Publications
293 results found
Georgiou A, Georgiopoulos G, Delialis D, et al., 2023, Causal Relationship Between Average Alcohol Consumption and Risk of Atrial Fibrillation: A Mendelian Randomization Study., Circ Genom Precis Med
Liontos A, Asimakopoulos A-G, Markopoulos GS, et al., 2023, Correlation of Lymphocyte Subpopulations, Clinical Features and Inflammatory Markers during Severe COVID-19 Onset., Pathogens, Vol: 12, ISSN: 2076-0817
BACKGROUND: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. MATERIALS/METHODS: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). RESULTS: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. CONCLUSIONS: Despite a low patient number, this
Chalitsios CV, Georgiou A, Bouras E, et al., 2023, Investigating modifiable pathways in psoriasis: A Mendelian randomization study., J Am Acad Dermatol, Vol: 88, Pages: 593-601
BACKGROUND: Potentially modifiable risk factors have previously been investigated only in conventional observational studies. OBJECTIVE: To assess whether genetically predicted exposures to modifiable factors are associated with the risk of psoriasis. METHODS: Two-sample Mendelian randomization (MR) analysis. RESULTS: An increased risk of psoriasis was noted for genetically predicted lifetime smoking index (odds ratio [OR]MR-IVW = 2.11; 95% confidence interval [CI], 1.28-3.51), childhood (OR MR-IVW = 1.40; 95% CI, 1.14-1.71) and adult body mass index (OR MR-IVW = 1.63; 95% CI, 1.32-2), waist (OR IVW = 1.86; 95% CI, 1.31-2.64), and hip circumference (OR MR-IVW = 1.55; 95% CI, 1.15-2.07). Protective association was also reported between genetically predicted longer sleep duration (OR MR-IVW = 0.56; 95% CI 0.37-0.84) and increased years of education (OR MR-IVW = 0.78; 95% CI, 0.62-0.98). This effect of education persisted in multivariable MR after adjusting for genetic predictors of smoking and adult body mass index (ORMVMR-IVW = 0.72; 95% CI, 0.56-0.92). LIMITATIONS: It was not possible to stratify for psoriasis severity. CONCLUSION: Smoking cessation and prevention of obesity are important strategies for decreasing the incidence of psoriasis. Similarly, targeting education inequality is expected to lead further to reductions in cases of psoriasis.
Bakker MK, Kanning JP, Abraham G, et al., 2023, Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity., Stroke, Vol: 54, Pages: 810-818
BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic predicti
Christakoudi S, Tsilidis KK, Evangelou E, et al., 2023, Sex differences in the associations of body size and body shape with platelets in the UK Biobank cohort, Biology of Sex Differences, Vol: 14, Pages: 1-14, ISSN: 2042-6410
Background: Obesity is accompanied with low-grade inflammation and leucocytosis and increases the risk of venous thromboembolism. Associations with platelet count, however, are unclear because several studies have reported positive associations only in women. Associations with body shape are also unclear, because waist and hip circumferences reflect overall body size, as well as body shape, and are correlated strongly positively with body mass index (BMI).Methods: We evaluated body shape with the allometric body shape index (ABSI) and hip index (HI), which reflect waist and hip size among individuals with the same weight and height and are uncorrelated with BMI. We examined the associations of BMI, ABSI, and HI with platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) in multivariable linear regression models for 125,435 UK Biobank women and 114,760 men. We compared men with women, post-menopausal with pre-menopausal women, and older (≥52 years) with younger (<52 years) men.Results: BMI was associated positively with platelet count in women, more strongly in pre-menopausal than in post-menopausal, and weakly positively in younger men but strongly inversely in older men. Associations of BMI with platelet count were shifted towards the inverse direction for daily alcohol consumption and current smoking, resulting in weaker positive associations in women and stronger inverse associations in men, compared to alcohol≤3 times/month and never smoking. BMI was associated inversely with MPV and PDW in pre-menopausal women but positively in post-menopausal women and in men. ABSI was associated positively with platelet count, similarly in women and men, while HI was associated weakly inversely only in women. ABSI was associated inversely and HI positively with MPV but not with PDW and only in women. Platelet count was correlated inversely with platelet size and positively with leucocyte counts, most strongly with neutrophils. Conclusions:
