Explore the vast range of titles available.

Previous work suggests that key factors for replicability, a necessary feature for theory building, include statistical power and appropriate research planning. These factors are examined by analyzing a collection of 12 standardized meta-analyses on language development between birth and 5 years. With a median effect size of Cohen's d = .45 and typical sample size of 18 participants, most research is underpowered (range = 6%-99%; median = 44%); and calculating power based on seminal publications is not a suitable strategy. Method choice can be improved, as shown in analyses on exclusion rates and effect size as a function of method. The article ends with a discussion on how to increase replicability in both language acquisition studies specifically and developmental research more generally.

INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort‐specific Cox proportional hazard regression analyses in a two‐step individual participant data meta‐analysis. RESULTS A one‐standard‐deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow‐up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights A two‐step individual participant data meta‐analysis was conducted. This was done at a global scale using data from 21 ethno‐regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

INTRODUCTION The extent to which the Big Five personality traits and subjective well‐being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia‐related neuropathology is unclear. METHODS Using data from eight independent studies (Ntotal= 44,531; Ndementia= 1703; baseline Mage= 49 to 81 years, 26 to 61% female; Mfollow‐up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia. RESULTS Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long‐term dementia diagnosis. There were no consistent associations with neuropathology. DISCUSSION This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy. Highlights N(+), C(−), E(−), PA(−), and NA(+) were associated with incident diagnosis. Results were consistent despite self‐report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death.

INTRODUCTION Risperidone is approved for behaviors and psychological symptoms of dementia (BPSD), despite modest efficacy and known risks. Identifying responsive symptoms, treatment modifiers, and predictors is crucial for personalized treatment. METHOD A one‐stage individual participant data meta‐analysis of six randomized controlled trials (risperidone: n = 1009; placebo: N = 712) was conducted. Mixed‐effects models assessed treatment effects, modifiers, and predictors, with BPSD measured via the Behavioral Pathology in Alzheimer's Disease scale. RESULTS Risperidone showed modest 8 week benefits for aggression (standardized mean difference [SMD]: −0.22; p < 0.001), psychosis (SMD: −0.23; p = 0.001), and anxiety/phobias (SMD: −0.19; p = 0.014), but not for activity, affective, or sleep disturbances. Pharmacokinetic/pharmacodynamic‐related factors (e.g., body mass index, endocrine disease, race/ethnicity) potentially modified treatment effects. Week 2 response predicted week 8 improvement (odds ratio: 4.46; p < 0.001). DISCUSSION Risperidone provided symptom‐specific benefits in reducing aggression, psychosis, and anxiety/phobias. Week 2 response predicted treatment outcomes, while certain patient characteristics may modify treatment response. Further research is needed to optimize the benefit–risk balance and individualize treatment. Highlights Risperidone modestly reduces symptoms of psychosis, aggression, and anxiety/phobias. Risperidone shows no effect on activity, affective, or sleep disturbances. Patient factors (body mass index, endocrine disease, race/ethnicity) may affect response. Positive response by week 2 predicts significant improvement later.

Abstract Aims Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: −0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls. Graphical Abstract Graphical Abstract CCA-IMT, common carotid artery intima-media thickness; CI, confidence interval; CVD, cardiovascular disease; Proof-ATHERO, Prospective Studies of Atherosclerosis.

Background The impact of commonly used non‐cancer medications on breast cancer outcomes remains underexplored in large datasets. Aims To evaluate the associations between commonly used non‐cancer medications and survival as well as adverse events in patients with breast cancer. Materials & Methods Individual participant data from 19 breast cancer clinical trials (n = 23,211) were pooled. Cox proportional hazards models and logistic regression analyses were used to assess associations between medication use and overall survival, progression‐free survival and grade ≥ 3 adverse events. Analyses were adjusted for demographic, cancer and comorbidity factors. Results Proton pump inhibitor use was associated with poorer overall survival (HR 1.19, 95% CI: 1.08–1.30), progression‐free survival (HR 1.11, 95% CI: 1.02–1.21) and an increased risk of grade ≥ 3 adverse events (OR 1.36, 95% CI: 1.21–1.53). Beta‐blockers, ACE inhibitors/ARBs and calcium channel blockers were linked with higher adverse event rates but showed no significant impact on survival. Statins and metformin demonstrated no significant associations with either survival or adverse events. Conclusion These findings emphasise the need for careful management of concomitant medications in breast cancer care and support ongoing research to optimise treatment safety and efficacy.

Background The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. Conclusions Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

