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.

The role of Electroencephalography in children with Acute Altered Mental Status of unknown etiology: a prospective study.

INTRODUCTION: Acute alterated mental status (AAMS) is often a challenge for clinicians, since the underlying etiologies cannot always easily be inferred based on the patient's clinical presentation, medical history or early examinations. The aim of this study is to evaluate the role of the electroencephalogram (EEG) as a diagnostic tool in AAMS of unknown etiology in children. MATERIALS AND METHODS: We conducted a prospective study involving EEG assessments on children presenting with AAMS between May 2017 and October 2019. Inclusion criteria were age 1 month to 18 years and acute (<1 week) and persistent (>5 minutes) Altered mental status (AMS). Patients with a known etiology of AAMS were excluded. A literature review was also performed. RESULTS: Twenty patients (median age: 7.7 years, range: 0.5-15.4) were enrolled. EEG contributed to the diagnosis in 14/20 cases, and was classified as diagnostic in 9/20 and informative in 5/20. Specifically, EEG was able to identify nonconvulsive status epilepticus (NCSE) in 5 children and psychogenic events in 4. EEG proved to be a poorly informative diagnostic tool at AAMS onset in 6 children, however in 5 of them, it proved useful during follow-up. CONCLUSIONS: Limited data exist regarding the role of EEG in children with AAMS of unknown etiology. In our population EEG proved to be valuable tool, and was especially useful in the prompt identification of NCSE and psychogenic events.

Impact of Inflammatory Burden on Voriconazole Exposure in Oncohematological Pediatric Patients Receiving Antifungal Prophylaxis after Allogeneic HCT.

(1) Background: The impact of inflammation on voriconazole exposure in oncohematological pediatric patients represents a debated issue. We aimed to investigate the impact of serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels on voriconazole exposure in oncohematological pediatric patients requiring allogeneic hematopoietic stem cell transplantation (HCT). (2) Methods: Pediatric patients undergoing allogeneic HCT and receiving therapeutic drug monitoring (TDM)-guided voriconazole as primary antifungal prophylaxis between January 2021 and December 2023 were included. The ratio between concentration and dose (C/D) of voriconazole was used as a surrogate marker of total clearance. A receiving operating characteristic curve analysis was performed by using CRP, PCT, or IL-6 values as the test variable and voriconazole C/D ratio > 0.188 or >0.375 (corresponding to a trough concentration value [Cmin] of 3 mg/L normalized to the maintenance dose of 16 mg/kg/day in patients of age < 12 years and of 8 mg/kg/day in those ≥12 years, respectively) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. (3) Results: Overall, 39 patients were included. The median (IQR) voriconazole Cmin was 1.7 (0.7-3.0) mg/L. A CRP value > 8.49 mg/dL (AUC = 0.72; 95%CI 0.68-0.76; p < 0.0001), a PCT value > 2.6 ng/mL (AUC = 0.71; 95%CI 0.63-0.77; p < 0.0001), and an IL-6 value > 27.9 pg/mL (AUC = 0.80; 95%CI 0.71-0.88; p < 0.0001) were significantly associated with voriconazole overexposure. Consistent results were found in patients aged <12 and ≥12 years. (4) Conclusions: A single specific threshold of inflammatory biomarkers may be linked to a significantly higher risk of voriconazole exposure in oncohematological pediatric patients after HCT, irrespective of age. Adopting a TDM-guided strategy could be useful for minimizing the risk of voriconazole overexposure.

Atypical clinical and sonographic manifestations of lymphadenopathy in a child with cat-scratch disease: A case report.

Cat-scratch disease is a well-known infection in childhood. It usually presents as tender lymphadenopathy and should be included in the differential diagnosis of any lymphadenopathy syndrome. An history of exposure to cats supports the suspect and a positive serologic test to Bartonella henselae confirms the diagnosis. Ultrasound is the first line radiologic imaging performed in case of lymphadenopathy. The presence of hypoechoic lobular or oval mass with central hyperaemia and a possible adjacent fluid collection and surrounding oedema may differentiate the disease from other aetiologies. We describe the case of a 7-year-old girl presenting with an axillary lymphadenopathy, without a reported recent history of exposure to cats, with sonographic findings suggestive for cat-scratch disease. In this case, ultrasound was very useful in orienteering the diagnosis and insist on the medical history. Serology resulted positive for B. henselae and at the end the family remembered that 6 months before the child was scratched by a kitten.

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.

