6 research outputs found
Hypoxia facilitates neurogenic dural plasma protein extravasation in mice : a novel animal model for migraine pathophysiology
New integral formulas involving the Meijer G-function are derived using recent results concerning distributional characterisations and distributional transformations in probability theory
Hypoxia facilitates neurogenic dural plasma protein extravasation in mice
Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice. Considering the role 5-HT receptors play in hypoxia-induced pulmonary vessel muscularization, we were encouraged to keep mice under hypoxic conditions and tested whether this treatment will render them susceptible to mCPP-induced dural PPE. Following four-week of hypoxia, PPE, associated with increased transendothelial transport, was induced by mCPP. The effect was blocked by sumatriptan. Chronic application of 5-HT receptor or nitric oxide synthase blockers during hypoxia prevented the development of susceptibility. Here we present a migraine model that distinguishes between a migraine-like state (hypoxic mice) and normal, normoxic mice and mimics processes that are related to chronic activation of 5-HT receptors under hypoxia. It seems striking, that chronic endogenous activation of 5-HT receptors is crucial for the sensitization since 5-HT receptor antagonists have strong, albeit delayed migraine prophylactic efficacy
Einsatz von kĂŒnstlicher Intelligenz im Screening auf diabetische Retinopathie an einer diabetologischen Schwerpunktklinik
Hintergrund
Seit 2018 ist mit IDx-DR ein Verfahren auf dem Markt, welches den Grad der diabetischen Retinopathie (DR) mittels kĂŒnstlicher Intelligenz (KI) bestimmt.
Methoden
Wir haben IDx-DR in die Sprechstunde an einer diabetologischen Schwerpunktklinik integriert und berichten ĂŒber die Ăbereinstimmung zwischen IDx-DR (IDx Technologies Inc., Coralville, IA, USA) und Funduskopie sowie IDx-DR und ophthalmologischer Bildbeurteilung sowie ĂŒber den Einfluss unterschiedlicher Kamerasysteme.
Ergebnisse
Mit der Topcon-Kamera (nâŻ=â456; NW400, Topcon Medical Systems, Oakland, NJ, USA) konnte im Vergleich zur Zeiss-Kamera (nâŻ=â47; Zeiss VISUCAM 500, Carl Zeiss Meditec AG, Jena, Deutschland) hĂ€ufiger eine ausreichende BildqualitĂ€t in Miosis erreicht werden. Insgesamt war bei etwa 60âŻ% der Patienten eine IDx-DR-Analyse in Miosis möglich. Alle Patienten, bei denen keine IDx-DR-Analyse in Miosis möglich war, konnten in Mydriasis funduskopiert werden. Innerhalb der Gruppe der auswertbaren Befunde zeigte sich eine Ăbereinstimmung zwischen IDx-DR und augenĂ€rztlicher Funduoskopie in ca. 55âŻ%, ein ĂberschĂ€tzen des Schweregrads durch IDx-DR in ca. 40âŻ% und ein UnterschĂ€tzen in ca. 4âŻ%. Die SensitivitĂ€t (SpezifitĂ€t) fĂŒr das Erkennen einer schweren, behandlungsbedĂŒrftigen Retinopathie lag bei 95,7âŻ% (89,1âŻ%) fĂŒr FĂ€lle mit auswertbaren Fundusaufnahmen und bei 65,2âŻ% (66,7âŻ%), wenn alle FĂ€lle betrachtet werden (inklusive derjeniger ohne verwertbare Aufnahme in Miosis). Der Kappa-Koeffizient zeigt mit 0,334 (pâŻ<â0,001) eine ausreichende Ăbereinstimmung zwischen IDx-DR und Ă€rztlicher Bildauswertung anhand des Fundusfotos unter BerĂŒcksichtigung aller Patienten mit auswertbarer IDx-DR-Analyse. Der Vergleich zwischen IDx-DR mit der Ă€rztlichen Funduskopie ergibt unter denselben Voraussetzungen eine geringe Ăbereinstimmung mit einem Kappa-Wert von 0,168 (pâŻ<â0,001).
Schlussfolgerung
Die vorliegende Studie zeigt Möglichkeiten und Grenzen des KI-gestĂŒtzten DR-Screenings auf. Eine wesentliche EinschrĂ€nkung liegt in der Tatsache, dass bei ca. 40âŻ% der Patienten keine ausreichenden Aufnahmen in Miosis gewonnen werden konnten. Wenn ausreichende Aufnahmen vorlagen, stimmten IDx-DR und augenĂ€rztliche Diagnose in ĂŒber 50âŻ% der FĂ€lle ĂŒberein. Ein UnterschĂ€tzen des Schweregrades durch IDx-DR kam selten vor. FĂŒr die Integration in augenĂ€rztlich unterstĂŒtzten Sprechstunden erscheint uns das System grundsĂ€tzlich geeignet. Die hohe Rate an fehlenden Aufnahmen in Miosis stellt allerdings eine Limitation dar, die einen Einsatz ohne augenĂ€rztliche Kontrollmöglichkeit schwierig erscheinen lĂ€sst.Background
In 2018, IDx-DR was approved as a method to determine the degree of diabetic retinopathy (DR) using artificial intelligence (AI) by the FDA.
Methods
We integrated IDx-DR into the consultation at a diabetology focus clinic and report the agreement between IDx-DR and fundoscopy as well as IDx-DR and ophthalmological image assessment and the influence of different camera systems.
Results
Adequate image quality in miosis was achieved more frequently with the Topcon camera (nâŻ=â456; NW400, Topcon Medical Systems, Oakland, NJ, USA) compared with the Zeiss camera (nâŻ=â47; Zeiss VISUCAM 500, Carl Zeiss Meditec AG, Jena, Germany). Overall, IDx-DR analysis in miosis was possible in approximately 60% of the patients. All patients in whom IDx-DR analysis in miosis was not possible could be assessed by fundoscopy with dilated pupils. Within the group of images that could be evaluated, there was agreement between IDx-DR and ophthalmic fundoscopy in approximately 55%, overestimation of severity by IDx-DR in approximately 40% and underestimation in approximately 4%. The sensitivity (specificity) for detecting severe retinopathy requiring treatment was 95.7% (89.1%) for cases with fundus images that could be evaluated and 65.2% (66.7%) when all cases were considered (including those without images in miosis which could be evaluated).
The kappa coefficient of 0.334 (pâŻ<â0.001) shows sufficient agreement between IDx-DR and physicianâs image analysis based on the fundus photograph, considering all patients with IDx-DR analysis that could be evaluated. The comparison between IDx-DR and the physicianâs funduscopy under the same conditions shows a low agreement with a kappa value of 0.168 (pâŻ<â0.001).
Conclusion
The present study shows the possibilities and limitations of AI-assisted DR screening. A major limitation is that sufficient images cannot be obtained in miosis in approximately 40% of patients. When sufficient images were available the IDx-DR and ophthalmological diagnosis matched in more than 50% of cases. Underestimation of severity by IDx-DR occurred only rarely. For integration into an ophthalmologistâs practice, this system seems suitable. Without access to an ophthalmologist the high rate of insufficient images in miosis represents an important limitation
A Community-Based Survey of Abdominal Pain Prevalence, Characteristics, and Health Care Use Among Children
Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation.
Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure.
Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64).
Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely