Universal newborn screening for congenital cytomegalovirus infection: feasibility and relevance in a French type-III maternity cohort.

OBJECTIVE: Evaluation of relevance and feasibility of universal newborn congenital cytomegalovirus infection (cCMVI) screening in saliva. DESIGN: Retrospective, population-based cohort study. SETTING: Clamart, France, 2016-2020. POPULATION: All neonates born consecutively in our level III maternity unit. METHODS: CMV PCR in saliva for all neonates at birth, and, if positive, CMV PCR in urine to confirm or exclude cCMVI. Prospective and retrospective characterisation of maternal infections. ROC curve analysis to assess saliva PCR performances. Acceptability of screening among staff members evaluated by a survey. MAIN OUTCOME MEASURES: Number of cCMVI neonates; number of expected and unexpected cCMVI. RESULTS: Among 15 341 tested neonates, 63 had cCMVI (birth prevalence of 0.4%, 95% CI 0.3-0.5). In 50% of cases, maternal infection was a non-primary infection (NPI) during pregnancy. cCMVI was expected or suspected (maternal primary infection [PI], antenatal or neonatal signs) in 24/63 neonates (38%), and unexpected in 39/63 neonates (62%). The best CMV saliva threshold to predict cCMVI was 356 (2.55 log) copies/ml [95% CI 2.52 log-3.18 log], with an area under the ROC curve of 0.97. Over 90% of the 72 surveyed staff members reported that the screening was easy and quick. No parent refused the screening. CONCLUSIONS: Universal screening for cCMVI with CMV PCR on saliva samples is feasible and highly acceptable to parents and healthcare providers. Over half (62%) of the cases had no prenatal/neonatal signs of cCMVI or a maternal history of CMV infection during pregnancy and would probably not have been diagnosed without universal screening. TWEETABLE ABSTRACT: In 62% of congenital cytomegalovirus infection cases, only universal neonatal screening in saliva can detect infection.

Introduction of point-of-care neonatal lung ultrasound in a developing country.

Despite neonatal lung ultrasound (LU) being diffused worldwide, its introduction in limited-resource areas has not been formally investigated. We conceived a project to introduce it in a level 3 NICU of a developing country and verify if, after a short protocolized training, clinicians may efficaciously use LU. Inter-rater agreement between ultrasound trainees and trainers was analyzed within both the local test and the diffusion phases of the project. High inter-rater agreements were found between expert trainers and the two neonatologists who were trained in a skilled European center (Cohen's Kappa, 0.951; 95%CI, 0.882-0.999), as well as between the two and the second round of locally trained colleagues (Cohen's Kappa, 0.896; 95%CI, 0.797-0.996). Moreover, a high agreement was found between the clinical respiratory diagnosis (used as the "gold standard") and the LU diagnosis given by the first two trainees (intraclass correlation, 0.992; 95%CI, 0.987-0.996) and the locally trained physicians (intraclass correlation, 0.97; 95%CI, 0.95-0.98). A final survey demonstrated that the project was perceived as efficacious and that LU was going to be integrated into routine clinical practice.Conclusions: А short LU training provided sufficient proficiency and allowed the LU introduction in clinical practice in the neonatal intensive care unit in a developing country.What is Known:• Lung ultrasound is a promising technique for evaluating neonatal respiratory distress at least in high-income countries. Previous studies revealed high specificity and sensitivity in diagnosing specific neonatal disorders.• An important barrier to the more extensive use of lung ultrasound in neonatal critical care is a lack of efficient and suitable training solutions.What is New:• Descriptive LU performed by neonatologist in a developing country after a short formal training is feasible with good quality.• A short formal LU training program provided good proficiency and allowed a correct descriptive diagnosis in a neonatal unit in a developing country.

Dexmedetomidine is effective and safe during NIV in infants and young children with acute respiratory failure.

