Clinical and Molecular Epidemiology

San Raffaele Cimena, Italy

Clinical and Molecular Epidemiology

San Raffaele Cimena, Italy
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Neri M.,Clinical and Molecular Epidemiology | Frustaci A.,Clinical and Molecular Epidemiology | Milic M.,Clinical and Molecular Epidemiology | Milic M.,Institute for Medical Research and Occupational Health | And 4 more authors.
Cephalalgia | Year: 2015

Background Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Methods Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Results Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. Conclusions The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels. © International Headache Society 2015.

Bonassi S.,Clinical and Molecular Epidemiology | Bonassi S.,San Raffaele University | Milic M.,Institute for Medical Research and Occupational Health | Neri M.,Clinical and Molecular Epidemiology
Mutation Research - Reviews in Mutation Research | Year: 2016

Airborne particles are small, solid particles projected into the air either by natural forces, or by mechanical or man-made processes, and include fibers and dusts. Their toxicity is usually subsequent to inhalation and can lead to pulmonary dysfunctions and diseases, including cancer. Cytochalasin B blocked micronucleus assay in lymphocytes (L-CBMN) has been shown as a sensitive and reliable technique in assessing genotoxic exposure, An extensive search of the PubMed and Web of Science databases allowed retrieval of 18 articles on occupational or environmental exposure evaluating L-CBMN in subjects exposed to fibers or dusts (asbestos, silica, rockwool, beryllium, tobacco, and wood). For each study, mean L-CBMN levels were compared in exposed subjects vs. unexposed controls providing a point estimate, the Mean Ratio (MR). The high heterogeneity among retrieved studies and their relatively limited number did not allow a quantitative meta-analysis. However, the inter-quartile range of all MRs fell within the interval between 1.25 and 2.23, supporting the hypothesis that exposure to airborne particles increases DNA damage, although mechanisms of genotoxicity should be further investigated. A borderline significant correlation was found with SCE, but not with chromosome aberrations or comet assay. Future research should focus on exposure assessment, in order to perform proper dose-response studies and disentangle the effect of different compounds in mixed exposures. To fully exploit the cytome assay, L-CBMN frequency should be integrated with other endpoints, such as nucleoplasmic bridges and nuclear buds. The use of alternative tissues, such as nasal and buccal mucosa, and the implementation of other cytogenetic assay, may help to understand the effects of this exposure. © 2016.

Stigliani S.,Italian National Cancer Institute | Coco S.,Italian National Cancer Institute | Moretti S.,French National Center for Scientific Research | Moretti S.,University of Paris Dauphine | And 9 more authors.
Neoplasia (United States) | Year: 2012

We aimed to identify novel molecular prognostic markers to better predict relapse risk estimate for children with high-risk (HR) metastatic neuroblastoma (NB). We performed genome- and/or transcriptome-wide analyses of 129 stage 4 HR NBs. Children older than 1 year of age were categorized as "short survivors" (dead of disease within 5 years from diagnosis) and "long survivors" (alive with an overall survival time ≥ 5 years). We reported that patients with less than three segmental copy number aberrations in their tumor represent a molecularly defined subgroup with a high survival probability within the current HR group of patients. The complex genomic pattern is a prognostic marker independent of NB-associated chromosomal aberrations, i.e., MYCN amplification, 1p and 11q losses, and 17q gain. Integrative analysis of genomic and expression signatures demonstrated that fatal outcome is mainly associated with loss of cell cycle control and deregulation of Rho guanosine triphosphates (GTPases) functioning in neuritogenesis. Tumors with MYCN amplification show a lower chromosome instability compared to MYCN single-copy NBs (P =.0008), dominated by 17q gain and 1p loss. Moreover, our results suggest that the MYCN amplification mainly drives disruption of neuronal differentiation and reduction of cell adhesion process involved in tumor invasion and metastasis. Further validation studies are warranted to establish this as a risk stratification for patients. © 2012 Neoplasia Press, Inc. All rights reserved.

