Serious Games in the new era of digital-health interventions: A narrative review of their therapeutic applications to manage neurobehavior in neurodevelopmental disorders.

Children and adolescents with neurodevelopmental disorders generally show adaptive, cognitive and motor skills impairments associated with behavioral problems, i.e., alterations in attention, anxiety and stress regulation, emotional and social relationships, which strongly limit their quality of life. This narrative review aims at providing a critical overview of the current knowledge in the field of serious games (SGs), known as digital instructional interactive videogames, applied to neurodevelopmental disorders. Indeed, a growing number of studies is drawing attention to SGs as innovative and promising interventions in managing neurobehavioral and cognitive disturbs in children with neurodevelopmental disorders. Accordingly, we provide a literature overview of the current evidence regarding the actions and the effects of SGs. In addition, we describe neurobehavioral alterations occurring in some specific neurodevelopmental disorders for which a possible therapeutic use of SGs has been suggested. Finally, we discuss findings obtained in clinical trials using SGs as digital therapeutics in neurodevelopment disorders and suggest new directions and hypotheses for future studies to bridge the gaps between clinical research and clinical practice.

Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease.

BACKGROUND: Diagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs. METHODS: A total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE). RESULTS: Compared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups. CONCLUSIONS: Our results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.

COVID-19 Pandemic and Reduced Physical Activity: Is There an Impact on Healthy and Asthmatic Children?

Physical activity (PA) has been seen to improve asthma symptoms, lung function, and quality of life, as well as to reduce airway inflammation and bronchial responsiveness. As a consequence of the COVID-19 pandemic, the minimal amount of PA recommended by the World Health Organization-i.e., about 60 min/day of moderate-to-high intensity-is difficult to achieve for many children, particularly those living in urban areas. Short-term changes in PA because of the COVID-19 pandemic may become habitual, increasing the risk of adverse asthma outcomes in children. Indeed, prolonged home confinement during the COVID-19 pandemic reduces PA levels and increases sedentary behaviors, possibly impairing immune system function and increasing susceptibility to inflammatory diseases. However, there is limited evidence regarding the effects of lockdown due to COVID-19 on PA and sedentary behaviors in asthmatic children. Given that children stay longer indoors, indoor air pollution represents a major issue to consider during home confinement. This narrative review aims to summarize the available evidence about the impact of decreased PA and increased sedentary behaviors on children with asthma during the COVID-19 pandemic. In addition, strategies for supporting PA in children with asthma during the COVID-19 pandemic are suggested, also looking at the issue of indoor air quality.

Is There a Chance of Normal Life in Severe Laryngeal web.

INTRODUCTION: Laryngeal web is a rare cause of pediatric stridor and respiratory distress. The clinical presentation is variable and symptoms usually correlate with the severity of the airway obstruction. CASE REPORTS: We describe the cases of three children unexpectedly diagnosed with laryngeal web after a severe episode of bronchiolitis and after thirteen and eleven years, respectively, of persistent symptoms despite asthma medications. CONCLUSION: Even if it is a rare cause of stridor and respiratory distress, congenital subglottic web could be a life threatening condition and clinicians should always consider it in the differential diagnosis of persistent noisy breathing, even in adolescents and young adults.

Impact of a supervised training course on spirometry competency for primary care pediatricians.

OBJECTIVE: Spirometry is the most commonly performed lung function test, and performance, adherence to acceptability and repeatability criteria, and accurate interpretation of results help optimize the test's usefulness. This study aimed to measure the effects of spirometry training courses supported by the Italian Pediatric Respiratory Society (IPRS) on primary care pediatricians' (PCP) knowledge of spirometry test quality, ability to interpret results, and overall degree of satisfaction with the course. METHODS: Of the six face-to-face courses, four lasted two days and two lasted one day: mean duration of theoretical lessons was five and four hours respectively; and practical sessions lasted eight and six hours, respectively. At the end of each course, participants took a learning test consisting of evaluating six flow-volume curves. Degree of satisfaction was assessed by asking participants to rank the relevance, quality, and usefulness of the course. RESULTS: 261 PCPs were involved, with most (67.43%) taking two-day courses. Nearly all participants correctly identified normal and restrictive patterns. Intrathoracic large-airway obstruction was the pattern most difficult to identify correctly (70.5% overall), whereas > 80% of the participants correctly classified artifacts, obstructive-restrictive, and obstructive patterns. Participants in longer courses reported significantly higher values on the learning score. The overall degree of satisfaction average ranged between "good" and "excellent". CONCLUSIONS: This pilot study showed the greater impact of two-day courses than one-day courses for training PCPs to properly interpret spirometry, confirming that a practical module lasting at least six hours is sufficient to deliver adequate training on spirometry for healthcare professionals.

