Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3).

BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab through 108 weeks of treatment in UNCOVER-3. METHODS: Patients (N = 1346) were randomized 2:2:2:1 to 80 mg ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to ixekizumab every 4 weeks during a long-term extension (LTE) period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified MI (mMI) methods. RESULTS: For patients (N = 385) receiving the recommended dose (ixekizumab every 2 weeks on weeks 0-12 and every 4 weeks during LTE), the 108-week as-observed, MI, and mMI response rates were 93.4%, 88.3%, and 83.6%, respectively, for patients achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index, and the 108-week as-observed, MI, and mMI response rates were 82.6%, 78.3%, and 74.1%, respectively, for patients with a static Physician's Global Assessment score of 0 or 1. During LTE, 1077 (84.5%) patients reported ≥1 treatment-emergent adverse event, and 85% were mild or moderate in severity. Discontinuation because of adverse events occurred in 6.4% of patients. LIMITATIONS: There was no comparison treatment group after week 12. CONCLUSION: Ixekizumab is well tolerated and demonstrates persistent efficacy through 108 weeks.

Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly.

Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved.

Comparing National Institutes of Health funding of emergency medicine to four medical specialties.

OBJECTIVES: The purpose of this study was to compare National Institutes of Health (NIH) funding received in 2008 by emergency medicine (EM) to the specialties of internal medicine, pediatrics, anesthesiology, and family medicine. The hypothesis was that EM would receive fewer NIH awards and less funding dollars per active physician and per medical school faculty member compared to the other four specialties. METHODS: Research Portfolio Online Reporting Tools (RePORT) were used to identify NIH-funded grants to 125 of the 133 U.S. allopathic medical schools for fiscal year 2008 (the most recent year with all grant funding information). Eight medical schools were excluded because six were not open in 2008, one did not have a website, and one did not have funding data available by medical specialty. From RePORT, all grants awarded to EM, internal medicine, family medicine, anesthesiology, and pediatric departments of each medical school were identified for fiscal year 2008. The authors extracted the project number, project title, dollars awarded, and name of the principal investigator for each grant. Funds awarded to faculty in divisions of EM were accounted for by identifying the department of the EM division and searching for all grants awarded to EM faculty within those departments using the name of the principal investigator. The total number of active physicians per medical specialty was acquired from the Association of American Medical Colleges' 2008 Physician Specialty report. The total number of faculty per medical specialty was collected by two research assistants who independently counted the faculty listed on each medical school website. The authors compared the total number of NIH awards and total funding per 1,000 active physicians and per 1,000 faculty members by medical specialty. RESULTS: Of the 125 medical schools included in the study, 84 had departments of EM (67%). In 2008, NIH awarded over 9,000 grants and approximately $4 billion to the five medical specialties of interest. Less than 1% of the grants and funds were awarded to EM. EM had the second-lowest number of awards and funding per active physician, and the lowest number of awards and funding per faculty member. A higher percentage of grants awarded to EM were career development awards (26%, vs. a range of 11% to 19% for the other specialties) and cooperative agreements (26%, vs. 2% to 10%). In 2008, EM was the only specialty of the five not to have a fellowship or T32 training grant. EM had the lowest proportion of research project awards (42%, vs. 58% to 73%). CONCLUSIONS: Compared to internal medicine, pediatrics, anesthesiology, and family medicine, EM received the least amount of NIH support per active faculty member and ranked next to last for NIH support by active physician. Given the many benefits of research both for the specialty and for society, EM needs to continue to develop and support an adequate cohort of independent investigators.

A randomized controlled trial of the effect of service delivery information on patient satisfaction in an emergency department fast track.

OBJECTIVES: The objective was to determine the effect on patient satisfaction of providing patients with predicted service completion times. METHODS: A randomized controlled trial was conducted in an urban, community teaching hospital. Emergency department (ED) patients triaged to fast track on weekdays between October 26, 2009, and December 30, 2009, from 9 am to 5 pm were eligible. Patients were randomized to: 1) usual care (n = 342), 2) provided ED process information (n = 336), or 3) provided ED process information plus predicted service delivery times (n = 333). Patients in group 3 were given an "average" and "upper range" estimate of their waiting room times and treatment times. The average and upper range predictions were calculated from quantile regression models that estimated the 50th and 90th percentiles of the waiting room time and treatment time distributions for fast track patients at the study site based on 2.5 years of historical data. Trained research assistants administered the interventions after triage. Patients completed a brief survey at discharge that measured their satisfaction with overall care, the quality of the information they received, and the timeliness of care. Satisfaction ratings of very good versus good, fair, poor, and very poor were modeled using logistic regression as a function of study group; actual service delivery times; and other patient, clinical, and temporal covariates. The study also modeled satisfaction ratings of fair, poor, and very poor compared to good and very good ratings as a function of the same covariates. RESULTS: Survey completion rates and patient, clinical, and temporal characteristics were similar by study group. Median waiting room time was 70 minutes (interquartile range [IQR] = 40 to 114 minutes), and median treatment time was 52 minutes (IQR = 31 to 81 minutes). Neither intervention affected any of the satisfaction outcomes. Satisfaction was significantly associated with actual waiting room time, individual providers, and patient age. Every 10-minute increase in waiting room time corresponded with an 8% decrease (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.89 to 0.95) in the odds of reporting very good satisfaction with overall care. The odds of reporting very good satisfaction with care were lower for several triage nurses and fast track nurses, compared to the triage nurse and fast track nurse who treated the most study patients. Each 10-minute increase in waiting room time was also associated with a 10% increase in the odds of reporting very poor, poor, or fair satisfaction with overall care (OR = 1.10; 95% CI = 1.06 to 1.14). The odds of reporting very poor, poor, or fair satisfaction with overall care also varied significantly among the triage nurses, fast track doctors, and fast track nurses. The odds of reporting very poor, poor, or fair satisfaction with overall care were significantly lower among patients aged 35 years and older compared to patients aged 18 to 34 years. CONCLUSIONS: Satisfaction with overall care was influenced by waiting room time and the clinicians who treated them and not by service completion time estimates provided at triage.