Ceppi M.,Italian National Cancer Institute | Gallo F.,Italian National Cancer Institute | Bonassi S.,Clinical and Molecular Epidemiology
Mutagenesis | Year: 2011

The most common study design performed in population studies based on the micronucleus (MN) assay, is the cross-sectional study, which is largely performed to evaluate the DNA damaging effects of exposure to genotoxic agents in the workplace, in the environment, as well as from diet or lifestyle factors. Sample size is still a critical issue in the design of MN studies since most recent studies considering gene-environment interaction, often require a sample size of several hundred subjects, which is in many cases difficult to achieve. The control of confounding is another major threat to the validity of causal inference. The most popular confounders considered in population studies using MN are age, gender and smoking habit. Extensive attention is given to the assessment of effect modification, given the increasing inclusion of biomarkers of genetic susceptibility in the study design. Selected issues concerning the statistical treatment of data have been addressed in this mini-review, starting from data description, which is a critical step of statistical analysis, since it allows to detect possible errors in the dataset to be analysed and to check the validity of assumptions required for more complex analyses. Basic issues dealing with statistical analysis of biomarkers are extensively evaluated, including methods to explore the dose-response relationship among two continuous variables and inferential analysis. A critical approach to the use of parametric and non-parametric methods is presented, before addressing the issue of most suitable multivariate models to fit MN data. In the last decade, the quality of statistical analysis of MN data has certainly evolved, although even nowadays only a small number of studies apply the Poisson model, which is the most suitable method for the analysis of MN data. © The Author 2010. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.

Giaquinto S.,Scientific Direction | Bruti L.,Outpatients Rehabilitation Center | Dall'Armi V.,Clinical and Molecular Epidemiology | Palma E.,Outpatients Rehabilitation Center | Spiridigliozzi C.,Outpatients Rehabilitation Center
International Journal of Geriatric Psychiatry | Year: 2011

Objective Personality changes are known to occur in idiopathic Parkinson's Disease (PD). The aim of the study was to evaluate whether religious and spiritual beliefs in PD patients are different from age-matched controls. Design Eighty-three PD participants, 79 hypertensive individuals not affected by PD and 88 healthy subjects participated to a cross-sectional study. The Royal Free Interview (RFI) was used to evaluate participants' beliefs. The Hospital Anxiety and Depression Scale (HADS) was applied to monitor emotional distress. Results There was no statistical evidence of a difference between PD participants and the two control groups, the only exception being observed between the left PD onset group and the controls, where the total RFI score was about 5 points higher (t-test: p = 0.0273). RFI total score was uncorrelated with age, severity of illness and depression, but was strongly dependent on the type of beliefs. The percentage of PD participants suffering from anxiety and depression was high (right onset: 54.8%; left onset: 68.6%), while only 15.2% of the hypertensive participants, and none of the healthy controls, had a HADS score above 10 points. Total RFI score was higher in women. Conclusion PD participants maintain their Faith in spite of the disease severity. Differences are found between right and left onset of PD. The possible beneficial effect of religious coping is discussed. Copyright © 2010 John Wiley & Sons, Ltd.

Ceppi M.,Italian National Cancer Institute | Biasotti B.,Italian National Cancer Institute | Fenech M.,CSIRO | Bonassi S.,Clinical and Molecular Epidemiology
Mutation Research - Reviews in Mutation Research | Year: 2010

Objectives: Micronucleus (MN) assay in buccal exfoliated cells is a minimally invasive method for monitoring genetic damage in human populations. Statistical and epidemiological issues related to the design and analysis of studies based on this biomarker are addressed. Methods: A systematic review of recent literature on the buccal MN assay has been carried out to provide a state-of-the-art evaluation of how critical topics such as control for confounding, sample size and statistical power, number of cells scored, endpoint selection, and statistical modelling, are considered. In addition, a meta-analysis has been performed to estimate the impact of most common confounders on MN frequency, and to provide a baseline value of MN frequency in the control population. Results: A total number of 63 eligible studies were included in the analysis. Age (98.4%), gender (85.7%), and smoking habit (90.5%) were the most commonly studied confounders. Univariate statistics were estimated in most studies while multivariate analysis was applied only in the 47.6%. Baseline MN frequency in controls was 1.10/1000 cells (95% confidence interval 0.70-1.72), and the relative increment in subjects exposed to genotoxic agents or affected by disease correlated with similar observations in lymphocytes (R2 = 0.74). A minimum number of 4000 cells is recommended to reduce the variability of the MN mean estimates, in contrast with the current practice of scoring only 2000 cells (81% of studies). Poisson or Negative Binomial are the preferred statistical models when more than 2000 cells are scored. Studies scoring smaller numbers of cells should consider the use of statistical models taking into account the excess of zeros, e.g., the Zero Inflated Poisson (ZIP) models. Conclusions: The quality of papers published on the buccal MN assay can be substantially improved, with better consideration of basic issues such as power analysis, control for confounding, choice of the statistical model, and the number of cells to be scored. © 2009 Elsevier B.V. All rights reserved.

