Redox biomarkers in asymptomatic latent human tuberculosis: a comparison with active disease.

BACKGROUND: The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. METHODS: We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. RESULTS: Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. CONCLUSION: This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.

Pre-COVID-19-pandemic RSV epidemiology and clinical burden in pediatric primary care in Italy: a comparative analysis across two regions for the 2019/2020 season.

BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.

Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Center Prospective Cohort Study.

OBJECTIVES: Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP). DESIGN: Prospective study. SETTING: PICU and pediatric emergency department. INTERVENTION: Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission. MEASUREMENTS AND MAIN RESULTS: We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels ( p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73. CONCLUSIONS: In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers.

Parents' Trigger Tool for Children with Medical Complexity - PAT-CMC: Development of a recognition tool for clinical deterioration at home.

AIM: To develop a trigger tool for parents and lay caregivers of children with medical complexity (CMC) at home and to validate its content. DESIGN: This was a multi-method study, using qualitative data, a Delphi method and a concept mapping approach. METHODS: A three-round electronic Delphi was performed from December 2021 to April 2022 with a panel of 23 expert parents and 30 healthcare providers, supplemented by a preliminary qualitative exploration of children's signs of deterioration and three consensus meetings to develop the PArents' Trigger Tool for Children with Medical Complexity (PAT-CMC). Cognitive interviews with parents were performed to assess the comprehensiveness and comprehensibility of the tool. The COREQ checklist, the COSMIN guidelines and the CREDES guidelines guided the reporting respectively of the qualitative study, the development and content validity of the trigger tool and the Delphi study. RESULTS: The PAT-CMC was developed and its content validated to recognize clinical deterioration at home. The tool consists of 7 main clusters of items: Breathing, Heart, Devices, Behaviour, Neuro-Muscular, Nutrition/Hydration and Other Concerns. A total of 23 triggers of deterioration were included and related to two recommendations for escalation of care, using a traffic light coding system. CONCLUSION: Priority indicators of clinical deterioration of CMC were identified and integrated into a validated trigger tool designed for parents or other lay caregivers at home, to recognize signs of acute severe illness and initiate healthcare interventions. IMPACT: The PAT-CMC was developed to guide families in recognizing signs of deterioration in CMC and has potential for initiating an early escalation of care. This tool may also be useful to support education provided by healthcare providers to families before hospital discharge. PATIENT OR PUBLIC CONTRIBUTION: Parents of CMC were directly involved in the selection of relevant indicators of children's clinical deterioration and the development of the trigger tool. They were not involved in the design, conducting, reporting or dissemination plans of this research.

AVNRT cryoablation in children <26 kg: efficacy and safety of electrophysiologically guided low-voltage bridge strategy.

The recently published "electrophysiologically guided low-voltage bridge (LVB) strategy" is effective in the ablation of atrioventricular nodal re-entry tachycardia (AVNRT) in children. This study aimed to evaluate its efficacy and safety in children <26 kgs. Fourteen children [64% males, median age 6.5 years (IQR 6-8 years), median weight 25.5 kg (IQR 24-26 kg)] with AVNRT were treated. In all patients, we detected a LVB associated to a typical slow pathway potential. The acute success rate was 100% with a mean of 5.5 cryoablation deliveries. All procedures were performed with near-zero fluoroscopic exposure (median time 0.15 min, IQR 0-0.7 min), in six patients fluoroscopy was 0 min. There were no complications or recurrences during the follow-up (median 20.91 months, IQR 11.7-26.7 months).

Respiratory syncytial virus: can we still believe that after pandemic bronchiolitis is not a critical issue for public health?

