Faculty Bibliography

Nearly 380,000 U.S. service members between 2000 and 2017 were, and at least 300,000 athletes annually are, diagnosed with concussion. It is imperative to establish a gold-standard diagnostic test to quickly and accurately diagnose concussion. In this non-randomized, prospective study, we examined the reliability and validity of a novel neurocognitive assessment tool, the Defense Automated Neurobehavioral Assessment (DANA), designed to be a more sensitive, yet efficient, measure of concussion symptomatology. In this study, the DANA Brief version was compared to an established measure of concussion screening, the Military Acute Concussion Evaluation (MACE), in a group of non-concussed service members. DANA Brief subtests demonstrated low to moderate reliability, as measured by intra-class correlation coefficient (ICC; values range: 0.28-0.58), which is comparable to other computerized neurocognitive tests that are widely-implemented to diagnose concussion. Statistically significant associations were found between learning and memory components of the DANA Brief and the diagnostic MACE cognitive test score (DANA Brief subtests: CDD: R ² = 0.05, p = 0.023; CDS: R ² = 0.10, p = 0.010). However, a more robust relationship was found between DANA Brief components involving attention and working memory, including immediate memory, and the MACE cognitive test score (DANA Brief subtests: GNG: R ² = 0.08, p = 0.003; PRO: R ² = 0.08, p = 0.002). These results provide evidence that the DANA Rapid version, a 5-min assessment self-administered on a hand-held portable device, based on the DANA Brief version, may serve as a clinically useful and improved neurocognitive concussion screen to minimize the time between injury and diagnosis in settings where professional medical evaluation may be unavailable or delayed. The DANA's portability, durability, shorter test time and lack of need for a medical professional to diagnose concussion overcome these critical limitations of the MACE.

Purpose Patients who overuse acute medicationsfor migraine generally experience more migraine days, greater disability, and more severe pain intensity. The FOCUS study of fremanezumab, a fully-humanized monoclonal antibody (IgG2DELTAa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with both chronic migraine (CM) and episodic migraine (EM) and documented inadequate response to 2 to 4 classes of migraine preventive medications.This subgroup analysis of the FOCUS study evaluated the efficacy of fremanezumab in patients with baseline medication overuse (use of any acute medication on >=15 days/month or use of triptans, ergots, or combination medications on >=10 days/month). Methods In the randomized, double-blind, placebo-controlled period of the phase 3b FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab (month 1: 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: CM, 675 mg; EM, 225 mg; months 2 and 3: 225 mg), or matched monthly placebo for 12 weeks. Changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures. Results Of 838 randomized patients, 435 had baseline medication overuse. Reductions from baseline in the monthly averagenumber of migraine days were significantly greater with quarterly fremanezumab (least-squares mean [standard error (SE)] change, -3.3 [0.61]) and monthly fremanezumab (-4.6 [0.55]) versus placebo (-0.5 [0.62]; both P <= 0.0001) during 12 weeks of treatment. Reductions from baseline in the monthly average number of headache days of at least moderate severity were also significantly greater with quarterly fremanezumab (least-squares mean [SE] change, -4.0 [0.61]) and monthly fremanezumab (-5.1 [0.54]) versus placebo (-0.8, [0.61]; both P < 0.0001) during 12 weeks of treatment. At 4 weeks of double-blind treatment, changes from baseline in the monthly average number of migraine days and monthly average number of headache days of at least moderate severity were also significantly greater with both dosing regimens of fremanezumab versus placebo (all P < 0.0001). Conclusions Quarterly and monthly fremanezumab provided early and sustained reductions in monthly migraine and monthly headache days of at least moderate severity versus placebo in migraine patients with medication overuse and documented inadequate response to 2 to 4 classes of migraine preventive medications

Background: Canagliflozin (CANA) reduces the risk of cardiovascular (CV) events and kidney failure in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Inherent in its mechanism of action is enhanced natriuresis and osmotic diuresis. It is unclear if the efficacy or safety of CANA is modified by concomitant diuretic use.
Method(s): CREDENCE randomized participants with T2DM and CKD to CANA or matching placebo. The primary outcome was a composite of end-stage kidney disease, doubling of serum creatinine, CV or renal death. We estimated effects on key efficacy and safety outcomes by baseline use of loop diuretics.
Result(s): Of 4401 CREDENCE participants, 955 (21.7%) received loop diuretics at baseline. These participants were older (mean age 63.5 vs 62.7 y; P=0.01), with a longer diabetes duration (17.0 vs 15.5 y), lower eGFR (49.7 vs 58.0 mL/min/1.73m²), and were more like to have a history of heart failure (27.6 vs 11.3%; all P<0.0001). Unadjusted event rates were higher in those using loop diuretics (Figure). Effects of CANA on the primary outcome and other CV and renal outcomes were consistent irrespective of loop diuretic use. The risk of renal-related adverse events, acute kidney injury, and volume depletion was not elevated by loop diuretic use (data not shown; all Pinteraction>0.05).
Conclusion(s): CANA reduces the risk of CV and renal outcomes in people with T2DM and CKD irrespective of baseline use of loop diuretics, without additional adverse effects. (Table Presented)

Neurologic infections during pregnancy represent a significant cause of maternal and fetal morbidity and mortality. Immunologic alterations during pregnancy increase the susceptibility of the premature brain to damage. This chapter summarizes the epidemiology, pathophysiology, and clinical manifestations in the pregnant woman and the infant, and the diagnosis, treatment, and prevention of the major viral, parasitic, and bacterial infections known to affect pregnancy. These organisms include herpes virus, parvovirus, cytomegalovirus, varicella, rubella, Zika virus, toxoplasmosis, malaria, group B streptococcus, listeriosis, syphilis, and tuberculosis. There is an emphasis on the important differences in diagnosis, treatment, and fetal outcome between trimesters. An additional overview is provided on the spectrum of neurologic sequelae of an affected infant, which ranges from developmental delay to hydrocephalus and seizures.