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Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.
Thomas, S, Patel, D, Bittel, B, Wolski, K, Wang, Q, Kumar, A, Il'Giovine, ZJ, Mehra, R, McWilliams, C, Nissen, SE, et al
JAMA network open. 2021;(2):e210369
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IMPORTANCE There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. OBJECTIVE To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. INTERVENTION Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. OUTCOMES The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. RESULTS A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04342728.
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Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding.
Stevens, J, Wyatt, C, Brown, P, Patel, D, Grujic, D, Freedman, SD
Journal of pediatric gastroenterology and nutrition. 2018;(4):527-532
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OBJECTIVES Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, enteral nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability, and improvement of fatty acid (FA) status in red blood cell (RBC) membranes, a marker of long-term FA absorption, with an in-line digestive cartridge (RELiZORB) that hydrolyzes fat in enteral formula. METHODS Patients with CF receiving EN participated in a multicenter, 90-day open-label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of docosahexaenoic acid (DHA)+ eicosapentaenoic acid (EPA). Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study. RESULTS A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω-6/ω-3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events. CONCLUSIONS RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Because improvement in omega-3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long-term therapeutic benefits in patients with CF.
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Amino acids in a targeted versus a non-targeted metabolomics LC-MS/MS assay. Are the results consistent?
Klepacki, J, Klawitter, J, Klawitter, J, Karimpour-Fard, A, Thurman, J, Ingle, G, Patel, D, Christians, U
Clinical biochemistry. 2016;(13-14):955-61
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BACKGROUND The results of plasma amino acid patterns in samples from kidney transplant patients with good and impaired renal function using a targeted LC-MS/MS amino acid assay and a non-targeted metabolomics assay were compared. METHODS EDTA plasma samples were prospectively collected at baseline, 1, 2, 4 and 6months post-transplant (n=116 patients, n=398 samples). Each sample was analyzed using both a commercial amino acid LC-MS/MS assay and a non-targeted metabolomics assay also based on MS/MS ion transitions. The results of both assays were independently statistically analyzed to identify amino acids associated with estimated glomerular filtration rates using correlation and partial least squares-discriminant analysis. RESULTS Although there was overlap between the results of the targeted and non-targeted metabolomics assays (tryptophan, 1-methyl histidine), there were also substantial inconsistencies, with the non-targeted assay resulting in more "hits" than the targeted assay. Without further verification of the hits detected by the non-targeted discovery assay, this would have led to different interpretation of the results. There were also false negative results when the non-targeted assay was used (hydroxy proline). Several of said discrepancies could be explained by loss of sensitivity during analytical runs for selected amino acids (serine and threonine), retention time shifts, signals above the range of linear detector response and integration of peaks not separated from background and interferences (aspartate) when the non-targeted metabolomics assay was used. CONCLUSIONS Whenever assessment of a specific pathway such as amino acids is the focus of interest, a targeted seems preferable to a non-targeted metabolomics assay.
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Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.
Wisinski, KB, Xu, W, Tevaarwerk, AJ, Saha, S, Kim, K, Traynor, A, Dietrich, L, Hegeman, R, Patel, D, Blank, J, et al
Clinical breast cancer. 2016;(4):256-61
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BACKGROUND Estrogen receptor beta (ERβ) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERβ has antiproliferative effects in TNBC cells expressing ERβ. This phase 2 study evaluated single-agent high-dose estradiol in patients with advanced TNBC. PATIENTS AND METHODS Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB, and PFS by ERβ status were also examined. RESULTS Seventeen evaluable women were enrolled. Median age was 58 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with one lasting more than 16 weeks. ERβ expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERβ-positive patients and 0% (0 of 4) in ERβ-negative patients (P = 1). PFS was poor (median, 1.9 months) and not statistically significantly different between ERβ-positive versus -negative patients. No new adverse events from estradiol were identified. The study closed after the first stage as a result of limited responses in these unselected patients. CONCLUSION In unselected TNBC, high-dose estradiol has limited efficacy. However, further evaluation of ERβ selective agonists in TNBC selected by ERβ expression may be warranted.
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Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.
