Epidemiological analysis to identify predictors of X-linked hypophosphatemia (XLH) diagnosis in an Italian pediatric population: the EPIX project.

PURPOSE: X-linked hypophosphatemia (XLH) is a rare multi-systemic disease characterized by low plasma phosphate levels. The aim of this study was to investigate the annual XLH prevalence and internally evaluate predictive algorithms' application performance for the early diagnosis of XLH. METHODS: The PediaNet database, containing data on more than 400,000 children aged up to 14 years, was used to identify a cohort of XLH patients, which were matched with up to 10 controls by date of birth and gender. The annual prevalence of XLH cases per 100,000 patients registered in PediaNet database was estimated. To identify possible predictors associated with XLH diagnosis, a logistic regression model and two machine learning algorithms were applied. Predictive analyses were separately carried out including patients with at least 1 or 2 years of database history in PediaNet. RESULTS: Among 431,021 patients registered in the PediaNet database between 2007-2020, a total of 12 cases were identified with a mean annual prevalence of 1.78 cases per 100,000 patients registered in PediaNet database. Overall, 8 cases and 60 matched controls were included in the analysis. The random forest algorithm achieved the highest area under the receiver operating characteristic curve (AUC) value both in the one-year prior ID (AUC = 0.99, 95% CI = 0.99-1.00) and the two-year prior ID (AUC = 1.00, 95% CI = 1.00-1.00) analysis. Overall, the XLH predictors selected by the three predictive methods were: the number of vitamin D prescriptions, the number of recorded diagnoses of acute respiratory infections, the number of prescriptions of antihistamine for systemic use, the number of prescriptions of X-ray of the lower limbs and pelvis and the number of allergology visits. CONCLUSION: Findings showed that data-driven machine learning models may play a prominent role for the prediction of the diagnosis of rare diseases such as XLH.

Epidemiology and Burden of Influenza in Children 0-14 Years Over Ten Consecutive Seasons in Italy.

BACKGROUND: In Europe, influenza vaccination coverage in the pediatric population is low. This study describes the influenza incidence and associated healthcare utilization in the pediatric population in Italy. METHODS: Deidentified data from electronic medical records for children 0-14 years old seen by >150 family pediatricians in the Pedianet network in Italy were evaluated for 10 influenza seasons spanning 2010-2020. Incidence of influenza (cases per 1000 person-months), related sequelae and associated healthcare resource use were determined using diagnostic, prescription and medical examination data. RESULTS: Over 10 seasons, an average of 8892 influenza cases (range, 4700-12,419; total 88,921) were diagnosed in a cohort of 1,432,384 children 0-14 years of age. Influenza vaccination coverage was 3.6% among children with an influenza diagnosis and 6.8% among children without. Influenza-related healthcare resource utilization included 1.58 family pediatrician visits per influenza episode and 220 ED and 111 hospital admissions, with the highest resource usage among children 1-4 years and lowest among children <6 months old. The most common influenza complications were acute otitis media (2.9% of influenza cases) and pneumonia (0.5%). Antibiotics were prescribed in 38.7% of influenza cases; no antiviral agents were prescribed. One intensive care unit admission and 2 cases requiring ventilatory support were documented. No influenza-related deaths were reported. CONCLUSION: Pediatric influenza vaccination was low despite the burden and healthcare use related to seasonal influenza in the pediatric population during a 10-year period in Italy.

Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19.

AIM: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. METHODS: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0-14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. RESULTS: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1-3.0) and neurological problems (aHR 2.4, 95% CI 1.4-4.1). CONCLUSION: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

Assessing the burden of bronchiolitis and lower respiratory tract infections in children ≤24 months of age in Italy, 2012-2019.