Italian pediatric respiratory society recommendations on pediatric pulmonary function testing during COVID-19 pandemic.

BACKGROUND: Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection. MAIN TEXT: The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic. CONCLUSION: Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.

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). For both 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 Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https://cran.r-project.org/mirrors.html). A p-value <0.05 was considered significant. MEASUREMENTS AND MAIN RESULTS: At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV1, FEF25-75% and TLC were <50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant. CONCLUSIONS: The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT.

Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: results of a crossover, randomized clinical trial.

BACKGROUND: This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. METHODS: Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. RESULTS: After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p < 0.0001) and of FEF25-75 (p = 0.019) were found in NS group. No differences were found in expiratory and inspiratory Rint in both groups. No serious adverse events occurred. CONCLUSIONS: Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinically stable conditions. TRIAL REGISTRATION: ISRCTN12345678 .

Cardiorespiratory fitness: a comparison between children with renal transplantation and children with congenital solitary functioning kidney.

Children with end-stage renal disease are known to have a cardiorespiratory fitness significantly reduced. This is considered to be an independent index predictive of mortality mainly due to cardiovascular accidents. The effects of renal transplantation on cardiorespiratory fitness are incompletely known. We compared the maximal oxygen uptake (VO2 max) of children with a functioning renal transplant with that of children with congenital solitary functioning kidney, taking into consideration also the amount of weekly sport activity.

Cardiorespiratory fitness and sports activities in children and adolescents with solitary functioning kidney.

BACKGROUND: An increasing number of children with chronic disease require a complete medical examination to be able to practice physical activity. Particularly children with solitary functioning kidney (SFK) need an accurate functional evaluation to perform sports activities safely. The aim of our study was to evaluate the influence of regular physical activity on the cardiorespiratory function of children with solitary functioning kidney. METHOD: Twenty-nine patients with congenital SFK, mean age 13.9 ± 5.0 years, and 36 controls (C), mean age 13.8 ± 3.7 years, underwent a cardiorespiratory assessment with spirometry and maximal cardiopulmonary exercise testing. All subjects were divided in two groups: sedentary (S) and trained (T) patients, by means of a standardized questionnaire about their weekly physical activity. RESULTS: We found that mean values of maximal oxygen consumption (VO2max) and exercise time (ET) were higher in T subjects than in S subjects. Particularly SFK-T presented mean values of VO2max similar to C-T and significantly higher than C-S (SFK-T: 44.7 ± 6.3 vs C-S: 37.8 ± 3.7 ml/min/kg; p < 0.0008). We also found significantly higher mean values of ET (minutes) in minutes in SFK-T than C-S subjects (SFK-T: 12.9 ± 1.6 vs C-S: 10.8 ± 2.5 min; p <0.02). CONCLUSION: Our study showed that regular moderate/high level of physical activity improve aerobic capacity (VO2max) and exercise tolerance in congenital SFK patients without increasing the risks for cardiovascular accidents and accordingly sports activities should be strongly encouraged in SFK patients to maximize health benefits.

Prevalence and risk factors for atopic disease in a population of preschool children in Rome: Challenges to early intervention.

