114 results on '"Owens CD"'
Search Results
2. Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial)
- Author
-
Conte, Michael, Grenon, SM, Owens, CD, Nosova, EV, Hughes-Fulford, M, Alley, HF, Chong, K, Perez, S, Yen, PK, Boscardin, J, and Hellmann, J
- Published
- 2015
3. Impact of Elagolix on Quality of Life Measured By SF-12 in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids: Evidence from A Phase 2B Randomized Trial
- Author
-
Soliman, AM, primary, Wang, A, additional, Owens, CD, additional, and Diamond, M, additional
- Published
- 2018
- Full Text
- View/download PDF
4. Survey of equine castration techniques, preferences and outcomes among Australian veterinarians
- Author
-
Owens, CD, primary, Hughes, KJ, additional, Hilbert, BJ, additional, Heller, J, additional, Nielsen, S, additional, and Trope, GD, additional
- Published
- 2017
- Full Text
- View/download PDF
5. Examining Health-Related Productivity Losses due To Uterine Fibroids in the United States Using the Health-Related Productivity Questionnaire
- Author
-
Soliman, AM, primary, Castelli-Haley, J, additional, Snabes, MC, additional, Owens, CD, additional, and Coyne, KS, additional
- Published
- 2016
- Full Text
- View/download PDF
6. PIH31 - Impact of Elagolix on Quality of Life Measured By SF-12 in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids: Evidence from A Phase 2B Randomized Trial
- Author
-
Soliman, AM, Wang, A, Owens, CD, and Diamond, M
- Published
- 2018
- Full Text
- View/download PDF
7. PIH33 - Examining Health-Related Productivity Losses due To Uterine Fibroids in the United States Using the Health-Related Productivity Questionnaire
- Author
-
Soliman, AM, Castelli-Haley, J, Snabes, MC, Owens, CD, and Coyne, KS
- Published
- 2016
- Full Text
- View/download PDF
8. Multi-contrast high spatial resolution black blood inner volume three-dimensional fast spin echo MR imaging in peripheral vein bypass grafts.
- Author
-
Rybicki FJ, Mitsouras D, Owens CD, Whitmore A, Gerhard-Herman M, Wake N, Cai T, Zhou Q, Conte MS, Creager MA, Mulkern RV, Rybicki, Frank J, Mitsouras, Dimitrios, Owens, Christopher D, Whitmore, Amanda, Gerhard-Herman, Marie, Wake, Nichole, Cai, Tianxi, Zhou, Qian, and Conte, Michael S
- Abstract
The purpose of this study is to primarily evaluate the lumen area and secondarily evaluate wall area measurements of in vivo lower extremity peripheral vein bypass grafts patients using high spatial resolution, limited field of view, cardiac gated, black blood inner volume three-dimensional fast spin echo MRI. Fifteen LE-PVBG patients prospectively underwent ultrasound followed by T1-weighted and T2-weighted magnetic resonance (MR) imaging. Lumen and vessel wall areas were measured by direct planimetry. For graft lumen areas, T1- and T2-weighted measurements were compared with ultrasound. For vessel wall areas, differences between T1- and T2-weighted measurements were evaluated. There was no significant difference between ultrasound and MR lumen measurements, reflecting minimal MR blood suppression artifact. Graft wall area measured from T1-weighted images was significantly larger than that measured from T2-weighted images (P < 0.001). The mean of the ratio of T1- versus T2-weighted vessel wall areas was 1.59 (95% CI: 1.48-1.69). The larger wall area measured on T1-weighted images was due to a significantly larger outer vessel wall boundary. Very high spatial resolution LE-PVBG vessel wall MR imaging can be performed in vivo, enabling accurate measurements of lumen and vessel wall areas and discerning differences in those measures between different tissue contrast weightings. Vessel wall area differences suggest that LE-PVBG vessel wall tissues produce distinct signal characteristics under T1 and T2 MR contrast weightings. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
9. Surgical site infections: epidemiology, microbiology and prevention.
- Author
-
Owens CD and Stoessel K
- Abstract
Surgical site infections (SSIs) are defined as infections occurring up to 30 days after surgery (or up to one year after surgery in patients receiving implants) and affecting either the incision or deep tissue at the operation site. Despite improvements in prevention, SSIs remain a significant clinical problem as they are associated with substantial mortality and morbidity and impose severe demands on healthcare resources. The incidence of SSIs may be as high as 20%, depending on the surgical procedure, the surveillance criteria used, and the quality of data collection. In many SSIs, the responsible pathogens originate from the patient's endogenous flora. The causative pathogens depend on the type of surgery; the most commonly isolated organisms are Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp. and Escherichia coli. Numerous patient-related and procedure-related factors influence the risk of SSI, and hence prevention requires a 'bundle' approach, with systematic attention to multiple risk factors, in order to reduce the risk of bacterial contamination and improve the patient's defences. The Centers for Disease Control and Prevention guidelines for the prevention of SSIs emphasise the importance of good patient preparation, aseptic practice, and attention to surgical technique; antimicrobial prophylaxis is also indicated in specific circumstances. Emerging technologies, such as microbial sealants, offer the ability to seal and immobilise skin flora for the duration of a surgical procedure; a strong case therefore exists for evaluating such technologies and implementing them into routine clinical practice as appropriate. Copyright © 2008 The Hospital Infection Society Published by Elsevier Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
10. Lower extremity peripheral vein bypass graft wall thickness changes demonstrated at 1 and 6 months after surgery with ultra-high spatial resolution black blood inner volume three-dimensional fast spin echo magnetic resonance imaging.
- Author
-
Rybicki FJ, Mitsouras D, Owens CD, Whitmore AG, Ersoy H, Mulkern RV, Creager MA, Conte MS, Rybicki, Frank John, Mitsouras, Dimitrios, Owens, Christopher D, Whitmore, Amanda G, Ersoy, Hale, Mulkern, Robert V, Creager, Mark A, and Conte, Michael S
- Abstract
Objective: To demonstrate lower extremity peripheral vein bypass graft wall thickness changes over time in a patient using very high spatial resolution cardiac gated, black blood inner volume three-dimensional (3D) fast spin echo (FSE) magnetic resonance imaging (MRI).Case Report: A 52-year-old diabetic man with a history of hyperlipidemia underwent uncomplicated bypass grafting for an asymptomatic 5.2 cm popliteal artery aneurysm using reversed great saphenous vein. A segment of the bypass graft was studied at 1 and 6 months after surgery with cardiac gated inner volume 3D-FSE imaging with non-interpolated 0.195 mm(3) voxel volumes (0.3125 x 0.3125 x 2 mm). T1- and T2-weighted images were acquired in 10 min per contrast weighting. Graft imaging at one month after implantation illustrates expansion of the outer wall of the graft that partially resolves 5 months later.Conclusion: In this patient, expansion of the lower extremity peripheral bypass graft wall can be characterized in clinical scan times with a 3D-FSE MRI protocol using highly selective inner volume excitation followed by non-selective refocusing pulses. The resulting 3D images can potentially be used to study the biology of the vessel wall. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
11. Medical management of peripheral arterial disease: bridging the 'gap'?
- Author
-
Owens CD and Conte MS
- Published
- 2012
- Full Text
- View/download PDF
12. Optimizing cardiopulmonary rehabilitation duration for long COVID patients: an exercise physiology monitoring approach.
- Author
-
Szarvas Z, Fekete M, Szollosi GJ, Kup K, Horvath R, Shimizu M, Tsuhiya F, Choi HE, Wu HT, Fazekas-Pongor V, Pete KN, Cserjesi R, Bakos R, Gobel O, Gyongyosi K, Pinter R, Kolozsvari D, Kovats Z, Yabluchanskiy A, Owens CD, Ungvari Z, Tarantini S, Horvath G, Muller V, and Varga JT
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Exercise Test methods, Quality of Life, SARS-CoV-2, Exercise Therapy methods, COVID-19 rehabilitation, Cardiac Rehabilitation methods, Post-Acute COVID-19 Syndrome
- Abstract
The presence of prolonged symptoms after COVID infection worsens the workability and quality of life. 200 adults with long COVID syndrome were enrolled after medical, physical, and mental screening, and were divided into two groups based on their performance. The intervention group (n = 100) received supervised rehabilitation at Department of Pulmonology, Semmelweis University with the registration number 160/2021 between 01/APR/2021-31/DEC/2022, while an age-matched control group (n = 100) received a single check-up. To evaluate the long-term effects of the rehabilitation, the intervention group was involved in a 2- and 3-month follow-up, carrying out cardiopulmonary exercise test. Our study contributes understanding long COVID rehabilitation, emphasizing the potential benefits of structured cardiopulmonary rehabilitation in enhancing patient outcomes and well-being. Significant difference was found between intervention group and control group at baseline visit in pulmonary parameters, as forced vital capacity, forced expiratory volume, forced expiratory volume, transfer factor for carbon monoxide, transfer coefficient for carbon monoxide, and oxygen saturation (all p < 0.05). Our follow-up study proved that a 2-week long, patient-centered pulmonary rehabilitation program has a positive long-term effect on people with symptomatic long COVID syndrome. Our data showed significant improvement between two and three months in maximal oxygen consumption (p < 0.05). Multidisciplinary, individualized approach may be a key element of a successful cardiopulmonary rehabilitation in long COVID conditions, which improves workload, quality of life, respiratory function, and status of patients with long COVID syndrome., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
13. Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.
