed after randomisation. Pre-specified subgroup analyses were conducted to assess heterogeneity in effect by follow-up time and baseline age groups, sex, body mass index categories, smoking status and previous use of antihypertensive drugs. Secondary outcomes were cause-specific cancer death and site-specific cancer risk comprising breast, colorectal, kidney, lung, prostate, and skin. Cox proportional hazard regression, stratified by trials, were used for statistical analyses. For site-specific cancers, analyses were complemented with Mendelian randomisation analyses using naturally randomised genetic variants associated with blood pressure lowering, retrieved from genome-wide association studies involving participants of European ancestry. Results Over a median of 4 years (interquartile range 2), 17,954 participants in RCTs were diagnosed with cancer of any type and 4,878 participants were reported to have died with cancer as the cause of death. In the IPD meta-analysis that compared the treatment arm with the comparator, no associations were identified between reductions in either systolic or diastolic blood pressure and the risk of incident cancer (hazard ratios [HRs] per 5 mmHg reduction in systolic and per 3 mmHg diastolic blood pressure were 1.03 (95% confidence interval [CI] 0.99-1.06) and 1.03 [0.98-1.07], respectively). We also found no pattern of increasing or decreasing relative risk for incident cancer during the follow-up period, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on the risk of cause-specific cancer death was identified for either systolic or diastolic blood pressure lowering. Considering site-specific cancers, we also found no evidence of effect, except for a possible link with lung cancer risk, with HRs of 1.17 [99.5% CI 1.02-1.32] for systolic blood pressure and 1.17 [99.5% CI 0.98-1.36] for diastolic blood pressure lowering. In Mendelian randomisation studies, no association was observed for genetically determined systolic and diastolic blood pressure and all the considered site-specific cancers, including overall lung cancer and its subtypes. Conclusion We found no consistent randomised evidence to suggest that blood pressure-lowering has a substantial effect, whether increasing or decreasing, on incident cancer, cause-specific cancer death, or selected site-specific cancers.

Stress Resilience And Resilience Factors Across 9 European Samples During The COVID-19 Pandemic

Abstract While many describe changes in mental health over the pandemic, we investigate change in resilience over time during the pandemic. Stress resilience can be operationalised as stressor reactivity, that is, how much a person’s mental health is affected by the stressors that they experience. Utilising the individual participant data (IPD) meta-analyses megadataset available we first define and quantify how many stressors individuals. We then regress this stressor exposure on mental health within each sample to compute each sample’s normative stressor reactivity. Each person’s individual stressor reactivity is then calculated as the residual to this line at each time points. Resilient outcomes can be understood as lower reactivity as this indicates lower susceptibility to stressors. Stressor reactivity (SR) scores control for individual stressor exposure, therefore allowing us to investigate resilience factors during a time in which exposure to macro and micro stressors varied greatly between individuals. Further, SR scores are a harmonised outcome that can easily compared across different samples in the IPD dataset. Using this outcome, we present findings on resilience trajectories and identify factors that are associated with resilient outcomes. We also disentangle the role of current stressor exposure and prior stressors, showing that prior exposure to stressors increases vulnerability in subsequent exposures. Our findings show that stressor reactivity over time was more stable than mental health symptoms during the pandemic, therefore indicating that SR as an outcome offers new insights into the impact of the pandemic.

6.M. Scientific session: Risk And Resilience Factors Of Mental Health During COVID: European Multi-country Data Findings

