61 research outputs found

    Use of behavioral economics and social psychology to improve treatment of acute respiratory infections (BEARI): rationale and design of a cluster randomized controlled trial [1RC4AG039115-01] - study protocol and baseline practice and provider characteristics

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    Background: Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care, antibiotic resistance among bacteria, and adverse drug events. Acute respiratory infections (ARIs) are the most common reason for inappropriate antibiotic use. Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs (e.g., educational or informational interventions) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs. If lack of guideline awareness is not the reason for inappropriate prescribing, educational interventions may have limited impact on prescribing rates. Instead, interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians. Methods/design The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections (BEARI) Trial is a multisite, cluster-randomized controlled trial with practice as the unit of randomization. The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs. We randomized practices in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses: 1) Accountable Justifications: When prescribing an antibiotic for an ARI, clinicians are prompted to record an explicit justification that appears in the patient electronic health record; 2) Suggested Alternatives: Through computerized clinical decision support, clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices (including prescription options) prior to completing the antibiotic prescription; and 3) Peer Comparison: Each provider’s rate of inappropriate antibiotic prescribing relative to top-performing peers is reported back to the provider periodically by email. We enrolled 269 clinicians (practicing attending physicians or advanced practice nurses) in 49 participating clinic sites and collected baseline data. The primary outcome is the antibiotic prescribing rate for office visits with non-antibiotic-appropriate ARI diagnoses. Secondary outcomes will examine antibiotic prescribing more broadly. The 18-month intervention period will be followed by a one year follow-up period to measure persistence of effects after interventions cease. Discussion The ongoing BEARI Trial will evaluate the effectiveness of behavioral economic strategies in reducing inappropriate prescribing of antibiotics. Trials registration ClinicalTrials.gov: NCT0145494

    Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

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    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

    Cognitive Neural Prosthetics: Brain Machine Interfaces Based in Parietal Cortex

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    Systems neuroscience has recently emerged as an applied field in the form of neural prosthetic development. This integration of empirical systems neuroscience with engineering in order to develop functional interfaces between external devices and the brain has not only been beneficial in its applied goal, but has resulted in observations of scientific interest. The body of work presented here demonstrates the efficacy of two varieties of brain machine interfaces (BMIs) based in Parietal Cortex. The first using information about intended reaches present in action potentials, the second using local field potentials (LFPs). Both studies were predicated and succeeded with offline analyses demonstrating feasibility and novel insight to the function and neural coding properties of Parietal Cortex. We found that using BMIs resulted in adaptive change which tended to improve performance. LFPs, though less successful than spikes for BMI control under these experimental conditions, appear to have a multiplexing of different types of information that might aid in BMIs as well as providing a different way of looking at the neural processing. A preliminary exploration of relative timing of spikes and LFPs might result in some of the adaptive properties observed during BMI use via spike timing dependent plasticity concludes the research presented here
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