Search

Phase I clinical trials represent a critical point in drug development because the investigational medicinal product is being tested in humans for the first time. For this reason, it is essential to evaluate and identify the Maximum Tolerated Dose (MTD) and the safety of the new compound. To mitigate the possible risks associated with drug administration and treatment, the European Competent Authority issued various guidelines to provide provisions and harmonize risk management processes. In the UK and Italy, particular attention should be paid to the Medicines & Healthcare Products Regulatory Agency (MHRA) phase I accreditation scheme and the specific rules set by the Italian Drug Authority through the AIFA Determination no. 809/2015. Both reference documents are based on the concept of quality risk management while conducting phase I clinical studies. Moreover, the AIFA determination outlines specific requirements for those sites that want to conduct non-profit phase I clinical trials. Indeed, the document reports peculiar activities to the “Clinical Trial Quality Team”, which is a team that should support the clinical site researchers in designing, starting, performing, and closing non-profit phase I studies. In this paper, we provide a general overview of the main European guidelines concerning the management of risks during phase I trials, focusing on the main peculiarities of the schemes and rules set by the MHRA and AIFA.

BackgroundThe 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.MethodsThis 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.ResultsIn 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.ConclusionNPIs 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.

BackgroundThe 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.MethodsThis 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.ResultsOverall, 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).ConclusionOur 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.

IntroductionThe aim of our single-center case–control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls.MethodsWe enrolled 40 patients (age: 56–179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients.ResultsIt was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD).DiscussionThe results of the present study may pave the way for further research and the evaluation of more possible advantages of TH.

Overuse and misuse of antibiotics have strongly accelerated the progressive increase in bacterial antimicrobial resistance (AMR). The evidence that antimicrobial selective pressure was greater the longer the antibiotic therapy was continued has led some experts to reconsider duration of antibiotic therapy testing the use of short-term drug administration. If as effective as long-term therapy, short-term therapy could have been an easy measure to limit AMR emergence. In the present narrative review, whether present knowledge on short-term therapy of acute streptococcal pharyngitis (ASF), acute otitis media (AOM) and mild to moderate community-acquired pneumonia (CAP) allows systematic use of short-term therapy in infants and children with these diseases is discussed. Literature analysis showed that reducing the duration of antibiotic therapy for some of the most common pediatric respiratory infections could be a valid measure to contain the antibiotic abuse and the consequent impact on the emergence of AMR. Several data seem to indicate that this type of intervention is possible, as short-term therapy has been found as effective as the traditionally recommended long-term therapy in some cases of ASF, AOM and mild to moderate CAP. However, further studies are needed to better characterize infants and children who can have benefit with short-term antibiotic therapy in common bacterial respiratory infections.

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard.

To describe microbiota profiles considering potential influencing factors in pre-school children with recurrent respiratory tract infections (rRTIs) and to evaluate microbiota changes associated with oral bacterial lysate OM-85 treatment, we analyzed gut and nasopharynx (NP) microbiota composition in patients included in the OM-85-pediatric rRTIs (OMPeR) clinical trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002705-19/IT). Relative percentage abundance was used to describe microbiota profiles in all the available biological specimens, grouped by age, atopy, and rRTIs both at inclusion (T0) and at the end of the study, after treatment with OM-85 or placebo (T1). At T0, Firmicutes and Bacteriodetes were the predominant genera in gut and Proteobacteria, Firmicutes, and Actinobacteria were the predominant genera in NP samples. Gut microbiota relative composition differed with age (

Inflammatory bowel diseases (IBD), including Crohn’s disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.

Myocarditis (MYO) is a relatively uncommon inflammatory disease that involves the heart muscle. It can be a very severe disease as it can lead to the development of acute or chronic heart failure and, in a not marginal number of cases, to death. Most of the cases are diagnosed in healthy people younger than 30 years of age. Moreover, males are affected about twice as much as females. Viruses are among the most common causes of MYO, but how viral infection can lead to MYO development is not precisely defined. After COVID-19 pandemic declaration, incidence rate of MYO has significantly increased worldwide because of the SARS-CoV-2 infection. After the introduction of anti-COVID-19 vaccines, reports of post-immunization MYO have emerged, suggesting that a further cause of MYO together with the SARS-CoV-2 infection could increase the risk of heart damage during pandemic. Main aim of this study is to discuss present knowledge regarding etiopathogenesis and clinical findings of MYO associated with COVID-19 vaccine administration and whether the risk of this adverse events can modify the initially suggested recommendation for the use of COVID-19 vaccines in pediatric age. Literature analysis showed that MYO is an adverse event that can follow the COVID-19 immunization with mRNA vaccines in few persons, particularly young adults, adolescents, and older children. It is generally a mild disease that should not modify the present recommendations for immunization with the authorized COVID-19 mRNA vaccines. Despite this, further studies are needed to evaluate presently undefined aspects of MYO development after COVID-19 vaccine administration and reduce the risk of development of this kind of vaccine complication. Together with a better definition of the true incidence of MYO and the exact role of the various factors in conditioning incidence variations, it is essential to establish long-term evolution of acute COVID-19 related MYO.

