Publications by authors named "Pagona Lagiou"

341 Publications

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Could Provide Better Accuracy Than Creatinine in Predicting Acute Kidney Injury Development in Critically Ill Patients.

J Clin Med 2021 Nov 18;10(22). Epub 2021 Nov 18.

First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National & Kapodistrian University of Athens, Evangelismos Hospital, 10676 Athens, Greece.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development ( = 98) or not ( = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not ( < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002-1.008), < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.
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http://dx.doi.org/10.3390/jcm10225379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625137PMC
November 2021

Viral Causality of Human Cancer and Potential Roles of Human Endogenous Retroviruses in the Multi-Omics Era: An Evolutionary Epidemiology Review.

Front Oncol 2021 29;11:687631. Epub 2021 Oct 29.

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Being responsible for almost 12% of cancers worldwide, viruses are among the oldest known and most prevalent oncogenic agents. The quality of the evidence for the tumorigenic potential of microorganisms varies, thus accordingly, viruses were classified in 4 evidence-based categories by the International Agency for Research on Cancer in 2009. Since then, our understanding of the role of viruses in cancer has significantly improved, firstly due to the emergence of high throughput sequencing technologies that allowed the "brute-force" recovery of unknown viral genomes. At the same time, multi-omics approaches unravelled novel virus-host interactions in stem-cell biology. We now know that viral elements, either exogenous or endogenous, have multiple sometimes conflicting roles in human pathophysiology and the development of cancer. Here we integrate emerging evidence on viral causality in human cancer from basic mechanisms to clinical studies. We analyze viral tumorigenesis under the scope of deep-in-time human-virus evolutionary relationships and critically comment on the evidence through the eyes of clinical epidemiology, firstly by reviewing recognized oncoviruses and their mechanisms of inducing tumorigenesis, and then by examining the potential role of integrated viruses in our genome in the process of carcinogenesis.
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http://dx.doi.org/10.3389/fonc.2021.687631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586426PMC
October 2021

Salivary HPV Persistence Following Treatment of Oropharyngeal Squamous Cell Carcinoma.

Ann Otol Rhinol Laryngol 2021 Nov 14:34894211055606. Epub 2021 Nov 14.

Department of Otolaryngology - Head & Neck Surgery, University of Ottawa, Ottawa, ON, Canada.

Objective: To determine the persistence of human papillomavirus (HPV) infection following treatment of HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC).

Methods: A cross-sectional study was undertaken at The Ottawa Hospital (Ottawa, ON, Canada), a tertiary academic hospital and regional cancer center. Adult patients who were diagnosed with HPV + OPSCC between the years of 2014 and 2016 and treated with curative intent, and who were alive and willing to consent were eligible for inclusion. A saliva assay was used to test for the presence of HPV DNA in a random sample of patients. qPCR was used to amplify DNA from saliva samples.

Results: Saliva samples were obtained from 69 patients previously treated with HPV + OPSCC. All patients had a minimum of 2 years of follow-up. 5 patients tested positive for HPV: 2 were positive for HPV-16, 2 for HPV-18, and 1 "other" HPV type. No patient in our study cohort had suffered recurrence post-treatment.

Conclusions: This study is the first to demonstrate the prevalence of persistent oncogenic HPV DNA in saliva following treatment for HPV + OPSCC. This prevalence appears to be low, despite the fact that persistent HPV infection is a precursor for the development of HPV + OPSCC. This finding raises questions about what factors influence the clearance or persistence of HPV DNA in saliva after treatment for HPV + OPSCC, and may add to our understanding about the longitudinal effects of HPV infection in these cancers.
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http://dx.doi.org/10.1177/00034894211055606DOI Listing
November 2021

Investigating the association between temperature and hospital admissions for major psychiatric diseases: A study in Greece.

J Psychiatr Res 2021 Oct 21;144:278-284. Epub 2021 Oct 21.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens, 115 27, Greece.

