39 results on '"Galassi, Claudia"'
Search Results
2. Using epigenetic modifiers to target cancer stem cell immunoevasion.
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Galassi, Claudia, Vitale, Ilio, and Galluzzi, Lorenzo
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CANCER stem cells , *EPIGENETICS , *STEM cells , *IMMUNE checkpoint inhibitors - Abstract
Two recent reports in Nature highlight a novel mechanism of immunoevasion that relies on the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-dependent epigenetic suppression of endogenous retroelements in melanoma cells. Because SETDB1 is highly expressed by the stem cell compartment, these findings delineate an innovative strategy for restoring cancer stem cell immunosurveillance. [ABSTRACT FROM AUTHOR]
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- 2021
- Full Text
- View/download PDF
3. Using epigenetic modifiers to target cancer stem cell immunoevasion.
- Author
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Galassi, Claudia, Vitale, Ilio, and Galluzzi, Lorenzo
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CANCER stem cells , *EPIGENETICS , *STEM cells , *IMMUNE checkpoint inhibitors , *MELANOMA - Abstract
Two recent reports in Nature highlight a novel mechanism of immunoevasion that relies on the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-dependent epigenetic suppression of endogenous retroelements in melanoma cells. Because SETDB1 is highly expressed by the stem cell compartment, these findings delineate an innovative strategy for restoring cancer stem cell immunosurveillance. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts.
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Zugna, Daniela, Galassi, Claudia, Annesi-Maesano, Isabella, Baïz, Nour, Barros, Henrique, Basterrechea, Mikel, Correia, Sofia, Duijts, Liesbeth, Esplugues, Ana, Fantini, Maria Pia, Forastiere, Francesco, Gascon, Mireia, Gori, Davide, Inskip, Hazel, Larsen, Pernille S, Mommers, Monique, Nybo Andersen, Anne-Marie, Penders, John, Petersen, Maria S, and Pike, Katharine
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PREGNANCY complications , *WHEEZE , *CHILDBIRTH , *BODY mass index , *MEDICAL statistics ,NEWBORN infant health - Abstract
Background: Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient.Methods: A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring.Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12–24 months of age.Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model.Results: The study included 85 509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98–1.06) and 1.20 (95% CI: 0.98–1.47) for hypertensive disorders; 1.09 (95% CI: 1.01–1.18) and 1.23 (95% CI: 1.07–1.43) for preeclampsia; 1.04 (95% CI: 0.97–1.13) and 1.24 (95% CI: 0.86–1.79) for diabetes; 1.08 (95% CI: 1.05–1.11) and 1.19 (95% CI: 1.12–1.26) for overweight; 1.12 (95% CI: 1.08–1.17) and 1.16 (95% CI: 0.97–1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P = 0.027).Conclusions: Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring. [ABSTRACT FROM AUTHOR]
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- 2015
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5. Thymoma and the increased risk of developing extrathymic malignancies: a multicentre study†.
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Filosso, Pier Luigi, Galassi, Claudia, Ruffini, Enrico, Margaritora, Stefano, Bertolaccini, Luca, Casadio, Caterina, Anile, Marco, and Venuta, Federico
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THYMOMA , *SURGICAL excision , *MYASTHENIA gravis , *AUTOIMMUNE diseases , *TUMOR risk factors - Abstract
OBJECTIVES Although thymoma is considered a relatively indolent neoplasia, patients affected by this disease are at high risk of developing second tumours (STs). The aim of this study is to assess the risk of developing STs after surgical thymoma resection. METHODS A multicentre retrospective study of patients operated on for thymoma within five Italian Thoracic Surgery Institutions, between 2000 and 2011, was conducted. The overall STs number and incidence were calculated. The number of metachronous STs was compared with the expected cancer number (ECN) in an Italian population, and the standardized incidence ratio (SIR) and 95% confidence intervals were calculated. Potential variables of STs predictors were also evaluated. RESULTS There were 302 patients; myasthenia gravis (MG) was observed in 166 (55%) and other autoimmune syndromes in 49 of them. In 118 patients (39.1%), the Masaoka thymoma stage was greater than II and in 194, the WHO histological type ranged from B1 to C. Fifty STs were observed (28 metachronous, 4 synchronous and 18 detected before thymoma). The observed metachronous STs number was significantly higher than ECN. An increased risk of STs development was observed in advanced stage thymomas and in those with histological high grade. On the contrary, MG seems to be a protective factor in STs development. CONCLUSIONS Our study confirms the high risk of developing STs in patients with thymoma. Aggressive forms of thymoma are those in which this risk appears to be more evident. The central role of an intrinsic immune system alteration might be the key to interpret this phenomenon. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Decreasing Frequency of Osteonecrosis of the Jaw in Cancer and Myeloma Patients Treated with Bisphosphonates: The Experience of the Oncology Network of Piedmont and Aosta Valley (North-Western Italy)
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Fusco, Vittorio, Galassi, Claudia, Berruti, Alfredo, Ortega, Cinzia, Ciuffreda, Libero, Scoletta, Matteo, Goia, Franco, Migliario, Mario, Baraldi, Anna, Boccadoro, Mario, Loidoris, Anastasios, and Bertetto, Oscar
- Abstract
Background. Data concerning frequency of Osteonecrosis of Jaws (ONJ) are mostly based on single center experiences. Patients and Methods. Since 2005 a multidisciplinary study group collected data of cases of ONJ in patients treated with Bisphosphonates (BP) and observed in oncology and hematology centers of a regional network. Results. By December 2008, 221 cases were registered. We report details of 200 cases, identified after cross-checking reports from centres of medical oncology, haematology, and oral care. Primary neoplasm was breast cancer (39%), myeloma (32%), prostate cancer (16%), and other types of cancer (8%). In about 50% of the cases a history of dental extraction was present. Zoledronic acid was administered (alone or with other BP) to 178 patients (89%). Median time from first infusion to ONJ diagnosis was 21.0 (zoledronic acid only) and 39.0 months (pamidronate only). The number of ONJ cases per year was 3 in 2003, 21 in 2004, 58 in 2005, 60 in 2006, 37 in 2007, and 21 in 2008. Conclusion. The number of new ONJ cases in cancer and myeloma patients increased until 2006 and then reduced. The possible reasons of this trend (introduction of zoledronic acid; increase of ONJ awareness; diffusion of preventive dental measures; late modifications of BP prescription) are herein discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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7. Decreasing Frequency of Osteonecrosis of the Jaw in Cancer and Myeloma Patients Treated with Bisphosphonates: The Experience of the Oncology Network of Piedmont and Aosta Valley (North-Western Italy).
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Fusco, Vittorio, Galassi, Claudia, Berruti, Alfredo, Ortega, Cinzia, Ciuffreda, Libero, Scoletta, Matteo, Goia, Franco, Migliario, Mario, Baraldi, Anna, Boccadoro, Mario, Loidoris, Anastasios, and Bertetto, Oscar
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DIPHOSPHONATES , *ZOLEDRONIC acid , *ACADEMIC medical centers , *OSTEONECROSIS , *CANCER patients , *MANDIBLE , *PATIENT monitoring , *PREVENTIVE health services , *PUBLIC health surveillance , *DISEASE incidence , *DESCRIPTIVE statistics , *THERAPEUTICS - Abstract
Background. Data concerning frequency of Osteonecrosis of Jaws (ONJ) are mostly based on single center experiences. Patients and Methods. Since 2005 a multidisciplinary study group collected data of cases of ONJ in patients treated with Bisphosphonates (BP) and observed in oncology and hematology centers of a regional network. Results. By December 2008, 221 cases were registered. We report details of 200 cases, identified after cross-checking reports from centres of medical oncology, haematology, and oral care. Primary neoplasm was breast cancer (39%), myeloma (32%), prostate cancer (16%), and other types of cancer (8%). In about 50% of the cases a history of dental extraction was present. Zoledronic acid was administered (alone or with other BP) to 178 patients (89%). Median time from first infusion to ONJ diagnosis was 21.0 (zoledronic acid only) and 39.0 months (pamidronate only). The number of ONJ cases per year was 3 in 2003, 21 in 2004, 58 in 2005, 60 in 2006, 37 in 2007, and 21 in 2008. Conclusion. The number of new ONJ cases in cancer and myeloma patients increased until 2006 and then reduced. The possible reasons of this trend (introduction of zoledronic acid; increase of ONJ awareness; diffusion of preventive dental measures; late modifications of BP prescription) are herein discussed. [ABSTRACT FROM AUTHOR]
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- 2013
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8. The socioeconomic determinants of cancer.
