rubrica

Cause ed epidemiologia analitica

  • Lorenzo Richiardi1

  1. Università di Torino

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Ricerca bibliografica periodo dal 16 aprile – 30 giugno 2014

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Stringa: ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2014/04/16"[PDat] : "2014/06/30"[PDat]) AND (“Case-Control” [All fields] OR “Cohort”[all fileds] OR “Cross-sectional”[All fields]) AND ("risk"[All Fields] OR "association"[all fields] OR "epidemiologic factors"[MeSH Terms]) and (“odds ratios”[all fields] OR “odds ratio”[all fields] OR “ORs”[all fields] OR “rate ratio”[all fileds] OR “rate ratios”[all fileds] OR “RR”[all fileds] OR “RRs” [all fileds] OR “risk ratio”[all fields] OR “risk ratios”[all fields] OR “prevalence ratio*” [all fields] OR “prevalence ratios” [all fields] OR “hazard ratio” [all fields] OR “hazard ratios” [all fields] OR “HR”[all fields] OR “HRs”[all fields]) NOT "Clinical Trials as Topic"[Mesh] NOT "Sensitivity and Specificity"[Mesh] NOT "Comorbidity"[Mesh] NOT "Predictive Value of Tests"[Mesh] NOT "Prognosis"[Mesh] NOT "Review"[publication type] NOT "Population Surveillance"[Mesh]

FOCUS: Generici, non tumori o malattie cardiovascolari NOT (("neoplasms"[Mesh] OR (neoplasm*[ti/ab]) OR tumor*[ti/ab] OR cancer*[ti/ab]) OR ("cardiovascular diseases"[MeSH Terms] OR (cardiovascular*[title/abstract] AND diseas*[title/abstract])))

1. Corrao G(1), Ibrahim B(2), Nicotra F(2), Soranna D(2), Merlino L(3), Catapano AL(4), Tragni E(5), Casula M(5), Grassi G(6), Mancia G(7). Statins and the risk of diabetes: evidence from a large population-based cohort study. Diabetes Care. 2014 Aug;37(8):2225-32. doi: 10.2337/dc13-2215. Epub 2014 Jun 26.
Author information: (1)Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy giovanni.corrao@unimib.it. (2)Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. (3)Operative Unit of Territorial Health Services, Region Lombardia, Milan, Italy. (4)Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, ItalyIRCCS Multimedica, Sesto San Giovanni, Milan, Italy. (5)Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy. (6)IRCCS Multimedica, Sesto San Giovanni, Milan, ItalyDepartment of Health Science, University of Milano-Bicocca, Milan, Italy. (7)Department of Health Science, University of Milano-Bicocca, Milan, ItalyIRCCS Istituto Auxologico Italiano, Milan, Italy.

Abstract
OBJECTIVE: To investigate the relationship between adherence with statin therapy and the risk of developing diabetes. RESEARCH DESIGN AND METHODS: The cohort comprised 115,709 residents of the Italian Lombardy region who were newly treated with statins during 2003 and 2004. Patients were followed from the index prescription until 2010. During this period, patients who began therapy with an antidiabetic agent or were hospitalized for a main diagnosis of type 2 diabetes were identified (outcome). Adherence was measured by the proportion of days covered (PDC) with statins (exposure). A proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% CIs for the exposure-outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: During follow-up, 11,154 cohort members experienced the outcome. Compared with patients with very-low adherence (PDC <25%), those with low (26-50%), intermediate (51-75%), and high (≥75%) adherence to statin therapy had HRs (95% CIs) of 1.12 (1.06-1.18), 1.22 (1.14-1.27), and 1.32 (1.26-1.39), respectively. CONCLUSIONS: In a real-world setting, the risk of new-onset diabetes rises as adherence with statin therapy increases. Benefits of statins in reducing cardiovascular events clearly overwhelm the diabetes risk.