- Author
-
Owens CD, Pinto CB, Mukli P, Gulej R, Velez FS, Detwiler S, Olay L, Hoffmeister JR, Szarvas Z, Muranyi M, Peterfi A, Pinaffi-Langley ACDC, Adams C, Sharps J, Kaposzta Z, Prodan CI, Kirkpatrick AC, Tarantini S, Csiszar A, Ungvari Z, Olson AL, Li G, Balasubramanian P, Galvan V, Bauer A, Smith ZA, Dasari TW, Whitehead S, Medapti MR, Elahi FM, Thanou A, and Yabluchanskiy A
- Subjects
- Humans, Female, Male, Aged, Magnetic Resonance Imaging, Spectroscopy, Near-Infrared, Middle Aged, Cognitive Dysfunction physiopathology, Extracellular Vesicles metabolism, Biomarkers blood, Neurovascular Coupling physiology
- Abstract
Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention., Methods: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry., Results: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification., Discussion: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology., Highlights: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
- Published
- 2024
- Full Text
- View/download PDF
14. Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19.
- Author
-
Owens CD, Bonin Pinto C, Detwiler S, Olay L, Pinaffi-Langley ACDC, Mukli P, Peterfi A, Szarvas Z, James JA, Galvan V, Tarantini S, Csiszar A, Ungvari Z, Kirkpatrick AC, Prodan CI, and Yabluchanskiy A
- Abstract
Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds and infection) alter cellular structures and physiologic processes within the neurovascular unit and contribute to cognitive dysfunction. COVID-19 has posed significant complications during acute and convalescent stages in multiple organ systems, including the brain. Cognitive impairment is a prevalent complication in COVID-19 patients, irrespective of severity of acute SARS-CoV-2 infection. Moreover, overwhelming evidence from in vitro, preclinical and clinical studies has reported SARS-CoV-2-induced pathologies in components of the neurovascular unit that are associated with cognitive impairment. Neurovascular unit disruption alters the neurovascular coupling response, a critical mechanism that regulates cerebromicrovascular blood flow to meet the energetic demands of locally active neurons. Normal cognitive processing is achieved through the neurovascular coupling response and involves the coordinated action of brain parenchymal cells (i.e. neurons and glia) and cerebrovascular cell types (i.e. endothelia, smooth muscle cells and pericytes). However, current work on COVID-19-induced cognitive impairment has yet to investigate disruption of neurovascular coupling as a causal factor. Hence, in this review, we aim to describe SARS-CoV-2's effects on the neurovascular unit and how they can impact neurovascular coupling and contribute to cognitive decline in acute and convalescent stages of the disease. Additionally, we explore potential therapeutic interventions to mitigate COVID-19-induced cognitive impairment. Given the great impact of cognitive impairment associated with COVID-19 on both individuals and public health, the necessity for a coordinated effort from fundamental scientific research to clinical application becomes imperative. This integrated endeavour is crucial for mitigating the cognitive deficits induced by COVID-19 and its subsequent burden in this especially vulnerable population., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2024
- Full Text
- View/download PDF
15. Impaired Neurovascular Coupling and Increased Functional Connectivity in the Frontal Cortex Predict Age-Related Cognitive Dysfunction.
- Author
-
Mukli P, Pinto CB, Owens CD, Csipo T, Lipecz A, Szarvas Z, Peterfi A, Langley ACDCP, Hoffmeister J, Racz FS, Perry JW, Tarantini S, Nyúl-Tóth Á, Sorond FA, Yang Y, James JA, Kirkpatrick AC, Prodan CI, Toth P, Galindo J, Gardner AW, Sonntag WE, Csiszar A, Ungvari Z, and Yabluchanskiy A
- Subjects
- Humans, Aged, Brain physiology, Frontal Lobe, Neurovascular Coupling physiology, Cognitive Dysfunction
- Abstract
Impaired cerebrovascular function contributes to the genesis of age-related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n-back) paradigm, oxy- and deoxyhemoglobin concentration changes from the frontal cortex using functional near-infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2-back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age-related decline in accuracy during the 2-back task. These findings suggest that task-related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
16. Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study.
- Author
-
Owens CD, Bonin Pinto C, Mukli P, Szarvas Z, Peterfi A, Detwiler S, Olay L, Olson AL, Li G, Galvan V, Kirkpatrick AC, Balasubramanian P, Tarantini S, Csiszar A, Ungvari Z, Prodan CI, and Yabluchanskiy A
- Subjects
- Humans, Aged, Brain, Prospective Studies, Longitudinal Studies, Pandemics, Disease Progression, Neuropsychological Tests, Observational Studies as Topic, COVID-19 epidemiology, Cognitive Dysfunction epidemiology, Dementia epidemiology
- Abstract
Introduction: Mild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15-20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern. The COVID-19 pandemic poses a significant impact on our aging population with cognitive decline as one of the leading complications following recovery from acute infection. Recent findings suggest that COVID-19 increases the conversion rate from MCI to dementia in older adults. Hence, we aim to uncover a mechanism for COVID-19 induced cognitive impairment and progression to dementia to pave the way for future therapeutic targets that may mitigate COVID-19 induced cognitive decline., Methodology: A prospective longitudinal study is conducted at the University of Oklahoma Health Sciences Center. Patients are screened in the Department of Neurology and must have a formal diagnosis of MCI, and MRI imaging prior to study enrollment. Patients who meet the inclusion criteria are enrolled and followed-up at 18-months after their first visit. Visit one and 18-month follow-up will include an integrated and cohesive battery of vascular and cognitive measurements, including peripheral endothelial function (flow-mediated dilation, laser speckle contrast imaging), retinal and cerebrovascular hemodynamics (dynamic vessel retinal analysis, functional near-infrared spectroscopy), and fluid and crystalized intelligence (NIH-Toolbox, n-back). Multiple logistic regression will be used for primary longitudinal data analysis to determine whether COVID-19 related impairment in neurovascular coupling and increases in white matter hyperintensity burden contribute to progression to dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Owens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
17. Cerebral small vessel disease pathology in COVID-19 patients: A systematic review.
- Author
-
Owens CD, Pinto CB, Detwiler S, Mukli P, Peterfi A, Szarvas Z, Hoffmeister JR, Galindo J, Noori J, Kirkpatrick AC, Dasari TW, James J, Tarantini S, Csiszar A, Ungvari Z, Prodan CI, and Yabluchanskiy A
- Subjects
- Humans, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage complications, Cerebral Hemorrhage pathology, Magnetic Resonance Imaging, COVID-19 complications, COVID-19 epidemiology, Cerebral Small Vessel Diseases complications, White Matter pathology, Hypertension pathology
- Abstract
Cerebral small vessel disease (CSVD) is the leading cause of vascular cognitive impairment and is associated with COVID-19. However, contributing factors that often accompany CSVD pathology in COVID-19 patients may influence the incidence of cerebrovascular complications. Thus, a mechanism linking COVID-19 and CSVD has yet to be uncovered and differentiated from age-related comorbidities (i.e., hypertension), and medical interventions during acute infection. We aimed to evaluate CSVD in acute and recovered COVID-19 patients and to differentiate COVID-19-related cerebrovascular pathology from the above-mentioned contributing factors by assessing the localization of microbleeds and ischemic lesions/infarctions in the cerebrum, cerebellum, and brainstem. A systematic search was performed in December 2022 on PubMed, Web of Science, and Embase using a pre-established search criterion related to history of, or active COVID-19 with CSVD pathology in adults. From a pool of 161 studies, 59 met eligibility criteria and were included. Microbleeds and ischemic lesions had a strong predilection for the corpus callosum and subcortical/deep white matter in COVID-19 patients, suggesting a distinct CSVD pathology. These findings have important implications for clinical practice and biomedical research as COVID-19 may independently, and through exacerbation of age-related mechanisms, contribute to increased incidence of CSVD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
18. Gait variability predicts cognitive impairment in older adults with subclinical cerebral small vessel disease.
- Author
-
Mukli P, Detwiler S, Owens CD, Csipo T, Lipecz A, Pinto CB, Tarantini S, Nyul-Toth A, Balasubramanian P, Hoffmeister JR, Csiszar A, Ungvari Z, Kirkpatrick AC, Prodan CI, and Yabluchanskiy A
- Abstract
Introduction: Advanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD., Methods: To test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions., Results: Patients with CSVD exhibited lower performance in a visual learning test ( p = 0.030) and in a sustained attention test ( p = 0.007). CSVD also affected step time variability ( p = 0.009) and step length variability ( p = 0.017). Step lengths of CSVD participants were more asymmetric ( p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups., Discussion: Our findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mukli, Detwiler, Owens, Csipo, Lipecz, Pinto, Tarantini, Nyul-Toth, Balasubramanian, Hoffmeister, Csiszar, Ungvari, Kirkpatrick, Prodan and Yabluchanskiy.)
- Published
- 2022
- Full Text
- View/download PDF
19. The COVID-19 Pandemic in a Hispanic Population: A Primary Care Perspective.
- Author
-
Owens CD, Pertuz GM, Sanchez JC, Ayala J, Pimentel LH, Lamb C, Lopez Mayo YE, and Yunez AL
- Subjects
- Hispanic or Latino, Humans, Pandemics, Primary Health Care, Retrospective Studies, SARS-CoV-2, COVID-19 epidemiology
- Abstract
Introduction: The COVID-19 global pandemic has affected all ethnic and minority groups although not equally. The goals of the present study are twofold: describe the diverse COVID-19-related care needs Hispanic patients presenting to a primary care facility and the symptom clusters and socioeconomic factors that may impact their wellbeing., Methods: This is a retrospective cohort of Hispanic patients in an outpatient clinic serving an urban lower socioeconomic demographic, between May 9 and July 31, 2020. COVID-19 infection was confirmed by polymerase chain reaction or rapid antibody test. Student's t-test was used for means and the chi
2 was used for comparisons of proportions., Results: A total of 6616 patients visited Alivio, 409 were triaged to a containment area, and 378 were tested for COVID-19; 230 with, 148 without symptoms. Of those tested, 161(42.6%) were positive, representing 2.4% of total patients seen. Age, temperature, and pulse rate were all significantly higher in patients with symptoms compared with those without. Symptoms were grouped into 5 clusters: constitutional, n = 143(62%), respiratory, n = 136 (59%), and somatic, n = 97(42%) were most common. No single cluster was particularly diagnostic of COVID-19, although those with symptoms in multiple clusters were more likely to test positive, P < .001. The majority worked in essential jobs, were uninsured, and had more than half had prolonged symptoms., Conclusions: Hispanic patients have diverse reasons for seeking health care and for testing in a pandemic. COVID-19 is a syndromic disease as evidenced from the clustering of symptoms. Essential workers and uninsured health status may lead to more prolonged disease course., Competing Interests: Conflicts of interest: There are no conflicts or competing interests to declare. Christopher Lamb, PhD, has worked with the manufacturers of SARS-CoV-2 tests for Emergency Use Authorization submissions to the US FDA., (© Copyright 2022 by the American Board of Family Medicine.)- Published
- 2022
- Full Text
- View/download PDF
20. Health Care Costs and Treatment Patterns Associated with Uterine Fibroids and Heavy Menstrual Bleeding: A Claims Analysis.
- Author
-
Wang A, Wang S, Owens CD, Vora JB, and Diamond MP
- Subjects
- Cohort Studies, Female, Health Care Costs, Humans, Insurance Claim Review, Retrospective Studies, United States epidemiology, Leiomyoma complications, Leiomyoma therapy, Menorrhagia drug therapy, Menorrhagia therapy
- Abstract
Background: Heavy menstrual bleeding (HMB) is one of the most common distressing complications of uterine fibroids (UF); however, data on the health care costs for treatments in women experiencing HMB associated with UF are lacking. The objective of this study was to compare the direct costs and treatments patterns for women diagnosed with UF+HMB, UF only, and HMB only in the United States. Materials and Methods: The study design was retrospective matched cohort study using claims data. Women, aged 18-51 years, comprising four cohorts (HMB only, UF only, UF+HMB, and controls) were identified in the IBM MarketScan
® Commercial Claims and Encounters Database (October 1, 2007‒September 30, 2018) and matched by demographics and Charlson Comorbidity Index score. Baseline characteristics and treatments during the 12 months post-diagnosis were summarized descriptively. Costs (2018 U.S. dollars) during the post-diagnosis year were compared using analysis of variance. Results: Before matching, women with UF+HMB represented 54% of UF cases. Following diagnosis, 32% in the matched UF+HMB cohort had no treatment, 49% underwent surgeries/procedures with (12%) or without (37%) medications, and 18% received medications only. The mean all-cause total costs for UF+HMB ($16,762) exceeded that for UF only by 24% ($13,506) and HMB only by 50% ($11,135), and almost tripled the mean cost for the control cohort ($6,691) (all, p < 0.001). The mean diagnosis-related costs were significantly higher for UF+HMB ($8,741) than for UF only ($4,550) and HMB only ($3,081) (all, p < 0.0001). Surgery/procedure costs comprised 80% of diagnosis-related medical costs for UF+HMB. Conclusions: UF with HMB were associated with significant economic burden, driven primarily by surgical/procedural costs and treatment patterns.- Published
- 2022
- Full Text
- View/download PDF
21. Microvascular dysfunction and neurovascular uncoupling are exacerbated in peripheral artery disease, increasing the risk of cognitive decline in older adults.
- Author
-
Owens CD, Mukli P, Csipo T, Lipecz A, Silva-Palacios F, Dasari TW, Tarantini S, Gardner AW, Montgomery PS, Waldstein SR, Kellawan JM, Nyul-Toth A, Balasubramanian P, Sotonyi P, Csiszar A, Ungvari Z, and Yabluchanskiy A
- Subjects
- Aged, Aging physiology, Arterioles, Cerebrovascular Circulation physiology, Humans, Cognitive Dysfunction, Neurovascular Coupling physiology, Peripheral Arterial Disease
- Abstract
Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n -back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline. NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.
- Published
- 2022
- Full Text
- View/download PDF
22. Urinary Biomarkers of Oxidative Stress in Aging: Implications for Prediction of Accelerated Biological Age in Prospective Cohort Studies.
- Author
-
Mukli P, Wu DH, Csipo T, Owens CD, Lipecz A, Racz FS, Zouein FA, Tabak A, Csiszar A, Ungvari Z, Tsitouras PD, and Yabluchanskiy A
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers urine, Cross-Sectional Studies, Deoxyguanosine urine, Humans, Middle Aged, Prospective Studies, Young Adult, Aging, Oxidative Stress
- Abstract
Background: Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age-related decline in organ/tissue function and the development of age-related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging., Aims: The objective of this cross-sectional study was to validate a novel panel of urinary oxidative stress biomarkers., Methods: Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects ( n = 198) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal., Results: Our findings showed that 8-oxo-7,8-deoxyguanosine (8-oxoG), 8-oxo-7,8-dihydroguanosine (8-OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F
2 -isoprostane (iPF2 α -VI) correlated negatively with age. We found that 8-oxoG, DTyr, and iPF2 α -VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion . Our results indicate that 8-oxoG and iPF2 α -VI levels in the urine reveal biological aging., Conclusion: Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age-related diseases., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2022 Peter Mukli et al.)- Published
- 2022
- Full Text
- View/download PDF
23. Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.
- Author
-
Stewart EA, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg EC, Gillispie-Bell V, Imudia AN, Liu R, Kim JH, and Al-Hendy A
- Subjects
- Female, Gonadotropin-Releasing Hormone therapeutic use, Humans, Hydrocarbons, Fluorinated, Pyrimidines, Leiomyoma complications, Leiomyoma drug therapy, Menorrhagia drug therapy, Uterine Neoplasms complications, Uterine Neoplasms drug therapy
- Abstract
Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.
- Published
- 2022
- Full Text
- View/download PDF
24. Keratometry, biometry, and prediction of intraocular lens power in adult tigers (Panthera tigris).
- Author
-
Owens CD, Michau TM, Boorstein J, Wynn ER, and McMullen RJ
- Subjects
- Animals, Biometry, Cornea, Refraction, Ocular, Retrospective Studies, Lenses, Intraocular veterinary, Phacoemulsification veterinary, Tigers
- Abstract
Objective: To calculate the necessary pseudophakic intraocular lens (IOL) power to approximate emmetropia in adult tigers., Animals: 17 clinically normal adult tigers., Procedures: 33 eyes of 17 clinically normal adult tigers underwent routine ophthalmic examination and B-scan ultrasonography while anesthetized for unrelated procedures. Specific ultrasound data (globe measurements and corneal curvature) and estimated postoperative IOL positions were utilized to calculate predicted IOL power by use of Retzlaff and Binkhorst theoretical formulas. Applanation tonometry and refraction were also performed., Results: Mean ± SD axial globe length was 29.36 ± 0.82 mm, preoperative anterior chamber depth was 7.00 ± 0.74 mm, and crystalline lens thickness was 8.72 ± 0.56 mm. Mean net refractive error (n = 33 eyes) was +0.27 ± 0.30 diopters (D). By use of the Retzlaff formula, mean predicted IOL power for the postoperative anterior chamber depth (PACD), PACD - 2 mm, and PACD + 2 mm was 43.72 ± 4.84 D, 37.62 ± 4.19 D, and 51.57 ± 5.72 D, respectively. By use of the Binkhorst equation, these values were 45.11 ± 4.91 D, 38.84 ± 4.25 D, and 53.18 ± 5.81 D, respectively. Mean intraocular pressure for all eyes was 14.7 ± 2.69 mm Hg., Clinical Relevance: The calculated tiger IOL was lower than reported values for adult domestic felids. Further studies evaluating actual PACD and pseudophakic refraction would help determine the appropriate IOL power to achieve emmetropia in this species.
