Safety and effectiveness of bubble continuous positive airway pressure as respiratory support for bronchiolitis in a pediatric ward.

The results of several clinical trials suggest that continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than high-flow nasal cannula (HFNC). The use of HFNC involved a minimum reduction (5%) in admissions to the pediatric intensive care unit (PICU) in our hospital. Our main aim was to evaluate its safety and effectiveness as respiratory support for patients with bronchiolitis in a pediatric general ward. A secondary goal was to compare the admissions to PICU and the invasive mechanical ventilation (IMV) rate of patients treated with HFNC and those treated with HFNC/b-CPAP during the 2018-2019 and 2019-2020 epidemic seasons, respectively. Two prospective single-centre observational studies were performed. For the main aim, a cohort study (CS1) was carried out from 1st of November 2019 to 15th of January 2020. Inclusion criteria were children aged up to 3 months with bronchiolitis treated with b-CPAP support when HFNC failed. Epidemiological and clinical parameters were collected before and 60 min after the onset of CPAP and compared between the responder (R) and non-responders (NR) groups. NR was the group that required PICU admission. One hundred fifty-eight patients were admitted to the ward with bronchiolitis and HFNC. Fifty-seven out of one hundred fifty-eight required b-CPAP. No adverse events were observed. Thirty-two out of fifty-seven remained in the general ward (R-group), and 25/57 were admitted to PICU (NR-group). There were statistically significant differences in respiratory rate (RR) and heart rate (HR) between both groups before and after the initiation of b-CPAP, but the multivariable models showed that the main differences were observed after 60 min of therapy (lower HR, RR, BROSJOD score and FiO2 in the R-group). For the secondary aim, another cohort study (CS2) was performed comparing data from a pre-b-CPAP bronchiolitis season (1st of November 2018 to 15th January 2019) and the b-CPAP season (2019-2020). Inclusion criteria in pre-b-CPAP season were children aged up to 3 months admitted to the same general ward with moderate-severe bronchiolitis and with HFNC support. Admissions to PICU during the CPAP season were significantly reduced, without entailing an increase in the rate of IMV. CONCLUSION: The implementation of b-CPAP for patients with bronchiolitis in a pediatric ward, in whom HFNC fails, is safe and effective and results in a reduction in PICU admissions. WHAT IS KNOWN: • Bronchiolitis is one of the most frequent respiratory infections in children and one of the leading causes of hospitalization in infants. • Several studies suggest that the use of continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than the high flow nasal cannula (HFNC). CPAP is a non-invasive ventilation (NIV) therapy used in patients admitted to pediatric intensive care unit (PICU) with progressive moderate-severe bronchiolitis. There is little experience in the literature on the use of continuous positive airway pressure (CPAP) for acute bronchiolitis in a general ward. WHAT IS NEW: • CPAP could be safely and effectively used as respiratory support in young infants with moderate-severe bronchiolitis in a general ward and it reduced the rate of patients who required PICU admission. • Patients' heart and respiratory rate and their FiO2 needs in the first 60 minutes may help to decide whether or not to continue the CPAP therapy in a general ward.

Clinical, biochemical and microbiological factors associated with the prognosis of pneumococcal meningitis in children.

BACKGROUND: Pneumococcal meningitis (PM) has a high morbidity and mortality. The aim of the study was to evaluate what factors are related to a poor PM prognosis. METHODS: Prospective observational study conducted on patients admitted to the Pediatric Intensive Care Unit in a tertiary hospital with a diagnosis of PM (January 2000 to December 2013). Clinical, biochemical and microbiological data were recorded. Variable outcome was classified into good or poor (neurological handicap or death). A multivariate logistic regression was performed based on the univariate analysis of significant data. RESULTS: A total of 88 patients were included. Clinical variables statistically significant for a poor outcome were younger age (p=.008), lengthy fever (p=.016), sepsis (p=.010), lower Glasgow Score (p<.001), higher score on Pediatric Risk Mortality Score (p=0.010) and Sequential Organ Failure Assessment (SOFA) (p<.001), longer mechanical ventilation (p=.004), and inotropic support (p=.008) requirements. Statistically significant biochemical variables were higher level of C-reactive protein (p<.001) and procalcitonin (p=.014) at admission, low cerebrospinal (CSF) pleocytosis (p=.003), higher level of protein in CSF (p=.031), and severe hypoglycorrhachia (p=.002). In multivariate analysis, independent indicators of poor outcome were age less than 2 years (p=.011), high score on SOFA (p=.030), low Glasgow Score (p=.042), and severe hypoglycorrhachia (p=.009). CONCLUSIONS: Patients younger than 2 years of age, with depressed consciousness at admission, especially when longer mechanical ventilation is required, are at high risk of a poor outcome.

Protocol for a multi-phase, multi-center, real-world, hybrid effectiveness-implementation study of a digital intervention for pediatric chronic pain co-designed with patients (Digital SPA).

