Association between immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome and long-term outcomes: A 10-year follow-up of the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study In Ongoing Neurological Surveillance
Kinkel R.P.,Beth Israel Deaconess Medical Center |
Dontchev M.,Jaeb Center for Health Research |
Kollman C.,Jaeb Center for Health Research |
Skaramagas T.T.,Cleveland Clinic |
And 2 more authors.
Archives of Neurology | Year: 2012
Objective: To determine whether immediate initiation of treatment at the time of a clinically isolated syndrome in patients at high risk for clinically definite multiple sclerosis alters disease course over 10 years. Design: Prospective follow-up study. Setting: Twenty-four Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) sites in the United States and Canada. Participants: A total of 81 patients originally randomly assigned to receive intramuscular interferon beta-1a (the immediate-treatment group) and 74 patients originally randomly assigned to receive placebo (the delayed-treatment group). All patients were from CHAMPS. Intervention: For the immediate-treatment group, treatment was initiated within a month after the onset of a clinically isolated syndrome, and for the delayed-treatment group, treatment was initiated a median of 30 months (interquartile range, 24-35 months) after CHAMPS randomization. Main Outcome Measures: Rate of developing clinically definite multiple sclerosis, annualized relapse rate, disease course classification, disability measures, and magnetic resonance imaging measures. Results: The immediate-treatment group showed a lower 10-year rate of clinically definite multiple sclerosis (unadjusted hazard ratio, 0.64 [95% CI, 0.48-0.87]; P=.004) and a lower annualized relapse rate between years 5 and 10 (P=.03). There was no differential effect on disability, magnetic resonance imaging T2-weighted lesions, or the proportion of patients developing progressive disease at 10 years. Few patients reached the Expanded Disability Status Scale milestone scores of 4.0 or greater (9% of patients) or 6.0 or greater (6% of patients). Conclusions: Immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome in high-risk patients reduces relapse rates over 10 years but does not improve disability outcomes compared with a control group that also initiated therapy relatively early in the disease course. Trial Registration: clinicaltrials.gov Identifier: NCT00179478. ©2012 American Medical Association. All rights reserved.
Block J.,Portland Veterans Affairs Medical Center
Journal of the American Academy of Psychiatry and the Law | Year: 2013
Mefloquine (previously marketed in the United States as Lariam®) is an antimalarial medication with potent psychotropic potential. Severe psychiatric side effects due to mefloquine intoxication are well documented, including anxiety, panic attacks, paranoia, persecutory delusions, dissociative psychosis, and anterograde amnesia. Exposure to the drug has been associated with acts of violence and suicide. In this article, we discuss the history of mefloquine use and describe plausible mechanisms of its psychotropic action. Mefloquine intoxication has not yet been successfully advanced in legal proceedings as a defense or as a mitigating factor, but it appears likely that it eventually will be. Considerations for the application of claims of mefloquine intoxication in forensic settings are discussed.
Standiford H.C.,University of Maryland, Baltimore |
Standiford H.C.,University of Maryland Baltimore County |
Chan S.,DuPont Company |
Tripoli M.,University of Maryland, Baltimore |
Forrest G.N.,Portland Veterans Affairs Medical Center
Infection Control and Hospital Epidemiology | Year: 2012
background. An antimicrobial stewardship program was fully implemented at the University of Maryland Medical Center in July 2001 (beginning of fiscal year [FY] 2002). Essential to the program was an antimicrobial monitoring team (AMT) consisting of an infectious diseases-trained clinical pharmacist and a part-time infectious diseases physician that provided real-time monitoring of antimicrobial orders and active intervention and education when necessary. The program continued for 7 years and was terminated in order to use the resources to increase infectious diseases consults throughout the medical center as an alternative mode of stewardship. design. A descriptive cost analysis before, during, and after the program. patients/setting. A large tertiary care teaching medical center. methods. Monitoring the utilization (dispensing) costs of the antimicrobial agents quarterly for each FY. results. The utilization costs decreased from $44,181 per 1,000 patient-days at baseline prior to the full implementation of the program (FY 2001) to $23,933 (a 45.8% decrease) by the end of the program (FY 2008). There was a reduction of approximately $3 million within the first 3 years, much of which was the result of a decrease in the use of antifungal agents in the cancer center. After the program was discontinued at the end of FY 2008, antimicrobial costs increased from $23,933 to $31,653 per 1,000 patient-days, a 32.3% increase within 2 years that is equivalent to a $2 million increase for the medical center, mostly in the antibacterial category. conclusions. The antimicrobial stewardship program, using an antimicrobial monitoring team, was extremely cost effective over this 7-year period. © 2012 by The Society for Healthcare Epidemiology of America. All rights reserved.
Subramanya A.R.,University of Pittsburgh |
Ellison D.H.,Oregon Health And Science University |
Ellison D.H.,Portland Veterans Affairs Medical Center
Clinical Journal of the American Society of Nephrology | Year: 2014
The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. Copyright © 2014 by the American Society of Nephrology.
Thompson E.M.,Oregon Health And Science University |
Neuwelt E.A.,Oregon Health And Science University |
Neuwelt E.A.,Portland Veterans Affairs Medical Center |
Frenkel E.P.,University of Texas at Dallas
Neurology | Year: 2011
One rationale behind the use of agents that inhibit vascular endothelial growth factor in the therapy of primary CNS malignancies is based upon the concept that normalization of tumor vasculature with a decrease in tumor interstitial pressure will improve access of cytoreductive drugs and improve radiotherapy efficacy due to increased oxygen delivery. However, several studies have raised the concern that these agents may both rapidly restore the low permeability characteristics of the blood-brain barrier and counteract the beneficial effect of pseudoprogression. The result may be decreased therapeutic efficacy while increasing infiltration by co-opting normal vessels. In this discussion, we examine both histologic and radiographic tumor progression in the context of antiangiogenic agents. Issues dealing with the safety of bevacizumab (Avastin®, Genentech, South San Francisco, CA) and its potential to decrease efficacy of standard radiochemotherapy when used to treat patients with newly diagnosed malignant glioma are emphasized. Copyright © by AAN Enterprisos, Inc.
