Browsing by Author "Bārzdiņa, Arta"
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Item Biomarķieru izvērtējums galvas traumas diagnostikā un prognozēšanā. Promocijas darba kopsavilkums(Rīgas Stradiņa universitāte, 2013) Bārzdiņa, Arta; Pilmane, Māra; Pētersons, AigarsGalvas traumas ir viens no biežākajiem nāves un invaliditātes cēloņiem visā pasaulē un rada nopietnas sociāli ekonomiskas problēmas. Procentuāli iedalot galvas traumas pēc smaguma pakāpēm, aptuveni 88% ir vieglas galvas traumas, 7% - vidēji smagas un 5% - smagas un fatālas galvas traumas, pēc kurām bērni bieži iegūst paliekamu invaliditāti. Ir pierādīts, ka visneprognozējamākās ir vieglās galvas traumas, kuras sākumā novērtētas ar GCS 13-15 ballēm, attālākā periodā pēc traumas notikuma pacientiem var izraisīt intrakraniālas asiņošanas, difūzu aksonālu bojājumu, tādēļ šo traumu guvušo pacientu grupai svarīga īpaši precīza akūtas diagnozes un gala rezultāta prognozes noteikšana. Līdz ar to īpaša loma tiek pievērsta biomarķieriem kā galvas traumas prognozes indikatoriem. Pētījuma mērķis bija smadzeņu sekundārajam bojājumam raksturīgu biomarķieru ekspresijas izpēte smadzeņu audu materiālā un perifēro asiņu paraugos dažādos laika periodos pēc traumas. Pētījuma morfoloģijas sadaļā tika iekļauti 28 dažāda vecuma pacienti pēc fatālām galvas traumām, klīniskajā sadaļā – 18 pacienti ar smagām, vidēji smagām un vieglām galvas traumām līdz septiņu gadu vecumam. Morfoloģijas sadaļā tika izpētīti un analizēti citoskeleta proteīna GFAP, diedziņu NF, citokīnu IL-6 un IL-10 ekspresija smadzeņu audos, tika noteikts apoptotisko šūnu daudzums un sadalījums smadzeņu audos traumas un pretsitiena vietās gan bērniem, gan pieaugušajiem, kuri miruši notikuma vietā, un tiem, kuri miruši attālinātā laikā pēc traumas. Klīniskajā sadaļā tika noteikti un analizēti 10 iekaisuma biomarķieri asins serumā bērniem vecumā līdz septiņiem gadiem četrās definētās laika vienībās (24;48;72 un 96 stundas pēc traumas) smagu, vidēji smagu un vieglu galvas traumu gadījumā.Item Biomarķieru izvērtējums galvas traumas diagnostikā un prognozēšanā. Promocijas darbs(Rīgas Stradiņa universitāte, 2013) Bārzdiņa, Arta; Pilmane, Māra; Pētersons, AigarsGalvas traumas ir viens no biežākajiem nāves un invaliditātes cēloņiem visā pasaulē un rada nopietnas sociāli ekonomiskas problēmas. Procentuāli iedalot galvas traumas pēc smaguma pakāpēm, aptuveni 88% ir vieglas galvas traumas, 7% - vidēji smagas un 5% - smagas un fatālas galvas traumas, pēc kurām bērni bieži iegūst paliekamu invaliditāti. Ir pierādīts, ka visneprognozējamākās ir vieglās galvas traumas, kuras sākumā novērtētas ar GCS 13-15 ballēm, attālākā periodā pēc traumas notikuma pacientiem var izraisīt intrakraniālas asiņošanas, difūzu aksonālu bojājumu, tādēļ šo traumu guvušo pacientu grupai svarīga īpaši precīza akūtas diagnozes un gala rezultāta prognozes noteikšana. Līdz ar to īpaša loma tiek pievērsta biomarķieriem kā galvas traumas prognozes indikatoriem. Pētījuma mērķis bija smadzeņu sekundārajam bojājumam raksturīgu biomarķieru ekspresijas izpēte smadzeņu audu materiālā un perifēro asiņu paraugos dažādos laika periodos pēc traumas. Pētījuma morfoloģijas sadaļā tika iekļauti 28 dažāda vecuma pacienti pēc fatālām galvas traumām, klīniskajā sadaļā – 18 pacienti ar smagām, vidēji smagām un vieglām galvas traumām līdz septiņu gadu vecumam. Morfoloģijas sadaļā tika izpētīti un analizēti citoskeleta proteīna GFAP, diedziņu NF, citokīnu IL-6 un IL-10 ekspresija smadzeņu audos, tika noteikts apoptotisko šūnu daudzums un sadalījums smadzeņu audos traumas un pretsitiena vietās gan bērniem, gan pieaugušajiem, kuri miruši notikuma vietā, un tiem, kuri miruši attālinātā laikā pēc traumas. Klīniskajā sadaļā tika noteikti un analizēti 10 iekaisuma biomarķieri asins serumā bērniem vecumā līdz septiņiem gadiem četrās definētās laika vienībās (24;48;72 un 96 stundas pēc traumas) smagu, vidēji smagu un vieglu galvas traumu gadījumā.Item Emergency medical services utilisation among febrile children attending emergency departments across Europe : an observational multicentre study(2023-09) Tan, Chantal D.; Vermont, Clementien L.; Zachariasse, Joany M.; Zavadska, Dace; On behalf of PERFORM consortium (Personalised Risk assessment in febrile children to optimize Real-life Management across the European Union); Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Sidorova, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityChildren constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.Item Evaluation of the Role of Biomarkers in Diagnostics and Prognostication of Head Injuries. Summary of the Doctoral Thesis(Rīga Stradiņš University, 2013) Bārzdiņa, Arta; Pilmane, Māra; Pētersons, AigarsHead trauma is one of the most common causes of death and disability throughout the world, and it causes serious social and economic problems. The proportions of severity of head trauma are as follows: approximately 88% is light head trauma, 7% - medium severe head trauma, and 5% severe and fatal head injuries, which are followed by permanent disability in children. It has