Although vaccines are the safest and the most effective measure to prevent disease, disability, and death from various pediatric infectious diseases, parental vaccine hesitancy is a common and increasing phenomenon worldwide. To contribute to improving our knowledge on parental willingness and hesitancy toward COVID-19 vaccine administration in children aged 5–11 years, an anonymous online questionnaire was disseminated in Italy after the COVID-19 vaccine’s authorization for this age group. An online survey was conducted using the Crowd Signal platform from 15 December 2021 to 15 January 2022 in Italy among parents of children 5–11 years old. A total of 3433 questionnaires were analyzed. Overall, a “Favorable” position was observed in 1459 (42.5%) parents, a “Doubtful” one in 1223 (35.6%) and a “Hesitant/Reluctant” one in 751 (21.9%). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, mostly female, with a secondary or middle school degree, an annual income below EUR 28,000, more than one child in the age range from 5 to 11 years, an underestimated consideration of the severity of COVID-19’s effects, and concern regarding the COVID-19 vaccines in general. These results show that in Italy, most parents of children aged 5 to 11 were doubtful or hesitant/reluctant to vaccinate their children against the COVID-19 virus. Poor trust in health institutions as well as poor consideration of the epidemiological and clinical relevance of COVID-19 in children seem to have played the biggest roles in forming these attitudes. Moreover, the negative attitude of several parents who previously agreed to immunize their children against other childhood illnesses according to the official national pediatric immunization schedule clearly indicates that only the COVID-19 vaccine was put in doubt or rejected. All these findings lead us to conclude that to improve COVID-19 vaccination coverage in children aged 5 to 11, health authorities should increase parental education on the true clinical relevance of COVID-19 and on the importance of its prevention to hinder the evolution of the pandemic in pediatric subjects and the emergence of new variants, and its relative weight in influencing the efficacy of vaccines.

Abstract Background In the last twenty years, several studies have been conducted in the search for new therapeutic strategies in patients with food allergy; in particular, after the failure of injection immunotherapy, three different routes of administration, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), have been tested. The aim of this manuscript is to review OIT, SLIT, and EPIT clinical trials on food allergies and to suggest advantages and limits of the different routes of immunotherapy administration. Main body Of the three different routes of immunotherapy used in the treatment of food allergy, OIT is, at present, the only one actually able to induce an increase in tolerance in the majority of patients. However, its use is affected by serious secondary effects, such as major abdominal symptoms and anaphylaxis. The combination with omalizumab reduces the percentage of serious side effects. There are not many studies with SLIT for food allergy, but they have nevertheless shown that it is possible to obtain an increase in tolerance; however, this increase is modest in comparison with that obtained by OIT. EPIT, performed through the diffusion of allergens on intact skin, is the most recent form of immunotherapy. Although there are many works on EPIT carried out in laboratory animals, only few clinical studies have been published in humans. EPIT, unlike OIT and SLIT, is not responsible for systemic secondary effects such as anaphylaxis and eosinophilic oesophagitis but only for local and mild effects in areas where the devices are applied. Moreover, EPIT is characterized by high patient adherence. Conclusion OIT seems to have a prevalent application in patients who do not report previous symptoms of systemic or gastroenteric anaphylaxis, while SLIT and EPIT, in particular, could be more preferentially used in patients with a risk of anaphylaxis.

This study was planned to evaluate whether a 3-month treatment with Lactobacillus rhamnosus GG (LGG) can modify immune system functions in children and adolescents with type 1 diabetes (T1D), leading to an increased immune response to an injectable quadrivalent inactivated influenza vaccine (QIV). A total of 87 pediatric patients with T1D were screened, although 34 patients in the Probiotic group and 30 in the Control group accepted to be vaccinated with QIV and completed the study. Vaccine immunogenicity and safety and the inflammatory cytokine response were studied. Results showed that QIV was immunogenic and safe in T1D pediatric patients and pre-administration of LGG for three months did not substantially modify the QIV humoral immunity. The combination of QIV and LGG reduced inflammatory responses (i.e., IFN-γ, IL17A, IL-17F, IL-6, and TNF-α) from activated PBMCs of pediatric patients with T1D, without dampening the production of seroprotective antibodies. In conclusion, QIV is associated with an adequate immunogenicity in children and adolescents with T1D in presence of a good safety profile. Although a systematic administration of LGG did not result in an improvement of humoral responses to an influenza vaccine, the probiotic did induce important anti-inflammatory effects.