Papandreou C, Papagiannopoulos C, Koutsonida M, et al., 2023, Mediterranean diet related metabolite profiles and cognitive performance., Clinical Nutrition, Vol: 42, Pages: 173-181, ISSN: 0261-5614
BACKGROUND & AIMS: Evidence suggests that adherence to the Mediterranean diet (MedDiet) affects human metabolism and may contribute to better cognitive performance. However, the underlying mechanisms are not clear. OBJECTIVE: We generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance. METHODS: A total of 1250 healthy Greek middle-aged adults from the Epirus Health Study cohort were included in the analysis. Adherence to the MedDiet was assessed using the 14-point Mediterranean Diet Adherence Screener (MEDAS); cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. A targeted metabolite profiling (n = 250 metabolites) approach was applied, using a high-throughput nuclear magnetic resonance platform. We used elastic net regularized regressions, with a 10-fold cross-validation procedure, to identify a metabolite profile for MEDAS. We evaluated the associations of the identified metabolite profile and MEDAS with cognitive tests, using multivariable linear regression models. RESULTS: We identified a metabolite profile composed of 42 metabolites, mainly lipoprotein subclasses and fatty acids, significantly correlated with MedDiet adherence (Pearson r = 0.35, P-value = 5.5 × 10-37). After adjusting for known risk factors and accounting for multiple testing, the metabolite profile and MEDAS were not associated with the cognitive tests. CONCLUSIONS: A plasma metabolite profile related to better adherence to the MedDiet was not associated with the tested aspects of cognitive performance, in a middle-aged Mediterranean population.
Antonatos C, Patsatsi A, Zafiriou E, et al., 2023, Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis., Pharmacogenomics J, Vol: 23, Pages: 8-13
Although cyclosporine comprises a well-established systemic therapy for psoriasis, patients show important heterogeneity in their treatment response. The aim of our study was the pharmacogenetic analysis of 200 Greek patients with psoriasis based on the cyclosporine pathway related protein-protein interaction (PPI) network, reconstructed through the PICKLE meta-database. We genotyped 27 single nucleotide polymorphisms, mapped to 22 key protein nodes of the cyclosporine pathway, via the utilization of the iPLEX®GOLD panel of the MassARRAY® System. Single-SNP analyses showed statistically significant associations between CALM1 rs12885713 (P = 0.0108) and MALT1 rs2874116 (P = 0.0006) polymorphisms with positive response to cyclosporine therapy after correction for multiple comparisons, with the haplotype analyses further enhancing the predictive value of rs12885713 as a pharmacogenetic biomarker for cyclosporine therapy (P = 0.0173). Our findings have the potential to improve our prediction of cyclosporine efficacy and safety in psoriasis patients, as well as provide the framework for the pharmacogenetics of biological therapies in complex diseases.
Koskeridis F, Evangelou E, Said S, et al., 2022, Pleiotropic genetic architecture and novel loci for C-reactive protein levels, Nature Communications, Vol: 13, ISSN: 2041-1723
C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci, we perform multi-trait analysis of genome-wide association studies on C-reactive protein levels along with cardiometabolic traits, followed by a series of in silico analyses including colocalization, phenome-wide association studies and Mendelian randomization. We find 41 novel loci and 19 gene sets associated with C-reactive protein with various pleiotropic effects. Additionally, 41 variants colocalize between C-reactive protein and cardiometabolic risk factors and 12 of them display unexpected discordant effects between the shared traits which are translated into discordant associations with clinical outcomes in subsequent phenome-wide association studies. Our findings provide insights into shared mechanisms underlying inflammation and lipid metabolism, representing potential preventive and therapeutic targets.