Maternal Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Otherwise Healthy Preterm and Term Infants: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVE: To date, there is no published, formal assessment of all maternal risk factors for respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) in infants. A systematic literature review and meta-analysis were undertaken to ascertain: What maternal risk factors are associated with an increased risk of RSV-LRTI in infants? METHODS: The systematic literature review used explicit methods to identify, select and analyze relevant data. PubMed, Embase and the Cochrane Library were searched (November 2022) using terms regarding: (1) RSV/LRTI; (2) risk factors; (3) pregnant/postpartum population. Bayesian meta-analysis compared RSV hospitalization (RSVH) risk in infants born to mothers with or without certain risk factors. RESULTS: A total of 2353 citations were assessed and 20 were included in the final review (10 individual studies; 10 pooled analyses). In 10 studies examining infants (<1 year) without comorbidities (primary outcome), 10 maternal risk factors were associated with RSV-LRTI/RSVH in multivariate analyses. Meta-analysis revealed smoking while pregnant increased infant RSVH risk by 2.01 (95% credible interval: 1.52-2.64) times, while breast-feeding was protective (0.73, 95% credible interval: 0.58-0.90). Risk scoring tools have reported that maternal risk factors contribute between 9% and 21% of an infant's total risk score for RSVH. CONCLUSIONS: A greater understanding of maternal risk factors and their relative contribution to infant RSV-LRTI will enable more accurate assessments of the impact of preventive strategies.

The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET.

Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin's lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation.

Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

National survey conducted among Italian pediatricians examining the therapeutic management of croup.

OBJECTIVES: Practice-to-recommendations gaps exist in croup management and have not been critically investigated. This study examined the therapeutic management of croup among a national sample of Italian pediatric providers. METHODS: A survey was administered online to a sample of primary care and hospital-based pediatricians. Demographic data, perception regarding disease severity, treatment and knowledge of croup, choices of croup treatment medications, and knowledge of and adherence to treatment recommendations were compared between hospital and primary care pediatricians. Oral corticosteroids alone, oral corticosteroids with or without nebulized epinephrine and nebulized epinephrine plus oral or inhaled corticosteroids were considered the correct management in mild, moderate and severe croup, respectively. The determinants for correct management were examined using multivariate logistic regression analysis. RESULTS: Six hundred forty-nine pediatricians answered at least 50% of the survey questions and were included in the analysis. Providers reported extensive use of inhaled corticosteroids for mild and moderate croup. Recommended treatment for mild, moderate and severe croup was administered in 46/647 (7.1%), 181/645 (28.0%) and 263/643 (40.9%) participants, respectively. Provider's age and knowledge of Westley Croup Score were significant predictors for correct management of mild croup. Being a hospital pediatrician and perception of croup as a clinically relevant condition were significant for moderate croup. CONCLUSIONS: Significant differences exist between recommended guidelines and clinical practice in croup management. This study suggests wide variability in both the treatment of croup and clinical decision making strategies among hospital and primary care pediatricians. Addressing this issue could lead to noteworthy clinical and economic benefits.

Parents' and nurses' affective perception of a pictorial intervention in a pediatric hospital environment: Quasi-experimental design pre-post-testing.

BACKGROUND/AIM: The humanization of the hospital environment of pediatric departments represents an area of research and intervention on improving the quality of life for hospitalized patients, but also that one of relatives and health professionals. The aim of the study was to test, in a sample of nurses and hospitalized children's parents, whether the pictorial intervention impacted the perceptions of affective qualities of hospital environment. METHODS: This quasi-experimental design study investigated the effects of a pictorial humanization intervention which consisted of some naturalistic and colorful illustrations in the corridor of two pediatric wards of an Italian hospital. A total of 425 parents of hospitalized children and 80 nurses were asked to complete the Italian version of the "Scale of measurement of the affective qualities of places" in two different moments: 1) before the pictorial intervention and 2) three months after its implementation. RESULTS: For all participants (parents and nurses), results showed a significant effect of pictorial intervention with the four positive dimensions investigated (Relaxing, Exciting, Pleasant, and Stimulating) reporting higher scores after being performed it, and with the four negative dimensions (Distressing, Gloomy, Unpleasant, Sleepy) showing lower scores. CONCLUSIONS: Data suggest that the pictorial intervention could be particularly useful to create more welcoming hospital environments, reducing distress levels from hospitalized patients, but also of relatives and healthcare professionals. IMPLICATIONS TO PRACTICE: Pictorial interventions improve the emotional atmosphere in pediatric healthcare settings. Integrating visual elements related to care and healing enhances user experience, creating a more welcoming environment.

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.

Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

Adherence to the Mediterranean Diet in Children and Adolescents and Association with Multiple Outcomes: An Umbrella Review.

The Mediterranean Diet (MD) has been linked to numerous health benefits. This umbrella review aims to synthesize evidence from systematic reviews on the MD's impact on children and adolescents aged 6 to 19 years. Following Joanna Briggs Institute guidelines, we included 11 systematic reviews focusing on the MD's effects on health outcomes, such as asthma, anthropometric measures, physical fitness, and inflammatory markers. The results indicate a protective role of the MD against childhood asthma due to its antioxidant-rich components. However, evidence for its impact on allergic conditions like rhinitis and eczema is inconclusive. Findings regarding anthropometric outcomes, particularly BMI, are limited and inconsistent. A positive correlation was observed between MD adherence and increased physical activity, improved physical fitness, quality of life, and reduced sedentary behavior. Additionally, the MD showed an inverse relationship with pro-inflammatory biomarkers, suggesting anti-inflammatory benefits. The inconsistency in BMI findings and the potential anti-inflammatory properties of the MD warrant further longitudinal research. Future studies should explore the MD's impact on cognitive functions, academic performance, and mental health in this age group, highlighting the significance of establishing healthy eating habits early in life.

