Change-point estimation in piecewise constant regression models and extensions

Short-Term Effects of Air Pollution on Cardiovascular Hospitalizations in the Pisan Longitudinal Study

Air pollution effects on cardiovascular hospitalizations in small urban/suburban areas have been scantly investigated. Such effects were assessed among the participants in the analytical epidemiological survey carried out in Pisa and Cascina, Tuscany, Italy (2009–2011). Cardiovascular hospitalizations from 1585 subjects were followed up (2011–2015). Daily mean pollutant concentrations were estimated through random forests at 1 km (particulate matter: PM10, 2011–2015

Inferential tools in penalized logistic regression for small and sparse data: A comparative study.

This paper focuses on inferential tools in the logistic regression model fitted by the Firth penalized likelihood. In this context, the Likelihood Ratio statistic is often reported to be the preferred choice as compared to the ‘traditional’ Wald statistic. In this work, we consider and discuss a wider range of test statistics, including the robust Wald, the Score, and the recently proposed Gradient statistic. We compare all these asymptotically equivalent statistics in terms of interval estimation and hypothesis testing via simulation experiments and analyses of two real datasets. We find out that the Likelihood Ratio statistic does not appear the best inferential device in the Firth penal…

Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial

<b><i>Background:</i></b> Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. <b><i>Methods:</i></b> In this 21-day,<b> </b>open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS…

An open-safety study of dual antiviral therapy in real-world patients with chronic hepatitis C

Purpose Treatment of patients with chronic hepatitis C with alpha-interferon and ribavirin usually produces adverse events within the first 3 months. We aimed to assess safety and predictors of discontinuation or dose modification of these drugs. Methods Observational study of 312 patients with predominantly genotype 1 chronic hepatitis C treated openly along 5 years in a clinical practice setting. Results Eighty-four percent of patients experienced at least one adverse event (853 events in total, 3.3 per patient on average). Incidence rate was higher during the first 90 days and decreased thereafter (<5%). Discontinuation rates at 30 and 90 days and at end of treatment were 2, 4 and 8%, re…

Feasibility of the Allergy Questionnaire for Athletes (AQUA © ) in pediatric age

A burden of respiratory and allergic symptoms up to almost 60% has been observed in young and adult athletes, influencing physical performances1 . The Allergy Questionnaire for Athletes (AQUA©) is a validated screening tool for the prediction of the atopic status in adult athletes2 ; it was recently tested in Belgian young elite athletes (12-14 years old)3 , but its actual feasibility and suitability for children and adolescent was not evaluated. Indeed, there is evidence that children are prone to employ "satisficing" response strategies, answering every question positively/negatively, or simply not answering4 . Therefore, the present cross-sectional survey was carried out to assess feasib…

A Critical Review of Statistical Methods for Twin Studies Relating Exposure to Early Life Health Conditions

International audience; When investigating disease etiology, twin data provide a unique opportunity to control for confounding and disentangling the role of the human genome and exposome. However, using appropriate statistical methods is fundamental for exploiting such potential. We aimed to critically review the statistical approaches used in twin studies relating exposure to early life health conditions. We searched PubMed, Scopus, Web of Science, and Embase (2011–2021). We identified 32 studies and nine classes of methods. Five were conditional approaches (within-pair analyses): additive-common-erratic (ACE) models (11 studies), generalized linear mixed models (GLMMs, five studies), gene…

Machine learning: A modern approach to pediatric asthma

Among modern methods of statistical and computational analysis, the application of machine learning (ML) to healthcare data has been gaining recognition in helping us understand the heterogeneity of asthma and predicting its progression. In pediatric research, ML approaches may provide rapid advances in uncovering asthma phenotypes with potential translational impact in clinical practice. Also, several accurate models to predict asthma and its progression have been developed using ML. Here, we provide a brief overview of ML approaches recently proposed to characterize pediatric asthma.

Pharmacogenomics: A Step forward Precision Medicine in Childhood Asthma.

Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, …

Association between Asthma Control and Exposure to Greenness and Other Outdoor and Indoor Environmental Factors: A Longitudinal Study on a Cohort of Asthmatic Children

Achieving and maintaining asthma control (AC) is the main goal of asthma management. Indoor and outdoor environmental factors may play an important role on AC. The aim of this longitudinal study was to evaluate the association between AC and exposure to greenness and other outdoor or indoor environmental factors in a cohort of asthmatic children. This study involved 179 asthmatic children (5&ndash;16 years). Parents were interviewed through a modified version of the SIDRIA questionnaire. AC was assessed at each visit. Exposure to greenness was measured using the normalized difference vegetation index (NDVI). A logistic regression model was applied for assessing risk factors for uncontrolled…

Additional file 1: of Associations of greenness, greyness and air pollution exposure with childrenâ s health: a cross-sectional study in Southern Italy

Table S1. Risk factors for self-reported ocular, nasal, pulmonary and general symptoms from children questionnaires: estimated odds ratios (OR) and 95% confidence intervals (95% CI) from univariable logistic regression models. Table S2. Risk factors for self-reported ocular, nasal, pulmonary and general symptoms from children questionnaires: estimated odds ratios (OR) and 95% confidence intervals (95% CI) from multivariable logistic ridge regression models using the full quartile for NDVI and NO2. Table S3 Multivariable Poisson ridge regression models, using the full quartile for NDVI and NO2, for symptoms score: estimated rate ratios (RR) and 95% confidence intervals (95% CI). (DOCX 25 kb)

Latent class identification in wheezing preschool children

Background and aim Since the forced oscillation technique (FOT) has not been used in previous studies on wheezing phenotyping in preschool children, we applied FOT in a large series of outpatients visited at IBIM. Methods We analyzed 256 consecutively enrolled ≤5 years children with doctor diagnosis of wheezing. Latent Class Analysis (LCA) was performed considering the following personal characteristics: type, cause, recurrence in last 12 months, respiratory resistance (Avr_R(8)), atopy, history of eczema, rhinitis and upper airways infections. High resistance is defined as positive residual of regression on sex, age, height and weight. Risk factors were considered meaningful when they yiel…

Asthma-Related Knowledge and Practices among Mothers of Asthmatic Children: A Latent Class Analysis

Mothers&rsquo; knowledge about childhood asthma influences management practices and disease control, but validating knowledge/practice questionnaires is difficult due to the lack of a gold standard. We hypothesized that Latent Class Analysis (LCA) could help identify underlying mother profiles with similar knowledge/practices. A total of 438 mothers of asthmatic children answered a knowledge/practice questionnaire. Using answers to the knowledge/practice questionnaire as manifest variables, LCA identified two classes: Class 1, &ldquo;poor knowledge&rdquo; (33%); Class 2, &ldquo;good knowledge&rdquo; (67%). Classification accuracy was 0.96. Mothers in Class 2 were more likely to be aware of …

Machine Learning: An Overview and Applications in Pharmacogenetics.

This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant, anti-cancer and warfarin drugs) over the past 10 years. ML deals with the study, the design and the development of algorithms that give computers capability to learn without being explicitly programmed. ML is a sub-field of artificial intelligence, and to date, it has demonstrated satisfactory performance on a wide range of tasks in biomedicine. According to the final goal, ML can be defined as Supervised (SML) or as Unsupervised (UML). SML techniques are applied when prediction is the focus of the research. On the other hand, UML…

Effects of Particulate Matter on the Incidence of Respiratory Diseases in the Pisan Longitudinal Study

The current study aimed at assessing the effects of exposure to Particulate Matter (PM) on the incidence of respiratory diseases in a sub-sample of participants in the longitudinal analytical epidemiological study in Pisa, Italy. Three hundred and five subjects living at the same address from 1991 to 2011 were included. Individual risk factors recorded during the 1991 survey were considered, and new cases of respiratory diseases were ascertained until 2011. Average PM10 and PM2.5 exposures (&micro

Associations of greenness, greyness and air pollution exposure with children's health: a cross-sectional study in Southern Italy

Background Due to the complex interplay among different urban-related exposures, a comprehensive approach is advisable to estimate the health effects. We simultaneously assessed the effect of “green”, “grey” and air pollution exposure on respiratory/allergic conditions and general symptoms in schoolchildren. Methods This study involved 219 schoolchildren (8–10 years) of the Municipality of Palermo, Italy. Data were collected through questionnaires self-administered by parents and children. Exposures to greenness and greyness at the home addresses were measured using the normalized difference vegetation index (NDVI), residential surrounding greyness (RSG) and the CORINE land-cover classes (C…