2. Gagliardi L(1), Rusconi F(2), Bellù R(3), Zanini R(3); Italian Neonatal Network. Association of maternal hypertension and chorioamnionitis with preterm outcomes. Pediatrics. 2014 Jul;134(1):e154-61. doi: 10.1542/peds.2013-3898. Epub 2014 Jun 9.
Collaborators: Mirri G, Condò M, Turoli D, Vanzati M, Mosca F, De Nisi G, Polacco P, Villa E, Barbarini M, Fasolato V, Franco C, Melloni MM, Contiero R, Ellero S, Cattarossi L, Abbiati L, Borroni C, Prandi G, Fabris C, Vielmi F, Borgione S, Agosti M, Tandoi F, Guidali R, De Curtis M, Tozzi C, Lucchini R, Battaglioli M, Lista GL, Introvini P, Buzzi M, Ferrari F, Gallo C, Bellante E, Bottura C, Zeringyte A, Pasquali F, Boccacci S, Latini G, Giannuzzi R, Martinelli S, Brunelli A, Di Nunzio ML, Vendemmiati A, Carli G, Bordigato MA, Filippone M, Meneghesso D, Romeo N, Mammoliti P, Mastretta E, Barberis L, Farina D, Gancia G, Dalmazzo C, Napolitano M, Messina F, Magaldi R, Rinaldi M, Litta R, Lago P, Zanardo V, Chiandetti L, Visentin S, Presta G, Cella D, Poggiani C, Ferrari D, Parati S, Lombardo F, Grigorio R, Barera G, Bove M, Poloniato A, Burgio G, Sala E, Barberi I, Tiralongo V, Arco A, Mazzeo D, Dani C, Pratesi S, Mignatti V, Ancora G, Faldella G, Grandi S, Locatelli C, Stronati M, Perotti G, Chirico G, Migliori C, De Marini S, Forleo V, Paludetto R, Capasso L, Mansi G, Raimondi F, Bona G, Stucchi I, Savastio S, Ferrero F, Parola A, Padovani EM, Viviani E, Pecoraro L, Agostino R, Gizzi C, Massenzi L, Messner H, Staffler A, Salvia G, Esposito L, Forziati V, Latorre G, Sandri F, Alati S, Demarca F, Lombardi O, Costabile CD, Scarpelli G, Cavalli C, Volante E, Moretti S, Ganguzza O, Spinella B, Haass C, Scapillati E, Consigli C, Gatta A, Quitadamo P, Rotondo SG, Boldrini A, Vuerich M, Sigali E, Fiorini P, Petrucci L, Moroni M, Meyer F, Bragetti P, Casucci P, Minelli L, Mezzetti D, Orfeo L, De Luca MG, Laforgia N, Grassi A, Dotta A, Savignoni F, Bagnoli F, De Felice C, Badii S, Biasini A, Belluzzi A, Stella M, Romagnoli C, Zecca E, Barone G, Colleselli P, Vecchiato L, Nicolussi S, Giliberti P, Chello G, Rojo S, De Vivo M, Giovanettoni C, Colnaghi CA, Manfredini V, Verucci E, Placidi G, Belloni C, Carrera G, Zambetti C, Biban P, Serra A, Sacco F, Vetrano G, Furcolo G, Pasquariello B, Falco L, Ausanio G, Bernardo I, Capasso A, Marchesano G, Nosari N, Sarnelli P, Inferiore N, Ciraci G, Merazzi D, Gazzolo D, Temperini F, Sabatini M, Colivicchi M, Del Vecchio A, Tarantino M, Gargano G, Pedori S, Bellettato M, Pesavento R, Cesaro A, Scollo M, Mondello I, Pugliese A, Iervolino C, Corsello G, Giuffré M, Betta P, Romeo MG, Saporito A, Leone MG, Rodonò A, Franceschi A, Risso FM, Carpentieri M, Vecchiano T, Cigliano MP, Paolillo P, Picone S, Marra A, Rossetti G, Testa T, Del Cuore F, Crescenzi F, Poloni G, Russo MC, Nigro F, Tina GL, Brindisino P, Gurrado R, Felice M, Formica I. Author information: (1)Department of Woman and Child Health, Ospedale Versilia, Viareggio, Italy; l.gagliardi@neonatalnet.org. (2)Unit of Epidemiology, A Meyer Children's University Hospital, Florence, Italy; and. (3)Neonatal ICU, Ospedale Alessandro Manzoni, Lecco, Italy.

Abstract
OBJECTIVES: We compared the relative effect of hypertensive disorders of pregnancy and chorioamnionitis on adverse neonatal outcomes in very preterm neonates, and studied whether gestational age (GA) modulates these effects. METHODS: A cohort of neonates 23 to 30 weeks' GA, born in 2008 to 2011 in 82 hospitals adhering to the Italian Neonatal Network, was analyzed. Infants born from mothers who had hypertensive disorders (N = 2096) were compared with those born after chorioamnionitis (N = 1510). Statistical analysis employed logistic models, adjusting for GA, hospital, and potential confounders. RESULTS: Overall mortality was higher after hypertension than after chorioamnionitis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.08-1.80), but this relationship changed across GA weeks; the OR for hypertension was highest at low GA, whereas from 28 weeks' GA onward, mortality was higher for chorioamnionitis. For other outcomes, the relative risks were constant across GA; infants born after hypertension had an increased risk for bronchopulmonary dysplasia (OR, 2.20; 95% CI, 1.68-2.88) and severe retinopathy of prematurity (OR, 1.48; 95% CI, 1.02-2.15), whereas there was a lower risk for early-onset sepsis (OR, 0.25; 95% CI, 0.19-0.34), severe intraventricular hemorrhage (OR, 0.65; 95% CI, 0.48-0.88), periventricular leukomalacia (OR, 0.70; 95% CI, 0.48-1.01), and surgical necrotizing enterocolitis or gastrointestinal perforation (OR, 0.47; 95% CI, 0.31-0.72). CONCLUSIONS: Mortality and other adverse outcomes in very preterm infants depend on antecedents of preterm birth. Hypertension and chorioamnionitis are associated with different patterns of outcomes; for mortality, the effect changes across GA weeks.

3. Iorio A(1), Polimanti R, Piacentini S, Liumbruno GM, Manfellotto D, Fuciarelli M. Deletion polymorphism of GSTT1 gene as protective marker for allergic rhinitis. Clin Respir J. 2014 Jun 5. doi: 10.1111/crj.12170. [Epub ahead of print]
Author information: (1)Department of Biology, University of Rome 'Tor Vergata', Rome, Italy; Clinical Pathophysiology Center, AFaR - 'San Giovanni Calibita' Fatebenefratelli Hospital, Rome, Italy.

