Coronary Arteries Lesions in Kawasaki Disease: Risk Factors in an Italian Cohort.

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort.

Effects of COVID-19-targeted non-pharmaceutical interventions on pediatric emergency department use: a quasi-experimental study interrupted time-series analysis in North Italian hospitals, 2017 to 2022.

Background: The use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important. Methods: This is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation. Results: In the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. "Symptoms, signs and Ill-defined conditions," "Injury and poisoning" and "Diseases of the Respiratory System" accounted for 74% of the reduction. A different pattern was instead seen for "Mental Disorders," which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12-0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13-1.33), with the sharpest decline (-94%) and rise (+36%) observed in the "Diseases of the Respiratory System" category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM. Conclusion: NPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Effects of COVID-19-targeted non-pharmaceutical interventions on pediatric hospital admissions in North Italian hospitals, 2017 to 2022: a quasi-experimental study interrupted time-series analysis.

Background: The use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs. Methods: This is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends. Results: Overall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for "Respiratory Diseases," whereas the "Mental Disorders" category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08-0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30-0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98-1.69). Conclusion: Our findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

Nationwide survey on the management of pediatric pharyngitis in Italian emergency units.

BACKGROUND: Acute pharyngitis is a frequent reason for primary care or emergency unit visits in children. Most available data on pharyngitis management come from primary care studies that demonstrate an underuse of microbiological tests, a tendency to over-prescribe antibiotics and a risk of antimicrobial resistance increase. However, a comprehensive understanding of acute pharyngitis management in emergency units is lacking. This study aimed to investigate the frequency of rapid antigen test use to diagnose acute pharyngitis, as well as other diagnostic approaches, the therapeutic attitude, and follow-up of children with this condition in the emergency units. METHODS: A multicentric national study was conducted in Italian emergency departments between April and June 2022. RESULTS: A total of 107 out of 131 invited units (response rate 82%), participated in the survey. The results showed that half of the units use a scoring system to diagnose pharyngitis, with the McIsaac score being the most commonly used. Most emergency units (56%) were not provided with a rapid antigen diagnostic test by their hospital, but the test was more frequently available in units visiting more than 10,000 children yearly (57% vs 33%, respectively, p = 0.02). Almost half (47%) of the units prescribe antibiotics in children with pharyngitis despite the lack of microbiologically confirmed cases of Group A ß-hemolytic streptococcus. Finally, about 25% of units prescribe amoxicillin-clavulanic acid to treat Group A ß-hemolytic streptococcus pharyngitis. CONCLUSIONS: The study sheds light on the approach to pharyngitis in emergency units, providing valuable information to improve the appropriate management of acute pharyngitis in this setting. The routinary provision of rapid antigen tests in the hospitals could enhance the diagnostic and therapeutic approach to pharyngitis.

UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

Triage Grading and Correct Diagnosis Are Critical for the Emergency Treatment of Anaphylaxis.

Introduction: Anaphylaxis is one of the most frequent and misdiagnosed emergencies in the pediatric emergency department (PED). We aimed to assess which factors play a major role for a correct diagnosis and an appropriate therapy. Methods: We reviewed the records of children discharged with a diagnosis of anaphylaxis or an allergic reaction over 11 years from 3 hospitals in the Bologna city area. Results: One hundred and sixteen cases matched the criteria (0.03% of the total admittances) and were divided according to the patients' symptoms at arrival: active acute patients [AP], n = 50, or non-acute patients ([NAP], n = 66). At the patients' discharge, anaphylaxis was diagnosed in 39 patients (33.6%). Some features seemed to favor a correct diagnosis: active symptoms at arrival (AP vs. NAP, p < 0.01), high-priority triage code (p < 0.01), and upper airway involvement (p < 0.01). Only 14 patients (12.1%), all in the AP group, received epinephrine, that was more likely administered to patients recognized to have anaphylaxis (p < 0.01) and with cardiovascular, respiratory, or persistent gastrointestinal symptoms (p < 0.02), as confirmed by logistic regression analysis. Conclusions: Anaphylaxis is still under-recognized and under-treated. Correct triage coding and a proper diagnosis seem to foster an appropriate treatment. Physicians often prefer third-line interventions. Specific training for nurses and physicians might improve the management of this disease.

Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice.

AIM: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. METHODS: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. RESULTS: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. CONCLUSION: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits.

Pediatric Adverse Drug Reactions: An Observational Cohort Study After Health Care Workers' Training.

