Individual Data Meta-analysis Research Articles

A META-ANALYTIC EXAMINATION OF THE EFFECT OF INDIVIDUAL AND SCHOOL-AVERAGE ACHIEVEMENT ON STUDENTS' SELF-CONCEPT IN SCIENCE

The purpose of the present study was to examine the effect of individual and school average achievement on students’ self-concept in science. The data of the last four Trends in International Mathematics and Science Study (TIMSS) cycles were used, and a two-stage individual data meta-analysis was conducted to examine the relationship between achievement and self-concept in science. In the first stage, multilevel structural equation modeling was performed for each dataset. Furthermore, the effect sizes were synthesized via meta-analysis with a three-level random-effect model. In addition, moderation analysis was conducted for the year, grade, and degree of stratification in countries. The results suggested a positive and significant effect of individual science achievement on the self-concept of students in science. On the other hand, the relation of the average school achievement was negative. The results were discussed by considering the big-fish-little-pond effect. Keywords: big fish little pond effect, TIMSS, self-concept, science education

Abstract WP248: Developing and Validating Post-Treatment HERMES Score to Predict Outcome From Anterior Circulation Large Vessel Occlusion Stroke: A Meta-Analysis of Individual Data From 7 Randomized Clinical Trials

Introduction: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making and family discussion. We aimed to develop and validate a simple prediction score applied at 24 hours to assist prognostication in patients with anterior circulation ischemic stroke due to large vessel occlusion. Methods: Using the HERMES collaboration dataset (n = 1764), patients in the endovascular therapy (EVT) arm were divided randomly into a derivation cohort (n = 430) and a validation cohort (n = 441). From a set of candidate predictors, forward selection using c-statistics was employed to select a model which was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in both the EVT validation cohort and in the control arm (n = 893) for mRS ≤2 and ≤3. Results: In the derivation cohort, two significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale [NIHSS] score at 24 h and age [β-coefficient 0.34 and 0.06]) were selected. Incorporating other variables did not much improve model performance. Among models with different weights, we derived the HERMES score: age (years)/10 + NIHSS score at 24 h, based on model performance and simplicity. The HERMES score was highly predictive for mRS ≤2 in the derivation cohort, validation cohort-EVT, and control arm (c-statistics 0.907, 0.914, and 0.909, respectively). Evaluation of the score against mRS ≤3 as an alternative outcome yielded similar results (c-statistics 0.911, 0.903, and 0.885). Among 435 subjects (24.7%) with HERMES score ≥25, the observed probability was 3.1-3.4% for mRS ≤2 and 9.4-16.7% for mRS ≤3 in the derivation cohort, validation cohort-EVT, and control arm (Figure). Conclusions: The HERMES score is a simple validated score to predict outcomes in patients with anterior circulation large vessel occlusion ischemic stroke regardless of intervention. HERMES score should be helpful in prognostic discussion with families on day two.

Granulocyte colony stimulating factor in decompensated cirrhosis, acute alcoholic hepatitis, and acute-on-chronic liver failure: A comprehensive meta-analysis of randomized controlled trials.

GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis. Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes. In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p=0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p=0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p=0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90. G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.

Predictive capacity of a genetic risk score for coronary artery disease in assessing recurrences and cardiovascular mortality among patients with myocardial infarction.

This study aimed to evaluate the capacity of a genetic risk score (GRS) for coronary artery disease (CAD) independent of classical cardiovascular risk factors to assess the risk of recurrence in patients with first myocardial infarction. The secondary aim was to determine the predictive value of this GRS. We performed a meta-analysis of individual data from three studies, namely, a prospective study including 75 patients aged <55 years, a prospective study including 184 patients with a mean age of 60.5 years, and a case-control study (77 cases and 160 controls) nested in a cohort of patients with first myocardial infarction. A GRS including 12 CAD genetic variants independent of classical cardiovascular risk factors was developed. The outcome was a composite of cardiovascular mortality and recurrent acute coronary syndrome. The GRS was associated with a higher risk of recurrence [hazard ratio = 1.24; 95% confidence interval (CI): 1.04-1.47]. The inclusion of the GRS in the clinical model did not increase the model's discriminative capacity (change in C-statistic/area under the curve: 0.009; 95% CI: -0.007 to 0.025) but improved its reclassification (continuous net reclassification index: 0.29; 95% CI: 0.08-0.51). The GRS for CAD, independent of classical cardiovascular risk factors, was associated with a higher risk of recurrence in patients with first myocardial infarction. The predictive capacity of this GRS identified a subgroup of high-risk patients who could benefit from intensive preventive strategies.

