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Elvira Isaeva,1 Azamat Akylbekov,2 Joakim Bloch,3 Anja Poulsen,3 Jørgen Kurtzhals,4,5 Volkert Siersma,6 Talant Sooronbaev,2 Rune Munck Aabenhus,6 Jesper Kjærgaard3 1Allergology Department, National Centre of Maternity and Childhood Care (NCMCC), Bishkek, Kyrgyzstan; 2Pulmonology Department, National Centre of Cardiology and Internal Medicine Named After Academician M. Mirrakhimov, Bishkek, Kyrgyzstan; 3Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 4Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 5Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; 6Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Elvira Isaeva, Allergology Department, National Centre of Maternity and Childhood Care (NCMCC), Postal Address: 720038, 190, Akhunbaev St, Bishkek, Kyrgyzstan, Tel +996 (709) 795 979, Email rhc358@sund.ku.dkBackground: In Kyrgyzstan, the morbidity prevalence of and morbidity from acute respiratory tract infections (ARTI) in children is high. Local healthcare workers (HCW) often prescribe antibiotics that are not indicative due to a mix of professional and societal factors. It is suggested to precede with a decision on antibiotics by a point-of-care test (POCT) on the appropriateness of the treatment, eg, a measurement of C-reactive protein (CRP). CRP-guided antibiotic stewardship in children with ARTI has not previously been studied in Central Asia.Purpose: This pilot study was conducted to examine the feasibility of the methods and procedures to be used in the upcoming randomised controlled COORDINATE clinical trial (NCT05195866) and in daily clinical practice in primary care.Patients and methods: HCWs from three selected rural healthcare facilities were trained in

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice., Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

BACKGROUND: In Kyrgyzstan, the morbidity prevalence of and morbidity from acute respiratory tract infections (ARTI) in children is high. Local healthcare workers (HCW) often prescribe antibiotics that are not indicative due to a mix of professional and societal factors. It is suggested to precede with a decision on antibiotics by a point-of-care test (POCT) on the appropriateness of the treatment, eg, a measurement of C-reactive protein (CRP). CRP-guided antibiotic stewardship in children with ARTI has not previously been studied in Central Asia.PURPOSE: This pilot study was conducted to examine the feasibility of the methods and procedures to be used in the upcoming randomised controlled COORDINATE clinical trial (NCT05195866) and in daily clinical practice in primary care.PATIENTS AND METHODS: HCWs from three selected rural healthcare facilities were trained in the CRP POCT and in interpretation of results. Children aged 6 months to 12 years attending the primary healthcare facilities with respiratory symptoms were randomly assigned to CRP-guided management or standard care, guided by clinical findings only. Children were followed up for 14 days by scheduled telephone calls to caregivers.RESULTS: Eighty-one children participated in this pilot study. The CRP POCT and the trial procedures were acceptable to the target group as well as to the HCWs. Children from both groups recovered equally well, with an observed significant lower use of antibiotics in the CRP group. HCWs generally adhered to the CRP guidelines, and only once was an antibiotic prescribed despite low CRP results. No safety concerns were observed. Four parents provided wrong phone numbers impeding follow-up. We will collect all mobile phone numbers in the household for the main trial.CONCLUSION: The pilot provided satisfactory results, suggesting that the COORDINATE trial of CRP POCT is effective, feasible with minor adjustments and without apparent safety concerns for t

Background: Previous studies on adult patients in hospital isolation show that it can be highly stressful, with some patients affected by depression and anxiety. This study aimed to explore how children, adolescents, and their parents perceive isolation and how it affects them physically, psychologically, and socially. Methods: A qualitative approach was used comprising semi-structured interviews, participant observations, and field notes. Findings: Two adolescents and 13 parents were selected to participate in the interviews, while three children and their parents participated in participant observation. Besides the participant observation one of the adolescents and one parent also participated in interviews. The children and adolescents were isolated at the hospital due to bacterial or viral infections or were carriers of an antibiotic resistant bacteria. After performing a thematic analysis to identify patterns in the data, four themes emerged: 1. Differing information provided about bacteria, virus, hygiene precautions, and isolation, 2. Dependence on healthcare professionals, 3. Impact of the environment, and 4. Coping and psychological reactions on isolation. Discussion: The participants conveyed positive and negative experiences and emotions during isolation in relation to daily activities, psychological well-being, and social life. Adolescents and their parents requested clear comprehensible and consistent information on isolation from healthcare professionals. Application to practice: To improve hospital isolation for children, adolescents, and their parents, well-written information on isolation and hygiene precautions is crucial, as are evolving strategies to minimise social exclusion and the emotional impact of isolation.