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Merletti, Franco, Galassi, Claudia, and Spadea, Teresa
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CANCER , *MORTALITY , *PROGNOSIS , *ESOPHAGUS - Abstract
This paper provides a synthesis on socioeconomic inequalities in cancer incidence, mortality and survival across countries and within countries, with particular focus on the Italian context; the paper also describes the underlying mechanisms documented for cancer incidence, and reports some remarks on policies to tackle inequalities. From a worldwide perspective, the burden of cancer appears to be particularly increasing in developing countries, where many cancers with a poor prognosis (liver, stomach and oesophagus) are much more common than in richer countries. As in the case of incidence and mortality, also in cancer survival we observe a great variability across countries. Different studies have suggested a possible impact of health care on the social gradients in cancer survival, even in countries with a National Health System providing equitable access to care. In developed countries, there is increasing awareness of social inequalities as an important public health issue; as a consequence, there is a variety of strategies and policies being implemented throughout Europe. However, recent reviews emphasize that present knowledge on effectiveness of policies and interventions on health inequalities is not sufficient to offer a robust and evidence-based guide to the choice and design of interventions, and that more evaluation studies are needed. The large disparities in health that we can measure within and between countries represent a challenge to the world; social health inequalities are avoidable, and their reduction therefore represents an achievable goal and an ethical imperative. [ABSTRACT FROM AUTHOR]
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- 2011
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9. The Yin and Yang of Type I IFNs in Cancer Promotion and Immune Activation.
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Musella, Martina, Galassi, Claudia, Manduca, Nicoletta, and Sistigu, Antonella
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TYPE I interferons , *INTERFERON inducers , *CANCER invasiveness , *NATURAL immunity , *TUMOR growth , *VIRUS diseases - Abstract
Simple Summary: The crucial immune stimulatory functions exerted by Type I Interferons (IFNs) in cancer settings have been not only widely demonstrated during the last fifty years but also recently harnessed for therapy. However, depending on the dose and timing, and the downstream induced signatures, Type I IFNs can and do foster cancer progression and immune evasion. Dysregulations of Type I IFN signaling cascade are more and more frequently found in the tumor microenvironment, representing critical determinants of therapeutic innate and adaptive resistance to several anticancer treatments. Understanding when and through which genetic signatures Type I IFNs control or promote cancer growth is extremely urgent in order to prevent and by-pass the deleterious clinical effects and develop optimized innovative (combinatorial) strategies for an effective cancer management. Type I Interferons (IFNs) are key regulators of natural and therapy-induced host defense against viral infection and cancer. Several years of remarkable progress in the field of oncoimmunology have revealed the dual nature of these cytokines. Hence, Type I IFNs may trigger anti-tumoral responses, while leading immune dysfunction and disease progression. This dichotomy relies on the duration and intensity of the transduced signaling, the nature of the unleashed IFN stimulated genes, and the subset of responding cells. Here, we discuss the role of Type I IFNs in the evolving relationship between the host immune system and cancer, as we offer a view of the therapeutic strategies that exploit and require an intact Type I IFN signaling, and the role of these cytokines in inducing adaptive resistance. A deep understanding of the complex, yet highly regulated, network of Type I IFN triggered molecular pathways will help find a timely and immune"logical" way to exploit these cytokines for anticancer therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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10. The Immune Privilege of Cancer Stem Cells: A Key to Understanding Tumor Immune Escape and Therapy Failure.
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Galassi, Claudia, Musella, Martina, Manduca, Nicoletta, Maccafeo, Ester, and Sistigu, Antonella
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CANCER stem cells , *IMMUNE system , *SUPPRESSOR cells - Abstract
Cancer stem cells (CSCs) are broadly considered immature, multipotent, tumorigenic cells within the tumor mass, endowed with the ability to self-renew and escape immune control. All these features contribute to place CSCs at the pinnacle of tumor aggressiveness and (immune) therapy resistance. The immune privileged status of CSCs is induced and preserved by various mechanisms that directly affect them (e.g., the downregulation of the major histocompatibility complex class I) and indirectly are induced in the host immune cells (e.g., activation of immune suppressive cells). Therefore, deeper insights into the immuno-biology of CSCs are essential in our pursuit to find new therapeutic opportunities that eradicate cancer (stem) cells. Here, we review and discuss the ability of CSCs to evade the innate and adaptive immune system, as we offer a view of the immunotherapeutic strategies adopted to potentiate and address specific subsets of (engineered) immune cells against CSCs. [ABSTRACT FROM AUTHOR]
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- 2021
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11. Patients who leave Emergency Department without being seen or during treatment in the Lazio Region (Central Italy): Determinants and short term outcomes.
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Mataloni, Francesca, Colais, Paola, Galassi, Claudia, Davoli, Marina, and Fusco, Danilo
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MEDICAL emergencies , *PHYSICIANS , *HOSPITAL care , *PATIENT readmissions , *RETROSPECTIVE studies - Abstract
Background and Aims: Patients who leave Emergency Department before physician’s visit (LWBS) or during treatment (LDT) represent a useful indicator of the emergency care's quality. The profile of patients LWBS was described: they are generally males, young, with lower urgency triage allocation and longer waiting time. They have a greater risk of ED re-admission compared to discharged patients, but effect on hospitalization and mortality are more controversial. The aims of this study are to identify determinants and adverse short term outcomes for LWBS and LDT patients. Methods: This is a retrospective cohort study that include all ED visits of LWBS, LDT and discharged patients in 2015 in the Lazio region, Central Italy. Determinants of LWBS or LDT were selected from gender, age, citizenship, residence area, triage category, chronic comorbidities, number of uncompleted ED visit in the previous year, mode of arrival in ED, time-band, day of the week, waiting time and ED crowding, using a multi-level logistic regression. A multivariate logistic regression was used to test if LWBS or LDT have a greater risk of short term adverse outcome compared to discharged patients. Results: The cohort consists in 835,440 visits in ED, 86.8% subjects visited and discharged, 8.9% subjects are LWBS patients and 4.3% LDT. LWBS and LDT patients are mainly young, males, with a less severe triage, with long waiting times in ED. Moreover, ED crowding and leaving ED before physician’s visit in the previous year are risk factors of self-discharging. LWBS and LDT patients have a higher risk of readmission (LWBS: OR = 4.63, 95%CI 4.5–4.7; OR = 2.89, 95%CI 2.8–2.9; LDT: OR = 3.12, 95%CI 3–3.2; OR = 2.25, 95%CI2.2–2.3 for readmissions within 2 and 7 days respectively) and hospitalization (LWBS: OR = 3.65, 95%CI 3.4–3.9; OR = 2.25, 95%CI 2.1–2.4; LDT: OR = 3.96, 95%CI 3.6–4.3; OR = 2.62, 95%CI 2.4–2.8 for hospitalization within 2 and 7 days respectively). Furthermore, we find a mortality excess of risk for LWBS patients compared to the reference group (OR = 2.56, 95%CI1.6–4.2; OR = 1.7, 95%CI 1.3–2.2 within 2 and 7 days respectively). Conclusions: Determinants of LWBS confirmed what already known, but LDT patients should be further investigated. There could be adverse health effects for people with LWBS and LDT behaviour. This could be an issue that the Regional Health System should deal with. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.
