The Italian Registry of GH Treatment: electronic Clinical Report Form (e-CRF) and web-based platform for the national database of GH prescriptions.

BACKGROUND: In Italy, the utilization and the reimbursement of Growth Hormone (rGH) therapy by the National Health System (Servizio Sanitario Nazionale) are regulated by the "Note #39" included in the "Notes for the use of drugs" by the Italian Medicines Agency (AIFA), which are published in the Official Gazette, thus having the force of law. The "Note #39" establishes the diagnosis for which the reimbursement is granted and confirms the assignment of the national health surveillance on the use of GH therapy to the Italian National Institute of Health, requesting its computerization. AIM: The aim of this work was to realize a dedicated electronic Clinical Report Form based on the mandatory data requested by the Note #39 and allowing the online reporting of the rGH prescriptions by the regional accredited centers. RESULTS AND CONCLUSIONS: This interface is at the base of the national database of the Italian Registry of GH Treatment, which allows obtaining and managing correct and complete data to provide public health surveillance on GH therapy, both at national and local levels, necessary for policymakers decisions. In addition, this national database could be a useful instrument for improving knowledge about aspects of this treatment still under discussion.

Long-term treatment with low-dose medicine in chronic childhood eczema: a double-blind two-stage randomized control trial.

BACKGROUND: The efficacy of low-dose medicine (LDM) in childhood mild/moderate eczema is not known. We conducted a double-blind, two-stage, randomized, placebo-controlled clinical trial, lasting 23 months, to address this issue. METHOD: Eighty children with chronic mild/moderate eczema were randomly allocated to Group A (placebo) or Group B (treatment group; Galium-Heel®, a low-dose multicomponent medicine based upon natural substances; Guna-Interleukin 12 and Guna-Interferon-γ administered twice a day for six non-consecutive months for each stage). LDM is characterized by the use of biological molecules, such as cytokines, neuropeptides, growth factors, hormones at very low concentrations, which correspond to physiological levels within the human body. The dosage of the cytokines used in this trial (IFN-γ and IL-12) is 10 fg/ml. The SCORAD index was evaluated by the same operator: subjects with a SCORAD index below 20 were considered to have mild eczema (61/80; mean: 10.79), whereas a SCORAD index between 20-50 indicated moderate eczema (19/80; mean: 26.84). The data of 66/80 children were analyzed in stage 1 and those of 62/66 children in stage 2. The primary outcome measure was reduction of eczema severity assessed by the SCORAD index. Secondary outcomes were disease-free interval, and treatment safety and tolerability. RESULTS: The decrease in disease severity was greater in Group B than in Group A already in stage 1 (a decrease 63.9% versus 53.2%), but the difference was not significant (p = 0.16). Moreover, subjective symptoms (itching and sleep disturbances) initially decreased and then worsened in Group A, whereas itching decreased linearly and sleep disturbances decreased significantly (p=0.049) in Group B. CONCLUSIONS: Preliminary evidence suggests potential benefit, but further work is needed to validate this approach. TRIAL REGISTRATION: The trial was registered with EudraCT number 2010-018640-13 through the database of the National Clinical Trials Monitoring Centre Database (Osservatorio delle Sperimentazioni Cliniche, OsSC) of the Italian Medicines Agency.

Serum Vitamin D levels and Vitamin D supplementation do not correlate with the severity of chronic eczema in children.

BACKGROUND: Eczema is one of the most common chronic inflammatory skin diseases, affecting about 20% of children. The pathogenic mechanisms of eczema are still not fully understood, and current treatment of moderate-severe eczema is often difficult. Recently, it has been suggested that Vitamin D plays a key role in this disease, even if mechanisms are only partially known. OBJECTIVE: The purpose of our study was to assess the 25-Hydroxyvitamin D serum levels in a pediatric population suffering from chronic eczema (IgE-mediated and non-IgE-mediated), and to correlate these phenotypes with the SCORAD severity and selected clinical and biological parameters. Moreover, we aimed to evaluate whether a supplementation of Vitamin D3 could affect the same clinical and laboratory parameters. METHODS: 89 children with chronic eczema were enrolled in the study. Severity of eczema was assessed with the SCORAD index. Past and present history was taken, and patients were divided into two groups according to the state of sensitization. According to a randomization schedule, the enrolled children were assigned to the following groups: supplementation group, which received a daily oral Vitamin D3 supplementation (2000 IUs) for 3 months; control group which received no supplementation. RESULTS: Vitamin D concentrations in patients with moderate and severe eczema were not statistically different from Vitamin D concentration detected in the serum of patients with mild eczema. Furthermore, we did not find any correlation between Vitamin D levels, total IgEs and SCORAD index, both in the Sensitized and in the Not-Sensitized group. The Vitamin D3 supplementation did not influence the SCORAD severity or the total IgEs concentration. CONCLUSION: To our knowledge, our study is the first one that shows no correlation between serum levels of Vitamin D, eczema severity and IgE sensitization in a pediatric population suffering from chronic eczema.

[Pharmaco-epidemiologic indicators for the analysis of drug consumption at the regional level]. / Indicatori farmacoepidemiologici per l'analisi del consumo di farmaci a livello territoriale.

The analysis of drug use is often limited to the description of per capita pharmaceutical expenditure. Differences that are observed in the comparison are attributable to the specific age and gender distribution of the compared populations, and to prescriptive behaviors of general practitioners. Aim of this paper is to analyze drug prescription in a local health unit of the Friuli-Venezia Giulia region. In order to take into account differences in age distribution among health districts we used "weighted" populations. An in depth analysis has been carried out on antihypertensive drugs to evaluate differences in GPs' prescriptive behavior. Both the differences among districts in the level of drug use, and variability observed in antihypertensive use in the population, suggest that drug prescription might be partly inappropriate.

