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.

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.

Prevalence and clinical presentation of long COVID in children: a systematic review.

A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms. CONCLUSION: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources. WHAT IS KNOWN: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock. WHAT IS NEW: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.

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 Effective Management of Fever in Pediatrics and Insights on Remote Management: Experts' Consensus Using a Delphi Approach.

Background: Even after the publication of the 2017 update of Italian guidelines on treatment of fever in pediatrics, some fundamental questions are still open and new ones emerged during the COVID-19 pandemic. Objective: To assess the level of consensus among Italian pediatricians on different topics related to treatment of fever in children by using the Delphi technique. Methods: A Delphi study was undertaken between June and September 2021, when two questionnaires were consecutively sent to a panel of experts to be answered anonymously. An invitation to participate was sent to 500 pediatricians distributed over the whole national territory and 80 (16%) of them accepted to participate on a voluntary basis. The questionnaires were structured into three specific topics: "therapeutic appropriateness and management of the febrile child," "management of the febrile child in the presence of other diseases," and "future perspectives in remote management." Each topic had six statements. Results: A first-round questionnaire was sent to 80 accepting pediatricians from different Italian regions. Of the 72 respondents (23% working in hospitals and 72% outside), 33% were from northern, 12% central, and 55% southern Italy or islands. A second-round questionnaire was sent to the same 80 pediatricians and 69 of them responded, without significant differences for workplaces or geographical distribution as compared with the first questionnaire. Overall, 75 participants answered at least one of the two questionnaires. All the statements on the topics of "therapeutic appropriateness and management of the febrile child" and "future perspectives in remote management" reached the predefined cut off for consensus (75% or more). Only one statement on "management of the febrile child in the presence of other diseases" did not achieve the consensus even after the second round. Conclusions: Italian pediatricians agree on several aspects of treatment of febrile children and their expert opinions could support everyday decision process complementary to recommendations by regulatory agencies and guidelines.

Management of BNT162b2 mRNA COVID-19 vaccine in children aged 5-11 years with allergies, asthma, and immunodeficiency: consensus of the Italian Society of Pediatric Allergy and Immunology (SIAIP).

BNT162b2 vaccine, developed by BioNTech and Pfizer ha recently approved for use in children aged 5 to 11 years. Recent data show evidence of safety on the administration and serious adverse events have been rarely reported. However, allergic systemic reactions could occur. In some cases, a correct allergic evaluation allows identifying patients at risk of developing an anaphylactic reaction. Risk assessment of allergic reactions to COVID-19 vaccines is useful to limit contraindications to vaccination and help to safely vaccinate people supposed to be at risk of allergic reactions.

Digital health in the management of allergic diseases.

In recent years there has been an important implementation in the medical field of both Mobile Health, such as the use of mobile communication devices, and of other telemedicine tools in general, with the aim of supporting the supervision of diseases from the moment of the first diagnosis to the therapeutic follow-up. In fact, Digital Health can also have a very positive impact on the management of allergic patients, who are known to have the greatest need for regular monitoring, simplifying contact between doctor and patient, but there is still a need to improve implementation regulations, define certification programs and adequate reimbursement systems, as well as to guarantee a high level of attention to the protection of sensitive data. The hope is that one positive outcome of the Covid-19 pandemic will be an acceleration, by all stakeholders involved, of the process of the modernization of health care.

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.

Paracetamol and Ibuprofen in the Treatment of Fever and Acute Mild-Moderate Pain in Children: Italian Experts' Consensus Statements.

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild-moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild-moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients' profiles, and the safety features of the drugs. Although patients' profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild-moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild-moderate pain management to enhance the milestones already achieved by Italian pediatricians.

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.

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.

Impact that the COVID-19 pandemic on routine childhood vaccinations and challenges ahead: A narrative review.