Abstract The COVID-19 pandemic significantly affected mental health. It worsened the mental health and well-being of those already vulnerable or exposed to excess pandemic-related stress. In addition, lockdowns and other measures created additional obstacles to mental health support access. In response, the European Commission funded the RESPOND project in 2020, aimed at enhancing the preparedness of mental health systems for pandemics and global crises. As part of the RESPOND project, (meta-)analyses were conducted on prospective cohort datasets, national health register data, and multi-country individual participant data (IPD). The aim was to examine whether there was a change in prevalence rates of mental health conditions (e.g., anxiety and depression) in the general adult population of the EU during, compared to before and in between, the COVID-19 pandemic waves. Analyses on risk factors (e.g. sociodemographic- and economic factors, severity of COVID-19 infection, (lack of) social activity and support, and loneliness) associated with psychological distress and mental disorders as well as resilience and well-being (coping strategies and core value orientations) in the general population or specific vulnerable groups were conducted as well. This workshop will feature five talks covering various aspects of the RESPOND epidemiological analyses. First, an introduction and rationale of the RESPOND study on short- and long-term impacts of the COVID-19 pandemic and outbreak response, will be provided. Subsequently, findings from the multi-country longitudinal COvid MEntal healTh Survey (COMET) on forecasting psychological distress throughout the pandemic will be presented. Second, findings from the French TEMPO (Trajectoires EpideMiologiques en POpulation) cohort and merged datasets will be presented indicating associations and interactions between socioeconomic factors, mental health, and public health behaviours during the pandemic. Third, using data of a large Belgian prospective cohort, fluctuations in risk of psychological distress across study waves and the factors associated with individual trajectories of psychological distress during the COVID-19 pandemic will be presented. Fourth, the risk of SARS-CoV-2 infection, severe COVID-19 outcomes, and death among individuals with various mental disorders, based on Spanish health records, will be presented with specific attention to sex differences. Finally, based on the IPD meta-analyses of 9 European cohorts, findings on stressor reactivity, resilience trajectories, and factors associated with resilient outcomes and vulnerability are presented. By presenting a selection of findings from large datasets together, we aim to facilitate discussions on critical topics such as vulnerability and resilience to mitigate mental health impacts in future public health crises. Key messages • Targeting specific individual vulnerabilities appears to be more effective in reducing the pandemics’ mental health impact than solely responding to pandemic-related fluctuations. • Research and harmonised data on vulnerability and resilience factors are essential for guiding the development of targeted interventions and support systems for vulnerable populations during crises.

Estimating reference intervals from an IPD meta-analysis using quantile regression

BackgroundReference intervals, which define an interval in which a specific proportion of measurements from a healthy population are expected to fall, are commonly used in medical practice. Synthesizing information from multiple studies through meta-analysis can provide a more precise and representative reference interval than one derived from a single study. However, the current approaches for estimating the reference interval from a meta-analysis mainly rely on aggregate data and require parametric distributional assumptions that cannot always be checked.MethodsWith the availability of individual participant data (IPD), non-parametric methods can be used to estimate reference intervals without any distributional assumptions. Furthermore, patient-level covariates can be introduced to estimate personalized reference intervals that may be more applicable to specific patients. This paper introduces quantile regression as a method to estimate the reference interval from an IPD meta-analysis under the fixed effects model.ResultsWe compared several non-parametric bootstrap methods through simulation studies to account for within-study correlation. Under fixed effects model, we recommend keeping the studies fixed and only randomly sampling subjects with replacement within each study. ConclusionWe proposed to use the quantile regression in the IPD meta-analysis to estimate the reference interval. Based on the simulation results, we identify an optimal bootstrap strategy for estimating the uncertainty of the estimated reference interval. An example of liver stiffness measurements, a clinically important diagnostic test without explicitly established reference range in children, is provided to demonstrate the use of quantile regression in estimating both overall and subject-specific reference intervals.

The effect of very preterm birth on the Five-Factor Model of personality traits: A meta-analysis of individual participant data

There is mixed evidence on personality differences among those born very preterm or with very low birth weight (VP/VLBW). This meta-analysis of individual participant data aimed to examine differences in personality traits between VP/VLBW ( n = 568) and term-born ( n = 1,060) adults, and the role of neonatal characteristics and neurosensory impairments in childhood, which have not been previously investigated. Six studies were identified from two research consortia and a systematic search of the literature (PubMed and Scopus); studies were eligible if they included VP/VLBW and term-born adults followed from birth and assessed personality using the Five-Factor Model. Risk of bias (Newcastle-Ottawa Scale) was generally not a concern apart from the use of self-reported measures and the rate of follow-up. Using a one-stage approach, VP/VLBW scored lower on extraversion and openness and higher on neuroticism and agreeableness than term-born participants after adjusting for sex and parental education. Within the VP/VLBW group, those with bronchopulmonary dysplasia scored lower on extraversion and higher on neuroticism, with similar findings after removing participants with neurosensory impairments. Altogether, these findings suggest that a proportion of the effect of VP/VLBW birth on personality may be attributed to neonatal morbidities and altered brain development, although other confounding factors require further research.

A tutorial on aggregating evidence from conceptual replication studies using the product Bayes factor.