Abstract
BACKGROUND AND AIMS: Allergic rhinitis (AR) is one of the most common respiratory diseases among human populations. Strong evidence suggests that genetic predisposition and environmental factors could contribute to the development of this complex disease. Glutathione S-transferases (GSTs) are biomarkers of inflammation and oxidative stress. These phase II enzymes play a significant role in detoxifying xenobiotic compounds. To analyze the role of GST gene polymorphisms in AR pathogenesis in a case-control population of 103 patients affected by AR and 200 healthy non-allergic subjects. METHODS: We screened genomic DNA extracted from buccal cells for GSTM1 positive/null, GSTP1*I105V (rs1695) and GSTT1 positive/null polymorphisms. The X(2) -test, odds ratio (OR) and logistic regression were used as statistical analyses. RESULTS: Significant differences in null genotype distribution between AR patients (13%) and healthy controls (30%) were found for the GSTT1 null genotype (OR = 0.30, 95% confidence interval = 0.14-0.65; P = 0.001). GSTM1 and GSTP1 polymorphisms did not show any significant results. CONCLUSION: Our data indicated that GSTT1 may be a susceptibility locus for AR. Specifically, the positive/null polymorphism of GSTT1 may be involved in an oxidative stress-related mechanism that may enhance pathogenic pathways related to AR. Moreover, beside GSTT1, this deletion polymorphism affects also another gene potentially related to AR phenotype, LOC391322. This gene belongs to MIF (macrophage migration inhibitory factor) gene family and several studies indicated the role of this gene in several immunology-related phenotypes. Therefore, two different scenarios may explain the observed genetic association.

4. Toffanello ED(1), Sergi G(2), Veronese N(2), Perissinotto E(3), Zambon S(4), Coin A(2), Sartori L(5), Musacchio E(5), Corti MC(6), Baggio G(7), Crepaldi G(8), Manzato E(9). Serum 25-Hydroxyvitamin D and the Onset of Late-Life Depressive Mood in Older Men and Women: The Pro.V.A. Study. J Gerontol A Biol Sci Med Sci. 2014 Jun 4. pii: glu081. [Epub ahead of print]
Author information: (1)Department of Medical and Surgical Sciences, Department of Medicine, Geriatrics Division, elenadebora.toffanello@sanita.padova.it. (2)Department of Medical and Surgical Sciences, Department of Medicine, Geriatrics Division. (3)Department of Environmental Medicine and Public Health, and. (4)Department of Medical and Surgical Sciences, University of Padua, Padova, Italy. National Research Council, Aging Branch, Institute of Neuroscience, Padova, Italy. (5)Department of Medical and Surgical Sciences, University of Padua, Padova, Italy. (6)Dipartimento Socio Sanitario dei Colli, Azienda Unità Locale Socio Sanitaria, Padova, Italy. (7)Internal Medicine Division, Azienda Ospedaliera, Padova, Italy. (8)National Research Council, Aging Branch, Institute of Neuroscience, Padova, Italy. (9)Department of Medical and Surgical Sciences, Department of Medicine, Geriatrics Division, National Research Council, Aging Branch, Institute of Neuroscience, Padova, Italy.

Abstract
INTRODUCTION: Biological evidence suggests that vitamin D might be involved in regulating mood. The relationship between 25-hydroxyvitamin D (25OHD) and the onset of depressive symptoms was examined over a 4.4-year follow-up in a sample of older adults. METHODS: This research was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study on a total of 1,039 women and 636 men aged 65 and older. Serum 25OHD levels were measured at baseline. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS) at the baseline and during the follow-up. Analyses were adjusted for relevant confounders, including health and performance status. RESULTS: 25OHD levels correlated inversely with baseline GDS scores, but only in women. After controlling for confounders, women deficient in vitamin D (25OHD < 50 nmol/L) had higher GDS scores than those who were replete (25OHD > 75 nmol/L), with mean [SE] GDS scores: 9.57 [0.37] vs 8.31 [0.31], respectively, p = .02. In men, the relationship between 25OHD levels and baseline GDS scores was no longer significant after controlling for covariates. Adjusted hazard ratios and 95% confidence intervals for incident depression in participants who were vitamin D deficient vs replete were not statistically significant (hazard ratio: 0.74, 95% confidence interval [0.47-1.16] in women; hazard ratio: 0.96 95% confidence interval [0.45-2.06] in men). CONCLUSION: Although an independent inverse association between 25OHD levels and GDS scores emerged for women on cross-sectional analysis, vitamin D deficiency showed no direct effect on the onset of late-life depressive symptoms in our prospectively studied population. Further studies are warranted to clarify the potential influence of vitamin D on psychological health.

5. Bo S(1), De Carli L, Venco E, Fanzola I, Maiandi M, De Michieli F, Durazzo M, Beccuti G, Cavallo-Perin P, Ghigo E, Ganzit GP. Impact of Snacking Pattern on Overweight and Obesity Risk in A Cohort of 11-13-y Adolescents. J Pediatr Gastroenterol Nutr. 2014 Jun 2. [Epub ahead of print]
Author information: (1)*Department of Medical Science, University of Torino, Torino, Italy †Sport Medicine Institute of Torino, Italy.