- Published
- 2021
- Full Text
- View/download PDF
25. Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life.
- Author
-
Watts NB, Binkley N, Owens CD, Al-Hendy A, Puscheck EE, Shebley M, Schlaff WD, and Simon JA
- Subjects
- Female, Humans, Lactation, Medroxyprogesterone Acetate, Pregnancy, Sulfones, Bone Density, Imidazoles
- Abstract
Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism ( e.g. , contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists ( e.g. , ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short- and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.
- Published
- 2021
- Full Text
- View/download PDF
26. Sleep deprivation alters task-related changes in functional connectivity of the frontal cortex: A near-infrared spectroscopy study.
- Author
-
Mukli P, Csipo T, Lipecz A, Stylianou O, Racz FS, Owens CD, Perry JW, Tarantini S, Sorond FA, Kellawan JM, Purebl G, Yang Y, Sonntag WE, Csiszar A, Ungvari ZI, and Yabluchanskiy A
- Subjects
- Brain, Brain Mapping, Humans, Magnetic Resonance Imaging, Male, Sleep Deprivation diagnostic imaging, Motor Cortex, Spectroscopy, Near-Infrared
- Abstract
Sleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task-related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near-infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger-tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
27. Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis.
- Author
-
Muneyyirci-Delale O, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg E, Gillispie V, Hurtado S, Kim JH, Wang A, Wang H, and Stewart EA
- Abstract
Objective: To determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids., Design: Pooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2)., Setting: A total of 153 gynecological clinical care settings in the United States and Canada., Patients: Premenopausal women (18-51 years) with >80 mL of menstrual blood loss (MBL)/cycle and uterine fibroids with and without coexisting adenomyosis diagnosed by ultrasound and/or magnetic resonance imaging at baseline., Interventions: Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily., Main Outcome Measures: The primary endpoint was the proportion of women who had <80 mL of MBL during the final month and ≥50% reduction in MBL from baseline to the final month. Adverse events were monitored., Results: Of 786 women treated across the two trials, 16% (126 women) had coexisting adenomyosis. Among this subset, a significantly greater proportion of women who received elagolix with add-back therapy (77.1% [95% confidence interval, 66.2, 88.0]) met both primary endpoint criteria compared with women who received placebo (12.2% [95% confidence interval, 1.0, 23.4]). Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%)., Conclusions: Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494)., (© 2021 The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
28. Increased cognitive workload evokes greater neurovascular coupling responses in healthy young adults.
- Author
-
Csipo T, Lipecz A, Mukli P, Bahadli D, Abdulhussein O, Owens CD, Tarantini S, Hand RA, Yabluchanska V, Kellawan JM, Sorond F, James JA, Csiszar A, Ungvari ZI, and Yabluchanskiy A
- Subjects
- Adult, Female, Hemodynamics, Humans, Male, Memory, Short-Term, Middle Cerebral Artery diagnostic imaging, Middle Cerebral Artery physiology, Prefrontal Cortex blood supply, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex physiology, Cognition, Neurovascular Coupling
- Abstract
Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
- Full Text
- View/download PDF
29. Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids.
- Author
-
Al-Hendy A, Bradley L, Owens CD, Wang H, Barnhart KT, Feinberg E, Schlaff WD, Puscheck EE, Wang A, Gillispie V, Hurtado S, Muneyyirci-Delale O, Archer DF, Carr BR, Simon JA, and Stewart EA
- Abstract
Background: Uterine fibroids are one of the most common neoplasms found among women globally, with a prevalence of approximately 11 million women in the United States alone. The morbidity of this common disease is significant because it is the leading cause of hysterectomy and causes significant functional impairment for women of reproductive age. Factors including age, body mass index, race, ethnicity, menstrual blood loss, fibroid location, and uterine and fibroid volume influence the incidence of fibroids and severity of symptoms. Elagolix is an oral gonadotropin-releasing hormone receptor antagonist that competitively inhibits pituitary gonadotropin-releasing hormone receptor activity and suppresses the release of gonadotropins from the pituitary gland, resulting in dose-dependent suppression of ovarian sex hormones, follicular growth, and ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids., Objective: This analysis aimed to evaluate the safety and efficacy of elagolix (300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day) in reducing heavy menstrual bleeding associated with uterine fibroids in various subgroups of women over 6 months of treatment., Study Design: Data were pooled from Elaris Uterine Fibroid-1 and Uterine Fibroid-2 studies, which evaluated premenopausal women (18-51 years) with heavy menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin methodology) and ultrasound-confirmed uterine fibroid diagnosis. Subgroups analyzed included age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume (largest fibroid identified by ultrasound). The primary endpoint was the proportion of women with <80 mL menstrual blood loss during the final month and ≥50% menstrual blood loss reduction from baseline to final month. Secondary and other efficacy endpoints included mean change in menstrual blood loss from baseline to final month, amenorrhea, symptom severity, and health-related quality of life. Adverse events and other safety endpoints were monitored., Results: The overall pooled Elaris Uterine Fibroid-1 and Uterine Fibroid-2 population was typical of women with fibroids, with a mean age of 42.4 (standard deviation, 5.4) years and a mean body mass index of 33.6 (standard deviation, 7.3) kg/m
2 and 67.6% of participants being black or African American women. A wide range of baseline uterine and fibroid volumes and menstrual blood loss were also represented in the overall pooled study population. In all subgroups, the proportion of responders to the primary endpoint, mean change in menstrual blood loss, amenorrhea, reduction in symptom severity, and improvement in health-related quality of life were clinically meaningfully greater for women who received elagolix with add-back therapy than those who received placebo and consistent with the overall pooled study population for the primary endpoint (72.2% vs 9.3%), mean change in menstrual blood loss (-172.5 mL vs -0.8 mL), amenorrhea (50.4% vs 4.5%), symptom severity (-37.1 vs -9.2), and health-related quality of life score (39.9 vs 8.9). Adverse events by subgroup were consistent with the overall pooled study population., Conclusion: Elagolix with hormonal add-back therapy was effective in reducing heavy menstrual bleeding associated with uterine fibroids independent of age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume., (Copyright © 2020 AbbVie Inc. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
30. Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas.
- Author
-
Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, Kim J, Liu R, Owens CD, Muneyyirci-Delale O, Wang A, Watts NB, and Schlaff WD
- Subjects
- Adult, Bone Density drug effects, Double-Blind Method, Drug Therapy, Combination, Estradiol adverse effects, Female, Gonadotropin-Releasing Hormone antagonists & inhibitors, Headache etiology, Hot Flashes etiology, Humans, Hydrocarbons, Fluorinated adverse effects, Leiomyoma complications, Leiomyoma pathology, Menorrhagia blood, Menorrhagia etiology, Middle Aged, Nausea etiology, Norethindrone adverse effects, Pyrimidines adverse effects, Quality of Life, Uterine Neoplasms complications, Uterine Neoplasms pathology, Estradiol administration & dosage, Hydrocarbons, Fluorinated administration & dosage, Leiomyoma drug therapy, Menorrhagia drug therapy, Norethindrone administration & dosage, Pyrimidines administration & dosage, Uterine Neoplasms drug therapy
- Abstract
Objective: To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas., Methods: Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of women with both less than 80 mL menstrual blood loss during final month and a 50% or greater reduction in menstrual blood loss from baseline to final month. Safety evaluations included adverse events and bone mineral density changes. The planned sample size of UF-EXTEND was based on estimated rollover and discontinuation rates in the two preceding studies., Results: From September 2016 to March 2019, 433 women were enrolled in UF-EXTEND. Of these women, 218 received up to 12 months of elagolix with add-back therapy; the mean±SD age of this group was 42.4±5.4 years and 67.3% were black. The percentage of women who met the primary endpoint in this elagolix with add-back group was 87.9% (95% CI [83.4-92.3]). The most frequently reported adverse events with up to 12 months of elagolix plus add-back therapy were hot flush (6.9%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Mean percent decreases in bone mineral density from baseline to extension month 6 were significantly less with elagolix plus add-back therapy than with elagolix alone {between-group difference in lumbar spine: -3.3 (95% CI [-4.1 to -2.5])}., Conclusion: Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy., Clinical Trial Registration: ClinicalTrials.gov, NCT02925494., Funding Source: AbbVie Inc funded this study.
- Published
- 2020
- Full Text
- View/download PDF
31. Elagolix for Fibroid-Associated Heavy Menstrual Bleeding. Reply.
- Author
-
Schlaff WD, Owens CD, and Muneyyirci-Delale O
- Subjects
- Female, Humans, Hydrocarbons, Fluorinated, Pyrimidines, Leiomyoma, Menorrhagia
- Published
- 2020
- Full Text
- View/download PDF
32. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.
