Publications by authors named "Brad J Kolls"

26 Publications

  • Page 1 of 1

Surgical intervention and patient factors associated with poor outcomes in patients with traumatic brain injury at a tertiary care hospital in Uganda.

J Neurosurg 2021 Mar 26:1-10. Epub 2021 Mar 26.

1Duke University Division of Global Neurosurgery and Neurology, Durham.

Objective: The purpose of this study was to investigate whether neurosurgical intervention for traumatic brain injury (TBI) is associated with reduced risks of death and clinical deterioration in a low-income country with a relatively high neurosurgical capacity. The authors further aimed to assess whether the association between surgical intervention and acute poor outcomes differs according to TBI severity and various patient factors.

Methods: Using TBI registry data collected from a national referral hospital in Uganda between July 2016 and April 2020, the authors performed Cox regression analyses of poor outcomes in admitted patients who did and did not undergo surgery for TBI, with surgery as a time-varying treatment variable. Patients were further stratified by TBI severity using the admission Glasgow Coma Scale (GCS) score: mild TBI (mTBI; GCS scores 13-15), moderate TBI (moTBI; GCS scores 9-12), and severe TBI (sTBI; GCS scores 3-8). Poor outcomes constituted Glasgow Outcome Scale scores 2-3, deterioration in TBI severity between admission and discharge (e.g., mTBI to sTBI), and death. Several clinical and demographic variables were included as covariates. Patients were observed for outcomes from admission through hospital day 10.

Results: Of 1544 patients included in the cohort, 369 (24%) had undergone surgery. Rates of poor outcomes were 4% (n = 13) for surgical patients and 12% (n = 144) among nonsurgical patients (n = 1175). Surgery was associated with a 59% reduction in the hazard for a poor outcome (HR 0.41, 95% CI 0.23-0.72). Age, pupillary nonreactivity, fall injury, and TBI severity at admission were significant covariates. In models stratifying by TBI severity at admission, patients with mTBI had an 80% reduction in the hazard for a poor outcome with surgery (HR 0.20, 95% CI 0.04-0.90), whereas those with sTBI had a 65% reduction (HR 0.35, 95% CI 0.14-0.89). Patients with moTBI had a statistically nonsignificant 56% reduction in hazard (HR 0.44, 95% CI 0.17-1.17).

Conclusions: In this setting, the association between surgery and rates of poor outcomes varied with TBI severity and was influenced by several factors. Patients presenting with mTBI had the greatest reduction in the hazard for a poor outcome, followed by those presenting with sTBI. However, patients with moTBI had a nonsignificant reduction in the hazard, indicating greater variability in outcomes and underscoring the need for closer monitoring of this population. These results highlight the importance of accurate, timely clinical evaluation throughout a patient's admission and can inform decisions about whether and when to perform surgery for TBI when resources are limited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.9.JNS201828DOI Listing
March 2021

COVID-19-Associated Guillain-Barre Syndrome: Atypical Para-infectious Profile, Symptom Overlap, and Increased Risk of Severe Neurological Complications.

SN Compr Clin Med 2020 Nov 21:1-13. Epub 2020 Nov 21.

Duke Division of Global Neurosurgery and Neurology, Department of Neurosurgery, Duke University Medical Center, Box 3807, Durham, NC 27705 USA.

The concurrence of COVID-19 with Guillain-Barre syndrome (GBS) can increase the likelihood of neuromuscular respiratory failure, autonomic dysfunction, and other life-threatening symptoms. Currently, very little is known about the underlying mechanisms, clinical course, and prognostic implications of comorbid COVID-19 in patients with GBS. We reviewed COVID-19-associated GBS case reports published since the outbreak of the pandemic, with a database search up to August 2020, including a manual search of the reference lists for additional relevant cases. Fifty-one (51) case reports of COVID-19 patients (aged 23-84 years) diagnosed with GBS in 11 different countries were included in this review. The results revealed atypical manifestations of GBS, including para-infectious profiles and onset of GBS without antecedent COVID-19 symptoms. Although all tested patients had signs of neuroinflammation, none had SARS-CoV-2 in the cerebrospinal fluid (CSF), and only four (4) patients had antiganglioside antibodies. The majority had a 1- to 10-day time interval between the onset of COVID-19 and GBS symptoms, and many had a poor outcome, with 20 out of the 51 (39.2%) requiring mechanical ventilation, and two deaths within 12 to 24 h. The atypical manifestations of COVID-19-associated GBS, especially the para-infectious profile and short time interval between the onset of the COVID-19 and GBS symptoms, increase the likelihood of symptom overlap, which can complicate the treatment and result in worsened disease progression and/or higher mortality rates. Inclusion of a neurological assessment during diagnosis of COVID-19 might facilitate timely identification and effective management of the GBS symptoms and improve treatment outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42399-020-00646-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680081PMC
November 2020

Barriers to biomedical care for people with epilepsy in Uganda: A cross-sectional study.

Epilepsy Behav 2021 01 20;114(Pt B):107349. Epub 2020 Sep 20.

