Publications by authors named "D Kern"

692 Publications

From structure to mechanism: skiing the energy landscape.

Authors:
Dorothee Kern

Nat Methods 2021 May;18(5):435-436

Department of Biochemistry and Howard Hughes Medical Institute, Brandeis University, Waltham, MA, USA.

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http://dx.doi.org/10.1038/s41592-021-01140-4DOI Listing
May 2021

Coronal Gradient Echo MRI to Visualize the Zona Incerta for Deep Brain Stimulation Targeting in Parkinson's Disease.

Stereotact Funct Neurosurg 2021 Apr 26:1-8. Epub 2021 Apr 26.

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Introduction: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson's disease patients to improve targeting for deep brain stimulation.

Methods: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson's disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed.

Results: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson's and non-Parkinson's patients for either structure.

Discussion/conclusion: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.
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http://dx.doi.org/10.1159/000515772DOI Listing
April 2021

Characteristics of patients with major depressive disorder switching SSRI/SNRI therapy compared with those augmenting with an atypical antipsychotic in a real-world setting.

Curr Med Res Opin 2021 Apr 29:1-8. Epub 2021 Apr 29.

Janssen Research & Development LLC, Titusville, NJ, USA.

Background: Following a partial response of first-line antidepressant therapy for the treatment of major depressive disorder (MDD), there is a choice to augment treatment with another agent or switch to a different antidepressant.

Objective: To report the prevalence and compare the characteristics of patients switching from their initial selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) to a new SSRI/SNRI versus those augmenting SSRI/SNRI therapy with a second-generation antipsychotic (SGA).

Methods: MDD patients receiving first-line SSRI/SNRI treatment were identified from a large US-based claims database during 2000-2019. Patients augmenting therapy with an SGA were compared with those who switched to a new SSRI/SNRI. The date of the treatment change was the index date. Previously diagnosed comorbid conditions, medication use and demographics were captured. Treatment patterns following the index date were also captured. Standardized differences (StdDiff) were used to quantify dissimilarities between the two groups.

Results: There were 4572 SGA add-on and 24,409 switching patients identified. SGA augmentation patients had more severe disease (diagnosed severe recurrent major depression: 24.7% vs. 9.5%, StdDiff = 0.41) and more diagnosed psychiatric conditions, including: suicidal thoughts (10.7% vs. 3.2%, StdDiff = 0.29), post-traumatic stress disorder (6.1% vs. 2.6%, StdDiff = 0.17) and alcohol abuse (5.4% vs. 2.7%, StdDiff = 0.14). SGA augmentation patients had higher rates of prior use of anxiolytics (37.4% vs. 28.2%, StdDiff = 0.20) and anticonvulsants (26.0% vs. 13.1%, StdDiff = 0.33).

Conclusions: Patients adding an SGA to their SSRI/SNRI therapy appeared to have more severe depression and comorbid psychiatric profile than those switching their SSRI/SNRI. These differences are important to consider and adequately control for in any future comparative outcome research between these two groups.
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http://dx.doi.org/10.1080/03007995.2021.1911975DOI Listing
April 2021

Medical University of South Carolina College of Medicine.

Acad Med 2020 Sep;95(9S A Snapshot of Medical Student Education in the United States and Canada: Reports From 145 Schools):S461-S464

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http://dx.doi.org/10.1097/ACM.0000000000003404DOI Listing
September 2020

Application of Real-World Data and the REWARD Framework to Detect Unknown Benefits of Memantine and Identify Potential Disease Targets for New NMDA Receptor Antagonists.

CNS Drugs 2021 Feb 4;35(2):243-251. Epub 2021 Feb 4.

Janssen Research and Development, 1125 Trenton Harbourton Rd, Titusville, NJ, 08560, USA.

Background: Observational data may inform novel drug development programs by identifying previously unappreciated, clinical benefits of existing drugs. Several preclinical and clinical studies have suggested emergent therapeutic utility of drugs acting on the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, including the antidementia drug memantine.

Methods: Using a self-controlled cohort study design, the association of exposure to the NMDA receptor antagonist memantine with the incidence of all observed disease outcomes in four US administrative claims databases, spanning from January 2000 through January 2019, was assessed. The databases used in this study were the IBM MarketScan Commercial Database (CCAE), the IBM MarketScan Multi-State Medicaid Database (MDCD), the IBM MarketScan Medicare Supplemental Database (MDCR), and the Optum De-Identified Clinformatics Data Mart Database. Outcomes were defined according to the unique Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) classification system codes and required a diagnosis on two or more distinct dates. Of 20,953 outcomes assessed, only those for which memantine was associated with a ≥ 50% reduction in risk in two or more databases were included. A meta-analysis with random effects was used to pool data across the databases.

Results: Overall, 312,336 patients were exposed to memantine during the study. After removing conditions related to dementia and memory loss, 60 outcomes met the threshold criteria. Results fell into five disease categories: mental disorders, substance use disorders, pain, gastrointestinal and colon disorders, and demyelinating disease. The bulk of findings fell into the first two groups, with 28 outcomes related to mental disorders and 24 related to substance use disorders.

Conclusion: The present results confirm that NMDA receptor antagonism may have broader therapeutic utility than previously recognized. Further observational and clinical research may be warranted to explore the therapeutic benefit of NMDA antagonists for the outcomes found in this study.
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http://dx.doi.org/10.1007/s40263-020-00789-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907035PMC
February 2021