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14
result(s) for
"Wittbrodt, Matthew T."
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Application of Noninvasive Vagal Nerve Stimulation to Stress-Related Psychiatric Disorders
by
Rapaport, Mark H.
,
Vaccarino, Viola
,
Shah, Amit J.
in
Antidepressants
,
Autonomic nervous system
,
Biomarkers
2020
Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
Journal Article
Diet, Stress and Mental Health
2020
Introduction: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established. Methods: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress. Results: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood as well as stimulate inflammation, which has led to efforts to assess polyunsaturated fats (PUFA) as a treatment for depression. Bidirectional relationships between these different factors are also likely. Finally, there has been increased attention recently on the relationship between the gut and the brain, with the realization that the gut microbiome has an influence on brain function and probably also mood and behavior, introducing another way diet can influence mental health and disorders. Brain areas and neurotransmitters and neuropeptides that are involved in both mood and appetite likely play a role in mediating this relationship. Conclusions: Understanding the relationship between diet, stress and mood and behavior could have important implications for the treatment of both stress-related mental disorders and obesity.
Journal Article
Sex differences in brain activation patterns with mental stress in patients with coronary artery disease
by
Lima, Bruno B.
,
Shah, Amit J.
,
Hammadah, Muhammad
in
Aged
,
Analysis
,
Biomedical and Life Sciences
2019
Background
Stress is an important contributor to myocardial ischemia and the progression of coronary artery disease (CAD), and women are more susceptible than men to these effects. Little is known, however, about the neural basis of these sex differences.
Methods
We investigated sex differences in neural correlates of mental stress in a sample of 53 female and 112 male participants (
N
= 165) with CAD, with and without mental stress-induced myocardial ischemia (MSI), during exposure to mental arithmetic tasks and public speaking stress tasks using high-resolution positron emission tomography (HR-PET) and radiolabeled water imaging of the brain.
Results
Women compared to men had significantly greater activation with stress in the right frontal (BA 9, 44), right parietal lobe (Area 3, 6, 40), right posterior cingulate gyrus (BA 31), bilateral cerebellum, and left temporal/fusiform gyrus (BA 37) and greater deactivation in bilateral anterior cingulate gyrus (BA 24, 32), bilateral medial frontal gyrus (BA 6, 8, 9, 10), right parahippocampal gyrus, and right middle temporal gyrus (BA 21). Women with MSI (but not those without MSI) showed significantly greater activation than men in the right posterior cingulate gyrus (BA 31) and greater deactivation in several frontal and temporal lobe areas.
Conclusion
Men and women with CAD show differences in responses to stress in brain limbic areas that regulate emotion, and these functional responses differ by MSI status. Our results suggest that the cingulate gyrus may be involved in sex differences in MSI.
Journal Article
Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation
by
Vaccarino, Viola
,
Gazi, Asim H
,
Wittbrodt, Matthew T
in
Biomarkers
,
Double-Blind Method
,
Heart Rate
2020
Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time.
The aim of the present study was to reveal the dynamics of relevant cardiovascular biomarkers, extracted from wearable sensing modalities, in response to tcVNS.
Twenty-four human subjects were recruited for a randomized double-blind clinical trial, for whom electrocardiography and photoplethysmography were used to measure heart rate and photoplethysmogram amplitude responses to tcVNS, respectively. Modeling these responses in state-space, we (1) compared the biomarkers in terms of their predictability and active vs sham differentiation, (2) studied the latency between stimulation onset and measurable effects, and (3) visualized the true and model-simulated biomarker responses to tcVNS.
The models accurately predicted future heart rate and photoplethysmogram amplitude values with root mean square errors of approximately one-fifth the standard deviations of the data. Moreover, (1) the photoplethysmogram amplitude showed superior predictability (P=.03) and active vs sham separation compared to heart rate; (2) a consistent delay of greater than 5 seconds was found between tcVNS onset and cardiovascular effects; and (3) dynamic characteristics differentiated responses to tcVNS from the sham stimulation.
This work furthers the state of the art by modeling pertinent biomarker responses to tcVNS. Through subsequent analysis, we discovered three key findings with implications related to (1) wearable sensing devices for bioelectronic medicine, (2) the dominant mechanism of action for tcVNS-induced effects on cardiovascular physiology, and (3) the existence of dynamic biomarker signatures that can be leveraged when titrating therapy in closed loop.
ClinicalTrials.gov NCT02992899; https://clinicaltrials.gov/ct2/show/NCT02992899.
RR2-10.1016/j.brs.2019.08.002.
Journal Article
Exercise‐heat stress with and without water replacement alters brain structures and impairs visuomotor performance
by
Mizelle, J. C.
,
Millard‐Stafford, Melinda L.
,
Sawka, Michael N.