Background: Bronchiolitis is the most common lower respiratory tract infection (LRTI) in children and is mainly caused by the Respiratory Syncytial Virus (RSV). Bronchiolitis presents seasonally and lasts about five months, usually between October to March, with peaks of hospitalizations between December and February, in the Northern Hemisphere. The burden of bronchiolitis and RSV in primary care is not well understood. Materials and methods: This retrospective analysis used data from Pedianet, a comprehensive paediatric primary care database of 161 family paediatricians in Italy. We evaluated the incidence rates (IR) of all-cause bronchiolitis (ICD9-CM codes 466.1, 466.11 or 466.19), all-cause LRTIs, RSV-bronchiolitis and RSV-LRTIs in children from 0 to 24 months of age, between January 2012 to December 2019. The role of prematurity (<37 weeks of gestational age) as a bronchiolitis risk factor was evaluated and expressed as odds ratio. Results: Of the 108,960 children included in the study cohort, 7,956 episodes of bronchiolitis and 37,827 episodes of LRTIs were recorded for an IR of 47 and 221 × 1,000 person-years, respectively. IRs did not vary significantly throughout the eight years of RSV seasons considered, showing a seasonality usually lasting five months, between October and March, while the peak of incidence was between December and February. Bronchiolitis and LRTI IRs were higher during the RSV season, between October and March, regardless of the month of birth, with bronchiolitis IR being higher in children aged ≤12 months. Only 2.3% of bronchiolitis and LRTI were coded as RSV-related. Prematurity and comorbidity increased the risk of bronchiolitis; however, 92% of cases happened in children born at term, and 97% happened in children with no comorbidities or otherwise healthy. Conclusions: Our results confirm that all children aged ≤24 months are at risk of bronchiolitis and LRTI during the RSV season, regardless of the month of birth, gestational age or underlying health conditions. The IRs of bronchiolitis and LRTI RSV-related are underestimated due to the poor outpatient epidemiological and virological surveillance. Strengthening the surveillance system at the paediatric outpatient level, as well as at the inpatient level, is needed to unveil the actual burden of RSV-bronchiolitis and RSV-LRTI, as well as to evaluate the effectiveness of new preventive strategies for anti-RSV.

Retrospective Analysis of the Real-World Use of Topical Antimicrobials in the Paediatric Population with Impetigo in Italy: Focus on the Role of Ozenoxacin 1% Cream.

Using electronic data from a large population-based network of Family Paediatricians (Pedianet), we aimed to describe the use of topical antimicrobials, including ozenoxacin 1% cream, in impetigo in children in Italy. We included 2929 children aged 6 months-14 years from 2016 to 2019 with at least one episode of impetigo treated with topical antimicrobials. Overall, 3051 cases of impetigo were included in the analysis. Treatment started in most cases on the same day as the impetigo diagnosis and lasted around eight days. In about 8% of the cases, a systemic antibiotic was prescribed after the topical antimicrobial, usually after 4-14 days. In this study, ozenoxacin was used in 8% of the cases. Treatment duration was significantly shorter for patients prescribed ozenoxacin compared to the whole study population (median of six vs. seven days, respectively). In contrast, the rate of treatment failure was similar. Very few adverse reactions were identified.

Monitoring the Epidemiology of Otitis Using Free-Text Pediatric Medical Notes: A Deep Learning Approach.

Free-text information represents a valuable resource for epidemiological surveillance. Its unstructured nature, however, presents significant challenges in the extraction of meaningful information. This study presents a deep learning model for classifying otitis using pediatric medical records. We analyzed the Pedianet database, which includes data from January 2004 to August 2017. The model categorizes narratives from clinical record diagnoses into six types: no otitis, non-media otitis, non-acute otitis media (OM), acute OM (AOM), AOM with perforation, and recurrent AOM. Utilizing deep learning architectures, including an ensemble model, this study addressed the challenges associated with the manual classification of extensive narrative data. The performance of the model was evaluated according to a gold standard classification made by three expert clinicians. The ensemble model achieved values of 97.03, 93.97, 96.59, and 95.48 for balanced precision, balanced recall, accuracy, and balanced F1 measure, respectively. These results underscore the efficacy of using automated systems for medical diagnoses, especially in pediatric care. Our findings demonstrate the potential of deep learning in interpreting complex medical records, enhancing epidemiological surveillance and research. This approach offers significant improvements in handling large-scale medical data, ensuring accuracy and minimizing human error. The methodology is adaptable to other medical contexts, promising a new horizon in healthcare analytics.

The Economic Burden of Pneumococcal Disease in Children: A Population-Based Investigation in the Veneto Region of Italy.