- Author
-
Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Feinberg EC, Hurtado SM, Kim J, Liu R, Mabey RG Jr, Owens CD, Poindexter A, Puscheck EE, Rodriguez-Ginorio H, Simon JA, Soliman AM, Stewart EA, Watts NB, and Muneyyirci-Delale O
- Subjects
- Adult, Bone Density drug effects, Double-Blind Method, Drug Therapy, Combination, Female, Hot Flashes chemically induced, Humans, Hydrocarbons, Fluorinated adverse effects, Menorrhagia etiology, Middle Aged, Pyrimidines adverse effects, Quality of Life, Severity of Illness Index, Surveys and Questionnaires, Estradiol therapeutic use, Estrogens therapeutic use, Gonadotropin-Releasing Hormone antagonists & inhibitors, Hydrocarbons, Fluorinated therapeutic use, Leiomyoma complications, Menorrhagia drug therapy, Pyrimidines therapeutic use
- Abstract
Background: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding., Methods: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation., Results: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy., Conclusions: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.)., (Copyright © 2020 Massachusetts Medical Society.)
- Published
- 2020
- Full Text
- View/download PDF
33. Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial.
- Author
-
Carr BR, Stewart EA, Archer DF, Al-Hendy A, Bradley L, Watts NB, Diamond MP, Gao J, Owens CD, Chwalisz K, Duan WR, Soliman AM, Dufek MB, and Simon JA
- Subjects
- Adult, Double-Blind Method, Drug Therapy, Combination, Female, Gonadotropin-Releasing Hormone antagonists & inhibitors, Hemoglobins metabolism, Humans, Hydrocarbons, Fluorinated adverse effects, Leiomyoma complications, Leiomyoma pathology, Menorrhagia blood, Menorrhagia etiology, Middle Aged, Pyrimidines adverse effects, Quality of Life, Tumor Burden drug effects, Uterine Neoplasms complications, Uterine Neoplasms pathology, Contraceptive Agents, Female administration & dosage, Estradiol administration & dosage, Estrogens administration & dosage, Hydrocarbons, Fluorinated therapeutic use, Leiomyoma drug therapy, Menorrhagia drug therapy, Norethindrone Acetate administration & dosage, Pyrimidines therapeutic use, Uterine Neoplasms drug therapy
- Abstract
Objective: To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas., Methods: This double-blind, randomized, placebo-controlled, parallel-group study evaluated efficacy and safety of elagolix in cohorts 1 (300 mg twice daily) and 2 (600 mg daily) with four arms per cohort: placebo, elagolix alone, elagolix with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate. A sample size of 65 per group was planned to compare elagolix with add-back to placebo on the primary end point: the percentage of women who had less than 80 mL menstrual blood loss and 50% or greater reduction in menstrual blood loss from baseline to the last 28 days of treatment. Safety assessments included changes in bone mineral density., Results: From April 8, 2013, to December 8, 2015, 571 women were enrolled, 567 were randomized and treated (cohort 1=259; cohort 2=308), and 80% and 75% completed treatment, respectively. Participants had a mean±SD age of 43±5 years (cohort 2, 42±5 years), and 70% were black (cohort 2, 74%). Primary end point responder rates in cohort 1 (cohort 2) were 92% (90%) for elagolix alone, 85% (73%) for elagolix with 0.5 mg estradiol/0.1 mg norethindrone acetate, 79% (82%) for elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate, and 27% (32%) for placebo (all P<.001 vs placebo). Elagolix groups had significant decreases compared with placebo in lumbar spine bone mineral density, which was attenuated by adding 1.0 mg estradiol/0.5 mg norethindrone acetate., Conclusion: Elagolix with and without add-back significantly reduced menstrual blood loss in women with uterine leiomyomas. Add-back therapy reduced hypoestrogenic effects on bone mineral density., Clinical Trial Registration: ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.
- Published
- 2018
- Full Text
- View/download PDF
34. Survey of equine castration techniques, preferences and outcomes among Australian veterinarians.
- Author
-
Owens CD, Hughes KJ, Hilbert BJ, Heller J, Nielsen S, and Trope GD
- Subjects
- Animals, Australia epidemiology, Castration adverse effects, Castration methods, Linear Models, Male, Orchiectomy methods, Orchiectomy veterinary, Postoperative Complications epidemiology, Postoperative Complications veterinary, Spermatic Cord surgery, Surveys and Questionnaires, Castration psychology, Castration veterinary, Horses surgery, Veterinarians psychology
- Abstract
Objectives: (1) To collect the perceptions of veterinarians performing equine castrations in Australia on techniques, preferences and outcomes, (2) to investigate veterinarian use and experience with the Henderson castrating instrument and (3) to investigate potential associations between demographics, castration methods and techniques, and complications., Design: Online survey of members of the Australian Veterinary Association's Special Interest Group, Equine Veterinarians Australia (EVA)., Methods: A link to the survey was included in the EVA e-newsletter and practices on the EVA website were contacted by telephone and follow-up email. Fisher's exact test was used to determine associations between ligation and complications. A generalised linear model with a negative binomial family was used to determine associations between count response variables and categorical independent variables., Results: Responses were obtained from 138 veterinarians (response rate, 13.1%) who performed 5330 castrations over 12 months. Castrations were most commonly performed in the field, on anaesthetised horses, using emasculators, via an open approach and without ligation of the spermatic cord. Estimated complications after use of emasculators were swelling (25%), haemorrhage (5%) and infection (5%). The Henderson instrument was used by approximately 10% of respondents and its use for castration was associated with fewer reports of postoperative swelling compared with emasculators (P = 0.002). Rates of evisceration with the Henderson and emasculator methods were comparable (0.43% and 0.9%, respectively)., Conclusion: Castration preferences varied widely among survey participants. Reported complication types and rates were comparable to those reported previously in other countries. Perceptions that the Henderson instrument was associated with less swelling should be investigated further via a prospective controlled investigation., (© 2017 Australian Veterinary Association.)
- Published
- 2018
- Full Text
- View/download PDF
35. Impact of uterine fibroid symptoms on health-related quality of life of US women: evidence from a cross-sectional survey.
- Author
-
Soliman AM, Margolis MK, Castelli-Haley J, Fuldeore MJ, Owens CD, and Coyne KS
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Female, Humans, Leiomyoma complications, Middle Aged, Surveys and Questionnaires, Young Adult, Leiomyoma physiopathology, Quality of Life
- Abstract
Background: Uterine fibroids (UF) are associated with significant health-related quality of life (HRQL) impact. This study examined the impact of UF symptoms on HRQL., Methods: An online cross-sectional survey of 18 to 49 year old US women was conducted and collected demographics, UF prevalence, symptoms, and HRQL using the UFS-QOL. Descriptive statistics were used to examine the impact of symptom presence, severity, bothersomeness, and number of UF symptoms on HRQL. Analyses were weighted to match the US female population distribution. Multivariate regressions were performed with each subscale as a dependent variable to examine the impact of individual UF symptoms on HRQL., Results: A total of 59,411 (15.5%) panel members completed the prevalence screener; 4848 met inclusion criteria; 955 had UF and no hysterectomy. Mean age was 40.3; 58% were white; 63% were married/civil union. Common UF symptoms were: lower back pain (65%), fatigue/weariness (63%), bloating (61%), pelvic pain/cramping during menses (63%), and heavy bleeding during menses (54%). Mean UFS-QoL subscale scores were significantly (p < .05) worse among women with a UF symptom versus women without the symptom. Women who rated their UF symptoms as severe had significantly (p < .001) worse UFS-QoL scores than women with mild or moderate symptoms. UFS-QoL subscale scores worsened as the number of symptoms increased. In the regressions, the presence of bleeding and non-bleeding symptoms were related to worse UFS-QoL subscale scores., Conclusion: HRQL among women with UF was significantly impacted by UF-related symptoms. Greater impact was observed as the number and severity of symptoms increased.
- Published
- 2017
- Full Text
- View/download PDF
36. Examining the Relationship Between Symptomatic Burden and Self-reported Productivity Losses Among Patients With Uterine Fibroids in the United States.
- Author
-
Soliman AM, Anand SB, Coyne KS, Castelli-Haley J, Snabes M, and Owens CD
- Subjects
- Absenteeism, Adolescent, Adult, Cost of Illness, Efficiency, Employment statistics & numerical data, Female, Humans, Middle Aged, Presenteeism statistics & numerical data, Self Report, Surveys and Questionnaires, United States epidemiology, Young Adult, Leiomyoma epidemiology
- Abstract
Objective: To evaluate the impact of uterine fibroid symptoms on employment and household productivity., Methods: An online survey of US women between 18 and 54 was conducted. Productivity was assessed using the health related productivity questionnaire (HRPQ). Descriptive statistics and logistic multivariable regressions examined the relationship between uterine fibroids (UF) symptom experience and employment and household productivity., Results: Of 1365 eligible women, 873 (64.0%) were employed. Women lost an average of 0.8 hours to employment-related absenteeism and 4.4 hours due to employment-related presenteeism for 5.1 hours of employment productivity lost/week. Women lost an average of 1.4 hours due to household-related absenteeism and 1.6 hours due to household-related presenteeism for a total of 3.0 hours of household lost productivity. Productivity losses increased with increases in symptom burden., Conclusion: UF has a substantial impact on employment-related and household-related productivity.
