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Improving influenza vaccination coverage in young children is crucial in reducing the spreading of influenza viruses, thus indirectly protecting the general population. Mass campaign needs to engage all the communities within the target population, overcoming socio-economic and cultural barriers. School-located interventions in some countries were successful in increasing vaccine acceptability and overall immunisation rates.Influenza-like illnesses (ILI) share several symptoms with the ongoing COVID-19 pandemic, posing an important challenge for both diagnostics and public health burden. Self-sampling using non-invasive saliva collection could represent a suitable tool for respiratory infection surveillance.This pilot study was carried out in a very densely populated Italian area, Milan, characterised by a high percentage of non-Italian citizens, often hard-to-reach by preventive programmes. We started a vaccine campaign with live-attenuated influenza vaccine (LAIV), recently recommended in Italy for children aged 2-6, coupled with a saliva-based ILI surveillance system in preschools.We enrolled 432 children from 5 schools in the Milan suburbs, 31.2% of which received the LAIV. Thanks to the undertaken multicultural approach, 59% of the vaccinated children were non-Italian citizens.Despite the COVID-19 preventive measures, i.e., school closure upon positive cases, highly affected the programmed surveillance, all the saliva samples from ILI cases, self-collected by parents at home, resulted adequate for viral molecular testing.With correction measures, this pilot experience could be broadened to a large population, simultaneously allowing for a widespread ILI surveillance and flu immunisation.

Background: Caffeine is indicated for the management of apnoea of prematurity and extubation in preterm infants. Early initiation of caffeine administration has increased in the past decades with the purpose of reducing respiratory morbidity. However, there might be harms associated with this approach. This systematic review aims to assess whether early administration of caffeine reduces morbidity and mortality in preterm infants. Methods: The methods were published in a preregistered protocol. The literature search was performed in February 2019 with no restrictions for language or publication date. Randomised controlled trials (RCTs) and cohort studies comparing early versus late caffeine administration to infants born before week 34 were included. Results: Two RCTs and 14 cohort studies were included. All studies but one had a serious/critical overall risk of bias. Few studies reported on long-term or patient-relevant outcomes. No meta-analysis could be performed. Conclusion: Based on the available evidence, no conclusions about the optimal timing of caffeine administration can be drawn. There are inherent methodological problems in the cohort studies. RCTs are needed to answer the question of optimal timing for caffeine administration in neonatal care. Future trials should focus on outcomes relevant to patients and their families and include long-term outcomes. (Less)

Background Hospital-acquired pneumonia is one of the most common hospital-acquired infections in children worldwide. Most of our understanding of hospital-acquired pneumonia in children is derived from adult studies. To our knowledge, no systematic review with meta-analysis has assessed the benefits and harms of different antibiotic regimens in neonates and children with hospital-acquired pneumonia. Objectives To assess the beneficial and harmful effects of different antibiotic regimens for hospital-acquired pneumonia in neonates and children. Search methods We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registers to February 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. Selection criteria We included randomised clinical trials comparing one antibiotic regimen with any other antibiotic regimen for hospital-acquired pneumonia in neonates and children. Data collection and analysis Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were all-cause mortality and serious adverse events; our secondary outcomes were health-related quality of life, pneumonia-related mortality, non-serious adverse events, and treatment failure. Our primary time point of interest was at maximum follow-up. Main results We included four randomised clinical trials (84 participants). We assessed all trials as having high risk of bias. We did not conduct any meta-analyses, as the included trials did not compare similar antibiotic regimens. Each of the four trials assessed a different comparison, as follows: cefepime versus ceftazidime; linezolid versus vancomycin; meropenem versus cefotaxime; and ceftobiprole versus cephalosporin. Only one trial reported our primary outcomes of all-cause mortality and serious adverse events. Three trials reported our secondary outcome of treatment failure. Two trials primarily included community-acquired pneumonia and hospitalised children with bacterial infections, hence the children with hospital-acquired pneumonia constituted subgroups of the total sample sizes. Where outcomes were reported, the certainty of the evidence was very low for each of the comparisons. We are unable to draw meaningful conclusions from the numerical results. None of the included trials assessed health-related quality of life, pneumonia-related mortality, or non-serious adverse events. Authors' conclusions The relative beneficial and harmful effects of different antibiotic regimens remain unclear due to the very low certainty of the available evidence. The current evidence is insufficient to support any antibiotic regimen being superior to another. Randomised clinical trials assessing different antibiotic regimens for hospital-acquired pneumonia in children and neonates are warranted.

Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.La sepsis neonatal es una causa importante de morbilidad y mortalidad. Es la tercera causa de mortalidad neonatal a nivel mundial y constituye el 13% de la mortalidad neonatal total. A pesar de la elevada carga de la sepsis neonatal, la evidencia de alta calidad en el diagnóstico y el tratamiento es escasa. Debido a las dificultades de diagnóstico de la sepsis y a la relativa inmunosupresión del neonato, muchos reciben antibióticos por sospecha de sepsis. Los antibióticos se han convertido en el tratamiento más utilizado en las unidades de cuidados intensivos neonatales, y los estudios observacionales realizados en países de ingresos altos indican que entre el 83% y el 94% de los neonatos tratados con antibióticos por sospecha de sepsis tienen hemocultivos negativos. La última revisión Cochrane se actualizó en 2005. Se necesita una revisión sistemática actualizada que evalúe los efectos de los diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío.Evaluar los efectos beneficiosos y perjudiciales de diferentes regímenes antibióticos para la sepsis neonatal de inicio tardío. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las siguientes bases de datos electrónicas: CENTRAL (2021, número 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED y Conference Proceedings Citation Index ‐ Science el 12 de marzo de 2021. También se buscaron ensayos controlados aleatorizados (ECA) y cuasialeatorizados en las bases de datos de ensayos clínicos y en las listas de referencias de artículos identificados. CRITERIOS DE SELECCIÓN: Se incluyeron ECA que compararon diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. Se incluyeron participantes mayores de 72 horas de vida en el momento de la asignación al azar, con sospecha o diagnóstico de sepsis neonatal, meningitis, osteomielitis, endocarditis o enterocolitis necrosante. Se excluyeron los ensayos que evaluaron el tratamiento de las infecciones micóticas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los estudios para inclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se utilizó el método GRADE para evaluar la certeza de la evidencia. El desenlace principal fue la mortalidad por todas las causas, y los desenlaces secundarios fueron: eventos adversos graves, asistencia respiratoria, apoyo circulatorio, nefrotoxicidad, deterioro del desarrollo neurológico, enterocolitis necrosante y ototoxicidad. El punto temporal principal de interés fue el seguimiento máximo.Se incluyeron cinco ECA (580 participantes). Todos los ensayos tuvieron alto riesgo de sesgo y evidencia de certeza muy baja. Los cinco ensayos incluidos evaluaron cinco comparaciones diferentes de antibióticos. No se realizó un metanálisis debido a la falta de datos relevantes. De los cinco ensayos incluidos, un ensayo comparó cefazolina más amikacina con vancomicina más amikacina; un ensayo comparó ticarcilina más ácido clavulánico con flucloxacilina más gentamicina; un ensayo comparó cloxacilina más amikacina con cefotaxima más gentamicina; un ensayo comparó meropenem con atención estándar (ampicilina más gentamicina o cefotaxima más gentamicina); y un ensayo comparó vancomicina más gentamicina con vancomicina más aztreonam. Ninguna de las cinco comparaciones encontró evidencia de una diferencia al evaluar la mortalidad por todas las causas, los eventos adversos graves, el apoyo circulatorio, la nefrotoxicidad, el deterioro del desarrollo neurológico o la enterocolitis necrosante; sin embargo, ninguno de los ensayos se acercó a un tamaño de información que pudiera contribuir significativamente a la evidencia de los beneficios y los riesgos comparativos de cualquier régimen antibiótico en particular. Ninguno de los ensayos evaluó la asistencia respiratoria o la ototoxicidad. Los efectos beneficiosos y perjudiciales de los diferentes regímenes de antibióticos aún no están claros debido a la falta de ensayos con un poder estadístico adecuado y al alto riesgo de errores sistemáticos.La evidencia actual no es suficiente para apoyar que un régimen de antibióticos sea superior a otro. Se justifica la realización de ECA con bajo riesgo de sesgo que evalúen diferentes regímenes antibióticos en la sepsis neonatal de inicio tardío.