AIM: To document the decline in vaccination coverage in the first months of 2020 as an indirect effect of the COVID-19 pandemic. METHODS: We performed a literature review in medical databases. Overall, 143 articles were initially retrieved, out of which 48 were selected and included in the review. RESULTS: Our review retrieved similar data in many countries worldwide, and, globally, preliminary data from the first 4 months of 2020 indicate a decline in diphtheria-tetanus-pertussis coverage, generally considered the marker of vaccination coverage across countries. World Health Organization recommends maintaining vaccination services, prioritising primary series vaccinations especially for measles-rubella or poliomyelitis, but it also lets each country decide whether to maintain the immunisation services evaluating the current epidemiology of vaccine-preventable diseases and the COVID-19 local transmission scenario. Successively, recovering of vaccinations should be planned. Moreover, during the pandemic, influenza vaccination should be promoted as a central public health measure. CONCLUSION: Future challenges will be to maintain the vaccination programmes, especially in children younger than 2 years old and adolescents, to plan the recovery of vaccinations for subjects who postponed them during the lockdown, and to early identify any vaccine-preventable disease outbreak.

Criteria for referral of pediatric SARS-CoV-2 infection: a real-life experience in the pandemic era.

A practical guidance on the management of children with COVID-19 to insure homogeneous criteria for referral to a higher-level facility, according to the disease severity, is pivotal in the pandemic era. A panel of experts in pediatric infectious diseases and intensive care at the tertiary-care Meyer Children's University Hospital, Florence, Italy, issued a practical document shared with Tuscany hospitals. The rationale was to target the referral for those children at risk of requiring an intensive support, since the above mentioned hospital has the pediatric intensive care unit. Overall, 378 patients between 0 and 19 years of age were diagnosed with COVID-19 infection in the Tuscany region with 24 (6.3%) hospitalizations. Only three children were centralized to Meyer Children's University Hospital according to reported criteria. Considering that appropriate referral criteria have been associated with reduced mortality in other conditions, our document might be useful to improve outcomes of children with COVID-19.

SARS-CoV-2 infection in pediatric population.

n December 2019, in Wuhan (Hubei, China), the first COVID-19 cases due to SARS-COV-2 had been reported. On July 1st 2020, more than 10.268.839 million people had developed the disease, with at least 506.064 deaths. At present, Italy is the third country considering the number of cases (n=240.760), after Spain, and the second for the cumulative number of deaths (n=249.271), after the United States. As regard pediatric COVID-19 cases, more than 4000 cases (have been reported; however, these figures are likely to be underestimated since they are influenced by the number of diagnostic tests carried out. Three pediatric deaths have been reported in Italy to date. We aimed to review the peculiar aspects of SARS-COV-2 infection in the pediatric population.

COVID-19 in Pregnant Women and Neonates: A Systematic Review of the Literature with Quality Assessment of the Studies.

The SARS-CoV-2 virus emerged in December 2019 and then spread globally. Little is still known about the impact of COVID-19 on pregnant women and neonates. A review of the literature was performed according to the PRISMA guideline recommendations, searching the MEDLINE and EMBASE databases. Studies' quality assessments were performed using the JBI Critical Appraisal Checklist. A total of 37 studies were included, involving 275 pregnant women with COVID-19 and 248 neonates. The majority of pregnant women presented with mild to moderate symptoms, only 10 were admitted in the ICU, and one died. Two stillbirths were reported and the incidence of prematurity was 28%. Sixteen neonates were tested positive for SARS-CoV-2 by RT-PCR, and nine of them were born from mothers infected during pregnancy. Neonatal outcomes were generally good: all the affected neonates recovered. RT-PCR for SARS-CoV-2 yielded negative results on amniotic fluid, vaginal/cervical fluids, placenta tissue, and breast milk samples. SARS-CoV-2 infection in pregnant women appeared associated with mild or moderate disease in most cases, with a low morbidity and mortality rate. The outcomes of neonates born from infected women were mainly favorable, although neonates at risk should be closely monitored. Further studies are needed to investigate the possibility of vertical transmission.