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Use of integrated genomic surveillance by local public health authorities: recommendations based on a mixed-methods study of current adoption, applications and success factors, Germany, 2023
No full textBackgroundIntegrated genomic surveillance (IGS), i.e. the integrated analysis of pathogen whole genome sequencing and classical epidemiological data, can contribute substantially to the disease surveillance and infection prevention activities of local public health authorities (LPHAs).AimOur aim was to characterise how LPHAs use IGS, and factors required or important for their implementation, in the context of the German public health system.MethodsWe employed a mixed-methods design combining a quantitative survey of 60 LPHAs in three German states with five qualitative case studies based on LPHAs in four German localities and one state-level public health authority.ResultsApproximately half of LPHAs reported adoption of IGS; applications included outbreak analysis (n = 25), targeting and evaluation of infection control measures (n = 25 and n = 18, respectively) and characterisation of pathogen transmission chains (n = 25). Factors identified as required or important for the implementation of IGS in LPHAs included fast sample-to-result turnaround times, organisational data interpretation capabilities and clearly defined surveillance sampling strategies. Based on the case studies in which the adoption of IGS was successful, we formulate recommendations for implementing IGS at the level of LPHAs, including establishment of dedicated IGS analysis teams within LPHAs, use of user-friendly digital solutions (e.g. browser-based dashboards) for data exchange and analysis, and implementation of IGS in collaboration with local academic institutions.ConclusionOur analysis paves the way for increasing the implementation of IGS by LPHAs in Germany and other countries with similarly structured public health systems
[18F]florzolotau PET for the differential diagnosis of parkinsonism in patients with suspected 4-repeat tauopathies
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Management of apnoea in extremely preterm infants: a European survey
No full textIntroduction: Episodes of apnoea are common in extremely preterm infants (EPIs) and usually treated with caffeine and respiratory support. Understanding differences in apnoea definitions, monitoring practices, and use of respiratory stimulants is essential to improve future treatment. Methods: Between March and July 2024, one lead consultant at European tertiary neonatal intensive care units (NICUs) was invited to complete a web-based survey on respiratory practices in EPIs. We sought information how they defined apnoea and monitored for it, and how they treated it with caffeine, doxapram, and non-invasive respiratory support. Results: We received replies from 447/721 (62%) NICUs across 24 European countries. Most NICUs (74%) use both electrocardiogram electrodes and pulse oximetry for apnoea monitoring. All NICUs reported using caffeine citrate, with 102 centres (23%) starting it in the delivery room. The median loading, maintenance and maximum maintenance doses used are 20 mg/kg, 5 and 10 mg/kg/day, respectively. Caffeine is occasionally given twice daily in some NICUs (30%) and stopped at 34–35 weeks of postmenstrual age at most of them (74%). Doxapram is used at 111 (25%) NICUs, with geographical differences. Strategies for the use and escalation of non-invasive respiratory support in case of persistent apnoea are not clearly defined. Automatic closed-loop oxygen delivery is used at 25% of NICUs. Conclusion: Despite consistency in the dosing and weaning of caffeine, there is much variation in the management of apnoea in preterm infants across Europe. Future research should focus on timing and dosage of caffeine, the use of doxapram, and strategies for optimising non-invasive respiratory support
Customized protein nanoreactors for affibody-directed activation of 5-fluorcytosin in HER2-positive cells
No full textCombined MRI morphometry and source imaging guide placement of stereo-EEG electrodes in focal epilepsy with subtle or absent lesions
No full textIntroduction: Planning stereo-electroencephalography (sEEG) for focal drug-resistant epilepsy with subtle or absent lesions requires accurate non-invasive spatial information about the hypothetical organization of the epileptic focus. The targeting of individual trajectories for a limited number of invasive depth electrodes is particularly challenging in patients who have undergone prior epilepsy surgery. This study investigated how information from multimodal imaging can guide sEEG planning and enable successful epilepsy surgery in patients with non-lesional focal epilepsy.Methods: We studied 15 patients who appeared non-lesional on conventional MRI and were suspected to have mono-focal epilepsy. These patients underwent sEEG implantation between October 2019 and October 2022, based on findings from non-invasive video-EEG monitoring and multimodal imaging. Among the participants, four had undergone prior epilepsy surgery, including three who had previously undergone invasive EEG. All patients underwent high-resolution 3 T MRI and MRI morphometry (MAP) as part of their non-invasive presurgical diagnostics. Electric and magnetic source imaging were performed in patient subgroups. sEEG planning incorporated findings from the available imaging methods registered within the stereotactic planning system.Results: A median of nine sEEG electrodes (range: 7–11) were implanted in each patient, targeting both primary and secondary hypotheses about the epileptic focus location. sEEG recordings revealed a monofocal seizure onset in 12 out of 15 patients, all of whom subsequently underwent epilepsy surgery. No bleeding complications occurred. Of these patients, nine achieved Engel 1 postsurgical outcomes, while three had Engel ≥2 outcomes. Surgery was not performed in three patients due to multifocal epilepsy (n = 2) or an unidentified seizure onset zone (SOZ, n = 1). Concordance across multiple imaging modalities was associated with favorable surgical outcomes.Conclusion: In patients with focal epilepsy and subtle or absent lesions, sophisticated sEEG diagnostics guided by advanced multimodal imaging can successfully identify the seizure onset zone. When focal onset is confirmed and multifocal epilepsy is excluded through sEEG, subsequent epilepsy surgery often results in seizure-free outcomes