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. Since the beginning of the COVID-19 pandemic, non-pharmacological interventions were applied, interfering with the circulation of most respiratory viruses, including RSV. The aim of this study is to analyze the RSV infection trend among hospitalized infants during the actual epidemic season (2022-2023) in comparison with the last pre-pandemic season (2018-2019), in order to outline whether significant differences emerge due to COVID-19 pandemia. We retrospectively reviewed medical data on infants hospitalized at the Bambino Gesù Children's Hospital with diagnosis of bronchiolitis in the current epidemic season and in the last pre-pandemic season, 2018-2019. RSV remains the main etiological agent of bronchiolitis in terms of frequency and severity of infections in the ongoing epidemic season. The first RSV case of the 2022-2023 season was detected at week 42 vs week 47 in the 2018-2019 season. The length of epidemic season was of 17 weeks in 2022-2023 vs 18 weeks in 2018-2019. Comparing the two seasons, age at admission was significantly higher in the current season (median age 2022-2023 65 days vs median age 2018-2019 58 days), but the disease severity was similar.       Conclusions: The 2022-2023 bronchiolitis season in Italy started earlier than the usual pre-pandemic seasons but seasonality pattern may be going back to the pre-pandemic one. This season was not more severe than the previous ones. The impact of RSV disease on health care systems and costs remains a critical issue. What is Known: • RSV is one of the major leading causes of hospitalization among children aged less than 3 months. SarsCOV2 pandemic interfered with the seasonal circulation of most respiratory viruses, Including RSV. What is New: • The 2022-2023 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons but seasonality pattern may be realigning to the pre-pandemic one. The impact of RSV disease on health care systems and costs is concerning.

Pediatric vital signs monitoring in hospital wards: Recognition systems and factors influencing nurses' attitudes and practices.

AIMS: To describe: 1) systems in place for recognition and response to deteriorating children in Italy, 2) attitudes and practices of registered nurses (RN) towards vital signs (VS) monitoring in pediatric wards, 3) the associations of nurses attitudes and pratices with nurses' and organizational characteristics. DESIGN AND METHODS: A multicentre cross-sectional correlational study. Data were collected between January-May 2020 using: an adapted version of the 'Survey on Recognition and Response Systems in Australia', and the 'Ped-V Scale'. Descriptive and adjusted linear regression analysis was performed, accounting for clustering. RESULTS: Ten Italian hospitals participated, 432 RNs responded to the Ped-V scale (response rate = 52%). Five (50%) hospitals had a VS policy in place, three hospitals (30%) had a Pediatric Early Warning System (PEWS), almost all hospitals had a system in place to respond to deteriorating children. Following multivariate regression analysis, having a PEWS was significantly associated with Ped-V scale 'Workload', 'Clinical competence', 'Standardization' dimensions; gender was associated with 'key indicators' and pediatric surgical ward with 'Clinical competence'. CONCLUSIONS: The use of VS policies and PEWS was not consistent across hospitals caring for children in Italy. Nurses' attitudes and practices (i.e., perception of workload, and clinical competence) were significantly lower in hospitals with increased complexity of care/PEWS. Gender was significantly associated with knowledge scores. PRACTICE IMPLICATIONS: System strategies to improve nurses' attitudes and practices towards VS monitoring and education are warranted to support effective behaviors towards VS monitoring, their interpretation, and appropriate communication to activate the efferent limb of the rapid response system.

A Cell-Phone Medication Error eHealth App for Managing Safety in Chronically Ill Young Patients at Home: A Prospective Study.

Introduction: Whereas ample information describes medication errors (MEs) in children or in mixed pediatric and adult populations discharged with acute or chronic diseases from hospital to community settings, little is known about MEs in children and adolescents with chronic diseases discharged home, a major concern. To promote home medication safety, we trained parents of children discharged with chronic diseases to record ME with a tailored cell-phone eHealth app. Methods: In a 1-year prospective study, we used the app to monitor ME in patients with chronic diseases discharged home from a tertiary hospital in Rome, Italy. Univariate and multivariate analyses detected the ME incidence rate ratio (IRR). Results: Of the 310 parents enrolled, 194 used the app. The 41 MEs involved all drug management phases. The ME IRR was 0.46 errors per child. Children <1 year had the highest ME risk (1.69 vs. 0.35, p = 0.002). Children discharged from the cardiology unit had a statistically higher ME IRR than others (3.66, 95% confidence interval: 1.01-13.23%). Conclusions: The highest ME risk at home involves children with chronic diseases <1 year old. A significant ME IRR at home concerns children with heart diseases of any age. Parents find a tailored eHealth app for monitoring and reporting ME at home easy to use. At discharge, clinical teams need to identify age-related and disease-residual risks to target additional actions for monitoring ME, thus increasing medication safety at home.

