Comparison between the Viral Illness Caused by SARS-CoV-2, Influenza Virus, Respiratory Syncytial Virus and Other Respiratory Viruses in Pediatrics.

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.

The impact of Antimicrobial Stewardship Programmes in paediatric emergency departments and primary care: a systematic review.

Background: Antibiotics remain the most prescribed medicine in children worldwide, but half of the prescriptions are unnecessary or inappropriate, leading to an increase in antibiotic resistance. This study aims to systemically review the effects of different Antimicrobial Stewardship Programmes (ASPs) on reducing the rates of both antibiotic prescriptions and changes in antimicrobial resistance, and on the economic impact in paediatric emergency departments (PED) and primary care settings. Materials and methods: Embase, MEDLINE, and Cochrane Library were systematically searched, combining Medical Subject Heading and free-text terms for 'children' and 'antimicrobial' and 'stewardship'. The search strategy involved restrictions on dates (from 1 January 2007 to 30 December 2020) but not on language. Randomized controlled trials, controlled and non-controlled before and after studies, controlled and non-controlled interrupted time series, and cohort studies were included for review. The review protocol was registered at the PROSPERO International Prospective Register of Systematic Reviews: Registration Number CRD42021270630. Results: Of the 47,158 articles that remained after removing duplicates, 59 were eligible for inclusion. Most of the studies were published after 2015 (37/59, 62.7%) and in high-income countries (51/59, 86.4%). Almost half of the studies described the implementation of an ASP in the primary care setting (28/59, 47.5%), while 15 manuscripts described the implementation of ASPs in EDs (15/59, 25.4%). More than half of the studies (43/59, 72.9%) described the implementation of multiple interventions, whereas few studies considered the implementation of a single intervention. Antibiotic prescriptions and compliance with guidelines were the most frequent outcomes (47/59, 79.7% and 20/59, 33.9%, respectively). Most of the articles reported an improvement in these outcomes after implementing an ASP. Meanwhile, only very few studies focused on health care costs (6/59, 10.2%) and antimicrobial resistance (3/59 5.1%). Conclusion: The implementation of ASPs has been proven to be feasible and valuable, even in challenging settings such as Emergency Departments and Primary care.

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale's severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

Point-of-Care and Rapid Tests for the Etiological Diagnosis of Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis.

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for respiratory tract infections on changing antibiotic prescription rate, length of stay, duration of therapy, and healthcare costs. Embase, MEDLINE, and Cochrane Library databases were systematically searched. All randomized control trials and non-randomized observational studies meeting inclusion criteria were evaluated using the NIH assessment tool. A meta-analysis was performed to assess the effects of rapid influenza diagnostic tests and film-array respiratory panel implementation on selected outcomes. From a total of 6440 studies, 57 were eligible for the review. The analysis was stratified by setting and POCT/rapid test type. The most frequent POCTs or rapid tests implemented were the Rapid Influenza Diagnostic Test and film-array and for those types of test a separate meta-analysis assessed a significant reduction in antibiotic prescription and an improvement in oseltamivir prescription. Implementing POCTs and rapid tests to discriminate between viral and bacterial infections for respiratory pathogens is valuable for improving appropriate antimicrobial prescriptions. However, more studies are needed to assess these findings in pediatric settings.

Multistep antimicrobial stewardship intervention on antibiotic prescriptions and treatment duration in children with pneumonia.

INTRODUCTION: The Italian antimicrobial prescription rate is one of the highest in Europe, and antibiotic resistance has become a serious problem with high costs and severe consequences, including prolonged illnesses, the increased period of hospitalization and mortality. Inadequate antibiotic prescriptions have been frequently reported, especially for lower respiratory tract infections (LRTI); many patients receive antibiotics for viral pneumonia or bronchiolitis or broad-spectrum antibiotics for not complicated community-acquired pneumonia. For this reason, healthcare organizations need to implement strategies to raise physicians' awareness about this kind of drug and their overall effect on the population. The implementation of antibiotic stewardship programs and the use of Clinical Pathways (CPs) are excellent solutions because they have proven to be effective tools at diagnostic and therapeutic levels. AIMS: This study evaluates the impact of CPs implementation in a Pediatric Emergency Department (PED), analyzing antibiotic prescriptions before and after the publication in 2015 and 2019. The CP developed in 2019 represents an update of the previous one with the introduction of serum procalcitonin. The study aims to evaluate the antibiotic prescriptions in patients with community-acquired pneumonia (CAP) before and after both CPs (2015 and 2019). METHODS: The periods analyzed are seven semesters (one before CP-2015 called PRE period, five post CP-2015 called POST 1-5 and 1 post CP-2019 called POST6). The patients have been split into two groups: (i) children admitted to the Pediatric Acute Care Unit (INPATIENTS), and (ii) patients evaluated in the PED and sent back home (OUTPATIENTS). We have analyzed all descriptive diagnosis of CAP (the assessment of episodes with a descriptive diagnosis were conducted independently by two pediatricians) and CAP with ICD9 classification. All antibiotic prescriptions for pediatric patients with CAP were analyzed. RESULTS: A drastic reduction of broad-spectrum antibiotics prescription for inpatients has been noticed; from 100.0% in the PRE-period to 66.7% in POST1, and up to 38.5% in POST6. Simultaneously, an increase in amoxicillin use from 33.3% in the PRE-period to 76.1% in POST1 (p-value 0.078 and 0.018) has been seen. The outpatients' group's broad-spectrum antibiotics prescriptions decreased from 54.6% PRE to 17.4% in POST6. Both for outpatients and inpatients, there was a decrease of macrolides. The inpatient group's antibiotic therapy duration decreased from 13.5 days (PRE-period) to 7.0 days in the POST6. Antibiotic therapy duration in the outpatient group decreased from 9.0 days (PRE) to 7.0 days (POST1), maintaining the same value in subsequent periods. Overlapping results were seen in the ICD9 group for both inpatients and outpatients. CONCLUSIONS: This study shows that CPs are effective tools for an antibiotic stewardship program. Indeed, broad-spectrum antibiotics usage has dropped and amoxicillin prescriptions have increased after implementing the CAP CP-2015 and the 2019 update.