The product Bayes factor (PBF) synthesizes evidence for an informative hypothesis across heterogeneous replication studies. It can be used when fixed- or random effects meta-analysis fall short. For example, when effect sizes are incomparable and cannot be pooled, or when studies diverge significantly in the populations, study designs, and measures used. PBF shines as a solution for small sample meta-analyses, where the number of between-study differences is often large relative to the number of studies, precluding the use of meta-regression to account for these differences. Users should be mindful of the fact that the PBF answers a qualitatively different research question than other evidence synthesis methods. For example, whereas fixed-effect meta-analysis estimates the size of a population effect, the PBF quantifies to what extent an informative hypothesis is supported in all included studies. This tutorial paper showcases the user-friendly PBF functionality within the bain R-package. This new implementation of an existing method was validated using a simulation study, available in an Online Supplement. Results showed that PBF had a high overall accuracy, due to greater sensitivity and lower specificity, compared to random-effects meta-analysis, individual participant data meta-analysis, and vote counting. Tutorials demonstrate applications of the method on meta-analytic and individual participant data. The example datasets, based on published research, are included in bain so readers can reproduce the examples and apply the code to their own data. The PBF is a promising method for synthesizing evidence for informative hypotheses across conceptual replications that are not suitable for conventional meta-analysis.

Prevalence of poststroke anxiety and its associations with global cognitive impairment: An individual participant data analysis

Background and purposeAnxiety is frequent after stroke; however, little is known about its determinants. This study aims to assess the prevalence and correlates of post stroke anxiety (PSA) within 3–6 months following ischemic stroke. MethodsThree cohort studies from the STROKOG consortium were involved. Demographic and clinical data were standardized. PSA and PSD were assessed using inventories. The criteria for post-stroke cognitive impairment (PSCI) were at least one cognitive domain impaired if applicable, or a Montreal Cognitive Assessment (MoCA) score. Descriptive analyses were conducted to ascertain the prevalence of anxiety. Comparisons between anxious and non-anxious patients in the total sample were made using χ2 and t-tests. A two-step individual participant data (IPD) meta-analysis was employed to identify factors associated with PSA. Results584 patients were included. The total prevalence of PSA was 35 % (95%CI = [31.23;38.97]) and ranged from 27 % to 45 % across cohorts. In the total sample, there was a higher proportion of females in the anxiety group than the non-anxiety group (χ2 = 19.62; p < 0.001). Anxious patients had lower education, (χ2 = 6.59; p = 0.03), higher stroke severity (t = 2.77; p = 0.002), and higher rates of PSD (χ2 = 118.09; p < 0.001), and PSCI (χ2 = 23.81, p < 0.001). The analysis demonstrates that the odds of presenting with PSA is larger in patients with PSCI (OR = 1.84, 95%CI = [1.14; 2.91]). ConclusionsAnxiety is frequent after stroke, especially in females, and is associated with depression and cognitive impairment.

Biomarkers of endothelial dysfunction and cognition: A two-step IPD meta-analysis.

This study assessed the association of plasma biomarkers of endothelial dysfunction with cognitive performance and decline. Data from 9414 individuals from eight Dutch cohorts were included (Ø age-range: 57-93 years). Plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin) were combined into a standardized composite score. Cognitive outcomes included executive function, processing speed, immediate and delayed memory, attention, and language. Linear regressions and linear mixed models were run in the individual cohorts and standardized coefficients were subsequently pooled using random-effects meta-analyses. A higher endothelial dysfunction composite score was cross-sectionally associated with worse performance on executive function, processing speed, delayed memory, and attention, but not immediate memory or language (pooled β-range: -0.04, -0.02). We found no association with change in cognition over time. This comprehensive two-step, individual participant data (IPD) meta-analysis showed a small, consistent cross-sectional association between endothelial dysfunction and worse cognitive performance across multiple domains but no support for a longitudinal association. Prior evidence on endothelial dysfunction (ED) biomarkers and cognition is conflicting. This two-step, individual participant data (IPD) meta-analysis used data from eight Dutch cohorts. ED was consistently associated with concurrent cognition. ED was not associated with a change in cognition over time. The association of ED with current cognition may be generic.

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis.

There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates. An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT. 429 (69%) patients' tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = .832). The test for interaction between RT and POLAR was statistically significant (p = .022). POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.