Abstract
OBJECTIVES:: The association between snacking habits and overweight is unclear in adolescents. We evaluated the relationship between snacking patterns and overweight/obesity in a cohort of 11-13-year adolescents. METHODS:: The dietary habits of 400 randomly selected adolescents were evaluated; those with BMI ≥ 85 percentile were considered as overweight/obese. Participants were classified by percent caloric intake from snacks (<15%, 15-20, >20%), snacking frequency (1, 2, ≥3), and timing of consuming the most caloric snack (morning, afternoon, evening). RESULTS:: A minority (13/400; 3.3%) did not consume any snacks; 5/13 (38.5) of them were overweight/obese. Among snackers (387/400), overweight/obesity prevalences were 10.4%,14.4%,20.5% respectively in those consuming < 15%,15-10%, and >20% of their energy intake from snacks. In a Poisson regression model, the overweight/obesity RRs were 1.35 (95%CI 0.58-3.15) and 2.32 (1.10-4.89) for 15-20% and >20% calories/day from snacks, respectively. Overweight/obesity prevalence (from 9.6 to 22.6%) was correlated with snacking frequency (RR = 2.20; 0.92-5.27, and RR = 4.17; 1.60-10.9, for 2 and ≥3 snacks/day, respectively). The most caloric snacks were consumed in the morning (180/387) and afternoon (179/387); 28.6% of the predominantly evening snackers (28/387) were overweight/obese (RR = 3.12; 1.17-8.34). CONCLUSIONS:: Increased snacking calories, frequency and evening snacking are independently associated with overweight/obesity in Italian middle-school adolescents.

6. Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R, Simonato L. Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol. 2014 Jul 1;180(1):76-85. doi: 10.1093/aje/kwu101. Epub 2014 May 22

Abstract
We conducted a population-based birth cohort study of approximately 203,000 babies born in northeastern Italy (1989-2012) to investigate perinatal variables, early infections leading to hospital admission, and antibiotic use in the first 12 months of life as possible risk factors for celiac disease (CD). Incident CD cases were identified from pathology reports, hospital discharge records, and exemptions from prescription charges for clinical tests. Multivariate Poisson regression models were fitted to estimate incidence rate ratios (IRRs). A total of 1,227 children had CD; CD was histopathologically confirmed in 866 (71%). Female sex, maternal age, and high maternal educational level were found to be significantly associated with CD. Gastrointestinal infections were strongly associated with a subsequent diagnosis of CD (IRR = 2.04, 95% confidence interval (CI): 1.30, 3.22). Antibiotic use was significantly associated with CD onset (IRR = 1.24, 95% CI: 1.07, 1.43), with a dose-response relationship for number of courses (P-trend < 0.01). Cephalosporin use strongly increased the risk of CD (IRR = 1.42, 95% CI: 1.18, 1.73). Use of antibiotics (supported by the dose-response relationship) and gastrointestinal infections in the first year of life may facilitate the early onset of CD by altering intestinal microflora and the gut mucosal barrier. Perinatal factors, including cesarean section, had little influence on the risk of childhood CD.

Commento a cura di Lorenzo Richiardi: Lo studio si base sul record-linkage di diversi registri di popolazione in Friuli Venezia Giulia per studiare fattori di rischio per il morbo celiaco. Lo studio riesce ad avere una buona abbondanza di informazioni su possibili fattori di rischio. In generale non trova associazioni per fattori prenatali come peso alla nascita , età gestazionale e punteggio Apgar, mentre trova un’associazione con ospedalizzazione per infezioni nel primo anno di vita e uso di di antibiotici nel primo anno di vita. Negli studi sul morbo celiaco bisogna sempre considerare il rischio di detection bias o, più in generale, il fatto che non tutti i casi vengono diagnosticati. Le esposizioni identificate come fattori di rischio possono essere quindi reali fattori di rischio o determinati della diagnosi. Questa fonte di difficoltà nell’interpetazione dei risultati viene accuratamente discussa nell’articolo.

7. Russo GI(1), Cimino S, Fragalà E, Privitera S, La Vignera S, Condorelli R, Calogero AE, Castelli T, Favilla V, Morgia G. Insulin resistance is an independent predictor of severe lower urinary tract symptoms and of erectile dysfunction: results from a cross-sectional study. J Sex Med. 2014 Aug;11(8):2074-82. doi: 10.1111/jsm.12587. Epub 2014 May 19.
Author information: (1)Department of Urology, University of Catania, Urology, Catania, Italy.