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Manzini, Paola Maria, Ciccone, Giovannino, De Rosa, Francesco Giuseppe, Cavallo, Rossana, Ghisetti, Valeria, D'Antico, Sergio, Galassi, Claudia, Saccona, Fabio, Castiglione, Anna, Birocco, Nadia, Francisci, Tiziana, Hu, Huijing, Pecoraro, Clara, Danielle, Franca, Labanca, Luciana, Bordiga, Anna Maria, Lorenzi, Marco, Camisasca, Giovanni, Giachino, Osvaldo, and Pagliarino, Mauro
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CONVALESCENT plasma , *COVID-19 treatment , *COVID-19 , *CLINICAL trials , *RANDOMIZED controlled trials , *ARTIFICIAL respiration , *RESPIRATORY therapists , *CRITICALLY ill children - Abstract
Background: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.Methods: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.Results: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.Conclusions: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020. [ABSTRACT FROM AUTHOR]- Published
- 2022
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13. The socioeconomic determinants of cancer.
- Author
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Merletti, Franco, Galassi, Claudia, and Spadea, Teresa
- Abstract
This paper provides a synthesis on socioeconomic inequalities in cancer incidence, mortality and survival across countries and within countries, with particular focus on the Italian context; the paper also describes the underlying mechanisms documented for cancer incidence, and reports some remarks on policies to tackle inequalities.From a worldwide perspective, the burden of cancer appears to be particularly increasing in developing countries, where many cancers with a poor prognosis (liver, stomach and oesophagus) are much more common than in richer countries. As in the case of incidence and mortality, also in cancer survival we observe a great variability across countries. Different studies have suggested a possible impact of health care on the social gradients in cancer survival, even in countries with a National Health System providing equitable access to care.In developed countries, there is increasing awareness of social inequalities as an important public health issue; as a consequence, there is a variety of strategies and policies being implemented throughout Europe. However, recent reviews emphasize that present knowledge on effectiveness of policies and interventions on health inequalities is not sufficient to offer a robust and evidence-based guide to the choice and design of interventions, and that more evaluation studies are needed.The large disparities in health that we can measure within and between countries represent a challenge to the world; social health inequalities are avoidable, and their reduction therefore represents an achievable goal and an ethical imperative. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
14. Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?
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Migliore, Enrica, Zugna, Daniela, Galassi, Claudia, Merletti, Franco, Gagliardi, Luigi, Rasero, Laura, Trevisan, Morena, Rusconi, Franca, and Richiardi, Lorenzo
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ACETAMINOPHEN , *WHEEZE , *THIRD trimester of pregnancy , *HEALTH outcome assessment , *PREGNANCY complications - Abstract
Background: Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding. Methods: We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy. Results: The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07–1.47] to 1.10 [0.94–1.30] in the first, and from 1.26 [1.08–1.47] to 1.10 [0.93–1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children. Conclusion: The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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15. Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?
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Rusconi, Franca, Gagliardi, Luigi, Galassi, Claudia, Forastiere, Francesco, Brunetti, Luigia, La Grutta, Stefania, Piffer, Silvano, and Talassi, Fiorella
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ACETAMINOPHEN , *ANTIBIOTICS , *WHEEZE , *JUVENILE diseases , *PHENOTYPES , *CROSS-sectional method , *DRUG administration , *THERAPEUTICS - Abstract
Background Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely treated with these drugs; in case of persistence of symptoms up to school age, this could explain the observed relationship.Methods We investigated the association between paracetamol and antibiotics use in the first year of life and wheezing phenotypes, i.e. wheezing starting in different time periods (early, persistent and late-onset) in the SIDRIA-2 study, a cross-sectional survey of 16 933 children aged 6–7 years. Directed acyclic graph (DAG) was used to depict the causal structure.Results Paracetamol and antibiotics administration in the first year were associated with early wheezing (first 2 years of life only) [odds ratio (OR): 2.27; 95% confidence interval (95% CI): 1.98–2.62 and OR = 3.76, 95% CI: 3.31–4.27] and with persistent wheezing (first 2 years + last 12 months) (OR = 1.77, 95% CI: 1.49–2.10 and OR = 3.06, 95% CI: 2.60–3.60), whereas the association with late-onset wheezing (in the last 12 months only) was weak (OR = 1.12, 95% CI: 0.97–1.31 and OR = 1.18, 95% CI: 1.02–1.38 for paracetamol and antibiotics, respectively). DAG shows that even in the absence of a direct (causal) arrow from early drugs use to wheezing at school age, the two are associated due to confounding (through the ‘infection’ node).Conclusions It is important to take into account different phenotypes in order to disentangle the association of paracetamol and antibiotics with wheezing. [ABSTRACT FROM AUTHOR]
- Published
- 2011
16. Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE).
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Weinmayr, Gudrun, Pedersen, Marie, Stafoggia, Massimo, Andersen, Zorana J., Galassi, Claudia, Munkenast, Jule, Jaensch, Andrea, Oftedal, Bente, Krog, Norun H., Aamodt, Geir, Pyko, Andrei, Pershagen, Göran, Korek, Michal, De Faire, Ulf, Pedersen, Nancy L., Östenson, Claes-Göran, Rizzuto, Debora, Sørensen, Mette, Tjønneland, Anne, and Bueno-de-Mesquita, Bas
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AIR pollution , *PARTICULATE matter , *CHEMICAL elements , *AIR pollutants , *STOMACH cancer risk factors - Abstract
Abstract Introduction Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM 2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM 2.5 and PM 10 and gastric and UADT cancer incidence in European adults. Methods Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. Results Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m3 of PM 2.5 _S was 1.92 (95%-confidence interval (95%-CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I2 = 0%), and 1.63 (95%-CI 0.88;3.01) for PM 2.5 _Zn (I2 = 70%). For the other elements in PM 2.5 and all elements in PM 10 including PM 10 _S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM 2.5 _S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM 2.5 decreased whereas that for PM 2.5 _S was robust. Conclusion This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM 2.5 _S but not PM 10 _S, suggesting that S in PM 2.5 or correlated air pollutants may contribute to the risk of gastric cancer. Highlights • Population-based cohorts from 6 European countries (227,044 participants) • Copper, iron, zinc, sulphur, nickel, vanadium, silicon and potassium in PM 2.5 and PM 10 were studied. • Statistically significant strong association of gastric cancer with sulphur in PM 2.5 , but not in PM 10 • No association of gastric cancer with any of the other 7 elements tested • No association with upper aerodigestive tract cancer [ABSTRACT FROM AUTHOR]
- Published
- 2018
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17. Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases.
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Jeong, Ayoung, Fiorito, Giovanni, Keski-Rahkonen, Pekka, Imboden, Medea, Kiss, Agneta, Robinot, Nivonirina, Gmuender, Hans, Vlaanderen, Jelle, Vermeulen, Roel, Kyrtopoulos, Soterios, Herceg, Zdenko, Ghantous, Akram, Lovison, Gianfranco, Galassi, Claudia, Ranzi, Andrea, Krogh, Vittorio, Grioni, Sara, Agnoli, Claudia, Sacerdote, Carlotta, and Mostafavi, Nahid
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AIR pollutants , *CARDIOVASCULAR disease etiology , *RESPIRATORY diseases ,ETIOLOGY of Asthma ,PHYSIOLOGICAL effects of linoleic acid - Abstract
Abstract Background Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. Objectives The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes (“meeting-in-the-middle”), thus shedding light on mechanisms and reinforcing causality. Methods We applied a statistical approach named ‘meet-in-the-middle’ to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways. Results A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000 particles/cm3). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD. Conclusions Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD. Highlights • Strong association of long-term ultrafine particle exposure with adult-onset asthma • Linoleate metabolism and carnitine shuttle as “meeting-in-the-middle” pathways. • Metabolic pathways mediate the air pollution effects on health outcomes. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Land use regression models for the oxidative potential of fine particles (PM2.5) in five European areas.
