Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

BACKGROUND: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. METHODS: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). RESULTS: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. CONCLUSIONS: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms. IMPACT: There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research.

HIDSAG: Hyperspectral Image Database for Supervised Analysis in Geometallurgy.

Supervised analysis using spectral data requires a well-informed characterisation of the response variables and abundant spectral data points. The presented hyperspectral dataset comes from five sets of geometallurgical samples, each characterised by different methods. To provide the spectral data, all mineral samples were scanned with SPECIM VNIR and SWIR hyperspectral cameras. For each subset the following data are provided 1) hyperspectral reflectance images in the VNIR spectral range (400-1000 nm wavelength); 2) hyperspectral reflectance images in the SWIR spectral range (900-2500 nm wavelength); 3) hyperspectral reflectance images in the VNIR-SWIR range (merged to SWIR spatial resolution); 4) RGB images constructed from hyperspectral data using a Bilateral Filter based sensor fusion method; 5) response variables representing mineral sample characterisation results, provided as training and validation data. This dataset is intended for use in general regression and classification research and experiments. All subsets were validated using machine learning models with satisfactory results.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Description of the Exposure of the Most-Followed Spanish Instamoms' Children to Social Media.

There is evidence of the risk of overexposure of children on social networks by parents working as influencers. A cross-sectional study of the profiles of the sixteen most-followed Instamoms in Spain was carried out. An analysis of these profiles was performed over a full month (April 2022), three times a week, to describe the representation of influencers' children in the posts shared by them, as well as their role in the Instamoms' marketing. A total of 192 evaluations of the profiles were performed in the study period. The average number of children exposed by an Instamom was three, generally preschoolers and schoolchildren. The children appear in a context of the family home and accompanied by their mother. The type of advertising that accompanies the appearance of underage children is usually women or children's clothing, but also food products, leisure, etc. Appearance of children in the posts had a statistically significant influence on followers measured by the number of likes. Results provided the identification of two Instamom clusters with differentiated behaviors in relation to appearance of children in posts. It is important to involve Social Pediatrics in the protection of the privacy and interests of children given the increase in sharenting. The authors believe that there are concerns about their explicit consent to public exposure from early childhood and about the medium and long-term effect that this may have on their future well-being.

Current pain management practices for preterm infants with necrotizing enterocolitis: a European survey.

BACKGROUND: Necrotizing enterocolitis (NEC) is a highly painful intestinal complication in preterm infants that requires adequate pain management to prevent short- and long-term effects of neonatal pain. There is a lack of international guidelines for pain management in NEC patients. Therefore, this study aims to describe current pain management for NEC patients in European neonatal intensive care units (NICUs). METHODS: An online survey was designed and conducted to assess current practices in pain management for NEC patients in European NICUs. The survey was distributed via neonatal societies, digital platforms, and professional contacts. RESULTS: Out of the 259 responding unique European NICUs from 36 countries, 61% had a standard protocol for analgesic therapy, 73% assessed pain during NEC, and 92% treated NEC patients with intravenous analgosedatives. There was strong heterogeneity in the used pain scales and initial analgesic therapy, which mainly included acetaminophen (70%), fentanyl (56%), and/or morphine (49%). A third of NICU representatives considered their pain assessment adequate, and half considered their analgesic therapy adequate for NEC patients. CONCLUSIONS: Various pain scales and analgesics are used to treat NEC patients in European NICUs. Our results provide the first step towards an international guideline to improve pain management for NEC patients. IMPACT: This study provides an overview of current pain management practices for infants with necrotizing enterocolitis (NEC) in European neonatal intensive care units. Choice of pain assessment tools, analgosedatives, and dosages vary considerably among NICUs and countries. A third of NICU representatives were satisfied with their current pain assessment practices and half of NICU representatives with their analgesic therapy practices in NEC patients in their NICU. The results of this survey may provide a first step towards developing a European pain management consensus guideline for patients with NEC.

Age-dependent nasal immune responses in non-hospitalized bronchiolitis children.