Zhang Y-R, Xu W, Zhang W, et al., 2022, Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence, JOURNAL OF AFFECTIVE DISORDERS, Vol: 314, Pages: 160-167, ISSN: 0165-0327
Rapti I, Asimakopoulos A, Liontos A, et al., 2022, Association of patient characteristics with clinical outcomes in a cohort of hospitalised patients with SARS-CoV-2 infection in a Greek referral centre for COVID-19, Epidemiology and Infection, Vol: 150, Pages: 1-9, ISSN: 0950-2688
Patient-important outcomes related to coronavirus disease 2019 (COVID-19) continue to drive the pandemic response across the globe. Various prognostic factors for COVID-19 severity have emerged and their replication across different clinical settings providing health services is ongoing. We aimed to describe the clinical characteristics and their association with outcomes in patients hospitalised with COVID-19 in the University Hospital of Ioannina. We assessed a cohort of 681 consecutively hospitalised patients with COVID-19 from January 2020 to December 2021. Demographic data, underlying comorbidities, clinical presentation, biochemical markers, radiologic findings, COVID-19 treatment and outcome data were collected at the first day of hospitalisation and up to 90 days. Multivariable Cox regression analyses were performed to investigate the associations between clinical characteristics (hazard ratios (HRs) per standard deviation (S.D.)) with intubation and/or mortality status. The participants' mean age was 62.8 (S.D., 16.9) years and 57% were males. The most common comorbidities were hypertension (45%), cardiovascular disease (19%) and diabetes mellitus (21%). Patients usually presented with fever (81%), cough (50%) and dyspnoea (27%), while lymphopenia and increased inflammatory markers were the most common laboratory abnormalities. Overall, 55 patients (8%) were intubated, and 86 patients (13%) died. There were statistically significant positive associations between intubation or death with age (HR: 2.59; 95% CI 1.52–4.40), lactate dehydrogenase (HR: 1.44; 95% CI 1.04–1.98), pO2/FiO2 ratio < 100 mmHg (HR: 3.52; 95% CI 1.14–10.84), and inverse association with absolute lymphocyte count (HR: 0.54; 95% CI 0.33–0.87). These data might help to identify points for improvement in the management of COVID-19 patients.
Adam GP, Pappas D, Papageorgiou H, et al., 2022, A novel tool that allows interactive screening of PubMed citations showed promise for the semi-automation of identification of Biomedical Literature, JOURNAL OF CLINICAL EPIDEMIOLOGY, Vol: 150, Pages: 63-71, ISSN: 0895-4356
Missiou A, Lionis C, Evangelou E, et al., 2022, Health outcomes in primary care: a 20-year evidence map of randomized controlled trials, FAMILY PRACTICE, ISSN: 0263-2136
Said S, Pazoki R, Karhunen V, et al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci (vol 13, 2198, 2022), Nature Communications, Vol: 13, Pages: 1-1, ISSN: 2041-1723
Christakoudi S, Riboli E, Evangelou E, et al., 2022, Associations of body shape phenotypes with sex steroids and their binding proteins in the UK Biobank cohort, Scientific Reports, Vol: 12, ISSN: 2045-2322
Associations of sex steroids and their binding proteins with body shape are unclear, because waist and hip circumference are correlated strongly with body size. We defined body shape using “a body shape index” (ABSI) and hip index (HI), which are independent of weight and height by design, and examined associations in multivariable generalised linear models for the UK Biobank cohort (179,902 men, 207,444 women). Total testosterone was associated inversely with ABSI, especially in men. Free testosterone was lowest for large-ABSI-large-HI (“wide”) and highest for small-ABSI-small-HI (“slim”) in men, but lowest for small-ABSI-large-HI (“pear”) and highest for large-ABSI-small-HI (“apple”) in women. Oestradiol was associated inversely with ABSI in obese pre-menopausal women but positively with HI in obese men and post-menopausal women not using hormone replacement therapy. Sex-hormone binding globulin (SHBG) was associated inversely with ABSI but positively with HI and was lowest for “apple” and highest for “pear” phenotype in both sexes. Albumin was associated inversely with HI in women, but matched the pattern of free testosterone in obese men (lowest for “wide”, highest for “slim” phenotype). In conclusion, sex steroids and their binding proteins are associated with body shape, including hip as well as waist size, independent of body size.