Mechanical ventilation in patients with acute brain injury: a systematic review with meta-analysis

ObjectiveTo describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation.DesignSystematic review with an individual data meta-analysis.SettingObservational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt < 8 ml/Kg of IBW versus Vt > = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) < or > = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes.PopulationPatients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h.Main outcome measuresThe primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio.ResultsThe meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p < 0.01).ConclusionsLow tidal volume, moderate to high PEEP, or protective ventilation were not associated with mortality and lower incidence of ARDS in patients with acute brain injury undergoing invasive mechanical ventilation. However, protective ventilation improved oxygenation and could be safely considered in this setting. The exact role of ventilatory management on the outcome of patients with a severe brain injury needs to be more accurately delineated.

Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis.

Although therapeutic drug monitoring of clozapine is recommended, its optimisation is often adjusted only on the basis of dosage. The aim of this study was to assess the link between clozapine plasma concentrations and clinical response by a meta-analysis of published studies and by an individual participant data meta-analysis. We conducted a computerised search of bibliographic databases (EMBASE, PubMed, Clinical Trials, and Web of Science) to identify studies that assessed the relationship between clozapine serum or plasma concentrations and clinical efficacy. Using pooled data, we investigated the association between improvement of clinical outcome and clozapine or norclozapine plasma concentrations, the sum of clozapine and norclozapine plasma concentrations, and the coefficient of variation of clozapine plasma concentrations. Using available individual data, we assessed the relationship between clozapine plasma concentrations and clinical response (changes in the Brief Psychiatric Rating Scale score) and identified a threshold level for a favourable clinical response. Fifteen studies satisfied inclusion criteria. Our meta-analysis showed that responders had clozapine plasma concentrations that were, on average, 117 ng/mL higher than non-responders. The patients with plasma clozapine concentrations above the thresholds identified in each study had a higher likelihood of responding (odds ratio = 2.94, p < 0.001). Norclozapine plasma concentrations were not associated with a clinical response. The meta-analysis of individual data supported this result and confirmed the link between clozapine concentrations and a change in the Brief Psychiatric Rating Scale score and/or the probability of clinical response. Finally, with the analysis of the coefficient of variation of clozapine plasma concentrations, we found that a greater inter-individual fluctuation in plasma concentrations was associated with a loss of clinical response. Our work confirmed that, in contrast to clozapine doses, clozapine plasma concentrations were related to a favourable clinical response, with a mean difference between responders and non-responders of 117 ng/mL. A threshold for a treatment response of 407 ng/mL was determined, with a high discriminatory capacity,and a sensitivity and specificity of 71% and 89.1%, respectively.

Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. Children aged 6 to 59 months. Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Serum zinc levels are associated with obesity and low-density lipoprotein cholesterol in Mexican adults

PurposeLittle is known about the association between serum zinc (Zn) levels and obesity in the Mexican population. Therefore, we tested the association between serum Zn levels, obesity status, and serum lipid levels in a sample of Mexican adults. MethodsAnthropometric data and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and triglycerides were analyzed in 96 Mexican adults. Serum Zn was measured with inductively coupled plasma mass spectrometry. An individual data meta-analysis of the association between serum Zn, overweight, and obesity status was performed in 172 adults from two different provinces in Mexico. ResultsSerum Zn was negatively associated with body mass index (BMI, β = −0.034 ± 0.013, p = 2.0 ×10-6) and obesity (odds ratio [OR]= 0.990, 95% confidence interval [CI]= 0.980–0.999, p = 3.4 ×10-5). The association between Zn level and obesity in Mexican adults was confirmed with an individual data meta-analysis (OR= 0.977, 95% CI= 0.966–0.988, p = 3.4 ×10-5). In addition, a significant interaction effect between serum Zn level and sex was observed on LDL-C level (β = 7.010 ± 3.295, p = 0.037). Serum Zn was negatively associated with LDL-C levels in women (β = −0.188 ± 0.074, p = 0.016). ConclusionOur results confirm the negative association of serum Zn level with obesity. For the first time, we show a sex-specific association between serum Zn and LDL-C levels in a Mexican population. However, further studies are needed in larger and more varied Mexican cohorts to replicate and confirm our findings.

Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity.

Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10−4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice’s weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

The nonlinear association between grandiose and vulnerable narcissism: An individual data meta-analysis.