Implementation of paediatric intensive care unit diaries: Feasibility and opinions of parents and healthcare providers.

BACKGROUND: The implementation of paediatric intensive care unit (PICU) diaries has been reported as feasible in routine care. To date no feasibility study has compared PICU healthcare providers' (HCPs) and parents' opinions on this tool. OBJECTIVES: The aim of this study is to describe the feasibility and perception of PICU diaries in an Italian PICU from the point of view of parents and HCPs. METHODS: This is a single-centre, prospective, observational study conducted in a tertiary care paediatric hospital from August 2020 to May 2021. Children admitted to the emergency department PICU, intubated, and sedated for ≥48 h were enrolled. To explore their perceptions and attitudes with the PICU diary, parents were interviewed at 30 days from their child's discharge from the PICU, whereas PICU HCPs were surveyed at the end of the study. Data were analysed as proportions for categorical variables and means and medians for continuous variables according to the distribution, whereas qualitative data were summarised in categories by two independent researchers. RESULTS: Twenty families were enrolled in this study. A total of 275 daily PICU diary entries were collected. Children's median age was 9 years (interquartile range = 2-13.25), and the length of stay ranged from 6 to 39 days. PICU diary applicability was rated high by parents and HCPs (>8 on a 1-10 Likert scale). Parents and HCPs perceived PICU diaries as beneficial for communication between staff and families, for parents by expressing their emotions and for staff by becoming aware of how parents experienced their child's admission. Reported barriers were the lack of a private environment, the risk of exposure to public reading, and PICU workload. CONCLUSIONS: PICU diaries were feasible and perceived as beneficial both by parents and HCPs. Future research is warranted to understand the effect of PICU diaries on post-PICU outcomes.

Expression analysis of miRNA hsa-let7b-5p in naso-oropharyngeal swabs of COVID-19 patients supports its role in regulating ACE2 and DPP4 receptors.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID-19). We previously observed that Angiotensin-converting enzyme 2 (ACE2) and Dipeptidyl peptidase-4 (DPP4) are significantly overexpressed in naso-oropharyngeal swabs (NPS) of COVID-19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID-19 patients may be associated to epigenetic mechanism, such as miRNA differential expression. We investigated if hsa-let7b-5p, reported to target both ACE2 and DPP4 transcripts, could be involved in the regulation of these genes. We verified that the inhibition and overexpression of hsa-let7b-5p matched to a modulation of both ACE2 and DPP4 levels. Then, we observed a statistically significant downregulation (FC = -1.5; p < 0.05) of hsa-let7b-5p in the same COVID-19 and control samples of our previous study. This is the first study that shows hsa-let7b-5p low expression in naso-oropharyngeal swabs of COVID-19 patients and demonstrates a functional role of this miR in regulating ACE2 and DPP4 levels. These data suggest the involvement of hsa-let7b-5p in the regulation of genes necessary for SARS-CoV-2 infections and its putative role as a therapeutic target for COVID-19.

Effective Rapid Diagnosis of Bacterial and Fungal Bloodstream Infections by T2 Magnetic Resonance Technology in the Pediatric Population.

Children are prone to bloodstream infections (BSIs), the rapid and accurate diagnosis of which is an unmet clinical need. The T2MR technology is a direct molecular assay for identification of BSI pathogens, which can help to overcome the limits of blood culture (BC) such as diagnostic accuracy, blood volumes required, and turnaround time. We analyzed results obtained with the T2Bacteria (648) and T2Candida (106) panels in pediatric patients of the Bambino Gesù Children's Hospital between May 2018 and September 2020 in order to evaluate the performance of the T2Dx instrument with respect to BC. T2Bacteria and T2Candida panels showed 84.2% and 100% sensitivity with 85.9% and 94.1% specificity, respectively. The sensitivity and specificity of the T2Bacteria panel increased to 94.9% and 98.7%, respectively, when BC was negative but other laboratory data supported the molecular result. T2Bacteria sensitivity was 100% with blood volumes <2 mL in neonates and infants. T2Bacteria and T2Candida provided definitive microorganism identification in a mean time of 4.4 and 3.7 h, respectively, versus 65.7 and 125.5 h for BCs (P < 0.001). T2 panels rapidly and accurately enable a diagnosis of a pediatric BSI, even in children under 1 year of age and for very small blood volumes. These findings support their clinical use in life-threatening pediatric infections, where the time to diagnosis is of utmost importance, in order to improve survival and minimize the long-term sequalae of sepsis. The T2 technology could be further developed to include more bacteria and fungi species that are involved in the etiology of sepsis.

