Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients Prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single-dose (60,000 units of epoetin alfa) efficacy phase involving 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Intervention Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. Main Outcome Measure Infarct size, expressed as a percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging 2–6 days after study medication administration. Results In the efficacy cohort (n=138), infarct size did not differ between groups at either 2–6 days (15.8±10.3 vs. 15.0±10.0, P=.666) or 12±2 weeks (10.6±8.6 vs. 10.4±7.6, P=.886). Left ventricular ejection fraction also did not differ between groups at either the early (48.2±9.1 vs. 48.9±8.7, P=.671) or late (52.5±9.3 vs. 52.0±8.8, P=.760) timepoints. In pre-specified analyses of patients aged ≥70 years (n=21), mean infarct size within the first week was larger in the epoetin alfa arm than in the placebo group (19.9±9.9 vs.11.7±7.2, P=.026). Patients who received epoetin alfa had a higher incidence of the composite endpoint of death, myocardial infarction, stroke, or stent thrombosis (4.0% vs. 0.0%, P=.042), and a higher incidence of serious adverse events (20.0% vs. 10.3%, P=.052). Conclusions In STEMI patients successfully reperfused with primary or rescue PCI, a single intravenous bolus of epoetin alfa did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Furthermore, it may be associated with increased infarct size in older patients. Trial Registration clinicaltrials.gov identifier NCT00378352.

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA.

Physical pain among persons seeking treatment for substance use disorders (SUD) and characteristics associated with pain were examined in a secondary analysis of data from the Drug Abuse Treatment Outcome Study (DATOS), a multi-site treatment outcome study. Patients (N = 7,876) in four treatment modalities - long-term residential (LTR), short-term inpatient (STI), outpatient methadone treatment (OMT), and outpatient drug-free (ODF) - reported severity of physical pain experienced during the preceding 12 months. Moderate to severe physical pain was reported by 21.2% of LTR patients, 26.8% of STI patients, 33.6% of OMT patients, and 17.6% of ODF patients. Individuals with and without physical pain were compared across treatment modalities. Patients with pain were more likely to report weekly heroin use [aOR = 1.73 (1.44-2.08)], weekly narcotics use [aOR = 1.43 (1.18-1.74)] and greater depressive symptoms [aOR = 1.30 (1.21-1.38)]. These findings support the presence of a sizable proportion of SUD patients with pain who may benefit from pain assessment as part of their SUD treatment.

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age ≥18 who met Diagnostic and Statistical Manual, 4 th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. NIH Public Access

IMPORTANCE Invasive candidiasis in premature infants causes mortality and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole is unknown. OBJECTIVE To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes—defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18–22-months corrected age. RESULTS Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%–22%) vs 21% in the placebo group (95% CI, 15%–28%; odds ratio 0.73 [95% CI 0.43–1.23]; P=.24; treatment difference −5% [95% CI, −13%–3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%–6%] vs the placebo group (9% [95% CI, 5%–14%]; P=.02; treatment difference −6% [95% CI, −11%–−1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole 31% [95% CI, 21–41%] vs placebo, 27% [95% CI, 18–37%]; P=.60; treatment difference 4% [95% CI, −10–17%]). CONCLUSIONS AND RELEVANCE Among infants with a birth weight of less 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely-low-birth-weight infants. TRIAL REGISTRATION ClinicalTrials.gov number NCT00734539

The collection efficiencies of the V6.0 procedure for both CD34+ cells and mature blood cells are lower than those of the V4.7 procedure. The lower collection efficiency for platelets results in a smaller drop in peripheral blood platelet count after the procedure. The automated features of the V6.0 procedure may simplify PBPC collection, but this procedure requires a longer apheresis.

Objective-Individuals with direct care responsibilities in 348 drug abuse treatment units were surveyed to obtain a description of the workforce and to assess support for evidence-based therapies.Methods-Surveys were distributed to 112 programs participating in the National Drug Abuse Treatment Clinical Trials Network (CTN). Descriptive analyses characterized the workforce. Analyses of covariance tested the effects of job category (counselors, medical staff, managersupervisors, and support staff) on opinions about evidence-based practices and controlled for the effects of education, modality (outpatient or residential), race, and gender.Results-Women made up two-thirds of the CTN workforce. One-third of the workforce had a master's or doctoral degree. Responses from 1,757 counselors, 908 support staff, 522 managerssupervisors, and 511 medical staff (71% of eligible participants) suggested that the variables that most consistently influenced responses were job category (19 of 22 items) and education (20 of 22 items). Managers-supervisors were the most supportive of evidence-based therapies, and support staff were the least supportive. Generally, individuals with graduate degrees had more positive opinions about evidence-based therapies. Support for using medications and contingency management was modest across job categories. Conclusions-The relatively traditional beliefs of support staff could inhibit the introduction of evidence-based practices. Programs initiating changes in therapeutic approaches may benefit from including all employees in change efforts.The National Drug Abuse Treatment Clinical Trials Network (CTN) began in 1999 with support from the National Institute on Drug Abuse. Research centers (currently 17) partner with five or more local alcohol and drug treatment centers (currently almost 150 distinct corporations) to conduct multisite clinical trials that test behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions in treatment programs with heterogeneous patient populations (1). Successful trials generate evidence of effectiveness and may promote the dissemination and adoption of science-based behavioral and pharmaceutical therapies. The first trials assessed buprenorphine detoxification (2,3), motivational interviewing and motivational enhancement therapy (4), and low-cost incentives for use with patients in methadone and outpatient programs (5,6). Initial results documented the feasibility of collaboration with community drug abuse treatment centers and provided a foundation for expansion and growth.Bridging the gap between practice and research, however, requires more than conducting clinical trials in community settings. Individuals who work in the treatment programs are essential to the introduction, adoption, and sustainability of science-based practices. Unfortunately, there is little current information on the workforce that provides treatment services for substance use disorders and on workers' opinions about the use of evidencebased therapies....

Background-Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results-In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20. P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency ≤60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions-Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.