Background COVID-19 pandemic resulted in about 165 million infections and 3.4 million deaths all over the world across 15 months. The most severe clinical presentation of COVID-19 diseases is interstitial pneumonia. Methods In this paper we describe clinical outcomes based on radiological features as well as the pattern of haematochemical parameters and IgG/IgM antibodies in 75 patients hospitalized due to COVID-related interstitial pneumonia not requiring intensive care assistance. Each patient underwent routine laboratory tests, including inflammatory markers and coagulation profile at baseline. Computed Tomography (CT) was performed at baseline and after 3 months to assess the persistence of radiological sequelae. A Generalized Linear Model (GLM) was used to test for each patient the association between individual haematochemical parameters at the time of hospital admission and the subsequent radiological features after three months. The presence of IgG antibodies was quantitatively determined in 70 patients at the time of hospital admission and after 3 months. A subgroup of 49 and 21 patients underwent additional dosage of IgG after 6 and 12 months, respectively. IgM serological antibodies were available for 17 patients at baseline and 61 at T3, with additional follow-up for 51 and 20 subjects after 6 and 12 months, respectively. Results Only 28 out of 75 patients discharged from the hospital were totally healed after 3 months, while 47 patients (62.7%) still presented radiological sequelae. According to the GLM model, specific haematochemical baseline parameters—such as IL-6, GPT, platelets and eosinophil count—showed a statistically significant association with the presence of radiological sequelae at month 3 highlighting an OR = 0.5, thus meaning that subjects completely healed after 3 months presented half levels of IL-6 at baseline compared to patients with sequelae. In general, IgG serum levels were always higher than IgM at the time of hospitalization (75% at T0; n = 12 out of 16 patients with data available in both visits), after 3 months (72.1%; n = 44 out of 61 pts.), after 6 months (56.8%; 25 out of 44 pts.), and one year after hospitalization (60%; 12 out of 20 pts.). Overall, IgG and IgM serum levels presented a statistically significant decreasing trend from the baseline to month 3, 6 and 12. One patient presented an increase in IgM between baseline and month 3 but negative PCR test for SARS-COV2 on throat swab. Conclusions As supported by our findings on 75 patients, COVID-related interstitial pneumonia triggers early IgG levels (higher than IgM) that gradually decrease over 12 months. Mid-term sequelae are still detectable at lung Computed Tomography after 3 months from the hospital admission. Occasionally, it is possible to observe increase of IgM levels in presence of low concentrations of IgG and negative PCR ELISA tests for SARS-COV2 RNA. Baseline levels of IL-6 could be proposed as predictor of radiological mid/long-term sequelae after COVID-related interstitial pneumonia.

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient’s characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.

In patients with cystic fibrosis (CF), multidrug-resistant (MDR) bacteria can predispose to exacerbations, limit the effectiveness of antibiotic treatments and promote the progression of lung disease. The aim of this retrospective study was to compare pulmonary exacerbations (Pex), hospitalizations, lung function and nutritional status in a group of children and adolescents with CF colonized by MDR bacteria and in a noncolonized control group. Overall, 7/54 pediatric patients (12.9%) were colonized by MDR bacteria and enrolled (3 with Achromobacter xyloxidans, 3 with Stenotrophomonas maltophilia and 1 with Burkholderia cepacia). The control group included 14 sex- and age-matched CF patients (8/14 colonized by Staphylococcus aureus, 2/14 by Pseudomonas aeruginosa, 2/14 by both microorganisms and 2/14 germ free). At the time of enrollment and 12 months before the first detection of the MDR microorganism, children colonized by MDR bacteria showed lower body mass index (BMI) and lower FEV1/FVC compared to the control group. Over the previous year before the first detection, children colonized with MDR had more Pex compared to control group; those colonized by S. maltophilia experienced the highest number of Pex. In the 12 months following the first detection of MDR bacteria, all seven patients colonized by MDR had at least one Pex and patients colonized by S. maltophilia had the highest number (mean ± SD: 6 ± 2.6 vs. 1.7 ± 2.3). Our study suggests that CF pediatric patients infected by MDR bacteria have lower BMI, more obstructive disease and experience more exacerbations than patients without MDR bacteria. These differences are present even before being infected, suggesting that children and adolescents with more severe disease are predisposed to be colonized by MDR bacteria. S. maltophilia appeared to be the most aggressive pathogen. Further studies and the implementation of antimicrobial stewardship programs are necessary to clarify when and how to treat patients with CF and MDR bacteria in order to avoid the improper use of antibiotics and the development of antibiotic resistance.