Despite widespread childhood immunization programs, pneumococcal disease (PD) continues to be associated with significant clinical and economic burden worldwide. This retrospective study assessed the PD-related economic burden in children from the Veneto region of Italy following the introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) to the Italian immunization schedule in 2010. Between 2010 and 2017, the annual incidences of pneumonia, acute otitis media (AOM), and invasive pneumococcal disease (IPD), as well as syndromic-disease-related episodes, declined. In our analysis of data from regional expenditure and healthcare resource utilization (HCRU) databases related to children < 15 years of age, we found that regional expenditures decreased between 2010 and 2017 for pneumonia (EUR 8.88 to EUR 3.59 million), AOM (EUR 3.78 to EUR 2.76 million), and IPD (EUR 1.40 to EUR 1.00 million). Despite reductions in PD-related expenditure following the introduction of PCV13, there continues to be an economic burden associated with PD in Veneto, Italy.

A Deep Learning Approach to Estimate the Incidence of Infectious Disease Cases for Routinely Collected Ambulatory Records: The Example of Varicella-Zoster.

The burden of infectious diseases is crucial for both epidemiological surveillance and prompt public health response. A variety of data, including textual sources, can be fruitfully exploited. Dealing with unstructured data necessitates the use of methods for automatic data-driven variable construction and machine learning techniques (MLT) show promising results. In this framework, varicella-zoster virus (VZV) infection was chosen to perform an automatic case identification with MLT. Pedianet, an Italian pediatric primary care database, was used to train a series of models to identify whether a child was diagnosed with VZV infection between 2004 and 2014 in the Veneto region, starting from free text fields. Given the nature of the task, a recurrent neural network (RNN) with bidirectional gated recurrent units (GRUs) was chosen; the same models were then used to predict the children's status for the following years. A gold standard produced by manual extraction for the same interval was available for comparison. RNN-GRU improved its performance over time, reaching the maximum value of area under the ROC curve (AUC-ROC) of 95.30% at the end of the period. The absolute bias in estimates of VZV infection was below 1.5% in the last five years analyzed. The findings in this study could assist the large-scale use of EHRs for clinical outcome predictive modeling and help establish high-performance systems in other medical domains.

A Retrospective Analysis to Estimate the Burden of Invasive Pneumococcal Disease and Non-Invasive Pneumonia in Children <15 Years of Age in the Veneto Region, Italy

Despite advances in preventative interventions, invasive pneumococcal disease and pneumonia cause significant morbidity and mortality in children. We studied the annual incidence of pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia in children <15 years of age during the early (2010−2013) and late (2014−2017) 13-valent pneumococcal conjugate vaccine (PCV13) periods in Veneto, Italy. In this retrospective observational study, pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia cases were identified from several sources, including the Pedianet database. Interrupted time series analysis and Mann−Kendall tests were conducted to explore trends in incidence rates (IRs). Among 72,570 patients <15 years of age between 2010−2017, 88 episodes of pneumococcal-specific and syndromic invasive disease and 3926 episodes of non-invasive pneumonia were reported. Overall IR of pneumococcal-specific and syndromic invasive disease was 0.4/1000 person-years and did not change significantly (p = 0.46) throughout the study. Overall IR of non-invasive pneumonia was 10/1000 person-years and decreased significantly (−0.64, p = 0.026) over the study period. Following PCV13 introduction, the IRs of non-invasive pneumonia in children <15 years of age declined significantly, with no significant change in the IRs of pneumococcal-specific and syndromic invasive disease. There is a continuing clinical burden associated with pediatric pneumococcal diseases in Veneto, Italy.

Non-bullous Impetigo: Incidence, Prevalence, and Treatment in the Pediatric Primary Care Setting in Italy.

Impetigo is a common skin infection in children. The worldwide prevalence in children is estimated to be 12%, but this may be lower since high-income countries are under-represented. This research aims to evaluate the incidence, prevalence, and management of children with non-bullous impetigo (NBI) residing in Italy. This retrospective cohort study included children up to 14 years of age enrolled in the Pedianet database from January 2004 to June 2018. Events were identified searching ICD9-CM codes (684 and 694.3) and free text fields for a diagnosis of NBI reported during a primary care visit. Diagnoses were manually validated, and events registered within 30-days after the index date were considered follow-ups. Incidence (IR) and prevalence (PR) rates of NBI were stratified by sex, age group, and calendar year. Topical and systemic antibiotic treatments were grouped based on ATC codes. 15,136 NBI episodes occurred in a total cohort of 225,979 children. The overall IR of NBI was 9.5 per 1,000 person-years, and children aged 1-4 years had the highest IR (13.2 per 1,000 person-years). A significant decrease in NBI IR from 13 per 1,000 person-years in 2004 to 7.46 per 1,000 person-years in 2018 (p < 0.0001) was noted. Most of the episodes were treated; systemic antibiotics were preferred over topical. Conclusion: The prevalence of NBI in children in Italy is less than one third than the global estimate and the trend in time is decreasing. Over prescriptions of systemic antibiotics pose a threat to the diffusion of antimicrobial resistance.

A Retrospective Database Analysis to Estimate the Burden of Acute Otitis Media in Children Aged <15 Years in the Veneto Region (Italy)

This study aimed to assess trends in the incidence of acute otitis media (AOM), a common childhood condition, following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in the Veneto region of Italy in 2010. AOM episodes (overall, simple, and recurrent (≥3 or ≥4 episodes in 6 or 12 months, respectively, with ≥1 episode in the preceding 6 months)) in children <15 years of age were identified in Pedianet from 2010−2017. Interrupted time series analyses were conducted to assess changes in the annual incidence rates (IRs) in early (2010−2013) and late (2014−2017) PCV13 periods. In total, 72,570 children (402,868 person-years) were identified; 21,048 had 41,683 AOM episodes. Mean annual AOM IR was 103/1000 person-years (95% confidence interval: 102−104), decreasing from 126 to 79/1000 person-years. AOM IRs were highest in children 2−4 years of age, followed by <2 and 5−14 years of age. Overall and simple AOM IRs decreased among children 0−14 years of age, including 2−4 and 5−14 years of age, while recurrent AOM IRs decreased in children <2 years of age. Following PCV13 introduction, AOM IRs decreased substantially in children <15 years of age, with the greatest benefit observed in older children, driven by a reduction in simple AOM IRs. AOM disease burden remains substantial.

Use of the Bacterial Lysate OM-85 in the Paediatric Population in Italy: A Retrospective Cohort Study.

BACKGROUND: In Italy, the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®) is registered for the prophylaxis of recurrent respiratory tract infections (RTIs) in adults and children above one year of age, but there are limited data on its use in the paediatric population. We aim to estimate the impact of OM-85 treatment on RTIs and antibiotic prescriptions in children. METHODS: This study included children aged 1 to 14 years enrolled in Pedianet, a paediatric general practice research database, from January 2007 to June 2017, having at least one prescription of OM-85. Children with less than 12 months of follow-up before (PRE period) and after (POST period) the OM-85 prescription were excluded. The frequency of antibiotic prescriptions and the frequency of RTI episodes in the PRE and POST periods were compared through the post-hoc test. Subgroup analysis was performed in children with recurrent RTIs. RESULTS: 1091 children received 1382 OM-85 prescriptions for a total follow-up of 619,525.5 person-years. Overall, antibiotic prescriptions decreased from a mean of 2.8 (SD (standard deviation) 2.7) prescriptions in the PRE period to a mean of 2.2 (SD 2.6) prescriptions in the POST period (p < 0.0001). RTIs decreased from a mean of 3.4 (SD 2.9) episodes in the PRE period to a mean of 2.5 (SD 2.6) episodes in the POST period (p < 0.0001). No change in antibiotic class was noted, and co-amoxiclav remained the preferred therapy in 28% of cases, followed by amoxicillin. These results were confirmed among children with recurrent RTIs. CONCLUSIONS: OM-85 is effective in preventing both antibiotic prescriptions and RTIs in children.

Impact of bronchiolitis guidelines publication on primary care prescriptions in the Italian pediatric population.

In Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0-24 months before (December 2012-December 2014), in between (December 2014-December 2015) and after (December 2015-December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, ß2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p < 0.001) after the publication of the second guideline; the highest reduction was in younger patients (from 57% to 44%, p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications.

Antibiotic Prescriptions for Children With Community-acquired Pneumonia: Findings From Italy.

