Bmc Med
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Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. ⋯ Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.
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Mass drug administration and mass-screen-and-treat interventions have been used to interrupt malaria transmission and reduce burden in sub-Saharan Africa. Determining which strategy will reduce costs is an important challenge for implementers; however, model-based simulations and field studies have yet to develop consensus guidelines. Moreover, there is often no way for decision-makers to directly interact with these data and/or models, incorporate local knowledge and expertise, and re-fit parameters to guide their specific goals. ⋯ The observed spatial variability and dependence on specified cost values support not only the need for location-specific intervention approaches but also the need to move beyond standard modeling approaches and towards interactive tools which allow implementers to engage directly with data and models. We believe that the framework demonstrated in this article will help connect modeling efforts and stakeholders in order to promote data-driven decision-making for the effective management of malaria, as well as other diseases.
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Prion disease is neurodegenerative disease that is typically fatal within months of first symptoms. Clinical trials in this rapidly declining symptomatic patient population have proven challenging. Individuals at high lifetime risk for genetic prion disease can be identified decades before symptom onset and provide an opportunity for early therapeutic intervention. However, randomizing pre-symptomatic carriers to a clinical endpoint is not numerically feasible. We therefore launched a cohort study in pre-symptomatic genetic prion disease mutation carriers and controls with the goal of evaluating biomarker endpoints that may enable informative trials in this population. ⋯ CSF PrP will be interpretable as a pharmacodynamic readout for PrP-lowering therapeutics in pre-symptomatic individuals and may serve as an informative surrogate biomarker in this population. In contrast, markers of prion seeding activity and neuronal damage do not reliably cross-sectionally distinguish mutation carriers from controls. Thus, as PrP-lowering therapeutics for prion disease advance, "secondary prevention" based on prodromal pathology may prove challenging; instead, "primary prevention" trials appear to offer a tractable paradigm for trials in pre-symptomatic individuals.
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A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression. ⋯ Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut.
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PREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups. ⋯ This large external validation demonstrates that PREDICT Prostate is a robust and generalisable model to aid clinical decision-making.