Sadlon A, Takousis P, Evangelou E, et al., 2022, A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials
<jats:title>Abstract</jats:title><jats:p>Identifying individuals before the onset of overt symptoms is a key prerequisite for the prevention of Alzheimer’s disease (AD). A wealth of data reports dysregulated microRNA (miRNA) expression in the blood of individuals with AD, but evidence in individuals at subclinical stages is sparse. In this study, a qPCR analysis of a prioritised set of 38 candidate miRNAs in the blood of 830 healthy individuals from the CHARIOT PRO cohort (West London, UK) was undertaken. Here, we identified six differentially expressed miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A pathway enrichment analysis for the six miRNAs indicated involvement of apoptosis and inflammation, relevant in early AD stages. Subsequently, we used whole genome sequencing (WGS) data from 750 individuals from the AD Neuroimaging Initiative (ADNI) to perform a genetic association analysis for polymorphisms within the significant miRNAs’ genes and CSF concentrations of phosphorylated-tau, total-tau, amyloid-β42 and soluble-TREM2 and BACE1 activity. Our analysis revealed 24 SNPs within <jats:italic>MIR29C</jats:italic> to be associated with CSF levels of amyloid-β42 and soluble-TREM2 and BACE1 activity. Our study shows the potential of a six-miRNA set as diagnostic blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within <jats:italic>MIR29C</jats:italic> suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.</jats:p>
Christakoudi S, Riboli E, Evangelou E, et al., 2022, Associations of body shape index (ABSI) and hip index with liver, metabolic, and inflammatory biomarkers in the UK Biobank cohort, Scientific Reports, Vol: 12, ISSN: 2045-2322
Associations of liver, metabolic, and inflammatory biomarkers in blood with body shape are unclear, because waist circumference (WC) and hip circumference (HC) are dependent on overall body size, resulting in bias. We have used the allometric “a body shape index” (ABSI = WC(mm)∗Weight(kg)-2/3∗Height(m)5/6) and hip index (HIwomen = HC(cm)∗Weight(kg)-0.482∗Height(cm)0.310, HImen = HC(cm)∗Weight(kg)-2/5∗Height(cm)1/5), which are independent of body mass index (BMI) by design, in multivariable linear regression models for 121,879 UK Biobank men and 135,559 women. Glucose, glycated haemoglobin (HbA1c), triglycerides, low-density-lipoprotein cholesterol, apolipoprotein-B, alanine aminotransferase (ALT), gamma-glutamyltransferase, and lymphocytes were associated positively with BMI and ABSI but inversely with HI. High-density-lipoprotein cholesterol and apolipoprotein-A1 were associated inversely with BMI and ABSI but positively with HI. Lipid-related biomarkers and ALT were associated only with HI in obese men. C-reactive protein, neutrophils, monocytes, and alkaline phosphatase were associated positively, while bilirubin was associated inversely, with BMI and ABSI but not with HI. Associations were consistent within the clinical reference ranges but were lost or changed direction for low or high biomarker levels. Our study confirms associations with waist and hip size, independent of BMI, for metabolic biomarkers but only with waist size for inflammatory biomarkers, suggesting different contribution of the mechanistic pathways related to body shape.
Antonatos C, Panoutsopoulou M, Georgakilas GK, et al., 2022, Gene Expression Meta-Analysis of Potential Shared and Unique Pathways between Autoimmune Diseases under Anti-TNFα Therapy., Genes (Basel), Vol: 13
While anti-TNFα has been established as an effective therapeutic approach for several autoimmune diseases, results from clinical trials have uncovered heterogeneous patients' response to therapy. Here, we conducted a meta-analysis on the publicly available gene expression cDNA microarray datasets that examine the differential expression observed in response to anti-TNFα therapy with psoriasis (PsO), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Five disease-specific meta-analyses and a single combined random-effects meta-analysis were performed through the restricted maximum likelihood method. Gene Ontology and Reactome Pathways enrichment analyses were conducted, while interactions between differentially expressed genes (DEGs) were determined with the STRING database. Four IBD, three PsO and two RA datasets were identified and included in our analyses through our search criteria. Disease-specific meta-analyses detected distinct pro-inflammatory down-regulated DEGs for each disease, while pathway analyses identified common inflammatory patterns involved in the pathogenesis of each disease. Combined meta-analyses further revealed DEGs that participate in anti-inflammatory pathways, namely IL-10 signaling. Our analyses provide the framework for a transcriptomic approach in response to anti-TNFα therapy in the above diseases. Elucidation of the complex interactions involved in such multifactorial phenotypes could identify key molecular targets implicated in the pathogenesis of IBD, PsO and RA.
Said S, Karhunen V, vosa U, et al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci, Nature Communications, Vol: 13, ISSN: 2041-1723
Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.