Background: Although the diagnosis of new coronavirus 2019 (COVID-19) is made through the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory secretions by means of molecular methods, a more accurate estimation of SARS-CoV-2 circulation can be obtained by seroprevalence studies. The main aim of this study was to evaluate the true epidemiology of SARS-CoV-2 infection among workers in the metal-mechanical sector who never stopped working during the pandemic period in an area with a high incidence of COVID-19 and to define whether and how they could continue the work without appreciable risks during a second wave.Methods: A total of 815 metal-mechanical workers who had never stopped working even during the pandemic period in three different factories in the Emilia-Romagna Region, Italy, and who had always used face masks during working hours, underwent a capillary blood rapid test for the determination of IgM and IgG against SARS-CoV-2 (COVID-19 IgG/IgM Rapid test, PrimaLab, Modena, Italy). In the event of a positive test, a nasopharyngeal was performed and tested for the presence of SARS-CoV-2.Results: The detection of serum IgG/IgM against SARS-CoV-2 was significantly more common among workers employed in Parma (21/345, 6.1%) than among those employed in Calerno (7/242, 2.9%) or in Spilamberto (3/228, 1.3%) (p

Abstract Background Over many years, OM-85, a lysate of 21 common bacterial respiratory pathogens, has been demonstrated to prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in the prevention of respiratory tract infections (RTIs) in children. This study was planned to further contribute to the evaluation of the role played by OM-85 in prevention of recurrent RTIs in children. Methods This study was a randomized (3:3:1), placebo-controlled, double-blind, single-centre, phase IV trial carried out in Italy to assess the efficacy of OM-85 (Broncho-Vaxom®; Vifor Pharma; Meyrin 2/Geneva, Switzerland) in reducing the number of new RTI episodes in 288 children aged 1 to 6 years with a history of recurrent RTIs and to compare the efficacy of the standard 3-month regimen with that of administration of OM-85 for 6 months during a 6-month study period. Results The number of RTIs and of children who experienced at least one RTI were significantly lower among patients receiving OM-85 for 3 months than among those given placebo (33% vs 65.1%, p

Abstract Background There are no guidelines concerning the best approach to improving sleep, but it has been shown that it can benefit the affected children and their entire families. The aim of this review is to analyse the efficacy and safety of melatonin in treating pediatric insomnia and sleep disturbances. Main body Sleep disturbances are highly prevalent in children and, without appropriate treatment, can become chronic and last for many years; however, distinguishing sleep disturbances from normal age-related changes can be a challenge for physicians and may delay treatment. Some published studies have shown that melatonin can be safe and effective not only in the case of primary sleep disorders, but also for sleep disorders associated with various neurological conditions. However, there is still uncertainty concerning dosing regimens and a lack of other data. The dose of melatonin should therefore be individualised on the basis of multiple factors, including the severity and type of sleep problem and the associated neurological pathology. Conclusions Melatonin can be safe and effective in treating both primary sleep disorders and the sleep disorders associated with various neurological conditions. However, there is a need for further studies aimed at identifying the sleep disordered infants and children who will benefit most from melatonin treatment, and determining appropriate doses based on the severity and type of disorder.