Aim: In Denmark, preterm infants are recommended to receive childhood vaccinations without correction for gestational age. This study aimed to describe the timeliness of the Danish Childhood Vaccination Program in preterm infants during the first 13 months of life and to evaluate possible determinants of delay. Methods: This retrospective cohort study included preterm infants admitted to a level III neonatal intensive care unit between October 2019 and October 2020. Clinical data were retrieved from medical records and the Danish Vaccination Register. Timely vaccination was defined corresponding to chronological age of 3-, 5- and 12 months, within a time interval of 30 days before to 29 days after the expected date. Results: Analyses included 365 infants. Timely vaccination occurred in 91%, 83% and 67% of preterm infants for the first, second and third vaccination, respectively, and timeliness was highest if born before gestational age 28 weeks. Gestational age 28–31 + 6 weeks and delayed former vaccinations negatively influenced the timeliness of the following vaccinations. Conclusion: Most preterm infants received the first vaccination timely; however, timeliness decreased with each subsequent vaccination. Efforts to improve timeliness should focus on counselling healthcare personnel and parents to follow the recommendations for the first and the following vaccinations.

BACKGROUND: More than 2 million third-trimester stillbirths occur yearly, most of them in low- and middle-income countries. Data on stillbirths in these countries are rarely collected systematically. This study investigated the stillbirth rate and risk factors associated with stillbirth in four district hospitals in Pemba Island, Tanzania.METHODS: A prospective cohort study was completed between the 13th of September and the 29th of November 2019. All singleton births were eligible for inclusion. Events and history during pregnancy and indicators for adherence to guidelines were analysed in a logistic regression model that identified odds ratios [OR] with a 95% confidence interval [95% CI].RESULTS: A stillbirth rate of 22 per 1000 total births in the cohort was identified; 35.5% were intrapartum stillbirths (total number of stillbirths in the cohort, n = 31). Risk factors for stillbirth were breech or cephalic malpresentation (OR 17.67, CI 7.5-41.64), decreased or no foetal movements (OR 2.6, CI 1.13-5.98), caesarean section [CS] (OR 5.19, CI 2.32-11.62), previous CS (OR 2.63, CI 1.05-6.59), preeclampsia (OR 21.54, CI 5.28-87.8), premature rupture of membranes or rupture of membranes 18 h before birth (OR 2.5, CI 1.06-5.94) and meconium stained amniotic fluid (OR 12.03, CI 5.23-27.67). Blood pressure was not routinely measured, and 25% of women with stillbirths with no registered foetal heart rate [FHR] at admission underwent CS.CONCLUSIONS: The stillbirth rate in this cohort was 22 per 1000 total births and did not fulfil the Every Newborn Action Plan's goal of 12 stillbirths per 1000 total births in 2030. Awareness of risk factors associated with stillbirth, preventive interventions and improved adherence to clinical guidelines during labour, and hence improved quality of care, are needed to decrease the stillbirth rate in resource-limited settings.