Escalation of care in children at high risk of clinical deterioration in a tertiary care children's hospital using the Bedside Pediatric Early Warning System.

BACKGROUND: Escalation and de-escalation are a routine part of high-quality care that should be matched with clinical needs. The aim of this study was to describe escalation of care in relation to the occurrence and timing of Pediatric Intensive Care Unit (PICU) admission in a cohort of pediatric inpatients with acute worsening of their clinical condition. METHODS: A monocentric, observational cohort study was performed from January to December 2018. Eligible patients were children: 1) admitted to one of the inpatient wards other than ICU; 2) under the age of 18 years at the time of admission; 3) with two or more Bedside-Paediatric-Early-Warning-System (BedsidePEWS) scores ≥ 7 recorded at a distance of at least one hour and for a period of 4 h during admission. The main outcome -the 24-h disposition - was defined as admission to PICU within 24-h of enrolment or staying in the inpatient ward. Escalation of care was measured using an eight-point scale-the Escalation Index (EI), developed by the authors. The EI was calculated every 6 h, starting from the moment the patient was considered eligible. Analyses used multivariate quantile and logistic regression models. RESULTS: The 228 episodes included 574 EI calculated scores. The 24-h disposition was the ward in 129 (57%) and the PICU in 99 (43%) episodes. Patients who were admitted to PICU within 24-h had higher top EI scores [median (IQR) 6 (5-7) vs 4 (3-5), p < 0.001]; higher initial BedsidePEWS scores [median (IQR) 10(8-13) vs. 9 (8-11), p = 0.02], were less likely to have a chronic disease [n = 62 (63%) vs. n = 127 (98%), p < 0.0001], and were rated by physicians as being at a higher risk of having a cardiac arrest (p = 0.01) than patients remaining on the ward. The EI increased over 24 h before urgent admission to PICU or cardiac arrest by 0.53 every 6-h interval (CI 0.37-0.70, p < 0.001), while it decreased by 0.25 every 6-h interval (CI -0.36-0.15, p < 0.001) in patients who stayed on the wards. CONCLUSION: Escalation of care was related to temporal changes in severity of illness, patient background and environmental factors. The EI index can improve responses to evolving critical illness.

Reduction of Waiting Times and Patients Leaving Without Being Seen in the Tertiary Pediatric Emergency Department: A Comparative Observational Study.

OBJECTIVES: Analyze the effectiveness of an intervention to reduce waiting time and patients leaving without being seen in the pediatric emergency department. METHODS: A comparative observational study was carried out from November 2018 to April 2019.Patients aged 3 months to 17 years were included. The new organizational model consisted of a dedicated outpatients' clinic for nonurgent codes and a fast track for traumatic and surgical emergency cases. RESULTS: The comparative group included 14,822, and the intervention group included 15,585 patients. The new organizational model significantly reduced the numbers of patients who left the ED without being seen from 12.9% to 5.9%. CONCLUSIONS: This new organizational model in the pediatric emergency department could be successfully used to reduce overcrowding, waiting time, and the numbers of patients leaving without being seen. However, more needs to be done by the pediatric services in the community to reduce nonurgent accesses to the emergency department.

Attitudes and practices towards vital signs monitoring on paediatric wards: Cross-validation of the Ped-V scale.

