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  • Abstract Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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  • Additional file 1: Figure S1. Provides the participant flow chart. Figure S2. Transitions to specific cancer and cardio-metabolic multimorbidity patterns. Figure S3. Results of subgroup analyses. Figure S4. CIFs for men and women of 55 years of age. Figure S5. Results of sensitivity analyses. Figure S6. Results for simplified HLI. Figure S7. CIFs for men and women of 55 years of age using the simplified HLI. and Figure S8. CIFs for men and women of 55 years of age for two groups of cancers. Table S1. Scoring of the healthy lifestyle index (HLI) and its simplified version.
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  • Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest in considering circulating ANG levels as an ALS disease biomarker although robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia (FTD) compared to controls and to explore correlations between ANG content and disease-related clinical variables. Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in 88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group). Results: ANG levels didn’t differ significantly between cases and controls. Patients with FTD or ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients without dementia and controls in a multivariate regression model (p C9orf72 repeat expansion, body mass index (BMI). Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS patients with concurrent FTD and suggest that it should be further explored as potential biomarker for FTD.
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  • Distribution of first line approach according to pharyngitis diagnosis. Pedianet, Italy, 2010–2015. (XLSX 9 kb)
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  • Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD). Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation. Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)). Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.
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  • Abstract Background Maternal caffeine intake has repeatedly been linked to babies being born small for gestational age (SGA). SGA babies are known to be at increased risk for adverse neonatal outcomes. The aim of this study was to explore the associations between prenatal caffeine exposure and neonatal health. Methods The study is based on 67,569 full-term singleton mother-infant pairs from the Norwegian Mother and Child Cohort Study. Caffeine consumption from different sources was self-reported in gestational week 22. Neonatal compound outcomes, namely (1) morbidity/mortality and (2) neonatal intervention, were created based on the Medical Birth Registry of Norway. Adjusted logistic regression was performed. Results Caffeine exposure was associated to SGA (OR = 1.16, 95%CI: 1.10; 1.23) and being born SGA was significantly associated with neonatal health (OR = 3.09, 95%CI: 2.54; 3.78 for morbidity/mortality; OR = 3.94, 95%CI: 3.50; 4.45 for intervention). However, prenatal caffeine exposure was neither associated with neonatal morbidity/mortality (OR = 1.01, 95%CI: 0.96; 1.07) nor neonatal intervention (OR = 1.02, 95%CI: 1.00; 1.05 for a 100 mg caffeine intake increase). Results did not change after additional adjustment for SGA status. Conclusions Moderate prenatal caffeine exposure (
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  • Abstract Background Acute otitis media (AOM) and pharyngitis are very common infections in children and adolescents. Italy is one of the European countries with the highest rate of antibiotic prescriptions. The aim of this study is to describe first-line treatment approaches for AOM and pharyngitis in primary care settings in Italy over six years, including the prevalence of ‘wait and see’ for AOM, where prescription of antibiotics is delayed 48 h from presentation, and differences in prescribing for pharyngitis when diagnostic tests are used. Methods The study is a secondary data analysis using Pedianet, a database including data at outpatient level from children aged 0–14 in Italy. Prescriptions per antibiotic group, per age group and per calendar year were described as percentages. “Wait and see” approach rate was described for AOM and pharyngitis prescriptions were further grouped according to the diagnostic test performed and test results. Results We identified 120,338 children followed by 125 family pediatricians between January 2010 and December 2015 for a total of 923,780 person-years of follow-up. Among them 30,394 (mean age 44 months) had at least one AOM diagnosis (n = 54,943) and 52,341 (mean age 5 years) had at least one pharyngitis diagnosis (n = 126,098). 82.5% of AOM diagnoses were treated with an antibiotic within 48 h (mainly amoxicillin and amoxicillin/clavulanate) and the “wait and see” approach was adopted only in 17.5% of cases. The trend over time shows an increase in broad spectrum antibiotic prescriptions in the last year (2015). 79,620 (63%) cases of pharyngitis were treated and among GABHS pharyngitis confirmed by rapid test 56% were treated with amoxicillin. The ones not test confirmed were treated mainly with broad spectrum antibiotics. Conclusions Despite guidance to use the ‘wait and see’ approach in the age group analyzed, this strategy is not often used for AOM, as previously noted in other studies in hospital settings. Broad-spectrum antibiotic prescription was more frequent when pharyngitis was not confirmed by rapid test, in keeping with evidence from other studies that diagnostic uncertainty leads to overuse of antibiotics.
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  • Association Between Small for Gestational Age (SGA) and Neonatal Outcomes, n = 67,569, Norwegian Mother and Child Cohort Study, 2002–2009. aOR – adjusted odds ratios, CI – confidence interval, SGA - small for gestational age. The table shows adjusted odds ratios for the association of small for gestational age (according to different definitions of SGA: Gardosi, Skjaerven and Marsal) with neonatal outcomes. The Wald 95% confidence intervals are provided for each estimate. ORs are adjusted for: maternal pre-pregnancy body mass index, household income, maternal education, marital status, parity, maternal age at delivery, smoking status, presence of nausea, folic acid supplementation, planned pregnancy and baby’s sex. (DOCX 22 kb)
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  • Distribution of first line treatment antibiotic therapy for non-defined pharyngitis. Pedianet, Italy, 2010–2015. (XLSX 9 kb)
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  • Association between caffeine intake and neonatal outcomes, additional adjustment for SGA. CI – confidence interval, OR – odds ratio, SGA – small for gestational age. OR for the outcomes of interest as a function of 100 mg change in total caffeine intake. ORs are adjusted for: maternal pre-pregnancy body mass index, household income, maternal education, marital status, parity, maternal age at delivery, smoking status, presence of nausea, folic acid supplementation, planned pregnancy, baby’s sex, total energy intake, with additional adjustment for small for gestational age (according to a given definition of small for gestational age). n = 67,569, in the Norwegian Mother and Child Cohort Study 2002 to 2009. (DOCX 19 kb)
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