Background: Children and adolescents with chronic pain are a vulnerable population who often lack the resources to manage their condition. Due to high personal, social, and economic consequences, proper management in its early stages is key to reducing disability. The aim of this project is to co-develop a digital intervention for pediatric chronic pain (Digital SPA) with end-users and to evaluate its effectiveness and implementation outcomes in Spain. Methods: (Phase 1) Focus groups with patients, parents, and clinicians (n = 5-6 each) will inform about unmet pain care needs and provide a starting point for co-designing the intervention. (Phase 2) Content creation and usability testing will be based on the results of Phase 1, and the theory-driven development will follow the latest available evidence. The intervention will use validated psychological techniques focused on improving functioning by teaching pain coping skills. (Phase 3) Hybrid effectiveness-implementation trial. Participants (n = 195) will be adolescents aged 12-17 years old with chronic pain and one of their parents. Assessments include physical function, pain, sleep, anxiety, mood, satisfaction and adherence to the treatment, and number of visits to the emergency room. A qualitative framework analysis will be conducted with data from Phase 1. Effects of the intervention will be evaluated using linear multilevel modeling. The Consolidated Framework for Implementation Research (CFIR) and Behavioral Interventions Using Technology (BIT) frameworks will be used to evaluate implementation. Discussion: This study is expected to produce a co-created evidence-based digital intervention for pediatric chronic pain and a roadmap for successful implementation. Trial registration number TRN and date of registration: ClinicalTrials.gov (registered on 26 June 2023: https://clinicaltrials.gov/study/NCT05917626). Contributions to the literature The implementation of digital health interventions has two major gaps: (1) adherence to treatment is suboptimal, and (2) the process of making the interventions available to the end-user in a sustainable way is often unsuccessful.In this study, we expect that assessing users' needs and co-designing an intervention with them will improve adherence.Documenting the implementation process from the project inception and integrating the results into an implementation framework will allow for replication and extension in different contexts.This study will increase the knowledge about implementation in a vulnerable population: adolescents with chronic pain without access to in-person multidisciplinary pain care.

Cytokine profile and brain biopsy in a case of childhood-onset central nervous system vasculitis in Noonan syndrome-like disorder due to a novel CBL variant.

The authors describe a 5-year-old girl who developed a Noonan syndrome-like disorder as a result of the CBL c.1194C>G/p.His398Gln variant, including headache, papilledema, intracranial hypertension, hyperproteinorrhachia, leucorrhachia, and brain inflammation and vasculitis with CD3 positive lymphocyte infiltration. The patient responded partially to corticosteroids, acetazolamide, and ventriculoperitoneal valve placement. The serum cytokine profile revealed persistently elevated levels of IL-1 RA, IL-2R alpha, IL-6, IL-18, MCP-1, and MCP-3. Cyclophosphamide was used as a bridge to allogeneic hematopoietic stem cell transplantation in this case.

[Measles outbreak in Barcelona. Clinical and epidemiological characteristics]. / Brote de sarampión en Barcelona. Características clínicas y epidemiológicas.

INTRODUCTION: Measles is an acute, highly contagious illness that affects humans, the only natural host. Although effective attenuated virus vaccines exist for this disease, outbreaks continue to occur in susceptible subgroups. From August 2006 to July 2007, an outbreak of measles occurred in the Barcelona (Spain) area, resulting from an imported case. The aim of this study was to describe the clinical and epidemiological characteristics of children with microbiologically confirmed measles diagnosed at our hospital. METHODS: Retrospective, descriptive study. The clinical histories and emergency records of children diagnosed with measles and evaluated at our hospital during the outbreak were analyzed. RESULTS: Of the 130 children with suspected measles evaluated, 99 cases were confirmed by laboratory tests. Median age at diagnosis was 12.4 months (25th-75th percentile: 9.6-14.4 months; 74.6% 6-15 months of age) and 51.4% were boys. Among the total, 23.6% of patients had been vaccinated against measles and 55.3% reported previous contact with a confirmed measles case. The most frequent symptoms/signs were fever (100%; mean evolution 4.3 days (standard deviation [SD]: 2.2 days), rash (82.7%), Koplik's spots (60.2%), and red eyes (59.2%). Complementary tests were performed in 35.7% of children. Most common complications were acute otitis media (20.4%) and pneumonia (15.3%). Among the total, 23.5% of patients were hospitalized for a mean duration of 6.6 days (SD: 3.6 days). CONCLUSION: Geographical mobility facilitates the reappearance of diseases having a low incidence. Infants 6-15 months of age were the patient group most highly affected by the measles outbreak. Most cases were diagnosed with typical signs and symptoms of the infection, but as the outbreak advanced, patients were diagnosed based on less specific symptoms because of the epidemiological context.

First neisseria gonorrhoeae genotyping analysis in france: identification of a strain cluster with reduced susceptibility to Ceftriaxone.