Evidence has emerged regarding the role of seasonality and several meteorological parameters on bipolar disorder, schizophrenia and depression. We investigated the relationship between ambient and apparent temperature and hospital admissions of major psychiatric diseases in a psychiatric clinic of a General Hospital situated in Northern Greece during 2013-19. Temperature data was provided by the National Observatory of Athens and diagnosis for psychotic, schizophrenic, manic and bipolar and unipolar depression were retrieved from medical records. A total of 783 admissions were recorded. Poisson regression models adjusted for time trends were applied to analyze the impact of temperature on monthly admissions. A summer peak was observed for the bipolar disorder, irrespectively of substance/alcohol use status. Seasonality emerged also for psychotic and schizophrenic patients with a through in winter. An increase of 1 °C in either ambient or apparent temperature was associated with an increase 1-2% in the monthly admissions in most outcomes under investigation. Alcohol and drug abuse did not modify this effect. Although our results indicate effects of temperature on psychiatric admissions, they are not consistent across subgroups populations and need to be replicated by other methodologically superior studies.
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http://dx.doi.org/10.1016/j.jpsychires.2021.10.029DOI Listing
October 2021

Investigating the association between long-term exposure to air pollution and greenness with mortality from neurological, cardio-metabolic and chronic obstructive pulmonary diseases in Greece.

Environ Pollut 2022 Jan 14;292(Pt B):118372. Epub 2021 Oct 14.

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Long-term exposure to air pollution has been associated with increased natural-cause mortality, but the evidence on diagnoses-specific mortality outcomes is limited. Few studies have examined the potential synergistic effects of exposure to pollutants and greenness. We investigated the association between exposure to air pollution and greenness with nervous system related mortality, cardiometabolic and chronic obstructive pulmonary diseases (COPD) mortality in Greece, using an ecological study design. We collected socioeconomic and mortality data for 1035 municipal units from the 2011 Census. Annual PM, NO, BC and O concentrations for 2010 were predicted at 100 × 100 m grids by hybrid land use regression models. The normalized difference vegetation index (NDVI) was used for greenness. We applied single and two-exposure Poisson regression models on standardized mortality rates accounting for spatial autocorrelation. We assessed interactions between pollutants and greenness. An interquartile range increase in PM, NO and BC was associated with increased risk in mortality from diseases of the nervous system (relative risk (RR): 1.14, 95% confidence interval (CI): 1.01, 1.28); 1.03 (95% CI: 0.99, 1.07); 1.05 (95% CI: 1.00, 1.10) respectively) and from cerebrovascular disease (RR: 1.14, 95% CI: 1.10, 1.18); 1.02 (95% CI: 1.01, 1.04); 1.02 (95% CI: 1.00, 1.04) respectively). PM was associated with ischemic heart disease mortality (RR: 1.05, 95% CI: 1.01, 1.10). We estimated inverse associations for all outcomes with O and for mortality from diseases of the nervous system or COPD with greenness. Estimates were mostly robust to co-exposure adjustment. Interactions were identified between NDVI and O or PM on mortality from the diseases of the nervous system, with higher effect estimates in greener areas. Our findings support the adverse effects of air pollution and the beneficial role of greenness on cardiovascular and nervous system related mortality. Further research is needed on diabetes mellitus.
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http://dx.doi.org/10.1016/j.envpol.2021.118372DOI Listing
January 2022

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Nat Commun 2021 10 12;12(1):5945. Epub 2021 Oct 12.

Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
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http://dx.doi.org/10.1038/s41467-021-26151-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511029PMC
October 2021

Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients.