Background: Previous studies have shown that during COVID-19 pandemic, mainly due to the imposed lockdown, significant psychological problems had emerged in a significant part of the population, including older children and adolescents. School closure, leading to significant social isolation, was considered one of the most important reasons for pediatric mental health problems. However, how knowledge of COVID-19 related problems, modification of lifestyle and age, gender and severity of COVID-19 pandemic had influenced psychological problems of older children and adolescents has not been detailed. To evaluate these variables, a survey was carried out in Italy.Methods: This cross-sectional survey was carried out by means of an anonymous online questionnaire administered to 2,996 students of secondary and high schools living in Italian Regions with different COVID-19 epidemiology.Results: A total of 2,064 adolescent students (62.8% females; mean age, 15.4 ± 2.1 years), completed and returned the questionnaire. Most of enrolled students showed good knowledge of COVID-19-related problems. School closure was associated with significant modifications of lifestyle and the development of substantial psychological problems in all the study groups, including students living in Regions with lower COVID-19 incidence. However, in some cases, some differences, were evidenced. Sadness was significantly more frequent in females (84%) than males (68.2%; p < 0.001) and in the 14–19-year-old age group than the 11–13-year-old age group (79.2% vs. 70.2%; p < 0.001). Missing the school community was a significantly more common cause of sadness in girls (26.5% vs. 16.8%; p < 0.001), in southern Italy (26.45% vs. 20.2%; p < 0.01) and in the 14–19-year-old group (24.2% vs. 14.7%; p < 0.001). The multivariate regression analysis showed that male gender was a protective factor against negative feelings (p < 0.01), leading to a decrease of 0.63 points in the total negative feelings index. Having a family member or an acquaintance with COVID-19 increased the negative feelings index by 0.1 points (p < 0.05).Conclusions: This study shows that school closures because of the COVID-19 pandemic outbreak was associated with significant lifestyle changes in all the students, regardless of age and gender. Despite some differences in some subgroups, the study confirms that school closure can cause relevant mental health problems in older children and adolescents. This must be considered as a reason for the maintenance of all school activities, although in full compliance with the measures to contain the spread of the pandemic.

Knowledge of the real incidence of small intestinal bacterial overgrowth (SIBO) in obese children and its role in obesity development seems essential for a more effective approach to the treatment of this condition. In this prospective, single-blind study, presence of SIBO was evaluated in a group of children with overweight/obesity. A blood sample for evaluation of cytokine profile was collected to establish the potential relationship with inflammatory condition and lactulose breath test (LBT) to diagnose SIBO was performed. A total of 36 patients with excess of adipose tissue were recruited. Among them, 16 (44.4%) were overweight and 20 (45.6%) were obese. Overall, 26 (72.2%) children had a positive LBT and were considered suffering from SIBO, 12 (75.0%) among those overweight and 14 (70.0%) among those obese. Measurement of cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-17, IFN-α2, IFN-γ, TNF-α), cytokine antagonists (IL-1ra), chemokines (IP10, MCP-1, MIP1α, MIP1β), and growth factors (EGF, G-CSF, GM-CSF, and VEGF) secreted in culture supernatants by PHA activated-PBMCs revealed that in the study population proinflammatory cytokines IL-1, IL-6, IL-8, IL-12, IFN-γ, IL-18, and TNF-α were high, whereas anti-inflammatory mediators IL-4 and IL-10 were low. However, no significance difference between children with SIBO and those without were evidenced. Evaluation of relationship of severity of SIBO showed a significant positive relationship between EGF or IFN-α2 and H2 but not CH4 levels and an inverse significant relationship with CH4 but not H2. Despite its limitations and further studies are needed, this study seems to indicate that SIBO is extremely common in overweight and obese children and can be demonstrated not only in severely obese subjects but also in moderately overweight patients. The inflammatory state seems to precede obesity development and SIBO does not seem to have relevance in obesity development, with no relationship found between severity of SIBO and inflammatory state.

The main aim of surgical antimicrobial prophylaxis (SAP) in urologic procedures is to prevent bacteraemia, surgical site infections (SSIs), and postoperative urinary tract infections (ppUTIs). Guidelines for SAP in paediatric urology are lacking. Only some aspects of this complex topic have been studied, and the use of antibiotic prophylaxis prior to surgical procedures seems to be more often linked to institutional schools of thought or experts’ opinions than to rules dictated by studies demonstrating the most correct and preferred management. Therefore, the aim of this Consensus document realized using the RAND/UCLA appropriateness method is to provide clinicians with a series of recommendations on SAP for the prevention of bacteraemia, SSIs, and ppUTIs after urologic imaging and surgical procedures in paediatric patients. Despite the few available studies, experts agree on some basilar concepts related to SAP for urologic procedures in paediatric patients. Before any urological procedure is conducted, UTI must be excluded. Clean procedures do not require SAP, with the exception of prosthetic device implantation and groin and perineal incisions where the SSI risk may be increased. In contrast, SAP is needed in clean-contaminated procedures. Studies have also suggested the safety of eliminating SAP in paediatric hernia repair and orchiopexy. To limit the emergence of resistance, every effort to reduce and rationalize antibiotic consumption for SAP must be made. Increased use of antibiotic stewardship can be greatly effective in this regard.

