Changes in inpatient brain arteriovenous malformation management in the United States following the ARUBA trial: analysis of an interrupted time series design.

The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates METHODS: This study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009-2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. RESULTS: Elective and asymptomatic patient admissions declined 2009-2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. CONCLUSIONS: The publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA's conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA's findings in managing unruptured brain AVMs.

Plasmodium berghei parasite transformed with green fluorescent protein for screening blood schizontocidal agents.

High priority has been given to new assays that facilitate and accelerate the development of novel antimalarial compounds. Unlike evaluation of drugs in vitro, in which new approaches have been used to expedite identification of parasites, the conventional in vivo murine assay requires determination of parasitemia by light microscopy, an incompatible technique to test large numbers of drugs. We have investigated the possibility of using an autonomously fluorescent Plasmodium berghei strain, stably transformed with the green fluorescent protein, to rapidly quantify parasite growth by flow cytometry. The major improvement of this method is that P. berghei line transformed with green fluorescent protein parasites can be quickly and specifically detected in a drop of parasite-infected blood without any manipulation of the sample. Our results showed a clear correlation between the numbers of fluorescent cells detected by flow cytometry and conventional parasitemia, including a correspondence in the peaks of parasitemia. The validation of P. berghei line transformed with green fluorescent protein for chemotherapy studies was performed by evaluating its response to conventional antimalarial drugs such as chloroquine, quinine and sodium artesunate. The results of drug-susceptibility assays as determined by flow cytometry were comparable with those obtained by microscopic examination of Giemsa-stained slides. This PbGFP parasite should prove to be a rapid, simple and sensitive tool for the examination of the large number of compounds and conditions involved in the initial stages of drug development.