Duke Division of Global Neurosurgery and Neurology, Department of Neurosurgery, Box 3807 Duke University Medical Center, Durham, NC 27705, USA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, DUMC Box 3119, Trent Drive, Durham, NC, USA; Duke University School of Medicine, Department of Neurology, Durham, NC, USA. Electronic address:

Objective: Epilepsy, a neurological disorder with effective biomedical treatment, remains largely untreated in Uganda. Potential reasons for this treatment gap (TG) include limited access to trained providers and clinics, social stigmata of seizures, cultural beliefs, or lack of public understanding of epilepsy as a treatable condition. The current study aimed to formally evaluate barriers faced by people with epilepsy (PWE) in Uganda when seeking biomedical care.

Methods: In a cross-sectional study, 435 participants drawn from a community prevalence study were enrolled. We included participants reporting a history of recurrent seizures suggestive of epilepsy, who completed a survey about barriers to obtaining care for their symptoms. Principal axis factor analysis (PFA) using a promax rotation was conducted for data reduction. Frequencies of barrier factors were compared across those who did not seek care for epilepsy (n = 228), those who sought care from biomedical facilities (n = 166), and those who sought care from a traditional or pastoral healer (n = 41).

Results: The PFA yielded a five-factor solution: 1) logistical and actual costs; 2) treatment effectiveness; 3) influence of the opinion of others; 4) doctors' care; and 5) contextual factors impacting decision-making. Variables related to logistical and actual costs were most endorsed. Comparison of groups by care sought did not reveal a difference in endorsement of factors, with the exception that those who sought biomedical care were more likely to endorse factors related to doctors' care compared with those that sought care from traditional or pastoral healers (P = .005).

Conclusions: People with repetitive seizures in Uganda report several barriers to obtaining biomedical care in Uganda, with those related to practical and actual costs endorsed the most. It is imperative that interventions developed to reduce the TG in Uganda consider these practical issues to improve access to effective epilepsy care. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107349DOI Listing
January 2021

Leveraging the lessons learned from studies on the cultural context of epilepsy care in Uganda: Opportunities and future directions.

Epilepsy Behav 2021 01 28;114(Pt B):107302. Epub 2020 Aug 28.

Duke Division of Global Neurosurgery and Neurology, Department of Neurosurgery, Box 3807 Duke University Medical Center, Durham, NC 27705, USA; Duke Global Health Institute, 310 Trent Dr, Durham, NC 27710, USA; Duke University, School of Medicine, Durham, NC, USA.

In this summary paper, we review the body of research contained in this special issue, The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda, and corollary recommendations for a way forward. We review key findings and conclusions for the studies, which tell a story of culture and care-seeking through discussions and data gleaned from a rich research landscape traversing community village dwellings, shared communal areas, churches, and urban hospitals. The voices and perspectives of over 16,000 study participants inclusive of people living with epilepsy, their neighbors and healthcare workers, traditional healers, and faith leaders are reported. From this, we synthesize findings and prioritize a set of recommendations to advance epilepsy care in Uganda. Progress will require infrastructure strengthening, multilevel educational investments, and an ambitious, extensive program of community sensitization. These proposed priorities and actions outline a way forward through formidable but surmountable challenges but require harmonized efforts by government and other relevant stakeholders, scholars, clinicians, and community leaders. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107302DOI Listing
January 2021

Hospital-based epilepsy care in Uganda: A prospective study of three major public referral hospitals.

Epilepsy Behav 2021 01 27;114(Pt B):107301. Epub 2020 Aug 27.

Duke Division of Global Neurosurgery and Neurology, Department of Neurosurgery, Box 3807 Duke University Medical Center, Durham, NC 27705, USA; Duke University School of Medicine, Department of Psychiatry and Behavioral Sciences, DUMC Box 3119, Trent Drive, Durham, NC, USA; Duke University School of Medicine, Department of Neurology, Durham, NC, USA. Electronic address:

Objective: This study sets out to describe the current demographics of people with epilepsy (PWE) attending hospital-based care in Uganda and the epilepsy treatment practices within three of the largest Ugandan public referral hospitals.

Methods: In a six-month prospective cohort study, 626 children and adults attending epilepsy clinics at Mulago National Referral Hospital, Butabika National Referral Mental Hospital and Mbarara Regional Referral Hospital were enrolled. Using a study questionnaire, data were collected at baseline and at 3 weeks, 3 months, and 6 months following enrollment. Specific data surrounding individual patient demographics, clinical characteristics and severity of epilepsy, and treatment of epilepsy with antiepileptic drugs (AEDs) were collected.

Results: Female patients totaled to 50.8%, with a nearly equal gender distribution at each hospital. There was no statistical difference in gender or age between sites. The majority of PWE had completed primary school, with less than 15% of patients completing more than a secondary education. Seizure severity was high, with most patients having multiple seizures per week at the initial onset of epilepsy, and greater than 90% of patients reporting a loss of consciousness with seizures. The majority of patients (54.95%) also reported a developmental or learning delay. Most patients were on 1 AED (46.01%) or 2 AEDs (36.90%), with carbamazepine being the most frequently prescribed AED. There was a trend towards improved seizure severity over the follow-up period, as assessed by the corresponding Personal Impact of Epilepsy Scale (PIES) subscale.