Warren H, Edwards T, Vaez A, et al., 2022, Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure
<jats:title>Abstract</jats:title> <jats:p>Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P < 5x10<jats:sup>− 8</jats:sup>) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10<jats:sup>− 73</jats:sup>) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10<jats:sup>− 33</jats:sup>) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10<jats:sup>− 22</jats:sup>). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.</jats:p>
Kyriakopoulos C, Gogali A, Ntritsos G, et al., 2022, Reply., Respirology, Vol: 27, Pages: 246-247
Bellou V, Tzoulaki I, van Smeden M, et al., 2022, Prognostic factors for adverse outcomes in patients with COVID-19: a field-wide systematic review and meta-analysis, European Respiratory Journal, Vol: 59, ISSN: 0903-1936
INTRODUCTION: The individual prognostic factors for COVID-19 are unclear. For this reason, we aimed to present a state-of-the-art systematic review and meta-analysis on the prognostic factors for adverse outcomes in COVID-19 patients. METHODS: We systematically reviewed PubMed from January 1, 2020 to July 26, 2020 to identify non-overlapping studies examining the association of any prognostic factor with any adverse outcome in patients with COVID-19. Random-effects meta-analysis was performed, and between-study heterogeneity was quantified using I2 metric. Presence of small-study effects was assessed by applying the Egger's regression test. RESULTS: We identified 428 eligible articles, which were used in a total of 263 meta-analyses examining the association of 91 unique prognostic factors with 11 outcomes. Angiotensin-converting enzyme inhibitors, obstructive sleep apnea, pharyngalgia, history of venous thromboembolism, sex, coronary heart disease, cancer, chronic liver disease, chronic obstructive pulmonary disease, dementia, any immunosuppressive medication, peripheral arterial disease, rheumatological disease and smoking were associated with at least one outcome and had >1000 events, p-value <0.005, I2 <50%, 95% prediction interval excluding the null value, and absence of small-study effects in the respective meta-analysis. The risk of bias assessment using the Quality In Prognosis Studies tool indicated high risk of bias in 302 of 428 articles for study participation, 389 articles for adjustment for other prognostic factors, and 396 articles for statistical analysis and reporting. CONCLUSIONS: Our findings could be used for prognostic model building and guide patients' selection for randomised clinical trials.
Koskeridis F, Evangelou E, Ntzani EE, et al., 2022, Treatment With Dupilumab in Patients With Atopic Dermatitis: Systematic Review and Meta-Analysis., J Cutan Med Surg, Vol: 26, Pages: 613-621
Atopic dermatitis (AD) is a type 2 chronic skin disorder associated with systemic and psychosocial comorbidities decreasing the quality of life for many patients. Dupilumab, a human monoclonal antibody that blocks interleukins IL-4 and IL-13, is a recently added systematic treatment option with an emerging evidence base. Here, we assessed the safety and efficacy of dupilumab in patients with AD. We conducted a systematic review and meta-analysis of placebo-controlled randomized clinical trials evaluating the safety and efficacy of dupilumab on AD-related outcomes including clinical symptoms, quality of life and adverse events (AE). Subgroup analysis was further performed in adults and children/adolescents. Fourteen trials were included: twelve in adults (n = 3,817) and two in children/adolescents (n = 618). Dupilumab decreased the Eczema Area Severity Index (EASI) score [standardized mean difference (SMD) = -0.98; 95% confidence interval (95% CI) = (-1.09, -0.88)], the percent change difference in Scoring Atopic Dermatitis (SCORAD) [mean difference (MD) = -31.56, 95% CI = (-33.75, -29.36)], and in pruritus Numeric Rating Scale (pNRS) [MD = -29.24, 95% CI = (-32.11, -26.37)]. It also achieved a reduction of at least ≥75% in the EASI score [Risk Ratio (RR) = 2.89, 95% CI = (2.47, 3.38)], the Investigator's Global Assessment (IGA) score ≤1 [RR = 3.47, 95% CI = (2.96, 4.06)] and eight additional endpoints with no signs of increased AE compared to placebo. In subgroup analysis, the results were concordant for both groups. Dupilumab improved clinical symptoms and quality of life in adults and children/adolescents with a safety profile comparable to placebo.
Papatheodorou SI, Evangelou E, 2022, Umbrella Reviews: What They Are and Why We Need Them., Methods Mol Biol, Vol: 2345, Pages: 135-146
Evidence in clinical research is accumulating and scientific publications have increased exponentially in the last decade across all disciplines. Available information should be critically assessed. Here, we focus on umbrella reviews, an approach that systematically collects and evaluates information from multiple systematic reviews and meta-analyses. To facilitate the design and the conduct of such a study, we provide a step-by-step guide on how to perform an umbrella review. We also present ways to report the summary findings, we describe various proposed grading criteria, and we discuss potential limitations.