Mika Kivimäki initiated the Individual Participant Data (IPD) Meta-Analysis Consortium, which currently has 50 members. The Consortium recently published several research reports on the relationship between job strain (high psychological demands and low decision latitude at work), on the one hand, and cardiovascular disease and its risk factors, on the other hand. Since IPD represents a novel way to conduct epidemiological research collaboration and as some of the findings from the IPD Consortium have been criticized, this commentary aims to address the rationales behind the approach and discuss some of the main criticisms of the Consortium. Researchers must tackle many problems when interpreting associations between a psychosocial work environment factor and a health outcome. First of all, work environment factors belong to a “distal” rather than a “proximal” group. In other words, the closer one gets to a biological mechanism relevant for disease development, the more likely it is that a relevant association will be strong. For instance, small samples are needed to establish an individual “brain” factor associated with depression or emotional exhaustion – simply because the brain factor is more or less depression. Factors related to work organization, on the other hand, are more “distal” since there are many factors that influence the relationship between the environment and the body’s organs. Accordingly, it is sometimes difficult to obtain sufficient statistical power for the establishment of an undisputable association. For instance, the long “distance” between job strain and the outcome, myocardial infarction (MI), explains why we should expect a weaker association than in the study of “proximal” factors, for instance myocardial metabolism in relation to MI. Nevertheless, on a societal level, job strain is very important since it affects many working people, with a prevalence in the working population (in the IPD Consortium study’s operational definition) of around 15%. Accordingly, if an unequivocal association is established, it is of major importance to those responsible for work organization and interventions designed to improve working conditions. However, large samples are needed to establish unequivocal proof. Since Karasek introduced his demand–control model (1), there have been many studies of the association between job strain and risk of MI. These studies have become increasingly sophisticated over the years. In addition, there is accumulated indirect evidence from longitudinal studies of the relationship between job strain, on the one hand, and blood pressure variations and endocrine, metabolic, and immunological parameters, on the other hand. The results from these studies give us a plausible physiological explanation of the assumed relationship between job strain and MI risk. A reason why this research field has attracted strong attention is that MI is an undisputable illness outcome. The study of MI risk, therefore, serves as a good scientific model for studying the relationship between job strain and adverse health outcomes in general. Establishment of and rationale behind the IPD Consortium There have been divided opinions about the relationship between job strain and risk of MI. The main reason for the controversy has been that, despite the relatively large size of several of the published cohort studies with number of observation years often in the range of 50 000, the statistical power has been too small for an unequivocal establishment of an association. As a result, Mika Kivimäki invited a number researchers, who had included psychosocial job factors in their study protocols and had or had not published results on the relationship between job strain and MI risk, to establish the IPD Consortium. Including unpublished cohorts was important as this provided a possibility to address the problem of publication bias – the tendency of researchers and journals to publish only positive findings that can lead to inflated associations. The IPD Consortium received financial support from research foundations in the UK, Sweden, Denmark, France, and Finland. The process started with the goal of testing the hypothesis that job strain is associated with MI risk. Research was divided into several stages, the first of which was to scrutinize questions regarding job strain in the participating cohorts. As expected, there were differences in formulations and response categories and also differences in the number of questions related to psychological demands and decision latitude. However, methodological work overseen by “judges” assessing the similarity between items in the different cohort questionnaires made it possible to establish which cohort questionnaires should be included as well as the minimum number of questions for each dimension in the total IPD study with acceptable precision for the two variables (ie, psychological demands and decision latitude). This was done and the results published (2) before the next phase started. Since the job strain variables in the different studies had been homogenized, it was possible to establish the median values for both demands and decision latitude within each cohort. According to the literature’s most common operationalization of job strain, the group with demand above median and, concomitantly decision latitude below median, was defined as the exposed group and the remaining population as the non-exposed. This enabled all individuals (almost 200 000) to be combined in a large cohort study. The average follow-up time was 7.5 years. The assessment of standard risk factors was treated in the same way – criteria were established before the analyses of the association between job strain and MI risk began. Two published articles (3, 4) described the scientific process in the IPD Consortium. Published findings The findings of the IPD Consortium have been published in The Lancet (5) and the Canadian Medical Association Journal (CMAJ) (6). They show a consistent and statistically significant age- and sex-adjusted relationship between job strain and MI risk, which remains even after further adjustments for country, socioeconomic position, and standard risk factors. The findings also show that exclusion of subjects with a short time lag between job strain assessment and onset of MI does not affect the statistical significance of the association – addressing the problem described above with possible vague pre-heart disease illness symptoms possibly influencing the job description. The findings also addressed a second question that had been raised in previous research (7): the risk associated with a combination of high psychological demands and low decision latitude was greater than the risks associated with each one of these two exposures. Finally, the IPD papers provided a response to the question regarding publication bias: Yes, there seemed to be some effect of publication bias since the odds ratio was lower in the unpublished versus published studies. However, even in the unpublished studies, there was a statistically significant relationship between job strain and subsequent MI risk. Criticism of the IPD findings Accordingly, the IPD Consortium has delivered clear responses to several of the questions that have been debated ever since Karasek introduced the model. The problem created by a “distal” relationship was solved by means of strict homogenization of the assessments in many cohorts so they could be used as one study. The findings were positive despite many conservative measures safeguarding against factors that could give rise to inflated relationships. Nevertheless, the IPD Consortium has been criticized for several reasons (8–10). The most critical voices have come from researchers involved in work-intervention research. The critical points can be divided into two groups. Standard risk factors’ role in the relationship between job strain and MI The first and most severe criticism relates to the way in which the role of the standard risk factors for heart disease (diabetes, high blood pressure, smoking, body mass index) has been presented in The Lancet and CMAJ. The latter article was based only on those cohorts that had full information about relevant lifestyle factors (102 000 participants), and the empirical conclusion has not been debated: job strain adds independently to illness risk even when standard risk factors have been taken into account. And, conversely, standard risk factors add independently to risk regardless of job strain. However, the independent association between job strain and MI risk is much weaker than the corresponding association between the standard risk factors and MI. No one could criticize the IPD Consortium for publishing that finding in itself. However, the practical interpretation formulated in The Lancet, “Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking” (5, p1491) has not been endorsed by all members of the IPD. In my mind, the conclusion goes beyond the analyses of the IPD study. I tried to change these formulations but of course in a large group of researchers (46 authors for The Lancet article) one has to compromise, and it becomes practically difficult to discuss changes particularly in the final phase before publication. Critics of the IPD Consortium argue this statement could be used as a justification among clinicians (cardiologists, occupational physicians, and general practitioners) for disregarding the patient’s psychosocial working conditions entirely. So what is the role of standard risk factors in the relationship between job strain and MI risk? In its studies (11, 12), the Consortium has shown that job strain is significantly associated with diabetes, physical inactivity, and obesity as well as to a summarized Framingham risk factor score. Accordi

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.