Browsing by Subject "paediatrics"

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  • Malmström, Kristiina; Lohi, Jouko; Malmberg, Leo Pekka; Kotaniemi-Syrjänen, Anne; Lindahl, Harry; Sarna, Seppo; Pelkonen, Anna S.; Mäkelä, Mika J. (2020)
    Abstract Background The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. Objective To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Methods Inclusion criteria: full-term, 3-23 months of age; doctor diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body pletysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analyzed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Results Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function correlated with AHR (p=0.047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (p=0.057 and 0.056 respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (p=0.031). Conclusions & Clinical Relevance These findings don not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.
  • Broderick, David T. J.; Waite, David W.; Marsh, Robyn L.; Camargo, Carlos A.; Cardenas, Paul; Chang, Anne B.; Cookson, William O. C.; Cuthbertson, Leah; Dai, Wenkui; Everard, Mark L.; Gervaix, Alain; Harris, J. Kirk; Hasegawa, Kohei; Hoffman, Lucas R.; Hong, Soo-Jong; Josset, Laurence; Kelly, Matthew S.; Kim, Bong-Soo; Kong, Yong; Li, Shuai C.; Mansbach, Jonathan M.; Mejias, Asuncion; O'Toole, George A.; Paalanen, Laura; Perez-Losada, Marcos; Pettigrew, Melinda M.; Pichon, Maxime; Ramilo, Octavio; Ruokolainen, Lasse; Sakwinska, Olga; Seed, Patrick C.; van der Gast, Christopher J.; Wagner, Brandie D.; Yi, Hana; Zemanick, Edith T.; Zheng, Yuejie; Pillarisetti, Naveen; Taylor, Michael W. (2021)
    Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.
  • Rehn, Marius; Chew, Michelle S.; Olkkola, Klaus T.; Sigurosson, Martin Ingi; Yli-Hankala, Arvi; Moller, Morten Hylander (2021)
    Background The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. The guideline can serve as a useful decision aid for clinicians managing children with suspected and confirmed septic shock and sepsis-associated organ dysfunction.
  • Hurme, Pekka; Homil, Kiara; Lehtinen, Pasi; Turunen, Riitta; Vahlberg, Tero; Vuorinen, Tytti; Camargo, Carlos A. Jr Jr; Gern, James E.; Jartti, Tuomas (2021)
    Background Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta(2)-agonist in this clinical scenario. Objective To study post hoc the short-term (up to 2 months) efficacy of inhaled beta(2)-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2-4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group x treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). Conclusions In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.
  • Vermeulen, Eric; van den Anker, John N.; Della Pasqua, Oscar; Hoppu, Kaarlo; van der Lee, Johanna H.; GRiP (2017)
    Objectives In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT. Methods Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies. Key findings The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose-finding study. Conclusions The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.
  • Cloesmeijer, Michael E.; van Esdonk, Michiel J.; Lynn, Anne M.; Smits, Anne; Tibboel, Dick; Daali, Youssef; Olkkola, Klaus T.; Allegaert, Karel; Mian, Paola (2021)
    Aims Ketorolac is a non-steroidal anti-inflammatory racemic drug with analgesic effects only attributed to its S-enantiomer. The aim of this study is to quantify enantiomer-specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants. Methods Data were pooled from 5 different studies in adults, children, and infants, with 1020 plasma concentrations following single intravenous ketorolac administration. An allometry-based enantiomer-specific population PK model was developed with NONMEM 7.3. Simulations were performed in typical adults and infants to investigate differences in S- and R-ketorolac exposure. Results S- and R-ketorolac PK were best described with a 3- and a 2-compartment model respectively. The allometry-based PK parameters accounted for changes between populations. No maturation function of ketorolac clearance could be identified. All model parameters were estimated with adequate precision (relative standard error
  • Mathioudakis, Alexander G.; Miligkos, Michael; Boccabella, Cristina; Alimani, Gioulinta S.; Custovic, Adnan; Deschildre, A.; Ducharme, Francine Monique; Kalayci, Omer; Murray, Clare; Garcia, Antonio Nieto; Phipatanakul, Wanda; Price, David; Sheikh, Aziz; Agache, Ioana Octavia; Bacharier, Leonard; Beloukas, Apostolos; Bentley, Andrew; Bonini, Matteo; Castro-Rodriguez, Jose A.; De Carlo, Giuseppe; Craig, Timothy; Diamant, Zuzana; Feleszko, Wojciech; Felton, Tim; Gern, James E.; Grigg, Jonathan; Hedlin, Gunilla; Hossny, Elham M.; Ierodiakonou, Despo; Jartti, Tuomas; Kaplan, Alan; Lemanske, Robert F.; Le Souef, Peter N.; Mäkelä, Mika J.; Mathioudakis, Georgios A.; Matricardi, Paolo; Mitrogiorgou, Marina; Morais-Almeida, Mario; Nagaraju, Karthik; Papageorgiou, Effie; Pite, Helena; Pitrez, Paulo M. C.; Pohunek, Petr; Roberts, Graham; Tsiligianni, Ioanna; Turner, Stephen; Vijverberg, Susanne; Winders, Tonya A.; Wong, Gary W. K.; Xepapadaki, Paraskevi; Zar, Heather J.; Papadopoulos, Nikolaos G. (2021)
    Introduction Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. Methods and analysis Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively. Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. Ethics and dissemination Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO registration numbers CRD42020132990, CRD42020171624.
