Host biomarkers and combinatorial scores for the detection of serious and invasive bacterial infection in pediatric patients with fever without source.

BACKGROUND: Improved tools are required to detect bacterial infection in children with fever without source (FWS), especially when younger than 3 years old. The aim of the present study was to investigate the diagnostic accuracy of a host signature combining for the first time two viral-induced biomarkers, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon γ-induced protein-10 (IP-10), with a bacterial-induced one, C-reactive protein (CRP), to reliably predict bacterial infection in children with fever without source (FWS) and to compare its performance to routine individual biomarkers (CRP, procalcitonin (PCT), white blood cell and absolute neutrophil counts, TRAIL, and IP-10) and to the Labscore. METHODS: This was a prospective diagnostic accuracy study conducted in a single tertiary center in children aged less than 3 years old presenting with FWS. Reference standard etiology (bacterial or viral) was assigned by a panel of three independent experts. Diagnostic accuracy (AUC, sensitivity, specificity) of host individual biomarkers and combinatorial scores was evaluated in comparison to reference standard outcomes (expert panel adjudication and microbiological diagnosis). RESULTS: 241 patients were included. 68 of them (28%) were diagnosed with a bacterial infection and 5 (2%) with invasive bacterial infection (IBI). Labscore, ImmunoXpert, and CRP attained the highest AUC values for the detection of bacterial infection, respectively 0.854 (0.804-0.905), 0.827 (0.764-0.890), and 0.807 (0.744-0.869). Labscore and ImmunoXpert outperformed the other single biomarkers with higher sensitivity and/or specificity and showed comparable performance to one another although slightly reduced sensitivity in children < 90 days of age. CONCLUSION: Labscore and ImmunoXpert demonstrate high diagnostic accuracy for safely discriminating bacterial infection in children with FWS aged under and over 90 days, supporting their adoption in the assessment of febrile patients.

Evaluation of Pupillometry for CYP2D6 Phenotyping in Children Treated with Tramadol.

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol's pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary response and tramadol PK. Our objective was to evaluate pupillometry as a phenotyping method to assess CYP2D6 activity in children treated with tramadol. We included 41 children (mean age 11 years) receiving a first dose of tramadol (2 mg/kg) in the emergency room (ER) as part of their routine care. CYP2D6 phenotyping and genotyping were performed. The concentrations of tramadol and its active metabolite, M1, were measured, and static and dynamic pupillometry was conducted using a handheld pupillometer at the time of tramadol administration and during the ER stay. Pupillometric measurements were obtained for 37 children. Tramadol affected pupillary parameters, with a decrease in pupil diameter in 83.8% of children (p = 0.002) (mean decrease 14.1 ± 16.7%) and a decrease in reflex amplitude constriction in 78.4% (p = 0.011) (mean decrease 17.7 ± 34.5%) at T150 compared to T0. We were unable to identify a correlation between pupillometry measurements and CYP2D6 activity. Likely confounding factors include light intensity, pain, and stress, making the procedure less feasible in paediatric emergency settings.

Outdoor Cold Air Versus Room Temperature Exposure for Croup Symptoms: A Randomized Controlled Trial.

OBJECTIVES: Croup is the most common cause of acute upper airway obstruction in children. The benefits of treating croup with steroids are well established, with an onset of effect 30 minutes after administration. We investigated whether a 30-minute exposure to outdoor cold air might improve mild to moderate croup symptoms before the onset of action of steroids. METHODS: This open-label, single-center, randomized controlled trial, enrolled children aged 3 months to 10 years with croup and a Westley Croup Score (WCS) ≥2 attending a tertiary pediatric emergency department. Participants were randomized (1:1) to either a 30-minute exposure to outdoor cold (<10°C) atmospheric air or to indoor ambient room air immediately after triage and administration of a single-dose oral dexamethasone. The primary endpoint was a decrease in WCS ≥2 points from baseline at 30 minutes. Analyses were intention to treat. RESULTS: A total of 118 participants were randomly assigned to be exposed to outdoor cold air (n = 59) or indoor room temperature (n = 59). Twenty-nine of 59 children (49.2%) in the outdoor group and 14 of 59 (23.7%) in the indoor group showed a decrease in WCS ≥2 points from baseline at 30 minutes after triage (risk difference 25.4% [95% confidence interval 7.0-43.9], P = .007). Patients with moderate croup benefited the most from the intervention at 30 minutes (risk difference 46.1% [20.6-71.5], P < .001). CONCLUSIONS: A 30-minute exposure to outdoor cold air (<10°C), as an adjunct to oral dexamethasone, is beneficial for reducing the intensity of clinical symptoms in children with croup, especially when moderate.