Microbiol Spectr 2021 10 6;9(2):e0126021. Epub 2021 Oct 6.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that human endogenous retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. By comparing transcriptomes of bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy controls, and peripheral blood monocytes (PBMCs) from patients and controls, we have shown that HERVs are intensely dysregulated in BALF of COVID-19 patients compared to those in BALF of healthy control patients but not in PBMCs. In particular, upregulation in the expression of specific HERV families was detected in BALF samples of COVID-19 patients, with HERV-FRD being the most highly upregulated family among the families analyzed. In addition, we compared the expression of HERVs in human bronchial epithelial cells (HBECs) without and after senescence induction in an oncogene-induced senescence model in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the process of cellular senescence. This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in the involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to that in noninduced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations. SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes. HERVs are remnants of ancient infections whose expression is upregulated in multiple conditions, including cancer and inflammation, and their expression is increased with increasing age. The significance of this work is that we were able to recognize dysregulated expression of endogenous retroviral elements in BALF samples but not in PBMCs of COVID-19 patients. At the same time, we were able to identify upregulated expression of multiple HERV families in senescence-induced HBECs in comparison to that in noninduced HBECs, a fact that could possibly explain the differences in disease severity among age groups. These results indicate that HERV expression might play a pathophysiological role in local inflammatory pathways in lungs afflicted by SARS-CoV-2 and their expression could be a potential therapeutic target.
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http://dx.doi.org/10.1128/Spectrum.01260-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510252PMC
October 2021

Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis.

Neurology 2021 11 5;97(21):e2136-e2147. Epub 2021 Oct 5.

From the Second Department of Neurology (L.P., M.-I.S., A.H.K., S.G., K.I.V., G.T.), Second Department of Psychiatry (I.M.), and Fourth Department of Internal Medicine (S.T.), "Attikon" University Hospital, Department of Hygiene, Epidemiology and Medical Statistics (P.L., A.N.), School of Medicine, and Third Department of Critical Care Medicine, Evgenideio Hospital, Medical School (T.I.V.), and Third Department of Pediatrics (V.P.), National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Canada; Department of Neurosciences and Mental Health (D.A.d.S.), Hospital de Santa Maria, CHULN, University of Lisbon, Portugal; Department of Neurology (J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Epidemiology (P.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Neurology (K.V.), University Hospital of Alexandroupolis, Democritus University of Thrace; Hellenic Centre for Disease Control and Prevention (S.T.), Athens, Greece; and Department of Neurology (G.T.), University of Tennessee Health Science Center, Memphis.

Background And Objectives: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.

Methods: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.

Results: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors.

Discussion: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.

Registration Information: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).
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http://dx.doi.org/10.1212/WNL.0000000000012896DOI Listing
November 2021

Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies.

Nutr Rev 2021 Oct 4. Epub 2021 Oct 4.

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Context: Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk.

Objective: Dose-response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer's Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance.

Data Sources: PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline.

Data Extraction: Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively.

Data Analysis: Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants' executive functions, but not on their overall cognitive performance.

Conclusion: The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual's executive functions, although there remain questions about the mechanisms linking the short- and long-term effects.

Systematic Review Registration: PROSPERO registration no. CRD42019139528.
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http://dx.doi.org/10.1093/nutrit/nuab078DOI Listing
October 2021

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

Vaccines (Basel) 2021 Sep 13;9(9). Epub 2021 Sep 13.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.
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http://dx.doi.org/10.3390/vaccines9091017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471735PMC
September 2021

Efficient and targeted COVID-19 border testing via reinforcement learning.

Nature 2021 11 22;599(7883):108-113. Epub 2021 Sep 22.

Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates. Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health.
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http://dx.doi.org/10.1038/s41586-021-04014-zDOI Listing
November 2021

Coffee consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling Project consortium.

Eur J Cancer Prev 2021 Sep 17. Epub 2021 Sep 17.

Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", University of Milan, Milan, Italy Hellenic Health Foundation, Athens, Greece Department of Biomedical and Clinical Sciences L. Sacco Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada Harbin Medical University, Harbin, China Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy EPIUnit - Instituto de Saúde Pública da Universidade do Porto Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan Nikkei Disease Prevention Center, São Paulo, Brazil Mexico National Institute of Public Health, Morelos, Mexico Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut, USA Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) Cancer Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid Research Group in Gene-Environment Interactions and Health, University of León, León Nutritional Epidemiology Unit, Instituto de Investigación Sanitaria y Biomédica de Alicante, ISABIAL-UMH, Alicante, Spain Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California Department of Medicine, Memorial Sloan Kettering Cancer Centre, New York, New York, USA Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Public and Community Health, School of Public Health, University of West Attica, Athens 2nd Pulmonary Medicine Department, National and Kapodistrian University of Athens, Medical School, "ATTIKON" University Hospital, Haidari, Greece Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran Centro Internacional de Pesquisa, A. C. Camargo Cancer Center, São Paulo, Brazil Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Objective: This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls.

Methods: A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer.

Results: Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only.

Conclusions: These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000680DOI Listing
September 2021

Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.

Lancet Diabetes Endocrinol 2021 10 2;9(10):681-694. Epub 2021 Sep 2.

Institute of Health Informatics, University College London, London, UK; Health Data Research UK, University College London, London, UK; National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, UK.

Background: Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods: In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings: We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation: A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding: The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.
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http://dx.doi.org/10.1016/S2213-8587(21)00207-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440227PMC
October 2021

Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium.

Cancers (Basel) 2021 Jul 30;13(15). Epub 2021 Jul 30.

Department of Public and Community Health, School of Public Health, University of West Attica, 12243 Athens, Greece.

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64-2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59-2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98-1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62-2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28-1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
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http://dx.doi.org/10.3390/cancers13153844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345354PMC
July 2021

Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.

Epidemiology 2021 09;32(5):744-755

From the Institute of Health Informatics, University College London (UCL), London, United Kingdom.

Background: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.

Methods: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.

Results: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.

Conclusion: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.
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http://dx.doi.org/10.1097/EDE.0000000000001393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318567PMC
September 2021

Hand hygiene education of Greek medical and nursing students: A cross-sectional study.

Nurse Educ Pract 2021 Jul 28;54:103130. Epub 2021 Jun 28.

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens GR-115 27, Greece. Electronic address:

Aim: To investigate medical and nursing students' education on hand hygiene, their attitude on hand hygiene education and how this education influences their hand hygiene knowledge and practices.

Background: Hospital-acquired infections are associated with prolonged hospitalisation and mortality. The most effective measure for their control is healthcare workers' hand hygiene compliance. Since medical and nursing students constitute the future healthcare workers, our study focuses on them.

Design: Cross-sectional study METHODS: This study was conducted during the academic year 2016-2017, using a modified World Health Organisation questionnaire. Our sample consisted of 132 medical and 111 nursing students from National and Kapodistrian University of Athens, Greece. In data analysis, the Mann-Whitney and Fisher's exact tests were applied to compare differences in continuous variables and proportions in categorical variables, respectively. Knowledge and practices overall scores were calculated per student group. Multiple linear regression analyses were performed to assess the influence of potential confounders on these scores.

Results: We found that 73.1% of medical and 98.2% of nursing students had received relevant education, which was reported as "only theoretical" by 77.4% of the former and as "hands-on and theoretical" by 88.1% of the latter group. Besides the risk of infection, knowledge acquired in lectures and trainer's behaviour were also considered very influential factors shaping hand hygiene attitude in both groups. Overall, medical students reported better hand hygiene practices than nursing ones (69.9% and 59.7%, respectively; p < 0.001). The opposite finding was observed regarding their overall knowledge on hand hygiene (57.2% of medical versus 60.4% of nursing students, p = 0.04). The majority of students (86.6% of all participants; p < 0.001) supported the inclusion of compulsory hand hygiene education in their curriculum. Compulsory education and seminars were assessed as the most effective measures to increase hand hygiene compliance (71.4% of all students).

