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- Baumgartner, T., et al.
(author)
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A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies
- 2021
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In: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:1, s. 160-170
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Journal article (peer-reviewed)abstract
- Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers. © 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
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- Chahla, J., et al.
(author)
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Posterolateral corner of the knee: an expert consensus statement on diagnosis, classification, treatment, and rehabilitation
- 2019
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In: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:8, s. 2520-2529
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Journal article (peer-reviewed)abstract
- PurposeTo develop a statement on the diagnosis, classification, treatment, and rehabilitation concepts of posterolateral corner (PLC) injuries of the knee using a modified Delphi technique.MethodsA working group of three individuals generated a list of statements relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries to form the basis of an initial survey for rating by an international group of experts. The PLC expert group (composed of 27 experts throughout the world) was surveyed on three occasions to establish consensus on the inclusion/exclusion of each item. In addition to rating agreement, experts were invited to propose further items for inclusion or to suggest modifications of existing items at each round. Pre-defined criteria were used to refine item lists after each survey. Statements reaching consensus in round three were included within the final consensus document.ResultsTwenty-seven experts (100% response rate) completed three rounds of surveys. After three rounds, 29 items achieved consensus with over 75% agreement and less than 5% disagreement. Consensus was reached in 92% of the statements relating to diagnosis of PLC injuries, 100% relating to classification, 70% relating to treatment and in 88% of items relating to rehabilitation statements, with an overall consensus of 81%.ConclusionsThis study has established a consensus statement relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries. Further research is needed to develop updated classification systems, and better understand the role of non-invasive and minimally invasive approaches along with standardized rehabilitation protocols.Level of evidenceConsensus of expert opinion, Level V.
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- Giannoni, E, et al.
(author)
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Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia
- 2022
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In: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11, s. e2243691-
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Journal article (peer-reviewed)abstract
- Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure.ObjectiveTo compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.Design, Setting, and ParticipantsThis is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022.ExposuresExposure to antibiotics started in the first postnatal week.Main Outcomes and MeasuresThe main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality.ResultsA total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered.Conclusions and RelevanceThe findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.
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- Lagae, Cis Raf, et al.
(author)
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Raising the observed metallicity floor with a 3D non-LTE analysis of SDSS J102915.14+172927.9
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672, s. A90-A90
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Journal article (peer-reviewed)abstract
- Context. The first stars marked the end of the cosmic dark ages, produced the first heavy elements, and set the stage for the formation of the first galaxies. Accurate chemical abundances of ultra metal-poor stars ([Fe/H] < −4) can be used to infer the properties of the first stars and thus the formation mechanism for low-mass second-generation stars in the early Universe. Spectroscopic studies have shown that most second-generation stars are carbon enhanced. A notable exception is SDSS J102915.14+172927.9, which is the most metal-poor star known to date, largely by virtue of the low upper limits of the carbon abundance reported in earlier studies.Aims. We re-analysed the composition of SDSS J102915.14+172927.9 with the aim of providing improved observational constraints on the lowest metallicity possible for low-mass star formation and constraining the properties of its Population III progenitor star.Methods. We developed a tailored three-dimensional model atmosphere for SDSS J102915.14+172927.9 with the Stagger code, making use of an improved surface gravity estimate based on the Gaia DR3 parallax. Snapshots from the model were used as input in the radiative transfer code Balder to compute 3D non-local thermodynamic equilibrium (non-LTE) synthetic spectra. These spectra were then used to infer abundances for Mg, Si, Ca, Fe, and Ni as well as upper limits on Li, Na, and Al. Synthetic 3D LTE spectra were computed with Scate to infer the abundance of Ti and upper limits on C and N.Results. In contrast to earlier works based on 1D non-LTE corrections applied to 3D LTE results, we are able to achieve ionisation balance for Ca I and Ca II when employing our consistent 3D non-LTE treatment. The elemental abundances are systematically higher than those found in earlier works. In particular, [Fe/H] is increased by 0.57 dex, and the upper limits of C and N are larger by 0.90 dex and 1.82 dex, respectively.Conclusions. We find that Population III progenitors with masses 10–20 M⊙ exploding with energy E ⪅ 3 × 1051 erg can reproduce our 3D non-LTE abundance pattern. Our 3D non-LTE abundances are able to better constrain the progenitor mass and explosion energy as compared to our 1D LTE abundances. Contrary to previous work, we obtain higher upper limits on the carbon abundance that are ‘marginally consistent’ with star formation through atomic line cooling, and consequently, these results prevent us from drawing strong conclusions about the formation mechanism of this low-mass star.
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