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.

Risk factors for severe COVID-19 in people with cystic fibrosis: A systematic review.

Background: People with cystic fibrosis (CF) are considered a clinically fragile population with an intrinsic higher risk of developing severe COVID-19, though a certain variability in terms of outcomes and hospitalization has been noticed. Aim: To highlight the main risk factors for severe COVID-19 in patients with CF. Methods: A systematic review of the current literature was conducted through PubMed and EMBASE databases. English-written articles reporting clinical data on CF subjects with SARS-CoV2 infection were included and analyzed. Selected reports were evaluated for adherence to STROBE recommendations. Results: After the selection phase, 9 observational studies were included, 5 of which reported data from CF Registry Global Harmonization Group. The hospitalization rate ranged from 18.2 to 58.1%. The main risk factors for severe outcome were as follows: FEV1 < 70%p, CF-related diabetes, age > 40 years, pancreatic insufficiency, underweight, previous transplant, azithromycin use. Use of dornase alfa was associated with decreased risk for severe disease, while there was insufficient evidence to establish the role of inhaled steroids or CFTR modulators. No solid data regarding specific SARS-CoV-2 therapies in patients with CF emerged. Conclusion: Most people with CF experience a mild course of SARS-CoV-2 infection, nevertheless subgroups with higher risk of severe outcome emerged. Maintenance therapies for CF overall did not show a clear preventive effect against severe outcomes, although dornase alfa seems to give some protection. Due to the current lack of data on specific COVID-19 therapies and immunization in patients with CF, further studies are needed to establish their impact in this population.

The use of antiviral drugs in children.

Viral infections are particularly common among children. They often have a mild course, are self-limiting and do not need any specific treatment. However, in some cases, the disease can be severe and lead to permanent disabilities. A variety of antiviral drugs are available for the treatments of certain infectious agents: for instance, acyclovir is used to treat herpes simplex virus encephalitis. Recommendations for flu treatment may change according to the current epidemiological surveillance data, on the basis of which antiviral sensibility can be forecast: recommended drugs for the 2020-21 flu season are oseltamivir, zanamivir, peramivir and baloxavir. Some drugs are used to treat congenital infections, such as valganciclovir and ganciclovir in congenital cytomegalovirus infection. Antiretroviral prophylaxis in newborns from HIV-1 infected mothers must be initiated as soon as possible, with one or more drugs according to therapeutic regimens based on the baby's risk category. According to the most recent guidelines, antiretroviral therapy must be started at diagnosis. Several antiretroviral drugs are available today and approved for use in children, so several combinations can be made. However, out of the 29 antiretroviral drugs approved for adults, only 38% (11/29) are approved for children under the age of two and about 60% (18/29) for children under the age of twelve. Treatment with direct antiviral agents against hepatitis C virus is approved for children over the age of three; it consists in different therapeutic regimens chosen on the basis of the viral genotype (ledipasvir/sofosbuvir for genotypes 1, 4, 5 and 6, sofosbuvir/ribavirin for genotypes 2 and 3, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for all genotypes) and it has dramatically changed the course of the illness. Many molecules have been studied in order to treat SARS-CoV-2 infection, but only remdesivir seems to play a role in shortening recovery time, although inclusion criteria are very specific and data on the use in children is limited.

Use of remdesivir in children with COVID-19 infection: a quick narrative review.

SARS-CoV-2 infection has a severe course in a small percentage of children. Remdesivir has shown promising results in reducing hospitalisation time in adults, but data on mortality rate are conflicting and few studies are available on its use use in antivirals in children. We performed a quick narrative review of the available literature data regarding the usage of remdesivir in children and neonates. In children, remdesivir showed good safety profile, however bradicardia events have been reported in children. Remdesivir is currently recommended by several guidelines in some subgroups of children with severe COVID-19, and should also be considered in critically ill patients, always in the context of the overall clinical picture and drug availability.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Gastrointestinal involvement in children with SARS-COV-2 infection: An overview for the pediatrician.

Gastrointestinal symptoms are common findings in children with SARS-CoV-2 infection. Diarrhea and vomiting have been reported in about 8%-9% of cases, reaching more than 20% in some studies. Children with gastrointestinal involvement appear to be younger than those without, but the severity of the disease seems to be similar between the two groups of subjects. Fecal shedding in children has been reported in 20%-30% of children and has been observed in both those with and those without overt gastrointestinal involvement. Moreover, prolonged fecal elimination, lasting several days after negativization of real-time polymerase chain reaction assay on respiratory swabs, has been reported with variable frequency in children with SARS-CoV-2 infection. These observations raise the question regarding the possibility of oral-fecal transmission and the possible role of children in spreading the infection, particularly when they appear asymptomatic or with gastrointestinal symptoms but with no respiratory involvement, as well as during their convalescent phase.

Italian primary care paediatricians' adherence to the 2019 National Guideline for the management of acute otitis media in children: A cross-sectional study.