Conclusion: In our study, medical students scored better in practices questions than nursing students; this did not apply for the knowledge score. The majority of students supported the inclusion of compulsory education on hand hygiene principles in their Departments' curricula, highlighting compulsory education and seminars as the most effective measures to increase compliance with hand hygiene.
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http://dx.doi.org/10.1016/j.nepr.2021.103130DOI Listing
July 2021

The association between diabetes and gastric cancer: results from the Stomach Cancer Pooling Project Consortium.

Eur J Cancer Prev 2021 Jun 25. Epub 2021 Jun 25.

College of Public Health, University of South Florida, Tampa, Florida, USA Department of Clinical Sciences and Community Health, University of Milan, Milan Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Department of Information Systems and Decision Sciences (ISDS), Muma College of Business, University of South Florida, Tampa, Florida, USA Department of Biomedical and Clinical Sciences, University of Milan, Milan Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy Department of Epidemiology, UCLA Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California, USA Department of Rehabilitation, Vinmec Hospital Times City, Vinmec Healthcare System Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System Department of Surgical Oncology, Viet-Duc University Hospital, Hanoi, Vietnam Medical Informatics Center, Peking University, Peking, China Department of Computer Sciences and Engineering, University of Nevada-Reno, Reno, Nevada Department of Public Health Sciences, Tobacco Center of Regulatory Science, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Japan Nikkei Disease Prevention Center, São Paulo, Brazil Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia CIBER Epidemiología y Salud Pública (CIBERESP), Madrid ISGlobal IMIM (Hospital del Mar Medical Research Institute) Universitat Pompeu Fabra (UPF), Barcelona Environmental and Cancer Epidemiology Unit, National Center of Epidemiology, Carlos III Health Institute, Madrid, Spain Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia Department of Medicine, Memorial Sloan Kettering Cancer Centre, New York, NY, USA Department of Public and Community Health, School of Health Sciences, University of West Attica Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Department of Public Health, Miguel Hernandez University, FISABIO-ISABIAL, Campus San Juan, Alicante, Spain Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Centro Internacional de Pesquisa, A. C. Camargo Cancer Center, São Paulo, Brazil Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal Stony Brook Cancer Center, Stony Brook University, New York, New York, USA Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.

Objective: To investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.

Methods: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.

Results: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.

Conclusion: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.
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http://dx.doi.org/10.1097/CEJ.0000000000000703DOI Listing
June 2021

The association of women's birth size with risk of molecular breast cancer subtypes: a cohort study.

BMC Cancer 2021 Mar 23;21(1):299. Epub 2021 Mar 23.

Faculty of Medicine and Health Sciences, Department of Public Health and Nursing, Norwegian University of Science and Technology, Post box 8905, N-7491, Trondheim, Norway.

Background: Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes.

Methods: A cohort of 22,931 women born 1920-1966 were followed up for breast cancer occurrence from 1961 to 2012, and 870 were diagnosed during follow-up. Archival diagnostic material from 537 patients was available to determine molecular breast cancer subtype, specified as Luminal A, Luminal B (human epidermal growth factor receptor 2 (HER2)-), Luminal B (HER2+), HER2 type, and Triple negative (TN) breast cancer. Information on the women's birth weight, birth length and head circumference at birth was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for each molecular subtype, applying Cox regression, and stratified by maternal height.

Results: Birth length (per 2 cm increments) was positively associated with Luminal A (HR = 1.2, 95% CI, 1.0-1.3), Luminal B (HER2+) (HR = 1.3, 95% CI, 1.0-1.7), and TN breast cancer (HR = 1.4, 95% CI, 1.0-1.9). No clear association was found for birth weight and head circumference. The positive associations of birth length were restricted to women whose mothers were relatively tall (above population median).

Conclusion: We found a positive association of birth length with risk of Luminal A, Luminal B (HER2+) and TN breast cancer that appears to be restricted to women whose mothers were relatively tall. This may support the hypothesis that breast cancer risk is influenced by determinants of longitudinal growth and that this finding deserves further scrutiny.
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http://dx.doi.org/10.1186/s12885-021-08027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989032PMC
March 2021

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

J Epidemiol Community Health 2021 08 23;75(8):779-787. Epub 2021 Feb 23.