BACKGROUND: Noninvasive ventilation (NIV) is increasingly utilized in infants and young children, though associated with high failure rates due to agitation and poor compliance, mostly if patient-ventilator synchronization is required. METHODS: A retrospective cohort study was carried out in an academic pediatric intensive care unit (PICU). Dexmedetomidine (DEX) was infused as unique sedative in 40 consecutive pediatric patients (median age 16 months) previously showing intolerance and agitation during NIV application. RESULTS: During NIV clinical application both COMFORT-B Score and Richmond Agitation-Sedation Scale (RASS) were serially evaluated. Four patients experiencing NIV failure, all due to pulmonary condition worsening, required intubation and invasive ventilation. 36 patients were successfully weaned from NIV under DEX sedation and discharged from PICU. All patients survived until home discharge. CONCLUSION: Our data suggest that DEX may represent an effective sedative agent in infants and children showing agitation during NIV. Early use of DEX in infants/children receiving NIV for acute respiratory failure (ARF) should be considered safe and capable of improving NIV, thus permitting both lung recruitment and patient-ventilator synchronization.

Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts.

Copy number variants (CNVs) have a major role in the etiology of autism spectrum disorders (ASD), and several of these have reached statistical significance in case-control analyses. Nevertheless, current ASD cohorts are not large enough to detect very rare CNVs that may be causative or contributory (that is, risk alleles). Here, we use a tiered approach, in which clinically significant CNVs are first identified in large clinical cohorts of neurodevelopmental disorders (including but not specific to ASD), after which these CNVs are then systematically identified within well-characterized ASD cohorts. We focused our initial analysis on 48 recurrent CNVs (segmental duplication-mediated 'hotspots') from 24 loci in 31 516 published clinical cases with neurodevelopmental disorders and 13 696 published controls, which yielded a total of 19 deletion CNVs and 11 duplication CNVs that reached statistical significance. We then investigated the overlap of these 30 CNVs in a combined sample of 3955 well-characterized ASD cases from three published studies. We identified 73 deleterious recurrent CNVs, including 36 deletions from 11 loci and 37 duplications from seven loci, for a frequency of 1 in 54; had we considered the ASD cohorts alone, only 58 CNVs from eight loci (24 deletions from three loci and 34 duplications from five loci) would have reached statistical significance. In conclusion, until there are sufficiently large ASD research cohorts with enough power to detect very rare causative or contributory CNVs, data from larger clinical cohorts can be used to infer the likely clinical significance of CNVs in ASD.

Management of analgosedation during noninvasive respiratory support: an expert Delphi consensus document developed by the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI).

BACKGROUND: Discomfort can be the cause of noninvasive respiratory support (NRS) failure in up to 50% of treated patients. Several studies have shown how analgosedation during NRS can reduce the rate of delirium, endotracheal intubation, and hospital length of stay in patients with acute respiratory failure. The purpose of this project was to explore consensus on which medications are currently available as analgosedatives during NRS, which types of patients may benefit from analgosedation while on NRS, and which clinical settings might be appropriate for the implementation of analgosedation during NRS. METHODS: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects of the use of analgesics and sedatives during NRS treatment. The methodology applied is in line with the principles of the modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales which were then subjected to blind votes for consensus. RESULTS: The use of an analgosedation strategy in adult patients with acute respiratory failure of different origins may be useful where there is a need to manage discomfort. This strategy should be considered after careful assessment of other potential factors associated with respiratory failure or inappropriate noninvasive respiratory support settings, which may, in turn, be responsible for NRS failure. Several drugs can be used, each of them specifically targeted to the main component of discomfort to treat. In addition, analgosedation during NRS treatment should always be combined with close cardiorespiratory monitoring in an appropriate clinical setting. CONCLUSIONS: The use of analgosedation during NRS has been studied in several clinical trials. However, its successful application relies on a thorough understanding of the pharmacological aspects of the sedative drugs used, the clinical conditions for which NRS is applied, and a careful selection of the appropriate clinical setting.

Perception of smoke-free policies among workers in an Italian Local Health Agency: survey of opinions, knowledge and behaviours.

