From evidence to practice: A systematic review-based diagnostic algorithm for paediatric eosinophilia across socioeconomic context.

AIM: Paediatric eosinophilia is a common clinical dilemma, often leading to resource- and time-consuming assessments. We aim to evaluate the main aetiologies of eosinophilia in children from different socioeconomic settings and propose a diagnostic algorithm. METHODS: A systematic literature review was conducted through PubMed, Embase and the Cochrane Library. Studies published from January 2012 to June 2023 reporting the incidence and aetiology of peripheral eosinophilia in children were included. Evidence from studies on children originating from low- or high-income countries was compared. RESULTS: A total of 15 observational studies, encompassing 3409 children, were included. The causes of eosinophilia varied based on the children's origin and the eosinophilia severity. In children from high-income countries, allergic diseases were the leading cause, with a prevalence of 7.7%-78.2%, while parasitosis ranged from 1.0% to 9.1%. In children from low-income countries, parasitosis was predominant, ranging from 17.7% to 88.3%, although allergic diseases were found in 2.5%-4.8% of cases. Concerning severity, allergic diseases were the leading cause of mild-to-moderate eosinophilia; parasitosis was associated with moderate-to-severe eosinophilia, while immunological disorders were mostly found in severe cases. CONCLUSION: We developed a step-up diagnostic algorithm that considers the child's origin and eosinophilia severity and could optimise resource allocation.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a delphi approach.

BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024.

A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination.

Biochemical and genetic tools to predict the progression to Cystic Fibrosis in CRMS/CFSPID subjects: A systematic review.

OBJECTIVES: Aim of this study was to identify risk factors for a progression to cystic fibrosis (CF) in individuals detected as CF Screening Positive, Inconclusive Diagnosis (CFSPID). METHODS: This is a systematic review through literature databases (2015-2023). Blood immunoreactive trypsinogen (b-IRT) values, CFTR genotype, sweat chloride (SC) values, isolation of Pseudomonas aeruginosa (Pa) from respiratory samples, Lung Clearance Index (LCI) values in CFSPIDs who converted to CF (CFSPID > CF) and age at CF transition were assessed. RESULTS: Percentage of CFSPID > CF varies from 5.3 % to 44 %. Presence of one CF-causing CFTR variant in trans with a variant with variable clinical consequences (VVCC), an initial SC ≥ 40 mmol/L, an increase of SC > 2.5 mmol/L/year and recurrent isolation of pseudomonas aeruginosa (Pa) from airway samples could allow identification of subjects at risk of progression to CF. CONCLUSIONS: CFSPIDs with CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up.

Does multiple gastric aspirate collection increase sensitivity of M. tuberculosis detection in children with pulmonary tuberculosis?

This study aims to investigate the sensitivity of microscopy, culture and polymerase chain reaction on three gastric aspirates (GAs) in the microbiological confirmation of active pulmonary tuberculosis (TB) and to identify possible changes in sensitivity derived from the collection of a different number of aspirates. Children with clinical and radiological diagnoses of active pulmonary TB who underwent three GAs between March 2007 and June 2019 were retrospectively evaluated. Clinical, radiological, and microbiological data were collected. The sensitivity of microbiological tests on GAs was calculated. Moreover, differences in sensitivity according to age and radiological pattern were investigated. Overall, 156 children with active pulmonary TB were enrolled with a median age of 51.5 (IQR: 25.2-113.2) months. Microbiological investigations on the first GA showed a sensitivity of 34% (95%CI 26.7, 42), the cumulative sensitivity of first and second GAs was 40.4% (95%CI 32.7, 48.5) and of the three GAs was 47.4% (95%CI 39.8, 55.2). The collection of three GAs leads to an overall increase in sensitivity of the first GA by 13.4% (95%CI 2.8, 24.1%; p=0.014). Moreover, the increase in sensitivity was significantly higher in children ≤ 4 years of age and in those with uncomplicated TB (p=0.008).Conclusions: Performing a higher number of GAs increases the sensitivity of microbiological confirmation of active pulmonary TB, particularly in children ≤ 4 years and with an uncomplicated radiological pattern. What is known: • The diagnosis of paediatric tuberculosis is a challenge for paediatricians • Despite their low sensitivity gastric aspirates represent the standard sample for microbiological confirmation of active pulmonary tuberculosis in children • Most international guidelines recommend performing three sequential gastric aspirates on three consecutive days What is new: • A significant increase in global sensitivity by 13.4% was found by the collection of three gastric aspirates compared to the first one • Performing a higher number of gastric aspirates increases the sensitivity of microbiological confirmation, particularly in children ≤ 4 years and with an uncomplicated radiological pattern.