Division of Public Health, Department of Family and Preventive Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Background: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures.

Methods: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs.

Results: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94).

Conclusions: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.
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http://dx.doi.org/10.1136/jech-2020-214913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292575PMC
August 2021

The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-Analysis.

Ann Neurol 2021 02 9;89(2):380-388. Epub 2020 Dec 9.

Second Department of Neurology, Attikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Objective: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations.

Methods: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

Results: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I = 45%).

Interpretation: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388.
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http://dx.doi.org/10.1002/ana.25967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753413PMC
February 2021

Associations of air pollution and greenness with mortality in Greece: An ecological study.

Environ Res 2021 05 28;196:110348. Epub 2020 Oct 28.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Epidemiological studies have documented the adverse effects of long-term exposure to fine particulate matter (PM) on health, while there has been less research on the effects of nitrogen dioxide (NO), black carbon (BC) and especially ozone (O). Furthermore, there is limited evidence for the synergistic effects of exposure to pollutants and greenness. We investigated the association of long-term exposure to air pollution and greenness with natural-cause, cardiovascular and respiratory mortality in Greece using an ecological study design.

Methods: Mortality and socioeconomic data were obtained from 1035 municipal units from the 2011 census data. Annual average PM, NO, BC and O concentrations for 2010 were derived from 100 × 100 m surfaces predicted by hybrid LUR models. The normalized difference vegetation index was used to assess greenness. We applied Poisson regression models on standardized mortality rates adjusted for socioeconomic indicators and lung cancer rates, accounting for spatial autocorrelation. The analysis was conducted initially for the whole country and then separately for urban and rural areas. We assessed interactions between pollutants and greenness and applied two-exposure models.

Results: An interquartile range (IQR) increase in PM, NO and BC was associated with increases in natural-cause mortality (Relative Risk (RR) 1.09, 95% confidence interval (CI): 1.08, 1.11; RR 1.03 (95% CI: 1.03, 1.04) and RR 1.02 (95% CI: 1.02, 1.03), respectively), while PM and NO were also associated with cause-specific mortality. Greenness was associated with lower natural-cause (RR 0.95, 95% CI: 0.94, 0.96 per IQR) and cause-specific mortality. For all outcomes we estimated a protective association with O (natural-cause mortality RR 0.79, 95% CI: 0.76, 0.82 per IQR). All associations were stronger in urban areas. We estimated negative statistically significant interactions between air pollution and greenness for respiratory morality and positive ones for cardiovascular mortality. Estimates were mostly robust to co-exposure adjustment.

Conclusions: Our findings support associations of air pollution and greenness with mortality, both in urban and rural areas of Greece. Further research is needed to elaborate on the synergies in cause-specific mortality. Our results on the interactions between pollutants and greenness may imply differential biological mechanisms for cause-specific mortality and warrant further investigation.
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http://dx.doi.org/10.1016/j.envres.2020.110348DOI Listing
May 2021

Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP).

Cancers (Basel) 2020 Oct 20;12(10). Epub 2020 Oct 20.

Research Group in Gene-Environment Interactions and Health, Instituto de Biomedicina (IBIOMED), University of León, 24071 León, Spain.

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54-0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55-0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56-0.92), flavanols (OR = 0.77, 95% CI = 0.66-0.88), flavanones (OR = 0.57, 95%CI = 0.44-0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55-0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57-0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51-1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58-1.06). Further investigations from longitudinal data are needed to confirm this association.
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http://dx.doi.org/10.3390/cancers12103064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588964PMC
October 2020

Adult height and risk of gastric cancer: a pooled analysis within the Stomach cancer Pooling Project.

Eur J Cancer Prev 2020 Sep 10. Epub 2020 Sep 10.

Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background: The association between height and risk of gastric cancer has been studied in several epidemiological studies with contrasting results. The aim of this study is to examine the association between adult height and gastric cancer within a large pooled analysis of case-control studies members of the Stomach cancer Pooling (StoP) Project consortium.

Methods: Data from 18 studies members of the StoP consortium were collected and analyzed. A multivariable logistic regression model was used to estimate the study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between 10-cm increase in height and risk of gastric cancer. Age, sex, tobacco smoking, alcohol consumption, social class, geographical area and Helicobacter pylori (H. pylori) status were included in the regression model. Resulting estimates were then pooled with random-effect model. Analyses were conducted overall and in strata of selected variables.

Results: A total of 7562 cases and 19 033 controls were included in the analysis. The pooled OR was 0.96 (95% CI 0.87-1.05). A sensitivity analysis was performed restricting the results to the studies with information on H. pylori status, resulting in an OR of 0.97 (95% CI 0.79-1.20).

Conclusion: Our study does not support a strong and consistent association between adult height and gastric cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000613DOI Listing
September 2020

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

Br J Cancer 2020 10 24;123(9):1456-1463. Epub 2020 Aug 24.

Institute of Oncology and Radiobiology, Havana, Cuba.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).

Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
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http://dx.doi.org/10.1038/s41416-020-01031-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592048PMC
October 2020

Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Eur J Cancer Prev 2020 09;29(5):408-415

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Background: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies.

Aim: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy.

Methods: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models.

Results: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before.

Conclusions: There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.
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http://dx.doi.org/10.1097/CEJ.0000000000000572DOI Listing
September 2020

Modified Mediterranean diet score adapted to a southern Mediterranean population and its relation to overweight and obesity risk.

Public Health Nutr 2021 09 29;24(13):4064-4070. Epub 2020 Jul 29.

Department of Epidemiology and Public Health, Faculty of Medicine, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Objectives: The current study aimed to develop a modified Mediterranean diet (MMD) score adjusted to the southern Mediterranean countries' cultural specificities and to evaluate associations between adherence to this modified score and overweight/obesity risk in Moroccan adults.

Design: Population-based cross-sectional study.

Setting: Rural and urban areas of the five greatest provinces of Morocco.

Participants: In total, 1516 participants were recruited between September 2009 and February 2017. Dietary assessment was obtained using a validated Moroccan FFQ. We constructed a MMD score focusing on twelve components. The MMD score ranged from 0 (no adherence to the traditional southern Mediterranean diet (MD)) to 12 (maximal adherence) and was categorised as low (scores 0-4), moderate (scores 5-7) and high (scores 8-12).

Results: Among the whole population, 754 (50·5 %) were women and 738 (49·5 %) were men, and the mean age was about 55·60 ± 13·70. In total, 58 % of participants were moderately active. Regarding educational level, 50·7 % were illiterate. The prevalence of overweight and obesity was 43·3 and 8·6 %, respectively. In multivariate analyses, close adherence to MMD (scores 8-12) was associated with reduced overweight/obesity risk (OR 0·61, 95 % CI 0·44, 0·84).

Conclusion: The prevalence of overweight and obesity was very high among Moroccan adults. Adherence to the traditional southern MD may help prevent overweight and obesity.
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http://dx.doi.org/10.1017/S1368980020002062DOI Listing
September 2021

Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project.

Int J Cancer 2020 12 29;147(11):3090-3101. Epub 2020 Jun 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.
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http://dx.doi.org/10.1002/ijc.33134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545605PMC
December 2020

The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design.

Hellenic J Cardiol 2020 Jan - Feb;61(1):42-45. Epub 2020 Apr 3.

Humanitas Clinical and Research Institute, Rozzano, Milan, Italy; Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Objective: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention.

Methods: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group.

Results: Trial results will be disseminated through peer-reviewed publications and conference presentations.

Conclusion: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).
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http://dx.doi.org/10.1016/j.hjc.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194546PMC
July 2020
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