Bronchiolitis in children is associated with significant rates of morbidity and mortality. Many studies have been performed using samples from hospitalized bronchiolitis patients, but little is known about the immunological responses from infants suffering from mild/moderate bronchiolitis that do not require hospitalization. We have studied a collection of nasal lavage fluid (NLF) samples from outpatient bronchiolitis children as a novel strategy to unravel local humoral and cellular responses, which are not fully characterized. The children were age-stratified in three groups, two of them (GI under 2-months, GII between 2-4 months) presenting a first episode of bronchiolitis, and GIII (between 4 months and 2 years) with recurrent respiratory infections. Here we show that elevated levels of pro-inflammatory cytokines (IL1ß, IL6, TNFα, IL18, IL23), regulatory cytokines (IL10, IL17A) and IFNγ were found in the three bronchiolitis cohorts. However, little or no change was observed for IL33 and MCP1, at difference to previous results from bronchiolitis hospitalized patients. Furthermore, our results show a tendency to IL1ß, IL6, IL18 and TNFα increased levels in children with mild pattern of symptom severity and in those in which non RSV respiratory virus were detected compared to RSV+ samples. By contrast, no such differences were found based on gender distribution. Bronchiolitis NLFs contained more IgM, IgG1, IgG3 IgG4 and IgA than NLF from their age-matched healthy controls. NLF from bronchiolitis children predominantly contained neutrophils, and also low frequency of monocytes and few CD4+ and CD8+ T cells. NLF from infants older than 4-months contained more intermediate monocytes and B cell subsets, including naïve and memory cells. BCR repertoire analysis of NLF samples showed a biased VH1 usage in IgM repertoires, with low levels of somatic hypermutation. Strikingly, algorithmic studies of the mutation profiles, denoted antigenic selection on IgA-NLF repertoires. Our results support the use of NLF samples to analyze immune responses and may have therapeutic implications.

Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies.

Millions of infants are born prematurely every year worldwide. Prematurity, particularly at lower gestational ages, is associated with high mortality and morbidity and is a significant global health burden. Pregnancy complications and preterm birth syndrome strongly impact neonatal clinical phenotypes and outcomes. The vascular endothelium is a pivotal regulator of fetal growth and development. In recent years, the key role of uteroplacental pathologies impairing endothelial homeostasis is emerging. Conditions leading to very and extremely preterm birth can be classified into two main pathophysiological patterns or endotypes: infection/inflammation and dysfunctional placentation. The first is frequently related to chorioamnionitis, whereas the second is commonly associated with hypertensive disorders of pregnancy and fetal growth restriction. The nature, timing, and extent of prenatal noxa may alter fetal and neonatal endothelial phenotype and functions. Changes in the luminal surface, oxidative stress, growth factors imbalance, and dysregulation of permeability and vascular tone are the leading causes of endothelial dysfunction in preterm infants. However, the available evidence regarding endothelial physiology and damage is limited in neonates compared to adults. Herein, we discuss the current knowledge on endothelial dysfunction in the infectious/inflammatory and dysfunctional placentation endotypes of prematurity, summarizing their molecular features, available biomarkers, and clinical impact. Furthermore, knowledge gaps, shadows, and future research perspectives are highlighted.

Variations in Antibiotic Use and Sepsis Management in Neonatal Intensive Care Units: A European Survey.

Management of neonatal sepsis and the use of antimicrobials have an important impact on morbidity and mortality. However, there is no recent background on which antibiotic regimens are used in different European neonatal intensive care units (NICUs). Our study aimed to describe the use of antibiotics and other aspects of early- and late-onset sepsis (EOS and LOS, respectively) management by European NICUs. We conducted an online survey among NICUs throughout Europe to collect information about antibiotic stewardship, antibiotic regimens, and general aspects of managing neonatal infections. NICUs from up to 38 European countries responded, with 271 valid responses. Most units had written clinical guidelines for EOS (92.2%) and LOS (81.1%) management. For EOS, ampicillin, penicillin, gentamicin, and amikacin were the most commonly used antibiotics. Analysis of the combinations of EOS regimens showed that the most frequently used was ampicillin plus gentamicin (54.6%). For LOS, the most frequently used antibiotics were vancomycin (52.4%), gentamicin (33.9%), cefotaxime (28%), and meropenem (15.5%). Other aspects of the general management of sepsis have also been analyzed. The management of neonatal sepsis in European NICUs is diverse. There was high self-reported adherence to the local clinical guidelines. There was homogeneity in the combination of antibiotics in EOS but less in LOS.

Design and Implementation of Intelligent Agent Training Systems for Virtual Vehicles.

