Browsing by Author "Pavāre, Jana"

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    ACUTE APPENDICITIS IN PAEDIATRIC PATIENTS WITH DELTA AND OMICRON VARIANTS OF SARS-COV-2 : CASE SERIES
    (2024-12-01) Eņģelis, Arnis; Smane, Liene; Zviedre, Astra; Ķīvīte-Urtāne, Anda; Zurmutai, Timurs; Pavāre, Jana; Bormotovs, Jurijs; Kakar, Mohit; Pētersons, Aigars; Department of Paediatric Surgery; Department of Paediatrics; Department of Public Health and Epidemiology; Department of Anaesthesiology, Intensive Care and Clinical simulations
    COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is generally milder in children. Acute appendicitis (AA) is a common diagnosis in children, but greater understanding is needed for more adjusted treatment of these patients when in conjunction with acute COVID-19 infection. We provide a retrospective case series study of comparison of patients with AA and positive SARS-CoV-2 Delta (B.1.671.2) and Omicron (B.1.1.529) variants. There were 16 paediatric patients admitted to a tertiary hospital with suspected acute appendicitis and COVID-19. Compared with the Delta variant (B.1.617.2), children infected with Omicron variant (B.1.1.529) of SARS-CoV-2 infection were more likely to have fever (p = 0.04) and pain migration to the right lower quadrant (RLQ) (p = 0.02). Further studies are needed to characterise the differences between SARS-CoV-2 variants (Delta vs Omicron) in cases of acute appendicitis in children.
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    Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries : results of an internet-based global point prevalence survey
    (2018-06) Global-PPS network; Pavāre, Jana
    Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux.
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    Diagnostic Value of Clinical Presentation, Parental Concern, and Clinician’s Non-Analytical Reasoning in Identifying Serious Bacterial Infections in Febrile Children. Doctoral Thesis
    (Rīga Stradiņš University, 2022) Urbāne, Urzula Nora; Pavāre, Jana; Zavadska, Dace
    Fever is one of the main reasons for visits to paediatric emergency departments (ED). Although in most cases the underlying cause is self-limiting viral infections, 4 to 25 % of children visiting ED with fever develop serious bacterial infections (SBI), which are significant causes of childhood mortality, even in developed countries. Due to high number of patients visiting ED with febrile illness, rapid discrimination between children with and without possible SBI is challenging.This study aimed to improve early recognition of SBI in children who present to ED by assessing the diagnostic value of clinical signs at presentation, clinician’s non-analytical reasoning, defined as “gut feeling” of serious illness and “sense of reassurance”, and parental concern of different / more severe illness. Based on these variables, derivation and external validation of two clinical prediction models (CPMs) for SBI was performed, and the performance of a CPM based on clinical variables alone was compared to a model integrating clinical features together with variables of non-analytical reasoning. The models were derived from a dataset of 517 febrile patients presenting to the ED of Children’s Clinical University Hospital (CCUH) in Riga, and externally validated in a dataset of 188 patients prospectively enrolled in six regional hospitals in Latvia.While the prognostic value of clinician’s “gut feeling” as an independent variable for diagnosing SBI was limited, “sense of reassurance” was significantly predictive of absence of SBI, and the performance of the CPM 2 integrating the non-analytical variables with clinical features was superior in both derivation (Receiver Operating Characteristic curve (ROC) Area Under Curve (AUC) 0.783, 95 % confidence interval (CI) 0.727–0.839) and validation cohorts (ROC AUC 0.752, 95 % CI 0.674–0.830), when compared to the performance of the CPM 1, which was based solely on clinical variables (ROC AUC in derivation population 0.738, 95 % CI 0.688–0.788, in validation population 0.677, 95 % CI 0.586–0.767). Both CPMs had moderate ability to predict SBI in febrile children presenting to ED and acceptable performance in the validation cohort. A scoring system based on the superior prediction model was created to distinguish between patients with high or low risk of SBI, as well as to identify patients in diagnostic “grey area”, in which the severity of manifestations of SBI and mild infections overlapped. Contrary to studies in primary care performed in other European countries, parental concern was not significantly predictive of SBI. Elements of fever-related anxiety were identified as factors influencig the level of parental concern and urging parents to present to healthcare early. A qualitative interview study including 34 parents of patients enrolled in derivation cohort revealed existing misconceptions regarding the possible negative effects of fever, which often were a result of unfulfilled educational and emotional needs when caring for a febrile child. This study suggests that educational intervention is necessary to reduce “fever phobia” in parents and to improve the diagnostic reliability of parental concern.