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy.

Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children's Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.

Fixed-dose antiretroviral combinations in children living with human immunodeficiency virus type 1 (HIV-1): a systematic review.

Fixed-Dose antiretroviral Combinations (FDCs) are the most used drug regimes in adult patients with human-immunodeficiency virus 1 infection, since they increase adherence to antiretroviral therapy and enable good quality of life. The European AIDS Clinical Society guidelines recommend the use of FDCs in paediatrics. However, the use of FDCs in paediatric population is restricted since studies in children and adolescents are mostly conducted in small sample sizes and are heterogeneous in settings and design. This systematic review aims to summarize the current knowledge about the use of FDCs in paediatric population, highlighting the relevant outcomes regarding efficacy and effectiveness, adherence, safety, and adverse events of these regimens.

Care Issues in Patients with Rett Syndrome: A Parental Perspective.

BACKGROUND: The purpose of this study is to better understand the way caregivers of patients with Rett syndrome perceive the quality of the health care services they receive and identify its main shortcomings. METHODS: A survey was distributed to all caregivers who are part of AIRETT (the Italian Association of Relatives of Patients with RS). The survey gathered information on the management of relatives of patients with Rett syndrome. RESULTS: The data refers to 52 patients, all females, with a median age of 15 years at the time of the survey. Concerning RS specificity, our data confirm the high complexity of this chronic, multifaceted condition, mainly characterized by the presence of epilepsy, apnea, severe scoliosis, and gastrointestinal symptoms. The specialists more frequently involved in the care of patients were general practitioners or family pediatricians (98%) and neurologists (92%), and more rarely physiatrists (71%). Only 15% of patients were followed by a pulmonologist, despite the fact that respiratory problems were frequent (apneas were present in 81% of patients, and 2% had a tracheostomy). Although 63.5% of patients presented with gastrointestinal symptoms and 2% had a gastrostomy, only 33% were followed by a gastroenterologist. Moreover, although orthopedic issues were present in 78.8% of patients, including severe scoliosis in 22% of them, only 25% were followed by an orthopedist. Furthermore, despite the fact that RS patients are fragile, about one quarter of them were not vaccinated. As far as organizational issues are concerned, several specialized centers are located in various regions throughout the country. As a consequence, the high mobility rate from one center to another resulted in non-homogeneous assistance. CONCLUSIONS: The study shows that caregivers of RS patients take over most obligations and burdens by increasing their perceived level of stress. For the majority of patients, the most frequent complications were not followed by the reference subspecialist, with the only exception of epilepsy. Moreover, improving vaccination strategies for these patients is necessary.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

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.

Stenotrophomonas maltophilia in people with Cystic Fibrosis: a systematic review of prevalence, risk factors and management.

To summarize the current knowledge of the clinical impact of Stenotrophomonas maltophilia (SM) in cystic fibrosis (CF) patients. A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline recommendations, was performed through searches in PubMed and EMBASE databases, and CF National and International Registries websites from 2000 to 2022. Overall, 184 articles were initially retrieved, out of which 15 were selected and included in the review. Data form 6 Registries and 9 pertinent articles from the references of the studies selected were also considered, resulting in 30 studies in total. The prevalence of SM in patients with CF is increasing in Europe while it is declining in North America. The role of chronic colonization of SM on lung function and clinical status in CF patients is still under debate. The most recent studies suggested a pathogenic role of SM chronic infections in CF patients with an acceleration in lung function decline, an increase in hospitalization rates and an association with co-infection. Reflecting the uncertainty about the role of SM in CF, little is available about antibiotic therapeutic strategies for both acute exacerbations and chronic infections. Antimicrobial therapy should be performed in the acute exacerbations, while it may be reasonable to attempt eradication when the first colonization is identified. Nevertheless, it is not established which antibiotic regimen should be preferred, and overtreatment could contribute to the selection of antimicrobial-resistant strains. Further studies are warranted in this regard.