This paper presents the results of the design, simulation, and implementation of a virtual vehicle. Such a process employs the Unity videogame platform and its Machine Learning-Agents library. The virtual vehicle is implemented in Unity considering mechanisms that represent accurately the dynamics of a real automobile, such as motor torque curve, suspension system, differential, and anti-roll bar, among others. Intelligent agents are designed and implemented to drive the virtual automobile, and they are trained using imitation or reinforcement. In the former method, learning by imitation, a human expert interacts with an intelligent agent through a control interface that simulates a real vehicle; in this way, the human expert receives motion signals and has stereoscopic vision, among other capabilities. In learning by reinforcement, a reward function that stimulates the intelligent agent to exert a soft control over the virtual automobile is designed. In the training stage, the intelligent agents are introduced into a scenario that simulates a four-lane highway. In the test stage, instead, they are located in unknown roads created based on random spline curves. Finally, graphs of the telemetric variables are presented, which are obtained from the automobile dynamics when the vehicle is controlled by the intelligent agents and their human counterpart, both in the training and the test track.

The immediate efficacy of inhaled nitric oxide treatment in preterm infants with acute respiratory failure during neonatal transport.

AIM: The aim of our review was to describe the clinical response to inhaled nitric oxide (iNO) in a series of preterm babies in respiratory failure during uplift transfers to a neonatal intensive care unit. METHODS: We performed a retrospective review of critical newborns with gestational age <34+0  weeks transferred from January 2013 to December 2018. Data were extracted from our Clinical Information System for transport. The primary measure of this review was to assess whether a significant improvement in the oxygenation saturation index (OSI) occurred following the use of iNO. RESULTS: Thirty preterm babies <34+0  weeks were included in our review. OSI, as a measure of oxygenation, did not statistically improve as an immediate response to iNO from referral to receiving hospital (17.1 vs 16.4; P = .7). We found that pH (7.15 vs 7.29; P = .004) and pCO2 (8.1 vs 6.3; P = .05) significantly improved probably based on ventilation management. CONCLUSION: Following the recommendations of the American Academy of Paediatrics and other organizations, iNO should not routinely be used during the neonatal transfer of preterm babies <34+0 in respiratory failure. We need to conduct further studies to establish which selected preterm patients would benefit from being treated with iNO.

Ações do enfermeiro na identificação precoce de alterações sistêmicas causadas pela sepse grave / Actions of nurses in early identification of systemic changes caused by severe sepsis

INTRODUÇÃO: As unidades de terapia intensiva (UTIs) têm sido organizadas como setores estratégicos para o suporte especializado de assistência ao paciente grave. OBJETIVO: Verificar as ações do enfermeiro para a identificação precoce das alterações sistêmicas causadas pela sepse grave relacionadas às alterações hemodinâmicas, neurológicas, respiratórias, renais e nutricionais dos pacientes internados em UTIs adulto. MÉTODOS: Estudo descritivo com 24 enfermeiros. Os dados foram coletados por meio de formulário composto de questões estruturadas. RESULTADOS: Apenas 36% dos enfermeiros possuem especialização em UTI adulto; verificou-se que os profissionais identificam parcialmente os sinais e sintomas apresentados pelo paciente séptico. CONCLUSÃO: Os enfermeiros encontram dificuldade na identificação precoce das alterações sistêmicas causadas pela sepse grave relacionada às alterações hemodinâmicas, neurológicas, respiratórias, renais e nutricionais dos pacientes internados em UTI adulto, o que pode estar relacionado com a falta de treinamento e de protocolos estabelecidos pelas instituições.

INTRODUCTION: Intensive care units (ICUs) have been organized as strategic sectors for specialized support assistance to critically ill patients. OBJECTIVE: To assess the actions of the nurse for the early identification of systemic changes caused by severe sepsis, related to hemodynamic, neurological, respiratory, renal and nutrition changes of patients in adult ICUs. METHODS: Descriptive studies with 24 nurses. Data were collected using a questionnaire composed of structured questions. RESULTS Only 36% of nurses have expertise in adult ICUs, professionals partially identify the signs and symptoms presented by the septic patient. CONCLUSION: Nurses find difficulty in the early identification of systemic changes caused by severe sepsis, related to hemodynamic, neurological, respiratory, renal and nutritional changes seen in patients in adult ICUs, which may be related to lack of training and of protocols established by the institutions.

Relation of depression with health behaviors and social conditions of dependent community-dwelling older persons in the Republic of Chile.