BACKGROUND: Allergic diseases are complex identities determined by an interplay of genetic and environmental factors, resulting in the clinical manifestation of the disease. So far in Italy, updated data about the prevalence and risk factors of respiratory and allergic diseases in preschool children are not available. METHODS: Children aged 3-5 years, attending four different nursery schools in an urban district of the city of Rome. A standardized questionnaire developed under the SIDRIA-2 protocol was administered to the parents of the children for the assessment of the potential risk factors and the outcomes. RESULTS: A total of 494 children were enrolled in the study; 289 of them (60.3%) performed a skin prick test (SPT). In the 12 months preceding the interviews, 15% of children experienced at least one episode of wheezing, 5.5% of allergic rhinitis, 11% of children had a doctor diagnosis of asthma, 12% of children who underwent the SPT were positive to at least one of the tested allergens, being diagnosed as atopic. The univariate analysis for the health outcomes of the study shows that asthma was positively associated with daycare attendance, mother's history of atopy, siblings' history of atopy, recurrent siblings' bronchitis, and dermatitis. Atopy was positively associated with mother's history of atopy and dermatitis, whereas there is a borderline protective association with recurrent siblings' bronchitis. CONCLUSIONS: This study represents a first comprehensive epidemiological evaluation of prevalence of respiratory and allergic diseases in children aged 3-5 years in the city of Rome and an updating of the evolution of allergic diseases.

Primary school children often underestimate their nasal obstruction.

BACKGROUND: No consensus has ever been reached about the correlation between nasal resistance and the subjective sensation of nasal patency. The aim of the present study was to better de ne whether primary school and secondary school aged children correctly estimate their nasal obstruction. MATERIALS AND METHODS: Two hundred eighty four children (168 males and 116 female) aged between 6 and 14 years (9.5+2.9 years) affected by Pediatric Allergic Rhinitis underwent Rhinomanometry and they were considered as correctly estimating their nasal obstruction when the grade of nasal patency corresponded to the severity of the NOSE score, overestimating when the grade of nasal patency was <1 when compared to the severity of the score, underestimating when the grade of nasal patency was >1 when compared to the severity of the score. RESULTS: Correlation between NOSE score and nasal patency was statistically significant (r -0.74; p<0.001). Children between 6 and 9 years of age underestimate (43.7%) and children >12 overestimate (34.7%) their symptoms more frequently than children among other age ranges (p<0.001). CONCLUSION: Although NOSE score approximately allow to quantify nasal obstruction, in children, especially between 6 and 9 years of age, an objective measurement of nasal patency should be performed to better define the therapeutic approach.

Sublingual immunotherapy in children and its potential beneficial collateral effect on respiratory tract infections.

Although directed to the control of allergic symptoms, a possible effect of sublingual immunotherapy (SLIT) on susceptibility to infections has been hypothesized. Two hundred sixty-five children aged between 3 and 4 years of age affected by allergic rhinitis completed a 6 year prospective case-control study. One hundred forty-three children after 2 years of SLIT reported a lower prevalence of respiratory tract infections when compared to children not undergoing SLIT.

Intranasal budesonide in children affected by persistent allergic rhinitis and its effect on nasal patency and Nasal Obstruction Symptom Evaluation (NOSE) score.

BACKGROUND: Intranasal steroids are recognized as an effective treatment for allergic rhinitis (AR) although their effect on nasal patency has never been evaluated with an objective instrument such as anterior rhinomanometry in children. Moreover this effect has been widely assessed with total Nasal Symptom Scores (NSS) including all symptoms of allergic rhinitis and not with scores specifically focused on nasal obstruction such as the Nasal Obstruction Symptom Evaluation score (NOSE). MATERIALS AND METHODS: Sixty children (42 males and 18 female) aged 6-10 years, affected by persistent AR, were randomized and divided in two groups of 30 children to be included in an unblinded trial: one group treated with intranasal budesonide and isotonic nasal saline for 2 weeks and the other group treated only with isotonic nasal saline for 2 weeks. Each child underwent rhinomanometry and completed the NSS and the NOSE scores before and after treatment. RESULTS: At the baseline nasal patency and NSS total score, NOSE total scores were correlated (r=-0.29, p<0.001; r=-60, p<0.001). After 2 weeks of treatment improvements in nasal patency, NSS and NOSE were seen (Δ NSS 4.13 ± 1.38 vs 1.33 ± 1.93, p<0.001; Δ NOSE 34 ± 17.97 vs 9 ± 18.21, p<0.001; Δ nasal patency -26.13 ± 25.25 vs -11.83 ± 11.31, p<0.001). Correlations were found between rhinitis duration and Δ nasal patency and Δ NOSE (r=-0.84, p<0.001; r=0.43, p<0.01). CONCLUSION: Intranasal budesonide is effective in increasing nasal patency in children. Moreover the NOSE score was strongly correlated with nasal flow and, hence, this score should be regarded as a valid and reliable instrument in children.

