Objective Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Prior open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, ages 3.5-16 years (n=55, mean age 9.2 (SD 3.6 years)). Participants were randomized to minocycline or placebo for three months, then switched to the other treatment. Results Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared to placebo (2.49 ±0.13, 2.97 ±0.13, respectively, p 0.0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analoge Scale (minocycline 5.26 cm ±0.46 cm, placebo 4.05 cm±0.46cm; p 0.0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators. Conclusion Minocycline treatment for three months in children with FXS resulted in greater global improvement than placebo. Treatment for three months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.

Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). Human-targeted treatment trials with minocycline have shown benefits in behavioral measures and parent reports. Event-related potentials (ERPs) may provide a sensitive method of monitoring treatment response and changes in coordinated brain activity. Measurement of electrocortical changes due to minocycline was done in a double-blind, placebo-controlled crossover treatment trial in children with FXS. Children with FXS (Meanage 10.5 years) were randomized to minocycline or placebo treatment for 3 months then changed to the other treatment for 3 months. The minocycline dosage ranged from 25–100 mg daily, based on weight. Twelve individuals with FXS (eight male, four female) completed ERP studies using a passive auditory oddball paradigm. Current source density (CSD) and ERP analysis at baseline showed high-amplitude, long-latency components over temporal regions. After 3 months of treatment with minocycline, the temporal N1 and P2 amplitudes were significantly reduced compared with placebo. There was a significant amplitude increase of the central P2 component on minocycline. Electrocortical habituation to auditory stimuli improved with minocycline treatment. Our study demonstrated improvements of the ERP in children with FXS treated with minocycline, and the potential feasibility and sensitivity of ERPs as a cognitive biomarker in FXS treatment trials.

Introduction In 2019 the United States Preventive Services Task Force (USPSTF) released draft guidelines recommending universal hepatitis C virus (HCV) screening for individuals aged 18–79. We aimed to assess the efficacy of an emergency department-based HCV screening program, by comparing screening practices before and after its implementation. Methods We performed a retrospective cohort analysis of two temporally matched, 11-month study periods, corresponding to before and after the implementation of a best practice advisory (BPA). Patients were screened for anti-HCV antibody (Ab), and positive results were followed by HCV viral load (VL) testing. The primary implementation outcome was ED testing volume (number of tests performed/month). The primary screening outcomes were the seroprevalence of anti-HCV Ab and HCV VL. We describe data with simple descriptive statistics. Results The median age of patients was similar between periods (pre: 50 years [interquartile range [IQR] 34–62], post: 47 years [IQR 33–59]). Patients screened were more likely to be males in the pre-BPA period (Male, pre: 60%, post: 49%). During the pre-BPA study period, a total of 69,604 patients were seen in the ED, and 218 unique patients were screened for HCV (mean 19.8 tests/month). During the post-BPA study period, a total of 68,225 patients were seen in the ED, and 14,981 unique patients were screened for HCV (mean 1361.9 tests/month). Anti-HCV Ab seroprevalence was 23% (51/218) and 9% (1340/14,981) in the pre-BPA and post-BPA periods, respectively. In the pre-BPA period, six patients with a positive anti-HCV Ab level had follow-up VL testing (detectable in three). In the post-BPA period, reflex VL testing was performed in most patients (91%, 1225/1,340), and there were 563 patients with detectable VLs, indicating active infection. Conclusion Our study shows that using a universal BPA-driven screening protocol can dramatically increase the number of patients screened for HCV and increase the number of new HCV diagnoses.

Background:The prevalence of syphilis is increasing in the United States.The emergency department (ED) is an important setting to screen and treat underserved populations. To tailor testing protocols to the local population, we aimed to identify risk factors for syphilis positivity in ED patients.Methods: We performed a retrospective analysis of ED patients who were screened for syphilis between November 2018 and August 2020. Patients were screened for Treponema pallidum antibody using a multiplex flow immunoassay, and positive results were confirmed by rapid plasma reagin or T. pallidum particle agglutination. Risk factors for new syphilis diagnoses were identified using multiple logistic regression.