OBJECTIVE: Adverse drug reactions (ADRs) in children are an important but underestimated public health issue. This study describes ADRs in a registered pediatric population of Bologna and demonstrates that ADRs might be better detected after health care personnel training. METHODS: A prospective cohort was recruited from July 1, 2016, to June 30, 2019, after health care worker sensitization, and compared to a retrospective cohort enrolled from 2013 to 2016. The ADRs are classified by system organ classes and drugs are categorized according to the Anatomical Therapeutic Chemical classification system. RESULTS: We retrospectively recruited 78 pediatric patients with ADRs in the 2013 to 2016 period, and we prospectively enrolled 127 children in the 2016 to 2019 period. In both periods, most of the ADRs reported were classified as non-serious reactions (68.8%). The most frequent ADRs were general and administration site disorders. During 2013 to 2016 vaccines were the most frequent cause of ADRs (83.3%;) and the main reporters were health care workers other than physicians (84.6%), whereas during the second period, medical doctors become the main signalers (65.4%) and ADRs related to vaccines significantly decreased (55.1%). During the 2016 to 2019 period the number of drug categories was higher than in the 2013 to 2016 period (24 vs 8). Patients with ADRs due to vaccinations present more frequently a favourable outcome (63%). CONCLUSIONS: This study demonstrates that active pharmacovigilance and health care personnel sensitization are associated with improved ADR detection, providing valuable information about drugs' safety profile in pediatric patients.

Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Children: One Year after the Onset of the Pandemic in a High-Incidence Area.

SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.

Vaccines in Children with Inflammatory Bowel Disease: Brief Review.

Incidence of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Children with IBDs have a dysfunctional immune system and they are frequently treated with immunomodulating drugs and biological therapy, which significantly impair immune system functions and lead to an increased risk of infections. Vaccines are essential to prevent at least part of these infections and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended. However, several factors might lead to insufficient immunization. In this paper, present knowledge on the use of vaccines in children with IBDs is discussed. Literature review showed that despite a lack of detailed quantification of the risk of infections in children with IBDs, these children might have infections more frequently than age-matched healthy subjects, and at least in some cases, these infections might be even more severe. Fortunately, most of these infections could be prevented when recommended schedules of immunization are carefully followed. Vaccines given to children with IBDs generally have adequate immunogenicity and safety. Attention must be paid to live attenuated vaccines that can be administered only to children without or with mild immune system function impairment. Vaccination of their caregivers is also recommended. Unfortunately, compliance to these recommendations is generally low and multidisciplinary educational programs to improve vaccination coverage must be planned, in order to protect children with IBD from vaccine-preventable diseases.

Myocarditis and coronary aneurysms in a child with acute respiratory syndrome coronavirus 2.

A 6-year-old African boy with multi-viral infection including parvovirus B19 and severe acute respiratory syndrome coronavirus 2 was admitted for persistent fever associated with respiratory distress and myocarditis complicated by cardiogenic shock needing ventilatory and inotropic support. Coronary aneurysms were also documented in the acute phase. Blood tests were suggestive of macrophage activation syndrome. He was treated with intravenous immunoglobulins, aspirin, diuretics, dexamethasone, hydroxychloroquine, and prophylactic low molecular weight heparin. Normalization of cardiac performance and coronary diameters was noticed within the first days. Cardiac magnetic resonance imaging, performed 20 days after the hospitalization, evidenced mild myocardial interstitial oedema with no focal necrosis, suggesting a mechanism of cardiac stunning related to cytokines storm rather than direct viral injury of cardiomyocytes.

Dural sinus mechanical thrombectomy and continuous local rt-PA infusion in a child with refractory intracranial hypertension and progressive visual loss: A case report.

BACKGROUND: Children with intracranial hypertension are at risk for visual loss and their visual function must be closely monitored. Surgery with the insertion of a ventriculoperitoneal shunt is imperative when vision is threatened. CASE DESCRIPTION: Herein, we report a case of a 5-year-old boy whose refractory intracranial hypertension and severe, progressive visual loss (secondary to a chronic, otogenic, right sigmoid sinus thrombosis, and a contralateral sinus tight stenosis) were resolved by a combination of continuous (6 h), locoregional, infusion of recombinant tissue plasminogen activator (rt-PA), and mechanical thrombectomy. CONCLUSION: The association of in loco and continuous infusion of recombinant tissue plasminogen activator (rt- PA) with mechanical thrombectomy resulted in effective in partially reopening the occluded sinus and facilitating a good clinical recovery. This combined endovascular approach may represent an alternative, less invasive, therapeutic option to surgery in children with intracranial hypertension caused by chronic cerebral venous sinus thrombosis.

Bilateral Facial Nerve Palsy in a Child: When the Smile Returns.

Bilateral facial nerve palsy (FNP) is an extremely rare clinical condition. Different from unilateral FNP, because of idiopathic or Bell's palsy in the majority of cases, bilateral FNP is most often correlated to an underlying medical condition, which can be congenital, neurological, infectious, neoplastic, traumatic, or metabolic. We describe the case of an 8-year-old girl with bilateral facial paralysis because of Epstein-Barr virus infection with late diagnosis and therapy. We discuss the differential diagnosis hypothesis, focusing on the different outcome and recovery times in relation to the timing of treatment.