Duration of a cow-milk exclusion diet worsens parents' perception of quality of life in children with food allergies.

BACKGROUND: In Italy, rigorous studies obtained with specific and validated questionnaires that explore the impact of exclusion diets on health-related quality of life (HRQoL) in children with food allergies are lacking. In this cross-sectional study, we wished to validate the Italian version of a disease-specific quality of life questionnaire, and assess the impact of exclusion diets on the HRQoL in a cohort of Italian children with IgE-mediated food allergies. METHODS: Children on an exclusion diet for ≥1 food were enrolled consecutively, and their parents completed the validated Italian version of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM). RESULTS: Ninety-six parents of children aged 0-12 years answered the FAQLQ-PF. The validity of the construct of the questionnaire was assessed by correlation between the FAQLQ-PF and FAIM-PF (r = 0.85). The Italian version of the FAQLQ had good internal consistency (Cronbach's α >0.70). Factors that mainly influenced the HRQoL were older age, severity of food allergy, and the duration of the cow milk-exclusion diet. CONCLUSIONS: The FAQLQ-PF, validated in Italian, is a reliable instrument. Worse QoL scores were observed among older children, those with severe systemic reactions, and those with a prolonged cow milk-free diet. It is very important to consider the QoL assessment as an integral part of food-allergy management. These results emphasize the need to administer exclusion diets only for the necessary time and the importance of assessment of the HRQoL in these patients.

Pediatric asthma evaluation: what's to be considered?

The increasing evidence that asthma begins very early in childhood leads the need for having outcome's measures able to identify the early damage and its evolution both for research than for clinical purposes. The current available methods are clinical questionnaires, pulmonary function tests, airway reactivity tests and direct or indirect inflammation markers' measures. Among the first, ISAAC questionnaire, for epidemiological purpose, Asthma Control Test, for clinical monitoring and Health Related Quality of Life questionnaire are the most used. There are many pulmonary function tests that may be used in all age for functional evaluation, but airway responsiveness measures may be commonly performed only in school age children. As regards respiratory inflammation measures the only currently useful is the exhaled nitric oxide evaluation. The complexity of the pathogenic mechanisms, molecular, cellular and inflammatory that realize the asthmatic syndrome and the effects of the disease on respiratory function, on the activity of the child, on the quality of life of the family and on the economic costs to society show that there is no a single outcome measure that can evaluate all these effects simultaneously.

Influence of physical activity on cardiorespiratory fitness in children after renal transplantation.

BACKGROUND: Cardiorespiratory fitness is significantly reduced in children with end-stage renal disease. The role of renal transplantation in improving cardiorespiratory fitness has not been thoroughly investigated. METHODS: In this work, we wanted to assess whether, in children after a successful renal transplant, the amount of weekly physical exercise affects cardiorespiratory fitness and left ventricular mass (LVM). The study was conducted on 16 children after renal transplantation and 36 matching healthy controls. Four groups were formed according to the weekly amount of physical exercise; all children received an echocardiogram and underwent a treadmill exercise test according to the Bruce protocol. RESULTS: Cardiorespiratory fitness is worst in renal transplant children with a weekly physical exercise<3 h; renal transplant children with a physical exercise of 3-5 h per week attain a cardiorespiratory fitness comparable to controls with a sedentary lifestyle (<3-h exercise per week); healthy controls with a weekly physical exercise of 3-5 h per week show the highest levels of cardiorespiratory fitness; the LVM assessed via echocardiography follows the same pattern. CONCLUSIONS: In children with a successful renal transplant, a weekly physical exercise of 3-5 h significantly improves the cardiorespiratory fitness and the LVM, up to the level of matching healthy controls with a sedentary lifestyle (<3 h exercise per week).