The Dietary Inflammatory Index and asthma burden in children: A latent class analysis

Introduction: Unbalanced dietary intake has been increasingly recognized as an important modifiable risk factor for asthma. In this study, we assessed whether a pro-inflammatory diet is associated with higher asthma burden in three steps: (1) identification of asthma latent classes (LC) based on symptoms, indoor exposures, and pulmonary function; (2) identification of risk factors associated with LC membership; and (3) estimation of the probabilities of LC membership with variation in DII. Methods: A cross-sectional study on 415 children aged 5–14 years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquant…

Rhinomanometry: point of care test (POCT) for allergic rhinitis in children?

Allergic rhinitis (AR) is a global health problem: its prevalence is 23% in Europe, although it is underestimated because as many as 45% of the cases remain undiagnosed. Globally, almost 500 million people suffer from AR, which shows its increasing incidences. The diagnostic course of AR is based on clinical history, supported by anterior rhinoscopy. This inspects the anterior part of the nasal cavity accompanied by allergic sensitivity tests (cutaneous allergic skin tests or specific immunoglobulin E levels). The availability of standardised diagnostic proceduresis able to provide objective evaluations of inflammatory situation, and the degree of nasal obstruction may give an advantage in …

Penalized logistic regression for small or sparse data: interval estimators revisited

This paper focuses on interval estimation in logistic regression models fitted through the Firth penalized log-likelihood. In this context, many authors have claimed superiority of the Likelihood ratio statistic with respect to the (wrong) Wald statistic via simulation evidence. We re-assess such findings by detailing the inferential tools also including in the comparisons the (right) Wald statistic and other statistics neglected in previous literature. In particular, we assess performances of the CIs estimators by simulation and compare them in a real data set. Differently from previous findings, the Likelihood ratio statistic does not appear to be the best inferential device in Firth pena…

Overrating Classifier Performance in ROC Analysis in the Absence of a Test Set: Evidence from Simulation and Italian CARATkids Validation

Background The use of receiver operating characteristic curves, or “ROC analysis,” has become quite common in biomedical research to support decisions. However, sensitivity, specificity, and misclassification rates are still often estimated using the training sample, overlooking the risk of overrating the test performance. Methods A simulation study was performed to highlight the inferential implications of splitting (or not) the dataset into training and test set. The normality assumption was made for the classifier given the disease status, and the Youden's criterion considered for the detection of the optimal cutoff. Then, an ROC analysis with sample split was applied to assess the disc…

Personal and Environmental Risk Factors at Birth and Hospital Admission: Direct and Vitamin D-Mediated Effects on Bronchiolitis Hospitalization

Abstract: Seasonal variations in UV-B radiation may influence vitamin D status, and this, in turn, may influence the risk of bronchiolitis hospitalization. The aim of this study was using a causal inference approach to investigate, simultaneously, the interrelationships between personal and environmental risk factors at birth/hospital admission (RFBH), serum vitamin D levels and bronchiolitis hospitalization. A total of 63 children (<2 years old) hospitalized for bronchiolitis (34 RSV-positive) and 63 controls were consecutively enrolled (2014-2016). Vitamin D levels and some RFBH (birth season, birth weight, gestational age, gender, age, weight, hospitalization season) were recorded. The d…

Salt intake and asthma in children and adolescents

Comparative Effect of Beclomethasone Dipropionate and Cetirizine on Acoustic Rhinometry Parameters in Children With Perennial Allergic Rhinitis: A Randomized Controlled Trial.

Background and objectives The effect of intranasal corticosteroids and oral antihistamines on acoustic rhinometry parameters has not been directly compared. The primary objective was to compare the effect of a 21-day course of treatment with nasal beclomethasone dipropionate (nBDP) with that of cetirizine (CTZ) on nasal patency measured using acoustic rhinometry in children with perennial allergic rhinitis (PAR). The secondary objective was to compare the effect of both drugs on nasal cytology, symptom severity, sleep quality, and quality of life. Methods In this 21-day, open-label, randomized controlled study, 34 children with PAR (age 6-14 years) with a Total 5-Symptom Score (T5SS) ≥5 rec…

Assessing Repeatability and Reproducibility of Anterior Active Rhinomanometry (AAR) in Children