been proven that the most unpredictable are the light head injuries, which on the initial evaluation show 13 – 15 points of GCS, later after the trauma moment they can cause intracranial bleeding, diffuse axonal damage, and that is the reason why it is very important to make precise diagnosis in the acute stage and also give prognosis about the end result in the group of patients with this kind of trauma. This brings focus on biomarkers as the prognostic indicators in patients with head injuries. The aim of the study was to investigate the biomarkers characteristic to the secondary injury, their expression in the brain tissue samples and in peripheral blood samples in different time points after the injury. The morphology chapter included 28 patients of different age after fatal head injuries. The patients were divided in several groups: children and adults. Each of those groups were sub-divided further – those, who died on the spot of the injury, and those who died after a period of time. In all patients cytoskeletal protein GFAP, filaments NF, cytokines IL-6 and IL-10 expression in the brain tissue, apoptotic cell count and distribution in the brain tissue in the spot of the injury and counterstroke were analyzed. The clinical chapter included 18 patients with severe, medium severe and light head injuries up to 7 years of age. In these patients of 10 inflammatory biomarkers were measured in four defined time points (24, 48, 72 and 96 hours after the trauma).Item Febrile illness in high-risk children : a prospective, international observational study(2023-02) van der Velden, Fabian J.S.; de Vries, Gabriella; Martin, Alexander; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Rudzāte, Aleksandra; Urbāne, Urzula Nora; Department of Paediatrics; Rīga Stradiņš UniversityTo assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population.What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low.What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.Item Guideline adherence in febrile children below 3 months visiting European Emergency Departments : an observational multicenter study(2022-12) Tan, Chantal D.; van der Walle, Eline E.P.L.; Vermont, Clementien L.; Zavadska, Dace; PERFORM consortium (Personalised Risk assessment in febrile children to optimize Real-life Management across the European Union); Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Urbāne, Urzula Nora; Deksne, Dārta; Selecka, Katrina; Sidorova, Aleksandra; Department of Paediatrics; Rīga Stradiņš UniversityFebrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0–2.3). Management per ED varied as follows: use of diagnostic tests 14–83%, antibiotic treatment 23–54%, admission 34–86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0–38%), partial adherence occurred in 56% (484/868, range 35–77%). Conclusion: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children.What is Known:• Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment.• There is practice variation in management of young febrile children due to differences in guidelines and their usage and adherence.What is New:• Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe.• Guideline revision including new biomarkers is needed to improve management in young febrile children.Item Il-6 and Il-10 Expression in Brain Tissue in Children and Adults after Fatal Traumatic Brain Injury(2011) Bārzdiņa, Arta; Pilmane, Māra; Pētersons, Aigars; Rīga Stradiņš University; Institute of Anatomy and AnthropologyIntroduction. One of the leading secondary damage processes determining the outcome of head injury is cerebral ischemia. The inflammatory reactions are important factors in cases of ischemic brain damage. Some studies characterize generalized reactions of cytokines in brain, but there are less studies about inflammatory reactions in the determined areas of the brain in different time points. Aim of the study. To determine the reaction of brain tissue after fatal brain injury in different time points after the trauma, by detecting IL-6 in the pyramidal neurons of CNS gray matter (GM) and in the white substance (WS) and IL-10 in the WS of the impact and counterstroke areas. Materials and methods. We used brain tissue material from the trauma and counterstroke spots of 11 patients died after fatal traumatic brain injury in different time points. Brain tissue specimens were routinely fixed, embedded into paraffin, cut in 5 μm thick slides. For immunohistochemistry we used monoclonal antibodies against recombinant IL-6 of human origin and polyclonal rabbit antibodies against IL-10 of human. Results. There were found statistically significant differences in IL-6 positive neurons in the GM, and IL-6 and IL-10 positive glial cell numbers in the WS in the spot of counterstroke and in the spot of direct impact in both patient groups (Mann-Whitney U Test p ≤ 0,001 for all groups). Conclusions. The IL-6 and IL-10 positive glial cell numbers correlate with the outcome of trauma. The inflammatory reaction in the WS in the spot of counterstroke was more marked than in the spot of direct impact. The