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Gulliver, John, Morley, David, Dunster, Chrissi, McCrea, Adrienne, van Nunen, Erik, Tsai, Ming-Yi, Probst-Hensch, Nicoltae, Eeftens, Marloes, Imboden, Medea, Ducret-Stich, Regina, Naccarati, Alessio, Galassi, Claudia, Ranzi, Andrea, Nieuwenhuijsen, Mark, Curto, Ariadna, Donaire-Gonzalez, David, Cirach, Marta, Vermeulen, Roel, Vineis, Paolo, and Hoek, Gerard
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LAND use , *OXIDATIVE stress , *REGRESSION analysis , *ENVIRONMENTAL exposure ,PARTICULATE matter & the environment - Abstract
Oxidative potential (OP) of particulate matter (PM) is proposed as a biologically-relevant exposure metric for studies of air pollution and health. We aimed to evaluate the spatial variability of the OP of measured PM 2.5 using ascorbate (AA) and (reduced) glutathione (GSH), and develop land use regression (LUR) models to explain this spatial variability. We estimated annual average values (m −3 ) of OP AA and OP GSH for five areas (Basel, CH; Catalonia, ES; London-Oxford, UK (no OP GSH ); the Netherlands; and Turin, IT) using PM 2.5 filters. OP AA and OP GSH LUR models were developed using all monitoring sites, separately for each area and combined-areas. The same variables were then used in repeated sub-sampling of monitoring sites to test sensitivity of variable selection; new variables were offered where variables were excluded (p > .1). On average, measurements of OP AA and OP GSH were moderately correlated (maximum Pearson's maximum Pearson's R = = .7) with PM 2.5 and other metrics (PM 2.5 absorbance, NO 2 , Cu, Fe). HOV (hold-out validation) R 2 for OP AA models was .21, .58, .45, .53, and .13 for Basel, Catalonia, London-Oxford, the Netherlands and Turin respectively. For OP GSH , the only model achieving at least moderate performance was for the Netherlands (R 2 = .31). Combined models for OP AA and OP GSH were largely explained by study area with weak local predictors of intra-area contrasts; we therefore do not endorse them for use in epidemiologic studies. Given the moderate correlation of OP AA with other pollutants, the three reasonably performing LUR models for OP AA could be used independently of other pollutant metrics in epidemiological studies. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Long-Term Exposure to Ambient Air Pollution and Incidence of Postmenopausal Breast Cancer in 15 European Cohorts within the ESCAPE Project.
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Andersen, Zorana J., Stafoggia, Massimo, Weinmayr, Gudrun, Pedersen, Marie, Galassi, Claudia, Jørgensen, Jeanette T., Oudin, Anna, Forsberg, Bertil, Olsson, David, Oftedal, Bente, Aasvang, Gunn Marit, Aamodt, Geir, Pyko, Andrei, Pershagen, Göran, Korek, Michal, De Faire, Ulf, Pedersen, Nancy L., Östenson, Claes-Göran, Fratiglioni, Laura, and Eriksen, Kirsten T.
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AIR pollution , *AUTOMOBILES , *BREAST tumors , *CHI-squared test , *CONFIDENCE intervals , *EPIDEMIOLOGICAL research , *LONGITUDINAL method , *MEDICAL cooperation , *META-analysis , *NITROGEN oxides , *PROBABILITY theory , *REGRESSION analysis , *RESEARCH , *RESEARCH funding , *EVIDENCE-based medicine , *PROFESSIONAL practice , *ENVIRONMENTAL exposure , *STATISTICAL significance , *PARTICULATE matter , *PROPORTIONAL hazards models , *POSTMENOPAUSE , *DATA analysis software , *DESCRIPTIVE statistics , *ODDS ratio - Abstract
BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women. METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts - Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2:5 μm, ≤10 μm, and 2:5-10 μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1:08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg = m3}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg = m3], PMcoarse [1.20 (95% CI: 0.96, 1.49 per 5 μg = m3], and NO2 [1.02 (95% CI: 0.98, 1.07 per 10 μg = m3], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg = m3, p = 0:04]. CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women. [ABSTRACT FROM AUTHOR]
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- 2017
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20. Adjuvant chemotherapy for large-cell neuroendocrine lung carcinoma: results from the European Society for Thoracic Surgeons Lung Neuroendocrine Tumours Retrospective Database.
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Filosso, Pier Luigi, Guerrera, Francesco, Evangelista, Andrea, Galassi, Claudia, Welter, Stefan, Rendina, Erino Angelo, Travis, William, Eric Lim, Sarkaria, Inderpal, and Thomas, Pascal Alexandre
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CANCER chemotherapy , *LUNG cancer , *NEUROENDOCRINE tumors , *THORACIC surgery , *CANCER patients - Abstract
OBJECTIVES: Large-cell neuroendocrine carcinoma (LCNC) is a rare tumour characterized by aggressive biological behaviour and poor prognosis. Due to its rarity and the lack of randomized clinical trials, the best treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Our goal was to evaluate this finding using a large series of patients with neuroendocrine tumours obtained from the European Society of Thoracic Surgeons database. METHODS: Data for 400 patients with LCNC operated on in 14 thoracic surgery institutions worldwide between 1992 and 2014 were collected retrospectively. Overall survival was the primary endpoint; we used a multivariable Cox regression model to evaluate which clinical variables may influence patient outcomes; we also focused on the possible prognostic role of adjuvant CT. A propensity score (PS) analysis using the inverse probability of treatment weighting was also carried out. RESULTS: The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, we found that increasing age, Eastern Cooperative Oncology Group Performance Status >2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56–0.96, P = 0.022) was observed. CONCLUSIONS: A trend towards benefit from adjuvant CT has been observed in patients with LCNC. Although surgical procedures remain the mainstay of curative options, combination with other treatments (e.g. neoadjuvant CT/radiotherapy) should be evaluated by future studies. [ABSTRACT FROM AUTHOR]
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- 2017
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21. Ambient air pollution and primary liver cancer incidence in four European cohorts within the ESCAPE project.
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Pedersen, Marie, Andersen, Zorana J., Stafoggia, Massimo, Weinmayr, Gudrun, Galassi, Claudia, Sørensen, Mette, Eriksen, Kirsten T., Tjønneland, Anne, Loft, Steffen, Jaensch, Andrea, Nagel, Gabriele, Concin, Hans, Tsai, Ming-Yi, Grioni, Sara, Marcon, Alessandro, Krogh, Vittorio, Ricceri, Fulvio, Sacerdote, Carlotta, Ranzi, Andrea, and Sokhi, Ranjeet
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LIVER cancer , *CANCER risk factors , *AIR pollution , *TOBACCO smoke pollution , *NITROGEN oxides , *REGRESSION analysis - Abstract
Background Tobacco smoke exposure increases the risk of cancer in the liver, but little is known about the possible risk associated with exposure to ambient air pollution. Objectives We evaluated the association between residential exposure to air pollution and primary liver cancer incidence. Methods We obtained data from four cohorts with enrolment during 1985–2005 in Denmark, Austria and Italy. Exposure to nitrogen oxides (NO 2 and NO X ), particulate matter (PM) with diameter of less than 10 µm (PM 10 ), less than 2.5 µm (PM 2.5 ), between 2.5 and 10 µm (PM 2.5–10 ) and PM 2.5 absorbance (soot) at baseline home addresses were estimated using land-use regression models from the ESCAPE project. We also investigated traffic density on the nearest road. We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and random-effects meta-analyses to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). Results Out of 174,770 included participants, 279 liver cancer cases were diagnosed during a mean follow-up of 17 years. In each cohort, HRs above one were observed for all exposures with exception of PM 2.5 absorbance and traffic density. In the meta-analysis, all exposures were associated with elevated HRs, but none of the associations reached statistical significance. The summary HR associated with a 10-μg/m 3 increase in NO 2 was 1.10 (95% confidence interval (CI): 0.93, 1.30) and 1.34 (95% CI: 0.76, 2.35) for a 5-μg/m 3 increase in PM 2.5 . Conclusions The results provide suggestive evidence that ambient air pollution may increase the risk of liver cancer. Confidence intervals for associations with NO 2 and NO X were narrower than for the other exposures. [ABSTRACT FROM AUTHOR]
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- 2017
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22. Development of West-European PM2.5 and NO2 land use regression models incorporating satellite-derived and chemical transport modelling data.
