Bruk av START/STOPP-kriterier for å optimalisere medikamentforskrivning blant pasienter på en geriatrisk avdeling.

Bakgrunn Suboptimal forskrivning hos pasienter over 65 år er et kjent problem, og er forbundet med økt morbiditet og sykehusinnleggelser. Suboptimal forskrivning kan inndeles i overbruk/polyfarmasi, uhensiktsmessig bruk og underbruk. Kunnskapsgrunnlag: START/STOPP er kriterier for å vurdere den totale forskrivningen av medikamenter til eldre pasienter og identifisere medikamenter som bør startes opp med eller seponeres. Det er evidens for at innføring av START/STOPP reduserer suboptimal forskrivning, noe som kan måles ved å bruke MAI (medication appropriateness index) som indikator. Tiltak og metode Vårt tiltak er å implementere START/STOPP kriteriene i akuttgeriatrisk avdeling ved Oslo Universitetssykehus, Ullevål, og se om dette kan optimalisere medikamentforskrivning hos eldre. I første omgang legges det opp som et pilotprosjekt som omfatter en visittgruppe på avdelingen. Etter en evaluering av prosjektet vurderes det om man skal innføre dette på hele avdelingen. Organisering Det blir organisert et møte der det blir orientert om problemet og tiltaket. Deretter får legene som er ansvarlig for førstedagsnotatene til pasientene ansvar for å gjennomgå medikamentlisten med START/STOPP-kriteriene. Man vil ha et møte underveis for å håndtere eventuelle problemstillinger som dukker opp underveis, og et evalueringsmøte etter at resultatet av prosjektet er klart. Resultater / Vurdering Resultatet av prosjektet vurderes i forhold til indikatoren. MAI-skåren i epikrisene sammenliknes før og etter implementering av tiltaket, for å vurdere om START/STOPP har redusert suboptimal forskrivning

Astroglial endfeet exhibit distinct Ca2+ signals during hypoosmotic conditions

Astrocytic endfeet cover the brain surface and form a sheath around the cerebral vasculature. An emerging concept is that endfeet control blood–brain water transport and drainage of interstitial fluid and waste along paravascular pathways. Little is known about the signaling mechanisms that regulate endfoot volume and hence the width of these drainage pathways. Here, we used the genetically encoded fluorescent Ca2+ indicator GCaMP6f to study Ca2+ signaling within astrocytic somata, processes, and endfeet in response to an osmotic challenge known to induce cell swelling. Acute cortical slices were subjected to artificial cerebrospinal fluid with 20% reduction in osmolarity while GCaMP6f fluorescence was imaged with two‐photon microscopy. Ca2+ signals induced by hypoosmotic conditions were observed in all astrocytic compartments except the soma. The Ca2+ response was most prominent in subpial and perivascular endfeet and included spikes with single peaks, plateau‐type elevations, and rapid oscillations, the latter restricted to subpial endfeet. Genetic removal of the type 2 inositol 1,4,5‐triphosphate receptor (IP3R2) severely suppressed the Ca2+ responses in endfeet but failed to affect brain water accumulation in vivo after water intoxication. Furthermore, the increase in endfoot Ca2+ spike rate during hypoosmotic conditions was attenuated in mutant mice lacking the aquaporin‐4 anchoring molecule dystrophin and after blockage of transient receptor potential vanilloid 4 channels. We conclude that the characteristics and underpinning of Ca2+ responses to hypoosmotic stress differ within the astrocytic territory and that IP3R2 is essential for the Ca2+ signals only in subpial and perivascular endfeet

Therapy-induced deletion in 11q23 leading to fusion of KMT2A with ARHGEF12 and development of B lineage acute lymphoplastic leukemia in a child treated for acute myeloid leukemia caused by t(9;11)(p21;q23)/ KMT2A-MLLT3

Background/Aim: Fusion of histone-lysine N-methyltransferase 2A gene (KMT2A) with the Rho guanine nucleotide exchange factor 12 gene (ARHGEF12), both located in 11q23, was reported in some leukemic patients. We report a KMT2A-ARHGEF12 fusion occurring during treatment of a pediatric acute myeloid leukemia (AML) with topoisomerase II inhibitors leading to a secondary acute lymphoblastic leukemia (ALL). Materials and Methods: Multiple genetic analyses were performed on bone marrow cells of a girl initially diagnosed with AML. Results: At the time of diagnosis with AML, the t(9;11)(p21;q23)/KMT2A-MLLT3 genetic abnormality was found. After chemotherapy resulting in AML clinical remission, a 2 Mb deletion in 11q23 was found generating a KMT2A-ARHGEF12 fusion gene. When the patient later developed B lineage ALL, a t(14;19)(q32;q13), loss of one chromosome 9, and KMT2A-ARHGEF12 were detected. Conclusion: The patient sequentially developed AML and ALL with three leukemia-specific genomic abnormalities in her bone marrow cells, two of which were KMT2A-rearrangements

Genetic Subtypes and Outcome of Patients Aged 1 to 45 Years Old With Acute Lymphoblastic Leukemia in the NOPHO ALL2008 Trial

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