Jon W. Yankey

Antimicrobial Resistance Trends and Outbreak Frequency in United States Hospitals

We assessed resistance rates and trends for important antimicrobial-resistant pathogens (oxacillin-resistant Staphylococcus aureus [ORSA], vancomycin-resistant Enterococcus species [VRE], ceftazidime-resistant Klebsiella species [K-ESBL], and ciprofloxacin-resistant Escherichia coli [QREC]), the frequency of outbreaks of infection with these resistant pathogens, and the measures taken to control resistance in a stratified national sample of 670 hospitals. Four hundred ninety-four (74%) of 670 surveys were returned. Resistance rates were highest for ORSA (36%), followed by VRE (10%), QREC (6%), and K-ESBL (5%). Two-thirds of hospitals reported increasing ORSA rates, whereas only 4% reported decreasing rates, and 24% reported ORSA outbreaks within the previous year. Most hospitals (87%) reported having implemented measures to rapidly detect resistance, but only approximately 50% reported having provided appropriate resources for antimicrobial resistance prevention (53%) or having implemented antimicrobial use guidelines (60%). The most common resistant pathogen in US hospitals is ORSA, which accounts for many recognized outbreaks and is increasing in frequency in most facilities. Current practices to prevent and control antimicrobial resistance are inadequate.

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine

Background Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established. Methods We conducted a randomized, double‐blind, placebo‐controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28‐day baseline period with the last 28 days of a 24‐week trial. Secondary outcomes were headache‐related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. Results A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between‐group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between‐group differences in headache‐related disability, headache days, or the percentage of patients who completed the 24‐week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt. Conclusions There were no significant differences in reduction in headache frequency or headache‐related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281).

Physician Process and Patient Outcome Measures for Diabetes Care: Relationships to Organizational Characteristics

Background:Optimal diabetes management relies on providers adhering to evidence-based practice guidelines in the processes of care delivery and patients adhering to self-management recommendations to maximize patient outcomes. Purpose:To explore: (1) the degree to which providers adhere to the guidelines; (2) the extent of glycemic, lipid, and blood pressure control in patients with diabetes; and (3) the roles of organizational and patient population characteristics in affecting both provider adherence and patient outcome measures for diabetes. Design:Secondary data analysis of provider adherence and patient outcome measures from chart reviews, along with surveys of facility quality managers. Sample:We sampled 109 Veterans Affairs medical centers (VAMCs). Results:Analyses indicated that provider adherence to diabetes guidelines (ie, hemoglobin A1c, foot, eye, renal, and lipid screens) and patient outcome measures (ie, glycemic, lipid, and hypertension control plus nonsmoking status) are comparable or better in VAMCs than reported elsewhere. VAMCs with higher levels of provider adherence to diabetes guidelines had distinguishing organizational characteristics, including more frequent feedback on diabetes quality of care, designation of a guideline champion, timely implementation of quality-of-care changes, and greater acceptance of guideline applicability. VAMCs with better patient outcome measures for diabetes had more effective communication between physicians and nurses, used educational programs and Grand Rounds presentations to implement the diabetes guidelines, and had an overall patient population that was older and with a smaller percentage of black patients. Conclusions:Healthcare organizations can adopt many of the identified organizational characteristics to enhance the delivery of care in their settings.

Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study

This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).

IMPLEMENTATION OF STRATEGIES TO PREVENT AND CONTROL THE EMERGENCE AND SPREAD OF ANTIMICROBIAL-RESISTANT MICROORGANISMS IN U.S. HOSPITALS

OBJECTIVE To examine the extent to which the strategies recommended by the National Foundation for Infectious Diseases (NFID)-Centers for Disease Control and Prevention (CDC) co-sponsored workshop, Antimicrobial Resistance in Hospitals: Strategies to Improve Antimicrobial Use and Prevent Nosocomial Transmission of Antimicrobial-Resistant Microorganisms, have been implemented and the relationship between the degree of implementation and hospital culture, leadership, and organizational factors. DESIGN Survey. SETTING A representative sample of U.S. hospitals stratified by teaching status, bed size, and geographic region. PARTICIPANTS Infection control professionals. RESULTS Surveyed hospitals had implemented strategies to optimize the use of antimicrobials and to detect, report, and prevent transmission of antimicrobial-resistant microorganisms. Multivariate analyses found that hospitals with a greater degree of implementation of the NFID-CDC strategic goals were more likely to have management support, education of staff, and interdisciplinary groups specifically to address these issues; they were also more likely to engage in benchmarking on broader quality of care indicators. CONCLUSIONS Most surveyed hospitals had implemented some measures to address the NFID-CDC recommendations; however, hospitals need to do much more to improve antimicrobial use and to increase their efforts to detect, report, and control the spread of antimicrobial resistance. A supportive hospital administration must foster a culture of ongoing support, education, and interdisciplinary work groups focused on this important issue to successfully accomplish these goals.