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    Diagnostic Value of Clinical Presentation, Parental Concern, and Clinician’s Non-Analytical Reasoning in Identifying Serious Bacterial Infections in Febrile Children. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2022) Urbāne, Urzula Nora; Pavāre, Jana; Zavadska, Dace
    Fever is one of the main reasons for visits to paediatric emergency departments (ED). Although in most cases the underlying cause is self-limiting viral infections, 4 to 25 % of children visiting ED with fever develop serious bacterial infections (SBI), which are significant causes of childhood mortality, even in developed countries. Due to high number of patients visiting ED with febrile illness, rapid discrimination between children with and without possible SBI is challenging.This study aimed to improve early recognition of SBI in children who present to ED by assessing the diagnostic value of clinical signs at presentation, clinician’s non-analytical reasoning, defined as “gut feeling” of serious illness and “sense of reassurance”, and parental concern of different / more severe illness. Based on these variables, derivation and external validation of two clinical prediction models (CPMs) for SBI was performed, and the performance of a CPM based on clinical variables alone was compared to a model integrating clinical features together with variables of non-analytical reasoning. The models were derived from a dataset of 517 febrile patients presenting to the ED of Children’s Clinical University Hospital (CCUH) in Riga, and externally validated in a dataset of 188 patients prospectively enrolled in six regional hospitals in Latvia.While the prognostic value of clinician’s “gut feeling” as an independent variable for diagnosing SBI was limited, “sense of reassurance” was significantly predictive of absence of SBI, and the performance of the CPM 2 integrating the non-analytical variables with clinical features was superior in both derivation (Receiver Operating Characteristic curve (ROC) Area Under Curve (AUC) 0.783, 95 % confidence interval (CI) 0.727–0.839) and validation cohorts (ROC AUC 0.752, 95 % CI 0.674–0.830), when compared to the performance of the CPM 1, which was based solely on clinical variables (ROC AUC in derivation population 0.738, 95 % CI 0.688–0.788, in validation population 0.677, 95 % CI 0.586–0.767). Both CPMs had moderate ability to predict SBI in febrile children presenting to ED and acceptable performance in the validation cohort. A scoring system based on the superior prediction model was created to distinguish between patients with high or low risk of SBI, as well as to identify patients in diagnostic “grey area”, in which the severity of manifestations of SBI and mild infections overlapped. Contrary to studies in primary care performed in other European countries, parental concern was not significantly predictive of SBI. Elements of fever-related anxiety were identified as factors influencig the level of parental concern and urging parents to present to healthcare early. A qualitative interview study including 34 parents of patients enrolled in derivation cohort revealed existing misconceptions regarding the possible negative effects of fever, which often were a result of unfulfilled educational and emotional needs when caring for a febrile child. This study suggests that educational intervention is necessary to reduce “fever phobia” in parents and to improve the diagnostic reliability of parental concern.
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    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 University
    Children 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.
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    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 University
    To 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.
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    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 University
    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 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.
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    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 University
    Mechanisms 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.