A Procalcitonin and C-Reactive Protein-Guided Clinical Pathway for Reducing Antibiotic Use in Children Hospitalized with Bronchiolitis.

Despite the lack of evidence that bronchodilators, corticosteroids, and antibiotics are useful in treating bronchiolitis, their use is still widespread. This study aimed to determine the consumption of antibiotics for bronchiolitis before and after a procalcitonin-guided clinical pathway (CP) implementation. In December 2019, a CP for lower respiratory tract infection management was implemented at the Department of Women's and Children's Health at Padua University Hospital. This was a pre-post, quasi-experimental study that assessed the changes in the treatment of bronchiolitis during two bimesters preceding the CP implementation (pre-period: January 2018-February 2018 and January 2019-February 2019) and during the bimester after CP implementation (post-period January 2020-February 2020). After the CP implementation, there was a significant reduction in antibiotic prescriptions from 36.2% to 12.5% (p = 0.036) in patients hospitalized for bronchiolitis. Co-amoxiclav treatment, the antibiotic most commonly administered, decreased from 66.6% to 33.3%. Among outpatients' bronchiolitis episodes, a statistically significant decrease in beta2-agonists' use (from 18.0% to 4.4%, pre and post periods) and a quasi-significant decrease in corticosteroid use (from 8.0% to 0% pre and post periods) were observed. An evidence-based CP supported by educational lectures was associated with significant changes in the physicians' prescribing habits.

Children's Hospital Management in the COVID-19 Era: The Reorganization of a Tertiary Care Pediatric Emergency Department in Northern Italy.

In the Veneto Region, an exponential spread of patients affected by 2019 novel Coronavirus disease (COVID-19) has been observed after February 21st. Since then, we have been evaluating children suspected or confirmed for SARS-CoV-2 infection. A protocol for pediatric hospital reorganization and children management has been developed, since the beginning of the epidemic. A pre-triage area has been created at the immediate entrance of the pediatric emergency room, for all uncritical pediatric patients. According to the epidemiologic and clinical risk factors, all children/adolescents have been addressing to one of the four different pathways created. The strict application of this protocol has been leading to quickly identification, isolation, and management of all positive children, preventing SARS-CoV-2 intrahospital spread.

The PIPER WEEKEND study. Children's and adults satisfaction regarding paediatric pain in Italian Emergency Department.

BACKGROUND: Despite pain being a crucial aspect of urgent-emergency care, the attention of healthcare workers towards this symptom in the Emergency Department (ED) is still inadequate. The aims of this study were to assess children's and their adults accompanier's satisfaction regarding pain management in Italian ED, considering healthcare workers' attention to the symptom as well as the appropriateness and efficacy of treatments received. METHODS: Questionnaires were administered face-to-face by trained interviewers over the period of one weekend in 29 Italian ED. The questionnaires were addressed to children 3-16 years old, assigned a green code at triage, and their adult accompaniers. RESULTS: Overall, 1581 questionnaires were administered (923 to parents or caregivers, 658 to children). The reported level of attention to pain by the care team was high (57.20%) as was the adults' satisfaction with the pain management (95.01%); a high level of satisfaction was related to the healthcare workers' attention to pain. According to the adults, 73.56% of the healthcare professionals collected accurate information about pain; this was confirmed by the children. Pain was managed by a doctor-and-nurse team in less than half the cases (43.77%). Therapy efficacy was reportedly poor: only 14.01% of children were pain-free when leaving the ED. CONCLUSIONS: Despite increasing understanding of pain and the availability of guidelines and effective analgesics, efficient pain relief in paediatric patients in the ED remains an unfulfilled goal: half of children with pain did not receive any treatments. Therefore the quality of pain management in the ED needs to be improved.

Posaconazole oral dose and plasma levels in pediatric hematology-oncology patients.

BACKGROUND: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level. METHODS: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included. RESULTS: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 µg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 µg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04. CONCLUSIONS: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.

Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia.

We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD) with severe and chronic pain who was successfully treated with zoledronic acid (ZOL): a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

Treatment of Acute Graft-versus-Host Disease in Childhood with Extracorporeal Photochemotherapy/Photopheresis: The Padova Experience.

Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease.