The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Incidence of congenital hypothyroidism in the Autonomous Province of Bolzano: benefit of increased iodine intake.

PURPOSE: Although a nation-wide salt iodization program on voluntary basis was implemented in 2005, many areas in our country are still characterized by mild iodine deficiency. Differently from the rest of Italy, an efficient program of iodine prophylaxis was implemented in 1981 in the Autonomous Province of Bolzano. The aim of this study was to investigate whether an adequate iodine intake in the population may affect the incidence of permanent congenital hypothyroidism (CH). METHODS: The incidence trends of permanent CH between 1987 and 2006 in Bolzano Province and in the rest of Italy were estimated. RESULTS: Over the years, the CH incidence has remained steadily lower in Bolzano than in the rest of the country. CONCLUSIONS: Primary prevention of permanent CH may be possible by assuring an adequate nutritional iodine intake in the population. However, the time needed to observe a decrease in the incidence of CH is about a decade under conditions of iodine sufficiency.

Heritability of arterial stiffness and carotid intima-media thickness: an Italian twin study.

BACKGROUND AND AIMS: Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. METHODS AND RESULTS: The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25-0.38), unshared environmental component was 0.25 (0.18-0.32) and age contribution was 0.44 (0.39-0.49). For AIx and PWV, heritabilities were 0.42 (0.29-0.55) and 0.49 (0.35-0.62), unshared environmental components were 0.31 (0.22-0.44) and 0.37 (0.26-0.51) and age contributions were 0.27 (0.16-0.39) and 0.14 (0.06-0.24), respectively. CONCLUSION: This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.

The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.

Psychological well-being (PWB): a natural life outlook? An Italian twin study on heritability of PWB in young adults.

BACKGROUND: To date, the genetic and environmental architecture of the dimensions of psychological well-being (PWB) remains unexplored. METHOD: PWB of 742 twins aged 23-24 years and enrolled in the Italian Twin Registry was assessed with the three-item version of Ryff's Scales of Psychological Well-Being (SPWB). These scales include items for evaluating the PWB dimensions of self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth. A twin design was used to obtain correlations in the PWB dimensions for monozygotic (MZ) and dizygotic (DZ) twins and to estimate the contribution of genetic and environmental factors to variation and covariation in the dimensions. RESULTS: Genetic factors explained moderate to substantial proportions of variance in the six SPWB dimensions, with heritability estimates between 37% and 64%. The estimates of genetic correlations were very high (range 0.77-0.99), indicating that genetic factors that influence the expression of the different dimensions of PWB may be shared to a large extent. Non-shared environmental correlations ranged from substantial to high, with the exception of the correlation between autonomy and the dimensions of purpose in life, self-acceptance and personal growth. CONCLUSIONS: This study presents a twin analysis of PWB measured by the SPWB dimensions; it was found that both genes and non-shared environment play a role in individual differences. The genetic and non-shared environmental correlations between SPWB dimensions suggest that common underlying genetic and non-shared environmental factors influence the expression of the different facets of PWB.

Retrospective, observational, multicentre study on an Italian population affected by chronic hepatitis C who failed to clear HCV-RNA after the combined therapy (PEG-IFN and ribavirin): NADIR study.

There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV-positive subjects with chronic liver diseases treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG-IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV-RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop-outs for noncompliance or adverse events and 28 (3.0%) were lost during follow-up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1-4 were observed in 76.9% of cases; genotypes 2-3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28-8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36-3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1-4. Co-morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age.

Risk factors for Sjögren's syndrome: a case-control study.

OBJECTIVE: The aim of this study was to investigate potential risk factors for Sjögren's syndrome (SS) by means of a multi-centre case-control study, focusing in particular on familial and environmental risk factors. 140 female SS patients and 109 female controls with orthopaedic problems were consecutively enrolled in seven university hospitals in Italy. METHODS: Information regarding the patient's lifestyle, her medical, menstrual and pregnancy history, and any family history of autoimmune diseases (AD) was obtained through a detailed structured questionnaire. The odds ratio (OR) and 95% confidence interval (95%CI) were calculated using unconditional logistic regression, adjusting for age and family size. The probability of first-degree relatives developing an autoimmune disease was also investigated. RESULTS: A positive family history of AD was significantly associated with SS. Subjects with a first-degree relative (FDR) with AD showed a seven-fold increase in the risk for SS compared to controls (OR=7.4, 95%CI 2.8-20.1); the strength of this association increased with the number of relatives affected. Similarly, the FDR of SS patients had a higher risk of AD in comparison to subjects without FDR affected by SS. Women with one or more pregnancies had an increased risk of SS (OR=2.1, 95%CI 1.0-4.3). CONCLUSION: This study suggests that a family history of AD is associated with SS.

