Recovery characteristics and parental satisfaction in pediatric procedural sedation.

BACKGROUND: Despite being a standard of care for children undergoing stressful procedures, little data exist on parental perception of pediatric sedation. AIMS: This study aimed to investigate recovery characteristics and parental satisfaction for pediatric sedations performed with four widely used sedative regimens. METHODS: A prospective observational study was conducted at the Institute for Maternal and Child Health of Trieste, Italy, enrolling children undergoing procedural sedation with one of the following pharmacological regimens: propofol, propofol + midazolam, ketamine + propofol, and dexmedetomidine + midazolam. A questionnaire was used to assess the occurrence of symptoms upon recovery from sedation and the following day, and the caregivers' satisfaction for both the recovery pattern and the overall sedation experience, according to a numerical rating scale (0-10). Answers were collected through a telephone survey. The primary outcome was the difference in the quality of the recovery as perceived by caregivers; the secondary and tertiary outcomes were the perceived quality of the overall sedation experience and the frequency of sedation-related adverse events, respectively. RESULTS: Data from 655 patients, 149 receiving propofol, 245 propofol + midazolam, 134 ketamine + propofol, and 127 dexmedetomidine + midazolam, were analyzed. The level of parents' satisfaction for both the recovery and the sedation experience was overall high and increased with the patients' age in all the pharmacological groups (Spearman's rank correlation, ρ .083, p = .033, and ρ .087, p = .026, respectively), with no statistically significant differences between groups when adjusting for age. The occurrence of irritability, prolonged sleepiness, hyperactivity, unsteadiness, hallucinations, emesis, and respiratory distress at any moment negatively affected parental satisfaction. CONCLUSIONS: In this study, caregivers' satisfaction with pediatric sedation was high, regardless of the regimen used. Lower parental satisfaction was associated with younger age, irritability after sedation, prolonged sleepiness, hyperactivity, unsteadiness, hallucinations, emesis, and respiratory distress.

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.

Monitoring oral iron therapy in children with iron deficiency anemia: an observational, prospective, multicenter study of AIEOP patients (Associazione Italiana Emato-Oncologia Pediatrica).

Oral ferrous salts are standard treatment for children with iron deficiency anemia (IDA). The objective of our study was to monitor oral iron therapy in children, aged 3 months-12 years, with IDA. We prospectively collected clinical and hematological data of children with IDA, from 15 AIEOP (Associazione Italiana di Ematologia ed. Oncologia Pediatrica) centers. Response was measured by the increase of Hb from baseline. Of the 107 analyzed patients, 18 received ferrous gluconate/sulfate 2 mg/kg (ferrous 2), 7 ferrous gluconate/sulfate 4 mg/kg (ferrous 4), 7 ferric iron salts 2 mg/kg (ferric), 62 bis-glycinate iron 0.45 mg/kg (glycinate), and 13 liposomal iron 0.7-1.4 mg/kg (liposomal). Increase in reticulocytes was evident at 3 days, while Hb increase appeared at 2 weeks. Gain of Hb at 2 and 8 weeks revealed a higher median increase in both ferrous 2 and ferrous 4 groups. Gastro-intestinal side effects were reported in 16% (ferrous 2), 14% (ferrous 4), 6% (glycinate), and 0 (ferric and liposomal) patients. The reticulocyte counts significantly increased after 3 days from the start of oral iron supplementation. Bis-glycinate iron formulation had a good efficacy/safety profile and offers an acceptable alternative to ferrous iron preparations.

Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks.

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.

Physical activity provides many benefits in patients with congenital bleeding disorders. Patients with hemophilia are encouraged to participate in exercise and sports, especially those patients receiving prophylaxis. Several publications and guidelines have explored this issue in hemophilia patients, evaluating in particular the impact of physical activity on patients' well-being and quality of life. The other rare congenital bleeding disorders are less studied; they are heterogeneous in terms of clinical bleeding phenotype, incidence of hemarthrosis, and arthropathy. Furthermore, prophylaxis in these patients is less common than in hemophilia patients, which must be considered when choosing the type of physical and sporting activity. In this review, the authors have analyzed the literature focusing their attention on those rare coagulation disorders that may be complicated by arthropathy and the role of exercise and sports in this context.