AbstractBackgroundRepeatability and reproducibility are essential for clinicians for several purposes. Although discouraged, use of the Coefficient of Variation (CV) for assessing repeatability and reproducibility, rather than the Intraclass Correlation Coefficient (ICC), is still widespread. The aim of the present study was to highlight how using inappropriate indices may lead to misleading results, and this is done by simulation study and using real data on Anterior Active Rhinomanometry (AAR) in both healthy children and ones with rhinitis.MethodsA simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and …

From research question to dissemination: how to design, analyse and present study results

Today, the term “study” is very frequently used in quite a broad sense: survey, clinical trial, analysis, research and other terms with deeply different meanings are often generally indicated as “studies”. A “study” can be generally defined as a process composed of several actions aimed to verify one or more hypotheses (objectives), with the ultimate goal of sharing the answers (results) with a target audience, in the form of a scientific paper, presentation or poster.

Our Assessment Using Palate Postoperative Problems Score (PPOPS): Tool for the Evaluation of Results in Palatal Surgery Techniques

Obstructive sleep apnoea syndrome is a chronic condition characterized by frequent episodes of collapse of upper airways during sleep. Prevalence of the disease is settled at about 3–7%. Today, palatal surgery is a reference point in OSAHS treatment and there are many different surgical techniques. The purpose of our work is to compare post-operative results of palate surgery techniques used in our practice in OSAHS patients, studying the degree of patients’ satisfaction with a recent score recommended by Rashwan et al. called PPOPS (Palate Post-Operative Problems Score). A retrospective study was performed on a sample of 40 patients subject to different palate surgery techniques for OSAS. …

New technologies for promoting physical activity in healthy children and in children with chronic respiratory diseases: A narrative review

Physical activity (PA) is proven to benefit children and adolescents in several ways. New technologies may provide children with stimulating modalities for organizing their leisure time, accessing fitness programs, and obtaining daily goal reminders and peer support. Due to the current COVID-19 pandemic, following WHO recommendations for PA is difficult for many children, especially for those living in urban areas. Therefore, the use of digital tools to support and maintain PA could be useful in healthy children, as well as in those with chronic respiratory diseases (CRDs). This narrative review aims to summarize the most recent evidence about the role of new technologies in promoting PA in…

Association between greenspace and lung function in Italian children-adolescents

Background: Few studies have examined the impact of urban greenspace exposure on lung function in children-adolescents, and the available evidence is still inconsistent. The aim of the current study was to verify the hypothesis that the effects of greenspace exposure vary with differing levels of lung function of children-adolescents. Methods: Between November 2005 and May 2006, 2150 children-adolescents (age-range: 10-15 years) living in the city of Palermo were enrolled in a cross-sectional survey. Parents were interviewed through a modified version of the Italian Studies on Respiratory Disorders in Children and the Environment (SIDRIA) questionnaire. All children-adolescents performed sp…

Global Lung Function Initiative 2012 reference values for spirometry in South Italian children

Rationale Despite the widespread use of the Global Lung Function Initiative (GLI) 2012 reference values, there is still the need of testing their applicability in local areas. Objectives The aims of this study are to evaluate applicability of GLI reference equations in a large population-based sample of normal schoolchildren from Sicily, and to compare GLI and previous prediction equations in terms of spirometry test interpretation. Methods GLI equations were evaluated in 1243 normal schoolchildren, 49% males, aged 7–16 years, height 116–187 cm. Normality assumptions for the GLI z-scores (FEV1, FVC, FEV1/FVC) were tested, and bootstrap confidence intervals for the mean (0 expected) and …

Artificial intelligence in the diagnosis of pediatric allergic diseases.

Abstract: Artificial intelligence (AI) is a field of data science pertaining to advanced computing machines capable of learning from data and interacting with the human world. Early diagnosis and diagnostics, self-care, prevention and wellness, clinical decision support, care delivery, and chronic care management have been identified within the healthcare areas that could benefit from introducing AI. In pediatric allergy research, the recent developments in AI approach provided new perspectives for characterizing the heterogeneity of allergic diseases among patients. Moreover, the increasing use of electronic health records and personal healthcare records highlighted the relevance of AI in …

Lower probability of FEV1 improvement in asthmatic children exposed to passive smoke