INTRODUCTION AND OBJECTIVE: Community-acquired pneumonia (CAP) is one of the most common reasons of prescribing antibiotics for children, often with overuse of broad-spectrum antibiotics. The aim of this study is to describe the antibiotic prescriptions for Italian children with CAP, at the primary care level. STUDY DESIGN: Retrospective cohort study conducted among children 3 months-14 years of age with CAP, enrolled in Pedianet (http://www.pedianet.it) from January 1, 2009 to December 31, 2018. Antibiotic treatment was defined as narrow-spectrum (NS-ABT) if amoxicillin and broad-spectrum (BS-ABT) if amoxicillin/clavulanic acid, cephalosporins or any combination. Crude and adjusted logistic regressions for the odds of receiving NS-ABT were conducted (all episodes of CAP and per patient). A P value <0.05 was considered statistically significant. RESULTS: Among 9691 CAP, 7260 episodes from 6409 children followed by 147 pediatricians were analyzed. The 16.7% of CAP [1216/7260, 95% confidence interval (CI): 15.9%-17.6%] received an NS-ABT while 53.3% (3863/7260, 95% CI: 52%-54.4%) received BS-ABTs and 30% (2181/7260, 95% CI: 28.9%-31.1%) macrolides. Within 10 years, a slight but increasing trend of NS-ABT prescription was observed (P < 0.001). Factors independently associated with reduced odds of receiving an NS-ABT compared with BS-ABT including macrolides were being older than 5 years [odds ratio (OR) 0.45, 95% CI: 0.39-0.52], living in Central/Southern Italy (OR 0.13, 95% CI: 0.10-0.16) and being exposed to ABT 3 months before (OR 0.61, 95% CI: 0.53-0.70). These findings were confirmed comparing NS-ABT versus BS-ABT excluding macrolides (n = 5079) and when the analysis was limited to index CAP. CONCLUSION: Our findings report a very limited prescription of narrow-spectrum antibiotics for Italian children with CAP.

Use of Machine Learning Techniques for Case-Detection of Varicella Zoster Using Routinely Collected Textual Ambulatory Records: Pilot Observational Study.

BACKGROUND: The detection of infectious diseases through the analysis of free text on electronic health reports (EHRs) can provide prompt and accurate background information for the implementation of preventative measures, such as advertising and monitoring the effectiveness of vaccination campaigns. OBJECTIVE: The purpose of this paper is to compare machine learning techniques in their application to EHR analysis for disease detection. METHODS: The Pedianet database was used as a data source for a real-world scenario on the identification of cases of varicella. The models' training and test sets were based on two different Italian regions' (Veneto and Sicilia) data sets of 7631 patients and 1,230,355 records, and 2347 patients and 569,926 records, respectively, for whom a gold standard of varicella diagnosis was available. Elastic-net regularized generalized linear model (GLMNet), maximum entropy (MAXENT), and LogitBoost (boosting) algorithms were implemented in a supervised environment and 5-fold cross-validated. The document-term matrix generated by the training set involves a dictionary of 1,871,532 tokens. The analysis was conducted on a subset of 29,096 tokens, corresponding to a matrix with no more than a 99% sparsity ratio. RESULTS: The highest predictive values were achieved through boosting (positive predicative value [PPV] 63.1, 95% CI 42.7-83.5 and negative predicative value [NPV] 98.8, 95% CI 98.3-99.3). GLMNet delivered superior predictive capability compared to MAXENT (PPV 24.5% and NPV 98.3% vs PPV 11.0% and NPV 98.0%). MAXENT and GLMNet predictions weakly agree with each other (agreement coefficient 1 [AC1]=0.60, 95% CI 0.58-0.62), as well as with LogitBoost (MAXENT: AC1=0.64, 95% CI 0.63-0.66 and GLMNet: AC1=0.53, 95% CI 0.51-0.55). CONCLUSIONS: Boosting has demonstrated promising performance in large-scale EHR-based infectious disease identification.

Preventing recurrent acute otitis media with Streptococcus salivarius 24SMB and Streptococcus oralis 89a five months intermittent treatment: An observational prospective cohort study.