Qaseem A.,The American College |
Barry M.J.,Massachusetts General Hospital |
Kansagara D.,Portland Veterans Affairs Medical Center
Annals of Internal Medicine | Year: 2016
Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. Methods: This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture,-3 fatty acids, S-adenosyl-L-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. Recommendation: ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient (Grade: strong recommendation, moderate-quality evidence). © 2016 American College of Physicians.
Turner E.H.,Oregon Health And Science University |
Turner E.H.,Portland Veterans Affairs Medical Center |
Knoepflmacher D.,Oregon Health And Science University |
Shapley L.,Oregon Health And Science University
PLoS Medicine | Year: 2012
Background: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. Methods and Findings: FDA Drug Approval Packages for eight second-generation antipsychotics-aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone-were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. Conclusions: The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. Please see later in the article for the Editors' Summary.
Haney E.M.,Oregon Health And Science University |
Warden S.J.,Indiana University |
Bliziotes M.M.,Oregon Health And Science University |
Bliziotes M.M.,Portland Veterans Affairs Medical Center
Bone | Year: 2010
Evidence regarding a functional serotonin (5-hydroxytryptamine) signaling system in bone has generated considerable recent interest. The specific biochemical nature of serotoninergic pathways and their direct and/or indirect effects on bone metabolism are still unclear. Clinical evidence supports an effect of serotonin and altered serotonin signaling on bone metabolism. Serotonin is involved in the pathophysiology of depression, and therefore studies of depression and antidepressant treatments (as modulators of the serotonin system) are relevant with regard to bone outcomes. Studies on the effect of depression on bone mineral density (BMD) and fractures have been mixed. Studies on the associations between antidepressant use and BMD and/or fractures are more consistent. SSRIs have been associated with lower BMD and increased rates of bone loss, as well as increased rates of fracture after accounting for falls. These studies are limited by confounding because depression is potentially associated with both the outcome of interest (BMD and fracture) and the exposure (SSRIs). With mounting evidence for an effect on bone, this review considers the question of causality and whether selective serotonin reuptake inhibitors should be considered among those medications that contribute to bone loss, and therefore prompt clinicians to evaluate BMD proactively. Future research will be required to confirm the serotoninergic effects on bone and the biochemical pathways involved, and to identify clinical implications for treatment based on this novel pathway. © 2009.
Shen K.-Z.,Oregon Health And Science University |
Johnson S.W.,Oregon Health And Science University |
Johnson S.W.,Portland Veterans Affairs Medical Center
Journal of Neuroscience | Year: 2010
Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons has been correlated with the bradykinesia and rigidity seen in Parkinson's disease. Consequently, there is much interest in characterizing mechanisms that promote burst firing, such as the regulation of NMDA receptor function. Using whole-cell recording techniques in rat brain slices, we report that inward currents evoked by NMDA are greatly potentiated by ATP-sensitive K+ (K-ATP) channel blocking agents in STN neurons but not in dopamine neurons in the substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP interaction may exert an important influence on basal ganglia output and thereby affect the clinical expression of Parkinson's disease. Copyright © 2010 the authors.
Kansagara D.,Portland Veterans Affairs Medical Center |
Kansagara D.,Oregon Health And Science University |
Englander H.,Oregon Health And Science University |
Salanitro A.,Geriatric Research |
And 6 more authors.
JAMA - Journal of the American Medical Association | Year: 2011
Context: Predicting hospital readmission risk is of great interest to identify which patients would benefit most from care transition interventions, as well as to risk-adjust readmission rates for the purposes of hospital comparison. Objective: To summarize validated readmission risk prediction models, describe their performance, and assess suitability for clinical or administrative use. Data Sources and Study Selection: The databases of MEDLINE, CINAHL, and the Cochrane Library were searched from inception through March 2011, the EMBASE database was searched through August 2011, and hand searches were performed of the retrieved reference lists. Dual review was conducted to identify studies published in the English language of prediction models tested with medical patients in both derivation and validation cohorts. Data Extraction: Data were extracted on the population, setting, sample size, follow-up interval, readmission rate, model discrimination and calibration, type of data used, and timing of data collection. Data Synthesis: Of 7843 citations reviewed, 30 studies of 26 unique models met the inclusion criteria. The most common outcome used was 30-day readmission; only 1 model specifically addressed preventable readmissions. Fourteen models that relied on retrospective administrative data could be potentially used to risk-adjust readmission rates for hospital comparison; of these, 9 were tested in large US populations and had poor discriminative ability (c statistic range: 0.55-0.65). Seven models could potentially be used to identify high-risk patients for intervention early during a hospitalization (c statistic range: 0.56-0.72), and 5 could be used at hospital discharge (c statistic range: 0.68-0.83). Six studies compared different models in the same population and 2 of these found that functional and social variables improved model discrimination. Although most models incorporated variables for medical comorbidity and use of prior medical services, few examined variables associated with overall health and function, illness severity, or social determinants of health. Conclusions: Most current readmission risk prediction models that were designed for either comparative or clinical purposes perform poorly. Although in certain settings such models may prove useful, efforts to improve their performance are needed as use becomes more widespread. ©2011 American Medical Association. All rights reserved.