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- Loeffen, Erik A. H., et al.
(författare)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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- van Houten, C. B., et al.
(författare)
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Antibiotic misuse in respiratory tract infections in children and adultsa prospective, multicentre study (TAILORED Treatment)
- 2019
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 38:3, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3years and 64.5years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p<0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p<0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.
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- Bager, Ninna, et al.
(författare)
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Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia : A NOPHO-DBH-AML study
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 183:4, s. 618-628
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Tidskriftsartikel (refereegranskat)abstract
- Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2.1 and 3.3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1.43, P = 0.03) and overall survival (OS; HR 1.48, P = 0.01). MK was associated with a poor EFS (HR 1.57, P = 0.03) but did not show an inferior OS compared to non-MK patients (HR 1.14, P = 0.62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.
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- Cohen, A., et al.
(författare)
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A multifaceted 'omics' approach for addressing the challenge of antimicrobial resistance
- 2015
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Ingår i: Future Microbiology. - : Future Medicine Ltd. - 1746-0913 .- 1746-0921. ; 10:3, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- The inappropriate use of antibiotics has severe global health and economic consequences, including the emergence of antibiotic-resistant bacteria. A major driver of antibiotic misuse is the inability to accurately distinguish between bacterial and viral infections based on currently available diagnostic solutions. A multifaceted 'omics' approach that integrates personalized patient data such as genetic predisposition to infections (genomics), natural microbiota composition and immune response to infection (proteomics and transcriptomics) together with comprehensive pathogen profiling has the potential to help physicians improve their antimicrobial prescribing practices. In this respect, the EU has funded a multidisciplinary project (TAILORED-Treatment) that will develop novel omics-based personalized treatment schemes that have the potential to reduce antibiotic consumption, and help limiting the spread of antibiotic resistance.
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- Gonzales-Siles, Lucia, et al.
(författare)
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Mass Spectrometry Proteotyping for detection, identification characterization and diagnostics of infectious bacteria in clinical respiratory-tract samples
- 2016
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Ingår i: 11th International Meeting on Microbial Epidemiological Markers (IMMEM XI) 9 - 12 March 2016, Estoril, Portugal.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background. Lower respiratory tract infection (LRTI) is the leading cause of childhood deaths in most developing countries and the world (?) and are the most common causes of hospital and out-patient visits within the EU, comprising 1 of 3 admissions annually. In general, the over-prescription and use of broad-spectrum antibiotics are common practices that lead to the evolution and development of resistance in infectious bacteria and will lead to loss of time and resources in patient handling and adverse patient outcomes. Conventional approaches have depended upon cultivation of bacteria with subsequent testing for antibiotic sensitivity. Therefore, reliable and time-effective microbiological diagnostics are essential for more effective treatment of respiratory infections. In this project, we apply state-of-the-art proteomics techniques for identifications of pathogens and antibiotic resistance from clinical samples, without prior cultivation. Material and methods. Nasopharyngeal swab samples were collected, in commercial Amies medium supplemented with 5x STGG, as a part of the EU-TAILORED-Treatment project (www.tailored-treatment.eu/). Samples were stored at -20°C until analyses. Different protocols for removal of human cells and mucus were tested, including non-ionic detergents, i.e., Igepal, Saponin, Urea-Chaps, as well as cytolysis. Samples were concentrated and analyzed by ‘proteotyping’ (1), using a Lipid-based Protein Immobilization (LPITM) technology (WO2006068619), in which intact bacterial cells or cell fractions are bound to a surface. Peptides were generated, using enzymatic digestion, and then separated and analyzed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mass spectra profiles were compared to a database of reference peptide sequences, consisting of all complete genomes of the NCBI Reference Sequence (RefSeq) Database. Results were confirmed by standard microbiology, including cultivation of bacteria in selective media, MALDI-TOF MS analyses and qPCR. Results. Proteotyping applied to clinical samples demonstrated that the number of viable bacteria and detected proteins determined were ten-times higher when nasal swabs were stored in Amies media supplemented with STGG 5X media compared to Amies media without STGG, after 1 and 2 months of storage at -70C. Among the different protocols tested to remove human biomaterial, all treatments proved effective to varying degrees, although the Igepal treatment was able to retain the highest number of discriminatory peptides. Using proteotyping, we were able to identify the pathogenic bacteria directly within clinical samples (nasopharyngeal and nasal swabs) that had been identified to be positive for respiratory infectious bacteria by standard methodologies at clinical bacteriology laboratories at Sahlgrenska University Hospital (Sweden) or Universitair Medisch Centrum Utrecht (Netherlands). Conclusions. Proteotyping of infectious bacteria, using tandem LC-MS/MS enabled the differentiation and identification of infectious bacteria in clinical samples from LRTIs. It has high levels of resolution and highly reproducible detection of protein biomarkers. Proteotyping identified biomarkers for species- and sub-species-level strain discrimination and antibiotic resistance, all from single MS analyses. 1) Karlsson et al., 2015. Syst. Appl. Microbiol. 38 :246-257.
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