- Published
- 2017
- Full Text
- View/download PDF
37. Diagnosis, classification, and treatment of femoropopliteal artery in-stent restenosis.
- Author
-
Ho KJ and Owens CD
- Subjects
- Amputation, Surgical, Constriction, Pathologic, Humans, Limb Salvage, Peripheral Arterial Disease diagnostic imaging, Peripheral Arterial Disease physiopathology, Predictive Value of Tests, Recurrence, Retreatment, Risk Factors, Treatment Outcome, Ultrasonography, Doppler, Color, Vascular Patency, Endovascular Procedures adverse effects, Endovascular Procedures instrumentation, Femoral Artery diagnostic imaging, Femoral Artery physiopathology, Peripheral Arterial Disease therapy, Popliteal Artery diagnostic imaging, Popliteal Artery physiopathology, Stents
- Abstract
In-stent restenosis is a pervasive challenge to the durability of stenting for the treatment of lower extremity ischemia. There is considerable controversy about the criteria for diagnosis, indications for treatment, and preferred algorithm for addressing in-stent restenosis. This evidence summary seeks to review existing information on strategies for the treatment of this difficult problem., (Copyright © 2016 Society for Vascular Surgery. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
38. Optimization of Peripheral Vascular Sizing with Conductance Guidewire: Theory and Experiment.
- Author
-
Choi HW, Berwick ZC, Sulkin MS, Owens CD, and Kassab GS
- Subjects
- Animals, Atherosclerosis, Catheterization instrumentation, Computer Simulation, Electric Conductivity, Electrodes, Equipment Design, Humans, Iliac Artery, Male, Models, Cardiovascular, Models, Theoretical, Peripheral Arterial Disease therapy, Reproducibility of Results, Swine, Blood Vessels anatomy & histology, Catheters, Coronary Vessels anatomy & histology
- Abstract
Although the clinical range of interventions for coronary arteries is about 2 to 5 mm, the range of diameters of peripheral vasculature is significantly larger (about 10 mm for human iliac artery). When the vessel diameter is increased, the spacing between excitation electrodes on a conductance sizing device must also increase to accommodate the greater range of vessel diameters. The increase in the excitation electrodes distance, however, causes higher parallel conductance or current losses outside of artery lumen. We have previously shown that the conductance catheter/guidewire excitation electrode distances affects the measurement accuracy for the peripheral artery lumen sizing. Here, we propose a simple solution that varies the detection electrode distances to compensate for parallel conductance losses. Computational models were constructed to simulate the conductance guidewire with various electrodes spacing combinations over a range of peripheral artery lumen diameters and surrounding tissue electrical conductivities. The results demonstrate that the measurement accuracy may be significantly improved by increased detection spacing. Specifically, an optimally configured detection/excitation spacing (i.e., 5-5-5 or an equidistant electrode interval with a detection-to-excitation spacing ratio of 0.3) was shown to accurately predict the lumen diameter (i.e., -10% < error < 10%) over a broad range of peripheral artery dimensions (4 mm < diameter < 10 mm). The computational results were substantiated with both ex-vivo and in-vivo measurements of peripheral arteries. The present results support the accuracy of the conductance technique for measurement of peripheral reference vessel diameter., Competing Interests: Dr. Choi is a consultant for 3DT Holdings, Dr. Berwick is the Director of Research, and Dr. Kassab is the founder. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2017
- Full Text
- View/download PDF
39. Posttraumatic Stress Disorder Is Associated With Worse Endothelial Function Among Veterans.
- Author
-
Grenon SM, Owens CD, Alley H, Perez S, Whooley MA, Neylan TC, Aschbacher K, Gasper WJ, Hilton JF, and Cohen BE
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Age Factors, Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Brachial Artery diagnostic imaging, Case-Control Studies, Checklist, Chi-Square Distribution, Comorbidity, Cross-Sectional Studies, Depression complications, Depression psychology, Endothelium, Vascular diagnostic imaging, Female, Humans, Hyperemia physiopathology, Hypertension complications, Hypertension drug therapy, Likelihood Functions, Linear Models, Male, Middle Aged, Multivariate Analysis, Outpatients, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease physiopathology, Predictive Value of Tests, Psychiatric Status Rating Scales, Regional Blood Flow, Risk Assessment, Risk Factors, San Francisco, Sex Factors, Stress Disorders, Post-Traumatic diagnosis, Stress Disorders, Post-Traumatic psychology, Ultrasonography, Doppler, Brachial Artery physiopathology, Endothelium, Vascular physiopathology, Peripheral Arterial Disease etiology, Stress Disorders, Post-Traumatic complications, Vasodilation, Veterans Health
- Abstract
Background: Current research in behavioral cardiology reveals a significant association between posttraumatic stress disorder (PTSD) and increased risk for cardiovascular disease and mortality; however, the underlying mechanisms remain poorly understood. We hypothesized that patients with PTSD would exhibit endothelial dysfunction, a potential mechanism involved in the development and progression of cardiovascular disease., Methods and Results: A total of 214 outpatients treated at the San Francisco Veterans Affairs Medical Center underwent tests of endothelial function and evaluation for PTSD. Flow-mediated vasodilation of the brachial artery was performed to assess endothelial function, and current PTSD status was defined by the PTSD Checklist, based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a score ≥40. Multivariable linear regression models were used to estimate the association between PTSD status and endothelial function. Patients with PTSD (n=67) were more likely to be male (99% versus 91%, P=0.04) and to have depression (58% versus 8%, P<0.0001) and were less likely to be on an angiotensin-converting enzyme inhibitor (17% versus 36%, P=0.007) or β-blocker treatment (25% versus 41%, P=0.03). Univariate analysis demonstrated that patients with PTSD had significantly lower flow-mediated vasodilation (5.8±3.4% versus 7.5±3.7%; P=0.003); furthermore, lower flow-mediated vasodilation was associated with increasing age (P=0.008), decreasing estimated glomerular filtration rate (P=0.003), hypertension (P=0.002), aspirin (P=0.03), and β-blocker treatments (P=0.01). In multivariable analysis, PTSD remained independently associated with lower flow-mediated vasodilation (P=0.0005)., Conclusions: After adjusting for demographic, comorbidity, and treatment characteristics, PTSD remained associated with worse endothelial function in an outpatient population. Whether poor endothelial function contributes to the higher risk of cardiovascular disease in patients with PTSD deserves further study., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Published
- 2016
- Full Text
- View/download PDF
40. Measurement of brachial artery endothelial function using a standard blood pressure cuff.
- Author
-
Maltz JS, Tison GH, Alley HF, Budinger TF, Owens CD, and Olgin J
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Reference Standards, Signal Processing, Computer-Assisted, Time Factors, Ultrasonic Waves, Vasodilation, Blood Pressure Determination standards, Brachial Artery physiology, Endothelium, Vascular physiology
- Abstract
The integrity of endothelial function in major arteries (EFMA) is a powerful independent predictor of heart attack and stroke. Existing ultrasound-based non-invasive assessment methods are technically challenging and suitable only for laboratory settings. EFMA, like blood pressure (BP), is both acutely and chronically affected by factors such as lifestyle and medication. Consequently, laboratory-based measurements cannot fully gauge the effects of medical interventions on EFMA. EFMA and BP have, arguably, comparable (but complementary) value in the assessment of cardiovascular health. Widespread deployment of EFMA assessment is thus a desirable clinical goal. To this end, we propose a device based on modifying the measurement protocol of a standard electronic sphygmomanometer. The protocol involves inflating the cuff to sub-diastolic levels to enable recording of the pulse waveform before and after vasodilatory stimulus. The mechanical unloading of the arterial wall provided by the cuff amplifies the distension that occurs with each pulse, which is measured as a pressure variation in the cuff. We show that the height of the rising edge of each pulse is proportional to the change in lumen area between diastole and systole. This allows the effect of vasodilatory stimuli on the artery to be measured with high sensitivity. We compare the proposed cuff flow-mediated dilation (cFMD) method to ultrasound flow-mediated dilation (uFMD). We find significant correlation (r = 0.55, p = 0.003, N = 27) between cFMD- and uFMD-based metrics obtained when the release of a 5 min cuff occlusion is employed to induce endothelial stimulus via reactive hyperemia. cFMD is approximately proportional to the square of uFMD, representing a typical increase in sensitivity to vasodilation of 300-600%. This study illustrates the potential for an individual to conveniently measure his/her EFMA by using a low-cost reprogrammed home sphygmomanometer.
- Published
- 2015
- Full Text
- View/download PDF
41. Analysis of nutritional habits and intake of polyunsaturated fatty acids in veterans with peripheral arterial disease.
