Drug Use in Outpatient Children: Epidemiological Evaluations

Background: Pharmacoepidemiology can be a useful tool for evaluating the appropriateness of drug prescriptions and for estimating therapeutic needs. In particular, pharmacoepidemiology can be valuable in the paediatric setting, which is characterized by the availability of only limited information on the safety and effectiveness of drug use. Methods: Data collected in regional and multiregional administrative prescription databases were analysed. Prevalence data by sex and age were calculated by dividing the number of drug users by the total number of male and female residents in each age group. The number of packages of medications (boxes) was used as indicator of drug consumption. Univariate and multivariate analyses were performed with the aim to identify the determinants of drug prescriptions. Results: Drug utilization studies reported quantitative and qualitative differences between countries in drug prescription to children and adolescents. In particular, Italian children have a threefold greater chance of receiving an antibiotic or an anti-asthmatic compared with children living in the Netherlands. Large differences also were found within Italy between different geographical settings, with prevalence ranging between 57.3% in northern Italy and 68.3% in southern Italy. Prevalence varied also between the local health units (LHUs) of a single region and between district of a single LHU. In the Lombardy Region prevalence ranged between 38.4% in Milan and 54.8% in Brescia, and the residence of the child was one of the main determinant of drug exposure. Conclusions: The studies described in this thesis suggest that pharmacoepidemiology is a valuable tool for monitoring the appropriateness of drug prescribing. However, the epidemiological evaluation of drug prescriptions in children should be improved with regards to the methodological quality of studies

Spirometry testing in a population of Italian children: Age and gender differences

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Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users

<p>Abstract</p> <p>Background</p> <p>Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices.</p> <p>Methods</p> <p>The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments.</p> <p>Results</p> <p>During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment.</p> <p>Conclusions</p> <p>This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.</p

Antidepressant and antipsychotic use in an Italian pediatric population

<p>Abstract</p> <p>Background</p> <p>The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects.</p> <p>In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed.</p> <p>Methods</p> <p>The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies.</p> <p>Results</p> <p>The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years.</p> <p>Conclusions</p> <p>Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments.</p

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking.</p> <p>Objectives</p> <p>To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT.</p> <p>Methods/Design</p> <p>Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled.</p> <p>Discussion</p> <p>The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01257672">NCT01257672</a></p

Ocular medicines in children: the regulatory situation related to clinical research

<p>Abstract</p> <p>Background</p> <p>Many ocular medications are prescribed for paediatric patients, but the evidence for their rational use is very scant. This study was planned to compare the availability and the licensing status of ocular medications marketed in Italy, the United Kingdom (UK), and the United States of America (USA) related to the amount of published and un-published RCTs testing these drugs in the paediatric population.</p> <p>Methods</p> <p>A quantitative analysis was performed to evaluate the number of ocular medications with a paediatric license in Italy, the UK, and the USA. A literature search was also performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on ophthalmic pharmacological therapy in children aged < 18 years, published up to December 2010. A search in the international clinical trial registries, the list of paediatric investigation plans (PIPs) approved by European Medicines Agency (EMA), and the table of medicines with new paediatric information approved by Food and Drug Administration (FDA) was also performed.</p> <p>Results</p> <p>In all, of 197 drugs identified, 68 (35%) single drugs are licensed for paediatric use at least in one considered country, while 23 (12%) were marketed in all three countries. More specifically, in Italy 43 single drugs (48% of those marketed) had a paediatric license, while 39 (64%) did in the UK and 22 (54%) did in the USA. Only 13 drugs were marketed with a paediatric license in all countries.</p> <p>The percentage of drugs licensed for paediatric use and for which at least one RCT had been performed ranged between 51% in Italy and 55% in the USA. No published RCTs were found for 11 (48%) drugs licensed for paediatric use in all three countries. In all, 74 (35%) of the retrieved RCTs involved mydriatic/cycloplegic medications.</p> <p>A total of 62 RCTs (56% completed) on 46 drugs were found in the international clinical trial registries. Cyclosporin and bevacizumab were being studied in many ongoing trials. Twenty-six drugs had new paediatric information approved by FDA based on new paediatric clinical trials, while only 4 PIPs were approved by EMA.</p> <p>Conclusions</p> <p>There is a pressing need for further research and clinical development in the pediatric ophthalmic area, where effective up-to-date treatments, and additional research and education on use in children, remain priorities.</p

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis