Maurizio Bonati

Reducing the costs of paediatric antibiotic prescribing in the community by implementing guideline recommendations.

Italian children receive a high number of antibiotic prescriptions, and the use of second‐choice antibiotics is common. A few studies in other countries have demonstrated that the implementation of international guidelines for the most common paediatric diseases may reduce the associated costs. A cost analysis of the expenditure for antibiotic prescriptions in outpatient children in the Lombardy region (Italy) and for each of the regions local health units (LHUs) was performed using a pharmacoepidemiological approach. The safety and cost impact associated with a quali‐quantitative improvement in antibiotic prescribing was estimated.

Tuberculosis care for pregnant women: a systematic review

BackgroundTuberculosis (TB) during pregnancy may lead to severe consequences affecting both mother and child. Prenatal care could be a very good opportunity for TB care, especially for women who have limited access to health services. The aim of this review was to gather and evaluate studies on TB care for pregnant women.MethodsWe used a combination of the terms “tuberculosis” and “pregnancy”, limited to human, to search for published articles. Studies reflecting original data and focusing on TB care for pregnant women were included. All references retrieved were collected using the Reference Manager software (Version 11).ResultsThirty five studies were selected for review and their data showed that diagnosis was often delayed because TB symptoms during pregnancy were not typical. TB prophylaxis and anti-TB therapy appeared to be safe and effective for pregnant women and their babies when suitable follow up and early initiation were present, but the compliance rate to TB prophylaxis is still low due to lack of follow up and referral services. TB care practices in the reviewed studies were in line in principle with the WHO International Standards for Tuberculosis Care (ISTC).ConclusionsIntegration of TB care within prenatal care would improve TB diagnosis and treatment for pregnant women. To improve the quality of TB care, it is necessary to develop national level guidelines based on the ISTC with detailed guidelines for pregnant women.

Drug use profile in outpatient children and adolescents in different Italian regions

BackgroundLarge differences exist in the prevalence rate of drugs prescribed to children and adolescents between and within countries. The aim of this study was to evaluate child and adolescent drug prescription patterns in Italy in an extra-hospital setting at the regional and Local Health Unit (LHU) levels.MethodsData sources were three regional prescription databases. Data concerning the year 2008 were evaluated. A total of 3.3 million children and adolescents were included. Drug prevalence and prescription rates were evaluated at the regional and LHU levels. The correlation between mean latitude, average annual income, hospitalisation rate, number of paediatricians per 1,000 resident children, and prevalence rate was evaluated by LHU using a linear multiple regression analysis.ResultsLarge differences were found across Italian regions and LHUs. The mean prevalence rate was 56.4% (95% CI 56.3-56.5%; 51.2-65.4% among regions) and, at the LHU level, ranged from 43.1% to 70.0% (higher in the South). A total of 878 drugs were prescribed, 175 of which were shared by all LHUs. Amoxicillin clavulanate was the most used drug in all regions and in 31 of 33 LHUs. Amoxicillin was the drug with the highest variability in use between LHUs (9.1-52.1% of treated children). An inverse correlation was found between prevalence rate and both latitude (pu2009<u20090.0001) and average annual income (pu2009=u20090.0002).ConclusionsThe use of drugs in children and adolescents is higher in southern Italy and is inversely related to latitude and average annual income. More efforts should be devoted to informing physicians, patients and policy makers in order to plan effective initiatives to improve the situation.

Transition to adult mental health services for young people with attention deficit hyperactivity disorder in Italy: Parents' and clinicians' experiences.

Abstract Objective. The aim of this study was to describe the experiences of parents and clinicians in relation to the transition from child and adolescent neuropsychiatric services (CANPS) to adult services for people with attention deficit hyperactivity disorder (ADHD) in Italy. Methods. Parents of people with ADHD who reached the transition boundary for CANPS were sampled from the A.I.F.A. association (Italian Association of ADHD Families). We thematically analyzed informative and qualitative questionnaires completed by parents and clinicians. Results. Parents’ (n = 24) and clinicians’ (n = 27) experiences differed slightly on challenges and unmet needs, whereas clinicians agreed on the variables required for an optimal transition process. Poor transition and multiple barriers to such care were identified. Specifically, far fewer people received services, especially public health services, after reaching the age of 18, and perceived barriers included problems with user access, limited transition protocols, poor service coordination, and possible lack of ADHD-related knowledge on the part of adult practitioners. Conclusions. Care continuity in mental healthcare remains a need to be prioritized and better defined also for ADHD patients (and their parents). Parents’ and clinicians’ experiences are more likely to be positive if transition management is characterized by a gradual preparation, a period of parallel care, and commonly acknowledged, clear information on available services and how to access them. Identifying the needs and barriers of the people representing the different roles (clinicians, parents, and users) involved in the transition to adult mental health services is of particular importance in designing effective, shared transfer planning procedures.

Impact of the systematic introduction of low-cost bubble nasal CPAP in a NICU of a developing country: a prospective pre- and post-intervention study.