Background: Guidelines advocate the use of spirometry to assess lung function in asthmatic. Inhaled corticosteroid(ICS) therapy is a mainstay of treatment for asthma, but the clinical response is variable. Aim: To assess the time variation of FEV1% in treated children with Persistent Asthma (PA). Methods: 110 children with PA, with two visits between September 2011 and December 2014 at the IBIM pediatric clinic were studied. Spirometry was performed using Pony FX, Cosmed, Italy; values were expressed as %pred using GLI-2012equation. The time trend of FEV1% for each subject was estimated through separate regressions. A linear regression model for the individual slopes (FEV1% average month va…

A model-based approach for assessing bronchodilator responsiveness in children: The conventional cutoff revisited

An increase in FEV1 >=12% has been proposed in international guidelines as a clue to airway reversibility for diagnosing asthma in both adults and children. However, the validity of this cut-off has been questioned in the pediatric population. The aim of this study was to provide evidence that different cut-off values in BDR may be associated with better performance in discriminating among outpatient children with naïve asthma (A) and without asthma (NA). We compared three approaches: i) the conventional cutoff (12%); ii) the cut-off estimated by Youden's criteria; and iii) the cut-off based on a model-driven approach. we found that the conventional cut-off of 12% showed poor sensitivity in…

Endotyping allergic rhinitis in children: A machine learning approach.

Introduction: The diversity of allergic rhinitis (AR) phenotypes is particularly evident in childhood, suggesting the need to analyze and identify new approaches to capture such clinical heterogeneity. Nasal cytology (NC) is a very useful diagnostic tool for identifying and quantifying nasal inflammation. Data-driven approaches such as latent class analysis (LCA) assign subjects to classes based on their characteristics. We hypothesized that LCA based on NC, including the assessment of neutrophils, eosinophils, and mast cells, may be helpful for identifying AR endotypes in children. Methods: A total of 168 children were enrolled. Sociodemographic characteristics and detailed medical history…

Nasal budesonide efficacy for nasal nitric oxide and nasal obstruction in rhinitis

Nasal nitric oxide (nNO) is a noninvasive tool that may be helpful in evaluating the inflammatory status in the upper airways [1]. Previous studies report that nNO is elevated in children with Allergic Rhinitis (AR) [2], especially in perennial sensitized subjects [3], and that it may be affected by topical administration of intranasal steroids (INSs) [4]. This article is protected by copyright. All rights reserved.

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molec…

Repeatability of exhaled breath fingerprint collected by a modern sampling system in asthmatic and healthy children

E-noses provide potential non-invasive metabolic biomarkers for diagnosing and monitoring pulmonary diseases. The primary aim of the present study was to assess the within-day and between-day repeatability of a modern breath sampling system (Pneumopipe® plus an array of e-nose sensors) in asthmatic and healthy children. The secondary aim was to compare the repeatability of the breath sampling system, spirometry and exhaled nitric oxide (eNO). Fifteen children (age 6-11 years) with asthma and thirty healthy children matched by age and gender (1:2 allocation) were recruited; of them, three healthy children did not complete the study. All measurements were collected twice during the baseline v…

Inquinamento ambientale, fumo e asma grave

The health burden of air pollution on the world’s children is immense. Environmental factors are responsible for an estimated 26% of all children’s death worldwide. A large body of research exists on the effects of air pollution on children’s health, including effects on fetal growth, birth outcomes, lung development and function, asthma, respiratory infection and otitis media. It is also clearly linked to a higher risk of developing asthma, a major cause of morbidity in children. Indoor environments contribute significantly to total human exposure to air pollutants. Overall, people spend most time indoors. Pollutants remain in the air longer inside than outside. Some pollutants may be two …

Personal and Environmental Risk Factors at Birth and Hospital Admission: Direct and Vitamin D-Mediated Effects on Bronchiolitis Hospitalization in Italian Children

Seasonal variations in UV-B radiation may influence vitamin D status, and this, in turn, may influence the risk of bronchiolitis hospitalization. The aim of this study was using a causal inference approach to investigate, simultaneously, the interrelationships between personal and environmental risk factors at birth/hospital admission (RFBH), serum vitamin D levels and bronchiolitis hospitalization. A total of 63 children (&lt

Rhinomanometry: point of care test (POCT) for allergic rhinitis in children?