Implementation of the WHO standards to assess the quality of care for children with acute diarrhoea: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is no documented experience in the use of the WHO standards for improving the quality of care (QOC) for children at the facility level. We describe the use of 10 prioritised WHO-Standard-based Quality Measures to assess QOC for children with acute diarrhoea (AD) in Italy. METHODS: In a multicentre observational study in 11 paediatric emergency departments with different characteristics and geographical location, we collected data on 3061 children aged 6 months to 15 years with AD and no complications. Univariate and multivariate analyses were conducted. RESULTS: Study findings highlighted both good practices and gaps in QoC, with major differences in QOC across facilities. Documentation of body weight and temperature varied from 7.7% to 98.5% and from 50% to 97.7%, respectively (p<0.001); antibiotic and probiotic prescription rates ranged from 0% to 10.1% and from 0% to 80.8%, respectively (p<0.001); hospitalisations rates ranged between 8.5% and 62.8% (p<0.001); written indications for reassessment were provided in 10.4%-90.2% of cases (p<0.001). When corrected for children's individual characteristics, the variable more consistently associated with each analysed outcome was the individual facility. Higher rates of antibiotics prescription (+7.6%, p=0.04) and hospitalisation (+52.9%, p<0.001) were observed for facilities in Southern Italy, compared with university centres (-36%, p<0.001), independently from children characteristics. Children's clinical characteristics in each centre were not associated with either hospitalisation or antibiotic prescription rates. CONCLUSIONS: The 10 prioritised WHO-Standard-based Quality Measures allow a rapid assessment of QOC in children with AD. Action is needed to identify and implement sustainable and effective interventions to ensure high QOC for all children.

Implementation of the WHO standards to assess quality of care for children with acute pain in EDs: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is little experience on the use of the WHO Standards for improving the quality of care (QOC) for children. We describe the use of four prioritised WHO Standard-based Quality Measures to assess the provision of care for children with pain in emergency departments (EDs). METHODS: In a multicentre observational study in 10 EDs with different characteristics in Italy, we collected data on 3355 children accessing the EDs between January 2019 and December 2020. The association between children and facility characteristics and quality measures was analysed through multivariate analyses. RESULTS: The proportion of children whose pain was measured was 68.7% (n=2305), with extreme variations across different centres (from 0.0% to 99.8%, p<0.001). The proportion of children treated for pain was 28.9% (n=970) again with a wide range (5.3%-56.3%, p<0.001). The difference between the frequency of children with pain measured and pain treated varied widely between the facilities (ranging from -24.3 to 82). Children with moderate and severe pain were more frequently treated (48.9% and 62.9% of cases, respectively), although with large variations across centres (ranges: 0%-74.8% and 0%-100% respectively, p<0.001). After correction for children's characteristics, the variable more strongly associated with analysed outcomes was the facility which the child accessed for care. Being a facility in Northern Italy was associated with a higher rate of pain measurement (67.3%-95% CI: 39.9% to 94.6%, p<0.001) compared with facilities in South Italy (-22.1% lower (95% CI: -41.7% to -2.50%, p=0.03). CONCLUSIONS: The use of few WHO Standard-based measures related to pain can help identifying priority gaps in QOC for children and in monitoring it over time. There is a need for more implementation research to establish which are the most sustainable and effective interventions to improve the QOC for acute pain in children.

Implementation of the WHO Standards to assess quality of paediatric care at the facility level using service users' perspective as source of data: a multicentre quality improvement study in Italy.

OBJECTIVES: There is little experience in the use of the WHO Standards for improving the quality of care (QOC) for children at the facility level. We describe the use of 75 WHO Standard based Quality Measures to assess paediatric QOC, using service users as a source of data, in Italy. STUDY DESIGN: In a cross-sectional study including 12 hospitals, parents/caregivers of admitted children completed a validated questionnaire including 75 Quality Measures: 40 pertinent to the domain of experience of care; 25 to physical/structural resources; 10 to COVID-19 reorganisational changes. Univariate and multivariate analyses were conducted. RESULTS: Answers from 1482 service users were analysed. Physical resources was the domain with the higher frequency of reported gaps in QOC, with key gaps (higher rates of responders reporting need for improvement and low variability across centres) being: (1) quality of meals (48.1%; range across facilities: 35.3%-61.7%); (2) presence of cooking areas (50.9%; range: 34.6%-70.0%); (3) spaces for family/friends (51.3%; range: 31.8%-77.4%). For experience of care, the most critical gap was the information on the rights of the child (76.6%; range: 59.9%-90.4%), with most other Quality Measures showing an overall frequency of reported need for improvement ranging between 5% and 35%. For reorganisational changes due to COVID-19 an improvement was felt necessary by <25% of responders in all Quality Measures, with low variability across centres. At the multivariate analyses, factors significantly associated with the QOC Index largely varied by QOC domain. CONCLUSIONS: The use of the 75 prioritised Quality Measures, specific to service users' perspective, enabled the identification of both general and facility-specific gaps in QOC. Based on these findings, quality improvement initiatives shall focus on a core list of selected Quality Measures common to all facilities, plus on an additional list of Quality Measures as more relevant in each facility.