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de Hoogh, Kees, Gulliver, John, Donkelaar, Aaron van, Martin, Randall V., Marshall, Julian D., Bechle, Matthew J., Cesaroni, Giulia, Pradas, Marta Cirach, Dedele, Audrius, Eeftens, Marloes, Forsberg, Bertil, Galassi, Claudia, Heinrich, Joachim, Hoffmann, Barbara, Jacquemin, Bénédicte, Katsouyanni, Klea, Korek, Michal, Künzli, Nino, Lindley, Sarah J., and Lepeule, Johanna
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PARTICULATE matter , *LAND use , *ARTIFICIAL satellites , *REGRESSION analysis , *AIR pollution , *HEALTH , *EPIDEMIOLOGY , *PHYSIOLOGY - Abstract
Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM 2.5 and NO 2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM 2.5 and NO 2 models for Europe. Four sets of models, all including local traffic and land use variables, were compared (LUR without SAT or CTM, with SAT only, with CTM only, and with both SAT and CTM). LUR models were developed using two monitoring data sets: PM 2.5 and NO 2 ground level measurements from the European Study of Cohorts for Air Pollution Effects (ESCAPE) and from the European AIRBASE network. LUR PM 2.5 models including SAT and SAT+CTM explained ~60% of spatial variation in measured PM 2.5 concentrations, substantially more than the LUR model without SAT and CTM (adjR 2 : 0.33–0.38). For NO 2 CTM improved prediction modestly (adjR 2 : 0.58) compared to models without SAT and CTM (adjR 2 : 0.47–0.51). Both monitoring networks are capable of producing models explaining the spatial variance over a large study area. SAT and CTM estimates of PM 2.5 and NO 2 significantly improved the performance of high spatial resolution LUR models at the European scale for use in large epidemiological studies. [ABSTRACT FROM AUTHOR]
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- 2016
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23. Spatial variation of PM elemental composition between and within 20 European study areas — Results of the ESCAPE project.
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Tsai, Ming-Yi, Hoek, Gerard, Eeftens, Marloes, de Hoogh, Kees, Beelen, Rob, Beregszászi, Timea, Cesaroni, Giulia, Cirach, Marta, Cyrys, Josef, De Nazelle, Audrey, de Vocht, Frank, Ducret-Stich, Regina, Eriksen, Kirsten, Galassi, Claudia, Gražuleviciene, Regina, Gražulevicius, Tomas, Grivas, Georgios, Gryparis, Alexandros, Heinrich, Joachim, and Hoffmann, Barbara
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PARTICULATE matter , *EPIDEMIOLOGY , *HEALTH impact assessment , *DATA analysis , *TRACE elements - Abstract
An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM 2.5 and PM 10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM 2.5 and PM 10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM 2.5 and from 0.93 (V) to 2.28 (Cu) for PM 10 . Our selected PM elements were variably correlated with the main pollutants (PM 2.5 , PM 10 , PM 2.5 absorbance, NO 2 and NO x ) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM 10 _Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO 2 and soot, signaling the importance of non-tailpipe (e.g., brake wear) emissions in PM. [ABSTRACT FROM AUTHOR]
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- 2015
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24. SETIL: Italian multicentric epidemiological case-control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy.
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Magnani, Corrado, Mattioli, Stefano, Miligi, Lucia, Ranucci, Alessandra, Rondelli, Roberto, Salvan, Alberto, Bisanti, Luigi, Masera, Giuseppe, Rizzari, Carmelo, Zambon, Paola, Cannizzaro, Santina, Gafà, Lorenzo, Luzzatto, Lia Lidia, Benvenuti, Alessandra, Michelozzi, Paola, Kirchmayer, Ursula, Cocco, Pierluigi, Biddau, Pierfranco, Galassi, Claudia, and Celentano, Egidio
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LEUKEMIA risk factors , *LYMPHOMA risk factors , *NEUROBLASTOMA , *ELECTROMAGNETIC fields , *INTERVIEWING , *RESEARCH methodology , *MEDICAL cooperation , *PARENTS , *QUESTIONNAIRES , *RESEARCH , *RESEARCH funding , *RISK assessment , *STATISTICAL sampling , *SMOKING , *TUMORS in children , *OCCUPATIONAL hazards , *ENVIRONMENTAL exposure , *HOME environment , *DISEASE prevalence , *CASE-control method , *DATA analysis software , *DESCRIPTIVE statistics , *DISEASE risk factors - Abstract
Background: Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case?control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. Methods: The study was carried out in 14 Italian regions (78.3% of Italian population aged 0?10). It included leukaemia, NHL and neuroblastoma cases incident in 0?10 year olds in 1998?2001, registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP) (accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child?s bed (48 hours measurement). Results: The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls. ELF-MF long term measurements were obtained for 61.1% of controls and 81.6% of leukaemia cases; 8.8% of controls were exposed at over 0.1 microTesla (p,T), 3.5% and 2.1% at respectively over 0.2 and 0.3 p,T. 25% of controls? fathers had smoked over 10 cigarettes/day during the year of conception, varying according to education and region. Maternal smoking was less common (71.4% did not smoke in pregnancy). Maternal passive smoking during pregnancy was reported by 31.2% of controls; the child?s passive smoking for 28.6%. Occupational exposure to solvents was estimated in 18.3% of controls? fathers and 7.7% of mothers. Contact with public was more frequent among mothers (36.1%) than fathers (23.4%). Conclusions: SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors. [ABSTRACT FROM AUTHOR]
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- 2014
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25. Long-Term Exposure to Ambient Air Pollution and Incidence of Cerebrovascular Events: Results from 11 European Cohorts within the ESCAPE Project.
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Stafoggia, Massimo, Cesaroni, Giulia, Peters, Annette, Andersen, Zorana J., Badaloni, Chiara, Beelen, Rob, Caracciolo, Barbara, Cyrys, Josef, de Faire, Ulf, de Hoogh, Kees, Eriksen, Kirsten T., Fratiglioni, Laura, Galassi, Claudia, Gigante, Bruna, Havulinna, Aki S., Hennig, Frauke, Hilding, Agneta, Hoek, Gerard, Hoffmann, Barbara, and Houthuijs, Danny
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AIR pollution , *CHI-squared test , *CONFIDENCE intervals , *LONGITUDINAL method , *META-analysis , *REGRESSION analysis , *RESEARCH funding , *ENVIRONMENTAL exposure , *PARTICULATE matter , *PROPORTIONAL hazards models , *DATA analysis software , *DESCRIPTIVE statistics ,STROKE risk factors - Abstract
Background: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. Objectives: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. Methods: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ≤ 2.5 μm in diameter], coarse PM (PM between 2.5 and 10 μm), PM10 (PM ≤ 10 μm), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation. Results: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-μg/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ≥ 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 μg/m3 (HR = 1.33, 95% CI: 1.01, 1.77). [ABSTRACT FROM AUTHOR]
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- 2014
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26. Performance of Multi-City Land Use Regression Models for Nitrogen Dioxide and Fine Particles.
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Wang, Meng, Beelen, Rob, Bellander, Tom, Birk, Matthias, Cesaroni, Giulia, Cirach, Marta, Cyrys, Josef, Hoogh, Kees de, Declercq, Christophe, Dimakopoulou, Konstantina, Eeftens, Marloes, Eriksen, Kirsten T., Forastiere, Francesco, Galassi, Claudia, Grivas, Georgios, Heinrich, Joachim, Hoffmann, Barbara, Ineichen, Alex, Korek, Michal, and Lanki, Timo
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NITROGEN oxide analysis , *MATHEMATICAL models , *ENVIRONMENTAL monitoring , *AIR pollution , *GEOGRAPHIC information systems , *REGRESSION analysis , *THEORY , *ENVIRONMENTAL exposure , *PARTICULATE matter , *DESCRIPTIVE statistics ,RESEARCH evaluation - Abstract
Background: Land use regression (LUR) models have been developed mostly to explain intraurban variations in air pollution based on often small local monitoring campaigns. Transferability of LUR models from city to city has been investigated, but little is known about the performance of models based on large numbers of monitoring sites covering a large area. Objectives: We aimed to develop European and regional LUR models and to examine their transferability to areas not used for model development. Methods: We evaluated LUR models for nitrogen dioxide (NO2) and particulate matter (PM; PM2.5, PM2.5 absorbance) by combining standardized measurement data from 17 (PM) and 23 (NO2) ESCAPE (European Study of Cohorts for Air Pollution Effects) study areas across 14 European countries for PM and NO2. Models were evaluated with cross-validation (CV) and hold-out validation (HV). We investigated the transferability of the models by successively excluding each study area from model building. Results: The European model explained 56% of the concentration variability across all sites for NO2, 86% for PM2.5, and 70% for PM2.5 absorbance. The HV R2s were only slightly lower than the model R2 (NO2, 54%; PM2.5, 80%; PM2.5 absorbance, 70%). The European NO2, PM2.5, and PM2.5 absorbance models explained a median of 59%, 48%, and 70% of within-area variability in individual areas. The transferred models predicted a modest-to-large fraction of variability in areas that were excluded from model building (median R2: NO2, 59%; PM2.5, 42%; PM2.5 absorbance, 67%). Conclusions: Using a large data set from 23 European study areas, we were able to develop LUR models for NO2 and PM metrics that predicted measurements made at independent sites and areas reasonably well. This finding is useful for assessing exposure in health studies conducted in areas where no measurements were conducted. [ABSTRACT FROM AUTHOR]
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- 2014
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27. Prognostic factors in neuroendocrine tumours of the lung: a single-centre experience†.