DeepBreath-automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries.

The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.

Deep learning diagnostic and severity-stratification for interstitial lung diseases and chronic obstructive pulmonary disease in digital lung auscultations and ultrasonography: clinical protocol for an observational case-control study.

BACKGROUND: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach. METHODS: A total of 120 consecutive patients (≥ 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls. DISCUSSION: This approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity. Trial registration Registration: August 8, 2022. CLINICALTRIALS: gov Identifier: NCT05318599.

Factors associated with nonadherence to the American Academy of Pediatrics 2014 bronchiolitis guidelines: A retrospective study.

The latest guideline from the American Academy of Pediatrics for the management of bronchiolitis has helped reduce unnecessary interventions and costs. However, data on patients still receiving interventions are missing. In patients with acute bronchiolitis whose management was assessed and compared with current achievable benchmarks of care, we aimed to identify factors associated with nonadherence to guideline recommendations. In this single-centre retrospective study the management of bronchiolitis pre-guideline (Period 1: 2010 to 2012) was compared with two periods post-guideline (Period 2: 2015 to 2016, early post-guideline; and Period 3: 2017 to 2018, late post-guideline) in otherwise healthy infants aged less than 1 year presenting at the Children's University Hospitals of Geneva (Switzerland). Post-guideline, bronchodilators were more frequently administered to older (>6 months; OR 25.8, 95%CI 12.6-52.6), and atopic (OR 3.5, 95%CI 1.5-7.5) children with wheezing (OR 5.4, 95%CI 3.3-8.7). Oral corticosteroids were prescribed more frequently to older (>6 months; OR 5.2, 95%CI 1.4-18.7) infants with wheezing (OR 4.9, 95% CI 1.3-17.8). Antibiotics and chest X-ray were more frequently prescribed to children admitted to the intensive care unit (antibiotics: OR 4.2, 95%CI 1.3-13.5; chest X-ray: OR 19.4, 95%CI 7.4-50.6). Latest prescription rates were all below the achievable benchmarks of care. In summary, following the latest American Academy of Pediatrics guideline, older, atopic children with wheezing and infants admitted to the intensive care unit were more likely to receive nonevidence-based interventions during an episode of bronchiolitis. These patient profiles are generally excluded from bronchiolitis trials, and therefore not specifically covered by the current guideline. Further research should focus on the benefit of bronchiolitis interventions in these particular populations.

Viremia as a predictor of absence of serious bacterial infection in children with fever without source.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia. CONCLUSION: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS. WHAT IS KNOWN: • Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI. WHAT IS NEW: • Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

Diagnostic variation for febrile children in European emergency departments.

The study aimed to explore the use of diagnostics for febrile children presenting to European emergency departments (EDs), the determinants of inter-hospital variation, and the association between test use and hospitalization. We performed a secondary analysis of a cross-sectional observational study involving 28 paediatric EDs from 11 countries. A total of 4560 children < 16 years were included, with fever as reason for consultation. We excluded neonates and children with relevant comorbidities. Our primary outcome was the proportion of children receiving testing after primary evaluation, by country and by focus of infection. Variability between hospitals and effects of blood testing on patient disposition were explored by multilevel regression analyses, adjusting for patient characteristics (age group, triage level, appearance, fever duration, focus of infection) and hospital type (academic, teaching, other). The use of routine diagnostics varied widely, mostly in the use of blood tests, ranging from 3 to 75% overall across hospitals. Age < 3 months, high-acuity triage level, ill appearance, and suspicion of urinary tract infection displayed the strongest association with blood testing (odds ratios (OR) of 8.71 (95% CI 5.23-14.53), 19.46 (3.66-103.60), 3.13 (2.29-4.26), 10.84 (6.35-18.50), respectively). Blood testing remained highly variable across hospitals (median OR of the final model 2.36, 1.98-3.54). A positive association was observed between blood testing and hospitalization (OR 13.62, 9.00-20.61). CONCLUSION: the use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. Focus groups of participating sites should help define reasons for unexpected variation. WHAT IS KNOWN: • Although previous research has shown variation in the emergency department (ED) management of febrile children, there is limited information on the use of diagnostics in European EDs. • A deeper knowledge of variability and its determinants can steer optimization of care. WHAT IS NEW: • The use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. • Data on between-centre comparison offer opportunities to further explore factors influencing unwarranted variation.