Narcissism can manifest in grandiose and vulnerable patterns of experience and behavior. While largely unrelated in the general population, individuals with clinically relevant narcissism are thought to display both. Our previous studies showed that trait measures of grandiosity and vulnerability were unrelated at low-to-moderate levels of grandiose narcissism, but related at high levels. We replicate and extend these findings in a preregistered individual data meta-analysis ("mega-analysis") using data from the Narcissistic Personality Inventory (NPI)/Hypersensitive Narcissism Scale (HSNS; N=10,519, k=28) and the Five-Factor Narcissism Inventory (FFNI; N=7,738, k=17). There was strong evidence for the hypothesis in the FFNI (βGrandiose<1 SD =.08, βGrandiose>1 SD =.36, βGrandiose>2 SD =.53), and weaker evidence in the NPI/HSNS (βGrandiose<1 SD =.00, βGrandiose>1 SD =.12, βGrandiose>2 SD =.32). Nonlinearity increased with age but was invariant across other moderators. Higher vulnerability was predicted by elevated antagonistic and low agentic narcissism at subfactor level. Narcissistic vulnerability increases at high levels of grandiosity. Interpreted along Whole Trait Theory, the effects are thought to reflect state changes echoing in trait measures and can help to link personality and clinical models.

Rapid Transient Transcriptional Adaptation to Hypergravity in Jurkat T Cells Revealed by Comparative Analysis of Microarray and RNA-Seq Data.

Cellular responses to micro- and hypergravity are rapid and complex and appear within the first few seconds of exposure. Transcriptomic analyses are a valuable tool to analyze these genome-wide cellular alterations. For a better understanding of the cellular dynamics upon altered gravity exposure, it is important to compare different time points. However, since most of the experiments are designed as endpoint measurements, the combination of cross-experiment meta-studies is inevitable. Microarray and RNA-Seq analyses are two of the main methods to study transcriptomics. In the field of altered gravity research, both methods are frequently used. However, the generation of these data sets is difficult and time-consuming and therefore the number of available data sets in this research field is limited. In this study, we investigated the comparability of microarray and RNA-Seq data and applied the results to a comparison of the transcriptomics dynamics between the hypergravity conditions during two real flight platforms and a centrifuge experiment to identify temporal adaptation processes. We performed a comparative study on an Affymetrix HTA2.0 microarray and a paired-end RNA-Seq data set originating from the same Jurkat T cell RNA samples from a short-term hypergravity experiment. The overall agreeability was high, with better sensitivity of the RNA-Seq analysis. The microarray data set showed weaknesses on the level of single upregulated genes, likely due to its normalization approach. On an aggregated level of biotypes, chromosomal distribution, and gene sets, both technologies performed equally well. The microarray showed better performance on the detection of altered gravity-related splicing events. We found that all initially altered transcripts fully adapted after 15 min to hypergravity and concluded that the altered gene expression response to hypergravity is transient and fully reversible. Based on the combined multiple-platform meta-analysis, we could demonstrate rapid transcriptional adaptation to hypergravity, the differential expression of the ATPase subunits ATP6V1A and ATP6V1D, and the cluster of differentiation (CD) molecules CD1E, CD2AP, CD46, CD47, CD53, CD69, CD96, CD164, and CD226 in hypergravity. We could experimentally demonstrate that it is possible to develop methodological evidence for the meta-analysis of individual data.

Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data.

Few studies have simultaneously investigated the impact of inflammation and genetic polymorphisms of cytochromes P450 2C19 and 3A4 on voriconazole trough concentrations. We aimed to define the respective impact of inflammation and genetic polymorphisms on voriconazole exposure by performing individual data meta-analyses. A systematic literature review was conducted using PubMed to identify studies focusing on voriconazole therapeutic drug monitoring with data of both inflammation (assessed by C-reactive protein level) and the pharmacogenomics of cytochromes P450. Individual patient data were collected and analyzed in a mixed-effect model. In total, 203 patients and 754 voriconazole trough concentrations from six studies were included. Voriconazole trough concentrations were independently influenced by age, dose, C-reactive protein level, and both cytochrome P450 2C19 and 3A4 genotype, considered individually or through a combined genetic score. An increase in the C-reactive protein of 10, 50, or 100 mg/L was associated with an increased voriconazole trough concentration of 6, 35, or 82%, respectively. The inhibitory effect of inflammation appeared to be less important for patients with loss-of-function polymorphisms for cytochrome P450 2C19. Voriconazole exposure is influenced by age, inflammatory status, and the genotypes of both cytochromes P450 2C19 and 3A4, suggesting that all these determinants need to be considered in approaches of personalization of voriconazole treatment.