Conclusions: People with epilepsy attending hospital-based care in Uganda tend to have severe forms of epilepsy requiring management with AEDs. Current hospital-based practices show a positive trend for seizure burden and quality of life of PWE in Uganda. Further interventions to improve overall access to biomedical care are required to continue to advance the management of PWE across all communities. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107301DOI Listing
January 2021

Sociocultural determinants and patterns of healthcare utilization for epilepsy care in Uganda.

Epilepsy Behav 2021 01 4;114(Pt B):107304. Epub 2020 Aug 4.

Duke Division of Global Neurosurgery and Neurology, Department of Neurosurgery, Box 3807, Duke University Medical Center, Durham, NC 27705, USA; Duke Global Health Institute, 310 Trent Dr, Durham, NC 27710, USA; Duke University, School of Medicine, 3100 Tower Blvd, Durham, NC 27707, USA.

Objective: Epilepsy is a global public health concern, with the majority of cases occurring in lower- and middle-income countries where the treatment gap remains formidable. In this study, we simultaneously explore how beliefs about epilepsy causation, perceived barriers to care, seizure disorder characteristics, and demographics influence the initial choice of healthcare for epilepsy and its impact on attaining biomedical care (BMC).

Methods: This study utilized the baseline sample (n = 626) from a prospective cohort study of people with epilepsy (PWE) attending three public hospitals in Uganda (Mulago National Referral Hospital, Butabika National Referral Mental Hospital, and Mbarara Regional Referral Hospital) for epilepsy care. Patient and household demographics, clinical seizure disorder characteristics, and sociocultural questionnaires were administered. Logistic regression and principal component analyses (PCA) were conducted to examine associations with the choice of primary seizure treatment.

Results: The sample was 49% female, and 24% lived in rural settings. A biomedical health facility was the first point of care for 355 (56.7%) participants, while 229 (36.6%) first sought care from a traditional healer and 42 (6.7%) from a pastoral healer. Preliminary inspection of candidate predictors using relaxed criteria for significance (p < 0.20) identified several factors potentially associated with a greater odds of seeking BMC first. Demographic predictors included older caredriver (decision-maker for the participant) age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: [0.99, 1.02], p-value: 0.09), greater caredriver education level (OR = 1.21, 95% CI: [1.07, 1.37], p-value = 0.003), and lower ratio of sick to healthy family members (OR = 0.77 [0.56, 1.05], P = 0.097). For clinical predictors, none of the proposed predictors associated significantly with seeking BMC first. Self-report causation predictors associated with a greater odds of seeking BMC first included higher belief in biological causes of epilepsy (OR = 1.31 [0.92, 1.88], P = 0.133) and lower belief in socio-spiritual causes of epilepsy (OR = 0.68 [0.56, 0.84], P < 0.001). In the multivariate model, only higher caredriver education (OR = 1.19 [1.04, 1.36], P = 0.009) and lower belief in socio-spiritual causes of epilepsy (OR = 0.69 [0.56, 0.86], P < 0.01) remained as predictors of seeking BMC first. Additionally, PCA revealed a pattern which included high income with low beliefs in nonbiological causes of epilepsy as being associated with seeking BMC first (OR = 1.32 [1.12, 1.55], p = 0.001). Despite reaching some form of care faster, individuals seeking care from traditional or pastoral healers experienced a significant delay to eventual BMC (P < 0.001), with an average delay of more than two years (traditional healer: 2.53 years [1.98, 3.24]; pastoral care: 2.18 [1.21, 3.91]).

Conclusions: Coupled with low economic and educational status, belief in spiritual causation of epilepsy is a dominant determinant of opting for traditional or pastoral healing over BMC, regardless of concurrent belief in biological etiologies. There is a prolonged delay to eventual BMC for PWE who begin their treatment seeking with nonallopathic providers, and although nonallopathic healers provide PWE with benefits not provided by BMC, this notable delay likely prevents earlier administration of evidence-based care with known efficacy. Based on these findings, initiatives to increase public awareness of neurobiological causes of epilepsy and effectiveness of biomedical drug treatments may be effective in preventing delays to care, as would programs designed to facilitate cooperation and referral among traditional, faith-based, and biomedical providers. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107304DOI Listing
January 2021

Autoimmune Encephalitis: NMDA Receptor Encephalitis as an Example of Translational Neuroscience.

Neurotherapeutics 2020 04;17(2):404-413

Department of Neurology, Duke University School of Medicine, Durham, NC, 27710, USA.

Autoimmune encephalitis (AE) is a group of disorders causing synaptic receptor dysfunction with a broad range of neurological symptoms that has been historically difficult to differentiate clinically. Today, AE represents an excellent example of the rapid determination of the cause of a disease and the ability to identify potential treatments using relatively simple basic science techniques of investigation. Of the number of autoimmune encephalitides identified thus far, one of the best examples of the impact of basic science studies on disease management is NMDA receptor mediated autoimmune encephalitis (NMDAr-AE). In this review, we will provide an overview of the epidemiology of NMDAr-AE, clinical features and treatments, and the basic science tools and techniques that were used to identify the cause, correlate symptoms to underlying pathophysiology, and to understand the mechanism of disease pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13311-020-00861-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283418PMC
April 2020

Implementation of Best Practices-Developing and Optimizing Regional Systems of Stroke Care: Design and Methodology.

Am Heart J 2020 04 15;222:105-111. Epub 2020 Jan 15.

Department of Neurology, Duke University School of Medicine, Durham, NC.

The AHA Guidelines recommend developing multi-tiered systems for the care of patients with acute stroke. An ideal stroke system of care should ensure that all patients receive the most efficient and timely care, regardless of how they first enter or access the medical care system. Coordination among the components of a stroke system is the most challenging but most essential aspect of any system of care. The Implementation of Best Practices For Acute Stroke Care-Developing and Optimizing Regional Systems of Stroke Care (IMPROVE Stroke Care) project, is designed to implement existing guidelines and systematically improve the acute stroke system of care in the Southeastern United States. Project participation includes 9 hub hospitals, approximately 80 spoke hospitals, numerous pre-hospital agencies (911, fire, and emergency medical services) and communities within the region. The goal of the IMPROVE Stroke program is to develop a regional integrated stroke care system that identifies, classifies, and treats acute ischemic stroke patients more rapidly and effectively with reperfusion therapy. The project will identify gaps and barriers to implementation of stroke systems of care, leverage existing resources within the regions, aid in designing strategies to improve care processes, bring regional representatives together to agree on and implement best practices, protocols, and plans based on guidelines, and establish methods to monitor quality of care. The impact of implementation of stroke systems of care on mortality and long-term functional outcomes will be measured.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2020.01.004DOI Listing
April 2020

Stroke in Patients With Peripheral Artery Disease.

Stroke 2019 06 16;50(6):1356-1363. Epub 2019 May 16.

Division of Cardiology, Department of Medicine (W.S.J., M.R.P.), Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.023534DOI Listing
June 2019

Implementation of Continuous Video-Electroencephalography at a Community Hospital Enhances Care and Reduces Costs.

Neurocrit Care 2018 04;28(2):229-238

Department of Neurology, Brain Injury Translational Research Laboratories, Duke University School of Medicine, 311 Research Drive, Bryan Research Building, DUMC 2900, Durham, NC, 27710, USA.

Background: Despite data indicating the importance of continuous video-electroencephalography (cvEEG) monitoring, adoption has been slow outside major academic centers. Barriers to adoption include the need for technologists, equipment, and cvEEG readers. Advancements in lower-cost lead placement templates and commercial systems with remote review may reduce barriers to allow community centers to implement cvEEG. Here, we report our experience, lessons learned, and financial impact of implementing a community hospital cvEEG-monitoring program.

Methods: We implemented an adult cvEEG service at Duke Regional Hospital (DRH), a community hospital affiliate, in June of 2012. Lead placement templates were used in the implementation to reduce the impact on technologists by using other bedside providers for EEG initiation. Utilization of the service, study quality, and patient outcomes were tracked over a 3-year period following initiation of service.

Results: Service was implemented at essentially no cost. Utilization varied from a number of factors: intensive care unit (ICU) attending awareness, limited willingness of bedside providers to perform lead placement, and variation in practice of the consulting neurologists. A total of 92 studies were performed on 88 patients in the first 3 years of the program, 24 in year one, 27 in year two, and 38 in year three, showing progressive adoption. Seizures were seen in 25 patients (27%), 19 were in status, of which 18 were successfully treated. Transfers to the main hospital, Duke University Medical Center, were prevented for 53 patients, producing an estimated cost savings of $145,750. The retained patients produced a direct contribution margin of about $75,000, and the margin was just over $100,000 for the entire monitored cohort.

Conclusion: ICU cvEEG service is feasible and practical to implement at the community hospital level. Service was initiated at little to no cost and clearly enhanced care, increased breadth of care, increased ICU census, and reduced transfers. The system allowed for successful management of ICU patients with underlying seizures and eliminated interfacility transfers, producing a savings of $145,750. The savings combined with the retained patient revenue produced a total revenue of over $250,000 with additional revenue in professional services as well. These results suggest expansion of cvEEG monitoring to community ICUs is practical, financially sustainable, improves the level and quality of care, and reduces costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12028-017-0468-6DOI Listing
April 2018

Cardiovascular adverse events in the drug-development program of bupropion for smoking cessation: A systematic retrospective adjudication effort.

Clin Cardiol 2017 Oct 12;40(10):899-906. Epub 2017 Jun 12.

Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California.

Background: In 2011, the US Food and Drug Administration requested that GlaxoSmithKline perform retrospective adjudication of cardiovascular (CV) events reported in the bupropion drug-development trials for smoking cessation.

Hypothesis: Retrospective adjudication of clinical trial data will not increase the identification of adverse events.

Methods: We performed a comprehensive retrospective analysis of adverse events in 19 previously completed controlled US clinical trials of bupropion marketed for the treatment of smoking cessation, yielding 9479 subjects (5290 bupropion, 2927 placebo, 1018 active control [ACT], and 244 treated concurrently with bupropion and ACT). All adverse events were sent to the Duke Clinical Research Institute for adjudication by Clinical Events Classification (CEC) physician reviewers. The primary endpoint was a composite of major adverse CV events: CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.

