Eleanor L. Olvey

Contemporary Pharmacologic Treatments for Spasticity of the Upper Limb After Stroke: A Systematic Review

BACKGROUND Muscle spasticity after stroke may be painful and severe and may restrict the patients ability to perform routine daily tasks, particularly when the affected muscles are in the upper limbs. Treatments targeted at reducing this spasticity have evolved over time. OBJECTIVE This was a systematic review of recent studies focusing on contemporary pharmacologic therapies for upper limb spasticity after stroke. METHODS MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched for clinical trials published in English from January 1995 to July 2010 using search terms that included spasticity, stroke, hemiplegia, phenol, baclofen, tizanidine, dantrolene, benzodiazepine, and botulinum toxin. The level of evidence of the identified publications was assessed using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS A total of 113 potentially relevant articles were identified by the search; of these, 54 studies were included in the review (23 randomized controlled trials [RCTs] and 31 open-label, nonrandomized, or observational studies). Of these, 51 involved treatment with botulinum toxin (BTX). All studies assessed spasticity; some also assessed additional outcomes, such as pain, disability, and functional status. Thirty-eight clinical trials reported a significant reduction in spasticity with BTX, either compared with baseline or with placebo (P < 0.05). A head-to-head comparison found a significant reduction in spasticity with BTX injections compared with oral tizanidine (TZD) (P < 0.001). Two studies of intrathecal baclofen (ITB) reported significant reductions in upper limb spasticity after 12 months of treatment, and 1 study of tizanidine reported significant reductions in upper limb spasticity after 16 weeks of treatment (all, P < 0.001). General or local weakness, injection-site pain, and fatigue were the most frequently reported adverse events with BTX type A, and dry mouth was the most frequently reported adverse event with BTX type B. No serious or life-threatening adverse events were reported in any trial of BTX. CONCLUSIONS The 54 studies included in this systematic review of treatments for upper limb spasticity after stroke measured multiple outcomes using a variety of instruments. Fifty-one studies focused on treatment with a BTX formulation. BTX appeared to be an effective and well-tolerated focal treatment for reducing tonicity in patients with upper limb spasticity after stroke, supporting current guideline recommendations.

Econometric approaches in evaluating costs and outcomes within pharmacoeconomic analyses

Cost and outcomes data within pharmacoeconomic analyses often possess distributional properties that require advanced statistical approaches to yield robust findings. An analyst’s failure to recognize and control for these characteristics may result in inappropriate evaluations of statistical associations or causal effects which may ultimately support incorrect policy decisionmaking. Given the importance of appropriate analysis and interpretation in pharmacoeconomics, the purpose of this paper is to address the more common statistical issues encountered in assessing healthcare costs or outcomes, emphasizing approaches that may be employed to analyze these data. More specifically, statistical methods used commonly with retrospective cohort analyses are presented including least squares (e.g., ordinary least squares, OLS), logarithmic transformations, log-plus-constant models, two-part models, maximum likelihood estimation (MLE), and generalized linear models (GLM) and extensions, among others.

The diagnosis of asthma and exercise-induced bronchospasm in division I athletes.

Objective:To determine the accuracy of clinically diagnosed exercise-induced bronchospasm (EIB) and asthma among National Collegiate Athletic Association Division I student athletes. Design:Cohort study. Setting:Division I university athletic department and primary care sports medicine clinic/athletic training room. Patients:All varsity athletes were eligible for the study. Seventy-five participants entered the study; 74 completed all the study protocols. Interventions:Study participants underwent measurement of exhaled nitric oxide (eNO), followed by baseline spirometry. Eucapnic voluntary hyperventilation (EVH) was then performed, followed by spirometry every 3 minutes for a total of 21 minutes to measure change in forced expiratory volume in 1 second. Main Outcome Measures:Exhaled nitric oxide levels, baseline spirometry, and response of forced expiratory volume in 1 second to EVH. Results:There were a total of 16 subjects with a positive EVH test. There were 16 (80%) individuals using a bronchodilator who had a negative EVH test versus 4 (20%) who had a positive test. Mean eNO values were different across subject groups defined by treatment status, although not statistically significant. The highest mean eNO value of 24.32 ppb was found in subjects only taking bronchodilators compared with the lowest mean value of 16.75 ppb in athletes who were not taking any medications. Conclusions:The results from this study provide further evidence to support the need for objective testing to correctly diagnose EIB. These data suggest that measuring eNO may help to distinguish truly isolated EIB from asthma in athletes, but a larger study is needed to confirm these initial observations.

The cost-effectiveness of sertraline in the treatment of depression

Depressive disorders are common conditions that place a large burden of illness on patients, employers, payers, and society. Although efficacious interventions exist to treat various forms of the condition, substantial gaps in care remain. The selective serotonin re-uptake inhibitors (SSRIs) represent the most commonly utilized drug class for the treatment of depression; sertraline is the most prescribed single agent and received generic drug approval in 2006. The results of pharmacoeconomic analyses comparing the costs and outcomes of sertraline with other antidepressants are mixed; in particular, investigations emphasize branded medications relative to costs. Continued research is needed to support decision making given recent changes in the antidepressant marketplace, particularly the introduction of generic sertraline and newer agents, and the complexity that surrounds the management of depressive disorders.

Cost-effectiveness of urokinase and alteplase for treatment of acute peripheral artery disease: comparison in a decision analysis model.

PURPOSE The cost-effectiveness of urokinase and alteplase for the treatment of acute peripheral artery disease (PAD) was compared using decision analysis. METHODS A literature-based decision model to evaluate cost-effectiveness was constructed using a base case of a 65-year-old man with acute PAD. Successful treatment outcomes were defined as clot lysis with a subsequent 30-day survival posttreatment. Direct medical costs were assessed from the payer perspective in the United States and analyzed using sensitivity analyses. A Monte Carlo analysis with 5000 patients was performed to obtain mean and incremental cost-effectiveness ratios (ICERs). RESULTS The mean cost-effectiveness ratio was

The 'fourth hurdle' of pharmacogenomics

67,581 (95% confidence interval [CI],

PMS46 TREATMENTS FOR UPPER-LIMB POST-STROKE SPASTICITY: A CRITICAL EVALUATION

36,899 to

Perspectives for Managed Care Organizations on the Burden of Multiple Sclerosis and the Cost-Benefits of Disease-Modifying Therapies

108,836) per 30-day treatment success for alteplase and

Cost-effectiveness of medication therapy management in part D diabetic enrollees

78,729 (95% CI,

Intramuscular interferon beta-1a and evolving treatment options and outcomes measurement for MS: considerations for managed care.

43,411 to