Gender-based medicine is an innovative branch of biomedical research and represents a new perspective for the future of health research. Many studies have been published on gender medicine in adults ...but very few data regarding children are available.
A literature search covering articles published between 1stJuly, 2006 and 1st February, 2017 and concerning children only was conducted using multiple keywords and standardized terminology in Pubmed database. The search was limited to English-language publications. All relevant articles on endocrines, neurological, psychiatric, gastrointestinal, immunological, oncological, rheumatic, pneumological disorders, infectious diseases and analgesia were evaluated and pertinent articles were included in this review. Most of the available studies on gender disparity in childhood are about endocrine and neuro-psychiatric disorders, while there are few data in other areas of medicine.
Even if several studies on pediatric gender differences can be found on literature, few of them move forwards to analyze the reasons of the observed diversity. No data on pharmacokinetic and pharmacodynamic differences between boys and girls can be found. Hence, more efforts should be directed to investigate these topics in childhood.
Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in ...Italian children's hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions.
A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected.
The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates (<30 days old) and children (> = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for prescribing antibiotic therapy in children was lower respiratory tract infections (LRTI), followed by febrile neutropenia/fever in oncologic patients, while, in neonates, sepsis was the most common indication for treatment. Focusing on prescriptions for LRTI, 43.3% of patients were treated with 3rd generation cephalosporins, followed by macrolides (26.9%), quinolones (16.4%) and carbapenems (14.9%) and 50.1% of LRTI cases were receiving more than one antibiotic. For neutropenic fever/fever in oncologic patients, the preferred antibiotics were penicillins with inhibitors (47.8%), followed by carbapenems (34.8%), aminoglycosides (26.1%) and glycopeptides (26.1%). Overall, the 60.9% of patients were treated with a combination therapy.
Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children's hospital, also considering the continuous and alarming emergence of MDR bacteria.
Staphylococcus aureus is an opportunistic pathogen and a leading cause of nosocomial infections. It can acquire resistance to all the antibiotics that entered the clinics to date, and the World ...Health Organization defined it as a high-priority pathogen for research and development of new antibiotics. A deeper understanding of the genetic variability of S. aureus in clinical settings would lead to a better comprehension of its pathogenic potential and improved strategies to contrast its virulence and resistance. However, the number of comprehensive studies addressing clinical cohorts of S. aureus infections by simultaneously looking at the epidemiology, phylogenetic reconstruction, genomic characterisation, and transmission pathways of infective clones is currently low, thus limiting global surveillance and epidemiological monitoring.
We applied whole-genome shotgun sequencing (WGS) to 184 S. aureus isolates from 135 patients treated in different operative units of an Italian paediatric hospital over a timespan of 3 years, including both methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) from different infection types. We typed known and unknown clones from their genomes by multilocus sequence typing (MLST), Staphylococcal Cassette Chromosome mec (SCCmec), Staphylococcal protein A gene (spa), and Panton-Valentine Leukocidin (PVL), and we inferred their whole-genome phylogeny. We explored the prevalence of virulence and antibiotic resistance genes in our cohort, and the conservation of genes encoding vaccine candidates. We also performed a timed phylogenetic investigation for a potential outbreak of a newly emerging nosocomial clone.
The phylogeny of the 135 single-patient S. aureus isolates showed a high level of diversity, including 80 different lineages, and co-presence of local, global, livestock-associated, and hypervirulent clones. Five of these clones do not have representative genomes in public databases. Variability in the epidemiology is mirrored by variability in the SCCmec cassettes, with some novel variants of the type IV cassette carrying extra antibiotic resistances. Virulence and resistance genes were unevenly distributed across different clones and infection types, with highly resistant and lowly virulent clones showing strong association with chronic diseases, and highly virulent strains only reported in acute infections. Antigens included in vaccine formulations undergoing clinical trials were conserved at different levels in our cohort, with only a few highly prevalent genes fully conserved, potentially explaining the difficulty of developing a vaccine against S. aureus. We also found a recently diverged ST1-SCCmecIV-t127 PVL- clone suspected to be hospital-specific, but time-resolved integrative phylogenetic analysis refuted this hypothesis and suggested that this quickly emerging lineage was acquired independently by patients.
Whole genome sequencing allowed us to study the epidemiology and genomic repertoire of S. aureus in a clinical setting and provided evidence of its often underestimated complexity. Some virulence factors and clones are specific of disease types, but the variability and dispensability of many antigens considered for vaccine development together with the quickly changing epidemiology of S. aureus makes it very challenging to develop full-coverage therapies and vaccines. Expanding WGS-based surveillance of S. aureus to many more hospitals would allow the identification of specific strains representing the main burden of infection and therefore reassessing the efforts for the discovery of new treatments and clinical practices.
A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of ...Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.
Scalp Eschar and Neck LymphAdenopathy after Tick bite is a zoonotic non-pathogen-specific disease most commonly due to Rickettsia slovaca and Rickettsia raoultii. Diagnosis is mostly based only on ...epidemiological and clinical findings, without serological or molecular corroboration. We presented a clinical case in which diagnosis was supported by entomological identification and by R. slovaca DNA amplifications from the tick vector.
A 6-year-old child presented with asthenia, scalp eschar and supraclavicular and lateral-cervical lymphadenopathy. Scalp Eschar and Neck LymphAdenopathy After Tick bite syndrome following a Dermacentor marginatus bite was diagnosed. Serological test on serum revealed an IgG titer of 1:1024 against spotted fever group rickettsiae, polymerase chain reaction assays on tick identified Rickettsia slovaca. Patient was successfully treated with doxycycline for 10 days.
A multidisciplinary approach including epidemiological information, clinical evaluations, entomological identification and molecular investigations on tick, enabled proper diagnosis and therapy.
In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual ...hormones on immunity is possible.
Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1st 1997 to December 31st 2011, were analyzed using the International Classification of Disease, 9th Revision, Clinical Modification.
During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children 0-14 years, 205 (1.9%) adolescents 15-18 years and 10,260 (95.5%) adults ≥ 18 years. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age.
Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1:1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB.
Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to ...promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (less than or equai to 2 years, 2-12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Based on our findings, monitoring patients' drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.
Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores ...are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.
...the available literature on pediatric treatment strategies for SARS-CoV-2 infection in children was reviewed up to 10 March 2021 on PubMed, the website of national and international scientific ...societies and of clinical trials. In particular, for the age group 12–17 years, the risk factors are the following: body mass index > 95 percentile for age, sickle cell anemia, congenital or acquired cardiac disease, neurodevelopment disease, device carriers (tracheostomy, gastrostomy, etc.), asthma or other respiratory disorders requiring daily treatment 17, 18. ...the best treatment for pediatric COVID-19 is currently not well defined, because randomized trials in children are lacking.
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