Results: Overall, 416 nonfatal CV events in 366 subjects, and 22 deaths, were identified and processed for adjudication. Of these, 7 nonfatal MIs (4 bupropion, 3 placebo, 0 ACT), 5 nonfatal strokes (1 bupropion, 3 placebo, 1 ACT), and 9 CV deaths (4 bupropion, 4 placebo, 1 ACT) were confirmed by the CEC Committee. The primary endpoint occurred in 3/4297 (0.07%) subjects in the bupropion group and in 4/2927 (0.14%) subjects in the placebo group (log-rank P value: 0.613).

Conclusions: CV events in bupropion clinical trials for smoking cessation were uncommon, with no observed increase among subjects assigned to bupropion vs placebo. However, this effort was limited by a paucity of quality data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.22744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490529PMC
October 2017

Apolipoprotein E mimetic peptide, CN-105, improves outcomes in ischemic stroke.

Ann Clin Transl Neurol 2017 04 9;4(4):246-265. Epub 2017 Mar 9.

Department of Neurology Duke University School of Medicine Durham North Carolina.

Objective: At present, the absence of a pharmacological neuroprotectant represents an important unmet clinical need in the treatment of ischemic and traumatic brain injury. Recent evidence suggests that administration of apolipoprotein E mimetic therapies represent a viable therapeutic strategy in this setting. We investigate the neuroprotective and anti-inflammatory properties of the apolipoprotein E mimetic pentapeptide, CN-105, in a microglial cell line and murine model of ischemic stroke.

Methods: Ten to 13-week-old male C57/BL6 mice underwent transient middle cerebral artery occlusion and were randomly selected to receive CN-105 (0.1 mg/kg) in 100 L volume or vehicle via tail vein injection at various time points. Survival, motor-sensory functional outcomes using rotarod test and 4-limb wire hanging test, infarct volume assessment using 2,3,5-Triphenyltetrazolium chloride staining method, and microglial activation in the contralateral hippocampus using F4/80 immunostaining were assessed at various time points. In vitro assessment of tumor necrosis factor-alpha secretion in a microglial cell line was performed, and phosphoproteomic analysis conducted to explore early mechanistic pathways of CN-105 in ischemic stroke.

Results: Mice receiving CN-105 demonstrated improved survival, improved functional outcomes, reduced infarct volume, and reduced microglial activation. CN-105 also suppressed inflammatory cytokines secretion in microglial cells in vitro. Phosphoproteomic signals suggest that CN-105 reduces proinflammatory pathways and lower oxidative stress.

Interpretation: CN-105 improves functional and histological outcomes in a murine model of ischemic stroke via modulation of neuroinflammatory pathways. Recent clinical trial of this compound has demonstrated favorable pharmacokinetic and safety profile, suggesting that CN-105 represents an attractive candidate for clinical translation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376751PMC
April 2017

Implanted electrodes for multi-month EEG.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:6543-8

An implanted electroencephalogram (EEG) recorder would help diagnose infrequent seizure-like events. A proof-of-concept study quantified the electrical characteristics of the electrodes planned for the proposed recorder. The electrodes were implanted in an ovine model for eight weeks. Electrode impedance was less than 800 Ohms throughout the study. A frequency-domain determination of sedation performed similarly for surface versus implanted electrodes throughout the study. The time-domain correlation between an implanted electrode and a surface electrode was almost as high as between two surface electrodes (0.86 versus 0.92). EEG-certified clinicians judged that the implanted electrode quality was adequate to excellent and that the implanted electrodes provided the same clinical information as surface electrodes except for a noticeable amplitude difference. No significant issues were found that would stop development of the EEG recorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC.2014.6945127DOI Listing
October 2015

Response to: reducing the cost of continuous EEG monitoring.

Authors:
Brad J Kolls

J Clin Neurophysiol 2014 Oct;31(5):505

Department of Neurology, Brain Injury Translational Research Center, Duke University School of Medicine, Durham, North Carolina, U.S.A. e-mail:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNP.0000000000000125DOI Listing
October 2014

Integration of EEG lead placement templates into traditional technologist-based staffing models reduces costs in continuous video-EEG monitoring service.

J Clin Neurophysiol 2014 Jun;31(3):187-93

*The Fuqua School of Business, Duke University, Durham, North Carolina, U.S.A.; †Department of Neurology, Duke University School of Medicine, Duke University Medical Center, Durham, North Carolina, U.S.A.; and ‡Brain Injury Translational Research Center, Durham, North Carolina, U.S.A.

Purpose: The purpose of this study was to determine the relative cost reductions within different staffing models for continuous video-electroencephalography (cvEEG) service by introducing a template system for 10/20 lead application.

Methods: We compared six staffing models using decision tree modeling based on historical service line utilization data from the cvEEG service at our center. Templates were integrated into technologist-based service lines in six different ways. The six models studied were templates for all studies, templates for intensive care unit (ICU) studies, templates for on-call studies, templates for studies of ≤ 24-hour duration, technologists for on-call studies, and technologists for all studies.