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    Klīnisko pazīmju kopuma, vecāku un ārstu intuitīvā novērtējuma nozīme smagu bakteriālu infekciju diagnostikā bērniem ar drudzi. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2022) Urbāne, Urzula Nora; Pavāre, Jana; Zavadska, Dace
    Drudzis bērniem ir viens no biežākajiem palīdzības meklēšanas iemesliem Neatliekamās palīdzības nodaļā. Lai gan visbiežāk drudzi izraisa pašlimitējošas vīrusu infekcijas, 4 līdz 25 % gadījumu bērniem, kuri vērsušies Neatliekamās palīdzības nodaļā ar drudzi, tiek diagnosticētas smagas bakteriālas infekcijas (SBI), kas joprojām ir viens no biežākajiem bērnu mirstības cēloņiem arī attīstītajās valstīs. Ātra febrilu pacientu ar iespējamu SBI atpazīšana ir nozīmīgs izaicinājums klīnicistiem lielās pacientu plūsmas Neatliekamās palīdzības nodaļā dēļ. Šī pētījuma mērķis bija uzlabot agrīnu SBI atpazīšanu bērniem ar drudzi, kuri vēršas pēc palīdzības Neatliekamās palīdzības nodaļā, izvērtējot dažādu klīnisko pazīmju, klīnicista intuitīvā novērtējuma (“gut feeling”) par iespējamu smagu saslimšanu, klīnicista intuitīvā novērtējuma par iespējamu pašlimitējošu saslimšanu (“sense of reassurance”), kā arī vecāku bažu par atšķirīgi / smagāk noritošu saslimšanu bērnam (parental concern) diagnostisko vērtību. Balstoties uz minētajiem faktoriem kā mainīgajiem, tika izveidoti un validēti divi klīniskie paredzēšanas modeļi. Modeļa, kurā iekļauti tikai klīniskie parametri, efektivitāte tika salīdzināta ar otra modeļa, kurā tika iekļauti klīnicista instinktu raksturojošie parametri, efektivitāti SBI atpazīšanā. Modeļi tika izveidoti, balsoties uz 517 prospektīvi iekļautu pacientu klīnisko informāciju, kuri pēc palīdzības vērsās Bērnu klīniskās universitātes slimnīcas (BKUS) Neatliekamās palīdzības nodaļā. Rezultāti tika validēti, balstoties uz datiem, kas iegūti no 188 prospektīvi iekļautu pacientu populācijas, kuri pēc palīdzības bija vērsušies sešās Latvijas reģionālajās slimnīcās.Lai gan klīnicista intuitīvā novērtējuma (“gut feeling”) par iespējamu smagu saslimšanu prognostiskā vērtība SBI atpazīšanā bija ierobežota, klīnicista intuitīvais novērtējums par iespējamu pašlimitējošu saslimšanu “sense of reassurance” bija nozīmīgs prognostisks rādītājs SBI neesamībai. Modelis, kurā klīnicista instinktu raksturojošie mainīgie tika integrēti kopā ar klīniskajām pazīmēm, efektīvāk atpazina SBI gan izveides (receiver operating characteristic curve (ROC) area under curve (AUC) 0,783, 95 % ticamības intervāls (TI) 0,727–0,839), gan validācijas populācijās (ROC AUC 0,752, 95 % TI 0,674–0,830), salīdzinot ar modeli, kurā tika iekļauti tikai klīniskie parametri (ROC AUC izveides populācijā – 0,738, 95 % TI 0,688–0,788, validācijas populācijā – 0,677, 95 % TI 0,586–0,767). Abiem modeļiem bija mērena efektivitāte SBI atpazīšanā drudža pacientiem, kuri vērsās pēc palīdzības Neatliekamās palīdzības nodaļā. Pamatojoties uz efektīvāko modeli, tika izveidota uz punktiem balstīta drudža pacientu vērtēšanas sistēma, kas vienkāršoja pacientu ar augstu vai zemu SBI risku atpazīšanu, kā arī nodalīja daļu pacientu tā sauktajā diagnostikas pelēkajā zonā, kurā SBI un vieglāk noritošu infekciju klīnisko izpausmju smagums bija līdzīgs. Atšķirībā no citu Eiropas valstu pētījumu rezultātiem primārās aprūpes līmenī vecāku bažu par atšķirīgi / smagāk noritošu saslimšanu prognostiskā vērtība SBI atpazīšanā pētījuma populācijā bija zema. Vecāku bažu līmeni ietekmēja satraukums, ko izraisīja drudzis bērnam jeb tā dēvētā drudža fobija, kas savukārt mudināja vecākus drudža gadījumā bērnam vērsties pēc palīdzības agrīni. Kvalitatīvā pētījumā, balstoties uz 34 vecāku intervijām, kuru bērni tika iekļauti BKUS kohortā, tika noskaidrots, ka vecākiem pastāv mīti par drudža iespējamu kaitīgu ietekmi uz bērna organismu. Šo nepareizo, uz pierādījumiem nebalstīto pieņēmumu saglabāšanos nereti veicināja nepietiekams klīnicistu skaidrojums par bērnu ar drudzi aprūpi, kā arī emocionālā atbalsta trūkums no medicīnas personāla puses, vecākiem rūpējoties par bērnu, kas slims ar drudzi. Pētījums parāda, ka “drudža fobijas” mazināšanai un vecāku bažu kā klīniskā rādītāja precizitātes uzlabošanai nepieciešama plašāka vecāku izglītošana par to, kā izvērtēt un aprūpēt bērnu ar drudzi.