AIM: This study evaluated the opinions and knowledge of the Health-Care-Workers and other employees about smoking in the workplace and investigated their perceptions about the implementation and strengthening of smoke-free policies and their views of proposed smoking cessation course. METHODS: This cross-sectional study analyzed data resulting from a questionnaire administered in the Local Health Agency of Rieti (Italy). Comparisons have been made according to smoking status of participants: Ever Smokers (ES) or Never Smokers (NS). RESULTS: The study was conducted on a sample of 300 workers, the majority of whom think that the smoking ban is not observed in the workplace due to lack of respect for colleagues (59.2% of NS vs 40% of ES, p=0.022). Exposure to Secondhand smoke (SHS) is reported by 15.2% of ES and 30.3% of NS (p=0.006). About 50% of the participants think that the smoking ban has led to an improvement in the quality of interpersonal relationships. Strengthening the smoking ban through frequent inspections would be very effective according to 78% of ES and 88% of NS (p=0.043); having smoking cessation courses within the agency would be considered useful by 56% of ES and 68% of NS (p= 0.064). Relatively few respondents knew of the association between smoking and bladder cancer (35.2% of ES and 47.2% of NS, p=0.061), and asthma exacerbation (66% of ES and 77% of NS, p=0.040). Logistic regression models adjusted for age, gender, work categories and smoking status show that ES report that they are less likely to be exposed to SHS (OR= 0.42, 95% CI 0.22-0.78, p=0.006) and to think that people smoke because of lack of respect (OR= 0.46, 95% CI 0.24-0.87, p=0.018). More frequent inspections (OR= 0.50, 95% CI 0.26-0.95, p=0.037) and smoking cessation courses (OR= 0.61, 95% CI 0.37-1.00, p=0.053) are considered less effective by ES. ES are less likely to know that smoking is a cause of bladder cancer (OR= 0.54, 95% CI 0.32-0.90, p=0.019) and asthma exacerbation (OR= 0.53, 95% CI 0.31-0.92, p=0.023). Fifty-seven percent of current smokers would like to quit, but only 41% would join a cessation course in the agency. CONCLUSION: The results obtained may be used to analyze the effectiveness of tobacco control policy and programs aimed at freeing companies from smoke. Policy makers should provide the best possible protection for workers against exposure to SHS, in particular with enforcement of the smoking ban and smoking cessation courses tailored to maximize potential benefits for both workers and employers.

Born into an isolating world: family-centred care for babies born to mothers with COVID-19.

Background: The benefits of facilitating breastmilk feeding and close contact between mother and neonate (family-centred care; FCC) in the perinatal period are well-established. The aim of this study was to determine how the delivery of FCC practices were impacted for neonates born to mothers with perinatal SARS-CoV-2 infection during the COVID-19 pandemic. Methods: Neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy were identified from the 'EsPnIC Covid paEdiatric NeonaTal REgistry' (EPICENTRE) multinational cohort between 10 March 2020 and 20 October 2021. The EPICENTRE cohort collected prospective data on FCC practices. Rooming-in and breastmilk feeding practice were the main outcomes, and factors influencing each were determined. Other outcomes included mother-baby physical contact prior to separation and the pattern of FCC components relative to time and local site guidelines. Findings: 692 mother-baby dyads (13 sites, 10 countries) were analysed. 27 (5%) neonates were positive for SARS-CoV-2 (14 (52%) asymptomatic). Most sites had policies that encouraged FCC during perinatal SARS-CoV-2 infection for most of the reporting period. 311 (46%) neonates roomed-in with their mother during the admission. Rooming-in increased over time from 23% in March-June 2020 to 74% in January-March 2021 (boreal season). 330 (93%) of the 369 separated neonates had no FCC physical contact with their mother prior, and 319 (86%) were asymptomatic. Maternal breastmilk was used for feeding in 354 (53%) neonates, increasing from 23% to 70% between March-June 2020 and January-March 2021. FCC was most impacted when mothers had symptomatic COVID-19 at birth. Interpretation: This is the largest report of global FCC practice during the COVID-19 pandemic to date. The COVID-19 pandemic may have impacted FCC despite low perinatal transmission rates. Fortunately, clinicians appear to have adapted to allow more FCC delivery as the COVID-19 pandemic progressed. Funding: The National Health and Medical Research Council (Australia): Grant ID 2008212 (DGT), Royal Children's Hospital Foundation: Grant ID 2019-1155 (EJP), Victorian Government Operational Infrastructure Support Program.

The HPV infection in males: an update.

The role of Human papillomavirus (HPV) in malignant and non-malignant genital diseases in females is well known and the corresponding epidemiological burden has been widely described, in males instead, less is known about the role of the virus in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases. There are many types of HPV that can infect the epithelium: some types can cause genital warts (low risk genotype), other types (high risk genotypes) can cause cancers of the penis, anus or oropharynx. Relative to females, males tend to be less knowledgeable about the infection: some may view its consequences as less likely and severe for themselves than for females, and thus could perceive vaccination as unnecessary. Including boys in the vaccination program generally exceeded conventional thresholds of good value for money, even under favorable conditions of vaccine protection and health benefits; however, uncertainty still exists in many areas that can either strengthen or attenuate the findings achieved.

Dietary habits in Italy: the importance of the Mediterranean diet.

The Mediterranean diet is the heritage of millennia of exchange of people, cultures and foodstuffs throughout the Mediterranean basin. This diet is characterized by abundance of vegetables and fruits, bread, fish, olive oil, poultry, a relatively low consumption of red meat and a moderate consumption of wine during a meal and is well-defined by the food pyramid. Nowadays a standard Western diet has become far more common in Italy, against Mediterranean diet, which stands as a model of health sustainability: it is therefore necessary also to promote suitable resource management and to support quality in food. Practical and large scale projects should be activated, aimed to produce advice about meals both for families and for the different kinds of community, respectively.

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review.

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.

Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia.

Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.

Measles-induced respiratory distress, air-leak and ARDS.

Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.

[Emerging and re-emerging diseases]. / Evoluzione delle malattie infettive: malattie emergenti e riemergenti.

The extraordinary progress in the knowledge of infectious disease, the discovery of antibiotics and effective vaccines are among the great achievements of the nineteenth and twentieth centuries. These achievements have led to a dramatic reduction in the levels of mortality from these diseases. However some factors may suggest that new infective agents may develop, that those diseases that already exist may become more aggressive, and that those diseases that had been practically conquered, may re-emerge in the future. Such factors include: antibiotic resistance, national and international migration, population increase and ageing, increase in the number of immuno-suppressed patients.

[Climate change and Kyoto protocol]. / Le conseguenze dei cambiamenti climatici sulla salute e sull'am- biente. Il protocollo di Kyoto.

Due to industrial revolution and the heavy use of fossil fuels, the concentration of greenhouse gases in the atmosphere has increased dramatically during the last hundred years, and this has lead to an increase in mean global temperature. The environmental consequences of this are: the melting of the ice caps, an increase in mean sea-levels, catastrophic events such as floodings, hurricanes and earthquakes, changes to the animal and vegetable kingdoms, a growth in vectors and bacteria in water thus increasing the risk of infectious diseases and damage to agriculture. The toxic effects of the pollution on human health are both acute and chronic. The Kyoto Protocol is an important step in the campaign against climatic changes but it is not sufficient. A possible solution might be for the States which produce the most of pollution to adopt a better political stance for the environment and to use renewable resources for the production of energy.

Evaluation of an 'all-in-one' seven-day whole-genome sequencing solution in the investigation of a Staphylococcus aureus outbreak in a neonatal intensive care unit.

BACKGROUND: Meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) are responsible for outbreaks in intensive care units. MSSA infections have the same morbidity and mortality rate as MRSA infections but are studied less often. Whole-genome sequencing (WGS) is used increasingly for outbreak monitoring, but still requires specific installation and trained personnel to obtain and analyse the data. AIM: To evaluate the workflow and benefits of EpiSeq solution (bioMérieux, Marcy l'Etoile, France) in exploring the increased incidence of S. aureus bloodstream infections in a neonatal intensive care unit (NICU). METHODS: Four S. aureus bacteraemia isolates and 27 colonization isolates obtained between January and July 2016 were submitted to the 'all in one solution' EpiSeq [WGS, quality data assessment, multi-locus sequence typing (MLST), spa typing, virulome and resistome characterization, and phylogenetic tree construction]. More in-depth analyses were performed (whole-genome MLST and whole-genome single nucleotide polymorphism (wgSNP)] with BioNumerics software (Applied Maths, Sint-Martens-Latem, Belgium). FINDINGS: Nine different sequence types and 13 different spa types were found among the 31 isolates studied. Among those isolates, 11 (seven patients) were ST146 spa type t002, five (four patients) were ST30 and four (four patients) were ST398. The 11 ST146 isolates had a maximum of seven pairwise SNP differences. CONCLUSION: Use of EpiSeq solution allowed fast demonstration of the polyclonal profile of the MSSA population in neonates, and enabled the suspicion of a global outbreak to be ruled out. However, wgSNP analysis showed the transmission and persistence of one sequence type for over six months in the NICU, and enabled the infection control team to adapt its response.