Results: Cost was linearly related to the study volume for all models with the "templates for all" model incurring the lowest cost. The "technologists for all" model carried the greatest cost. Direct cost comparison shows that any introduction of templates results in cost savings, with the templates being used for patients located in the ICU being the second most cost efficient and the most practical of the combined models to implement. Cost difference between the highest and lowest cost models under the base case produced an annual estimated savings of $267,574. Implementation of the ICU template model at our institution under base case conditions would result in a $205,230 savings over our current "technologist for all" model.

Conclusions: Any implementation of templates into a technologist-based cvEEG service line results in cost savings, with the most significant annual savings coming from using the templates for all studies, but the most practical implementation approach with the second highest cost reduction being the template used in the ICU. The lowered costs determined in this work suggest that a template-based cvEEG service could be supported at smaller centers with significantly reduced costs and could allow for broader use of cvEEG patient monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNP.0000000000000053DOI Listing
June 2014

Seizure predisposition after perinatal hypoxia: effects of subsequent age and of an epilepsy predisposing gene mutation.

Epilepsia 2013 Oct 13;54(10):1789-800. Epub 2013 Sep 13.

Division of Pediatric Neurology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, U.S.A.

Purpose: There is a gap in our knowledge of the factors that modulate the predisposition to seizures following perinatal hypoxia. Herein, we investigate in a mouse model the effects of two distinct factors: developmental stage after the occurrence of the perinatal insult, and the presence of a seizure predisposing mutation.

Methods: Effects of age: P6 (postnatal day 6) mouse pups were subjected to acute hypoxia down to 4% O2 over the course of 45 min. Seizure susceptibilities to flurothyl-induced seizures (single exposures) and to flurothyl kindling were determined at specific subsequent ages. Effects of mutation: Heterozygote mice, with deletion of one copy of the Kcn1a gene, subjected to P6 hypoxia were compared as adults to wild-type mice with respect to susceptibility to a single exposure to flurothyl and to the occurrence of spontaneous seizures as detected by hippocampal electroencephalography (EEG) and video recordings.

Key Findings: Effects of age: As compared to controls, wild-type mice exposed to P6 hypoxia had a shortened seizure latency in response to a single flurothyl exposure at P50, but not at P7 or P28 (p < 0.04). In addition, perinatal hypoxia at P6 enhanced the rate of development of flurothyl kindling performed at P28-38 (p < 0.03), but not at P7-17. Effects of mutation: Kcn1a heterozygous mice subjected to P6 hypoxia exhibited increased susceptibility to flurothyl-induced seizures at P50 as compared to Normoxia heterozygote littermates, and to wild-type Hypoxia and Normoxia mice. In addition, heterozygotes exposed to P6 hypoxia were the only group in which spontaneous seizures were detected during the period of long-term monitoring (p < 0.027 in all comparisons).

Significance: Our data establish a mouse model of mild perinatal hypoxia in which we document the following: (1) the emergence, after a latent period, of increased susceptibility to flurothyl-induced seizures, and to flurothyl induced kindling; and (2) an additive effect of a gene mutation to the seizure predisposing consequences of perinatal hypoxia, thereby demonstrating that a modifier (or susceptibility) gene can exacerbate the long-term consequences of hypoxic injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12347DOI Listing
October 2013

N-methyl-D-aspartate receptors strongly regulate postsynaptic activity levels during optic nerve regeneration.

J Neurosci Res 2013 Oct 19;91(10):1263-79. Epub 2013 Jul 19.

Department of Developmental and Cell Biology, University of California Irvine, Irvine, California; Brain Injury Translational Research Center, Division of Neurology, Duke University Medical Center, Durham, North Carolina.

During development, neuronal activity is used as a cue to guide synaptic rearrangements to refine connections. Many studies, especially in the visual system, have shown that the N-methyl-D-aspartate receptor (NMDAr) plays a key role in mediating activity-dependent refinement through long-term potentiation (LTP)-like processes. Adult goldfish can regenerate their optic nerve and utilize neuronal activity to generate precise topography in their projection onto tectum. Although the NMDAr has been implicated in this process, its precise role in regeneration has not been extensively studied. In examining NMDAr function during regeneration, we found salient differences compared with development. By using field excitatory postsynaptic potential (fEPSP) recordings, the contribution of the NMDAr at the primary optic synapse was measured. In contrast to development, no increase in NMDAr function was detectable during synaptic refinement. Unlike development, LTP could not be reliably elicited during regeneration. Unexpectedly, we found that NMDAr exerted a major effect on regulating ongoing tectal (postsynaptic) activity levels during regeneration. Blocking NMDAr strongly suppressed spontaneous activity during regeneration but had no significant effect in the normal projection. This difference could be attributed to an occlusion effect of strong optic drive in the normal projection, which dominated ongoing tectal activity. During regeneration, this optic drive is largely absent. Optic nerve stimulation further indicated that the NMDAr had little effect on the ability of optic fibers to evoke early postsynaptic impulse activity but was important for late network activity. These results indicate that, during regeneration, the NMDAr may play a critical role in the homeostatic regulation of ongoing activity and network excitability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.23246DOI Listing
October 2013

Targeting telestroke: benchmarking time performance in telestroke consultations.

J Stroke Cerebrovasc Dis 2013 May;22(4):470-5

Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA.

Objective: To describe the length of time physicians spend completing telestroke consultations and examine factors associated with that period.

