Rare diseases and congenital malformations integrated registry in Tuscany-Italy

Aims: Rare diseases (RD) are life-threatening or chronically debilitating diseases with prevalence of fewer than 5 cases among 10,000. For these conditions there is lack of scientific information, research, diagnosis, and treatment. To obtain epidemiological information the Italian Network of RD was set up in 2001. The Network is formed by Presidia specifically identified by each Region for diagnosis/treatment and by regional and national Registries. Among the 583 RDs eligible for free healthcare treatment, congenital malformation (CM) is the most frequent group with 254 diseases. Analysis of data and information available from both registries is therefore crucial to improve knowledge on the actual size of the CMs phenomenon also by activating an integrated system of registration. Methods: Linkage analysis was performed on data of the Tuscany Registries of CMs (RTDC) and of RDs (RTMR) for cases observed from 1992 to 2006 over approximately 420,000 surveilled resident births. Five specific rare CMs were selected: microcephaly, acrocephalosyndactyly, lissencephaly, oesophageal atresia, Down syndrome. Variables used for linkage were CM, names, date of birth, and residence. Results: Undernotification of rare CM cases more difficult to diagnose at birth like the lissencephaly was observed in the RTDC compared to the RTMR, while overlapping of record of cases emerged for other anomalies such as the Down syndrome. Linkage has allowed in some cases to better specify the diagnosis and to provide missing information. Conclusions: Use of different information sources has enabled to reduce undernotification of cases and to mutually validate information

Case-Control Study on Congenital Malformation Risk in the Petrochemical Area of Gela (Sicily-Italy)

Objective: A study on congenital malformations (CMs) prevalence in newborns residing in the Gela municipality over 1991 to 2002 showed statistically significant excesses of total CMs, spina bifida, microcephaly, heart defects, hypospadias, if compared with the Italian EUROCAT registries (Bianchi, 2006). Many environmental and occupational risk factors reported as potentially associated with CMs have been documented in Gela and other similar industrial areas. Among toxic substances documented in the Gela site several are known as teratogenic and mutagenic (heavy metals, chloro- and organophosphates solvents, PCBs, aromatic polycyclic hydrocarbons), some of which are documented or suspected to be endocrine disruptors. A case-control study was carried out to evaluate whether among malformed subjects there was risk excess due to environmental, occupational, or lifestyle exposures, particularly eating habits. Material and Methods: Among 91 cases with malformations found in excess, 77 were selected by specialty medical visits; 91 matched controls were included. The questionnaire included information on pregnancy, parents\u27 work (particularly in the industrial plants) before and during pregnancy, parents\u27 eating habits, purchase place (shop, street vendor, growing own food plants/fishing). Statistical analyses were performed for all CMs and for hypospadias only. Results: Significant risk associations resulted for consumers of fish, fruit, and vegetables if purchased at street vendors or for fishing and growing own food plants (OR from 6.0 to 51.3). Conclusions: Results on food consumption suggest a possible reproductive risk for fish, fruit, or vegetables purchased at street vendors or for fishing or growing own food plants potentially locally contaminated either by men (eg, pesticides) or by substances released in the environment. Notwithstanding the impossibility of making a distinction between effects of the 2 potential contamination sources and the possible bias and misclassification problems typical of retrospective studies, results obtained still represent major concern on food chain and on possible effects on reproductive health

Infant Mortality in 27 Italian Municipalities With Solid Waste Incinerators (1981-2001)

Objective: Recently, an epidemiological study was carried out to verify the hypothesis of an association between infant mortality and residence near incinerators (Tango, 2004). Limits to the study were represented by rarity of death events and heterogeneity of infant mortality. However, availability of mortality data and of an incinerator database has allowed performing an exploratory investigation. Materials and Methods: Infant mortality was investigated over 2 periods (1981-1991, 1992-2001) in 27 municipalities with active incinerators in the 1981-2001 time frame. For each municipality the observed/expected ratio (O/E) was obtained. To calculate expected mortality, municipalities were included inside a 50-km radius circle. A pooled estimation of the O/E ratio obtained by meta-analysis was performed for the 27 municipalities. A multiple metaregression model was used to analyze the study, activity and latency periods, the incinerator burning capacity, the number of resident newborns, the residence density, the deprivation index. Results: Mortality analysis was performed on resident population for the whole period on approximately 250,000 infants under 1 year of age. In the overall period 1673 cases of infant mortality were observed. The pooled estimation of the O/E ratio resulted 1.04 (CI 95%: 0.97-1.11) for total cases. The multiple metaregression model showed the incinerator burning capacity as a statistically significant factor (P=0.011). Municipalities having incinerators with a burning capacity >50,000 ton/year showed a higher mortality excess (O/E=1.11, CI 95% 1.03-1.20) compared to municipalities with incinerators of <50,000 ton/year (O/E=0.95; CI 95%: 0.86-1.04). Conclusions: Findings call for further insight by analytic epidemiologic studies to confirm possible association between infant mortality and living near incinerators