Decisions about antihypertensive treatment should focus on reducing cardiovascular risk

Epidemiological studies 1 Lewington S Clarke R Qizilbash N Peto R Collins R Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360: 1903-1913 Summary Full Text Full Text PDF PubMed Scopus (7223) Google Scholar , 2 Rapsomaniki E Timmis A George J et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people. Lancet. 2014; 383: 1899-1911 Summary Full Text Full Text PDF PubMed Scopus (819) Google Scholar provide strong evidence for an association between high blood pressure and fatal cardiovascular complications, and interventional studies have shown that antihypertensive treatments reduce cardiovascular events and all-cause mortality. 3 Thomopoulos C Parati G Zanchetti A Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and meta-regression analyses of randomized trials. J Hypertens. 2014; 32: 2285-2295 Crossref PubMed Scopus (167) Google Scholar , 4 Ettehad D Emdin CA Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016; 387: 957-967 Summary Full Text Full Text PDF PubMed Scopus (1541) Google Scholar Although the target blood pressure for patients with hypertension receiving treatment in the current US guidelines 5 Whelton PK Carey RM Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2018; 71: e127-e248 Crossref PubMed Scopus (2007) Google Scholar is less than 130/80 mm Hg and European recommendations indicate achieving 120–129/70–79 mm Hg for people younger than 65 years (and 130–139/70–79 mm Hg for those ≥65 years), 6 Williams B Mancia G Dessormais E et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). J Hypertens. 2018; 36: 1953-2041 Crossref PubMed Scopus (1073) Google Scholar other guidelines such as those from the UK 7 National Institute for Health and Care ExcellenceHypertension in adults: diagnosis and management. NICE Guideline 136. National Institute for Health and Care Excellence, London2019https://www.nice.org.uk/guidance/ng136Date accessed: April 4, 2021 Google Scholar recommend higher target values for treatment. Thus, threshold blood pressure levels for initiating therapy and target blood pressure levels with treatment remain controversial. Furthermore, the effect of initial blood pressure on outcome, and the benefit for patients treated in primary versus secondary prevention settings have not been settled. 4 Ettehad D Emdin CA Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016; 387: 957-967 Summary Full Text Full Text PDF PubMed Scopus (1541) Google Scholar , 8 Brunström M Carlberg B Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Intern Med. 2018; 178: 28-36 Crossref PubMed Scopus (177) Google Scholar Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysisIn this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Full-Text PDF Open Access

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334935 men.

BackgroundThe role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC.MethodsWe obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status.ResultsDuring 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26).ConclusionsThis first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data

BackgroundHigher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.MethodsIn an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5–25.0 kg/m2; 25.0–30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival.ResultsMean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.ConclusionsThe present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF.Graphic abstractCategories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

Neutralizing Antibodies Against SARS-CoV-2 Variants Induced by Natural Infection or Vaccination: A Systematic Review and Individual Data Meta-Analysis

Background: Recently emerged SARS-CoV-2 variants may pose a threat to immunity derived from prototypical SARS-CoV-2 infection or vaccination. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. Methods: We systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. Through pooled analyses we estimated lineage-specific GMTs across different study participants and types of neutralization assays. Findings: We identified 76 studies, including 2,876 individuals and 10,526 neutralization tests, meeting the eligibility criteria. Compared with reference lineage B, B.1.351 and B.1.617 significantly escaped natural-infection-mediated neutralization, with an average of 3.8-fold (95% CI: 3.4-4.4) and 4.0-fold (95% CI: 2.3-6.9) reduction in live virus neutralization assay, while neutralizing antibody titers against B.1.1.7 decreased slightly (1.3-fold, 95%CI: 1.1-1.6). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 and B.1.617, with a 32.6-fold (95% CI: 18.7-56.9) and 11.4-fold (95% CI: 8.6-15.2) for non-replicating vector vaccines, while 4.4-fold (95% CI: 4.0-5.0) and 2.1-fold (95%CI: 1.6-2.8) for mRNA platform vaccine. Neutralizing antibodies levels induced mRNA vaccines against SARS-CoV-2 variants were similar, or higher, than that derived from naturally-infected individuals. Interpretation: Antibody responses established by natural infection or vaccination have similar ability to neutralize B.1.1.7, but neutralizing titers against B.1.351 and B.1.617 were significantly reduced. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. Registration Information: The study has been registered with PROSPERO and is awaiting approval (ID: 256932). Funding Information: This study was funded by the National Science Fund for Distinguished Young Scholars (grant no. 81525023), Program of Shanghai Academic/Technology Research Leader (grant no.18XD1400300), National Science and Technology Major project of China (grant no. 2018ZX10713001-007, 2017ZX10103009-005, 2018ZX10201001-010), the US National Institutes of Health (R01 AI135115 to D.T.L. and A.S.A.) Declaration of Interests: H.Y. has received research funding from Sanofi Pasteur, and Shanghai Roche Pharmaceutical Company; D.T.L. and A.S.A. has received research funding from the US National Institutes of Health. None of those research funding is related to COVID-19. All other authors report no competing interests.

