Pietro Panei

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.

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.

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 diseases 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.

Atomoxetine in the treatment of attention deficit hyperactivity disorder and suicidal ideation

Objective: Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric childhood disorder. The most commonly used drugs in the treatment of ADHD are methylphenidate (MPH) and atomoxetine (ATX); the former of the two is prescribed in USA more than it is in Western Europe. Some of the most important safety concerns about ADHD drug treatment are sudden cardiac death and suicidal behavior. In this study, we present a series of cases of Italian children who had presented suicidal ideation during ADHD pharmacological therapy with ATX. Research design and methods: Data were obtained from the ADHD Italian Register. The data assessed the use of MPH and ATX, which had been prescribed to patients who were aged < 18 years and diagnosed with ADHD. All patients enrolled in the ADHD Italian Register treated with ATX or MPH who experienced suicidal thoughts or thoughts of self-harming were considered and assessed. Results: We describe the clinical cases of seven Italian children (enrolled in the ADHD Italian Register) treated with ATX and affected by suicidal ideation, self-harming or other similar symptoms. Our results highlighted that all seven patients developed suicidal ideation or intentional self-harming during pharmaceutical treatment with ATX and, particularly, after the dose increase of the drug. Conclusion: There is a need to improve our knowledge about the efficacy and safety of ATX, MPH and other drugs used in the treatment of ADHD both in children and adults during the post-marketing experience.

Attention-Deficit/Hyperactivity Disorder Drugs and Growth: An Italian Prospective Observational Study

OBJECTIVE This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children. DESIGN The study was an observational, post-marketing, fourth phase study. METHODS Data on height and weight were collected at baseline and every 6 months up to 24 months. RESULTS Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanners percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH. CONCLUSIONS We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH.

A DIFFERENCE IN RELATIVE EFFICACY OF TWO DTaP VACCINES IN CONTINUED BLINDED OBSERVATION OF CHILDREN FOLLOWING A CLINICAL TRIAL. • 1021

In 1992-94, a randomized, double blind, placebo-controlled clinical trial of two acellular and one whole-cell pertussis vaccines was conducted in Italy. Each acellular vaccine (one manufactured by SmithKline Beecham [SB] and one by Chiron Biocine [CB]) contained filamentous hemagglutinin, pertactin and inactive pertussis toxin, the latter being detoxified by formalin and glutaraldehyde in SB DTaP and genetically detoxified in CB DTaP. Primary immunization at 2, 4 and 6 months of age provided an efficacy for each DTaP of 84% in preventing confirmed pertussis of 21 or more days of paroxysmal cough, over an average of 17 months of follow-up. The incidence rate ratio (IRR) of pertussis in recipients of SB and CB vaccines was 1.0 with 37 cases in 4,481 children and 36 cases in 4,452, respectively. In 1995, during additional blinded follow-up of the same cohorts through September 30, a total of 53 pertussis cases have been diagnosed in DTaP recipients through an average age of 35 months. Thirty-five cases of confirmed pertussis occurred in SB DTaP recipients in the nine-month period and 18 cases in CB DTaP recipients. Although initially both vaccines exhibited equivalent high efficacy, in a further period of observation the incidence in CB DTaP recipients was significantly lower. Table

Il registro dell'ADHD: valutazione post-marketing del profilo beneficio-rischio dei farmaci e promozione dell'appropriatezza

INTRODUCTION: The Register was aimed at assessing the benefit-risk profile of the treatment of attention deficit hyperactivity disorder (ADHD) with atomoxetine and methylphenidate. METHODS: Post-marketing observational study, phase IV. Prescription medication to children and adolescents with ADHD aged between 6 and 18 years in the centres of reference for ADHD accredited by the Italian regions. RESULTS: In the period from September 2007 to October 2011, 1098 children and adolescents were treated with methylphenidate and 951 with atomoxetine. 411 (21.5%) patients are released from the register: 274 treated with atomoxetine and 167 with methylphenidate, with a greater risk of discontinuation for atomoxetine: RR 1.4 (1.3-1.6) p<0.001. The length of treatment at the time of removal from the register is 4.1 months for atomoxetine and 2 months for methylphenidate. Patients treated with atomoxetine are more likely to experience an adverse event compared to those treated with methylphenidate (RR 2.8; 1.9-4.2). The total number of serious adverse events observed was 110: 82 (75%) patients treated with atomoxetine and 28 (25%) individuals treated with methylphenidate. For 98 patients with serious adverse events, the adverse event led to the interruption of treatment with exit from the registry. The chance of a serious adverse event among those treated with atomoxetine compared to those with methylphenidate is RR 2.8 (1.8-4.2). There have been 14 cardiovascular events, all grown positively. 69 were found with a ECG alterations, with an increased risk for methylphenidate (RR 2.4; 1.4-4.2). The incidence of suicidal ideation was 4.5/1000 patients treated with atomoxetine. Hepatic alterations occurred with an incidence of 1/1000 subjects treated with methylphenidate and 4/1000 of those who received atomoxetine. DISCUSSION: The survey was carried out on a population which represents appropriately the paediatric population. The observed prevalence of ADHD corresponds to the expectation based on data from previous epidemiological investigations in Italy but considerably lower than what is reported in the international scientific literature. The rate of exposure to pharmacological treatments is similar to that of other European countries.