Evaluation of saliva and nasopharyngeal swab sampling for genomic detection of SARS-CoV-2 in children accessing a pediatric emergency department during the second pandemic wave.

SARS-CoV-2 infection is mainly detected by multiplex real-time RT-PCR from upper respiratory specimens, which is considered the gold-standard technique for SARS-CoV-2 infection diagnosis. A nasopharyngeal (NP) swab represents the clinical sample of choice, but NP swabbing can be uncomfortable to the patients, especially for pediatric-age participants, requires trained healthcare personnel, and may generate an aerosol, increasing the intrinsic exposure risk of healthcare workers. The objective of this study was to compare paired NP and saliva samples (SS) collected from pediatric patients to evaluate whether the saliva collection procedure may be considered a valuable alternative to the classical NP swab (NPS) sampling in children. In this study, we describe a SARS-CoV-2 multiplex real-time RT-PCR protocol for SS, comparing the results with the paired NPS specimens from 256 pediatric patients (mean age 4.24 ± 4.40 years) admitted to the hospital emergency room of Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, and randomly enrolled between September 2020 and December 2020. The saliva sampling demonstrated consistent results when compared to NPS use. The SARS-CoV-2 genome was detected in 16 out of 256 (6.25%) NP samples, among which 13 (5.07%) were positive even when paired SS were analyzed. Moreover, SARS-CoV-2-negative NPS and SS were consistent, and the overall concordances between NPS and SS were detected in 253 out of 256 samples (98.83%). Our results suggest that saliva samples may be considered a valuable alternative to NPS for SARS-CoV-2 direct diagnosis with multiplex real-time RT-PCR in pediatric patients.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.

Frequency and type of domestic injuries among children during COVID-19 lockdown: what changes from the past? An Italian multicentre cohort study.

Accidents are the main cause of injury in children, more than half events happen at home. Aims of this study were to assess if SARS-CoV-2 lockdown influence emergency department (ED) visits due to children domestic accident (DAs) and to identify factors associated with hospitalization. This was a multicentre, observational, and retrospective cohort study involving 16 EDs in Italy and enrolling children (3-13 years) receiving a visit in ED during March-June 2019 and March-June 2020. Risk factors for hospitalization were identified by logistic regression models. In total, 8860 ED visits due to domestic accidents in children occurred before (4380) and during (4480) lockdown, with a mean incidence of DA of 5.6% in 2019 and 17.9% in 2020 (p < 0.001) (IRR: 3.16; p < 0.001). The risk of hospitalization was influenced by the type of occurred accident, with fourfold higher for poisoning and twofold lower risk for stab-wound ones. In addition, a higher risk was reported for lockdown period vs 2019 (OR: 1.9; p < 0.001), males (OR: 1.4; p < 0.001), and it increased with age (OR: 1.1; p < 0.001).    Conclusions: The main limitation of this study is the retrospective collection of data, available only for patients who presented at the hospital. This does highlight possible differences in the total number of incidents that truly occurred. In any case, the COVID-19 lockdown had a high impact on the frequency of DAs and on hospitalization. A public health campaign aimed at caregivers would be necessary to minimize possible risks at home. What is Known: • In Italy, domestic accidents are the second leading cause of paediatric mortality after cancer. • During the first SARS-CoV-2 lockdown in 2020, a sharp decrease in the total number of Emergency Departments visits for all causes was observed, both in children and in adults. What is New: • During the first SARS-CoV-2 lockdown in 2020, domestic accidents involving children increased threefold from the previous year. • Higher risk of hospitalization was showed in minors accessing during 2020 vs 2019, in males than in females and it increased with advancing age. Considering the type of injury, a significant higher risk of hospitalization for poisoning was observed.

Paracetamol and ibuprofen combination for the management of acute mild-to-moderate pain in children: expert consensus using the Nominal Group Technique (NGT).

BACKGROUND: Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia. METHODS: An investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn. RESULTS: The board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management. CONCLUSIONS: The use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.

The PAWPER tape as a tool for rapid weight assessment in a Paediatric Emergency Department: Validation study and comparison with parents' estimation and Broselow tape.