Sexually transmitted infections are a major public health problem in France and other European countries. Particularly, surveillance data about Neisseria gonorrhoeae infections have clearly indicated an increase in the incidence of gonorrhoea in France in 2006. The French laboratories participated on voluntary basis in the RENAGO (Réseau National du Gonocoque) network and sent all of their collected strains to the National Reference Center for Neisseria gonorrhoeae. In this first French molecular epidemiological study, 93 isolates collected in 2006 and representative of the French gonorrhoea epidemiology were selected. Antibiotic susceptibility to six antibiotics was determined, and serotyping and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed. NG-MAST identified 53 sequence types (STs), of which 13 STs contained 2 to 16 isolates. The major STs identified in France were previously described elsewhere. However, two newly described STs, ST1479 and ST1987, had only been found in France until now. ST1479 was characterized by a multiple-resistance phenotype, whereas ST1987 presented a susceptibility phenotype. Moreover, among the predominant French STs, ST225, which had already been described in many countries, comprised isolates (14/16) resistant to ciprofloxacin and with reduced susceptibility to ceftriaxone. Thus, the surveillance of resistance to antibiotics is a priority in order to adapt treatment and decrease the transmission of resistant strains. Of note, no predominant ST was identified among rectal isolates from men who have sex with men.

Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear.

The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa kappa = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.

P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear.

OBJECTIVE: To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears. STUDY DESIGN: A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard. RESULTS: p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.

Extreme Hyperferritinemia in Dizygotic Twins With Human Parechovirus-3 Infection.

Human parechovirus-3 has been associated with severe clinical manifestations in infants, such as sepsis-like illness and meningoencephalitis. Nevertheless, the vast majority of patients have a favorable outcome. We report the occurrence of this infection in dizygotic infants with extreme hyperferritinemia and a transient impairment of natural killer cell cytotoxicity.

Detection of human papillomavirus genotypes among high-risk women: a comparison of hybrid capture and linear array tests.

OBJECTIVES: To assess the concordance and performance of 2 different assays in detection of human papillomavirus (HPV) genotypes among women with abnormal Pap smear. STUDY DESIGN: A series of 575 women referred for colposcopy due to an abnormal Pap smear were analyzed with the Linear Array HPV Genotyping test detecting 37 HPV types and compared with Hybrid Capture II (HCII) assay for detection of carcinogenic HPV. Histologic outcomes of cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) and CIN3+ were the primary endpoints. Clinical performance, including receiver operating characteristics, was determined for both tests. RESULTS: HCII and linear array (LA) were concordant in 88.1% (433/491; 95% CI 85.3%-91.0%), having a substantial agreement with regular kappa (kappa = 0.70, 95% CI 0.62-0.77) and almost perfect agreement with weighted kappa (ICC = 0.82, 95% CI 0.7-0.85). In detecting CIN2+ and CIN3+, LA is 5% and 6% more sensitive but 9.5% and 8.7% less specific than HCII (area under ROC curve; P = 0.317 and P = 0.875, respectively). CONCLUSIONS: Performance of HCII and LA does not significantly differ in detecting CIN2+ or CIN3+.

Performance of the Roche AMPLICOR human papillomavirus (HPV) test in prediction of cervical intraepithelial neoplasia (CIN) in women with abnormal PAP smear.

OBJECTIVES: To assess the performance of a novel PCR-based assay (Roche AMPLICOR HPV test) in detection of cervical pathology as a part of management for abnormal PAP smear (MAPS) and in women participating in cervical cancer screening. STUDY DESIGN: Altogether, 504 women comprising 270 patients referred for colposcopy due to an abnormal Pap smear and another 234 women participating in cervical cancer screening (tested for comparison) were analyzed for oncogenic (HR) Human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 using the Roche AMPLICOR HPV test in cervical samples collected in PreservCyt liquid media. Colposcopic biopsy and/or LEEP cone biopsy was used as the gold standard in the triage group, while liquid-based cytology (LBC) was the reference test in the screening group. RESULTS: The prevalence of HPV was significantly higher in the MAPS group (65.9%) than in the screening group (31.2%) (P = 0.0001). There was a poor concordance between the referral PAP and the current LBC, being only moderate in the screening series, ICC (weighted kappa) = 0.291 (95%CI 0.070-0.459) (P = 0.007), and almost poor in the MAPS Series, with ICC = 0.217 (95%CI 0.04-0.384) (P = 0.023). AMPLICOR HPV positivity increased linearly with the increasing grade of cervical lesions. In detecting high-grade (CIN2-3), colposcopy was the most sensitive test (96.5%), very similar to AMPLICOR (95.2%) (P = 0.731), while LBC with HSIL cutoff was by far the most specific test (99.5%) and showed the highest PPV (96.1%). NPV of colposcopy (97.2%) and AMPLICOR (96.7%) were similar (P = 0.839). Together with abnormal colposcopy and HSIL cytology, the AMPLICOR HPV test is a powerful independent predictor of high-grade CIN2-3, and as such suitable to replace cervical cytology in management of women with abnormal PAP test (MAPS). CONCLUSIONS: The Roche AMPLICOR HPV test is comparable to other HPV tests (HCII, PCR) in detecting CIN in MAPS. However, more data are clearly needed on the performance of AMPLICOR test in management of abnormal PAP and particularly as a screening tool.