BACKGROUND: Depressive symptoms are a leading cause of disability and emotional suffering, particularly in old age. However, evidence on depression and old age in developing countries remains largely ignored. The aim of this study was to examine the relation between health behavior and social conditions with depression among dependent community-dwelling older persons in the Republic of Chile. METHODS: This is a cross-sectional and inferential study, using nationally representative secondary data. Two models used logistic regression on 640 dependent community-dwelling older persons from all over Chile, who personally answered a depression assessment, excluding those taking antidepressants. The geriatric depression scale (GDS-15) was used as outcome. The first model aims at any kind of depression (GDS 5>). The second aims at severe depression (GDS 10>). As exposure, we used the health behavior and social conditions of the older persons. Socio-demographic and physical conditions were used as adjustment. RESULTS: 44.5% of the older persons presented depressive symptoms. Among them, 11% had severe depression. Logistic regression showed that significant detrimental factors for being depressed in both models were visiting the doctor five times or over because of acute diseases, feeling uncomfortable with their living arrangement, and feeling discriminated. On the other hand, every additional day of physical exercise and living alone had a beneficial and detrimental effect only in model one. CONCLUSION: Analyses on ways to support older persons living alone and the promotion of physical exercise to avoid depression are needed, along with a deeper understanding of the comfort with their living arrangement. Finally, ways to address the discrimination among older persons should be further explored.

Mental Health of Parents as Caregivers of Children with Disabilities: Based on Japanese Nationwide Survey.

The number of children with disability is increasing gradually in Japan. Previous researches in other countries have reported that parents as caregivers (CGs) of children with disability have mental health problems, but the actual situation has not been examined nationwide in Japan so far. The aim of this study was to evaluate the association between mental health of CGs who had children with disability and characteristics of children, CGs, and household based on the nation-wide survey. This study utilized data from 2010 Comprehensive Survey of the Living Conditions, and defined children with disability aged 6 to 17. Individual data of children and CGs were linked, and 549 pairs of them were extracted. The Japanese version of Kessler 6 (K6) was used to assess mental health status of caregiver, scored 5 and over represented to general psychological distress. Logistic regression was used to evaluate the associations of interest. The almost half (44.4%) of CGs had psychological distress (k6 score; 5 +) in nationwide, and 8.9% of CGs might have serious mental illness (K6 score; 13 +). After adjusting covariates of child, CG, and household factors, CG having a current symptom (OR, 95% CI: 3.26, 1.97-5.39), CG's activity restriction (OR, 95% CI: 2.95, 1.38-6.32), low social support (OR, 95%CI: 9.31, 1.85-46.8), three generation family (OR, 95% CI: 0.49, 0.26-0.92), and lower 25% tile group of monthly household expenditure (OR, 95% CI:1.92, 1.05-3.54), were significantly associated with psychological distress of CGs. This study encourages health care providers to pay more attentions toward parent's mental health, especially for in case of having low social support, and lower income family. Further research should examine the detailed information of child's disease and disability, medical service use, and quality and quantity of social support in nationwide to straighten the system for supporting services of both children with disabilities and their CGs.

Relationship between structural characteristics and outcome quality indicators at health care facilities for the elderly requiring long-term care in Japan from a nationwide survey.

AIM: To clarify the performance situation of selected quality indicators: falls, pressure ulcers and dehydration, at health care facilities for the elderly in Japan, and what structural characteristics are related to them. METHODS: The operational population consisted of 1057 institutionalized users (approximately 10 randomly selected per facility) from a survey answered by the care staff. The facilities were divided into two groups according to their prevalence of negative outcomes (falls, pressure ulcers, dehydration): the best 25% (the very good performers) and the remaining 75% (not so good performers). Logistic regression analysis was carried out to examine the relationship between the structure characteristics of the facilities and their performance regarding each quality indicator. RESULTS: After controlling for sex, years of operation and average age of the users, our results showed a beneficial significant relationship between falls and the total number of nurses per 100 users with an adjusted odds ratio (AOR) of 0.77 (95% CI 0.59-0.98); In contrast, for pressure ulcers, harmful associations between a higher number of registered nurses (AOR 1.23, 95% CI 1.01-1.05) and the availability of 24-h nurse staffing (AOR 4.95, 95% CI 1.19-24.91) were found; regarding dehydration, we did not find any related staffing characteristics. CONCLUSION: Nursing staff might be considered as a potentially related variable in the quality of care in health care facilities for the elderly. The present study is the first to show a relationship between structural characteristics and quality outcomes in health care facilities for the elderly.