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Filosso, Pier Luigi, Ruffini, Enrico, Di Gangi, Stefania, Guerrera, Francesco, Bora, Giulia, Ciccone, Giovannino, Galassi, Claudia, Solidoro, Paolo, Lyberis, Paraskevas, Oliaro, Alberto, and Sandri, Alberto
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NEUROENDOCRINE tumors , *THORACIC surgery , *CARCINOID , *SMALL cell carcinoma , *CANCER remission , *PROGNOSIS - Abstract
OBJECTIVES To assess the independent prognostic role of histological subtypes, tumour size and lymph nodal involvement upon survival in lung neuroendocrine tumours (NETs). METHODS A retrospective search of the database of the Department of Thoracic Surgery (Turin, Italy) identified 157 patients operated on for a newly diagnosed NET between January 1995 and December 2011. Multivariable Cox models were used to analyse predictors of overall survival and progression-free survival. RESULTS According to histology, 71 (45.2%) were typical carcinoids (TCs), 35 (22.3%) atypical carcinoids (ACs), 37 (23.6%) large-cell neuroendocrine carcinomas (LCNCs) and 14 (8.9%) small-cell lung carcinomas (SCLCs). After a median follow-up time of 6.5 years, 60 patients died and 73 had a recurrence or died. The overall 5-, 10- and 15-year survival rates were 64%, 53% and 46%, respectively. Older age, histology (ACs, LCNCs and SCLCs vs TCs) and lymph nodal involvement were confirmed to be independent negative prognostic factors in the multivariable models for overall survival and progression-free survival. CONCLUSIONS Tumour histology and lymph nodal involvement are definitively the predominant and relevant factors influencing survival. ACs showed an intermediate prognosis between TCs and poorly differentiated NETs. [ABSTRACT FROM PUBLISHER]
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- 2014
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28. Variation of NO2 and NO x concentrations between and within 36 European study areas: Results from the ESCAPE study
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Cyrys, Josef, Eeftens, Marloes, Heinrich, Joachim, Ampe, Christophe, Armengaud, Alexandre, Beelen, Rob, Bellander, Tom, Beregszaszi, Timea, Birk, Matthias, Cesaroni, Giulia, Cirach, Marta, de Hoogh, Kees, De Nazelle, Audrey, de Vocht, Frank, Declercq, Christophe, Dėdelė, Audrius, Dimakopoulou, Konstantina, Eriksen, Kirsten, Galassi, Claudia, and Grąulevičienė, Regina
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NITROGEN oxides , *AIR pollution , *SPATIAL variation , *EPIDEMIOLOGY , *ASTHMA in children , *PARTICULATE matter , *GEOGRAPHIC information systems - Abstract
Abstract: The ESCAPE study (European Study of Cohorts for Air Pollution Effects) investigates long-term effects of exposure to air pollution on human health in Europe. This paper documents the spatial variation of measured NO2 and NO x concentrations between and within 36 ESCAPE study areas across Europe. In all study areas NO2 and NO x were measured using standardized methods between October 2008 and April 2011. On average, 41 sites were selected per study area, including regional and urban background as well as street sites. The measurements were conducted in three different seasons, using Ogawa badges. Average concentrations for each site were calculated after adjustment for temporal variation using data obtained from a routine monitor background site. Substantial spatial variability was found in NO2 and NO x concentrations between and within study areas; 40% of the overall NO2 variance was attributable to the variability between study areas and 60% to variability within study areas. The corresponding values for NO x were 30% and 70%. The within-area spatial variability was mostly determined by differences between street and urban background concentrations. The street/urban background concentration ratio for NO2 varied between 1.09 and 3.16 across areas. The highest median concentrations were observed in Southern Europe, the lowest in Northern Europe. In conclusion, we found significant contrasts in annual average NO2 and NO x concentrations between and especially within 36 study areas across Europe. Epidemiological long-term studies should therefore consider different approaches for better characterization of the intra-urban contrasts, either by increasing of the number of monitors or by modelling. [Copyright &y& Elsevier]
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- 2012
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29. Spatial variation of PM2.5, PM10, PM2.5 absorbance and PMcoarse concentrations between and within 20 European study areas and the relationship with NO2 – Results of the ESCAPE project
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Eeftens, Marloes, Tsai, Ming-Yi, Ampe, Christophe, Anwander, Bernhard, Beelen, Rob, Bellander, Tom, Cesaroni, Giulia, Cirach, Marta, Cyrys, Josef, de Hoogh, Kees, De Nazelle, Audrey, de Vocht, Frank, Declercq, Christophe, Dėdelė, Audrius, Eriksen, Kirsten, Galassi, Claudia, Gražulevičienė, Regina, Grivas, Georgios, Heinrich, Joachim, and Hoffmann, Barbara
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PARTICULATE matter , *SPATIAL variation , *NITROGEN oxides , *AIR pollution , *LAND use , *COHORT analysis , *GEOGRAPHIC information systems - Abstract
Abstract: The ESCAPE study (European Study of Cohorts for Air Pollution Effects) investigates relationships between long-term exposure to outdoor air pollution and health using cohort studies across Europe. This paper analyses the spatial variation of PM2.5, PM2.5 absorbance, PM10 and PMcoarse concentrations between and within 20 study areas across Europe. We measured NO2, NO x , PM2.5, PM2.5 absorbance and PM10 between October 2008 and April 2011 using standardized methods. PMcoarse was determined as the difference between PM10 and PM2.5. In each of the twenty study areas, we selected twenty PM monitoring sites to represent the variability in important air quality predictors, including population density, traffic intensity and altitude. Each site was monitored over three 14-day periods spread over a year, using Harvard impactors. Results for each site were averaged after correcting for temporal variation using data obtained from a reference site, which was operated year-round. Substantial concentration differences were observed between and within study areas. Concentrations for all components were higher in Southern Europe than in Western and Northern Europe, but the pattern differed per component with the highest average PM2.5 concentrations found in Turin and the highest PMcoarse in Heraklion. Street/urban background concentration ratios for PMcoarse (mean ratio 1.42) were as large as for PM2.5 absorbance (mean ratio 1.38) and higher than those for PM2.5 (1.14) and PM10 (1.23), documenting the importance of non-tailpipe emissions. Correlations between components varied between areas, but were generally high between NO2 and PM2.5 absorbance (average R 2 = 0.80). Correlations between PM2.5 and PMcoarse were lower (average R 2 = 0.39). Despite high correlations, concentration ratios between components varied, e.g. the NO2/PM2.5 ratio varied between 0.67 and 3.06. In conclusion, substantial variability was found in spatial patterns of PM2.5, PM2.5 absorbance, PM10 and PMcoarse. The highly standardized measurement of particle concentrations across Europe will contribute to a consistent assessment of health effects across Europe. [Copyright &y& Elsevier]
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- 2012
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30. Authors's Response to Letter on the study of Rusconi et al.