Aim: To validate the PAWPER tape and assess its inter-observer reliability in children accessing a Paediatric Emergency Department (PED). As secondary outcome we compared the accuracy of the PAWPER tape with that of parents' estimation, the Broselow tape and the European Paediatric Life Support (EPLS) formula. Methods: This was a cross-sectional study of children (0-12 years) enrolled in a tertiary Paediatric Emergency Department in Italy. Children's weight was estimated by parents and by trained healthcare providers using the PAWPER tape, the Broselow tape and the EPLS formula. The root mean squared percentage error (RMSPE) for the estimation of precision was calculated. Overall accuracy was evaluated using the percentage of weight estimation falling within 10% (PW10) and 20% (PW20) of real weight. Results: The study included 2060 children. Parental estimation was the most accurate and precise method. The PAWPER tape was accurate throughout all habitus sizes except for extreme underweight and overweight categories. Furthermore, it was more accurate and more precise than the Broselow tape and the EPLS formula (p adjusted <0.001). Conclusions: The PAWPER tape served as an accurate method for weight estimation in children accessing a Paediatric Emergency Department, with excellent inter-rater reliability. It performed significantly better than other length or age-based tools, showing good accuracy and precision except for very extreme weights. Whilst parents' estimation yielded to be the most accurate and precise method, the age-based EPLS formula was not reliable for estimating weight in all subcategories of habitus.

Prevalence of SARS-CoV-2 positivity in infants with bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the leading acute respiratory tract infection in infants during the winter season. Since the beginning of the SARS-CoV-2 pandemic, a reduction in the number of bronchiolitis diagnoses has been registered. OBJECTIVE: The present study aimed to describe the incidence and clinical features of bronchiolitis during the 2020-2021 winter season in a large cohort of children in Europe and Israel, and to clarify the role of SARS-CoV-2. SETTING, PATIENTS, INTERVENTIONS: We conducted a multicentre observational cross-sectional study in 23 paediatric emergency departments in Europe and Israel. Clinical and demographic data about all the cases of infants diagnosed with bronchiolitis from 1 October 2020 to 30 April 2021 were collected. For each enrolled patient, diagnostic tests, treatments and outcomes were reported. MAIN OUTCOME MEASURES: The main outcome was the prevalence of SARS-CoV-2-positive bronchiolitis. RESULTS: Three hundred and fourteen infants received a diagnosis of bronchiolitis during the study period. Among 535 infants who tested positive for SARS-CoV-2, 16 (3%) had bronchiolitis. Median age, male sex predominance, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. Rhinovirus was the most common involved pathogen, while respiratory syncytial virus (RSV) was detected in one case. SARS-CoV-2 bronchiolitis had a mild clinical course, with one patient receiving oxygen supplementation and none requiring paediatric or neonatal intensive care unit admission. CONCLUSIONS: During the SARS-CoV-2 pandemic, a marked decrease in the number of bronchiolitis diagnoses and the disappearance of the RSV winter epidemic were observed. SARS-CoV-2-related bronchiolitis was rare and mostly displayed a mild clinical course.

Management of fever in infants and children in the emergency setting and during home discharge: recommendations from an Italian panel.

In infants and children, fever is very common in the emergency setting. The overall aim of the present publication was to overview guidance and provide an algorithm for use in the emergency setting as well as recommendations to inform parents for home care. To obtain consensus, a core steering committee drafted a management algorithm and general consensus was obtained by remote voting among experts. A number of common messages are found in current guidelines: management of fever depends on age, antipyretics are indicated only for discomfort; paracetamol or ibuprofen can be recommended; physical methods for lowering temperature are discouraged. A consensus algorithm is presented in which infants <28 days are considered separately, while those >28 days and <90 days are divided into those ill or well appearing. All infants <28 days with fever ≥37.5 °C should undergo complete work-up for sepsis, strongly considered to receive empirical antibiotics ± acyclovir, and be hospitalized. All infants (between 28 and 90 days) ill appearing should undergo diagnostic work-up for sepsis, receive empirical antibiotics, and be hospitalized. In well appearing infants, diagnostic work-up should be carried out to decide admission to hospital and administration of antibiotics. Specific recommendations are also given for home discharge that can be used to inform parents about the actions to take during home care in the attempt to reinforce existing guidelines. At present, physical examination and laboratory tests, along with best clinical judgement and postdischarge guidance following a defined algorithm, are the foundation of management of febrile children.

Neonatal and Pediatric Emergency Room Visits in a Tertiary Center during the COVID-19 Pandemic in Italy.