Ramprasath, VR, Jenkins, DJ, Lamarche, B, Kendall, CW, Faulkner, D, Cermakova, L, Couture, P, Ireland, C, Abdulnour, S, Patel, D, et al
Nutrition journal. 2014;:101
Abstract
BACKGROUND Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. OBJECTIVE The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. METHODS Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. RESULTS No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. CONCLUSION Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00438425.
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Effect of cystatin C levels on angiographic atherosclerosis progression and events among postmenopausal women with angiographically decompensated coronary artery disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).
Patel, D, Ahmad, S, Silverman, A, Lindsay, J
The American journal of cardiology. 2013;(12):1681-7
Abstract
End-stage renal disease and mild renal insufficiency are associated with increased cardiovascular risk. Cystatin C, a novel marker of kidney function, was found to be associated with a higher frequency of cardiovascular events and mortality independent of glomerular filtration rate. It remained uncertain, however, whether enhanced cardiovascular risk associated with cystatin C is due to accelerated progression of atherosclerosis or to plaque instability. The aim of this study was to examine the effects of baseline cystatin C on annual change in coronary artery narrowing and clinical events in 423 postmenopausal women with angiographically documented coronary artery disease enrolled in the Women's Angiographic Vitamin and Estrogen (WAVE) trial. Baseline and follow-up (mean 2.8 ± 0.9 years) angiography was performed in 320 women. Angiographic progression of disease and clinical events in each cystatin C quartile were compared. Women with cystatin C levels in the highest quartile were older and more likely to have histories of heart failure and stroke. Annualized changes in minimal and average luminal diameters were similar in diseased and nondiseased segments. All-cause death or myocardial infarction (3.6% vs 15.6%, p <0.001), cardiovascular death or myocardial infarction (2.3% vs 13.5%, p <0.001), and cardiovascular events (3.6% vs 13.5%, p <0.001) were significantly higher in women with baseline cystatin C levels in the highest quartile compared with women with cystatin C levels in the lower 3 quartiles. The risk for clinical events associated with cystatin C remained significantly higher in multivariate logistic regression analysis after adjusting for baseline differences and cardiovascular risk factors. The risk for clinical events was also independent of estimated glomerular filtration rate. In conclusion, in postmenopausal women with angiographically documented coronary artery disease, baseline cystatin C levels were associated with worse clinical outcomes without accelerated progression of atherosclerosis.
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Discordant association of C-reactive protein with clinical events and coronary luminal narrowing in postmenopausal women: data from the Women's Angiographic Vitamin and Estrogen (WAVE) study.
Patel, D, Jhamnani, S, Ahmad, S, Silverman, A, Lindsay, J
Clinical cardiology. 2013;(9):535-41
Abstract
BACKGROUND The incidence of cardiovascular events had been shown to be associated with C-reactive protein (CRP). However, it is unclear that the cardiovascular risk associated with CRP is due to progressive coronary narrowing or to other factors such as formation of unstable plaque. This study was designed to determine the effect of baseline CRP on cardiovascular events and on the progression of atherosclerotic narrowing among 423 postmenopausal women with angiographic stenosis between 15% and 75%. HYPOTHESIS Baseline CRP levels may affect cardiovascular events and progression of atherosclerotic coronary artery narrowing among postmenopausal women. METHODS Baseline and follow-up (2.8 years) angiographic data were analyzed among 320 women. Women were stratified into 4 quartiles according to baseline CRP levels. The changes in lumen diameter and clinical events in each quartile were compared. RESULTS The annualized changes in minimal and average lumen diameter in diseased and nondiseased coronary segments were not significantly associated with baseline CRP levels. The composite end point of all-cause mortality and myocardial infarction (MI) increased from 3% (3/107) in the first CRP quartile to 14% (14/98) in fourth CRP quartile (P < 0.001). Similar results were found for cardiovascular death and MI (increased from 1% (2/107) in the first quartile to 11% (11/98) in fourth quartile). The difference remained significant even after adjustment for baseline differences and cardiovascular risk factors. CONCLUSIONS Higher baseline CRP was associated with increased risk of clinical events but was not associated with annualized change in luminal diameters. Thus, increased risk of adverse events among patients with higher baseline CRP events was independent of progression of atherosclerosis as measured by change in minimal or average luminal diameter.