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Rusconi, Franca, Gagliardi, Luigi, Galassi, Claudia, and Forastiere, Francesco
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ACETAMINOPHEN , *PUBLISHING , *EPIDEMIOLOGICAL research , *HEALTH periodicals , *COHORT analysis , *SCIENTIFIC observation - Published
- 2011
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31. Re: 'Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children'.
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Gagliardi, Luigi, Rusconi, Franca, Galassi, Claudia, and Forastiere, Francesco
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- 2011
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32. Re: "Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children".
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Gagliardi, Luigi, Rusconi, Franca, Galassi, Claudia, and Forastiere, Francesco
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ANTIBIOTICS , *AGE factors in disease , *ASTHMA in children , *DISEASE susceptibility , *RESPIRATORY organ sounds , *MATHEMATICAL variables , *PHENOTYPES , *CHILDREN - Abstract
A letter to the editor is presented in response to the article " Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children" by K. R. Risnes, K. Belanger, W. Murk and colleagues in the February 2011 issue.
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- 2011
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33. An Educational and Physical Program to Reduce Headache, Neck/Shoulder Pain in a Working Community: A Cluster-Randomized Controlled Trial.
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Mongini, Franco, Evangelista, Andrea, Milani, Chantal, Ferrero, Luca, Ciccone, Giovannino, Ugolini, Alessandro, Piedimonte, Alessandro, Sigaudo, Monica, Carlino, Elisa, Banzatti, Emanuela, and Galassi, Claudia
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HEADACHE , *CLINICAL trials , *SHOULDER pain , *PAIN management , *HEALTH programs - Abstract
Background: Noninvasive physical management is often prescribed for headache and neck pain. Systematic reviews, however, indicate that the evidence of its efficacy is limited. Our aim was to evaluate the effectiveness of a workplace educational and physical program in reducing headache and neck/shoulder pain. Methodology/Principal Findings: Cluster-randomized controlled trial. All municipal workers of the City of Turin, Italy, were invited to participate. Those who agreed were randomly assigned, according to their departments, to the intervention group (IG) or to the control group and were given diaries for the daily recording of pain episodes for 1 month (baseline). Subsequently, only the IG (119 departments, 923 workers) began the physical and educational program, whereas the control group (117 departments, 990 workers) did not receive any intervention. All participants were again given diaries for the daily recording of pain episodes after 6 months of intervention. The primary outcome was the change in the frequency of headache (expressed as the proportion of subjects with a ≥50% reduction of frequency; responder rate); among the secondary outcomes there were the absolute reduction of the number of days per month with headache and neck/shoulder pain. Differences between the two groups were evaluated using mixed-effect regression models. The IG showed a higher responder rate [risk ratio, 95% confidence interval (CI)] for headache (1.58; 1.28 to 1.92) and for neck/shoulder pain (1.53; 1.27 to 1.82), and a larger reduction of the days per month (95% CI) with headache (-1.72; -2.40 to -1.04) and with neck/shoulder pain (-2.51; -3.56 to -1.47). Conclusions: The program effectively reduced headache and neck/shoulder pain in a large working community and appears to be easily transferable to primary-care settings. Further trials are needed to investigate the program effectiveness in a clinical setting, for highly selected patients suffering from specific headache types. [ABSTRACT FROM AUTHOR]
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- 2012
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34. Short-Term Effects of Nitrogen Dioxide on Mortality and Susceptibility Factors in 10 Italian Cities: The EpiAir Study.
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Chiusolo, Monica, Cadum, Ennio, Stafoggia, Massimo, Galassi, Claudia, Berti, Giovanna, Faustini, Annunziata, Bisanti, Luigi, Vigotti, Maria Angela, Dessì, Maria Patrizia, Cernigliaro, Achille, Mallone, Sandra, Pacelli, Barbaralli, Minerba, Sante, Simonato, Lorenzo, and Forastiere, Francesco
- Abstract
Background: Several studies have shown an association between nitrogen dioxide (NO2) and mortality. In Italy, the EpiAir multicentric study, "Air Pollution and Health: Epidemiological Surveillance and Primary Prevention," investigated short-term health effects of air pollution, including NO2. Objectives: To study the individual susceptibility, we evaluated the association between NO2 and cause-specific mortality, investigating individual sociodemographic features and chronic/acute medical conditions as potential effect modifiers. Methods: We considered 276,205 natural deaths of persons > 35 years of age, resident in 10 Italian cities, and deceased between 2001 and 2005. We chose a time-stratified case-crossover analysis to evaluate the short-term effects of NO2 on natural, cardiac, cerebrovascular, and respiratory mortality. For each subject, we collected information on sociodemographic features and hospital admissions in the previous 2 years. Fixed monitors provided daily concentrations of NO2, particulate matter ≤10 µm in aerodynamic diameter (PM10) and ozone (O3). Results: We found statistically significant associations with a 10-µg/m3 increase of NO2 for natural mortality [2.09% for lag 0-5; 95% confidence interval (CI), 0.96-3.24], for cardiac mortality (2.63% for lag 0-5; 95% CI, 1.53-3.75), and for respiratory mortality (3.48% for lag 1-5; 95% CI, 0.75-6.29). These associations were independent from those of PM10 and O3. Stronger associations were estimated for subjects with at least one hospital admission in the 2 previous years and for subjects with three or more specific chronic conditions. Some cardiovascular conditions (i.e., ischemic heart disease, pulmonary circulation impairment, heart conduction disorders, heart failure) and diabetes appeared to confer a strong susceptibility to air pollution. Conclusions: Our results suggest significant and likely independent effects of NO2 on natural, cardiac, and respiratory mortality, particularly among subjects with specific cardiovascular preexisting chronic conditions and diabetes. [ABSTRACT FROM AUTHOR]
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- 2011
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35. Effectiveness of an educational and physical program in reducing accompanying symptoms in subjects with head and neck pain: a workplace controlled trial.
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Rota, Eugenia, Evangelista, Andrea, Ciccone, Giovannino, Ferrero, Luca, Ugolini, Alessandro, Milani, Chantal, Ceccarelli, Manuela, Galassi, Claudia, and Mongini, Franco
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MIGRAINE diagnosis , *CHI-squared test , *COMPARATIVE studies , *CONFIDENCE intervals , *MENTAL depression , *EPIDEMIOLOGY , *EPIDEMIOLOGICAL research , *HEADACHE , *INTERVIEWING , *RESEARCH methodology , *CLASSIFICATION of mental disorders , *NECK pain , *PATIENT compliance , *PATIENT education , *PHYSICAL diagnosis , *INDUSTRIAL research , *SELF-evaluation , *SHOULDER pain , *U-statistics , *DATA analysis , *STATISTICAL significance , *REPEATED measures design , *DISEASE prevalence , *CASE-control method , *GENERALIZED anxiety disorder - Abstract
The objective of this study is to evaluate the effectiveness of an educational and physical program in reducing behavioral or somatic symptoms along with headache, neck and shoulder pain in a working community. A controlled, non-randomized trial was carried out in a working community and 384 employees were enrolled and divided into a study group (Group 1) and a control group (Group 2). The Group 1 received a physical and educational intervention, consisting of relaxation and posture exercises and the use of visual feedback. After 6 months, the intervention was administered to the Group 2. Both groups were then followed for an additional 6 months until the end of the trial. The presence of accompanying symptoms was investigated with a semi-structured interview using a checklist of 20 items, along with headache, neck, and shoulder pain parameters and the prevalence of generalized anxiety disorder and depression, in three clinical examinations at baseline, after 6 months and after 12 months. For each symptom, as well as the presence of any type of symptom, the differences between groups in the prevalence at the clinical examinations following the baseline were evaluated by applying logistic models. After 6 months, the probability of the presence of any type of symptom was significantly lower in the Group 1 (OR 0.69, 95% CI 0.56-0.85) with respect to the Group 2. After 12 months, the pooled estimation did not show any significant difference of symptom prevalence between groups (OR 0.80, 95% CI 0.64-1.00). In conclusion, this is the first longitudinal study relative to accompanying symptoms. Its results suggest the effectiveness of this cognitive program in reducing the burden of physical and psychiatric complaints in a large, working population. [ABSTRACT FROM AUTHOR]
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- 2011
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36. Further evidence of the positive effects of an educational and physical program on headache, neck and shoulder pain in a working community.