Abstract
INTRODUCTION: Several studies have linked the association between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and the presence of insulin resistance (IR) due to an underlined metabolic syndrome (MetS). AIM: This study aims to determine the relationship between IR, sexual function, and LUTS and to demonstrate the ability of IR in predicting ED and severe LUTS. METHODS: Between January 2008 to January 2013, 544 consecutive patients with benign prostatic hyperplasia-related LUTS were enrolled. LUTS and sexual function of the patients were evaluated by the International Index of Erectile Function (IIEF) and the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation. IR was defined as a homeostasis model assessment (HOMA) index of 3 or greater. MAIN OUTCOME MEASURES: Uni- and multivariate logistic regression analysis was performed to assess significant predictors of severe LUTS (IPSS ≥20) and ED (IIEF-Erectile Function [IIEF-EF] <26), including MetS component, prostate volume, prostate-specific antigen, total testosterone, and HOMA index. RESULTS: IR patients resulted in higher values of IPSS (19.0 vs. 15.0; P < 0.01), IPSS-storage (6.0 vs. 5.0; P < 0.01), IPSS-voiding (12.0 vs. 9.0; P < 0.01), total prostate volume (54.8 vs. 36.5; P < 0.01), and lower values of IIEF-EF (17.0 vs. 20.0; P < 0.01), IIEF-Intercourse Satisfaction (3.0 vs. 10.0; P < 0.01), IIEF-Orgasmic Function (8.0 vs. 9.0; P < 0.01), IIEF-Overall Satisfaction (6.0 vs. 8.0; P < 0.01), and total testosterone (3.83 vs. 4.44; P < 0.01). IR was demonstrated to be a strong predictor of ED (IIEF-EF <26) (odds ratio [OR] = 6.20, P < 0.01) after adjusting for confounding factors. Finally, IR was also an independent predictor of severe LUTS (IPSS ≥20) (OR = 2.0, P < 0.01) after adjusting for confounding factors. CONCLUSIONS: IR patients are at high risk of having severe LUTS and contemporary sexual dysfunctions. We strongly suggest to prevent LUTS and ED by reducing insulin resistance. Russo GI, Cimino S, Fragalà E, Privitera S, La Vignera S, Condorelli R, Calogero AE, Castelli T, Favilla V, and Morgia G. Insulin resistance is an independent predictor of severe lower urinary tract symptoms and of erectile dysfunction: Results from a cross-sectional study. J Sex Med 2014;11:2074-2082.

8. Grosso G(1), Marventano S, Galvano F, Pajak A, Mistretta A. Factors associated with metabolic syndrome in a mediterranean population: role of caffeinated beverages. J Epidemiol. 2014 Jul 5;24(4):327-33. Epub 2014 May 3.
Author information: (1)Department of G.F. Ingrassia, Section of Hygiene and Public Health, University of Catania.

Abstract
Background: Intake of caffeinated beverages, such as coffee and tea, has been related to improvements in components of metabolic syndrome (MetS), but studies conducted in the Mediterranean region are scarce. The aim of this study was to evaluate whether or not consumption of a variety of beverages containing caffeine was associated with components of MetS in an Italian population.Methods: From May 2009 to December 2010, a cross-sectional survey was conducted on 1889 inhabitants living in Sicily, southern Italy. Data regarding demographic characteristics, habitual beverage intake, and adherence to the Mediterranean diet were collected, and clinical information was retrieved from the general practitioners' computer records.Results: After adjusting for all covariates, coffee (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.27-0.70) and tea (OR 0.51, 95% CI 0.34-0.78) were associated with MetS, whereas no association was observed between caffeine intake and MetS. Among other factors, age, body mass index, physical activity, current smoking, and adherence to Mediterranean diet were associated with having MetS. Triglycerides were inversely associated with consumption of both espresso coffee and tea. The healthy effects of such beverages were more evident in individuals with unhealthy dietary habits.Conclusions: Although no direct association between caffeine intake and MetS or its components was observed, coffee and tea consumption was significantly related to reduced odds of MetS.

9. Indolfi G(1), Mangone G, Calvo PL, Bartolini E, Regoli M, Serranti D, Calitri C, Tovo PA, de Martino M, Azzari C, Resti M. Interleukin 28B rs12979860 single-nucleotide polymorphism predicts spontaneous clearance of hepatitis C virus in children. J Pediatr Gastroenterol Nutr. 2014 May;58(5):666-8. doi: 10.1097/MPG.0000000000000275.
Author information: (1)*Pediatric and Liver Unit †Immunology Unit and Laboratory at Meyer Children's University Hospital of Florence ‡Department of Pediatrics, Infectious Diseases Unit, University of Turin, Regina Margherita Children's Hospital, Turin §Department of Health Sciences, University of Florence, Firenze, Italy.

Abstract
OBJECTIVE: Recent genome-wide association studies performed in adults correlated single-nucleotide polymorphisms (SNPs rs12979860 and rs8099917) located on chromosome 19, upstream of the interleukin 28B gene, with spontaneous clearance of hepatitis C virus and with response to treatment with paginated interferon and ribavirin. The aim of the present collaborative study was to evaluate the rs12979860 SNP in a large cohort of Italian children with perinatal acquisition of hepatitis C. METHODS: Children were prospectively enrolled in 2 Italian centers. The interleukin 28B rs12979860 SNP was studied according to the diagnosis of chronic infection or spontaneous clearance. RESULTS: One hundred thirty children (86.7%) with chronic infection and 23 (13.3%) with spontaneous clearance of the virus were enrolled. Overall, the interleukin 28B C/C and C/T-T/T genotypes were found in 57 (37.3%) and 96 (62.7%) children, respectively. The proportion of C/C genotype was higher among children who cleared infection (14/23; 60.9%) compared with children with chronic infection (43/130; 33.1%; P = 0.01; odds ratio 3.15; 90% confidence intervals 1.34-7.53). CONCLUSIONS: The present study showed that, as already demonstrated in adults, children with the rs12979860 C/C SNP of the interleukin 28B gene have a higher probability of spontaneous clearance of hepatitis C virus.