The digital child: A cross-sectional survey study on the access to electronic devices in paediatrics.

AIM: To explore the use of electronic devices in children and possible risk factors for smartphone ownership and cyberbullying. METHODS: A cross-sectional survey study was conducted involving 62 Italian general paediatricians who administered a close-ended questionnaire about the use of electronic devices to 1732 parents/caregivers. RESULTS: Data of 2563 children aged 0-14 years were collected. Investigating the electronic device use by parents/caregivers of children aged 0-1 years, 72.5% of mothers were revealed to have the habit to use a smartphone during breastfeeding and bottle-feeding. The ownership of a smartphone was found in 29.5% of children aged 2-14 years, 68.1% considering only children aged 10-14. A higher parental degree level was identified as a protective factor for smartphone ownership by children (OR 0.59; 95% CI 0.36-0.98; p = 0.04 for father; OR 0.51; 95% CI 0.33-0.78; p = 0.002 for mother). A higher risk of cyberbullying was found when caregivers did not use any restrictions on smartphone use (OR 11.92; 95% CI 3.41-41.68; p < 0.001). CONCLUSION: The absence of rules for smartphone use represents a risk factor for cyberbullying. In this context, the general paediatrician might play an important role in helping parents/caregivers and their children adopt safer use of electronic devices.

Effectiveness of Antimicrobial Lock Therapy for the Treatment of Catheter-Related and Central-Line-Associated Bloodstream Infections in Children: A Single Center Retrospective Study.

Antimicrobial lock solutions (ALT) in combination with systemic antibiotics can represent a valid option to attempt central venous catheter (CVC) salvage in the case of catheter-related and central-line-associated bloodstream infections (CRBSI and CLABSI). However, data concerning the effectiveness and safety of ALT in children are limited. We aimed to share our center's experience in order to contribute to investigations into the causes of ALT failure in the pediatric population. All children consecutively admitted to Meyer Children's Hospital, University of Florence, Italy, from 1 April 2016 to 30 April 2022, who received salvage ALT to treat an episode of CRBSI/CLABSI, were reviewed. According to ALT failure or success, children were compared with the aim of identifying the risk factors for unsuccessful ALT outcome. Data from 28 children, 37 CLABSI/CRBSI episodes, were included. ALT was associated with clinical and microbiologic success in 67.6% (25/37) of children. No statistically significant differences were observed between the two groups, successes and failures, considering age, gender, reason for use, duration, insertion, type and presence of insertion site infection of the CVC, laboratory data and number of CRBSI episodes. Nevertheless, a trend towards a higher success rate was observed for a dwell time of 24 h for the entire duration of ALT (88%; 22/25 vs. 66.7%; 8/12; p = 0.1827), while the use of taurolidine and the infections sustained by MDR bacteria were associated with a tendency toward greater failure (25%; 3/12 vs. 4%; 1/25; p = 0.1394; 60%; 6/10 vs. 33.3%; 8/24; p = 0.2522). No adverse events, except one CVC occlusion, were observed. ALT combined with systemic antibiotics appears to be an effective and safe strategy for treating children with CLABSI/CRBSI episodes.

Childhood fever and medical students: A multicentre, educational intervention.

AIM: Misconceptions and non-evidence-based practices toward childhood fever are reported worldwide. Medical students might be ideal candidates to introduce long-lasting changes in clinical practice. However, no study has gauged the effectiveness of an educational intervention to improve fever management in this population. We conducted an educational, interventional study on childhood fever among final-year medical students. METHODS: We conducted a prospective, multicentre interventional study employing a pre/post-test design. Participants from three Italian Universities filled in a questionnaire just before the intervention (T0), immediately after (T1) and 6 months later (T2) in 2022. The intervention was a two-hour lecture focused on the pathophysiology of fever, recommendations for its treatment and risks associated with improper management. RESULTS: 188 final-year medical students (median age of 26 years, 67% females) were enrolled. Relevant improvements in the criterion for treating fever and conceptions about the beneficial effects of fever were observed at T1 and T2. Similar data were found for the reduction of physical methods advice to decrease body temperature and concerns for brain damage from fever. CONCLUSION: This study shows for the first time that an educational intervention is effective in changing students' conceptions and attitudes toward fever both in the short and medium term.