activity of inflammatory reaction depends on the time period after the traumatic event.Item Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens(2023-08-18) Willems, Esther; Gloerich, Jolein; Suppers, Anouk; PERFORM consortium; Zavadska, Dace; Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Urbāne, Urzula Nora; Pavāre, Jana; Pučuka, Zanda; Rīga Stradiņš UniversityMechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.Item A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM) : a multi-cohort machine learning study(2023-11) Jackson, Heather R; Zandstra, Judith; Menikou, Stephanie; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Sidorova, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBACKGROUND: Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. METHODS: In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. FINDINGS: 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. INTERPRETATION: This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. FUNDING: European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation.Item Prospective paediatric intensive care registry in Latvia : one year outcomes(2019) Veģeris, Ivars; Daukšte, Iveta; Bārzdiņa, Arta; Parslow, Roger C; Balmaks, Reinis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of Doctoral Studies; Department of Clinical Skills and Medical TechnologiesBackground: In Latvia, there is a single eight-bed paediatric intensive care unit (PICU) where all critically ill children are admitted. A recent retrospective audit of the outcomes of paediatric critical care in this unit revealed a high number of unplanned extubations and excess crude mortality. In 2017, our centre joined the UK and Ireland based Paediatric Intensive Care Audit Network (PICANet) as a pilot project to investigate the feasibility of developing a paediatric critical care registry in Latvia and in the Baltic states. Methods: Riga Stradins University Ethics Committee approved the study. Anonymized data on all patients admitted to our unit from 1 June, 2017 to 31 May 2018 were prospectively entered onto the PICANet database. Results: A total of 774 PICU admissions were analysed; 45% of admissions were elective. The median age was 59 months (IQR: 14-149). The highest admission rate was on Wednesdays representing the flow of elective surgical patients. The median length of stay was 0.95 days (IQR: 0.79-1.98). Twenty-five percent required respiratory support. The expected number of deaths estimated using the Paediatric Index of Mortality 3 (PIM 3) 15.16; 15 patients (1.94%) died resulting in Standartized Mortality Ratio (SMR) of 0.99 (95% CI 0.57-1.60). The emergency readmission rate within 48 hours after PICU discharge was 0.9%. There were 1.8 unplanned extubations per 100 invasive ventilation days. Other paediatric intensive care audit networks reported similar adjusted mortality rates but lower rates of unplanned extubations. Thirty days after PICU discharge, 653 (84.36%) patients were alive and outside hospital, 98 (12.66%) were inpatients, six (0.78%) had died, two (0.26%) were lost to the follow-up. We observed a marked peak of infant emergency respiratory admissions in February. Conclusions: This project explored the possibility of prospective paediatric critical care audit in Latvia by joining an established international network. This allowed direct comparison of outcomes between the countries. Excess mortality was not observed during one-year data collection period, however a high rate of unplanned extubations was revealed. The results allowed a better planning of elective patient flow by spreading elective cases over the week to avoid "rush hours".Item Raising AWaRe-ness of antimicrobial stewardship challenges in pediatric emergency care : results from the PERFORM study assessing consistency and appropriateness of antibiotic prescribing across Europe(2024-03-15) Kolberg, Laura; Khanijau, Aakash; van der Velden, Fabian J S; Herberg, Jethro; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Rudzāte, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBackground. Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Methods. Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final “bacterial” or “viral” phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Results. Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the “Watch” category. Conclusions. Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics.Item Relationship between molecular pathogen detection and clinical disease in febrile children across Europe : a multicentre, prospective observational study(2023-09) Shah, Priyen; Voice, Marie; Calvo-Bado, Leonides; Rudzate, Aleksandra; Zavadska, Dace; PERFORM consortium; Bārzdiņa, Arta; Deksne, Dārta; Balode, Anda; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBACKGROUND: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. METHODS: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. FINDINGS: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. INTERPRETATION: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. FUNDING: EU Horizon 2020 grant 668303.