Il Registro Regionale Malattie Rare della Toscana

Rare diseases (RDs) are life-threatening or chronically debilitating diseases with a prevalence lower than 5 cases among 10,000. For these conditions there is a lack of scientific information, research, diagnosis, treatment and expert availability. In 2001 the Italian Network for RDs was set up in order to obtain epidemiological information on these diseases. Presidia specifically identified by the Regions for diagnosis/treatment and by the Regional and National Registries are part of the national Network. Some RDs Registries were also created at the regional level. The Tuscany Registry for Rare Diseases (RTMR) is a network of presidia identified by the regional administration. The single presidium refers to a coordination centre for each group of RDs. The "G. Monasterio" Foundation for Medical Research and Public Health, formerly Institute of Clinical Physiology of the CNR, in charge of the Registry management, has produced a protocol, a questionnaire and a software allowing electronic registration of RD cases treated in Tuscany health centres via the Internet. Additionally, the local Register uploads local cases into the National Registry for RDs, coordinated by the Istituto Superiore di Sanit? (ISS). The registration questionnaire is divided in several sections and seeks information on patient, disease, diagnosis, tests performed for diagnosis, besides health condition and treatment. Cases are patients, dead or alive, diagnosed and followed by the Tuscan Presidia of the Regional Health System, including those residing outside the Region, properly diagnosed with one of the RDs included in the 279/2001 Ministerial Decree\u27s list. To ensure privacy, data can only be accessed using a login username and password assigned to each user. Further information is available on the Tuscan Registry for Rare Diseases website: www.rtmr.i

Drug treatment demand data: influence on policy and practice =Demandes de traitment des consommateurs de drogues.

The Pompidou Group has advocated the systematic and routine collection of information on patients entering treatment for problem drug use (treatment demand data) since the mid-1980s. Two decades later, the question now being asked is whether or not this data has been used as evidence in the development of policies and practices. In this publication, authors Hamish Sinclair, Carlo Bertorello, Michela Rial and Dusan Nolimal, all members of the Pompidou Group research platform, attempt to answer this question. Three case studies describe how treatment demand data has been used in the development of drug policies and services in Ireland, Italy and Slovenia. One strong message coming out of this report is the need for more information on the outcome of treatment. Policy makers clearly need more information on patients at the end of their treatment, including information on further treatment and its effectiveness

Awareness knowledge and use of folic acid among womwn in Tuscany (Italy)

The intake of folic acid (FA) prior the conception and during the early stages of pregnancy plays a key role preventing neural tube defects (NTDS) and other birth anomalies

NON-Hodgkin\u27s lymphomas mortality in 25 Italian municipalities with solid waste incenerators (1981-2001)

Recently epidemiological studies suggested an increased risk of Non-Hodgkin\u27s Lymphomas (NHLs) among population residing near solid waste incinerators (SWIs)(Viel 2003,Floret 2003,Biggeri 2005). An ecological study on NHLs mortality in 25 municipalities whit SWIs was conducted to tes hypothesis of an association by using a large sample size of active incinerators in Ital

Computing of Low Shear Stress-Driven Endothelial Gene Network Involved in Early Stages of Atherosclerotic Process

Background. In the pathogenesis of atherosclerosis, a central role is represented by endothelial inflammation with influx of chemokine-mediated leukocytes in the vascular wall. Aim of this study was to analyze the effect of different shear stresses on endothelial gene expression and compute gene network involved in atherosclerotic disease, in particular to homeostasis, inflammatory cell migration, and apoptotic processes. Methods. HUVECs were subjected to shear stress of 1, 5, and 10 dyne/cm2 in a Flow Bioreactor for 24 hours to compare gene expression modulation. Total RNA was analyzed by Affymetrix technology and the expression of two specific genes (CXCR4 and ICAM-1) was validated by RT-PCR. To highlight possible regulations between genes and as further validation, a bioinformatics analysis was performed. Results. At low shear stress (1 dyne/cm2) we observed the following: (a) strong upregulation of CXCR4; (b) mild upregulation of Caspase-8; (c) mild downregulation of ICAM-1; (d) marked downexpression of TNFAIP3. Bioinformatics analysis showed the presence of network composed by 59 new interactors (14 transcription factors and 45 microRNAs) appearing strongly related to shear stress. Conclusions. The significant modulation of these genes at low shear stress and their close relationships through transcription factors and microRNAs suggest that all may promote an initial inflamed endothelial cell phenotype, favoring the atherosclerotic disease

Vascular injury post stent implantation: Different gene expression modulation in Human Umbilical Vein Endothelial Cells (HUVECs) model

To explore whether stent procedure may influence transcriptional response of endothelium, we applied different physical (flow changes) and/or mechanical (stent application) stimuli to human endothelial cells in a laminar flow bioreactor (LFB) system. Gene expression analysis was then evaluated in each experimental condition. Human umbilical vein endothelial cells (HUVECs) were submitted to low and physiological (1 and 10 dyne/cm2) shear stress in absence (AS) or presence (PS) of stent positioning in a LFB system for 24 h. Different expressed genes, coming from Affymetrix results, were identified based on one-way ANOVA analysis with p values 3 in modulus. Low shear stress was compared with physiological one in AS and PS conditions. Two major groups include 32 probes commonly expressed in both 1AS versus 10AS and 1PS versus 10PS comparison, and 115 probes consisting of 83 in addition to the previous 32, expressed only in 1PS versus 10PS comparison. Genes related to cytoskeleton, extracellular matrix, and cholesterol transport/metabolism are differently regulated in 1PS versus 10PS condition. Inflammatory and apoptotic mediators seems to be, instead, closely modulated by changes in flow (1 versus 10), independently of stent application. Low shear stress together with stent procedure are the experimental conditions that mainly modulate the highest number of genes in our human endothelial model. Those genes belong to pathways specifically involved in the endothelial dysfunction

Flow chamber.

<p>The flow chamber is realized in polydimethylsiloxane and designed to enable cells to be subject to a large range of shear stress (a). The geometrical configuration has been modified to obtain an optimal laminar flow in the central zone (b) of the chamber.</p