PubMed | CliCon S.r.l. Health, Clinical and Molecular Epidemiology, Catholic University of the Sacred Heart, University of Florence and 4 more.
Type: Journal Article | Journal: The Journal of clinical psychiatry | Year: 2017

This study aimed to evaluate prevalence of prescription of and adherence to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and whether adherence to these classes of drugs affects overall medication adherence in older persons.In a cross-sectional analysis of administrative data comprehensive of all prescribed drugs reimbursed by the Italian national health care system, new prescriptions of SSRIs and SNRIs to persons aged 65 years or older were analyzed (n = 380,400 in 2011; 395,806 in 2012; 409,741 in 2013, from a total sample of 3,762,299 persons aged 65 years or older) as well as prescriptions of antihypertensives, statins, other psychiatric drugs, antidiabetics, antiplatelets, anticoagulants, drugs for chronic obstructive pulmonary disease, and antiosteoporotics. Adherence was estimated by calculating the proportion of days covered by drugs dispensed during a period of 365 days. Adherence was defined as a proportion of days covered of more than 80%.Prevalence of SSRI and SNRI prescriptions varied from 11.4% in 2011 to 12.1% in 2013. Adherence to SSRI and SNRI prescriptions ranged from 31.2% in persons aged 95 years in 2011 to 41.8% in persons aged 75-84 years in 2013. Persons adherent to SSRI and SNRI prescriptions were more likely to be adherent to the other medications, after adjustment for age, gender, and number of drugs prescribed. The highest association was found for adherence to psychiatric drugs (OR = 1.9; 95% CI, 1.8-2.0).Adherence to SSRI and SNRI prescriptions is poor in older persons. However, people adherent to these classes of antidepressants are more likely to be adherent to the other medications they are prescribed. Studies are needed to evaluate the reasons for and the potential benefits of increasing adherence to antidepressants on overall adherence.

Bovolenta F.,Medicine Rehabilitation NOCSAE Hospital AUSL of Modena | Sale P.,IRCCS San Raffaele Pisana | Dall'Armi V.,Clinical and Molecular Epidemiology | Clerici P.,Medicine Rehabilitation NOCSAE Hospital AUSL of Modena | Franceschini M.,IRCCS San Raffaele Pisana
Journal of NeuroEngineering and Rehabilitation | Year: 2011

This study was aimed at verifying the improvement on the motor impairment and functionality in 19 patients with chronic hemiparesis after stroke treated with a robot-aided rehabilitation protocol using the ReoGo system (Motorika Medical Ltd, Israel), and at evaluating the persistence of the effects after 1 month. The study also focused on the actual possibility of administering the robot-aided therapy with the ReoGo for the upper limbs and on the patients' degree of acceptance and compliance with the treatment. Subjects underwent an assessment prior to the start of the rehabilitation project (T-1), one at the start (T0), one at the end of the treatment (T1) and one after one month from the end of the treatment (T2). The following tests were administered: (i) Fugl-Meyer (FM) upper limb; Ashworth scale (AS); Functional Independence Measure (FIM) (T-1 - T2); (ii) strength evaluation; Visual Analogue Scale (VAS) for pain; Frenchay Arm test (FAT); Box and Block test (BBT); Timed Up and Go (TUG) test (T0 - T2). Additionally, the Euro-QoL questionnaire and a VAS for the treatment satisfaction were administered to the subjects. Non-statistical difference of scores at T-1 and T0 on almost the entire battery of tasks suggested a stable patients' performance prior to the start of the rehabilitation. With the exception of the Medical Research Council (MRC) and the AS sub-scales measuring -as appropriate- strength and spasticity of the shoulder, triceps and wrist, all scores showed a significant increase between T0 and T1. The improvement on the pain could not be proved significant (p = 0.10). A significant increase between T0 and T2 was found for all assessment scores, with the exception of the MRC for external shoulder rotators (p = 0.05) and of the AS for shoulder (p = 0.32) and wrist (p = 0.08). Substantial stability was observed between T1 and T2. Patients were capable of completing the treatment and showed good participant satisfaction. This pilot study led to the finding of a clinical improvement and excellent patients compliance. It is possible that the learning process experienced by the patients was robot-dependent, especially in consideration of the general maintenance of the achievements observed on all activities. © 2011 Bovolenta et al; licensee BioMed Central Ltd.

