Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood

This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies

Antibody response of healthy children to pandemic A/H1N1/2009 influenza virus

<p>Abstract</p> <p>Background</p> <p>Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (<it>p </it>< 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus.</p> <p>Conclusions</p> <p>Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.</p

How the heterogeneity of the severely injured brain affects hybrid 2 diffuse optical signals: case examples and guidelines

Significance: A shortcoming for the routine clinical use of diffuse optics (DO) in the injured head has been that the results from commercial near-infrared spectroscopy-based devices are not reproducible, often give phys iologically invalid values and differ between systems. Besides the limitations due to the physics of continuous23 wave light sources, one culprit is the head heterogeneity and the underlying morphological and functional abnor malities of the probed tissue. Aim: To investigate the effect that different tissue alterations in the damaged head has on DO signals and provide guidelines to avoid data misinterpretation. Approach: DO measurements and computed tomography scans were acquired on brain-injured patients. The relationship between the signals and the underlying tissue types was classified on a case-by-case basis. Results: Examples and suggestions to establish quality control routines were provided. The findings suggested guidelines for carrying out DO measurements and speculations towards improved devices. Conclusions: This study advocates for the standardization of the DO measurements to secure a role for DO in neurocritical care. We suggest that blind measurements are unacceptably problematic due to confounding effects and care using a priori and a posteriori quality control routines that go beyond an assessment of the signal-to-noise ratio that is typically utilized.Preprin

Time-domain functional diffuse optical tomography system based on fiber-free silicon photomultipliers

Based on recent developments in both single-photon detectors and timing electronic circuits, we designed a compact and cost effective time-domain diffuse optical tomography system operated at 1 Hz acquisition rate, based on eight silicon photomultipliers and an 8-channel time-to-digital converter. The compact detectors are directly hosted on the probe in a circular arrangement around a single light injection fiber, so to maximize light harvesting. Tomography is achieved exploiting the depth sensitivity that is encoded in the arrival time of detected photons. The system performances were evaluated on simulations to assess possible the limitations arising from the use of a single injection point, and then on phantoms and in vivo to prove the eligibility of these technologies for diffuse optical tomography

Transcranial optical monitoring for detecting intracranial pressure alterations in children with benign external hydrocephalus: a proof-of-concept study

Hydrocephalus; Optical techniques; PathophysiologyHidrocefalia; Técnicas ópticas; FisiopatologíaHidrocefàlia; Tècniques òptiques; FisiopatologiaSignificance Benign external hydrocephalus (BEH) is considered a self-limiting pathology with a good prognosis. However, some children present a pathological intracranial pressure (ICP) characterized by quantitative and qualitative alterations (the so-called B-waves) that can lead to neurological sequelae. Aim Our purpose was to evaluate whether there were cerebral hemodynamic changes associated with ICP B-waves that could be evaluated with noninvasive neuromonitoring. Approach We recruited eleven patients (median age 16 months, range 7 to 55 months) with BEH and an unfavorable evolution requiring ICP monitoring. Bedside, nocturnal monitoring using near-infrared time-resolved and diffuse correlation spectroscopies synchronized to the clinical monitoring was performed. Results By focusing on the timing of different ICP patterns that were identified manually by clinicians, we detected significant tissue oxygen saturation (StO2) changes (p = 0.002) and blood flow index (BFI) variability (p = 0.005) between regular and high-amplitude B-wave patterns. A blinded analysis looking for analogs of ICP patterns in BFI time traces achieved 90% sensitivity in identifying B-waves and 76% specificity in detecting the regular patterns. Conclusions We revealed the presence of StO2 and BFI variations—detectable with optical techniques—during ICP B-waves in BEH children. Finally, the feasibility of detecting ICP B-waves in hemodynamic time traces obtained noninvasively was shown.This work was realized with the support of the Department of Cirugía and Ciencias Morfológicas of the Universitat Autònoma de Barcelona. The work was supported by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie (Grant No. 675332) (BitMap: brain injury and trauma monitoring using advanced photonics) and the European Union’s Horizon 2020 Research and Innovation Program [Grant No. 101017113 (TinyBrains) and Grant No. 101016087 (VASCOVID)]; Fondo de Investigación Sanitaria (Instituto de Salud Carlos III) (Grant No. PI18/00468); Fundació CELLEX Barcelona, Fundació Mir Puig, Agencia Estatal de Investigación (PHOTOMETABO, Grant No. PID2019106481RBC31); the “Severo Ochoa” Program for Centers of Excelence in R&D (Grant No. CEX2019-000910-S); the Obra social “La Caixa” Foundation (LlumMedBcn), Generalitat de Catalunya (CERCA, AGAUR-2017-SGR-1380, RIS3CAT-001-P-001682 CECH), FEDER EC and LASERLAB EUROPE V (EC H2020 No. 871124); KidsBrainIT (ERANET NEURON); Fundació La Marató de TV3 (Grant Nos. 201724.31 and 201709.31)