INTRODUCTION: Acute otitis media (AOM) is the most common childhood disease leading to antibiotic use. More than 80% of children under three years of age experience at least one episode, and about one-third of these report significant recurrence of episodes. In recent years, several studies reported that normal nasopharyngeal flora inhibits growth of common otopathogens, suggesting that maintenance of an "adequate" nasopharyngeal flora might prevent occurrence of upper respiratory tract infections, including AOM. This study aims to determine whether five-month treatment with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray prevents recurrence of AOM and prescription of antibiotics in children with diagnosis of recurrent AOM. METHODS: Observational prospective cohort study including children aged 1-6 years with diagnosis of recurrent AOM registered with 31 Italian family pediatricians. 81 children were enrolled in the study from September 2016 to the end of the five therapeutic cycles of the Streptococcus salivarius 24SMB and Streptococcus oralis 89a supplied 7 days each month for 5 consecutive months. For each treated child, one untreated control was randomly selected, 1:1 matched for gender, age, and follow-up. RESULTS: 158 children (79 treated and 70 untreated) were included into the analysis (mean age, 3.9 years; 47% female). Univariate analysis showed a statistically significant 34% (95% CI 1%-56%) reduction in number of AOM episodes in treated children compared with those not treated. Significantly fewer antibiotics were dispensed among treated children (24%, 95% CI 1%-41%). CONCLUSIONS: Our findings suggest that intermittent treatment of children with diagnosis of recurrent AOM with nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a for a period of five months might be effective in preventing antibiotic use associated with recurrent episodes of AOM. Additional larger studies to address this important clinical problem are recommended.

Impact of a vaccination programme in children vaccinated with ProQuad, and ProQuad-specific effectiveness against varicella in the Veneto region of Italy.

BACKGROUND: Monovalent varicella vaccines have been available in the Veneto Region of Italy since 2004. In 2006, a single vaccine dose was added to the immunisation calendar for children aged 14 months. ProQuad®, a quadrivalent measles-mumps-rubella-varicella vaccine, was introduced in May 2007 and used, among other varicella vaccines, until October 2008. This study aimed to evaluate the effectiveness of a single dose of ProQuad, and the population impact of a vaccination program (VP) against varicella of any severity in children who received a first dose of ProQuad at 14 months of age in the Veneto Region, METHODS: All children born in 2006/2007, i.e., eligible for varicella vaccination after ProQuad was introduced, were retrospectively followed through individual-level data linkage between the Pedianet database (varicella cases) and the Regional Immunization Database (vaccination status). The direct effectiveness of ProQuad was estimated as the incidence rate of varicella in ProQuad-vaccinated children aged < 6 years compared to children with no varicella vaccination from the same birth cohort. The impact of the VP on varicella was measured by comparing children eligible for the VP to an unvaccinated historical cohort from 1997/1998. The vaccine impact measures were: total effect (the combined effect of ProQuad vaccination and being covered by the Veneto VP); indirect effect (the effect of the VP on unvaccinated individuals); and overall effect (the effect of the VP on varicella in the entire population of the Veneto Region, regardless of their vaccination status). RESULTS: The adjusted direct effectiveness of ProQuad was 94%. The vaccine impact measures total, indirect, and overall effect were 97%, 43%, and 90%, respectively. CONCLUSIONS: These are the first results on the effectiveness and impact of ProQuad against varicella; data confirmed its high effectiveness, based on immunological correlates for protection. Direct effectiveness is our only ProQuad-specific measure; all impact measures refer at least partially to the VP and should be interpreted in the context of high vaccine coverage and the use of various varicella vaccines in this region. The Veneto Region offered a unique opportunity for this study due to an individual data linkage between Pedianet and the Regional Immunization database.

Galacto-Oligosaccharide/Polidextrose Enriched Formula Protects against Respiratory Infections in Infants at High Risk of Atopy: A Randomized Clinical Trial.