Usability Testing and Technology Acceptance of an mHealth App at the Point of Care During Simulated Pediatric In- and Out-of-Hospital Cardiopulmonary Resuscitations: Study Nested Within 2 Multicenter Randomized Controlled Trials.

BACKGROUND: Mobile apps are increasingly being used in various domains of medicine. Few are evidence-based, and their benefits can only be achieved if end users intend to adopt and use them. To date, only a small fraction of mobile apps have published data on their field usability and end user acceptance results, especially in emergency medicine. OBJECTIVE: This study aims to determine the usability and acceptance of an evidence-based mobile app while safely preparing emergency drugs at the point of care during pediatric in- and out-of-hospital cardiopulmonary resuscitations by frontline caregivers. METHODS: In 2 multicenter randomized controlled parent trials conducted at 6 pediatric emergency departments from March 1 to December 31, 2017, and 14 emergency medical services from September 3, 2019, to January 21, 2020, the usability and technology acceptance of the PedAMINES (Pediatric Accurate Medication in Emergency Situations) app were evaluated among skilled pediatric emergency nurses and advanced paramedics when preparing continuous infusions of vasoactive drugs and direct intravenous emergency drugs at pediatric dosages during standardized, simulation-based, pediatric in- and out-of-hospital cardiac arrest scenarios, respectively. Usability was measured using the 10-item System Usability Scale. A 26-item technology acceptance self-administered survey (5-point Likert-type scales), adapted from the Unified Theory of Acceptance and Use of Technology model, was used to measure app acceptance and intention to use. RESULTS: All 100% (128/128) of nurses (crossover trial) and 49.3% (74/150) of paramedics (parallel trial) were assigned to the mobile app. Mean total scores on the System Usability Scale were excellent and reached 89.5 (SD 8.8; 95% CI 88.0-91.1) for nurses and 89.7 (SD 8.7; 95% CI 87.7-91.7) for paramedics. Acceptance of the technology was very good and rated on average >4.5/5 for 5 of the 8 independent constructs evaluated. Only the image construct scored between 3.2 and 3.5 by both participant populations. CONCLUSIONS: The results provide evidence that dedicated mobile apps can be easy to use and highly accepted at the point of care during in- and out-of-hospital cardiopulmonary resuscitations by frontline emergency caregivers. These findings can contribute to the implementation and valorization of studies aimed at evaluating the usability and acceptance of mobile apps in the field by caregivers, even in critical situations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03021122; https://clinicaltrials.gov/ct2/show/NCT03021122. ClinicalTrials.gov NCT03921346; https://clinicaltrials.gov/ct2/show/NCT03921346. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3726-4.

Study protocol for a two-site clinical trial to validate a smartphone-based artificial intelligence classifier identifying cervical precancer and cancer in HPV-positive women in Cameroon.

INTRODUCTION: Cervical cancer remains a major public health challenge in low- and middle-income countries (LMICs) due to financial and logistical issues. WHO recommendation for cervical cancer screening in LMICs includes HPV testing as primary screening followed by visual inspection with acetic acid (VIA) and treatment. However, VIA is a subjective procedure dependent on the healthcare provider's experience. Its accuracy can be improved by computer-aided detection techniques. Our aim is to assess the performance of a smartphone-based Automated VIA Classifier (AVC) relying on Artificial Intelligence to discriminate precancerous and cancerous lesions from normal cervical tissue. METHODS: The AVC study will be nested in an ongoing cervical cancer screening program called "3T-study" (for Test, Triage and Treat), including HPV self-sampling followed by VIA triage and treatment if needed. After application of acetic acid on the cervix, precancerous and cancerous cells whiten more rapidly than non-cancerous ones and their whiteness persists stronger overtime. The AVC relies on this key feature to determine whether the cervix is suspect for precancer or cancer. In order to train and validate the AVC, 6000 women aged 30 to 49 years meeting the inclusion criteria will be recruited on a voluntary basis, with an estimated 100 CIN2+, calculated using a confidence level of 95% and an estimated sensitivity of 90% +/-7% precision on either side. Diagnostic test performance of AVC test and two current standard tests (VIA and cytology) used routinely for triage will be evaluated and compared. Histopathological examination will serve as reference standard. Participants' and providers' acceptability of the technology will also be assessed. The study protocol was registered under ClinicalTrials.gov (number NCT04859530). EXPECTED RESULTS: The study will determine whether AVC test can be an effective method for cervical cancer screening in LMICs.

