Christopher S Coffey

University of Iowa, Iowa City, Iowa, United States

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Publications (127)723.72 Total impact

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    ABSTRACT: This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits. Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ((123) I)ioflupane dopamine transporter (DAT) single-photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra. A repeated-measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD. Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26325 · 5.68 Impact Factor
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    ABSTRACT: Numerous studies have demonstrated the value of including pharmacists in team-based care to improve adherence to cardiovascular (CV) guidelines, medication adherence, and risk factor control. However, there is limited information on whether these models can be successfully implemented more widely in diverse settings and populations. The purpose of this study is to evaluate whether a centralized, web-based cardiovascular risk service (CVRS) managed by clinical pharmacists will improve guideline adherence in multiple primary care medical offices with diverse geographic and patient characteristics. This study is a prospective trial in 20 primary care offices stratified by the percent of under-represented minorities and then randomized to either the CVRS intervention or usual care. The intervention will last for 12 months and all subjects will have research visits at baseline and 12 months. The primary outcome is the difference in guideline adherence between groups. Data will also be abstracted from the medical record at 24 months to determine if the intervention effect is sustained after it is discontinued. Patient enrollment will continue through 2016, with results expected in 2019. This study will provide information on whether a distant, centralized CVRS can be implemented in large numbers of medical offices, if it is effective in diverse populations, and if there is a long-term sustained effect. © 2015 Pharmacotherapy Publications, Inc.
    Pharmacotherapy 06/2015; DOI:10.1002/phar.1603 · 2.20 Impact Factor
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    ABSTRACT: This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls. Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10. Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD. This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 06/2015; DOI:10.1002/mds.26248 · 5.68 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Diffusion tensor tractography was performed on 50 drug-naïve PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 04/2015; DOI:10.1002/mds.26251 · 5.68 Impact Factor
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    ABSTRACT: The objective of this study was to describe medication adherence and medication intensification in a physician-pharmacist collaborative management (PPCM) model compared with usual care. This study was a prospective, cluster, randomized study in 32 primary care offices from 15 states. The primary outcomes were medication adherence and anti-hypertensive medication changes during the first 9 months of the intervention. The 9-month visit was completed by 539 patients, 345 of which received the intervention. There was no significant difference between intervention and usual care patients in regards to medication adherence at 9 months. Intervention patients received significantly more medication changes (4.9 vs.1.1; P = .0003) and had significantly increased use of diuretics and aldosterone antagonists when compared with usual care (P = .01).The PPCM model increased medication intensification; however, no significant change in medication adherence was detected. PPCM models will need to develop non-adherence identification and intervention methods to further improve the potency of the care team. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
    Journal of the American Society of Hypertension 04/2015; 9(4):e1-e2. DOI:10.1016/j.jash.2015.03.012 · 2.68 Impact Factor
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    ABSTRACT: This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD). Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS. Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy. Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P < 0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P < 0.001) and apathy (P < 0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P = 0.51). Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 03/2015; 30(7). DOI:10.1002/mds.26170 · 5.68 Impact Factor
  • Christopher S Coffey
    Stroke 01/2015; 46(2). DOI:10.1161/STROKEAHA.114.004288 · 6.02 Impact Factor
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    ABSTRACT: Medical and health policy decision-makers require improved design and analysis methods for comparative effectiveness research (CER) trials. In CER trials, there may be limited information to guide initial design choices. In general settings, adaptive designs (ADs) have effectively overcome limits on initial information. However, CER trials have fundamental differences from standard clinical trials including population heterogeneity and a vaguer concept of a “minimum clinically meaningful difference”. The objective of this article is to explore the use of a particular form of ADs for comparing treatments within the CER trial context. To achieve this, the authors review the current state of clinical CER. They also identify areas of CER as particularly strong candidates for application of novel AD and illustrate the potential usefulness of the designs and methods for two group comparisons. The authors found that ADs can stabilize power. Furthermore, the designs ensure adequate power for true effects are at least at clinically significant pre-planned effect size, or when variability is larger than expected. The designs allow for sample size savings when the true effect is larger or when variability is smaller than planned. The authors conclude that ADs in CER have great potential to allow trials to successfully and efficiently make important comparisons.