Transcranial, noninvasive evaluation of the potential misery perfusion during hyperventilation therapy of traumatic brain injury patients

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP) where the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making it vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising since they noninvasively measure OEF and CBF.Peer ReviewedPostprint (author's final draft

Non-invasive estimation of intracranial pressure by diffuse optics: a proof-of-concept study

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants (n = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults (n = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of 0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.This work leading to the results was funded by the European Union’s Horizon 2020 project “BitMap: Brain injury and trauma monitoring using advanced photonics” (No. 675332); Fundació CELLEX Barcelona; Ministerio de Economía y Competitividad /FEDER (PHOTODEMENTIA, DPI2015-64358-C2-1-R); Instituto de Salud Carlos III / FEDER (MEDPHOTAGE, DTS16/00087 and PI18/00468); the “Severo Ochoa” Programme for Centers of Excellence in R&D (SEV-2015-0522); the Obra social “laCaixa” Foundation (LlumMedBcn); Institució CERCA, AGAUR-Generalitat (2017 SGR 1380); LASERLAB-EUROPE IV; KidsBrainIT (ERA-NET NEURON) and la Fundació La Marató de TV3 (201709.31 and 201724.31).Peer ReviewedPostprint (author's final draft

Streptococcus pneumoniae colonisation in children and adolescents with asthma: Impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

none14noBackground: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. Results: S. pneumoniae was identified in the swabs of 192 subjects (45.4 %): 48.4 % of whom were aged = 15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95 % confidence interval [95 % CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95 % CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95 % CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95 % CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. Conclusions: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.Esposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, Gian Luigi; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, NicolaEsposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, GIAN LUIGI; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, Nicol

Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia

Cerebral blood flow; Diffuse optics; Propofol-induced anesthesiaFlujo sanguíneo cerebral; Óptica difusa; Anestesia inducida por propofolFlux sanguini cerebral; Òptica difusa; Anestèsia induïda per propofolSignificance The optical measurement of cerebral oxygen metabolism was evaluated. Aim Compare optically derived cerebral signals to the electroencephalographic bispectral index (BIS) sensors to monitor propofol-induced anesthesia during surgery. Approach Relative cerebral metabolic rate of oxygen (rCMRO2) and blood flow (rCBF) were measured by time-resolved and diffuse correlation spectroscopies. Changes were tested against the relative BIS (rBIS) ones. The synchronism in the changes was also assessed by the R-Pearson correlation. Results In 23 measurements, optically derived signals showed significant changes in agreement with rBIS: during propofol induction, rBIS decreased by 67% [interquartile ranges (IQR) 62% to 71%], rCMRO2 by 33% (IQR 18% to 46%), and rCBF by 28% (IQR 10% to 37%). During recovery, a significant increase was observed for rBIS (48%, IQR 38% to 55%), rCMRO2 (29%, IQR 17% to 39%), and rCBF (30%, IQR 10% to 44%). The significance and direction of the changes subject-by-subject were tested: the coupling between the rBIS, rCMRO2, and rCBF was witnessed in the majority of the cases (14/18 and 12/18 for rCBF and 19/21 and 13/18 for rCMRO2 in the initial and final part, respectively). These changes were also correlated in time (R > 0.69 to R = 1, p-values < 0.05). Conclusions Optics can reliably monitor rCMRO2 in such conditions.This work received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 675332 (BitMap), No. 101016087 (VASCOVID) and No. 101017113 (TinyBRAINS), KidsBrainIT (ERA-NET NEURON), FEDER EC and LASERLAB-EUROPE V (EC H2020 no. 871124). It was also supported by Fundació CELLEX Barcelona, Fundació Mir-Puig the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra social “la Caixa” Foundation (LlumMedBcn), Generalitat de Catalunya (CERCA, AGAUR-2017-SGR-1380, RIS3CAT-001-P-001682 CECH), la Fundació La Marató de TV3 (201724.31 and 201709.31), and by Agencia Estatal de Investigación (PHOTOMETABO, PID2019-106481RB-C31/10.13039/501100011033)

Comparison of nasopharyngeal nylon flocked swabs with universal transport medium and rayon- bud swabs with a sponge reservoir of viral transport medium in the diagnosis of paediatric influenza