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.

Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis.

We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.

Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice versa: a case-control study.

The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases. The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR = 4.1; two or more, OR = 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR = 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).

A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991-1998).

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.

High frequency of antithyroid autoantibodies in pregnant women at increased risk of gestational diabetes mellitus.

BACKGROUND: Thyroid autoantibodies (ThyAb) and subclinical hypothyroidism occur more frequently in pregnant women with insulin-dependent diabetes mellitus than in healthy pregnant women. Few studies have investigated the presence of ThyAb in women with gestational diabetes mellitus (GDM), and no significant association between diabetes in pregnancy and thyroid function has been reported. OBJECTIVE: To assess the thyroid biochemical profile and estimate the prevalence of ThyAb in a group of pregnant women at increased risk of GDM due to family and personal risk factors, and to investigate the relationship between a positive family history of diabetes or thyroid diseases and the eventual presence of ThyAb during pregnancy. METHODS: Oral glucose tolerance, serum ThyAb and thyroid function were evaluated in 181 pregnant women with increased risk for GDM (study group). Seventeen healthy pregnant women without risk factors for GDM and with a normal glucose tolerance were recruited as controls. RESULTS: The women who developed GDM showed a mean free thyroxine concentration significantly lower than that observed in the healthy pregnant women and in those with impaired gestational glucose tolerance and normal glucose tolerance. Twenty-nine of the 181 women in the study group (16%) were ThyAb positive. However, the risk of being ThyAb positive during pregnancy was three times greater in the women with positive family history of both diabetes mellitus and thyroid disease than in those with no family history of these conditions. CONCLUSIONS: This study showed that women with increased risk of GDM, mostly those with family history of diabetes mellitus and thyroid disease, also have an increased risk of being ThyAb positive during pregnancy. It also highlighted the importance of evaluating thyroid function in pregnant women with impaired glucose tolerance, in view of their increased risk of subclinical hypothyroidism.

Family planning KAP survey in Gaza.

This study explores the reproductive attitudes, contraceptive use, demand for family planning and related topics of a representative sample of the female population of reproductive age resident in a Refugee Camp in the Gaza Strip. A cluster sample of 841 resident women of reproductive age (15-49 years) was interviewed in their homes. Univariate and multivariate statistical analyses were performed using BMDP software. 98% of the interviewees favour family planning and 88% plan to use a contraceptive in the future. However, 52% of the women at risk do not use any contraception because of their husband's opposition, fear of side effects or lack of knowledge. The risk of having seven or more children is positively associated with a woman's low educational level and husband's desire for more than seven children. Despite favourable attitudes regarding family planning, there is ignorance and the prevalence of contraception use is low. There is a gap between fertility preference and achievement.

Sex education in secondary schools: an Italian experience.

PURPOSE: To evaluate the impact on Italian teenagers' knowledge and attitudes of an experimental program in sex education. METHODS: The program consisted of five workshops in five public secondary schools in Rome. The impact of the program was evaluated with three questionnaires designed for this study. A pretest evaluated baseline knowledge, a posttest measured the gain in knowledge, and a third questionnaire estimated retention of information 4-6 months later. Three hundred seventy-six students attending secondary school participated in the program. Thirteen questions were selected for the analysis, and improvement was measured by the difference between pretest and posttest scores. RESULTS: Ninety-six percent of the sample was in favor of sex education programs in schools. The students had an average 50% gain in the percentage of correct answers following the course. The mean score based on the number of correct answers to questions showed a baseline value of 5.00, a posttest value of 11.80, and a test value 4-6 months later of 10.7. Results showed students' positive attitude toward school sex education courses, low baseline knowledge, and a good ability to learn. CONCLUSIONS: In Italy there is a need for collaboration between schools and local health services to promote knowledge and prevention in reproductive health among teenagers.

Safety profile and causes of withdrawal due to adverse events in systemic lupus erythematosus patients treated long-term with cyclosporine A.