INTRODUCTION: While lower respiratory tract infections are the main cause of death for children under 5 globally, only a small proportion of children with respiratory tract infections need antibiotics. Overuse of antibiotics globally is leading to increasing rates of antibiotic resistance. In Kyrgyzstan, healthcare workers regularly prescribe antibiotics when clinical uncertainty is present to err on the side of caution. Targeting antibiotic use with biomarkers of inflammation such as C reactive protein (CRP) testing at the point-of-care test (POCT) has been shown to reduce antibiotic use in general, but only few studies have been done in children and no studies exist from Central Asia. This study aims to assess whether the use of a CRP POCT can safely decrease prescription of antibiotics for children with acute respiratory symptoms in primary level healthcare centres in Kyrgyzstan. METHODS AND ANALYSIS: Multicentre, open-label, individually randomised, controlled clinical trial with 14 days follow-up (follow-up by phone on days 3, 7 and 14) in rural lowland Chui and highland Naryn regions of Kyrgyzstan. The population are children aged 6 months to 12 years attending the primary level healthcare centres during normal business hours with acute respiratory symptoms. CRP POCT equipment will be supplied to healthcare centres, along with a short training session in CRP use, including the interpretation of results to support the clinical evaluation of the child with acute respiratory infection. The primary outcomes are the proportion of patients prescribed an antibiotic within 14 days of index consultation (superiority analysis) and days to recovery (non-inferiority analysis). Secondary outcomes are antibiotics prescribed at index consultation, reconsultations, hospital admission and vital status within 14 days. Analysis of the first primary outcome, antibiotic use, will be intention to treat using a logistic regression model. Analysis of the second primary outcome, da

BACKGROUND: The highest neonatal mortality is in Sub-Saharan Africa, where neonatal sepsis accounts for approximately 50%. At Pemba Island, Tanzania, we examined the use of prophylactic antibiotics in neonates and related it to WHO guidelines and compared clinical signs of infection with the use of antibiotic treatment; furthermore, we aimed to investigate all use of antibiotic treatment in the neonatal period. METHOD: This prospective observational cohort study was performed from 1 January 2022 to 15 April 2022 at a district hospital on Pemba Island, Tanzania. Women admitted in early established or active labour, and their neonates, were eligible for inclusion. We used questionnaires for mother and health worker and examined the neonates 2 h after birth. Follow-up was made at discharge or at 18 h of life, and days 7 and 28. RESULTS: We included 209 women and their 214 neonates. The neonatal mortality was 5 of 214 (23 per 1000 live births). According to WHO guidelines 29 (13.6%) had ≥ 1 risk factor for infection. Of these, three (10.3%) received prophylactic antibiotic treatment; only one (3.4%) received the correct antibiotic drug recommended in guidelines. Thirty-nine (18.2%) neonates had ≥ 1 clinical indicator of infection and 19 (48.7%) of these received antibiotic treatment. A total of 30 (14.0%) neonates received antibiotics during the study period. Twenty-three (76.7%) were treated with peroral antibiotics. CONCLUSION: Adherence to WHO guidelines for prophylactic antibiotic treatment to prevent neonatal infection was low. Further, only half of neonates with clinical signs of infection received antibiotics.

Managing critically ill children is a rare and challenging event requiring training to ensure adequate and timely quality of care. Thus, health professionals train for pediatric emergencies in a simulated setting. Virtual reality (VR) is a promising modality for simulation, and current evidence highlights the potential of VR for simulating pediatric emergencies. However, more studies are needed to determine the aspects of VR design and implementation that support transfer of learning.

Purpose: The optimal choice of protocol for diagnostic imaging in children with tuberculosis (TB) is a contemporary challenge due to the war in Ukraine, which potentially can create a steep rise in TB cases in Western Europe. We aimed to gather all primary research comparing imaging modalities and their diagnostic accuracies for pulmonary findings in children with suspected or confirmed pulmonary tuberculosis (PTB). Method: We searched the databases PubMed and Embase using pre-specified search terms, for English- and non-English published and un-published reports from the period 1972 to 2022. We retrieved reports via citation search in excluded literature reviews and systematic reviews. Studies were eligible if most of the study population was between 0 and 18 years of age with confirmed or suspected PTB, and study participants had described diagnostic images from two or more different imaging modalities. Results: A total of 15 studies investigated conventional chest X-Ray (CXR) and computed tomography (CT) in diagnosing PTB in children. Nine studies investigated the number of participants in where CT or CXR confirmed the diagnosis of TB, and all of them, including a total of 1244 patients, reported that findings compatible with TB were more frequently detected on CT than CXR. Only two studies did not include radiological findings as part of their diagnostic criteria for PTB, and combined they showed that CT diagnosed 54/54 (100 %) children with confirmed PTB, while CXR diagnosed 42/54 (78 %). Two studies compared magnetic resonance imaging (MRI) with CXR and showed that MRI diagnosed more children with PTB than CXR. One study reported a higher positive predictive value (PPV), sensitivity and specificity for PTB findings for MRI than CXR. One study compared CXR with high-kilovolt (high-kV) CXR, finding compatible sensitivity and specificity regarding confirmation of PTB. Two studies compared ultrasound (US) with CXR and found that US had a higher diagnostic yield