The COVID-19 pandemic is affecting healthcare services worldwide. We investigated the impact of a strict lockdown policy on the characteristics of neonatal and pediatric attendances to our pediatric emergency department (PED). The clinical features of PED visits in March-April 2020 (COVID-19) and March-April 2019 (non-COVID-19) were analyzed. During the COVID-19 lockdown period, visits reduced by 67%, from 3159 to 1039. Neonatal access decreased from 78 to 59, mainly due to fewer pathological conditions, with a complete disappearance of respiratory infections. On the other hand, minor neonatal clinical conditions rose from 44 (56.4%) to 48 (81.4%), mostly due to feeding-related issues. Communicable diseases, particularly respiratory infections and gastroenteritis, dropped from 1552 (49.1%) to 288 (27.7%). Accident-related visits also decreased during COVID-19, from 535 (16.9%) to 309 (29.7%), becoming the most common cause of PED access. Hospital admissions reduced from 266 to 109, while PICU (pediatric intensive care unit) admissions decreased from 27 to 11, with a comparable rate of 10.1% in both periods. The lockdown due to COVID-19 had a substantial impact on our PED visits, which markedly decreased, mainly due to fewer respiratory infections. Unexpectedly, neonatal visits for minor conditions did not decline, but rather slightly increased. Among the children admitted to the PICU, none had respiratory disease.

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

COnsensus on Pediatric Pain in the Emergency Room: the COPPER project, issued by 17 Italian scientific societies.

In the pediatric setting, management of pain in the emergency department - and even in common care - is a challenging exercise, due to the complexity of the pediatric patient, poor specific training of many physicians, and scant resources.A joint effort of several Italian societies involved in pediatrics or in pain management has led to the definition of the PIPER group and the COPPER project. By applying a modified Delphi method, the COPPER project resulted in the definition of 10 fundamental statements. These may represent the basis for improving the correct management of children pain in the emergency department.

Acute pain management: acetaminophen and ibuprofen are often under-dosed.

Most children with pain are managed by either acetaminophen or ibuprofen. However, no study has so far investigated if children are prescribed adequate doses of acetaminophen or ibuprofen in emergency department. Aim of this retrospective study was to investigate the prevalence of under-dosage of these drugs in children presenting with pain in emergency department. Children initially prescribed with acetaminophen or ibuprofen for pain management were included. The χ 2 automatic interaction detection method was used considering the percentage variation from the minimum of the appropriate dose as dependent variable while prescribed drug, age, gender, body weight, type of hospital (pediatric or general), and availability of internal guidelines on pediatric pain management in the emergency department as independent variables. Data on 1471 children managed for pain were available. Under-dosage was prescribed in 893 subjects (61%), of whom 577 were prescribed acetaminophen and 316 ibuprofen. The use of acetaminophen suppositories, body weight <12 kg or >40 kg, and the use of oral ibuprofen identified clusters of children associated with under-dosage prescription. CONCLUSION: Prescription of acetaminophen and ibuprofen was frequently under-dosed. The use of suppositories, lower and higher body weight, and the use of ibuprofen were associated with under-dosage. Under-dosing may reflect prescription of anti-pyretic doses. CLINICAL TRIAL REGISTRATION: Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment.

Diagnostic pitfalls in the assessment of congenital hypopituitarism.

BACKGROUND: The diagnosis of congenital hypopituitarism is difficult and often delayed because its symptoms are nonspecific. AIM: To describe the different clinical presentations of children with congenital hypopituitarism to reduce the time for diagnosis and to begin a precocious and appropriate treatment. STUDY DESIGN: We analyzed a cohort of five children with congenital hypopituitarism, describing their clinical, biochemical and radiological characteristics from the birth to diagnosis. RESULTS: As first sign of the disease, all of five patients presented a neonatal hypoglycemia, associated in four cases with jaundice. In all these four cases, the clinicians hypothesized a metabolic disease delaying the diagnosis, which was performed in only two cases within the neonatal period. In the other three cases, the diagnosis was formulated at 2, 5 and 8 years of life because there was severe and precocious growth impairment. CONCLUSIONS: It is important to suspect congenital hypopituitarism in the presence of persistent neonatal hypoglycemia associated with jaundice and of a precocious and severe reduction of the growth velocity in childhood. In all these cases, it is necessary to undertake a hypothalamic-pituitary magnetic resonance imaging scan as soon as possible, and to start appropriate treatment.

Italia-Netherland PhD Program: the I.O. PhD Research Program.

In the framework of long-term scientific collaboration among the founder members coming from Holland and Italy there was a growing consensus to activate a philosophical doctorate (PhD) program, involving young Italian researchers in the field of perinatal medicine, neonatology and pediatrics. The aims were to promote excellence in research, offering to young Italian physicians the opportunity to maturate an International research experience leading to PhD degree, and to promote human and technological improvement energies in perinatal, neonatal and pediatrics research. Thus, an official collaboration among the Dutch Universities from Maastricht and Utrecht and the Italian Children's Hospital from Alessandria, has been activated on March 1st 2010, finalized to the PhD program. The experimental phase included the selection of projects and relative candidates after an interview-selection focusing on their scientific attitudes and the availability on their research projects. Candidates' selection started on May 2010 and on September 29th ten projects and candidates have been approved by the scientific commission. Research topics included: perinatal asphyxia, aging and the origin of adulthood neurodegenerative disease, neuroprotective strategies, biochemical pulmonology, intrauterine growth retardation and perinatal teratology. To date, all projects have been approved by local Ethics Committee from the University/Hospital of origin of the candidates. Five manuscripts have been published and/or submitted to international Journals regarding pneumology, perinatal asphyxia and teratology, whilst about 60-70% of data regarding clinical studies have already been collected.