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Mongini, Franco, Evangelista, Andrea, Rota, Eugenia, Ferrero, Luca, Ugolini, Alessandro, Milani, Chantal, Ceccarelli, Manuela, Joffrain, Laura, Ciccone, Giovannino, and Galassi, Claudia
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HEADACHE , *NECK pain , *SHOULDER pain , *ANALYSIS of variance , *COMPUTER software , *CONFIDENCE intervals , *PAIN , *PERSONNEL management , *RELAXATION for health , *PUBLIC sector , *DATA analysis , *DISEASE incidence , *CASE-control method , *EDUCATION , *DRUG therapy , *PREVENTION - Abstract
In a controlled trial to evaluate the effectiveness of a simple educational and physical program administered to a large cohort of public servants, we previously found that 6 months following treatment the monthly frequency of headache and neck and shoulder pain and drug intake was reduced by 40% in the experimental compared with controls. These results were stable at a 12-month follow up. The program consists of brief shoulder and neck exercises to be performed several times a day, a relaxation exercise, and instructions on how to reduce parafunction and hyperfunction of the craniofacial and neck muscles during the day. The purpose of this work was to investigate whether the data previously obtained could be confirmed also in the group of 192 subjects that served as controls in first phase of the study and received the intervention in the second phase of the study. The primary endpoint was the change in frequency of headache and neck and shoulder pain expressed as the number of days per month with pain, and as the proportion of subjects with a ≥50% reduction of frequency (responder rate) at the last 2 months of the 6-month intervention period compared to the 2 months preceding the intervention (baseline). The number of days of analgesic drug consumption was also recorded. Days per month with headache at the baseline and at the end of intervention period were 6.40 and 4.58 (mean change −1.81, p < 0.0001), respectively; days with neck and shoulder pain were 7.48 and 6.18 (mean change −1.30, p = 0.0179); days of analgesic consumption were 1.67 and 1.17 (mean change −0.50, p = 0.0222). The responder rate was 42.3% for headache, 42% for neck and shoulder pain and 58.3% for drug consumption. In conclusion, this study adds further evidence on the efficacy of our program and its high acceptability in a large, unselected, working population. [ABSTRACT FROM AUTHOR]
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- 2010
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37. Prevalence, Persistence, and Factors Associated with SARS-CoV-2 IgG Seropositivity in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital in Northern Italy.
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Scozzari, Gitana, Costa, Cristina, Migliore, Enrica, Coggiola, Maurizio, Ciccone, Giovannino, Savio, Luigi, Scarmozzino, Antonio, Pira, Enrico, Cassoni, Paola, Galassi, Claudia, and Cavallo, Rossana
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MEDICAL personnel , *SARS-CoV-2 , *IMMUNOGLOBULIN G , *PANDEMICS , *TERTIARY care , *UNIVERSITY hospitals , *COVID-19 - Abstract
This observational study evaluated SARS-CoV-2 IgG seroprevalence and related clinical, demographic, and occupational factors among workers at the largest tertiary care University-Hospital of Northwestern Italy and the University of Turin after the first pandemic wave of March–April 2020. Overall, about 10,000 individuals were tested; seropositive subjects were retested after 5 months to evaluate antibodies waning. Among 8769 hospital workers, seroprevalence was 7.6%, without significant differences related to job profile; among 1185 University workers, 3.3%. Self-reporting of COVID-19 suspected symptoms was significantly associated with positivity (Odds Ratio (OR) 2.07, 95%CI: 1.76–2.44), although 27% of seropositive subjects reported no previous symptom. At multivariable analysis, contacts at work resulted in an increased risk of 69%, or 24% for working in a COVID ward; contacts in the household evidenced the highest risk, up to more than five-fold (OR 5.31, 95%CI: 4.12–6.85). Compared to never smokers, being active smokers was inversely associated with seroprevalence (OR 0.60, 95%CI: 0.48–0.76). After 5 months, 85% of previously positive subjects still tested positive. The frequency of SARS-COV-2 infection among Health Care Workers was comparable with that observed in surveys performed in Northern Italy and Europe after the first pandemic wave. This study confirms that infection frequently occurred as asymptomatic and underlines the importance of household exposure, seroprevalence (OR 0.60, 95%CI: 0.48–0.76). [ABSTRACT FROM AUTHOR]
- Published
- 2021
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38. The Targeting of MRE11 or RAD51 Sensitizes Colorectal Cancer Stem Cells to CHK1 Inhibition.
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Mattiello, Luca, Soliman Abdel Rehim, Sara, Musella, Martina, Sistigu, Antonella, Guarracino, Andrea, Vitale, Sara, Corradi, Francesca, Galassi, Claudia, Sperati, Francesca, Manic, Gwenola, De Maria, Ruggero, Vitale, Ilio, and Wong, David
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COLON tumors , *STATISTICS , *KRUSKAL-Wallis Test , *PROTEIN kinase inhibitors , *ONE-way analysis of variance , *MANN Whitney U Test , *T-test (Statistics) , *STEM cells , *DNA-binding proteins , *DESCRIPTIVE statistics , *CELL lines , *DATA analysis software , *DATA analysis ,RECTUM tumors - Abstract
Simple Summary: The ATR-CHK1 axis of the DNA damage response is crucial for the survival of most colorectal cancer stem cells (CRC-SCs), but a significant fraction of primary CRC-SCs either is resistant to ATR or CHK1 inhibitors or survives the abrogation of the ATR-CHK1 cascade despite an initial response. Here, we demonstrate that the targeting of RAD51 or MRE11 improves the sensitivity of primary CRC-SCs to the CHK1/2 inhibitor prexasertib by sequentially inducing replication stress, the abrogation of cell cycle checkpoints, and the emergence of mitotic defects. This results in the induction of mitotic catastrophe and CRC-SC killing via a caspase-dependent apoptosis. Cancer stem cells (CSCs) drive not only tumor initiation and expansion, but also therapeutic resistance and tumor relapse. Therefore, CSC eradication is required for effective cancer therapy. In preclinical models, CSCs demonstrated high capability to tolerate even extensive genotoxic stress, including replication stress, because they are endowed with a very robust DNA damage response (DDR). This favors the survival of DNA-damaged CSCs instead of their inhibition via apoptosis or senescence. The DDR represents a unique CSC vulnerability, but the abrogation of the DDR through the inhibition of the ATR-CHK1 axis is effective only against some subtypes of CSCs, and resistance often emerges. Here, we analyzed the impact of druggable DDR players in the response of patient-derived colorectal CSCs (CRC-SCs) to CHK1/2 inhibitor prexasertib, identifying RAD51 and MRE11 as sensitizing targets enhancing prexasertib efficacy. We showed that combined inhibition of RAD51 and CHK1 (via B02+prexasertib) or MRE11 and CHK1 (via mirin+prexasertib) kills CSCs by affecting multiple genoprotective processes. In more detail, these two prexasertib-based regimens promote CSC eradication through a sequential mechanism involving the induction of elevated replication stress in a context in which cell cycle checkpoints usually activated during the replication stress response are abrogated. This leads to uncontrolled proliferation and premature entry into mitosis of replication-stressed cells, followed by the induction of mitotic catastrophe. CRC-SCs subjected to RAD51+CHK1 inhibitors or MRE11+CHK1 inhibitors are eventually eliminated, and CRC-SC tumorspheres inhibited or disaggregated, via a caspase-dependent apoptosis. These results support further clinical development of these prexasertib-based regimens in colorectal cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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39. Re: Trends in Radical Prostatectomy Rates.
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Fedeli, Ugo, Alba, Natalia, Ciccone, Giovannino, Galassi, Claudia, and Spolaore, Paolo
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LETTERS to the editor , *PROSTATECTOMY - Abstract
A letter to the editor is presented in response to the article "Trends in Radical Prostatectomy Rates" in a previous issue.
- Published
- 2007
- Full Text
- View/download PDF
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