PURPOSE: To develop and psychometrically test an instrument measuring the attitudes and practices towards vital signs (VS) monitoring in nurses caring for children on paediatric wards (Ped-V scale). DESIGN AND METHODS: This is a multicentre cross-validation study with a cross-sectional design. The Ped-V scale was developed by adapting the V-scale to the paediatric context and administered to a convenience sample of clinical nurses working in paediatric wards from January to May 2020. The content validity of the Ped-V scale was evaluated by a group of 10 experts. The psychometric properties of the scale were tested through Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). RESULTS: Overall, 10 Italian hospitals participated in the study, and 640 questionnaires were completed (87% female). At EFA a 30-item version of the scale and four factors emerged. This solution was confirmed at CFA: F1) 'Inaccuracy of VS monitoring and workload'; F2) 'Clinical competence and communication'; F3) 'Standardization and protocol adherence'; F4) 'Misconceptions about key indicators'. Cronbach's alpha ranged between 0.63 and 0.85. CONCLUSIONS: The Ped-V scale is valid and reliable for use in the paediatric context to identify barriers concerning nurses' self-efficacy, competences, and knowledge of clinical indicators of paediatric critical deterioration, attitudes towards accuracy, standardization, communication to senior team members and the appropriate use of technology in paediatric VS monitoring. PRACTICE IMPLICATIONS: The Ped-V scale may assist in identifying gaps in nurses' attitudes and devising strategies to change nurses' beliefs, knowledge, skills and decreasing individual, local cultural or organizational barriers towards VS monitoring.

Participation of nurses and allied health professionals in research activities: a survey in an academic tertiary pediatric hospital.

BACKGROUND: Involvement in research activities is complex in pediatric nursing and allied health professionals (AHPs). It is important to understand which individual factors are associated with it to inform policy makers in promoting research. METHODS: A cross-sectional observational study was conducted to describe the level of participation in research activities over the last ten years of nurses and AHPs working in a tertiary pediatric hospital. A large sample of nurses and AHPs working in an Italian academic tertiary pediatric hospital completed an online self-report questionnaire between June and December 2018. Three multivariate logistic regression analyses were performed to predict participation in research projects, speaking at conferences, and writing scientific articles. RESULTS: Overall, data from 921 health professionals were analyzed (response rate = 66%), of which about 21% (n = 196) reported participating in a research project, while 33% (n = 297) had attended a scientific conference as a speaker, and 11% (n = 94) had written at least one scientific paper. Having a Master or a Regional Advanced Course, working as an AHP or a ward manager, as well as regularly reading scientific journals and participation in an internal hospital research group or attendance in a specific course about research in the hospital, significantly predicted participation in research projects, speaking at conferences and writing scientific papers. It is important to foster research interest and competencies among health professionals to improve participation in research projects, speaking at conferences, and writing scientific papers. CONCLUSIONS: Overall, we found a good level of attendance at conferences as speakers (33%), a moderate level of participation in research (21%), and low levels for writing scientific papers (11%). Our study highlighted the need to support participation in research activities among nurses and AHPs. Policymakers should identify strategies to promote research among nurses and AHPs, such as protected rewarded time for research, specific education, strengthened collaboration with academics, and financial support. Moreover, hospital managers should promote the development of research culture among health professionals, to improve their research competencies and evidence-based practice.

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: A quality improvement study.

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy.

Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients.

BACKGROUND: Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East respiratory syndrome ( MERS-CoV ), the severe acute respiratory syndrome corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. METHODS: As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children's Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females). RESULTS: We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient. CONCLUSIONS: Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.

The role of air conditioning in the diffusion of Sars-CoV-2 in indoor environments: A first computational fluid dynamic model, based on investigations performed at the Vatican State Children's hospital.