Approach to fever in children among final-year nursing students: a multicenter survey.

BACKGROUND: Unfounded concerns regarding fever are increasingly observed among nurses worldwide. However, no study has so far explored the preferred approach towards pediatric fever among nursing students. Therefore, we aimed to investigate the attitude towards pediatric fever among final-year nursing students. METHODS: Between February and June 2022, final-year nursing students of 5 Italian university hospitals were asked to answer an online survey on their approach to fever in children. Both quantitative and qualitative methods were utilized. Multiple regression models were employed to explore the existence of moderators on fever conceptions. RESULTS: The survey was filled in by 121 nursing students (response rate 50%). Although most students (98%) do not consider discomfort to treat fever in children, only a minority would administer a second dose of the same antipyretic in nonresponsive cases (5.8%) or would alternate antipyretic drugs (13%). Most students would use physical methods to decrease fever (84%) and do not think that fever has mainly beneficial effects in children (72%). The own know-how adequacy on fever was inversely associated (OR 0.33, 95% CI 0.13-0.81) with the beliefs that high fever might lead to brain damage. No further predictive variable was significantly associated with the concern that fever might be associated with brain damage, the advice of physical methods use, and the assumption that fever has mostly positive effects. DISCUSSION: This study shows for the first time that misconceptions and inappropriate attitudes towards fever in children are common among final-year nursing students. Nursing students could potentially be ideal candidates for improving fever management within clinical practice and amongst caregivers.

Discomfort relief after paracetamol administration in febrile children admitted to a third level paediatric emergency department.

Background: international guidelines recommend treating fever in children not at a predefined body temperature limit but based on the presence of discomfort. However few studies evaluated discomfort relief after administration of antipyretics in children. Methods: Between 1st January and 30th September 2021 a single-center prospective observational study was performed in febrile children consecutively admitted to a pediatric emergency department and treated with paracetamol orally. For each child, body temperature, presence and severity of discomfort, defined using a previously published semiquantitative likert scale, were evaluated at baseline and 60 min after administration of paracetamol, and differences were analyzed. Results: 172 children (males: 91/172; 52.9%; median age: 41.7 months) were included. Significant reductions in body temperature (median body temperature at T0: 38.9 °C; IQR: 38.3-39.4, median body temperature at T60: 36.9 °C; IQR: 36.4-37.5; P < 0.0001), and in the level of discomfort (proportion of children with severe discomfort at T0: 85% and at T60:14%; P < 0.0001) were observed. Severe discomfort at T60 persisted in a minority of children (24/172; 14%) and it was not related to body temperature values. Conclusions: paracetamol in febrile children is associated not only with significantly reduction in body temperature but also with discomfort relief.

Management of pulmonary aspergillosis in children: a systematic review.

Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify this issue, a literature search was performed through MEDLINE/PubMed database to describe current risk factors and diagnostic, therapeutic and prophylactic tools for invasive pulmonary aspergillosis (IPA) in the paediatric age. Observational studies and clinical trials regarding diagnosis, treatment and prophylaxis were considered, and results were summarised. Five clinical trials and 25 observational studies (4453 patients) were included.Haematological malignancies, previous organ transplant and other primary or acquired immunodeficiency were identified as risk factors for IPA in children.Current diagnostic criteria distinguish between "proven", "probable" and "possible" disease. Consecutive galactomannan assays have good sensitivity and specificity, especially when performed on broncho-alveolar lavage. At the same time, ß-D-glucan should not be used since cut-off in children is unclear. PCR assays cannot currently be recommended for routine use.Voriconazole is the recommended first-line agent for IPA in children older than 2 years of age. Liposomal amphotericin B is preferred in younger patients or cases of intolerance to voriconazole. Its plasma concentrations should be monitored throughout the treatment. The optimal duration of therapy has yet to be determined. Posaconazole is the preferred prophylactic agent in children older than 13 years old, whereas oral voriconazole or itraconazole are the drugs of choice for those between 2-12 years. Further good-quality studies are warranted to improve clinical practice.