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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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- Fadanelli, S., et al.
(författare)
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Four-Spacecraft Measurements of the Shape and Dimensionality of Magnetic Structures in the Near-Earth Plasma Environment
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 124:8, s. 6850-6868
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Tidskriftsartikel (refereegranskat)abstract
- We present a new method for determining the main relevant features of the local magnetic field configuration, based entirely on the knowledge of the magnetic field gradient four‐spacecraft measurements. The method, named “magnetic configuration analysis” (MCA), estimates the spatial scales on which the magnetic field varies locally. While it directly derives from the well‐known magnetic directional derivative and magnetic rotational analysis procedures (Shi et al., 2005, htpps://doi.org/10.1029/2005GL022454; Shen et al., 2007, https://doi.org/10.1029/2005JA011584), MCA was specifically designed to address the actual magnetic field geometry. By applying MCA to multispacecraft data from the Magnetospheric Multiscale (MMS) satellites, we perform both case and statistical analyses of local magnetic field shape and dimensionality at very high cadence and small scales. We apply this technique to different near‐Earth environments and define a classification scheme for the type of configuration observed. While our case studies allow us to benchmark the method with those used in past works, our statistical analysis unveils the typical shape of magnetic configurations and their statistical distributions. We show that small‐scale magnetic configurations are generally elongated, displaying forms of cigar and blade shapes, but occasionally being planar in shape like thin pancakes (mostly inside current sheets). Magnetic configurations, however, rarely show isotropy in their magnetic variance. The planar nature of magnetic configurations and, most importantly, their scale lengths strongly depend on the plasma β parameter. Finally, the most invariant direction is statistically aligned with the electric current, reminiscent of the importance of electromagnetic forces in shaping the local magnetic configuration.
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- Maas, R. R., et al.
(författare)
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Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
- 2017
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 82:6, s. 1004-1015
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Tidskriftsartikel (refereegranskat)abstract
- Objective: 3-Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. Methods: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic “putaminal eye” was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. Interpretation: MEGDHEL syndrome is a progressive deafness–dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004–1015. © 2017 American Neurological Association
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- Heard, J. M., et al.
(författare)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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- Schiff, MH, et al.
(författare)
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Integrated safety in tocilizumab clinical trials
- 2011
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:5, s. R141-
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