Tsabouri S, Ntritsos G, Koskeridis F, et al., 2021, Omalizumab for the treatment of allergic rhinitis: a systematic review and meta-analysis., Rhinology, Vol: 59, Pages: 501-510, ISSN: 0300-0729
BACKGROUND: Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. METHODS: We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. RESULTS: The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points with large heterogeneity; omalizumab significantly reduced the DNSSS both in the 3 cedar pollen-induced AR trials by -0.97 points and to a lower extent in the remaining five non-cedar trials by -0.19 points. Omalizumab also improved the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points with large heterogeneity; the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points with no heterogeneity and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 with large heterogeneity. No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo. CONCLUSION: Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with a conventional treatment.
Kyriakopoulos C, Ntritsos G, Gogali A, et al., 2021, Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis., Respirology, Vol: 26, Pages: 1027-1040
Tocilizumab has been repurposed against the 'cytokine storm' in the setting of coronavirus disease 2019 (COVID-19). Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID-19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non-ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate-to-critical COVID-19.
Christakoudi S, Tsilidis K, Evangelou E, et al., 2021, Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk, BMC Cancer, Vol: 21, Pages: 1-15, ISSN: 1471-2407
BackgroundBody mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk.MethodsWe used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large-ABSI-small-HI (“apple”), small-ABSI-large-HI (“pear”), small-ABSI-small-HI (“slim”), large-ABSI-large-HI (“wide”). We evaluated differences in body composition in linear models and associations with colon cancer risk in Cox proportional hazards models adjusted for confounders and explored heterogeneity by BMI.ResultsAmong individuals with the same height and weight, visceral adipose tissue (VAT) was lowest for “pear” and highest for “apple”, while abdominal subcutaneous adipose tissue (ASAT) was lowest for “slim” and highest for “wide” phenotype. In the gynoid region, differences between “apple” and “pear” phenotypes were accounted for mainly by fat mass in women but by lean mass in men. In men, lean mass was inversely associated with waist size, while the pattern of gynoid fat resembled ASAT in women. Lean and fat mass were higher for higher BMI, but not hand grip strength. Compared to normal weight “pear”, the risk of colon cancer in men (1029 cases) was higher for “apple” phenotype for normal weight (hazard ratio HR =&thi
Koutsonida M, Kanellopoulou A, Markozannes G, et al., 2021, Adherence to Mediterranean diet and cognitive abilities in the Greek cohort of Epirus Health Study, Nutrients, Vol: 13, ISSN: 2072-6643
The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21–77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.
Sun X, Ho JE, Gao H, et al., 2021, Associations of Alcohol Consumption with Cardiovascular Disease-Related Proteomic Biomarkers: The Framingham Heart Study, JOURNAL OF NUTRITION, Vol: 151, Pages: 2574-2582, ISSN: 0022-3166
Bellou V, Belbasis L, Evangelou E, 2021, Tobacco Smoking and Risk for Pulmonary Fibrosis: A Prospective Cohort Study From the UK Biobank., Chest, Vol: 160, Pages: 983-993
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown origin. A limited number of small studies show an effect of tobacco smoking on risk of IPF, but second-hand smoking has not been examined. RESEARCH QUESTION: Are smoking-related exposures associated with risk of IPF and does interaction between them exist? STUDY DESIGN AND METHODS: We designed a prospective cohort study using UK Biobank data, including 437,453 nonrelated men and women of White ethnic background (40-69 years of age at baseline). We assessed the effect of tobacco smoking-related exposures on risk for IPF using Cox regression adjusted for age, sex, Townsend deprivation index, and home area population density. We also examined potential additive and multiplicative interaction between these exposures. Multiple imputation with chained equations was used to address missing data. RESULTS: We identified 802 incident IPF cases. We showed an association between smoking status (hazard ratio [HR], 2.12; 95% CI, 1.81-2.47), and maternal smoking (HR, 1.38; 95% CI, 1.18-1.62) with risk of IPF. In ever smokers, a dose-response relationship was observed between pack-years of smoking and risk of IPF (HR per 1-pack-year increase, 1.013; 95% CI, 1.009-1.016). Furthermore, an additive and multiplicative interaction was observed between maternal smoking and smoking status, with a relative excess risk due to interaction of 1.00 (95% CI, 0.45-1.54) and a ratio of HRs of 1.50 (95% CI, 1.05-2.14). INTERPRETATION: Active and maternal tobacco smoking have an independent detrimental effect on risk of IPF and work synergistically. Also, intensity of smoking presents a dose-response association with IPF, strengthening the hypothesis for a potentially causal association.
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