This study compared a kit containing a nasopharyngeal nylon flocked swab and a tube with a liquid universal transport medium (UTM) with a kit containing a plastic-shafted rayon-budded swab with a sponge reservoir of viral transport medium for the molecular detection of influenza viruses in children. Respiratory samples were collected from 314 children aged ,5 years with influenza-like illness (186 males; mean age 2.32±2.27 years) using both swabs in a randomized sequence for each patient. The flocked swabs permitted the detection of 28 influenza A (8.9 %) and 45 influenza B (14.3 %) cases, and the rayon-bud swabs 26 influenza A (8.3 %) and 43 influenza B (13.7 %) cases, with detection rates of 23.2 and 22.0 %, respectively, and similar cycle threshold values. Paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. These findings show that the flocked swabs with UTM and the rayon-bud swabs with a sponge transport medium are similarly efficient in preserving influenza virus nucleic acid, but that the kit containing a flocked swab with a UTM allows easier and more rapid collection and processing of specimens. INTRODUCTION Respiratory infections are the most common diseases of infants and children Antigen detection tests and PCR-based methods are both currently used to detect viruses in respiratory secretions There are various kits containing a nasopharyngeal swab and a tube with transport medium on the market, but only a few studies, mainly of adults, have compared their efficiency in collecting respiratory cells and preserving influenza virus nucleic acid Sample collection. Two samples were collected from each patient and transported by means of two kits: one containing a flexible nasopharyngeal nylon flocked swab and a mini-tube with 1 ml liquid universal transport medium (UTM; Copan Italia), and the other a rayon-budded swab with a tube containing a sponge pre-impregnated with transport medium (Virocult; Medical Wire &amp; Equipment). Using the swabs in a randomized sequence, two nasopharyngeal samples were collected from each child (one from each nostril) by trained paediatricians (L. C., L. G. and S. B.). The distance between the patient&apos;s nares and ear lobe was measured to estimate the length of insertion, after which the swabs were gently inserted towards the pharynx until resistance was felt and then rotated three times to obtain epithelial cells. They were then withdrawn and put into the tube containing the specific transport medium. All of the specimens were kept cool and delivered to the laboratory within 3 h of collection. Sample processing. In the laboratory, each swab was processed in triplicate by three researchers (C. G. M., C. D. and A. V.) as indicated by the manufacturers: 190 ml of the liquid transport medium for the flocked swabs was used directly, whereas the rayon-budded swabs were placed in a tube containing 1 ml liquid lysis buffer (the same amount as that contained in the mini-UTM), the tube was vortexed and incubated for 10 min at room temperature, and 190 ml of the solution was used for extraction. PCR. Viral RNA was extracted from all of the samples by means of a NucliSENS EasyMAG automated extraction system (bioMeriéux), using phocine distemper virus (PDV) as an extraction/PCR inhibition control as described previously (Bosis et al., 2005; Staff satisfaction. Trained paediatricians and members of the laboratory staff were asked to record their satisfaction with the simplicity and rapidity using the swabs after the enrolment of each patient or the completion of the analysis of each pair of swabs by completing a 5-point scale (from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;). Statistical analysis. The data relating to the paired specimens collected from 314 children (186 males, 59.2 %), with a mean age of 2.32±2.27 years, were compared using SAS version 9.1 software (SAS Institute). Continuous variables were analysed using Wilcoxon&apos;s signed rank test or rank sum test as appropriate, and the categorical variables by means of contingency tables and a x 2 or Fisher&apos;s test. RESULTS AND DISCUSSION Satisfaction was based on a 5-point scale from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;. .20 for influenza B virus. However, the paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and the rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. Our study showed that the flocked swabs with UTM and the rayon-budded swabs with transport medium preimpregnated sponge were similarly efficient in preserving influenza virus nucleic acid, but that the former were considered better in terms of the simplicity and rapidity of collection and laboratory testing. Systematic evaluation of the aetiology of paediatric respiratory infections is increasingly being considered an important means of preventing their spread and rationalizing therapy Our main finding was that the paediatricians preferred the flocked swabs because they were more flexible and made it easier and quicker to collect the samples. In addition, the laboratory staff found that the kit containing a flocked swab and liquid transport medium was advantageous insofar as it allowed RNA extraction and PCR to be performed directly on the liquid without the need to add further buffer, whereas the kit containing a transport medium pre-impregnated sponge required an additional step that made the procedure more complicated, timeconsuming and at risk of contamination. One limitation of this study is represented by the fact that the interpretation of the results on simplicity and rapidity of collection and laboratory testing may be devalued by repeated scoring and clustering by the same staff members. This means that further studies that involve several swab collectors and laboratory researchers are required to confirm our results. Moreover, our aim was to compare the efficiency of the two kits in detecting influenza virus nucleic acid, but further studies are required to evaluate the sensitivity of the two transport systems with serial dilutions of positive samples of influenza A and B viruses. Finally, a complete comparison of the sensitivity and specificity of the two kits should also include detection of other respiratory viruses that are commonly found in respiratory samples (e.g. respiratory syncytial virus, adenovirus, rhinovirus), and future research should address this aim. In conclusion, both the flocked swabs with UTM and the rayon-bud swabs with a sponge reservoir of viral transport medium allow adequate collection, transport and preservation of nasal secretions for influenza detection. However, the kit containing a flocked swab with a liquid transport medium facilitated rapid specimen collection and processing. These factors should be considered together with local costs when choosing a product to use in clinical practice. ACKNOWLEDGEMENT