Individual Participant Data Meta-analysis: Individual Differences in Mediators of Parenting Program Effects on Disruptive Behavior

Although parenting programs are the most widely used approach to reduce children's disruptive behavior, there is a notable lack of understanding of the exact changes in parenting that underlie their effects. Challenges include the frequent use of composite measures of parenting behavior, and insufficient power to detect mediation effects and individual differences in these in individual trials. We pooled individual participant data from 14 European randomized controlled trials of social learning-based parenting programs to examine which specific parenting behaviors best explain program effects. Participants were 3,252 families with children aged 1 to 13 years. As putative mediators, we included parental use of praise, tangible rewards, physical discipline, harsh verbal discipline, and not following through on discipline. Additionally, we explored whether subgroups of families showing different mediational pathways exist. Changes in parenting partially mediated program effects, with all included parenting behaviors, except parental use of praise, serving as unique mediators. Less harsh verbal discipline and increased following through on discipline were the strongest mediators. We identified three subgroups with distinct responses to parenting programs. Most families benefited, partly through increased following through on discipline; those with the least or most difficulties were more likely to benefit less, or not at all. Our findings offer insight into the specific parenting behavior changes key to reducing disruptive child behavior, while highlighting the need for innovative research methodologies to gain a deeper understanding of individual differences in parenting program benefits and mechanisms.

Disruptive child behavior severity and parenting program session attendance: Individual participant data meta-analysis.

We tested if baseline disruptive child behavior problem severity predicts parental attendance at sessions of a parenting group program. We used a database of randomized trials of the Incredible Years parenting program in Europe and restricted the sample to participants randomized to the intervention arm. Using baseline Eyberg Child Behavior Inventory scores, we distinguished between trial-level problem severity and child-level problem severity, compared linear and quadratic functional forms at both levels, and considered cross-level interactions, all in a multilevel Poisson regression framework. Drawing on 918 participants in 12 trials, we found that within trials, parents of children with the least and most severe problems attended fewer sessions. Between trials, each additional 10-point increase in the Eyberg Child Behavior Inventory trial mean predicted an 11% increase in attendance. Models including child sex, age, or family low-income did not change coefficients or their interpretation. Our findings suggest that although generally attendance is higher in parents of children with more challenging behavior, it seems difficult for group programs to keep families with the least or most severe problems engaged. Our findings call for the need to better understand the conditions under which lower attendance translates into equivalent or lesser program benefits. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Is concurrent LR-5 associated with a higher rate of hepatocellular carcinoma in LR-3 or LR-4 observations? An individual participant data meta-analysis.

The Liver Imaging Reporting and Data System (LI-RADS) does not consider factors extrinsic to the observation of interest, such as concurrent LR-5 observations. To evaluate whether the presence of a concurrent LR-5 observation is associated with a difference in the probability that LR-3 or LR-4 observations represent hepatocellular carcinoma (HCC) through an individual participant data (IPD) meta-analysis. Multiple databases were searched from 1/2014 to 2/2023 for studies evaluating the diagnostic accuracy of CT/MRI for HCC using LI-RADS v2014/2017/2018. The search strategy, study selection, and data collection process can be found at https://osf.io/rpg8x . Using a generalized linear mixed model (GLMM), IPD were pooled across studies and modeled simultaneously with a one-stage meta-analysis approach to estimate positive predictive value (PPV) of LR-3 and LR-4 observations without and with concurrent LR-5 for the diagnosis of HCC. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Twenty-nine studies comprising 2591 observations in 1456 patients (mean age 59years, 1083 [74%] male) were included. 587/1960 (29.9%) LR-3 observations in 1009 patients had concurrent LR-5. The PPV for LR-3 observations with concurrent LR-5 was not significantly different from the PPV without LR-5 (45.4% vs 37.1%, p = 0.63). 264/631 (41.8%) LR-4 observations in 447 patients had concurrent LR-5. The PPV for LR-4 observations with concurrent LR-5 was not significantly different from LR-4 observations without concurrent LR-5 (88.6% vs 69.5%, p = 0.08). A sensitivity analysis for low-risk of bias studies (n = 9) did not differ from the primary analysis. The presence of concurrent LR-5 was not significantly associated with differences in PPV for HCC in LR-3 or LR-4 observations, supporting the current LI-RADS paradigm, wherein the presence of synchronous LR-5 may not alter the categorization of LR-3 and LR-4 observations.