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    LONG COVID-19 SYMPTOM PROFILE IN CHILDREN AND ADOLESCENTS TESTED FOR SARS-COV-2
    (2024-02-01) Meiere, Anija; Smane, Liene; Ķīvīte-Urtāne, Anda; Kļaviņa, Lizete; Račko, Iveta; Roģe, Ieva; Pučuka, Zanda; Pavāre, Jana; Department of Paediatrics; Department of Public Health and Epidemiology
    Even though more than two years have passed since the global pandemic started, COVID-19 continues to impact children all over the world. The most common course of SARS-CoV-2 infection in children is short term with no or mild symptoms. However, there are two long-term consequences: long COVID and multisystem inflammatory syndrome (MIS-C). A post-COVID19 programme for children has been created in Latvia; however, we know that the availability of this service is limited. We developed an online survey so that we could screen for those paediatric patients with long COVID who needed to see a specialist as soon as possible. The cross-sectional study from 1 November 2021 to 27 March 2022 included 220 patients. In our study, the most frequent symptoms in the age group < 1.5 years were irritability (50%), mood swings (50%), persistent cough (33.3%) and loss of appetite (33.3%). In the group aged 1.5–5 years, a persistent cough (54.4%), mood swings (43.9%) and irritability (42.1%) were the most common symptoms, while in the group aged 6–10 years, fatigue (56.6%), abdominal pain (55.3%), headache (50%), and mood swings (50%) were seen most often. Meanwhile in the 11–18 age group, impaired physical activity (66.7%), fatigue (62.3%) and drowsiness (62.3%) were the most frequently seen symptoms.
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    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 University
    BACKGROUND: 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.
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    Qualitative Study on Family Health-Related Quality of Life Due to Pediatric COVID-19 Infection In Latvia
    (2024-02-01) Pučuka, Zanda; Meiere, Anija; Ķīvīte-Urtāne, Anda; Smane, Liene; Stars, Inese; Roģe, Ieva; Račko, Iveta; Kļaviņa, Lizete; Pavāre, Jana; Department of Paediatrics; Institute of Public Health; Department of Public Health and Epidemiology
    The coronavirus disease (COVID-19) pandemic and ensuing public health policies have immensely affected the lives of billions of people worldwide and been challenging for families. There have been studies exploring mental health of different age groups during a pandemic, but few have focused on family health-related quality of life (HRQoL). This qualitative study investigates the emotional well-being of families while caring for an acutely sick child with COVD-19, using semi-structured in-depth interviews. The results demonstrate that it is one of the most affected components of the family HRQoL.
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    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 University
    Background. 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.
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    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 University
    BACKGROUND: 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.
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    SARS-CoV-2 seroprevalence among children in Latvia : a cross-sectional study
    (2023-02-10) Sapronova, Krista; Kaķe, Rūta; Pavāre, Jana; Grāvele, Dagne; Šēla, Ivita; Ērgle, Estere; Isarova, Dana; Grīnberga, Zanda; Zavadska, Dace; Rīga Stradiņš University
    Coronavirus disease 2019 (COVID-19) is a major global health concern. In contrast to adults, the course of the disease has been observed to be mild or even asymptomatic in children. It is therefore both clinically and epidemiologically important to measure the seroprevalence in children and adolescents to discern the overall morbidity of the disease and to compare these findings with similar data collected globally. We conducted a cross-sectional study between March and July of 2022 at the Children Clinical University Hospital in Riga, Latvia, to evaluate the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Participants aged 0 to 18 years were enrolled during hospitalization for reasons other than COVID19. The levels of SARS-CoV-2 spike protein and nucleocapsid antibodies were measured in blood samples. The possibility of transplacental antibody transport was evaluated by directly interviewing the mothers of participants aged 18 months and younger. Various demographic and epidemiological risk factors and their association with seroprevalence were analyzed. Positive SARSCoV-2 nucleocapsid antibodies were designated the main criterion for seropositivity. Of 200 enrolled children, 173 were found to be seropositive, resulting in an overall seroprevalence of 86.5%. The highest seroprevalence was detected in children and adolescents aged 12 to 18 years. With the progression of the COVID-19 pandemic, the seroprevalence in children has increased significantly. We found that almost 1-third of seropositive children in our study population were unaware of being previously infected with SARS-CoV-2 due to an asymptomatic course of the disease. Our study findings pertaining to high seropositivity among children and adolescents might be beneficial for public authorities to adapt epidemiological strategies and prevention measures. The high seroprevalence rate reported here and in many other populations around the world suggests that COVID-19 will likely become one of the many seasonal viral infections.
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