Evaluation of the WHO standards to assess quality of care for children with acute respiratory infections: findings of a baseline multicentre assessment (CHOICE) in Italy.

BACKGROUND: Experience is lacking on the implementation of the WHO standards for improving the quality of care (QOC) for children at facility level. We describe the use of 10 prioritised WHO standard-based quality measures to assess provision of care for children with acute respiratory infections (ARI) in Italy. METHODS: In a multicentre observational study across 11 emergency departments with different characteristics, we collected 10 WHO standard-based quality measures related to case management of children with ARI and no emergency/priority signs. Univariate and multivariate analyses were conducted. RESULTS: Data from 3145 children were collected. Major differences in QOC across facilities were observed: documentation of saturation level and respiratory rate varied from 34.3% to 100% and from 10.7% to 62.7%, respectively (p<0.001); antibiotic prescription rates ranged from 22.6% to 80.0% (p<0.001), with significant differences in the pattern of prescribed antibiotic; hospitalisations rates ranged between 2.3% and 30.6% (p<0.001). When corrected for children's individual sociodemographic and clinical characteristics, the variable more consistently associated with each analysed outcome was the individual facility where the child was managed. Higher rates of antibiotics prescription (+33.1%, p<0.001) and hospitalisation (+24.7%, p<0.001) were observed for facilities in Southern Italy, while university centres were associated with lower hospitalisation rates (-13.1%, p<0.001), independently from children's characteristics. CONCLUSIONS: The use of 10 WHO standard-based measures can help quickly assess QOC for children with ARI. There is an urgent need to invest more in implementation research to identify sustainable and effective interventions to ensure that all children receive high QOC.

Congenital erythrocytosis associated with gain-of-function HIF2A gene mutations and erythropoietin levels in the normal range.

Hypoxia-inducible factor 2α (HIF-2α) plays a pivotal role in the balancing of oxygen requirements throughout the body. The protein is a transcription factor that modulates the expression of a wide array of genes and, in turn, controls several key processes including energy metabolism, erythropoiesis and angiogenesis. We describe here the identification of two cases of familial erythrocytosis associated with heterozygous HIF2A missense mutations, namely Ile533Val and Gly537Arg. Ile533Val is a novel mutation and represents the genetic HIF2A change nearest to Pro-531, the primary hydroxyl acceptor residue, so far identified. The Gly537Arg missense mutation has already been described in familial erythrocytosis. However, our patient is the only described case of a de novo HIF2A mutation associated with the development of congenital polycythemia. Functional in vivo studies, based on exogenous expression of hybrid HIF-2α transcription factors, indicated that these genetic alterations lead to the stabilization of HIF-2α protein. All the identified polycythemic subjects with HIF2A mutations show serum erythropoietin in the normal range, independently of the hematocrit values and phlebotomy frequency. The erythroid precursors obtained from the peripheral blood of patients showed an altered phenotype, including an increased rate of growth and a modified expression of some HIF-2α target genes. These results suggest the novel proposal that polycythemia observed in subjects with HIF2A mutations might also be due to primary changes in hematopoietic cells and not only secondary to increased erythropoietin levels.

Clinical and molecular description of a Wilms tumor in a patient with tuberous sclerosis complex.

We report on a girl affected with tuberous sclerosis, carrying a germline de novo TSC2 mutation, c.4934-4935delTT, leading to a p.F1645CfsX7, who developed a unilateral Wilms tumor (WT). Molecular investigation of the tumor biopsy at diagnosis revealed the loss of the constitutional wild-type TSC2 allele, and loss of heterozygosity for the WT1 gene. Deletion of the WTX gene was also present, but it involved the functionally inactive X chromosome. No mutation affecting the remaining WT1 and WTX alleles, as well as the CTNNB1 gene was found. Pathological examination of the surgical specimen documented the presence of diffuse anaplasia and p53 immunoreactivity. To the best of our knowledge, this is the second report of a patient with tuberous sclerosis who developed a WT, and it represents the first case in which a detailed clinical and molecular description is provided.

Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association.

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.