Zampolini M.,ASL No | Zaccaria B.,University of Parma | Tolli V.,Institute San Raffaele Velletri | Frustaci A.,Clinical and Molecular Epidemiology | Franceschini M.,IRCCS San Raffaele Pisana
Brain Injury | Year: 2012

Objectives: The aims of this study were to analyse TBI rehabilitation in Italy, identifying the main factors conditioning motor and functional recovery and destination upon discharge of traumatic severe acquired brain injury (sABI) patients who had undergone intensive rehabilitative treatment. Design: An observational prospective study of 863 consecutive patients admitted to 52 Rehabilitation Centres from January 2001 to December 2003. Results: The main cause of trauma was road accidents (79.8%), the mean length of stay was 87.31±77.26 days and 40.4% access to rehabilitation facilities after a month. Pressure sore rates fell from 26.1% to 6.6% during the rehabilitation programme. After discharge 615 patients returned home, whilst 212 were admitted to other health facilities. Discussion: This study highlights some major criticisms of rehabilitation of TBI. The delay of admission and evitable complications such as pressure sores are correlated to a worse outcome. While LOS causes a problem of cost-effectiveness, the rate of home discharge is prevalent and very high compared with other studies. © 2012 Informa UK Ltd All rights reserved.

Albertini G.,IRCCS San Raffaele Pisana | Bonassi S.,Clinical and Molecular Epidemiology | Dall'Armi V.,Clinical and Molecular Epidemiology | Giachetti I.,Scientific Direction | And 2 more authors.
Research in Developmental Disabilities | Year: 2010

The voice quality of individuals with Down Syndrome (DS) is generally described as husky, monotonous and raucous. On the other hand, the voice of DS children is characterized by breathiness, roughness, and nasality and is typically low pitched. However, research on phonation and intonation in these participants is limited. The present study was designed to provide data from the spectral analysis of the human voice in DS people. A cross-sectional, observational design was applied. Thirty DS adults and 48 DS children were enrolled after clinical evaluation. Thirty men, 30 women and 46 children constituted the control group. The participants had to repeat a set of Italian words twice. The Real Time Pitch software manufactured by KayPENTAX recorded the voice. The following spectral descriptors were obtained for each word: Mean Frequency and standard deviation, Energy, Duration, Jitter and Shimmer. Test-retest performance was also checked. The voice of DS adults was characterized by a significantly higher Mean Frequency, particularly in males (p<0.0001), by a smaller variation (p=0.0044 in males and p=0.0046 in females) and by a significantly lower level of Energy (p=0.0037 in males and p=0.0025 females). Furthermore, limited to male adults, a shorter Duration (p=0.0156) and a smaller value of Shimmer (p=0.0014) was observed. The difference between DS children and age-matched controls was limited, reaching significance only for the Coefficient of Variation (CV) (p=0.031). The difference in Mean Frequency between adults and children was more evident in the control males than in all other groups. The lack of marked difference between voice characteristics of children with and without DS is outlined by findings. Pearson's correlation coefficients on repeated productions ranged from 0.23 (Jitter) to 0.86 (Mean Frequency) in children, and from 0.07 (Shimmer) to 0.86 (Mean Frequency) in adults. In the control group, all the coefficients ranged between 0.85 and 0.98. As expected, women had a higher Mean Frequency than men, but the CV was around 0.1 for both. By contrast, children had a significantly higher Mean Frequency and a lower CV. In conclusion, spectral analysis of the human voice is recommended in each laboratory of speech and language rehabilitation to exploit the accuracy of voice descriptors. © 2010 Elsevier Ltd.

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