Abstract Background Type 1 diabetes (DM1) is one of the most common chronic diseases in childhood and requires life-long insulin therapy and continuous health care support. An artificial pancreas (AP) or closed-loop system (CLS) have been developed with the aim of improving metabolic control without increasing the risk of hypoglycaemia in patients with DM1. As the impact of APs have been studied mainly in adults, the aim of this review is to evaluate the efficacy and safety of the AP in the paediatric population with DM1. Main body The real advantage of a CLS compared to last-generation sensor-augmented pumps is the gradual modulation of basal insulin infusion in response to glycaemic variations (towards both hyperglycaemia and hypoglycaemia), which has the aim of improving the proportion of time spent in the target glucose range and reducing the mean glucose level without increasing the risk of hypoglycaemia. Some recent studies demonstrated that also in children and adolescents an AP is able to reduce the frequency of hypoglycaemic events, an important limiting factor in reaching good metabolic control, particularly overnight. However, the advantages of the AP in reducing hyperglycaemia, increasing the time spent in the target glycaemic range and thus reducing glycated haemoglobin are less clear and require more clinical trials in the paediatric population, in particular in younger children. Conclusions Although the first results from bi-hormonal CLS are promising, long-term, head-to-head studies will have to prove their superiority over insulin-only approaches. More technological progress, the availability of more fast-acting insulin, further developments of algorithms that could improve glycaemic control after meals and physical activity are the most important challenges in reaching an optimal metabolic control with the use of the AP in children and adolescents.

Several studies have shown that in recent years incidence of acute otitis media (AOM) has declined worldwide. However, related medical, social, and economic problems for patients, their families, and society remain very high. Better knowledge of potential risk factors for AOM development and more effective preventive interventions, particularly in AOM-prone children, can further reduce disease incidence. However, a more accurate AOM diagnosis seems essential to achieve this goal. Diagnostic uncertainty is common, and to avoid risks related to a disease caused mainly by bacteria, several children without AOM are treated with antibiotics and followed as true AOM cases. The main objective of this manuscript is to discuss the most common difficulties that presently limit accurate AOM diagnosis and the new approaches and technologies that have been proposed to improve disease detection. We showed that misdiagnosis can be dangerous or lead to relevant therapeutic mistakes. The need to improve AOM diagnosis has allowed the identification of a long list of technologies to visualize and evaluate the tympanic membrane and to assess middle-ear effusion. Most of the new instruments, including light field otoscopy, optical coherence tomography, low-coherence interferometry, and Raman spectroscopy, are far from being introduced in clinical practice. Video-otoscopy can be effective, especially when it is used in association with telemedicine, parents’ cooperation, and artificial intelligence. Introduction of otologic telemedicine and use of artificial intelligence among pediatricians and ENT specialists must be strongly promoted in order to reduce mistakes in AOM diagnosis.

Febrile neutropenia (FN) is a common complication of chemotherapy in oncological children and one of the most important causes of morbidity and mortality in these patients. The early detection of a bacteremia and the rapid therapeutic intervention are crucial to improve the outcome. We analyzed the literature in order to clarify the epidemiology of FN in children undergoing chemotherapy, the specific factors associated with a negative outcome, the most common etiology, and the value of biological markers as a tool to make an early diagnosis or to monitor the evolution of the infection. Several studies have tried to identify specific factors that could help the clinician in the detection of an infection and in its microbiological identification. However, due to the heterogenicity of the available studies, sufficient evidence is lacking to establish the role of these risk factors in clinical practice and future research on this topic appear mandatory. Determinations of risk factors, etiology, and markers of febrile episodes in these patients are complicated by the characteristics of the underlying illness and the effects of treatments received. Although some studies have tried to develop an evidence-based guideline for the empiric management of FN in pediatrics, validated predictive scores and algorithms are still lacking and urgently needed.

Lymphadenopathy is an irregularity in the size and texture of the lymph nodes, which is quite common in childhood. When the enlargement of lymph nodes is caused by inflammatory and infectious processes, it is called lymphadenitis. The main objective of this manuscript is to summarize the common infectious etiologies and presentations of lymphadenitis in children providing a management guide for clinical practice. PubMed was used to search for all of the studies published up to April 2021 using keywords such as “lymphadenitis” and “children”. Literature analysis showed that the differential diagnosis for lymphadenitis in pediatrics is broad. Although lymph node enlargement in children is usually benign and self-limited, it is important to exclude malignant etiology. In most cases, history and physical examination allow to identify the correct diagnosis and start a proper treatment with a prompt resolution of the lymphadenopathy. However, particularly in the case of persistent lymphadenitis, determining the cause of lymph node enlargement may be difficult, and the exact etiology may not be identified despite extensive investigations. Further studies should develop and validate an algorithm to assist pediatricians in the diagnosis and timely treatment of lymphadenitis, suggesting situations in which a watchful waiting may be considered a safe approach, those in which empiric antibiotic therapy should be administered, and those requiring a timely diagnostic work-up.