Body Mass Index (BMI) Is the Strongest Predictor of Systemic Hypertension and Cardiac Mass in a Cohort of Children.

BACKGROUND: Hypertension (HTN) is a well-established cardiovascular (CV) risk factor in adults. The presence of HTN in children appears to predict its persistence into adulthood. Early diagnosis of HTN is crucial to reduce CV morbidity before the onset of organ damage. AIM: The aim of this study is to investigate cardiac damage in HTN, its risk factors (RFs), and evolution. METHODS: We conducted a prospective/retrospective study involving children referred to the Childhood Hypertension Outpatient Clinic. This study included clinical and echocardiographic assessments of cardiac morphology and function at three time points: enrollment (T0) and follow-up (T1 and T2). RESULTS: Ninety-two patients (mean age 11.4 ± 3 years) were enrolled. Cardiac eccentric and concentric hypertrophy were present in 17.9% and 9%, respectively, with remodeling in 10.5%. Overweight/obese subjects exhibited significantly higher systolic blood pressure (SBP), frequency of HTN, and body mass index (BMI) at T0 compared with patients with chronic kidney disease (CKD). SBP and BMI persisted more during follow-up. Normal-weight vs. overweight/obese patients were significantly more likely to have normal geometry. Positive correlations were found between BMI and left ventricular (LV) mass at T0, BMI and SBP at T0 and T1. Gender, BMI, SBP, and diastolic blood pressure (DBP) significantly predicted LV mass index (LVMI), but only BMI added significance to the prediction. During follow-up, the variation of BMI positively correlated with the variation of SBP, but not with LVMI. CONCLUSIONS: In our cohort, body weight is strongly associated with HTN and cardiac mass. Importantly, the variation in body weight has a more significant impact on the consensual variation of cardiac mass than blood pressure (BP) values. A strict intervention on weight control through diet and a healthy lifestyle from early ages might reduce the burden of CV morbidity in later years.

Innovative strategies to predict and prevent the risk for malnutrition in child, adolescent, and young adult cancer survivors.

Children, adolescents, and young adult cancer survivors (CAYAs) constitute a growing population requiring a customized approach to mitigate the incidence of severe complications throughout their lifetimes. During cancer treatment, CAYAs cancer survivors undergo significant disruptions in their nutritional status, elevating the risks of mortality, morbidity, and cardiovascular events. The assessment of nutritional status during cancer treatment involves anthropometric and dietary evaluations, emphasizing the necessity for regular assessments and the timely identification of risk factors. Proactive nutritional interventions, addressing both undernutrition and overnutrition, should be tailored to specific age groups and incorporate a family-centered approach. Despite encouraging interventions, a notable evidence gap persists. The goal of this review is to comprehensively examine the existing evidence on potential nutritional interventions for CAYAs cancer survivors. We explore the evidence so far collected on the nutritional intervention strategies elaborated for CAYAs cancer survivors that should target both undernutrition and overnutrition, being age-specific and involving a family-based approach. Furthermore, we suggest harnessing artificial intelligence (AI) to anticipate and prevent malnutrition in CAYAs cancer survivors, contributing to the identification of novel risk factors and promoting proactive, personalized healthcare.

A 10-Year Retrospective Study on Pediatric Visceral Leishmaniasis in a European Endemic Area: Diagnostic and Short-Course Therapeutic Strategies.

BACKGROUND: Visceral leishmaniasis (VL) is a potentially fatal disease, with an increasing occurrence in northern Italy, affecting children and both immunocompetent and immunocompromised adults. METHODS: This retrospective study conducted at the St. Orsola University Hospital of Bologna, Italy, evaluates the characteristics of 16 children (with a median age of 14.3 months) who were hospitalized between 2013 and 2022 for VL. RESULTS: Seventy-five percent of patients presented with a triad of fever, cytopenia, and splenomegaly. An abdominal ultrasound examination revealed splenomegaly and hypoechoic spleen abnormalities in 93.8% and 73.3% of cases, respectively. Five VL cases were complicated by secondary hemophagocytic lymphohistiocytosis. Eleven patients were treated with a single 10 mg/kg dose of Liposomal Amphotericin B (L-AmB), while five received two doses (total of 20 mg/kg); one of the former groups experienced a recurrence. The fever generally decreased 48 h after the first L-AmB dose, and hemoglobin levels normalized within a month. The splenomegaly resolved in approximately 4.5 months. CONCLUSIONS: Pediatricians should consider VL in children with fever of an unknown origin, anemia, cytopenia, and splenomegaly. In our experience, abdominal ultrasounds and molecular tests on peripheral blood contributed to diagnosis without the need for bone marrow aspiration. The short-course therapy with two 10 mg/kg doses of L-AmB is safe and effective.