Several case reports and uncontrolled trials have established the use of cyclosporine A (CsA) in systemic lupus erythematosus (SLE) but some concerns have been raised because of its kidney damaging effects. We here report the results of a retrospective follow-up study designed to assess the safety profile and causes of discontinuation due to adverse events in SLE patients treated with CsA. We treated 56 SLE patients with oral CsA at doses of 3-5 mg/kg for an average of 26 months. Adverse events not leading to the discontinuation of therapy were observed in 62.5% of the patients, the most frequent being hypertrichosis. CsA was stopped because of the occurrence of side effects in 9/56 (16%) of the patients. The most common were nephrotoxicity (3/9) and the occurrence of tremors (3/9). These effects were always reversible within three months of CsA withdrawal. The patients who were older than 40 y had a significant slightly increased risk of stopping CsA therapy for any adverse events (RR 1.08; CI 95% 1.03-1.14). In comparison with previous studies, this study involved a larger cohort of SLE patients who were evaluated for a longer period of follow-up, and confirmed the good tolerability of CsA in these subjects.

[Congenital forms of hypothyroidism: study of risk factors and preventive interventions]. / Forme congenite di ipotiroidismo: studio dei fattori di rischio e interventi di prevenzione. Gruppo di Studio per il Registro Nazionale degli Ipotiroidei Congeniti.

Maternal and child health represents one of the most relevant fields of interest in public health and particular attention is given to congenital pathologies. In Italy, the incidence of congenital hypothyroidism (CH) is 1:3200 live birth. CH is diagnosed at birth by neonatal thyroid screening. This allows a precocious onset of substitutive therapy which avoids severe psychomotor deficits in infants with CH. Moreover, the newborn screening program have permitted to identify transient disorders of thyroid function in newborns. These are essentially due to neonatal, maternal and environmental risk factors, especially iodine deficiency. The National Register (NR) of infants with CH was established in 1987. The aim of the NR is to provide disease surveillance and to monitor efficiency and effectiveness of neonatal screening. Furthermore, the NR represents an useful tool for developing epidemiological studies to identify possible environmental and/or familial risk factors of CH.

[Incidence of measles in Italy in the 1985-1994 period]. / L'incidenza del morbillo in Italia nel periodo 1985-1994.

Measles notifications in Italy underestimate the actual incidence by a factor of ten, as it is ascertained by seroepidemiological investigation. In the decade 1980-89, 45,000 measles cases were notified, on average, per year. Since 1988 mass vaccination campaigns were implemented in several Italian regions. The strategy aimed to offer the prophylaxis actively to all children aged 13 months to 8-12 year for whom a sure recollection of measles was absent. The study has aimed to evaluate the impact of the strategy that worked in the period 1989-91, on the standardised average annual incidence of measles notification, comparing the periods 1985-89 and 1990-94. A reduction of 45% resulted all over Italy. On the contrary the incidence of chickenpox notifications has increased, indicating that the notification system did not worse.

[Pilot study on compulsory vaccination coverage]. / Studio pilota sulle coperture vaccinali obbligatorie.

The disappearance of diphtheria and poliomyelitis is the best evidence of the efficacy of the vaccination strategies adopted in Italy. The active offer of the prophylaxis, reinforced by law, has characterised the operational aspects of the strategy. The active surveillance system is the main tool to take under control the effectiveness of health services responsible for vaccination. This system could be more easily implemented if the health services will be given a specific software aiming to handle and evaluate vaccination registers. The present pilot study, performed in the regions Marche and Sardegna, is an example of active surveillance and it is based on the ARVA software produced by the Istituto Superiore di Sanità. The results show a good level of coverage (> 95%) within the second year of life. Unsatisfactory results were obtained on the timing of vaccinations, as recommended by the vaccination schedule, mostly for the third doses.

Occurrence of anti-thyroid autoantibodies in children vertically infected with HIV-1.

Autoimmune phenomena, especially occurrence of non organ-specific autoantibodies, are common in congenitally acquired HIV infection, mostly in the symptomatic stages of the disease. Anti-thyroid autoantibodies detected in adult patients represent the only type of organ-specific autoantibodies reported in HIV infection. As far as we know, occurrence of these autoantibodies has not been observed in HIV infected children. In this study thyroid biochemical pattern and possible occurrence of anti-thyroid autoantibodies were investigated in 40 vertically HIV infected, 18 seroreverted and 22 healthy children. 34% of HIV infected symptomatic children showed anti-thyroglobulin antibodies. Asymptomatic patients, seroreverted and healthy controls did not show any anti-thyroid antibodies at the time of the study. High Tg levels were observed in 38% of the 40 HIV infected patients and high TSH concentrations were found in 27.5% of the HIV children. High TSH values were more frequently observed in the infected children with moderate or severe immunocompromised status. Thyroxine binding globulin levels were high in 68% of the HIV children and in 22% of the seroreverted. The finding of anti-thyroid autoantibodies in congenital HIV infected children confirms the thyroid's involvement in HIV infection and provides more information about the wide spectrum of autoimmune phenomena observed in the infection.