The concentration of the majority of hemostatic proteins differs considerably in early life, especially in neonates compared to adulthood. Knowledge of the concept of developmental hemostasis is an essential prerequisite for the proper interpretation of conventional coagulation tests (CCT) and is critical to ensure the optimal diagnosis and treatment of hemorrhagic and thrombotic diseases in neonatal age. Viscoelastic tests (VETs) provide a point-of-care, real-time, global, and dynamic assessment of the mechanical properties of the coagulation system with the examination of both cellular and plasma protein contributions to the initiation, formation, and lysis of clots. In this work, we provide a narrative review of the basic principles of VETs and summarize current evidence regarding the two most studied point-of-care VETs, thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®), in the field of neonatal care. A literature analysis shows that viscoelastic hemostatic monitoring appears to be a useful additive technique to CCT, allowing targeted therapy to be delivered quickly. These tools may allow researchers to determine the neonatal coagulation profile and detect neonatal patients at risk for postoperative bleeding, coagulation abnormalities in neonatal sepsis, and other bleeding events in a timely manner, guiding transfusion therapies using the goal-oriented transfusion algorithm. However, diagnosis and treatment algorithms incorporating VETs for neonatal patients in a variety of clinical situations should be developed and applied to improve clinical outcomes. Further studies should be performed to make routinary diagnostic and therapeutic application possible for the neonatal population.

Vaccines remain the best measure to reduce total influenza burden. However, presently available influenza vaccines have some limitations that cause a reduced efficacy compared to immunization practices with other respiratory pathogens. This paper shows the clinical roles of antiviral drugs against influenza that have been licensed in at least one country and the potential roles of compounds that are in development. Several attempts have been made to develop new agents against influenza viruses to overcome the supposed or demonstrated limitations of neuraminidase inhibitors (NAIs). Antibodies against the highly conserved stem region of the haemagglutinin molecule of influenza A viruses and drugs that target different stages of the influenza virus life cycle than NAIs in human cells have been developed and tested. Among these preparations, baloxavir marboxil (BAM), and favipiravir (FP) (i.e., polymerase inhibitors) are the only drugs that have reached the market (the first in Japan and the USA, and the second only in Japan). Other antiviral compounds and monoclonal antibodies are in advanced stage of development, but none of these new drugs and monoclonal antibodies in development have adequate characteristics to substitute for NAIs at present. However, although NAIs remain the drug of choice for influenza treatment, their overuse has to be avoided. Accurate selection of patients for whom treatment is truly needed is required.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that usually affects children and young adults after an infection or vaccination. The presence of several conditions mimicking ADEM, added to the lack of specific biomarkers, makes diagnosis potentially hard. Prompt diagnosis is necessary to start adequate treatment to improve the clinical course and long-term outcome. Because of its heterogeneity in both clinical presentation and course, challenges remain in establishing the most appropriate therapeutic approach in each patient. The aim of this review is to provide an update on management of this disease with a focus on acute treatment and to give suggestions for future research. We showed that there are currently no guidelines that help clinicians manage ADEM and therapeutic decisions are often made on a case-by-case basis. Further studies are necessary to identify clinical, laboratory, and instrumental criteria that could be correlated with outcomes and guide clinicians in choosing when and what treatment should be given in each case.

Telemedicine is the remote practice of medicine through the use of information and communication technologies for the prevention, diagnosis, treatment and management of diseases. In this narrative review, we illustrate how telemedicine technologies are increasingly integrated into pediatric infectious disease programs with the aim of facilitating access to specialist care and reducing costs. There is widespread use of telemedicine for the management of acute and chronic infectious diseases, particularly in countries in which the majority of the population lives in rural areas, far from third-level hospital centers located in large urban centers. Obviously, telemedicine is also used in developed countries, and its importance has been further increased recently given the COVID-19 pandemic. It has many advantages for patients, such as saving time, money and working hours, and reducing cancelled appointments and delays, while there are also many advantages for doctors, allowing collaborations with specialists and continuous updating. Among the disadvantages are the limitation in carrying out an objective examination, which is particularly important for children under 2 years of age, and the need for cutting-edge technology and reliable connectivity. Telemedicine increasingly represents the future and the beginning of a new healthcare system that also will redefine medical care for the treatment of infectious diseases, both acute and chronic. However, the majority of the experience has involved adults, and its validation in pediatric care, as well as its application in real-life practices, are urgently needed.