SwissPedData: Standardising hospital records for the benefit of paediatric research.

BACKGROUND: Improvement of paediatric healthcare is hampered by inefficient processes for generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS: SwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS: A taskforce of paediatricians from large Swiss children's hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS: All Swiss children's hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 CDEs: 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional. CONCLUSION: SwissPedData is a set of CDEs for information to be collected in EHR of Swiss children's hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Impact of a Mobile App on Paramedics' Perceived and Physiologic Stress Response During Simulated Prehospital Pediatric Cardiopulmonary Resuscitation: Study Nested Within a Multicenter Randomized Controlled Trial.

BACKGROUND: Out-of-hospital cardiac arrests (OHCAs) are stressful, high-stake events that are associated with low survival rates. Acute stress experienced in this situation is associated with lower cardiopulmonary resuscitation performance in calculating drug dosages by emergency medical services. Children are particularly vulnerable to such errors. To date, no app has been validated to specifically support emergency drug preparation by paramedics through reducing the stress level of this procedure and medication errors. OBJECTIVE: This study aims to determine the effectiveness of an evidence-based mobile app compared with that of the conventional preparation methods in reducing acute stress in paramedics at the psychological and physiological levels while safely preparing emergency drugs during simulated pediatric OHCA scenarios. METHODS: In a parent, multicenter, randomized controlled trial of 14 emergency medical services, perceived and physiologic stress of advanced paramedics with drug preparation autonomy was assessed during a 20-minute, standardized, fully video-recorded, and highly realistic pediatric OHCA scenario in an 18-month-old child. The primary outcome was participants' self-reported psychological stress perceived during sequential preparations of 4 intravenous emergency drugs (epinephrine, midazolam, 10% dextrose, and sodium bicarbonate) with the support of the PedAMINES (Pediatric Accurate Medication in Emergency Situations) app designed to help pediatric drug preparation (intervention) or conventional methods (control). The State-Trait Anxiety Inventory and Visual Analog Scale questionnaires were used to measure perceived stress. The secondary outcome was physiologic stress, measured by a single continuous measurement of the participants' heart rate with optical photoplethysmography. RESULTS: From September 3, 2019, to January 21, 2020, 150 advanced paramedics underwent randomization. A total of 74 participants were assigned to the mobile app (intervention group), and 76 did not use the app (control group). A total of 600 drug doses were prepared. Higher State-Trait Anxiety Inventory-perceived stress increase from baseline was observed during the scenario using the conventional methods (mean 35.4, SD 8.2 to mean 49.8, SD 13.2; a 41.3%, 35.0 increase) than when using the app (mean 36.1, SD 8.1 to mean 39.0, SD 8.4; a 12.3%, 29.0 increase). This revealed a 30.1% (95% CI 20.5%-39.8%; P<.001) lower relative change in stress response in participants who used the app. On the Visual Analog Scale questionnaire, participants in the control group reported a higher increase in stress at the peak of the scenario (mean 7.1, SD 1.8 vs mean 6.4, SD 1.9; difference: -0.8, 95% CI -1.3 to -0.2; P=.005). Increase in heart rate during the scenario and over the 4 drugs was not different between the 2 groups. CONCLUSIONS: Compared with the conventional method, dedicated mobile apps can reduce acute perceived stress during the preparation of emergency drugs in the prehospital setting during critical situations. These findings can help advance the development and evaluation of mobile apps for OHCA management and should be encouraged. TRIAL REGISTRATION: ClinicalTrials.gov NCT03921346; https://clinicaltrials.gov/ct2/show/NCT03921346. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3726-4.

Clinical data for paediatric research: the Swiss approach : Proceedings of the National Symposium in Bern, Switzerland, Dec 5-6, 2019.

BACKGROUND AND PURPOSE: Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project "Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)" was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. KEY HIGHLIGHTS: The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. IMPLICATIONS: Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland.

Pneumococcal Carriage in Burkina Faso After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results From 2 Cross-sectional Population-Based Surveys.

BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

Effect of a Mobile App on Prehospital Medication Errors During Simulated Pediatric Resuscitation: A Randomized Clinical Trial.

Importance: Medication errors are a leading cause of injury and avoidable harm, affecting millions of people worldwide each year. Children are particularly susceptible to medication errors, but innovative interventions for the prevention of these errors in prehospital emergency care are lacking. Objective: To assess the efficacy of an evidence-based mobile app in reducing the occurrence of medication errors compared with conventional preparation methods during simulated pediatric out-of-hospital cardiac arrest scenarios. Design, Setting, and Participants: This nationwide, open-label, multicenter, randomized clinical trial was conducted at 14 emergency medical services centers in Switzerland from September 3, 2019, to January 21, 2020. The participants were 150 advanced paramedics with drug preparation autonomy. Each participant was exposed to a 20-minute, standardized, fully video-recorded, realistic pediatric out-of-hospital cardiac arrest cardiopulmonary resuscitation scenario concerning an 18-month-old child. Participants were tested on sequential preparations of 4 intravenous emergency drugs of varying degrees of preparation difficulty (epinephrine, midazolam, 10% dextrose, and sodium bicarbonate). Intervention: Participants were randomized (1:1 ratio) to the support of an app designed to assist with pediatric drug preparation (intervention; n = 74) or to follow conventional drug preparation methods without assistance (control; n = 76). Main Outcomes and Measures: The primary outcome was the rate of medication errors, defined as a failure in drug preparation according to predefined, expert consensus-based criteria. Logistic regression models with mixed effects were used to assess the effect of the app on binary outcomes. Secondary outcomes included times to drug preparation and delivery, assessed with linear regression models with mixed effects. Results: In total, 150 advanced paramedics (mean [SD] age, 35.6 [7.2] years; 101 men [67.3%]; mean [SD] time since paramedic certification, 8.0 [6.2] years) participated in the study and completed 600 drug preparations. Of 304 preparations delivered using the conventional method, 191 (62.8%; 95% CI, 57.1%-68.3%) were associated with medication errors compared with 17 of 296 preparations delivered using the app (5.7%; 95% CI, 3.4%-9.0%). When accounting for repeated measures, with the app, the proportion of medication errors decreased in absolute terms by 66.5% (95% CI, 32.6%-83.8%; P < .001), the mean time to drug preparation decreased by 40 seconds (95% CI, 23-57 seconds; P < .001), and the mean time to drug delivery decreased by 47 seconds (95% CI, 27-66 seconds; P < .001). The risk of medication errors varied across drugs with conventional methods (19.7%-100%) when compared with the app (4.1%-6.8%). Conclusions and Relevance: Compared with conventional methods, the use of a mobile app significantly decreased the rate of medication errors and time to drug delivery for emergency drug preparation in a prehospital setting. Dedicated mobile apps have the potential to improve medication safety and change practices in pediatric emergency medicine. Trial Registration: ClinicalTrials.gov Identifier: NCT03921346.

Diagnostic Accuracy of SARS-CoV-2 Rapid Antigen Detection Testing in Symptomatic and Asymptomatic Children in the Clinical Setting.

Antigen-based rapid diagnostic tests (RDTs) are used in children despite the lack of data. We evaluated the diagnostic performance of the Panbio-COVID-19 Ag Rapid Test Device (P-RDT) in children. Symptomatic and asymptomatic participants 0 to 16 years old had two nasopharyngeal swabs (NPS) for both reverse transcription-PCR (RT-PCR) and P-RDT. A total of 822 participants completed the study, of which 533 (64.9%) were symptomatic. Among the 119 (14.5%) RT-PCR-positive patients, the P-RDT sensitivity was 0.66 (95% confidence interval [CI] 0.57 to 0.74). Mean viral load (VL) was higher among P-RDT-positive patients than negative ones (P < 0.001). Sensitivity was 0.91 in specimens with VL of >1.0E6 IU/ml (95% CI 0.83 to 0.99) and decreased to 0.75 (95% CI 0.66 to 0.83) for specimens >1.0E3 IU/ml. Among symptomatic participants, the P-RDT displayed a sensitivity of 0.73 (95% CI 0.64 to 0.82), which peaked at 1.00 at 2 days post-onset of symptoms (DPOS) (95% CI 1.00 to 1.00), then decreased to 0.56 (95% CI 0.23 to 0.88) at 5 DPOS. There was a trend toward lower P-RDT sensitivity in symptomatic children <12 years (0.62 [95% CI 0.45 to 0.78]) versus ≥12 years (0.80 [95% CI 0.69 to 0.91]; P = 0.09). In asymptomatic participants, the P-RDT displayed a sensitivity of 0.43 (95% CI 0.26 to 0.61). Specificity was 1.00 in symptomatic and asymptomatic children (95% CI 0.99 to 1.00). The overall 73% and 43% sensitivities of P-RDT in symptomatic and asymptomatic children, respectively, was below the 80% cutoff recommended by the World Health Organization. We observed a correlation between VL and P-RDT sensitivity, as well as variation of sensitivity according to DPOS, a major determinant of VL. These data highlight the limitations of RDTs in children, with the potential exception in early symptomatic children ≥12yrs.