Predictors of adverse events after the administration of acellular and whole-cell diphtheria-tetanus-pertussis vaccines.

Recurrence of adverse events, the effect of site of injection, and concurrent administration of oral polio vaccine (OPV) and hepatitis B vaccine (HBV) on reactogenicity were assessed in recipients of two acellular pertussis vaccines given in combination with diphtheria and tetanus toxoids (DTaP), one whole-cell DTP vaccine (DTPwc) and one DT vaccine during a double blind, randomized, controlled clinical trial. Local and systemic side reactions were more likely to recur after the administration of DTaP and DT compared with DTPwc. In all vaccine groups, injection in the buttock was associated with a lower rate of common adverse events compared with injection in the thigh, while simultaneous administration of OPV and/or HBV did not increase the risk of onset of side reactions.

Outbreak of paralytic poliomyelitis in Albania, 1996: high attack rate among adults and apparent interruption of transmission following nationwide mass vaccination.

After >10 years without detection of any cases of wild virus-associated poliomyelitis, a large outbreak of poliomyelitis occurred in Albania in 1996. A total of 138 paralytic cases occurred, of which 16 (12%) were fatal. The outbreak was due to wild poliovirus type 1, isolated from 69 cases. An attack rate of 10 per 100,000 population was observed among adults aged 19-25 years who were born during a time of declining wild poliovirus circulation and had been vaccinated with two doses of monovalent oral poliovirus vaccines (OPVs) that may have been exposed to ambient temperatures for prolonged periods. Control of the epidemic was achieved by two rounds of mass vaccination with trivalent oral poliovirus vaccine targeted to persons aged 0-50 years. This outbreak underscores the ongoing threat of importation of wild poliovirus into European countries, the importance of delivering potent vaccine through an adequate cold chain, and the effectiveness of national OPV mass vaccination campaigns for outbreak control.

Incidence of invasive Haemophilus influenzae type b disease in Italian children.

To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis. The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation. The incidence density of all invasive Hib disease was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years. Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis. The child with sepsis died. The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries. Cost-benefit analyses are needed for planning Italian vaccination policy.

Predicting the accrual rate in a vaccine clinical trial: an a posteriori evaluation of the feasibility study.

To estimate the expected accrual rate in a double blinded controlled randomized trial of the absolute clinical efficacy of three anti-pertussis vaccines in infants, we performed a series of surveys among mothers and physicians in the areas to be considered for participation in the trial. In this paper, we compared the predicted enrollment with the actual enrollment achieved at the end of the recruitment phase of the trial. The predicted enrollment rate was 27%, while the observed rate was 26%. Results from the feasibility study were highly predictive of actual enrollment rate. In the local health units (USL) where such assessments were carried out, the accrual rate, was higher than those not participating in the feasibility phase.

A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group.

BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. METHODS: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing. RESULTS: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group. CONCLUSIONS: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

[Epidemiology of invasive infections with Haemophilus influenzae type b in the world and in Italy]. / Epidemiologia delle infezioni invasive da Haemophilus influenzae di tipo b nel mondo e in Italia.

The incidence of Haemophilus influenzae type b (Hib) disease in the 0-5 years age group has been studied in many countries. In the United States, before the introduction of mass vaccination, the incidence of invasive Hib disease ranged from 7 per 100,000 in the 4-5 years age group to 452 pert 100,000 in the 6-11 months age group. In Europe, the incidence of this disease has been estimated to range from 21 to 60 per 100,000 per year in the 0-5 years age group. Hib infection is mainly transmitted by the respiratory route. Risk factors of the disease include: attending a day-care center, a high number of household members, low socio-economic level, age less than two years, and belonging to certain ethnic groups. Accurate estimates of the incidence of invasive Hib disease do not exist in Italy. Among the 15,601 children participating in the "Progetto Pertosse", a clinical trial for the evaluation of antipertussis vaccines, there occurred six cases of Hib meningitis, one of Hib sepsis, and one of Hib cellulitis. These episodes yield an incidence density of 28.7 per 100,000 person-years in the 2-30 month age group. Incidence data will also need to be collected for children in the 30 months-5 years age group before attempting a cost-benefit analysis with the aim of planning a mass vaccination.

Use of a specific oral hyposensitization therapy to Dermatophagoides pteronyssinus in children with atopic dermatitis.

The aim of the present study was to evaluate the efficacy of an oral specific hyposensitization therapy in children with atopic dermatitis and positive prick skin tests and/or RAST to Dermatophagoides pteronyssinus (D.pt.). A total of 60 patients, in three different clinical groups, were selected for a three years clinical trial. Group A: children with atopic dermatitis and allergic asthma and/or rhinitis; groups B and C: children with exclusively atopic dermatitis. Groups A and B received specific hyposensitization therapy. Group C was the control group. The clinical evaluation of the dermatological lesions, at the end of our study, didn't show any significant difference among the three groups. Moreover, the onset of respiratory symptoms between the two groups with exclusively atopic dermatitis was similar and not related to the positivity of prick skin tests and/or RAST to seasonal allergens. Our study suggests that specific hyposensitisation therapy with extracts of D.pt., although with no side effects, does not affect the natural history of atopic dermatitis.

Familial male pseudohermaphroditism with gynaecomastia due to 17 beta-hydroxysteroid dehydrogenase deficiency. A report of 3 cases.

Three sisters with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4-5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma androstenedione to testosterone ratio was 20-25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.