Methods: This is a retrospective review of data from telestroke software. Clinical data obtained between July 2010 and February 2011 from 8 hub and 24 spoke hospitals were abstracted for 235 consecutive consultations and linked to time metadata generated by software interaction. Consult length was defined as the time logged on to the robot and was exclusive of any telephone interaction or documentation time. Response time was defined as patient arrival to physician log-on.

Results: Mean consult length for 203 complete, time-stamped cases was 14.5 minutes. There was no independent association between consult length and age, diagnosis, time of arrival from symptom onset, neurological exam findings, known recombinant tissue plasminogen activator (r-tPA) contraindications, and absence of vascular risk factors. Mean consult length was statistically longer in r-tPA-recommended cases (20.0 versus 15.3 minutes; P = .04). Mean response time was 76.3 minutes.

Conclusions: The relatively short consult length suggests a workflow model in which acute stroke care is largely completed before telestroke consultation with a specialist rendering an expert opinion on previously gathered data performed off-line. The findings for prolonged response times indicate an area for improvement. Future workflow models for telestroke consultation will need to be reconsidered to optimize quality of care and clinical efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.03.010DOI Listing
May 2013

Lacosamide improves outcome in a murine model of traumatic brain injury.

Neurocrit Care 2013 Aug;19(1):125-34

Department of Anesthesiology, Shandong University Shandong Provincial Hospital, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.

Background: Use of antiepileptic drugs (AED's) is common in the neurocritical care setting. However, there remains a great deal of controversy regarding the optimal agent. Studies associating the prophylactic use of AED's with poor outcomes are heavily biased by the prevalent use of phenytoin, an agent highly associated with deleterious effects. In the current study, we evaluate lacosamide for neuroprotective properties in a murine model of closed head injury.

Methods: Mice were subjected to moderate closed head injury using a pneumatic impactor, and then treated with either low-dose (6 mg/kg) or high-dose (30 mg/kg) lacosamide or vehicle at 30 min post-injury, and twice daily for 3 days after injury. Motor and cognitive functional assessments were performed following injury using rotarod and Morris Water Maze, respectively. Neuronal injury and microglial activation were measured by flourojade-B, NeuN, and F4/80 staining at 1 and 7 days post-injury. Timm's staining was also performed to assess lacosamide effects on mossy fiber axonal sprouting. To evaluate possible mechanisms of lacosamide effects on the inflammatory response to injury, an RNA expression array was used to evaluate for alterations in differential gene expression patterns in injured mice following lacosamide or vehicle treatments.

Results: High-dose lacosamide was associated with improved functional outcome on both the rotarod and Morris Water Maze. High-dose lacosamide was also associated with a reduction of neuronal injury at 24 h post-injury. However, the reduction in neuronal loss observed early did not result in greater neuronal density at 31 days post-injury based on unbiased stereology of NeuN staining. High-dose lacosamide was also associated with a significant reduction in microglial activation at 7 days post-injury. The therapeutic effects of lacosamide are associated with a delay in injury-related changes in RNA expression of a subset of inflammatory mediator genes typically seen at 24 h post-injury.

Conclusions: Administration of lacosamide improves functional performance, and reduces histological evidence of acute neuronal injury and neuroinflammation in a murine model of closed head injury. Lacosamide effects appear to be mediated via a reduction or delay in the acute inflammatory response to injury. Prior clinical and animal studies have found antiepileptic treatment following injury to be detrimental, though these studies are biased by the common use of older medications such as phenytoin. Our current results as well as prior work on levetiracetam suggest the newer AED's may be beneficial in the setting of acute brain injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12028-012-9808-8DOI Listing
August 2013

Electroencephalography leads placed by nontechnologists using a template system produce signals equal in quality to technologist-applied, collodion disk leads.

J Clin Neurophysiol 2012 Feb;29(1):42-9

Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA.

The purpose of this study was to compare the quality of the electroencephalographic (EEG) data obtained with a BraiNet template in a practical use setting, to that obtained with standard 10/20 spaced, technologist-applied, collodion-based disk leads. Pairs of 8-hour blocks of EEG data were prospectively collected from 32 patients with a Glasgow coma score of ≤9 and clinical concern for underlying nonconvulsive status epilepticus over a 6-month period in the Neurocritical Care Unit at the Duke University Medical Center. The studies were initiated with the BraiNet template system applied by critical care nurse practitioners or physicians, followed by standard, collodion leads applied by registered technologists using the 10/20 system of placement. Impedances were measured at the beginning and end of each block recorded and variance in impedance, mean impedance, and the largest differences in impedances found within a given lead set were compared. Physicians experienced in reading EEG performed a masked review of the EEG segments obtained to assess the subjective quality of the recordings obtained with the templates. We found no clinically significant differences in the impedance measures. There was a 3-hour reduction in the time required to initiate EEG recording using the templates (P < 0.001). There was no difference in the overall subjective quality distributions for template-applied versus technologist-applied EEG leads. The templates were also found to be well accepted by the primary users in the intensive care unit. The findings suggest that the EEG data obtained with this approach are comparable with that obtained by registered technologist-applied leads and represents a possible solution to the growing clinical need for continuous EEG recording availability in the critical care setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNP.0b013e318246ae76DOI Listing
February 2012

Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors.