Cardiopulmonary response to exercise and cardiac assessment in patients with turner syndrome.

Turner syndrome (TS) is a chromosomal disorder; however, little is known about the exercise tolerance of patients with this syndrome. The aim of the present study was to measure the maximal aerobic capacity and cardiac function using cardiopulmonary exercise testing and lung function tests and to evaluate the cardiac parameters using echocardiography in patients with TS and control subjects. A total of 50 women with TS (mean age 21.3 ± 8.5 years) and 56 age-matched controls (mean age 21.1 ± 3.7 years) were enrolled from the Pediatric Department of "Sapienza" University of Rome and underwent cardiopulmonary exercise testing, lung function testing, and echocardiography. The maximal oxygen uptake was lower in the patients with TS than in the controls (28.4 ± 4.0 vs 35.6 ± 6.2 ml/min/kg; p <0.0001). Also, the forced expiratory volume in 1 second, expressed as a percentage of the predicted value, was greater in the patients with TS than in the controls (116.2 ± 15.2% vs 102.8 ± 4.8%, p <0.0001). The patients with TS had a smaller left ventricle than did the controls. Tissue Doppler imaging revealed subclinical systolic and diastolic dysfunction in the left ventricle in those with TS but not in the controls. The left ventricular mass index was greater in the patients with TS than in the controls (38.6 ± 9.3 vs 27.2 ± 4.5 g/m(2.7), p <0.0001). In conclusion, the patients with TS had a lower maximal aerobic capacity and exercise tolerance than did the controls. The anatomic and functional cardiac aspects were peculiar to those with TS and might represent a specific cardiac phenotype.

Microaspiration in infants with laryngomalacia.

OBJECTIVES/HYPOTHESIS: Laryngomalacia is the most common congenital laryngeal anomaly and the most frequent cause of stridor in infants. Infants with laryngomalacia may have associated respiratory symptoms other than stridor. In this study, we evaluated whether infants with laryngomalacia have episodes of microaspiration by calculating the amount of lipids present in the alveolar macrophages. STUDY DESIGN: We reviewed bronchoalveolar lavage (BAL) findings obtained in 14 infants with laryngomalacia and in 11 control children. METHODS: BAL was performed during flexible fiberoptic bronchoscopy (FFB) to diagnose persistent stridor. The presence of microaspiration was determined by evaluating the amount of lipid per single macrophage, assigning each cell a score from 0 to 4 according to the amount of lipid in the cytoplasm. RESULTS: The lipid-laden macrophage index was similar in patients and controls (31.5, range 12-177 vs. 45, range 35-106). In 5 of the 14 (36%) patients the index exceeded 100, and more than 25% of the cells were graded 3 and 4, indicating the presence of microaspiration. The lipid-laden macrophage index correlated significantly with the number and percentage of BAL neutrophils (Pearson correlation test, r = 0.83, P < .001 and r = 0.925, P < .001) as a marker of lung inflammation. CONCLUSIONS: Infants with laryngomalacia may have episodes of microaspiration. BAL performed during FFB to evaluate stridor may add helpful therapeutic information without increasing the risks of the procedure.

Bronchial adenoma: an unusual cause of recurrent pneumonia in childhood.

Primary lung tumors are rare in childhood and often overlooked owing to the nonspecific presentation. We report the case of a 15-year-old boy with a 3-year history of recurrent pneumonia always involving the right lower lobe due to bronchial mucinous adenoma. After endoscopic removal the tumor recurred locally, necessitating open surgical resection of the tumor. In a child with localized recurrent pneumonia of uncertain pathogenesis, the differential diagnosis should include a primary lung tumor. Bronchial adenomas should not be removed endoscopically; patients must undergo open thoracotomy for surgical excision.