    Clinical Research and Regulatory Affairs 11/2014; 32(1). DOI:10.3109/10601333.2014.977490
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    ABSTRACT: Objective To determine if asthma control improves in patients who receive physician–pharmacist collaborative management (PPCM) during visits to primary care medical offices.DesignProspective pre–post study of patients who received the intervention in primary care offices for 9 months. The primary outcome was the sum of asthma-related emergency department (ED) visits and hospitalizations at 9 months before, 9 months during, and 9 months after the intervention. Events were analyzed using linear mixed-effects regression. Secondary analysis was conducted for patients with uncontrolled asthma (Asthma Control Test [ACT] less than 20). Additional secondary outcomes included the ACT, the Asthma Quality of Life Questionnaire by Marks (AQLQ-M) scores, and medication changes.InterventionPharmacists provided patients with an asthma self-management plan and education and made pharmacotherapy recommendations to physicians when appropriate.ResultsOf 126 patients, the number of emergency department (ED) visits and/or hospitalizations decreased 30% during the intervention (p=0.052) and then returned to preenrollment levels after the intervention was discontinued (p=0.83). Secondary analysis of patients with uncontrolled asthma at baseline (ACT less than 20), showed 37 ED visits and hospitalizations before the intervention, 21 during the intervention, and 33 after the intervention was discontinued (p=0.019). ACT and AQLQ-M scores improved during the intervention (ACT mean absolute increase of 2.11, AQLQ-M mean absolute decrease of 4.86, p<0.0001) and sustained a stable effect after discontinuation of the intervention. Inhaled corticosteroid use increased during the intervention (p=0.024).Conclusions The PPCM care model reduced asthma-related ED visits and hospitalizations and improved asthma control and quality of life. However, the primary outcome was not statistically significant for all patients. There was a significant reduction in ED visits and hospitalizations during the intervention for patients with uncontrolled asthma at baseline. Our findings support the need for further studies to investigate asthma outcomes achievable with the PPCM model.
    Pharmacotherapy 10/2014; 34(10). DOI:10.1002/phar.1468 · 2.20 Impact Factor
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    ABSTRACT: Background and Purpose-The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. Methods-We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. Results-During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin <13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m(2) decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). Conclusions-Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain.
    Stroke 08/2014; 45(10). DOI:10.1161/STROKEAHA.114.005789 · 6.02 Impact Factor
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    ABSTRACT: Interventional Management of Stroke (IMS) III is a randomized, parallel arm trial comparing the approach of intravenous tissue plasminogen activator followed by endovascular treatment with intravenous tissue plasminogen activator alone in patients with acute ischemic stroke presenting <3 hours of symptom onset. The trial intended to enroll 900 subjects to ensure adequate statistical power to detect an absolute 10% difference in the percentage of subjects with good outcome, defined as modified Rankin Scale score of 0 to 2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the National Institute of Neurological Disorders and Stroke based on the prespecified criterion for futility using conditional power <20%. Conditional power was defined as the likelihood of finding statistical significance at the end of the study, given the accumulated data to date and with the assumption that a minimum hypothesized difference of 10% truly exists between the 2 groups. The evolution of study data leading to futility determination is described, including the interaction between the unblinded study statisticians and the Data and Safety Monitoring Board in the complex deliberation of analysis results. The futility boundary was crossed at the trial's fourth interim analysis. At this point, based on the conditional power criteria, the Data and Safety Monitoring Board recommended termination of the trial. Even in spite of prespecified interim analysis boundaries, interim looks at data pose challenges in interpretation and decision making, underscoring the importance of objective stopping criteria. http://www.clinicaltrials.gov. Unique identifier: NCT00359424.
    Stroke 04/2014; 45(5). DOI:10.1161/STROKEAHA.113.003925 · 6.02 Impact Factor
  • Journal of the American Society of Hypertension 04/2014; 8(4):e126. DOI:10.1016/j.jash.2014.03.288 · 2.68 Impact Factor
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    ABSTRACT: Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP >4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
    Stroke 03/2014; 45(3):707-16. DOI:10.1161/STROKEAHA.113.004562 · 6.02 Impact Factor
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    ABSTRACT: Adaptive designs are increasingly used in clinical trials. The Drug Information Association’s Adaptive Design Scientific Working Group (ADSWG) works to foster collaboration among regulatory agencies, academia, and pharmaceutical and biotech companies to further the science of adaptive clinical development. The ADSWG Survey Subteam has collected data on the usage of adaptive designs in clinical research from multiple sources, including a recent ADSWG survey regarding the perception and usage of adaptive designs in academia and industry for studies between 2008 and 2011, as well as barriers to usage; a literature review examining publications of adaptive design methodology and usage between 2000 and 2011; and a trial registry review of adaptive design references from 1996 to 2011. The comprehensive results of the ADSWG 2012 survey are provided in this article with comparisons to our previous 