10. Giardina E, Oddone F, Lepre T, Centofanti M, Peconi C, Tanga L(1), Quaranta L, Frezzotti P, Novelli G, Manni G. Common sequence variants in the LOXL1 gene in pigment dispersion syndrome and pigmentary glaucoma. BMC Ophthalmol. 2014 Apr 16;14:52. doi: 10.1186/1471-2415-14-52.
Author information: (1)Fondazione G,B, Bietti-IRCCS, Via Livenza 3, 00198 Rome, Italy. lucia.tanga@gmail.com.

Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of our study is to investigate a potential involvement of LOXL1 gene in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). METHODS: A cohort of Caucasian origin of 84 unrelated and clinically well-characterised patients with PDS/PG and 200 control subjects were included in the study. Genomic DNA from whole blood was extracted and the coding and regulatory regions of LOXL1 gene were risequenced in both patients and controls to identify unknown sequence variations. Genotype and haplotype analysis were performed with UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from peripheral blood lymphocytes by quantitative real-time RT-PCR. RESULTS: A significant allele association was detected for SNP rs2304722 within the fifth intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis revealed the existence of risk and protective haplotypes associated with PG-PDS (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively). Expression analysis suggests that associated haplotypes can regulate the expression level LOXL1. CONCLUSIONS: Haplotypes of LOXL1 are associated with PG-PDS independently from rs1048661, leading to a differential expression of the transcript.

11. Ranzi A(1), Porta D, Badaloni C, Cesaroni G, Lauriola P, Davoli M, Forastiere F. Exposure to air pollution and respiratory symptoms during the first 7 years of life in an Italian birth cohort. Occup Environ Med. 2014 Jun;71(6):430-6. doi: 10.1136/oemed-2013-101867. Epub 2014 Mar 21.
Author information: (1)Environmental Health Reference Centre, Regional Agency for Environmental Prevention of Emilia-Romagna, Modena, Italy.

Abstract
BACKGROUND: Ambient air pollution has been consistently associated with exacerbation of respiratory diseases in schoolchildren, but the role of early exposure to traffic-related air pollution in the first occurrence of respiratory symptoms and asthma is not yet clear. METHODS: We assessed the association between indexes of exposure to traffic-related air pollution during different periods of life and respiratory outcomes in a birth cohort of 672 newborns (Rome, Italy). Direct interviews of the mother were conducted at birth and at 6, 15 months, 4 and 7 years. Exposure to traffic-related air pollution was assessed for each residential address during the follow-up period using a Land-Use Regression model (LUR) for nitrogen dioxide (NO2) and a Geographic Information System (GIS) variable of proximity to high-traffic roads (HTR) (>10 000vehicles/day). We used age-specific NO2 levels to develop indices of exposure at birth, current, and lifetime time-weighted average. The association of NO2 and traffic proximity with respiratory disorders were evaluated using logistic regression in a longitudinal approach (Generalised Estimating Equation). The exposure indexes were used as continuous and categorical variables (cut-off points based on the 75th percentile for NO2 and the 25th percentile for distance from HTRs). RESULTS: The average NO2 exposure level at birth was 37.2 μg/m(3) (SD 7.2, 10-90th range 29.2-46.1). There were no statistical significant associations between the exposure indices and the respiratory outcomes in the longitudinal model. The odds ratios for a 10-µg/m(3) increase in time-weighted average NO2 exposure were: asthma incidence OR=1.09; 95 CI% 0.78 to 1.52, wheezing OR=1.07; 95 CI% 0.90 to 1.28, shortness of breath with wheezing OR=1.16; 95 CI% 0.94 to 1.43, cough or phlegm apart from cold OR=1.11; 95 CI% 0.92 to 1.33, and otitis OR=1.08; 95 CI% 0.89 to 1.32. Stronger but not significant associations were found considering the 75th percentile of the NO2 distribution as a cut-off, especially for incidence of asthma and prevalence of wheeze (OR=1.41; 95 CI% 0.88 to 2.28 and OR=1.27; 95 CI% 0.95 to 1.70, respectively); the highest OR was found for wheezing (OR=2.29; 95 CI% 1.15 to 4.56) at the 7-year follow-up. No association was found with distance from HTRs. CONCLUSIONS: Exposure to traffic-related air pollution is only weakly associated with respiratory symptoms in young children in the first 7 years of life.