Allergic rhinitis (AR) is a global health problem: its prevalence is 23% in Europe, although it is underestimated because as many as 45% of the cases remain undiagnosed. Globally, almost 500 million people suffer from AR, which shows its increasing incidences. The diagnostic course of AR is based on clinical history, supported by anterior rhinoscopy. This inspects the anterior part of the nasal cavity accompanied by allergic sensitivity tests (cutaneous allergic skin tests or specific immunoglobulin E levels). The availability of standardised diagnostic procedures is able to provide objective evaluations of inflammatory situation, and the degree of nasal obstruction may give an advantage in…

Resolvin D1 and miR‐146a are independent distinctive parameters in children with moderate and severe asthma

To date, a large number of mediators and biomarkers have been detected in childhood asthma, with a potential role in monitoring the disease course. Lung function evaluation through spirometry, forced oscillation technique and multiple breath washout proved its role in asthma monitoring, especially for investigating small airway impairment in children with more severe symptoms. Recently, novel specialized pro-resolving mediators, such as resolvins and lipoxins, have been recognized as crucial in promoting the resolution of lung inflammation. Increasing evidence suggests that miRNAs are crucially entailed in asthma. Partial least squares discriminant analysis (plsDA) is a modern technique for…

Respiratory disease phenotypes in a general population sample: latent transition analysis

Background: Few data are available on the temporal pattern of respiratory disease phenotypes in general population. Aim: To detect longitudinal patterns of disease phenotypes related to risk factors and physician visits. Methods: Pisan general population sample from 2 cross-sectional studies (PI1: 1991-93; PI2: 2009-11; n=1107), questionnaire-based data. Latent transition analysis (LTA) was performed to assess respiratory disease phenotypes at PI1 and PI2, labelled according to disease/symptom occurrence. Possible patterns were persistence, worsening and improvement of the phenotype. Multiple logistic regression models were estimated to assess the association among phenotype patterns, risk …

An association analysis to identify genetic variants linked to asthma and rhinoconjunctivitis in a cohort of Sicilian children

Abstract Asthma and rhino-conjunctivitis are common chronic diseases in childhood. In this cross-sectional study, we performed a gene association analysis with current asthma and rhino-conjunctivitis in a cohort of Sicilian children aged 10–15 years. Overall, our findings reveal the importance of different genetic variants at 4p14, 16p12.1, 17q12, 6p12.2 and 17q21.1, identifying possible candidate genes responsible for susceptibility to asthma and rhino-conjunctivitis.

The induced smoothed LASSO

We propose a new lasso-type estimator of regression coefficients for regression models. Our proposal relies on the recent idea of induced smoothing and leads to estimators with sampling distribution somewhat close to the Normal one, regardless of their true value, along with the corresponding reliable covariance matrix. As a consequence inference (e.g. p-values) may be carried out relatively easily. We present results from some simulation experiments.

Validity and repeatability of the Pediatric Allergy Questionnaire for Athletes (AQUAped) for the screening of atopy.

BACKGROUND High atopy prevalence has been reported in athletes. Having an age-specific questionnaire for predicting atopy is important for an optimal management of young athletes. The study objectives were as follows: (i) developing a scoring system for the Pediatric Allergy Questionnaire for Athletes (AQUAped); (ii) identifying the optimal age target within the range 7-14 years; (iii) assessing AQUAped validity and repeatability in the identified target population. METHODS A total of 133 young athletes (age 7-14 years) were recruited. Following a screening visit, the participants filled AQUAped at baseline (T0) and after 7 days (T1), concomitantly undergoing skin prick testing. Using atopy…

Rapid systematic review shows that using a high-flow nasal cannula is inferior to nasal continuous positive airway pressure as first-line support in preterm neonates.