An Individual Patient Data Meta-Analysis with Colombian Studies on the Effect of Dark Chocolate Consumption on Cardiovascular Risk Parameters.

Background It is postulated that cocoa solids possess cardioprotective capacity by various mechanisms. In the different cocoa studies evaluating cardiovascular disease, there are no conclusive data on the role it plays in controlling the lipid profile and anthropometric variables, perhaps because the concentration of cocoa, the geographical origin of the population, and the different concentrations supplied lead to a high heterogeneity of results. This study aims to estimate the effect of consuming cocoa-rich chocolate compared to placebo on the lipid profile and anthropometric variables based on data from three clinical trials conducted in Colombia. Methods Meta-analysis of individual data from three randomized clinical trials conducted in Colombia. The entire population of the primary studies was included, which was reassigned into intervention groups if they consumed 50 grams of 70% concentrated cocoa or placebo, which was considered to be cocoa-free or with a concentration less than 50 grams. The variables at the beginning of the study were analyzed with medians, interquartile ranges, means, and deviations according to whether they met the normality assumption. Multiple imputations were used to manage missing data and were analyzed using the two approaches proposed for this type of study, that of one and two stages. In the two-stage approach, the data were weighted on a conventional Forrest plot, while in the one-stage approach, linear regressions with mixed models were applied. This study is governed by the regulations described in the 2013 Declaration of Helsinki and by article 11 of Resolution 8430 of 1993, which classifies it as a risk-free study. Results A total of 275 participants were included, who consumed cocoa or placebo for 81 days on average; 52.7% were female and few smoked at the time of the intervention (31/275). Physical activity performed in number of hours per week was comparable between the intervention groups. When evaluating total cholesterol, low-density cholesterol (LDL), high-density cholesterol (HDL), triglycerides, abdominal circumference, and final body mass index with both the one-stage and two-stage approaches, there were no significant differences between the two groups. Conclusions According to the results obtained in the meta-analysis, the consumption of cocoa in the Colombian population does not seem to significantly modify variables such as lipid profile, abdominal circumference, and body mass index. This conclusion according to the quality of the evidence has a weak recommendation and a low-to-moderate certainty. However, the analysis through the two proposed approaches yielded similar results.

Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data

Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS. We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients. Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323-0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307-0.896; P= .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253-0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy. In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.

Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women.

Recent animal and small clinical studies have suggested depression is related to altered lipid and amino acid profiles. However, this has not been examined in a population-based sample, particularly in women. We identified multiple metabolites associated with depression as potential candidates from prior studies. Cross-sectional data from three independent samples of postmenopausal women were analyzed, including women from the Women's Health Initiative-Observational Study (WHI-OS, n=926), the WHI-Hormone Trials (WHI-HT; n=1,325), and the Nurses' Health Study II Mind-Body Study (NHSII-MBS; n=218). Positive depression status was defined as having any of the following: elevated depressive symptoms, antidepressant use, or depression history. Plasma metabolites were measured using liquid chromatography-tandem mass spectrometry (21 phosphatidylcholines [PCs], 7 lysophosphatidylethanolamines, 5 ceramides, 3 branched chain amino acids and 9 neurotransmitters). Associations between depression status and metabolites were evaluated using multivariable linear regression; results were pooled by random-effects meta-analysis with multiple testing adjustment using the Benjamini-Hochberg false discovery rate (FDR). Prevalence rates of positive depression status were 24.4% (WHI-OS), 25.7% (WHI-HT) and 44.7% (NHSII-MBS). After multivariable adjustment, positive depression status was associated with higher levels of glutamate and PC 36:1/38:3, and lower levels of tryptophan and GABA-to-glutamate and GABA-to-glutamine ratio (FDR-p<0.05). Positive associations with LPE 18:0/18:1 and inverse associations with valine and serotonin were also observed, although these associations did not survive FDR adjustment. Associations of positive depression status with several candidate metabolites including PC 36:1/38:3 and amino acids involved in neurotransmission suggest potential depression-related metabolic alterations in postmenopausal women, with possible implications for later chronic disease.