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

BACKGROUND Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. METHODS SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100mg/day) or placebo for 96weeks. Imaging is conducted every 24weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. RESULTS A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. CONCLUSION SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.

Impact of functional limitations and medical comorbidity on subsequent weight changes and increased depressive symptoms in older adults.

Objectives: The primary goal of this study was to determine the effect of the onset of major medical comorbidity and functional decline on subsequent weight change and increased depressive symptoms. Methods: The sample included a prospective cohort of 53 to 63 year olds (n = 10,150) enrolled in the Health and Retirement Study. Separate lagged covariate models for men and women were used to study the impact of functional decline and medical comorbidity on subsequent increases in depressive symptoms and weight change 2 years later. Results: Functional decline and medical comorbidity were individual predictors of subsequent weight changes but not increased depressive symptoms. Most specific incident medical comorbidities or subtypes of functional decline predicted weight changes in both directions. Discussion: The elevated risk of weight gain subsequent to functional decline or onset of medical comorbidities may require the receipt of preventive measures to reduce further weight-related complications.

Consistency of Quantitative Scores of Hypoglycemia Severity and Glycemic Lability and Comparison with Continuous Glucose Monitoring System Measures in Long-Standing Type 1 Diabetes

BACKGROUND In long-standing type 1 diabetes (T1D), loss of endogenous insulin secretion and glucose dysregulation can lead to severe hypoglycemia and associated complications. Here, we report the serial consistency and the correlation between different scores that characterize glucose dysregulation using self-monitoring of blood glucose (SMBG), in a cohort of T1D individuals being evaluated for transplant eligibility in Clinical Islet Transplantation Consortium trials. SUBJECTS AND METHODS In total, 152 C-peptide-negative T1D subjects with at least one severe hypoglycemia episode in the prior year documented SMBG at enrollment and every 6 months until deemed ineligible or transplanted. SMBG was used to calculate the HYPO score, Lability Index (LI), and mean amplitude of glycemic excursion (MAGE). Additionally, a blinded continuous glucose monitoring system (CGMS) was worn for 72 h at enrollment and every 12 months. RESULTS In this cohort, LI was the most consistent (intraclass correlation coefficient=0.70) over time, followed by the HYPO score (0.51), with MAGE being the least consistent (0.36). Although MAGE and LI were highly correlated with each other, neither correlated with CGMS SD or glucose coefficient of variation (CV). Subjects spent a median of 97 min/day at <54 mg/dL using CGMS. The HYPO score correlated with CGMS time below 54 mg/dL and glucose CV. CONCLUSIONS The HYPO score and LI are more consistent than MAGE in patients with established T1D experiencing severe hypoglycemic events and may be especially useful both for identifying subjects experiencing the greatest difficulty in maintaining glycemic control and for longitudinal assessment of novel interventions.

The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report on Baseline Characteristics of Participants

To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double‐blinded, placebo‐controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).

Variation in the Use of Procedures to Monitor Antimicrobial Resistance in U.S. Hospitals

BACKGROUND Antimicrobial resistance is a growing clinical and public health crisis. Experts have recommended measures to monitor antimicrobial resistance; however, little is known regarding their use. OBJECTIVE We describe the use of procedures to detect and report antimicrobial resistance in U.S. hospitals and the organizational and epidemiologic factors associated with their use. METHODS In 2001, we surveyed laboratory directors (n = 108) from a random national sample of hospitals. We studied five procedures to monitor antimicrobial resistance: (1) disseminating antibiograms to physicians at least annually, (2) notifying physicians of antimicrobial-resistant infections, (3) reporting susceptibility results within 24 hours, (4) using automated testing procedures, and (5) offering molecular typing. Explanatory variables included organizational characteristics and patterns of antimicrobial resistance for oxacillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, quinolone-resistant Escherichia coli, and extended-spectrum beta-lactamase-producing Klebsiella species. Generalized estimating equations accounting for the correlation among outcomes at the facility level were used to identify predictors of the five outcomes. RESULTS Use of the procedures ranged from 85% (automated testing) to 33% (offering molecular typing) and was related to teaching hospital status (OR, 3.1; CI95, 1.5-6.5), participation of laboratory directors on the infection control committee (OR, 1.7; CI95, 1.1-2.8), and having at least one antimicrobial-resistant pathogen with a prevalence greater than 10% (OR, 2.2; CI95, 1.4-3.3). CONCLUSION U.S. hospitals underutilize procedures to monitor the spread of antimicrobial resistance. Use of these procedures varies and is related to organizational and epidemiologic factors. Further efforts are needed to increase their use by hospitals.