Fat cell size, insulin sensitivity, and inflammation in obese children.

OBJECTIVE: To assess the association between adiposity indexes (body mass index [BMI], fat mass, adipocyte size) and circulating inflammation markers with known metabolic relevance or insulin sensitivity in overweight/obese children. STUDY DESIGN: Twenty-eight children (males/females: 13/15) with different degrees of overweight (BMI z-score: 1.64-3.1; fat mass: 14.1-49.8 kg) were studied. BMI, body composition (dual-energy x-ray absorptiometry scanning), subcutaneous adipocyte diameter (needle biopsy of subcutaneous abdominal fat), blood tumor necrosis factor-alpha and interleukin-6 concentrations and insulin sensitivity (frequently sampled intravenous glucose tolerance test) were assessed. RESULTS: Adipocyte diameter, more than BMI and fat mass, was significantly associated with interleukin-6 (r = 0.62, P < .001) and tumor necrosis factor-alpha (r = 0.61, P < .001). Moreover adipocyte size was associated with insulin sensitivity (R2 = 0.15, F = 4.69, P = .04) independently from fat mass. CONCLUSIONS: Adipocyte size is a factor linked to both inflammation and insulin resistance in overweight/obese children. This is similar to the findings in adults and lends support to the tenet that the earlier obesity ensues, the more severe the biologic consequences may be.

Prevalence of overweight and obesity in 2- to 6-year-old Italian children.

OBJECTIVE: To assess the prevalence of overweight and obesity in 2- to 6-year-old Italian children and to compare the prevalence between the north and the south of the country. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of 2150 subjects (M/F: 1137/1013), 5.36 +/- 0.83 years of age. The sampling areas were Verona (north Italy) and Messina (south Italy). We used definitions of overweight and obesity using BMI values, with cut-off values proposed by the International Obesity Task Force. RESULTS: The prevalence of overweight was 16.6% (males: 13.9%, females: 19.6%), and it was higher in the south (males: 17.8%, females: 22.4%) than in the north (males: 11.3%, females: 17.9%). The prevalence of obesity was 8.0% (males: 8.3%, females: 7.7%), and it was higher in the south (males: 12.3%, females: 10.7%) than in the north (males: 5.7%, females: 5.8%). Using the Centers for Disease Control reference charts, the prevalence of overweight and obesity of Italian children was close to that reported in children living in the United States (32% vs. 32.7%, respectively). DISCUSSION: The prevalence of overweight and obesity in young Italian children is very high, and it is rapidly growing. In the south of the country, the prevalence is higher than in the north.

Obesity and inflammation: evidence for an elementary lesion.

In obesity, an inflammatory process of the adipose tissue has been hypothesized; however, direct evidence for a tissue lesion is still lacking. Macrophage infiltration in the adipose tissue of obese individuals seems to be proven, but other alterations of the tissue have not been demonstrated. Moreover, in humans it has not been clarified whether inflammation is an early characteristic of obesity, because no data from obese children are available. In the present study, we assessed the inflammatory involvement of the adipose tissue and identified the elementary "inflammatory" lesion in a group of obese children. The study of children gives us the chance to investigate adipose tissue during early phases of obesity. In all the obese subjects, ultramicroscopic analysis of the adipose tissue demonstrated inflammatory involvement, and the extent of the lesions seemed to depend on the SD score of body mass index. The elementary lesion is a microgranuloma, with fragments of adipocytes, that evolves to fibrosis. Macrophages (and less frequently, lymphocytes or granulocytes) were found in perivascular positions. The lesions were not found in nonobese children. Our study proved that an "inflammatory" process exists in the adipose tissue of obese children, confirming previous findings in animals and obese adults and demonstrating that it is an early alteration in humans. However, the accumulation of macrophages was just one of the components of the inflammatory lesion, which also involved adipocyte degeneration, fibrosis, and, to a lesser extent, granulocyte/lymphocyte accumulation. The finding of fragments of adipocytes in the elementary lesion suggests that, at the beginning of the process, adipocytes may degenerate and that the materials generated by this process can recruit macrophages and other leukocytes. These preliminary results suggest that additional studies should be designed to clarify the cause of adipocyte fragility in obese children.