BACKGROUND: Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide/polydextrose (GOS/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes. METHODS: A total of 201 and 199 infants were randomized to receive a PF and standard formula (SF), respectively; 140 infants remained on exclusive breastfeeding (BF). RESULTS: The cumulative incidence of AD and its intensity and duration were not statistically different among the three groups. The number of infants with at least one episode of respiratory infection (RI) and the mean number of episodes until 48 weeks of age were significantly lower in the PF group than in the SF group. The number of patients with recurrent RIs and incidence of wheezing lower RIs until 96 weeks were lower in the PF group than the SF group, but similar to the BF group. Bifidobacteria and Clostridium cluster I colonization increased over time in the PF group but decreased in the SF and BF groups. Bifidobacteria had a protective role in RIs, whereas Clostridium cluster I was associated with atopy protection. CONCLUSION: The early administration of PF protects against RIs and mediates a species-specific modulation of the intestinal microbiota. TRIAL REGISTRATION: clinicaltrial.gov Identifier: NCT02116452.

Epidemiology of Frequently Occurring Skin Diseases in Italian Children from 2006 to 2012: A Retrospective, Population-Based Study.

BACKGROUND: Recent estimates indicate an increase in the prevalence of skin diseases in children. Few large epidemiologic studies have examined prevalence trends in Europe. This study evaluated the incidence and prevalence of frequently occurring pediatric skin diseases (PSDs) in Italy as seen by family pediatricians (FPs). METHODS: Data were retrospectively extracted from the Pedianet database (2006-2012) in children ages 0 to 14 years presenting with a skin disease at their FP. The incidence and prevalence estimates were calculated per year and stratified according to sex, age, and geographic area. RESULTS: A mean of 145,233 children (52.1% male) across five Italian regions were registered with their participating FP for a total of 913,253 person-years of follow-up. The majority of patients were from the northeast (44.6%) and 37.7% were ages 5-9 years. Incidence estimates (new cases/1,000 person-years) for most PSDs increased from 2006 to 2012, the highest being for atopic dermatitis (AD) (14.1 vs 16.5), acute urticaria (10.1 vs 11.6), and contact dermatitis (9.3 vs 10.8), whereas psoriasis remained unchanged over the 7 years (0.61 vs 0.57). In contrast, prevalence estimates (cases/100 patients) increased two to three times for several PSDs, including AD (2.7% vs 8.5%), seborrheic dermatitis (0.5% vs 1.6%), chronic urticaria (0.4% vs 0.8%), and psoriasis (0.09% vs 0.22%). Differences in prevalence according to age range and geographic area were observed for psoriasis, AD, and urticaria. CONCLUSION: This study provides comprehensive evidence of the increasing prevalence and incidence of PSDs across Italy. Additional causality studies to address this important clinical and psychosocial problem are recommended.

Burden of acute otitis media in primary care pediatrics in Italy: a secondary data analysis from the Pedianet database.

BACKGROUND: The incidence of acute otitis media (AOM) vary from country to country. Geographical variations together with differences in study designs, reporting and settings play a role. We assessed the incidence of AOM in Italian children seen by primary care paediatricians (PCPs), and described the methods used to diagnose the disease. METHODS: This secondary data analysis from the Pedianet database considered children aged 0-6 years between 01/2003 and 12/2007. The AOM episodes were identified and validated by means of patient diaries. Incidence rates/100 person-years (PY) were calculated for total AOM and for single or recurrent AOM. RESULTS: The 92,373 children (52.1% males) were followed up for a total of 227,361 PY: 23,039 (24.9%) presented 38,241 episodes of AOM (94.6% single episodes and 5.4% recurrent episodes). The total incidence rate of AOM in the 5-year period was 16.8 episodes per 100 PY (95% CI: 16.7-16.9), including single AOM (15.9 episodes per 100 PY; 95% CI: 15.7-16.1) and recurrent AOM (0.9 episodes per 100 PY; 95% CI: 0.9-0.9). There was a slight and continuously negative trend decrease over time (annual percent change -4.6%; 95%CI: -5.3, -3.9%). The AOM incidence rate varied with age, peaking in children aged 3 to 4 years (22.2 episodes per 100 PY; 95% CI 21.8-22.7). The vast majority of the AOM episodes (36,842/38,241, 96.3%) were diagnosed using a static otoscope; a pneumatic otoscope was used in only 3.7%. CONCLUSIONS: Our data fill a gap in our knowledge of the incidence of AOM in Italy, and indicate that AOM represents a considerable burden for the Italian PCP system. Educational programmes concerning the diagnosis of AOM are needed, as are further studies to monitor the incidence in relation to the introduction of wider pneumococcal conjugate vaccines.