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.

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.

Comparison of capillary blood versus venous blood samples in the assessment of immunity to measles.

Seroepidemiological investigations are essential for assessing the efficacy of measles vaccination programmes. However, when large-scale sampling is needed, a major difficulty is the problem of taking venous blood, especially in children. An alternative method is the collection of capillary blood samples spotted on filter papers. The eluted extract from these 'blood' spots can be used instead of serum samples for measles laboratory diagnosis or investigations. Measles antibody detection is readily carried out by ELISA on serum samples. The same technique can be used on eluates from capillary blood spots. Measles antibody titres determined on matched serum and blood spot samples from 27 children were compared. A strong correlation was found between the results obtained with the two methods of blood sampling.

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.

Comparative clinical evaluation of the effect on carbohydrate and lipid metabolism of two norethisterone-containing hormonal contraceptives: Mesigyna and TriNovum.

The effect on carbohydrate and lipid metabolism of two hormonal contraceptive preparations containing norethisterone (commercially known as Mesigyna and TriNovum) was studied in a total of 60 women, before and after 6 months of treatment. Carbohydrate metabolism was evaluated by means of a euglycemic glucose clamp test; lipid metabolism was monitored by measuring total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglycerides. The two groups were properly matched with the exception of pretreatment levels of cholesterol and LDL-cholesterol. At the end of treatment, no difference was found within or between groups in fasting glucose and insulin levels and in glucose rate of disappearance. A significant increase in total cholesterol, HDL-cholesterol, and VLDL-cholesterol was found in both groups at the end of the treatment period; in addition, TriNovum caused a significant increase also in triglycerides. In conclusion, the safety of both preparations with regard to carbohydrate metabolism was confirmed using the most accurate method available; furthermore, changes in lipid metabolism were such as to have little clinical significance.

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.

Reducing pain of first trimester abortion under local anaesthesia.

The study aimed to estimate the pain related to first trimester abortion under local and general anaesthesia. One hundred and eighty-one women undergoing abortion of first trimester under local anaesthesia and 198 under general anaesthesia were interviewed 1 h after the end of the procedure. About 50% of all women described their experience as less painful than expected. Over 50% of the women described the pain during the procedure as mild or moderate according to the verbal rating scale. The step-up logistic regression analyses identified four important variables: time interval less than 2 min from local anaesthesia injection to the beginning of the procedure (RR = 3), lack of choice between local and general anaesthesia (RR = 1.9), history of frequent use of analgesics (RR = 1.9) and nulliparity (RR = 1.7). These data indicate that skillfully performed abortion with local anaesthesia is a procedure tolerated by most women. Moreover, because it carries lower risk of complications and costs less, its use should be encouraged.

PIP: The World Health Organization has urged a reduction in the number of first-trimester induced abortions performed under general anesthesia. To determine the implications of this recommendation for pain control, 181 women undergoing first-trimester abortion under local anesthesia and 198 aborted under general anesthesia at University Hospital in Rome, Italy, were interviewed 1 hour after the procedure. Pain intensity was assessed through both the visual analogue and verbal rating scales. Women who selected or were assigned to general anesthesia tended to be younger (mean age, 27 years) and nulliparous. Over 50% of local anesthesia patients described their pain during the procedure as mild or moderate, 30% rated it severe, and 18% characterized it as distressing but time-limited. 60 minutes after the abortion, pain scores were higher in the general anesthesia group. Logistic regression analysis identified four significant predictors of pain: time interval less than 2 minutes from local anesthetic injection to the beginning of the procedure (relative risk (RR), 3.0), lack of choice between general or local anesthesia (RR, 1.9), history of frequent use of analgesics (RR, 1.9), and nulliparity (RR, 1.7). 91% of general anesthesia and 73% of local anesthesia patients stated they would recommend their method of anesthesia to a friend undergoing abortion. These findings suggest that local anesthesia, less costly and with a lower risk of complications than general anesthesia, is feasible for pain control, especially if administered 2-5 minutes before the procedure begins.

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.

[The evaluation of the risk factors for congenital hypothyroidism: the outlook of a case-control study]. / Valutazione dei fattori di rischio dell'ipotiroidismo congenito: prospettive di uno studio caso-controllo.

The availability of a National Register of congenital hypothyroid infants allowed to perform descriptive studies on characteristics of the cases and the efficiency of the neonatal screening. Continuous and exhaustive recording of data concerning congenital hypothyroidism cases provided valuable epidemiological informations about congenital hypothyroidism in Italy. Moreover, the National Register allowed to develop a network of collaboration which can promote a population based case-control study. As the etiopathogenesis of congenital hypothyroidism has not been completely elucidated, performing of a case-control study can contribute to evidence the most important risk factors of congenital hypothyroidism and to improve the prevention also by prenatal diagnosis of this disease. Screening centers will be involved in the study and questionnaires of the National Register for congenital hypothyroidism will be used to record case and control informations. A biological bank concerning cases, controls and their parents, will be organized.

[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.

Endocrine response to HIV infection. Involvement of thyroid gland.

Endocrine dysfunctions were associated at different stages of infection, including those early in the course of HIV infection. In fact adrenal insufficiency, hyporeninemic hypoaldosteronism, hyponatremia, reduced gonadotropins levels, gonadal abnormalities and changes in hormone-binding proteins were reported in HIV infection. Also a thyroid involvement with autoimmune phenomena was observed in HIV infection by several studies giving different explanations of altered thyroid conditions. These findings suggest an effect of HIV on endocrine system. Recognition of endocrine manifestations in these patients may contribute to better characterize different stages of the infection and improve the management of HIV patients.