- Author
-
Nosova EV, Bartel K, Chong KC, Alley HF, Conte MS, Owens CD, and Grenon SM
- Subjects
- Aged, Aged, 80 and over, Ankle Brachial Index methods, Female, Habits, Humans, Male, Middle Aged, Nutrition Assessment, Prospective Studies, Diet, Fatty Acids, Unsaturated metabolism, Hypertension metabolism, Peripheral Arterial Disease metabolism, Peripheral Arterial Disease physiopathology, Veterans
- Abstract
Inadequate nutrient intake may contribute to the development and progression of peripheral arterial disease (PAD). This study's aim was to assess intake of essential fatty acids and nutrients among veterans with PAD. All 88 subjects had ankle-brachial indices of <0.9 and claudication. A validated food frequency questionnaire evaluated dietary intake, and values were compared to guidelines established by the American Heart Association (AHA) and American College of Cardiology (ACC), as well as the AHA/ACC endorsed Dietary Approaches to Stop Hypertension (DASH) eating plan. The mean age was 69 ± 8 years. Compared to the AHA/ACC guidelines, subjects with PAD had an inadequate intake of long-chain polyunsaturated fatty acids (n-3 PUFA; 59% consumed >1 gram daily). Our subjects with PAD had an increased intake of cholesterol (31% met the cut-off established in the DASH plan), total fat (5%) and sodium (53%). They had an inadequate intake of magnesium (3%), calcium (5%), and soluble fiber (3%). Dietary potassium intake met the recommended guidelines. In our subjects with PAD, intake of critical nutrients deviated substantially from the recommended amounts. Further prospective studies should evaluate whether PAD patients experience clinical benefit if diets are modified to meet the AHA/ACC recommendations., (© The Author(s) 2015.)
- Published
- 2015
- Full Text
- View/download PDF
42. Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).
- Author
-
Grenon SM, Owens CD, Nosova EV, Hughes-Fulford M, Alley HF, Chong K, Perez S, Yen PK, Boscardin J, Hellmann J, Spite M, and Conte MS
- Subjects
- Administration, Oral, Aged, Biomarkers blood, Brachial Artery drug effects, Brachial Artery physiopathology, Double-Blind Method, Exercise Tolerance drug effects, Fatty Acids, Omega-3 blood, Female, Fish Oils blood, Humans, Inflammation Mediators blood, Male, Middle Aged, Peripheral Arterial Disease blood, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease physiopathology, San Francisco, Surveys and Questionnaires, Time Factors, Treatment Outcome, Triglycerides blood, Vasodilation drug effects, Dietary Supplements, Fatty Acids, Omega-3 administration & dosage, Fish Oils administration & dosage, Peripheral Arterial Disease drug therapy
- Abstract
Background: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD., Methods and Results: Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: -34±46 mg/dL, P<0.001; placebo -10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group., Conclusions: High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids-derived products and mediators in patients with PAD., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Published
- 2015
- Full Text
- View/download PDF
43. Vascular inflammation in a growing iliac artery aneurysm.
- Author
-
Hope MD, Gasper WJ, Rapp J, Owens CD, Haraldsson H, and Saloner D
- Subjects
- Humans, Iliac Aneurysm pathology, Inflammation, Male, Middle Aged, Iliac Aneurysm diagnostic imaging, Magnetic Resonance Imaging, Multimodal Imaging, Positron-Emission Tomography
- Abstract
We have used a multimodality imaging approach to assess the inflammatory component of a growing iliac artery aneurysm in a 53-year-old man who presented with related ureteral obstruction. Research suggests that episodic and heterogeneous inflammatory processes are important for the progression of aneurysms. The combined PET and MRI evaluation of inflammation that we present here is a novel approach to vascular imaging that is well suited for emerging hybrid PET/MRI systems., Competing Interests: Conflicts of Interest: None declared.
- Published
- 2015
- Full Text
- View/download PDF
44. Ferumoxytol-enhanced magnetic resonance angiography is a feasible method for the clinical evaluation of lower extremity arterial disease.
- Author
-
Walker JP, Nosova E, Sigovan M, Rapp J, Grenon MS, Owens CD, Gasper WJ, and Saloner DA
- Subjects
- Aged, Feasibility Studies, Glomerular Filtration Rate, Humans, Kidney physiopathology, Male, Middle Aged, Peripheral Arterial Disease complications, Peripheral Arterial Disease pathology, Pilot Projects, Predictive Value of Tests, Prospective Studies, Renal Insufficiency complications, Renal Insufficiency diagnosis, Renal Insufficiency physiopathology, Risk Factors, San Francisco, Contrast Media adverse effects, Ferrosoferric Oxide, Gadolinium DTPA adverse effects, Lower Extremity blood supply, Magnetic Resonance Angiography methods, Peripheral Arterial Disease diagnosis
- Abstract
Background: Renal toxicity from conventional, iodinated, intravenous contrast agents is a common complication in patients with peripheral artery disease (PAD). Similarly, the potential for serious side effects prevents the use of gadolinium-based agents in many patients with depressed renal function. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a novel technique that uses an intravenous, ultrasmall, superparamagnetic, iron oxide preparation, currently approved by the Food and Drug Administration for the treatment of iron deficiency anemia in adults with chronic kidney disease. Our objective was to determine the feasibility of Fe-MRA for clinical decision making in PAD patients., Methods: This was a prospective pilot study assessing 10 patients with suspected arterial occlusive disease with contrast-enhanced MRA of the aorta and lower extremities. Of those, 5 had renal insufficiency and were imaged with Fe-MRA, whereas the remainder underwent gadolinium-enhanced MRA. Qualitative and quantitative evaluations of deidentified images at each arterial station were independently performed by 4 blinded vascular surgeons., Results: All patients were men, with an average age of 68 ± 4 years. The 2 groups had similar incidences of diabetes, hypertension, hyperlipidemia, and coronary artery disease. Patients undergoing Fe-MRA had significantly decreased renal function (estimated glomerular filtration rate, 35.4 vs. 77.6; P = 0.02). There were no adverse events during contrast administration in either group. No difference was found in the overall quality of the ferumoxytol versus the gadolinium studies (7.1 ± 2.0 vs. 7.4 ± 2.4, P = 0.67). Similarly, reviewers felt comfortable basing clinical decisions on the images 89% of the time with both the ferumoxytol and gadolinium groups (P = 1.00)., Conclusions: This is the first report of an important alternative to conventional computed tomography angiography and MRA in PAD patients, particularly in the setting of renal insufficiency. Fe-MRA provides a useful tool in patients with suspected lower extremity PAD without the potential risks of gadolinium., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
45. Vein graft failure.
- Author
-
Owens CD, Gasper WJ, Rahman AS, and Conte MS
- Subjects
- Animals, Graft Occlusion, Vascular metabolism, Graft Occlusion, Vascular pathology, Graft Occlusion, Vascular physiopathology, Hemodynamics, Humans, Hyperplasia, Ischemia diagnosis, Ischemia physiopathology, Neointima, Risk Factors, Stress, Mechanical, Time Factors, Treatment Failure, Vascular Grafting methods, Veins metabolism, Veins pathology, Veins physiopathology, Wound Healing, Graft Occlusion, Vascular etiology, Ischemia surgery, Lower Extremity blood supply, Vascular Grafting adverse effects, Vascular Remodeling, Veins transplantation
- Abstract
After the creation of an autogenous lower extremity bypass graft, the vein must undergo a series of dynamic structural changes to stabilize the arterial hemodynamic forces. These changes, which are commonly referred to as remodeling, include an inflammatory response, the development of a neointima, matrix turnover, and cellular proliferation and apoptosis. The sum total of these processes results in dramatic alterations in the physical and biomechanical attributes of the arterialized vein. The most clinically obvious and easily measured of these is lumen remodeling of the graft. However, although somewhat less precise, wall thickness, matrix composition, and endothelial changes can be measured in vivo within the healing vein graft. Recent translational work has demonstrated the clinical relevance of remodeling as it relates to vein graft patency and the systemic factors influencing it. By correlating histologic and molecular changes in the vein, insights into potential therapeutic strategies to prevent bypass failure and areas for future investigation are explored., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
46. Relationship between kidney disease and endothelial function in peripheral artery disease.
- Author
-
Chong KC, Owens CD, Park M, Alley HF, Boscardin WJ, Conte MS, Gasper WJ, and Grenon SM
- Subjects
- Aged, Comorbidity, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Humans, Intermittent Claudication diagnosis, Intermittent Claudication epidemiology, Kidney Diseases diagnosis, Kidney Diseases epidemiology, Linear Models, Male, Middle Aged, Multivariate Analysis, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease epidemiology, Predictive Value of Tests, Prognosis, Risk Factors, San Francisco epidemiology, Vasodilation, Veterans Health, Brachial Artery physiopathology, Endothelium, Vascular physiopathology, Intermittent Claudication physiopathology, Kidney physiopathology, Kidney Diseases physiopathology, Peripheral Arterial Disease physiopathology
- Abstract
Objective: We have previously shown that peripheral artery disease (PAD) is associated with marked impairment of endothelial function (EF). Given that poor EF is associated with functional status of PAD patients as well as with increased morbidity and mortality in patients undergoing vascular procedures, determination of factors associated with poor EF in a PAD cohort is important. We hypothesized that decreased kidney function is associated with impaired EF in patients with PAD., Methods: This was a cross-sectional study of PAD patients presenting to a vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center including patients enrolled in the OMEGA-PAD I trial (NCT01310270) and the OMEGA-PAD Cohort. Brachial artery flow-mediated vasodilation was performed to assess EF. Kidney function was characterized by estimated glomerular filtration rate with the abbreviated Modification of Diet in Renal Disease formula. Linear regression was performed to assess the relationship between EF and kidney function in claudicants., Results: Ninety-seven patients with intermittent claudication participated in this study. Mean age was 69 ± 8 years, 97% were male, and 79% were white. Comorbidities included hypertension (91%), dyslipidemia (87%), coronary artery disease (42%), and diabetes mellitus (38%). Mean ankle-brachial index was 0.73 ± 0.14 and mean flow-mediated vasodilation was 7.0% ± 3.8%, indicating impaired EF. Linear regression showed an association between kidney function and EF (by 10 mL/min/1.73 m(2); β, 0.12; confidence interval, 0.05-0.20; P = .001). After multivariable regression adjusting for age, race, log tumor necrosis factor α, hypertension, dyslipidemia, and diabetes, estimated glomerular filtration rate remained significantly associated with EF (P = .033)., Conclusions: In patients with PAD, decreased kidney function is associated with endothelial dysfunction. Further longitudinal studies are needed to better understand the impact of kidney function on PAD progression and the role of endothelial dysfunction in this process., (Published by Elsevier Inc.)