in
Adult
,
Body mass
,
Brain anatomy
2018
Effects of exercise‐heat stress with and without water replacement on brain structure and visuomotor performance were examined. Thirteen healthy adults (23.6 ± 4.2 years) completed counterbalanced 150 min trials of exercise‐heat stress (45°C, 15% RH) with water replacement (EHS) or without (~3% body mass loss; EHS‐DEH) compared to seated rest (CON). Anatomical scans and fMRI Blood‐Oxygen‐Level‐Dependent responses during a visuomotor pacing task were evaluated. Accuracy decreased (P < 0.05) despite water replacement during EHS (−8.2 ± 6.8% vs. CON) but further degraded with EHS‐DEH (−8.3 ± 6.4% vs. EHS and −16.5 ± 10.2% vs. CON). Relative to CON, EHS elicited opposing volumetric changes (P < 0.05) in brain ventricles (−5.3 ± 1.7%) and periventricular structures (cerebellum: 1.5 ± 0.8%) compared to EHS‐DEH (ventricles: 6.8 ± 3.4, cerebellum: −0.7 ± 0.7; thalamus: −2.7 ± 1.3%). Changes in plasma osmolality (EHS: −3.0 ± 2.1; EHS‐DEH: 9.3 ± 2.1 mOsm/kg) were related (P < 0.05) to thalamus (r = −0.45) and cerebellum volume (r = −0.61) which, in turn, were related (P < 0.05) to lateral (r = −0.41) and fourth ventricle volume (r = −0.67) changes, respectively; but, there were no associations (P > 0.50) between structural changes and visuomotor accuracy. EHS‐DEH increased neural activation (P < 0.05) within motor and visual areas versus EHS and CON. Brain structural changes are related to bidirectional plasma osmolality perturbations resulting from exercise‐heat stress (with and without water replacement), but do not explain visuomotor impairments. Negative impacts of exercise‐heat stress on visuomotor tasks are further exacerbated by dehydration. Whether prior exercise‐heat stress with or without dehydration impairs cognitive‐motor performance is controversial. We found that exercise‐heat stress (despite water ingestion matching sweat loss) significantly impaired visuomotor performance by 8% which was further exacerbated with dehydration by another 8%. However, structural changes in brain tissue and ventricular volumes in motor‐related areas did not explain impaired performance.
Journal Article
Sex and Performance: Nature versus Nurture
2019
This chapter discusses the term \"sex\" differences relative that is based upon the biological genetic difference between men and women rather than the term \"gender\" differences. A far wider concept than biological sex, \"gender\" implies life conditions, cultural and societal expectations about femininity/masculinity, and fundamentally one's own sense of self. Sport performance is affected by societal influences as one of many factors that ultimately coalesce and contribute to athletic success. Since the modern era of the Olympic Games, women have been playing \"catch-up\" to men in terms of societal acceptance for female participation and the available opportunities for sport competition. Across many sport disciplines, women had few role models in sport and started competing chronologically later than their male counterparts. Age is also an inherent factor contributing to sport performance. Using data on elite athletes' performances to understand the sex difference may be challenging when attempting to tease out the influence of environmental or \"nurture\" factors.
Book Chapter
Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study
by
Chen, Hungta
,
Järbrink, Krister
,
Schneider, Markus P
in
Adolescent
,
Adult nephrology
,
Chronic renal failure
2023
ObjectivesREVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD).DesignMultinational, observational study.SettingData from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]).ParticipantsEligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index).Main outcome measuresThe primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates.ResultsThe prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29–1.77), stage 3a CKD (vs 3b, 1.81–3.66), no medical history (vs a history) of diabetes (1.26–2.77) or hypertension (1.35–1.78).ConclusionsThere are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention.Trial registrationNCT04847531.
Journal Article
Generative Artificial Intelligence for Chest Radiograph Interpretation in the Emergency Department
by
Bailitz, John
,
Melnick, David
,
Phull, Amit
in
Artificial intelligence
,
Emergency medical care
,
Generative artificial intelligence
2023
Importance Multimodal generative artificial intelligence (AI) methodologies have the potential to optimize emergency department care by producing draft radiology reports from input images. Objective To evaluate the accuracy and quality of AI–generated chest radiograph interpretations in the emergency department setting. Design, Setting, and Participants This was a retrospective diagnostic study of 500 randomly sampled emergency department encounters at a tertiary care institution including chest radiographs interpreted by both a teleradiology service and on-site attending radiologist from January 2022 to January 2023. An AI interpretation was generated for each radiograph. The 3 radiograph interpretations were each rated in duplicate by 6 emergency department physicians using a 5-point Likert scale. Main Outcomes and Measures The primary outcome was any difference in Likert scores between radiologist, AI, and teleradiology reports, using a cumulative link mixed model. Secondary analyses compared the probability of each report type containing no clinically significant discrepancy with further stratification by finding presence, using a logistic mixed-effects model. Physician comments on discrepancies were recorded. Results A total of 500 ED studies were included from 500 unique patients with a mean (SD) age of 53.3 (21.6) years; 282 patients (56.4%) were female. There was a significant association of report type with ratings, with post hoc tests revealing significantly greater scores for AI (mean [SE] score, 3.22 [0.34];P < .001) and radiologist (mean [SE] score, 3.34 [0.34];P < .001) reports compared with teleradiology (mean [SE] score, 2.74 [0.34]) reports. AI and radiologist reports were not significantly different. On secondary analysis, there was no difference in the probability of no clinically significant discrepancy between the 3 report types. Further stratification of reports by presence of cardiomegaly, pulmonary edema, pleural effusion, infiltrate, pneumothorax, and support devices also yielded no difference in the probability of containing no clinically significant discrepancy between the report types. Conclusions and Relevance In a representative sample of emergency department chest radiographs, results suggest that the generative AI model produced reports of similar clinical accuracy and textual quality to radiologist reports while providing higher textual quality than teleradiologist reports. Implementation of the model in the clinical workflow could enable timely alerts to life-threatening pathology while aiding imaging interpretation and documentation.
Journal Article
Methods and rationale of the DISCOVER CKD global observational study
by
Lam, Carolyn S P
,
Heerspink, Hiddo J L
,
Kashihara, Naoki
in
Analysis
,
Chronic kidney failure
,
Clinical outcomes
2021
Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis.
DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries.
The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews).
The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting.
Journal Article
Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data
by
Lam, Carolyn S. P.
,
Jørgensen, Marit E.
,
Surmont, Filip
in
Aged
,
Angiology
,
Blood Glucose - drug effects
2021
Background
Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics.
Methods
De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects.
Results
Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region.
Conclusions
This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups.
Trial registration
NCT02993614
Journal Article