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1.  Does Pre-existing Antiplatelet Treatment Influence Post-thrombolysis Intracranial Hemorrhage in Community-treated Ischemic Stroke Patients? An Observational Study 
Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between pre-existing antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether pre-existing antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders.
Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004, and 24 distinct hospitals from 2007 to 2010 as part of a cluster randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a pre-specified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to post-thrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques.
There were 830 patients included, with 47% having documented pre-existing antiplatelet treatment. The mean age was 69 years (SD ± 15 years), and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use, and 19.3% with antiplatelet use (absolute risk difference 4.2%, 95% CI = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio 1.1, 95% CI = 0.8 to 1.7), or sICH (odds ratio 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted odds ratio of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4).
The authors did not find that pre-existing antiplatelet use was associated with post-thrombolysis ICH or sICH in this cohort of community treated patients. Pre-existing tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with pre-existing antiplatelet use.
PMCID: PMC3576048  PMID: 23406073
2.  Anti-hypertensive treatment prolongs tPA door-to-treatment time: Secondary analysis of the INSTINCT trial. 
Identifying modifiable tPA treatment delays may improve stroke outcomes. We hypothesized that pre-thrombolytic anti-hypertensive treatment (AHT) may prolong door-to-treatment time (DTT).
Analysis of consecutive tPA-treated patients at 24 randomly selected community hospitals in the INSTINCT trial between 2007-2010. DTTs among stroke patients who received pre-thrombolytic AHT were compared to those that did not receive pre-thrombolytic AHT. We then calculated a propensity score for the probability of receiving pre-thrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (NIHSS), onset-to-door time, admission glucose, pretreatment blood pressure, EMS transport and location at time of stroke as independent variables. A paired t-test was performed to compare the DTTs between the propensity matched groups.
Of 534 tPA treated stroke patients analyzed, 95 received pre-thrombolytic AHT. In the unmatched cohort, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 9 minutes; 95% confidence interval (CI) 2-16 minutes) than patients who did not. After propensity matching, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 10.4 minutes, 95% CI 1.9 - 18.8) than patients who did not receive pre-thrombolytic AHT.
Pre-thrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality improvement initiatives. Further research evaluating optimum pre-thrombolytic hypertension management is warranted.
PMCID: PMC3508250  PMID: 23033348
3.  Intermediate Cognitive Phenotypes in Bipolar Disorder 
Journal of affective disorders  2009;122(3):285-293.
Intermediate cognitive phenotypes (ICPs) are measurable and quantifiable states that may be objectively assessed in a standardized method, and can be integrated into association studies, including genetic, biochemical, clinical, and imaging based correlates. The present study used neuropsychological measures as ICPs, with factor scores in executive functioning, attention, memory, fine motor function, and emotion processing, similar to prior work in schizophrenia.
Healthy control subjects (HC, n=34) and euthymic (E, n=66), depressed (D, n=43), or hypomanic/mixed (HM, n=13) patients with bipolar disorder (BD) were assessed with neuropsychological tests. These were from eight domains consistent with previous literature; auditory memory, visual memory, processing speed with interference resolution, verbal fluency and processing speed, conceptual reasoning and set-shifting, inhibitory control, emotion processing, and fine motor dexterity.
Of the eight factor scores, the HC group outperformed the E group in three (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity), the D group in seven (all except Inhibitory Control), and the HM group in four (Inhibitory Control, Processing Speed with Interference Resolution, Fine Motor Dexterity, and Auditory Memory).
The HM group was relatively small, thus effects of this phase of illness may have been underestimated. Effects of medication could not be fully controlled without a randomized, double-blind, placebo-controlled study.
Use of the factor scores can assist in determining ICPs for BD and related disorders, and may provide more specific targets for development of new treatments. We highlight strong ICPs (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity) for further study, consistent with the existing literature.
PMCID: PMC3773480  PMID: 19800130
Bipolar disorder; cognition; executive function; emotion; phenotype; intermediate phenotype; mania; depression
4.  The Impact of Emergency Physician Turnover on Planning for Prospective Clinical Trials 
Emergency physician (EP) turnover is a significant issue that can have strong economic impact on hospital systems, as well as implications on research efforts to test and improve clinical practice. This work is particularly important to researchers planning randomized trials directed toward EPs because a large degree of turnover within a physician group would attenuate the effectiveness of the desired intervention. We sought to determine the incidence and factors associated with EP workforce changes.
In an attempt to determine EP turnover and workforce change, data from the INSTINCT (INcreasing Stroke Treatment through INterventional behavior Change Tactics) trial were used. The INSTINCT trial is a prospective, cluster-randomized, controlled trial evaluating a targeted behavioral intervention to increase appropriate use of tissue plasminogen activator in acute ischemic stroke. Individual EPs staffing each of the study hospitals were identified at baseline and 18 months. Surveys were sent to EPs at both intervals. Models were constructed to investigate relationships between physician/hospital characteristics and workforce change.
A total of 278 EPs were identified at baseline. Surveys were sent to all EPs at baseline and 18 months with a response rate of 72% and 74%, respectively. At 18 months, 37 (15.8%) had left their baseline hospital and 66 (26.3%) new EPs were working. Seven EPs switched hospitals within the sample. The total number of EPs at 18 months was 307, a 10.8% overall increase. Among the 24 hospitals, 6 had no EP departures and 5 had no new arrivals. The median proportion of EP workforce departing by hospital was 16% (interquartile range [IQR] = 4%–25%; range = 0%–73%), and the median proportion added was 21% (IQR = 7%–41%; range = 0%–120%). None of the evaluated covariates investigating relationships between physician/hospital characteristics and workforce change were significant.
EP workforce changes over an 18-month period were common. This has implications for emergency department directors, researchers, and individual EPs. Those planning research involving interventions upon EPs should account for turnover as it may have an impact when designing clinical trials to improve performance on healthcare delivery metrics for time-sensitive medical conditions such as stroke, acute myocardial infarction, or trauma.
PMCID: PMC3582518  PMID: 23447752
5.  Provider perceptions of barriers to the emergency use of tPA for Acute Ischemic Stroke: A qualitative study 
Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care.
Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist).
The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines.
Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful.
Trial Registration identifier: NCT00349479
PMCID: PMC3112102  PMID: 21548943
6.  Gender Specific Disruptions in Emotion Processing in Younger Adults with Depression 
Depression and anxiety  2009;26(2):182-189.
One of the principal theories regarding the biological basis of Major Depressive Disorder (MDD) implicates a dysregulation of emotion processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. The current study sought to explore how gender and depression status relate to emotion processing.
This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N = 151).
For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did non-depressed women and men with MDD, particularly for fearful and sad stimuli (ps < .02), which they were likely to misinterpret as angry (ps < .04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared with non-depressed women (p = .01). Men with MDD, conversely, performed similarly to control men (p = .61).
These results provide novel and intriguing evidence that depression in younger adults (< 35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men.
PMCID: PMC3013355  PMID: 18800371
psychiatric disorders; affect perception; sex differences

Results 1-6 (6)