  • Nikander, Kirsi; Hermanson, Elina; Vahlberg, Tero; Kaila, Minna; Kosola, Silja (2022)
    Objective To evaluate the association between the concerns of parents, teachers, and nurses regarding each child's well-being and the school doctor actions conducted in routine general health checks. Design A blinded, observational study. Prior to the health check parents, teachers, and nurses completed questionnaires assessing their concerns. Doctors, blinded to the responses, routinely examined all children accompanied by parents and reported their actions after each health check. Multilevel logistic regression was used to analyse the association of the concerns with the actions. Setting 21 primary schools in four municipalities in Finland. Participants Between August 2017 and August 2018, we randomly recruited 1341 children from grades 1 and 5, aged 7 and 11 years, respectively. Outcome measures Outcome measures were the respondents' concerns and the school doctor actions. The extent of concerns was assessed on a five-point Likert scale. Concern refers to Quite a lot or a great deal of concern' by at least one respondent. The school doctor actions included instructions and/or significant discussions, prescriptions, laboratory tests and/or medical imaging, scheduling of follow-up appointments, referrals to other professionals, and referrals to specialised care. Results Altogether, respondents were concerned about 47.5% of children. The top three concerns comprised growth/and or physical symptoms (22.7%), emotions (16.2%), and concentration (15.1%). All concerns were associated with some type of school doctor action (ORs: 1.66-4.27, p≤0.05); but only concerns regarding growth and/or physical symptoms were associated with all actions. Almost all concerns were associated with referrals to other professionals (ORs: 1.80-4.52, p≤0.01); emotions had the strongest association OR 4.52 (95% CI 3.00 to 6.80, p<0.0001). Conclusions Health checks by school doctors may lead to referrals of children to other professionals especially for children's psychosocial problems. This should be considered when developing the roles, training, and multiprofessional collaboration of school health care professionals. Trial registration NCT03178331.
  • Björkman, Kristoffer; Vissing, John; ostergaard, Elsebet; Bindoff, Laurence A.; de Coo, Irenaeus F. M.; Engvall, Martin; Hikmat, Omar; Isohanni, Pirjo; Kollberg, Gittan; Lindberg, Christopher; Majamaa, Kari; Naess, Karin; Uusimaa, Johanna; Tulinius, Mar; Darin, Niklas (2023)
    Background Large-scale mitochondrial DNA deletions (LMD) are a common genetic cause of mitochondrial disease and give rise to a wide range of clinical features. Lack of longitudinal data means the natural history remains unclear. This study was undertaken to describe the clinical spectrum in a large cohort of patients with paediatric disease onset. Methods A retrospective multicentre study was performed in patients with clinical onset
  • Mäklin, Tommi; Thorpe, Harry A.; Pöntinen, Anna K.; Gladstone, Rebecca A.; Shao, Yan; Pesonen, Maiju; McNally, Alan; Johnsen, Pål J.; Samuelsen, Ørjan; Lawley, Trevor D.; Honkela, Antti; Corander, Jukka (2022)
    Opportunistic bacterial pathogen species and their strains that colonise the human gut are generally understood to compete against both each other and the commensal species colonising this ecosystem. Currently we are lacking a population-wide quantification of strain-level colonisation dynamics and the relationship of colonisation potential to prevalence in disease, and how ecological factors might be modulating these. Here, using a combination of latest high-resolution metagenomics and strain-level genomic epidemiology methods we performed a characterisation of the competition and colonisation dynamics for a longitudinal cohort of neonatal gut microbiomes. We found strong inter- and intra-species competition dynamics in the gut colonisation process, but also a number of synergistic relationships among several species belonging to genus Klebsiella, which includes the prominent human pathogen Klebsiella pneumoniae. No evidence of preferential colonisation by hospital-adapted pathogen lineages in either vaginal or caesarean section birth groups was detected. Our analysis further enabled unbiased assessment of strain-level colonisation potential of extra-intestinal pathogenic Escherichia coli (ExPEC) in comparison with their propensity to cause bloodstream infections. Our study highlights the importance of systematic surveillance of bacterial gut pathogens, not only from disease but also from carriage state, to better inform therapies and preventive medicine in the future.
  • GlobalSurg Collaborative; Drake, Thomas M.; Tolonen, Matti; Leppäniemi, Ari; Sallinen, Ville; Sund, Malin (2020)
    Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.