Neurocrit Care 2012 Feb;16(1):109-13

Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Background: There were nearly 700,000 patients in the United States in 2010 living with brain tumor diagnoses. The incidence of seizures in this population is as high as 70% and is historically difficult to control. Approximately 30-40% of brain tumors patients who present with status epilepticus (SE) will not respond to typical therapy consisting of benzodiazepines and phenytoin (PHT), resulting in patients with refractory status epilepticus (RSE). RSE is usually treated with anesthetic doses of propofol or midazolam infusions. This therapy can have significant risk, particularly in patients with cancer.

Methods: A retrospective chart review was performed on 23 patients with primary or metastatic brain tumors whose SE was treated with intravenous PHT, levetiracetam (LEV), and oral pregabalin (PGB).

Results: In all the patients under study, PHT or LEV was used as first-line therapy. PGB was typically used as third-line treatment. The median daily dose of PGB was 375 mg (usually divided BID or TID), and the median daily dose of LEV 3000 mg (usually divided BID). Cessation of SE was seen in 16/23 (70%) after administration of PHT, LEV, and PGB. SE was aborted, on average, 24 h after addition of the third antiepileptic drug. Only one patient in the responder group required intubation. Mortality rate was zero in the responder group. No adverse reactions to this medication regimen were observed.

Conclusion: Our study suggests that the administration of PHT, LEV, and PGB in brain tumor patients with RSE is safe and highly effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12028-011-9626-4DOI Listing
February 2012

Neuroprotection in subarachnoid hemorrhage.

Stroke 2010 Oct;41(10 Suppl):S79-84

Departments of Medicine Neurology, Duke University, Durham NC 27710, USA.

Despite advances in aneurysm ablation and the initial management of patients presenting with aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia remains a significant source of morbidity. Traditionally, delayed cerebral ischemia was thought to be a result of vasospasm of the proximal intracranial vessels, and clinical trials have relied largely on radiographic evidence of vasospasm as a surrogate for functional outcome. However, a number of trials have demonstrated a dissociation between angiographic vasospasm and outcome, and more recent data suggest that other mechanisms of injury, such as microvascular dysfunction and complex neuronal-glial interactions, may influence the development of delayed ischemic deficit after aneurysmal subarachnoid hemorrhage. Our evolving understanding of the pathophysiology of delayed cerebral ischemia may offer the opportunity to test new therapeutic strategies in this area and improve clinical trial design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.110.595090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376008PMC
October 2010

Assessment of hairline EEG as a screening tool for nonconvulsive status epilepticus.

Epilepsia 2007 May 13;48(5):959-65. Epub 2007 Apr 13.

Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.

Purpose: Because of the high incidence of nonconvulsive status epilepticus (NCSE), the attraction of a "quick and easy" screening electroencephalogram (EEG) is obvious. Previous studies have shown utility of hairline EEG in diagnosing epilepsy. However, this technique has not been evaluated as a screening tool for NCSE. We wanted to provide proof of principle that a screening hairline EEG has sufficient sensitivity to use as a screening tool for diagnosing NCSE.

Methods: A total of 120, 2- to 3-min EEG samples of normal and various abnormal digital EEG studies were reformatted in three six-channel montages (A, longitudinal bipolar; B, referential to ipsilateral ear; C, referential to contralateral ear) that mimicked a hairline recording and were interpreted by five neurophysiologists. The test data interpretation was compared with the original EEG interpretation.

Results: Performance was best with montages A and B; 71% and 70.5% of the samples were interpreted correctly by using these montages. Only 65% of the samples were correctly interpreted by using montage C. With the best montage (A), the sensitivities ranged from 91% for normal EEG to 54% for periodic lateralized epileptiform discharges (PLEDs). The sensitivity for seizures was only 72%. Seizures were frequently misinterpreted as more benign patterns such as normal and diffuse slowing.

Conclusions: EEG data reformatted to resemble a hairline EEG had low sensitivity for detecting seizures. As a result, we do not recommend further pursuit of hairline EEG as a "quick and easy" screening tool for NCSE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2007.01078.xDOI Listing
May 2007

Apomorphine: a rapid rescue agent for the management of motor fluctuations in advanced Parkinson disease.

Clin Neuropharmacol 2006 Sep-Oct;29(5):292-301

Division of Neurology, Duke University Medical School, Durham, NC 27705, USA.

Parkinson disease is one of the most common neurodegenerative diseases in the United States, and the number of late stage patients is rising. In advance-stage disease, fluctuations in motor function, variability in response to dopaminergic therapy, and dyskinesias related to increasing doses of dopamine agonists and levodopa, present a variety of challenges to a managing physician. Traditional methods of treatment have concentrated on therapies to anticipate or prevent states of poor motor function. With the approval of apomorphine as a rapid-acting, subcutaneous injectable anti-Parkinson disease therapy, these off periods may now be treated with apomorphine as a "rescue" medication when they occur. This article reviews the pharmacology of apomorphine, the clinical data that support its use and suggest dosing and methods for initiating therapy in this challenging population of patients with Parkinson disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.WNF.0000220824.57769.E5DOI Listing
November 2006