- Published
- 2014
- Full Text
- View/download PDF
47. Clinical correlates of red blood cell omega-3 fatty acid content in male veterans with peripheral arterial disease.
- Author
-
Nosova EV, Chong KC, Alley HF, Harris WS, Boscardin WJ, Conte MS, Owens CD, and Grenon SM
- Subjects
- Age Factors, Aged, Ankle Brachial Index, Biomarkers blood, Body Mass Index, Chi-Square Distribution, Cross-Sectional Studies, Dietary Supplements, Docosahexaenoic Acids administration & dosage, Eicosapentaenoic Acid administration & dosage, Female, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Obesity complications, Obesity diagnosis, Peripheral Arterial Disease diagnosis, Peripheral Arterial Disease etiology, Prospective Studies, Risk Factors, Smoking adverse effects, Smoking blood, Docosahexaenoic Acids blood, Eicosapentaenoic Acid blood, Erythrocyte Membrane chemistry, Peripheral Arterial Disease blood, Veterans Health
- Abstract
Objective: Despite available medical therapies, patients with peripheral arterial disease (PAD) remain at high risk for cardiovascular events. The n-3 polyunsaturated fatty acids (PUFA), derived from marine sources, have been shown to improve cardiovascular mortality. The Omega-3 Index (O3I), a proportion of the n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid in the red blood cell membrane, correlates with cardiovascular risk. Previous investigations have found that n-3 PUFA supplementation, fish consumption, older age, and smoking history affect the O3I in different patient populations, although similar correlations have never been explored in PAD. We hypothesized that in our PAD cohort, blood content of omega-3 fatty acids would directly and positively correlate with a history of fish oil supplementation and older age and inversely correlate with a smoking history and obesity., Methods: This cross-sectional study included 111 patients who had an ankle-brachial index of <0.9 associated with claudication symptoms. We used linear regression to determine the association between clinical factors and the O3I., Results: The mean age of the cohort was 69 ± 8 years; 37% had diabetes mellitus (hemoglobin A1c, 7% ± 1%), and 94% reported current smoking or a history of smoking. The mean O3I was 5% ± 2%. In multivariate linear regression analysis, the O3I was associated with older age, increasing body mass index, and a history of smoking and fish oil intake., Conclusions: This is the first report of the relation between blood content of omega-3 fatty acids and clinical factors in a PAD population. In patients with PAD, older age, elevated body mass index, and prior fish oil supplementation predicted a higher O3I. A history of smoking correlated with a lower O3I. These results demonstrate that the O3I is a reliable measure of dietary n-3 PUFA intake and that clinical factors related to the O3I in PAD are similar to those observed in other populations., (Published by Elsevier Inc.)
- Published
- 2014
- Full Text
- View/download PDF
48. Ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery in clinical research.
- Author
-
Alley H, Owens CD, Gasper WJ, and Grenon SM
- Subjects
- Aged, Brachial Artery physiology, Endothelium, Vascular physiology, Female, Humans, Male, Peripheral Arterial Disease diagnostic imaging, Peripheral Arterial Disease physiopathology, Regional Blood Flow physiology, Ultrasonography, Vasodilation physiology, Brachial Artery diagnostic imaging, Endothelium, Vascular diagnostic imaging
- Abstract
The vascular endothelium is a monolayer of cells that cover the interior of blood vessels and provide both structural and functional roles. The endothelium acts as a barrier, preventing leukocyte adhesion and aggregation, as well as controlling permeability to plasma components. Functionally, the endothelium affects vessel tone. Endothelial dysfunction is an imbalance between the chemical species which regulate vessel tone, thombroresistance, cellular proliferation and mitosis. It is the first step in atherosclerosis and is associated with coronary artery disease, peripheral artery disease, heart failure, hypertension, and hyperlipidemia. The first demonstration of endothelial dysfunction involved direct infusion of acetylcholine and quantitative coronary angiography. Acetylcholine binds to muscarinic receptors on the endothelial cell surface, leading to an increase of intracellular calcium and increased nitric oxide (NO) production. In subjects with an intact endothelium, vasodilation was observed while subjects with endothelial damage experienced paradoxical vasoconstriction. There exists a non-invasive, in vivo method for measuring endothelial function in peripheral arteries using high-resolution B-mode ultrasound. The endothelial function of peripheral arteries is closely related to coronary artery function. This technique measures the percent diameter change in the brachial artery during a period of reactive hyperemia following limb ischemia. This technique, known as endothelium-dependent, flow-mediated vasodilation (FMD) has value in clinical research settings. However, a number of physiological and technical issues can affect the accuracy of the results and appropriate guidelines for the technique have been published. Despite the guidelines, FMD remains heavily operator dependent and presents a steep learning curve. This article presents a standardized method for measuring FMD in the brachial artery on the upper arm and offers suggestions to reduce intra-operator variability.
- Published
- 2014
- Full Text
- View/download PDF
49. Short-term physical inactivity impairs vascular function.
- Author
-
Nosova EV, Yen P, Chong KC, Alley HF, Stock EO, Quinn A, Hellmann J, Conte MS, Owens CD, Spite M, and Grenon SM
- Subjects
- Biomarkers blood, Blood Pressure, Female, Healthy Volunteers, Humans, Hydroxyeicosatetraenoic Acids blood, Inflammation blood, Male, Young Adult, Bed Rest adverse effects, Endothelium, Vascular physiopathology, Inflammation etiology, Sedentary Behavior, Vascular Stiffness
- Abstract
Background: Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening, and increased vascular inflammation., Methods: Five healthy subjects (four men and one woman) underwent 5 d of bed rest (BR) to simulate inactivity. Measurements of vascular function (flow-mediated vasodilation to evaluate endothelial function; applanation tonometry to assess arterial resistance), inflammation, and metabolism were made before BR, daily during BR, and 2 d after BR recovery period. Subjects maintained an isocaloric diet throughout., Results: BR led to significant decreases in brachial artery and femoral artery flow-mediated vasodilation (brachial: 11 ± 3% pre-BR versus 9 ± 2% end-BR, P = 0.04; femoral: 4 ± 1% versus 2 ± 1%, P = 0.04). The central augmentation index increased with BR (-4 ± 9% versus 5 ± 11%, P = 0.03). Diastolic blood pressure increased (58 ± 7 mm Hg versus 62 ± 7 mm Hg, P = 0.02), whereas neither systolic blood pressure nor heart rate changed. 15-Hydroxyeicosatetraenoic acid, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged., Conclusions: Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased diastolic blood pressure, and an increase in 15-hydroxyeicosatetraenoic acid. We speculate that inactivity promotes a vascular "deconditioning" state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored., (Published by Elsevier Inc.)
- Published
- 2014
- Full Text
- View/download PDF
50. Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end-stage renal disease.
- Author
-
Walker JP, Hiramoto JS, Gasper WJ, Auyang P, Conte MS, Rapp JH, Lovett DH, and Owens CD
- Subjects
- Age Factors, Aged, Aged, 80 and over, Blood Vessel Prosthesis adverse effects, Calcifediol blood, Calcium blood, Catheterization, Central Venous, Cholesterol blood, Coronary Disease epidemiology, Follow-Up Studies, Humans, Hyperlipidemias epidemiology, Kaplan-Meier Estimate, Kidney Failure, Chronic complications, Kidney Failure, Chronic therapy, Middle Aged, Proportional Hazards Models, Retrospective Studies, Risk Factors, Serum Albumin metabolism, Vitamin D Deficiency blood, Vitamin D Deficiency complications, Arteriovenous Shunt, Surgical adverse effects, Calcifediol deficiency, Kidney Failure, Chronic mortality, Vitamin D Deficiency mortality
- Abstract
Background: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1α-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease., Methods: This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at <20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes., Results: The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin D deficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model., Conclusions: Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population., (Copyright © 2014 Society for Vascular Surgery. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.