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease is essential for the prognosis. The subsequent use of suppressive therapy with oral acyclovir has further enhanced the long-term prognosis. This review presents evidence of risk factors, clinical presentation, prevention, and management of HSV in newborns.

Background: High-quality essential newborn care (ENC) can improve newborn health and reduce preventable newborn mortality. The World Health Organization recommends specific ENC interventions. Video recordings have potential as a tool for assessment of clinical care also in low and middle-income countries. Objective: To use video observations of healthy newborns to describe ENC practices in a low-income setting and compare actual clinical practice with WHO recommendations. Method: This is a cross-sectional observational study. Video records of neonatal interventions to 324 healthy newborns were assessed. They were obtained at baseline of a pre-post intervention study during a 10-week study period in Pemba, Tanzania. Data also included postnatal structured questionnaires. Eight ENC interventions and quality indicators were defined as per the WHO recommendations. Descriptive statistics were used to summarize ENC practices and maternal and neonatal characteristics. Results: None of the newborns received all eight recommended ENC interventions. The median duration of separation from the mother was 25 minutes and 15 seconds (ranging from 22 seconds to 3 hours and 36 minutes), 51% of the newborns received proper thermal care during the separation. Twenty-one percent had sufficient umbilical cord care, 8% were stimulated for breathing, 69% were observed at least once by healthcare staff and 9% did undergo suctioning. None of the newborns received antibiotic ointments or vitamin K. Conclusion: Video recording of healthy newborns was feasible. The study identified omission of key ENC practices including proper thermal care, skin-to-skin contact and establishment of breastfeeding within the first hour of life, vitamin K administration as well as application of unnecessary practices such as excessive suctioning of breathing newborns.

Aim: To explore [fluorine-18]-fluoro-2-deoxy-d-glucose positron-emission-tomography/computed tomography (18FDG-PET/CT) in patients where standard investigations were non-diagnostic. Methods: We reviewed medical records of previously healthy children who had 18FDG-PET/CT performed at Copenhagen University Hospital in 2015–2020 due to unexplained fever. Results: Thirty-five of 819 paediatric 18FDG-PET/CT were performed due to unexplained fever. The final diagnoses were malignancy (11%), infections (23%), inflammatory diseases (43%) and miscellaneous (26%). 18FDG-PET/CT was diagnostic in six cases with Takayasu's arteritis, tuberculosis, Langerhans cell histiocytosis and Ewing sarcoma. Sixteen cases had focal 18FDG-uptake, but 18FDG-PET/CT could only differentiate malignancy, infection and inflammation in three cases. In six cases with inflammatory diseases and no focal signs, PET/CT was normal except increased non-specific 18FDG-uptake in bone marrow and spleen in five cases. One case was false positive (suspicion of appendicitis) and two false negative (leukaemia and inflammatory disease). Conclusion: 18FDG-PET/CT was diagnostic, or contributed to the diagnosis, in several children with unexplained fever referred to a tertiary centre. Challenges comprised (i) only increased non-specific 18FDG-uptake in bone marrow and spleen in half of cases with inflammatory diseases, (ii) no differentiation between complicated infections, malignancy and inflammation in most cases with focal processes and (iii) a small risk of false positive and false negative results.

This brief report investigated the impact of clinical, biochemical, and endoscopic activity of IBD on the severity and long-term outcomes of COVID-19 in a prospective population-based cohort. The study did not identify any association between IBD activity and COVID-19 outcomes.