12. Sonnenschein-van der Voort AM(1), Arends LR(2), de Jongste JC(3), Annesi-Maesano I(4), Arshad SH(5), Barros H(6), Basterrechea M(7), Bisgaard H(8), Chatzi L(9), Corpeleijn E(10), Correia S(6), Craig LC(11), Devereux G(11), Dogaru C(12), Dostal M(13), Duchen K(14), Eggesbø M(15), van der Ent CK(16), Fantini MP(17), Forastiere F(18), Frey U(19), Gehring U(20), Gori D(17), van der Gugten AC(16), Hanke W(21), Henderson AJ(22), Heude B(23), Iñiguez C(24), Inskip HM(25), Keil T(26), Kelleher CC(27), Kogevinas M(28), Kreiner-Møller E(8), Kuehni CE(12), Küpers LK(10), Lancz K(29), Larsen PS(30), Lau S(31), Ludvigsson J(14), Mommers M(32), Nybo Andersen AM(30), Palkovicova L(29), Pike KC(33), Pizzi C(34), Polanska K(21), Porta D(18), Richiardi L(34), Roberts G(5), Schmidt A(35), Sram RJ(13), Sunyer J(36), Thijs C(32), Torrent M(37), Viljoen K(27), Wijga AH(38), Vrijheid M(39), Jaddoe VW(40), Duijts L(41). Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J Allergy Clin Immunol. 2014 May;133(5):1317-29. doi: 10.1016/j.jaci.2013.12.1082. Epub 2014 Feb 12.
Author information: (1)Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Paediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. (2)Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands; Institute of Pedagogical Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands; Institute of Psychology, Erasmus University Rotterdam, Rotterdam, The Netherlands. (3)Department of Paediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. (4)EPAR, UMR-S 707 INSERM Paris, Paris, France; EPAR, UMR-S 707, Université Pierre et Marie Curie Paris 06, Paris, France. (5)David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom. (6)Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal. (7)Public Health Division of Gipuzkoa, Gipuzkoa, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Barcelona, Spain. (8)Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. (9)Department of Social Medicine, School of Medicine, University of Crete, Crete, Greece. (10)Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. (11)Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom. (12)Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. (13)Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. (14)Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, and Pediatric Clinic, County Council of Östergötland County Council, Linköping, Sweden. (15)Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. (16)Department of Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. (17)Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. (18)Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. (19)University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland. (20)Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. (21)Nofer Institute of Occupational Medicine, Department of Environmental Epidemiology, Lodz, Poland. (22)School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. (23)INSERM, Center for Research in Epidemiology and Population Health, U1018, Lifelong Epidemiology Of Obesity, Diabetes, and Renal Disease Team, Villejuif, France; University Paris-Sud, Villejuif, France. (24)Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Center for Public Health Research (CSISP), University of Valencia, Valencia, Spain; Faculty of nursery and chiropody, University of Valencia, Valencia, Spain. (25)MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom. (26)Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany; Institute for Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. (27)School of Public Health, Physiotherapy and Population Science, University College Dublin, Dublin, Ireland. (28)National School of Public Health, Athens, Greece. (29)Department of Environmental Medicine, Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia. (30)Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. (31)Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany. (32)Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands. (33)Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. (34)Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy. (35)Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland. (36)Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain; Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Barcelona, Spain. (37)IB-SALUT, Area de Salut de Menorca, Balearic Islands, Spain. (38)Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. (39)Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain. (40)Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Paediatrics, Erasmus Medical Center, Rotterdam, The Netherlands. (41)Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Paediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Paediatrics, Division of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: l.duijts@erasmusmc.nl. Comment in J Allergy Clin Immunol. 2014 May;133(5):1330-1.

Abstract
BACKGROUND: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

13. Andreoli V(1), De Marco EV, Trecroci F, Cittadella R, Di Palma G, Gambardella A. Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease. J Neural Transm. 2014 May;121(5):533-42. doi: 10.1007/s00702-013-1125-7. Epub 2013 Dec 1.
Author information: (1)Institute of Neurological Sciences, National Research Council, Pianolago di Mangone, Cosenza, Italy, v.andreoli@isn.cnr.it.

Abstract
Increasing evidence links dysregulation of NR2B-containing N-methyl-D-aspartate receptor remodelling and trafficking to Alzheimer's disease (AD). This theme offers the possibility that the GRIN2B gene, encoding this selective NR2B subunit, represents a potential molecular modulating factor for this disease. Based on this hypothesis, we carried out a mutation scanning of exons and flanking regions of GRIN2B in a well-characterized cohort of AD patients, recruited from Southern Italy. A "de novo" p.K1293R mutation, affecting a highly conserved residue of the protein in the C-terminal domain, was observed for the first time in a woman with familial AD, as the only genetic alteration of relevance. Moreover, an association study between the other detected sequence variants and AD was performed. In particular, the study was focused on five identified single nucleotide polymorphisms: rs7301328, rs1805482, rs3026160, rs1806191 and rs1806201, highlighting a significant contribution from the GRIN2B rs1806201 T allele towards disease susceptibility [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.40-2.63, p < 0.001, after correction for sex, age, and APOE ε4 genotype]. This was confirmed by haplotype analysis that identified a specific haplotype, carrying the rs1806201 T allele (CCCTC), over-represented in patients versus controls (adjusted OR = 6.03; p < 0.0001). Although the pathogenic role of the GRIN2B-K1293R mutation in AD is not clear, our data advocate that genetic variability in the GRIN2B gene, involved in synaptic functioning, might provide valuable insights into disease pathogenesis, continuing to attract significant attention in biomedical research on its genetic and functional role.