Aim We reviewed using a high-flow nasal cannula (HFNC) as first-line support for preterm neonates with, or at risk of, respiratory distress. Methods This rapid systematic review covered biomedical databases up to June 2017. We included randomised controlled trials (RCTs) published in English. The reference lists of the studies and relevant reviews we included were also screened. We performed the study selection, data extraction, study quality assessment, meta-analysis and quality of evidence assessment following the Grading of Recommendations Assessment, Development and Evaluation system. Results Pooled results from six RCTs covering 1227 neonates showed moderate-quality evidence that HFNC …

Measuring lung function in asthmatic children: A spirometry and forced oscillation technique (FOT) comparison

Background: Spirometry is the most common pulmonary function test used in asthma diagnosing. However, it requires good patient co-operation. FOT has gained increasing attention for the measurement of pulmonary function in children because it is performed at steady state breathing. Aim: To compare spirometry and FOT in order to discriminate severity of asthma according to GINA. Methods: Spirometry and FOT were performed in 176 out-patient asthmatic children (5-16 year), 100 (57%) with naive Persistent Asthma (PA) and 76 (43%) with Intermittent Asthma (IA), consecutively enrolled at the IBIM pediatric clinic. Two principal component analyses (PCA) were performed, the first (PCA1) based on FEV…

Change-point estimation in piecewise constant regression models with random effects

We propose an iterative algorithm to estimate change-points in general regression models. The algorithm avoids grid search to obtain maximum likelihood estimates, and thus it guarantees moderate computational time regardless of the sample size and the number of change-points to be estimated. Furthermore, it allows estimation in random effects models, where grid search is unfeasible. We present the proposed approach in practice by analyzing variations of lung functionality on a sample of transplant recipients.

The Effect of Outdoor Aeroallergens on Asthma Hospitalizations in Children in North-Western Tuscany, Italy.

Few data are currently available on the effects of aeroallergens in triggering respiratory symptoms in children. To evaluate the potential effects of daily outdoor aeroallergens loads on childhood admissions, in this case-crossover study, we analyzed data from 85 children hospitalized at the University Hospital of Pisa, Italy, for asthma or asthma-like symptoms without respiratory infection, between 2010 and 2019. Data were linked to outdoor allergens, temperature, nitrogen dioxide, and relative humidity observed during the same period. A 10-grains/m3 increase in the total aeroallergen concentration was associated with an increased risk of admission at lag 0 (OR = 1.054, 95% CI: 1.011&ndash…

A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction t…

RAPP-children: A new tool for assessing quality of life in patients with asthma and rhinitis

Background: RhinAsthma Patient Perspective (RAPP) is a short, validated questionnaire for assessing health-related quality of life (HRQoL) in adult patients with comorbid asthma and rhinitis, while a paediatric version is still not available. Objective: The current study aimed to develop and validate the RAPP-children questionnaire. Methods: RAPP-children was derived by combining RhinAsthma-children subscales into five unique items. At baseline (T0) and after 30 days (T1), 150 children (6-11 years) with comorbid asthma (predominantly intermittent or mild persistent) and rhinitis were given the following: RAPP-children, RhinAsthma-children, Paediatric Asthma Quality of Life Questionnaire (PA…

Robotic-Assisted Neck Dissection: Our Experience

Abstract Introduction Robotic neck dissection surgery allows less invasiveness to significantly improve the aesthetic impact even though it does not compromise the principles of radical cancer procedure. Objective The aim of our work is to describe our personal experience with robotic neck dissection surgery. Methods A retrospective study was conducted by analyzing 10 patients subjected to a robotic neck dissection surgery. In the period from August 2012 to December 2018, these patients have been treated exclusively with robotic lateral-cervical dissection. Five of them were subjected to robotic-assisted transaxillary neck dissection (RATAND) and the other 5 treated with robotic-assisted re…

Flexible latent trait aggregation to analyze employability after the Ph.D. in Italy

The analysis of satisfaction, employability and economic perspectives after the Ph.D. in Italy has not received adequate attention in the past, especially in terms of comparison among universities. To analyze these aspects, in this paper we consider data from the survey ‘Statistica in TEma di Laureati e LAvoro’ on doctors who achieved the title on 2007, 2008 and 2009 [CILEA, Laureati STELLA, indagine occupazionale post-dottorato, dottori di ricerca 2007–2008, Tech. Rep., CILEA, Segrate, 2010; CILEA,Laureati STELLA, indagine occupazionale post-dottorato, dottori di ricerca 2008–2009, Tech. Rep., CILEA, Segrate, 2011]. To deal with the complex, multidimensional nature of the concept, we propo…

A heuristic, iterative algorithm for change-point detection in abrupt change models