INTRODUCTION: The Italian Guideline for the management of acute otitis media (AOM) in children has been recently updated. We conducted a cross-sectional survey to investigate the adherence of Italian primary care paediatricians to the guideline recommendations. METHODS: A questionnaire including 13 closed-ended questions was administered to the paediatricians participating in the 24th National Congress of Practical Pediatrics, held in Florence in November 2019. The answers were collected and analyzed. RESULTS: Eight hundred fifty-four out of 1000 questionnaires were collected (85.4%). Most of the participants declared that they did not remove the cerumen (63.9%). Pneumatic otoscope and tympanometry were routinely used by a minority of paediatricians (9.6% and 3.9%, respectively); all the participants declared to routinely prescribe oral analgesic drugs and 97.6% of them considered amoxicillin or amoxicillin/clavulanic acid as the first-choice antibiotic. In an uncomplicated unilateral AOM case, the preferred strategy was immediate antibiotic therapy in children under two years of age (83.1%) and watchful waiting in those >2 years (77.3%). Oral amoxicillin was most commonly prescribed at the 80-100 mg/kg/day (56.6%), in 3 daily doses (87.7%), while amoxicillin/clavulanic acid was equally prescribed at 80-100 or 50 mg/kg/day (47.1%-48.5%), mainly in 2 doses (58.6%). However, both drugs are recommended at a dosage of 80-90 mg/kg/day (calculated on amoxicillin), in 3 daily doses. Although the Guideline recommends ten days of therapy, both drugs were most commonly prescribed for 7-8 days (55.5%-57.7%). Pneumococcal and flu vaccines were recommended only by 41.6% and 31.6% of participants, respectively. CONCLUSIONS: Our data suggest adequate adherence of the guideline recommendations considering the preferred antibiotic drug, pain management and the choice between immediate antibiotic therapy and watchful waiting. Conversely, targeted training programs are needed to improve adherence to recommendations on cerumen removal, use of pneumatic otoscopy, correct use of antibiotics in terms of optimal dosage, duration and number of daily administrations, and to implement proper AOM prevention strategies.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: Diagnosis.

BACKGROUND: In recent years, new progress has been made regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society therefore decided to issue an update to the previous guidelines published in 2010. METHODS: Literature searches were conducted on MEDLINE by Pubmed, including studies in children, in English or Italian, published between January 1, 2010, and December 31, 2018. The quality of the included studies was assessed using the grading of recommendations, assessment, development and evaluations (GRADE) methodology. In particular, the quality of the systematic reviews was evaluated using the AMSTAR 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. RESULTS: The diagnosis of AOM is based on acute clinical symptoms and otoscopic evidence; alternatively, the presence of otorrhea associated with spontaneous tympanic membrane perforation allows the AOM diagnosis. The diagnosis of AOM must be certain and the use of a pneumatic otoscope is of fundamental importance. As an alternative to the pneumatic otoscope, pediatricians can use a static otoscope and a tympanometer. To objectively establish the severity of the episode for the formulation of a correct treatment program, an AOM severity scoring system taking into account clinical signs and otoscopic findings was developed. CONCLUSIONS: The diagnosis of AOM is clinical and requires the introduction of specific medical training programs. The use of pneumatic otoscopes must be promoted, as they are not sufficiently commonly used in routine practice in Italy.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: Prevention.

BACKGROUND: In recent years, new information has been acquired regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society, therefore, decided to issue an update to the Italian Pediatric Society guidelines published in 2010. METHODS: The search was conducted on Pubmed, and only those studies regarding the pediatric age alone, in English or Italian, published between January 1, 2010 and December 31, 2018, were included. Each study included in the review was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The quality of the systematic reviews was evaluated using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. RESULTS: The importance of eliminating risk factors (passive smoking, environmental pollution, use of pacifier, obesity, limitation of day-care center attendance) and the promotion of breastfeeding and hygiene practices (nasal lavages) was confirmed. The importance of pneumococcal vaccination in the prevention of AOM was reiterated with regard to the prevention of both the first episode of AOM and recurrences. Grommets can be inserted in selected cases of recurrent AOM that did not respond to all other prevention strategies. Antibiotic prophylaxis is not recommended for the prevention of recurrent AOM, except in certain carefully selected cases. The use of complementary therapies, probiotics, xylitol and vitamin D is not recommended. CONCLUSIONS: The prevention of episodes of AOM requires the elimination of risk factors and pneumococcal and influenza vaccination. The use of other products such as probiotics and vitamin D is not supported by adequate evidence.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: Treatment.

BACKGROUND: New insights into the diagnosis, treatment and prevention of acute otitis media (AOM) have been gained in recent years. For this reason, the Italian Paediatric Society has updated its 2010 guidelines. METHODS: A literature search was carried out on PubMed. Only pediatric studies published between January 1, 2010 and December 31, 2018 in English or Italian were included. Each included study was assessed according to the GRADE methodology. The quality of the systematic reviews was assessed using AMSTAR 2. The recommendations were formulated by a multidisciplinary panel of experts. RESULTS: Prompt antibiotic treatment is recommended for children with otorrhea, intracranial complications and/or a history of recurrence and for children under the age of 6 months. For children 6 months to 2 years of age, prompt antibiotic treatment is recommended for all forms of unilateral and bilateral AOM, whether mild or severe. Prompt antibiotic treatment is also recommended for children over 2 years with severe bilateral AOM. A watchful-waiting approach can be applied to children over 2 years with mild or severe unilateral AOM or mild bilateral AOM. High doses of amoxicillin, or amoxicillin-clavulanic acid for patients with a high risk of infection by Beta-lactamase producing strains, remain the first-line antibiotics. CONCLUSIONS: AOM should be managed on a case-by-case basis that takes account of the child's age, the severity of the episode and whether it is unilateral or bilateral. In patients under 2 years, prompt antibiotic treatment is always recommended.