2008 survey, the literature and registry reviews, and recent surveys carried out by the US Food and Drug Administration (FDA) and the European Medicines Agency. Results of the ADSWG 2012 survey illustrate that industry and academia are showing more enthusiasm for adaptive trials, accompanied by an increase in the number of trials using designs described as less well understood in the FDA draft guidance on adaptive designs, published in 2010. The increased use of these methods in exploratory trials is consistent with the FDA draft guidance. The survey also identified several examples of successful marketing applications supported by confirmatory trials utilizing adaptive designs that were considered, at least at the time of the draft guidance, as less well understood. While some of the technological barriers to adaptive design usage identified in the 2008 survey are now less common, there are several important persistent barriers to usage. Organizations can help overcome these barriers through education, preplanning, and early engagement in discussions with the regulators.
    Therapeutic Innovation and Regulatory Science 02/2014; DOI:10.1177/2168479014522468
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    ABSTRACT: With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.
    Journal of the American Society for Experimental NeuroTherapeutics 11/2013; 11(1). DOI:10.1007/s13311-013-0221-6 · 3.88 Impact Factor
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    ABSTRACT: IMPORTANCE We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. RESULTS Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression.
    08/2013; 70(10). DOI:10.1001/jamaneurol.2013.3861
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    ABSTRACT: Background Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. Methods In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. Findings 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3.7 (SD 2.0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0.81, 95% CI 0.64-1.03, p=0.08), disabling or fatal stroke (0.81, 0.53-1.23, p=0.32), and the composite outcome of myocardial infarction or vascular death (0.84, 0.68-1.04, p=0.32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0.37, 0.15-0.95, p=0.03). Treatment-related serious adverse events were infrequent. Interpretation Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial.
    The Lancet 08/2013; 382(9891):507-515. DOI:10.1016/S0140-6736(13)60852-1 · 45.22 Impact Factor
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    ABSTRACT: Background: There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value. Methods: We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit. Results: The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001). Conclusions: The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units.
    Cerebrovascular Diseases 07/2013; 36(1):69-73. DOI:10.1159/000351514 · 3.70 Impact Factor
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    ABSTRACT: This paper examines baseline characteristics from a prospective, cluster-randomized trial in 32 primary care offices. Offices were first stratified by percentage of minorities and level of clinical pharmacy services and then randomized into 1 of 3 study groups. The only differences between randomized arms were for marital status (P=.03) and type of insurance coverage (P<.001). Blood pressures (BPs) were similar in Caucasians and minority patients, primarily blacks, who were hypertensive at baseline. On multivariate analyses, patients who were 65 years and older had higher systolic BP (152.4±14.3 mm Hg), but lower diastolic BP (77.3±11.8 mm Hg) compared with those younger than 65 years (147.4±15.0/88.6±10.6 mm Hg, P<.001 for both systolic and diastolic BP). Other factors significantly associated with higher systolic BP were a longer duration of hypertension (P=.04) and lower basal metabolic index (P=.011). Patients with diabetes or chronic kidney disease had a lower systolic BP than those without these conditions (P<.0001). BP was similar across racial and socioeconomic groups for patients with uncontrolled hypertension in primary care, suggesting that patients with uncontrolled hypertension and an established primary care relationship likely have different reasons for poor BP control than other patient populations.
    Journal of Clinical Hypertension 06/2013; 15(6):404-12. DOI:10.1111/jch.12091 · 2.96 Impact Factor
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    ABSTRACT: Background Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents. MethodsCHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24). Conclusions The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.
    Headache The Journal of Head and Face Pain 05/2013; 53(5). DOI:10.1111/head.12105 · 3.19 Impact Factor

Publication Stats

3k Citations
723.72 Total Impact Points

Institutions

  • 2010–2015
    • University of Iowa
      • Department of Biostatistics
      Iowa City, Iowa, United States
  • 2012
    • University of Texas Health Science Center at San Antonio
      • School of Nursing
      San Antonio, TX, United States
  • 2001–2012
    • University of Alabama at Birmingham
      • Department of Biostatistics
      Birmingham, Alabama, United States
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2009
    • Morehouse School of Medicine
      • Department of Surgery
      Atlanta, Georgia, United States
  • 2008
    • Kansas State University
      • Department of Statistics
      Manhattan, KS, United States
  • 2005
    • University of Alabama
      Tuscaloosa, Alabama, United States
  • 2004
    • University of Toronto
      • Division of Cardiology
      Toronto, Ontario, Canada
  • 2003
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States
  • 2002
    • Centers for Disease Control and Prevention
      • Epidemiology and Analysis Program Office
      Druid Hills, GA, United States
  • 2000–2002
    • Vanderbilt University
      • Division of Urologic Surgery
      Нашвилл, Michigan, United States
  • 1999
    • University of North Carolina at Chapel Hill
      North Carolina, United States