14. Forni D(1), Cleynen I(2), Ferrante M(2), Cassinotti A(3), Cagliani R(1), Ardizzone S(3), Vermeire S(2), Fichera M(3), Lombardini M(3), Maconi G(3), de Franchis R(3), Asselta R(4), Biasin M(5), Clerici M(6), Sironi M(7). ABO histo-blood group might modulate predisposition to Crohn's disease and affect disease behavior. J Crohns Colitis. 2014 Jun 1;8(6):489-94. doi: 10.1016/j.crohns.2013.10.014. Epub 2013 Nov 21.
Author information: (1)Bioinformatics, Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini, LC, Italy. (2)Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. (3)IBD Unit, Chair of Gastroenterology, Luigi Sacco University Hospital, 20157 Milan, Italy. (4)Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, Italy. (5)Chair of Immunology, DISC LITA Vialba, University of Milano, Milano, Italy. (6)Chair of Immunology, Department of Physiopathology and Transplantation, University of Milan, 20090 Milano, Italy; Fondazione Don C. Gnocchi, IRCCS, 20148 Milano, Italy. (7)Bioinformatics, Scientific Institute IRCCS E. Medea, 23842 Bosisio Parini, LC, Italy. Electronic address: manuela.sironi@bp.lnf.it.

Abstract
BACKGROUND AND AIMS: ABO encodes a glycosyltranferase which determines the major human histo-blood group. The FUT2 fucosyltransferase allows expression of ABO antigens on the gastrointestinal mucosa and in bodily secretions (secretor phenotype). A nonsense allele in FUT2 represents a susceptibility variant for Crohn's disease, and both the secretor and ABO blood group status affect the composition of the gut microbiota. Thus, we evaluated if variants in ABO might represent good candidates as Crohn's disease susceptibility loci. METHODS: We recruited two case-control cohorts, from Italy (n=1301) and Belgium (n=2331). Subjects were genotyped for one SNP in FUT2 and two variants in ABO. RESULTS: No effect on Crohn's disease risk was detected for ABO variants, whereas an association was observed between the FUT2 polymorphism and Crohn's disease susceptibility in the Belgian sample, but not in the Italian cohort. The effect of histo-blood groups was evaluated using group O as the reference. Most non-O groups had odds ratios (ORs) higher than 1 in both cohorts, and combined analysis of the two samples indicated a predisposing effect for the A and B groups (OR=1.17, 95% CI: 1.02-1.32 and OR=1.33, 95% CI: 1.09-1.58, respectively). In Crohn's disease patients, the non-O blood group and the non-secretor status were associated with higher risk of developing a stricturing or penetrating disease. CONCLUSIONS: ABO histo-blood group might confer susceptibility to Crohn's disease and modulate disease severity.

15. Trento M(1), Trevisan M, Coppo E, Raviolo A, Zanone MM, Cavallo F, Porta M. Diagnosis of type 1 diabetes within the first five years of life influences quality of life and risk of severe hypoglycemia in adulthood. Acta Diabetol. 2014 Jun;51(3):509-11. doi: 10.1007/s00592-013-0530-6. Epub 2013 Nov 16.
Author information: (1)Laboratory of Clinical Pedagogy, Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy, marina.trento@unito.it.

Abstract
Progressive adaptation to disease is paramount to improve quality of life (QoL) and other psychological dimensions in type 1 diabetes (T1DM). This study aimed at identifying possible correlations between QoL, locus of control (LoC) and clinical variables in patients with T1DM followed up for 16 years. Fifty-nine patients (27 women) with T1DM, part of a cohort of 112 followed since 1996, accepted to participate. Patients were divided into those in whom onset of T1DM had been during the first 5 years of life (n = 16) or later. They were also stratified into worsened, stable and improved, based on whether their HbA1c had increased/decreased by 1 percentage point between baseline and last follow-up visit. QoL was measured by the Diabetes Quality of Life questionnaire (DQOL), translated into Italian and re-validated. The LoC was measured by the Peyrot- and Rubin-specific questionnaire. Patients who developed T1DM before age 5 had a better total DQOL score than those who developed it later in life, mainly due to the satisfaction dimension and a tendency to decreased fatalism in adult age. All subjects whose HbA1c had worsened from baseline had had their diagnosis after age 5 and reported more frequent episodes of hypoglycemia. Onset of diabetes after age 5 and more frequent hypoglycemia was more likely in subjects with worsened HbA1c (ORs 7.6, p < 0.10 and 20.3, p < 0.01, respectively, from a multivariate logistic model with HbA1c, dichotomized in 'worsened' vs all others, as dependent variable). Onset of T1DM during the first 5 years of life may result in better QoL and less fatalism in the long term. Presumably, these patients have no memory of disease onset, which may reduce trauma and facilitate adaptation to managing life with diabetes.

16. Lossius A(1), Riise T, Pugliatti M, Bjørnevik K, Casetta I, Drulovic J, Granieri E, Kampman MT, Landtblom AM, Lauer K, Magalhaes S, Myhr KM, Pekmezovic T, Wesnes K, Wolfson C, Holmøy T. Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study. Mult Scler. 2014 May;20(6):669-74. doi: 10.1177/1352458513505693. Epub 2013 Sep 26.
Author information: (1)Institute of Clinical Medicine, University of Oslo, Norway.

Abstract
BACKGROUND: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). METHODS: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). RESULTS: IM was generally reported more frequently in Norway (p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64-2.73) and Italy (OR 1.72, 95% CI 1.17-2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall (p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08-2.31), 2.26 in summer (95% CI 1.46-3.51), 2.86 in fall (95% CI 1.69-4.85) and 2.30 in winter (95% CI 1.45-3.66). CONCLUSIONS: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.

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