BACKGROUND: About 15 million people worldwide were affected by the Sars-Cov-2 infection, which already caused 600,000 deaths. This virus is mainly transmitted through exhalations from the airways of infected persons, so that Heating, Ventilation and Air Conditioning (HVAC) systems might play a role in increasing or reducing the spreading of the infection in indoor environments. METHODS: We modeled the role of HVAC systems in the diffusion of the contagion through Computational Fluid Dynamics (CFD) simulations of cough at the "Bambino Gesù" Vatican State Children's Hospital. Both waiting and hospital rooms were modeled as indoor scenarios. A specific Infection-Index (η) parameter was used to estimate the amount of contaminated air inhaled by each person present in the simulated indoor scenarios. The potential role of exhaust air ventilation systems placed above the coughing patient's mouth was also assessed. RESULTS: Our CFD-based simulations of the waiting room show that HVAC air-flow remarkably enhances infected droplets diffusion in the whole indoor environment within 25 s from the cough event, despite the observed dilution of saliva particles containing the virus. At the same time also their number is reduced due to removal through the HVAC system or deposition on the surfaces. The proper use of Local Exhaust Ventilation systems (LEV) simulated in the hospital room was associated to a complete reduction of infected droplets spreading from the patient's mouth in the first 0.5 s following the cough event. In the hospital room, the use of LEV system completely reduced the η index computed for the patient hospitalized at the bed next to the spreader, with a decreased possibility of contagion. CONCLUSIONS: CFD-based simulations for indoor environment can be useful to optimize air conditioning flow and to predict the contagion risk both in hospitals/ambulatories and in other public/private settings.

Adherence to the bedside paediatric early warning system (BedsidePEWS) in a pediatric tertiary care hospital.

BACKGROUND: The aim of this study is to describe the adherence to the Bedside Pediatric Early Warning System (BedsidePEWS) escalation protocol in children admitted to hospital wards in a large tertiary care children's hospital in Italy. METHODS: This is a retrospective observational chart review. Data on the frequency and accuracy of BedsidePEWS score calculations, escalation of patient observations, monitoring and medical reviews were recorded. Two research nurses performed weekly visits to the hospital wards to collect data on BedsidePEWS scores, medical reviews, type of monitoring and vital signs recorded. Data were described through means or medians according to the distribution. Inferences were calculated either with Chi-square, Student's t test or Wilcoxon-Mann-Whitney test, as appropriate (P < 0.05 considered as significant). RESULTS: A total of 522 Vital Signs (VS) and score calculations [BedsidePEWS documentation events, (DE)] on 177 patient clinical records were observed from 13 hospital inpatient wards. Frequency of BedsidePEWS DE occurred < 3 times per day in 33 % of the observations. Adherence to the BedsidePEWS documentation frequency according to the hospital protocol was observed in 54 % of all patients; in children with chronic health conditions (CHC) it was significantly lower than children admitted for acute medical conditions (47 % vs. 69 %, P = 0.006). The BedsidePEWS score was correctly calculated and documented in 84 % of the BedsidePEWS DE. Patients in a 0-2 BedsidePEWS score range were all reviewed at least once a day by a physician. Only 50 % of the patients in the 5-6 score range were reviewed within 4 h and 42 % of the patients with a score ≥ 7 within 2 h. CONCLUSIONS: Escalation of patient observations, monitoring and medical reviews matching the BedsidePEWS is still suboptimal. Children with CHC are at higher risk of lower compliance. Impact of adherence to predefined response algorithms on patient outcomes should be further explored.

Sustainability of paediatric radiology in Italy.

Italy is the sixth most populous country in Europe and has the second highest average life expectancy, reaching 79.4 years for men and 84.5 for women. However, Italy has one of the lowest total fertility rates in the world: in 2018 it was 1.3 births per woman, with the population older than 65 comprising more than 30%, and those younger-than-19 less than 15%. Older people are the main concern of the Italian health system. Weighted coefficients for the allocation of funds favour older adults. As confirmed by our study, paediatric radiology is expensive, and the reimbursement based on Italian adult rates is not sufficient. The negative impact on the budget discourages the diffusion of paediatric radiology both in the private practices that provide services paid for by the state government and in the public hospitals. The 501 paediatric hospital units in Italy are not homogeneously distributed throughout the national territory. Furthermore, in Italy there are 12 highly specialised children's hospitals whose competences were defined in 2005 by the Ministry of Health. Paediatric radiology is not included among the highly qualified specialties. The quality gap in paediatric radiology between children's hospitals and general hospitals, the latter often without paediatric radiologists, is evident in daily practice with misdiagnoses and investigations not carried out.