Impact of a shared decision-making mHealth tool on caregivers' team situational awareness, communication effectiveness, and performance during pediatric cardiopulmonary resuscitation: study protocol of a cluster randomized controlled trial.

BACKGROUND: Effective team communication, coordination, and situational awareness (SA) by team members are critical components to deliver optimal cardiopulmonary resuscitation (CPR). Complexity of care during CPR, involvement of numerous providers, miscommunication, and other exogenous factors can all contribute to negatively influencing patient care, thus jeopardizing survival. We aim to investigate whether an mHealth supportive tool (the Interconnected and Focused Mobile Apps on patient Care Environment [InterFACE]) developed as a collaborative platform to support CPR providers in real-time and share patient-centered information would increase SA during pediatric CPR. METHODS: We will conduct a prospective, cluster randomized controlled trial by groups of 6 participants in a tertiary pediatric emergency department (33,000 consultations/year) with pediatric physicians and nurses. We will compare the impact of the InterFACE tool with conventional communication methods on SA and effective team communication during a standardized pediatric in-hospital cardiac arrest and a polytrauma high-fidelity simulations. Forty-eight participants will be randomized (1:1) to consecutively perform two 20-min video-recorded scenarios using either the mHealth tool or conventional methods. The primary endpoint is the SA score, measured with the Situation Awareness Global Assessment Technique (SAGAT) instrument. Enrollment will start in late 2020 and data analysis in early 2021. We anticipate that the intervention will be completed by early 2021 and study results will be submitted in mid 2021 for publication. DISCUSSION: This clinical trial will assess the impact of a collaborative mHealth tool on increasing situational awareness and effective team communication during in-hospital pediatric resuscitation. As research in this area is scarce, the results generated by this study may become of paramount importance in improving the care of children receiving in-hospital CPR, in the era of increasing communication technology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04464603 . Registered on 9 July 2020.

Pneumococcal vaccine implementation in the African meningitis belt countries: the emerging need for alternative strategies.

Introduction: Besides meningococcal disease, the African meningitis belt (AMB) region is also affected by pneumococcal disease. Most AMB countries have introduced pneumococcal conjugate vaccines (PCV) following a schedule of three primary doses without a booster or a catch-up campaign. PCV is expected to help control pneumococcal disease through both direct and indirect effects. Whether and how fast this will be achieved greatly depends on implementation strategies. Pre-PCV data from the AMB indicate high carriage rates of the pneumococcus, not only in infants but also in older children, and a risk of disease and death that spans lifetime. Post-PCV data highlight the protection of vaccinated children, but pneumococcal transmission remains important, resulting in a lack of indirect protection for unvaccinated persons.Areas covered: A non-systematic literature review focused on AMB countries. Relevant search terms were used in PubMed, and selected studies before and after PCV introduction were summarized narratively to appraise the suitability of current PCV programmatic strategies.Expert opinion: The current implementation strategy of PCV in the AMB appears suboptimal regarding the generation of indirect protection. We propose and discuss alternative programmatic strategies, including the implementation of broader age group mass campaigns, to accelerate disease control in this high transmission setting.

Deep learning diagnostic and risk-stratification pattern detection for COVID-19 in digital lung auscultations: clinical protocol for a case-control and prospective cohort study.

BACKGROUND: Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation. METHODS: A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories. DISCUSSION: This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring. TRIAL REGISTRATION: PB_2016-00500, SwissEthics. Registered on 6 April 2020.