Background Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. Objectives To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. Search methods We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. Selection criteria We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. Data collection and analysis Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. Main results We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. Authors' conclusions Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.

Background: Mechanical ventilation is a potentially painful and discomforting intervention that is widely used in neonatal intensive care. Newborn infants demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes. The use of drugs that reduce pain might be important in improving survival and neurodevelopmental outcomes. Objectives: To determine the benefits and harms of opioid analgesics for neonates (term or preterm) receiving mechanical ventilation compared to placebo or no drug, other opioids, or other analgesics or sedatives. Search methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 29 September 2020); Embase (1980 to 29 September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 29 September 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Selection criteria: We included randomised and quasi-randomised controlled trials comparing opioids to placebo or no drug, to other opioids, or to other analgesics or sedatives in newborn infants on mechanical ventilation. We excluded cross-over trials. We included term (≥ 37 weeks' gestational age) and preterm (< 37 weeks' gestational age) newborn infants on mechanical ventilation. We included any duration of drug treatment and any dosage given continuously or as bolus; we excluded studies that gave opioids to ventilated infants for procedures. Data collection and analysis: For each of the included trials, we independently extracted data (e.g. number of participants, birth weight, gestational age, types of opioids) using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence. Main results: We included 23 studies (enrolling 2023 infants) published between 1992 and 2019. Fifteen studies (1632 infants) compared the use of morphine or fentanyl versus placebo or no intervention. Four studies included both term and preterm infants, and one study only term infants; all other studies included only preterm infants, with five studies including only very preterm infants. We are uncertain whether opioids have an effect on the Premature Infant Pain Profile (PIPP) Scale in the first 12 hours after infusion (MD -5.74, 95% confidence interval (CI) -6.88 to -4.59; 50 participants, 2 studies) and between 12 and 48 hours after infusion (MD -0.98, 95% CI -1.35 to -0.61; 963 participants, 3 studies) because of limitations in study design, high heterogeneity (inconsistency), and imprecision of estimates (very low-certainty evidence - GRADE). The use of morphine or fentanyl probably has little or no effect in reducing duration of mechanical ventilation (MD 0.23 days, 95% CI -0.38 to 0.83; 1259 participants, 7 studies; moderate-certainty evidence because of unclear risk of bias in most studies) and neonatal mortality (RR 1.12, 95% CI 0.80 to 1.55; 1189 participants, 5 studies; moderate-certainty evidence because of imprecision of estimates). We are uncertain whether opioids have an effect on neurodevelopmental outcomes at 18 to 24 months (RR 2.00, 95% CI 0.39 to 10.29; 78 participants, 1 study; very low-certainty evidence because of serious imprecision of the estimates and indirectness). Limited data were available for the other comparisons (i.e. two studies (54 infants) on morphine versus midazolam, three (222 infants) on morphine versus fentanyl, and one each on morphine versus diamorphine (88 infants), morphine versus remifentanil (20 infants), fentanyl versus sufentanil (20 infants), and fentanyl versus remifentanil (24 infants)). For these comparisons, no meta-analysis was conducted because outcomes were reported by one study. Authors' conclusions: We are uncertain whether opioids have an effect on pain and neurodevelopmental outcomes at 18 to 24 months; the use of morphine or fentanyl probably has little or no effect in reducing the duration of mechanical ventilation and neonatal mortality. Data on the other comparisons planned in this review (opioids versus analgesics; opioids versus other opioids) are extremely limited and do not allow any conclusions. In the absence of firm evidence to support a routine policy, opioids should be used selectively - based on clinical judgement and evaluation of pain indicators - although pain measurement in newborns has limitations. (Less)