Change-point detection in abrupt change models is a very challenging research topic in many fields of both methodological and applied Statistics. Due to strong irregularities, discontinuity and non-smootheness, likelihood based procedures are awkward; for instance, usual optimization methods do not work, and grid search algorithms represent the most used approach for estimation. In this paper a heuristic, iterative algorithm for approximate maximum likelihood estimation is introduced for change-point detection in piecewise constant regression models. The algorithm is based on iterative fitting of simple linear models, and appears to extend easily to more general frameworks, such as models i…

Cluster analysis of clinical data reveals three pediatric eosinophilic gastrointestinal disorder phenotypes

Primary eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of emerging inflammatory diseases, which may involve any part of the gastrointestinal (GI) tract and lead to a pathological eosinophilic mucosal infiltration.1,2 Based on the anatomical site of the eosinophil inflammation, EGIDs are classified into eosinophilic esophagitis (EoE) and nonesophageal EGIDs.This study aimed to characterize EGIDs heterogeneity by performing cluster analysis on a cohort of children and adolescents followed at the Pediatric Center for Eosinophilic Gastrointestinal Disorders (CPED) in Pavia, Italy, using an extensive pediatric primary care database from our University Hospital

Endotyping Seasonal Allergic Rhinitis in Children: A Cluster Analysis.

BackgroundSeasonal Allergic Rhinitis (SAR) is a heterogeneous inflammatory disease. We hypothesized that a cluster analysis based on the evaluation of cytokines in nasal lavage (NL) could characterize distinctive SAR endotypes in children.MethodsThis cross-sectional study enrolled 88 children with SAR. Detailed medical history was obtained by well-trained physicians. Quality of life and sleep quality were assessed through standardized questionnaires [Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Pittsburgh Sleep Quality Index (PSQI) respectively]. Children were grouped through K-means clustering using Interleukin (IL)-5, IL-17, IL-23, and Interferon (INF)-γ in NL.R…

Effects of Polycyclic Aromatic Hydrocarbons on Lung Function in Children with Asthma: A Mediation Analysis.

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children with asthma. This single-center prospective study was conducted in Palermo, Italy, between March and July 2017 and involved 50 children with persistent mild-moderate asthma, aged 6–11 years. At each time visit (day 0, 30, 60, and 90), physical examination, spirometry, and urine collection for detection of urinary cotinine and PAHs were performed. A…

Asthma Comorbidities: Frequency, Risk Factors, and Associated Burden in Children and Adolescents

Identifying asthma comorbidities in children is fundamental for improving disease management. We aimed to investigate the frequency of allergy-related comorbidities in children and adolescents with asthma, and to identify associated risk factors and disease burden. Between September 2015 and December 2018, 508 asthmatic patients (5&ndash;17 years) were consecutively enrolled. Parents answered a standardized questionnaire on the history of disease and risk factors. Comorbidities were classified based on the involvement of respiratory and/or extra-respiratory districts: asthma only (A, 13%), asthma with respiratory comorbidities (AR, 37%), asthma with extra-respiratory comorbidities (AER, 10%…

Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis

Background: Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). Forboth aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. Methods: 47 pre-pubertal GHD children (aged 5–14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Contr…

New Flexible Probability Distributions for Ranking Data

Recently, several models have been proposed in literature for analyzing ranks assigned by people to some object. These models summarize the liking feeling for this object, possibly also with respect to a set of explanatory variables. Some recent works have suggested the use of the Shifted Binomial and of the Inverse Hypergeometric distribution for modelling the approval rate, while mixture models have been developed for taking into account the uncertainty of the ranking process. We propose two new probabilistic models, based on the Discrete Beta and the Shifted-Beta Binomial distributions, that ensure much flexibility and allow the joint modelling of the scale (approval rate) and the shape …

RHINASTHMA-Children: A new quality of life tool for patients with respiratory allergy

Background Specific instruments for health-related quality of life (HRQoL) assessment in adolescents with rhinoconjunctivitis or asthma are available. None of them evaluates rhinitis and asthma together, although they often coexist. Our aim was to validate a HRQoL questionnaire for adolescents with rhinoconjunctivitis, asthma, or both. Methods A pool of 38 items covering the main symptoms and problems related to respiratory allergy was generated based on literature review, clinical experience, and unstructured interviews to 54 adolescents. The items were randomly listed and presented to 88 consecutive outpatients (44 M; mean age 15.2 ± 3.1). Patients had to indicate which item they had expe…