BackgroundThe use of Nasal Continuous Positive Airway Pressure Ventilation (NCPAP) has begun to increase and is progressively replacing conventional mechanical ventilation (MV), becoming the cornerstone treatment for newborn respiratory distress syndrome (RDS). Howerver, NCPAP use in Lower-Middle Income Countries (LMICs) is poor. Moreover, bubble NCPAP (bNCPAP), for efficacy, cost effectiveness, and ease of use, should be the primary assistance technique employed in newborns with RDS.Objective: To measure the impact on in-hospital newborn mortality of using a bNCPAP device as the first intervention on newborns requiring ventilatory assistance.MethodsDesign: Prospective pre-intervention and post-intervention study.Setting: The largest Neonatal Intensive Care Unit (NICU) in Nicaragua.Participants: In all, 230 (2006) and 383 (2008) patients were included.Intervention: In May 2006, a strategy was introduced to promote the systematic use of bNCPAP to avoid intubation and MV in newborns requiring ventilatory assistance. Data regarding gestation, delivery, postnatal course, mortality, length of hospitalisation, and duration of ventilatory assistance were collected for infants assisted between May and December 2006, before the project began, and between May and December 2008, two years afterwards.Outcome measures: The pre- vs post-intervention proportion of newborns who died in-hospital was the primary end point. Secondary endpoints included rate of intubation and duration of NICU stay.ResultsSignificant differences were found in the rate of intubation (72 vs 39%; p < 0.0001) and the proportion of patients treated exclusively with bNCPAP (27% vs 61%; p <0.0001). Mortality rate was significantly reduced (40 vs 23%; p < 0.0001); however, an increase in the mean duration of NICU stay was observed (14.6 days in 2006 and 17.5 days in 2008, p = 0.0481).The findings contribute to the evidence that NCPAP, particularly bNCPAP, is the first-line standard of care for efficacy, cost effectiveness, and ease of use in newborns with respiratory distress in LMICs.ConclusionsThis is the first extensive survey performed in a large NICU from a LMICs, proving the efficacy of the systematic use of a bNCPAP device in reducing newborn mortality. These findings are an incentive for considering bNCPAP as an elective strategy to treat newborns with respiratory insufficiency in LMICs.

Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry

Background Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. Methods We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Results Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Conclusion Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients.

Clinical trial registries: more international, converging efforts are needed

Clinical trial registries are being increasingly acknowledged worldwide. We searched for possibly trustworthy online registries that are not already included in the International Clinical Trials Registry Platform to evaluate whether other useful trial data sources exist and whether they could potentially be consulted, since the strategy search within this platform has recently been questioned. Fifty-nine registries were initially identified, and 11 of them fit the criteria applied and were analyzed for quality and usability. Four additional, potentially reliable registries were identified that researchers could exploit in order to obtain a more global view of the issue being investigated.

Comparing recurrent antibiotic prescriptions in children treated with a brand name or a generic formulation.

The aim of this study was to investigate the rate of recurrent prescriptions and hospital admissions in children receiving a brand name or generic antibiotic prescription.

Childhood asthma management pre- and post-incident asthma hospitalization.

Many hospitalizations for asthma could potentially be avoided with appropriate management. The aim of this study was to analyze data on disease management of a paediatric population with a hospitalization for asthma. The study population comprised 6–17 year old subjects belonging to three local health units of the Lombardy Region, northern Italy. Regional administrative databases were used to collect data on: the number of children with an incident hospitalization for asthma during the 2004–2006 period, anti-asthma therapy, specialist visit referrals, and claims for spirometry, released in the 12 months before and after hospitalization. Each patient’s asthma management profile was compared with GINA guideline recommendations. Among the 183 hospitalized subjects, 101 (55%) received therapy before hospitalization and 82 (45%) did not. 10% did not receive any therapy either before or after hospital admission and in 13% the therapy was discontinued afterward. Based on GINA guidelines, asthma management adhered to recommendations only for 55% of subjects. Results may suggest that for half of hospitalized subjects, inaccurate diagnosis, under-treatment/scarce compliance with asthma guidelines by physicians, and/or scarce compliance to therapy by patients/their parents occurred. In all these cases, hospitalization would be a proxy indicator of preventable poor control of disease, rather than a proxy indicator of severity.

ANTIEPILEPTIC DRUG PRESCRIBING FOR CHILDREN IN ITALY

The aim of the study was to evaluate prescription profile of antiepileptic drugs (AEDs) in pediatric population. Prescriptions reimbursed by the National Health System, involving 1,669,370 children and adolescents, dispensed between 2003–2012 by the retail pharmacies in the Lombardy Region, were analysed. AEDs classified according to International Anatomic-Therapeutical-Chemical Classification system (ATC subgroup: N03A). Prevalence was defined as the number of patients received at least one AED prescription per 1000 inhabitants and incidence was defined as the number of patients received an AED prescription for the first time (no AED prescriptions in the previous 12u2005months) per 1000 inhabitants. The first prescription dispensed to incident cases was analyzed. During 2012, 6,088 children and adolescents (3.6‰ of the population) received at least one AED prescription. The incident cases were 1,465 (incidence 0.86‰). Prevalence and incidence showed significant differences across time. In 2012 about 96% of incident cases was treated with only one AED and of these approximately 78% was treated with an older, while 22% with a newer AED. Valproic acid was the most used at the first prescription (56.2%), followed by carbamazepine (11.5%) and levetiracetam (9.2%). The use of newer AEDs increased across time (χ2t=23.75 P<0.005): in particular the prescriptions of carbamazepine decreased accross time (CAGR: −5.3%), while those of levetiracetam increased (CAGR: +35.4%). Despite conventional AEDs were still the main treatment for epileptic children, there was a decrease of carbamazepine and an increase of levetiracetam. These findings are consistent with results from drug utilization studies performed in other countries.