Background and objectives Continuous glucose monitoring (CGM) could be a valuable instrument for measurement of glucose concentration in preterm neonate. We undertook a systematic review and meta-analysis to compare the diagnostic accuracy of CGM devices to intermittent blood glucose evaluation methods for the detection of hypoglycaemic or hypoglycaemic events in preterm infants. Data sources A structured electronic database search was performed for studies that assessed the accuracy of CGM against any intermittent blood glucose testing methods in detecting episodes of altered glycaemia in preterm infants. No restrictions were used. Three review authors screened records and included studies. Data extraction Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. From individual patient data (IPD), sensitivity and specificity were determined using predefined thresholds. The mean absolute relative difference (MARD) of the studied CGM devices was assessed and if those satisfied the accuracy requirements (EN ISO 15197). IPD datasets were meta-analysed using a logistic mixed-effects model. A bivariate model was used to estimate the summary receiver operating characteristic curve (ROC) curve and extract the area under the curve (AUC). The overall level of certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Results Among 4481 records, 11 were included. IPD datasets were obtained for five studies. Only two of the studies showed an MARD lower than 10%, with none of the five CGM devices studied satisfying the European Union (EU) ISO 15197 requirements. Pooled sensitivity and specificity of CGM devices for hypoglycaemia were 0.39 and 0.99, whereas for hyperglycaemia were 0.87 and 0.99, respectively. The AUC was 0.70 and 0.86, respectively. The certainty of the evidence was considered as low to moderate. Limitations primarily related to the lack of representative population, reference standard and CGM device. Conclusions CGM devices demonstrated low sensitivity for detecting hypoglycaemia in preterm infants, however, provided high accuracy for detection of hyperglycaemia. PROSPERO registration number CRD42020152248.

Background and objectives Continuous glucose monitoring (CGM) could be a valuable instrument for measurement of glucose concentration in preterm neonate. We undertook a systematic review and meta-analysis to compare the diagnostic accuracy of CGM devices to intermittent blood glucose evaluation methods for the detection of hypoglycaemic or hypoglycaemic events in preterm infants.Data sources A structured electronic database search was performed for studies that assessed the accuracy of CGM against any intermittent blood glucose testing methods in detecting episodes of altered glycaemia in preterm infants. No restrictions were used. Three review authors screened records and included studies.Data extraction Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. From individual patient data (IPD), sensitivity and specificity were determined using predefined thresholds. The mean absolute relative difference (MARD) of the studied CGM devices was assessed and if those satisfied the accuracy requirements (EN ISO 15197). IPD datasets were meta-analysed using a logistic mixed-effects model. A bivariate model was used to estimate the summary receiver operating characteristic curve (ROC) curve and extract the area under the curve (AUC). The overall level of certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.Results Among 4481 records, 11 were included. IPD datasets were obtained for five studies. Only two of the studies showed an MARD lower than 10%, with none of the five CGM devices studied satisfying the European Union (EU) ISO 15197 requirements. Pooled sensitivity and specificity of CGM devices for hypoglycaemia were 0.39 and 0.99, whereas for hyperglycaemia were 0.87 and 0.99, respectively. The AUC was 0.70 and 0.86, respectively. The certainty of the evidence was considered as low to moderate. Limitations primarily related to the lack of representative population, reference standard and CGM device.Conclusions CGM devices demonstrated low sensitivity for detecting hypoglycaemia in preterm infants, however, provided high accuracy for detection of hyperglycaemia.PROSPERO registration number CRD42020152248.

While source separation of waste packaging materials for recycling is well established in several metropolitan areas, the collection of food waste from the households is less widespread because of its more difficult implementation. Source segregation of food waste in densely populated areas is raising new interest, as the availability of biogas following its anaerobic digestion (AD) paves the road to a number of possibilities, from electric energy production to its upgrading to biomethane and subsequent feeding in to the natural gas network or in vehicles as a fuel. The study addresses this waste management option by analysing a real metropolitan situation where food waste currently ends up mixed with the residual waste in a waste-to-energy plant (WTE). We assume to establish a new collection scheme for household food waste, followed by its treatment in a new AD and post-composting facility. A comparative life cycle assessment was carried out, where possible synergies between the existing WTE plant and the new one were evaluated. All new scenarios based on AD attained similar or better results compared with the reference scenario for almost all of the impact indicators. The most robust indication is related to global warming potential, with a potential improvement of up to 37%. Finally, a sensitivity analysis was carried out to assess the effect of the variation of the most relevant parameters. Results have proven to be very sensible to the hypothesis on the type of substituted electric energy. All the other examined sensitivities resulted in variations well below 10%.