In children with cancer, chemotherapy can produce cytotoxic effects, resulting in immunosuppression and an augmented risk of febrile neutropenia and bloodstream infections. This has led to widespread use of antibiotic prophylaxis which, combined with intensive chemotherapy treatment, could have a long-term effect on the gastrointestinal microbiome. In this review, we aimed to analyze the current literature about the widespread use of antibiotic prophylaxis in children experiencing infectious complications induced by chemotherapy and its effects on the gut microbiome. Our review of the literature shows that antimicrobial prophylaxis in children with cancer is still a trending topic and, at the moment, there are not enough data to define universal guidelines. Children with cancer experience long and painful medical treatments and side effects, which are associated with great economic and social burdens, important psychological consequences, and dysbiosis induced by antibiotics and also by chemotherapy. Considering the importance of a healthy gut microbiota, studies are needed to understand the impact of dysbiosis in response to therapy in these children and to define how to modulate the microbiome to favor a positive therapeutic outcome.

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19.

Unexpected events of breath, tone, and skin color change in infants are a cause of considerable distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared protocol among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from ‘1’ (extremely inappropriate) to ‘9’ (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permitted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions.

Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.

Artificial intelligence (AI) is a field of science and engineering concerned with the computational understanding of what is commonly called intelligent behavior. AI is extremely useful in many human activities including medicine. The aim of our narrative review is to show the potential role of AI in fighting antimicrobial resistance in pediatric patients. We searched for PubMed articles published from April 2010 to April 2020 containing the keywords “artificial intelligence”, “machine learning”, “antimicrobial resistance”, “antimicrobial stewardship”, “pediatric”, and “children”, and we described the different strategies for the application of AI in these fields. Literature analysis showed that the applications of AI in health care are potentially endless, contributing to a reduction in the development time of new antimicrobial agents, greater diagnostic and therapeutic appropriateness, and, simultaneously, a reduction in costs. Most of the proposed AI solutions for medicine are not intended to replace the doctor’s opinion or expertise, but to provide a useful tool for easing their work. Considering pediatric infectious diseases, AI could play a primary role in fighting antibiotic resistance. In the pediatric field, a greater willingness to invest in this field could help antimicrobial stewardship reach levels of effectiveness that were unthinkable a few years ago.

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

Acute bacterial skin and soft tissue infections (aSSTIs) are a large group of diseases that can involve exclusively the skin or also the underlying subcutaneous tissues, fascia, or muscles. Despite differences in the localization and severity, all these diseases are due mainly to Gram-positive bacteria, especially Staphylococcus aureus and Streptococcus pyogenes. aSSTI incidence increased considerably in the early years of this century due to the emergence and diffusion of community-acquired methicillin-resistant S. aureus (CA-MRSA). Despite the availability of antibiotics effective against CA-MRSA, problems of resistance to these drugs and risks of significant adverse events have emerged. In this paper, the present knowledge on the potential role new antibiotics for the treatment of pediatric aSSTIs is discussed. The most recent molecules that have been licensed for the treatment of aSSTIs include ozenoxacin (OZ), ceftaroline fosamil (CF), dalbavancin (DA), oritavancin (OR), tedizolid (TD), delafloxacin (DL), and omadacycline (OM). However, only OZ and CF have been licensed for use in children with aSSTIs, although the superiority of these antibiotics to those routinely used for the treatment of aSSTIs should be further demonstrated. Waiting for additional studies, OZ and CF should be prescribed for aSSTI treatment in the presence of the potential failure of old molecules.

The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.

Introduction. Among neonates and infants

Back pain in children and adolescents is quite common, so developing preventive strategies for back pain is highly desirable. This article describes a planned school-based postural education project (PoSE) to promote healthy behaviors among middle school students and their families and to moderate postural diseases. As first s tep, we e valuated which a spects of postural behaviors were integrated in children’s lifestyle through a questionnaire. Then, the educational program consisted of interactive lessons on back posture and good principles both in class and at home. A participatory approach was used to evaluate attempts to involve all who have a stake in outcomes in order to take action and effect change. The strength of the participatory approach used in this study lies in the contribution to empowerment social change.

Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.