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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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Abstract
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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Clinical Trial in a Dish: Personalized Stem Cell-Derived Cardiomyocyte Assay Compared With Clinical Trial Results for Two QT-Prolonging Drugs.
Blinova, K, Schocken, D, Patel, D, Daluwatte, C, Vicente, J, Wu, JC, Strauss, DG
Clinical and translational science. 2019;(6):687-697
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Abstract
Induced pluripotent stem cells (iPSCs) have shown promise in investigating donor-specific phenotypes and pathologies. The iPSC-derived cardiomyocytes (iPSC-CMs) could potentially be utilized in personalized cardiotoxicity studies, assessing individual proarrhythmic risk. However, it is unclear how closely iPSC-CMs derived from healthy subjects can recapitulate a range of responses to drugs. It is well known that QT-prolonging drugs induce subject-specific clinical response and that all healthy subjects do not necessarily develop arrhythmias or exhibit similar amounts of QT prolongation. We previously reported this variability in a study of four human ether-a-go-go-related gene (hERG) potassium channel-blocking drugs in which each subject underwent intensive pharmacokinetic and pharmacodynamic sampling such that subjects had 15 time-matched plasma drug concentration and electrocardiogram measurements throughout 24 hours after dosing in a phase I clinical research unit. In this study, iPSC-CMs were generated from those subjects. Their drug-concentration-dependent QT prolongation response from the clinic was compared with in vitro drug-concentration-dependent action potential duration (APD) prolongation response to the same two hERG-blocking drugs, dofetilide and moxifloxacin. Comparative results showed no significant correlation between the subject-specific APD response slopes and clinical QT response slopes to either moxifloxacin (P = 0.75) or dofetilide (P = 0.69). Similarly, no significant correlation was found between baseline QT and baseline APD measurements (P = 0.93). This result advances our current understanding of subject-specific iPSC-CMs and facilitates discussion into factors obscuring correlation and considerations for future studies of subject-specific phenotypes in iPSC-CMs.
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Pain Control Interventions in Preterm Neonates: A Randomized Controlled Trial.
Shukla, VV, Bansal, S, Nimbalkar, A, Chapla, A, Phatak, A, Patel, D, Nimbalkar, S
Indian pediatrics. 2018;(4):292-296
Abstract
OBJECTIVE To compare individual efficacy and additive effects of pain control interventions in preterm neonates. DESIGN Randomized controlled trial. SETTING Level-3 University affiliated neonatal intensive care unit. PARTICIPANTS 200 neonates (26-36 wk gestational age) requiring heel-prick for bedside glucose assessment. Exclusion criteria were neurologic impairment and critical illness precluding study interventions. INTERVENTION Neonates were randomly assigned to Kangaroo mother care with Music therapy, Music therapy, Kangaroo Mother care or Control (no additional intervention) groups. All groups received expressed breast milk with cup and spoon as a baseline pain control intervention. MAIN OUTCOME MEASURES Assessment of pain using Premature Infant Pain Profile (PIPP) score on recorded videos. RESULTS The mean (SD) birth weight and gestational age of the neonates was 1.9 (0.3) kg and 34 (2.3) wk, respectively. Analysis of variance showed significant difference in total PIPP score across groups (P<0.001). Post-hoc comparisons using Sheffe's test revealed that the mean (SD) total PIPP score was significantly lower in Kangaroo mother care group [7.7 (3.9) vs. 11.5 (3.4), 95% CI(-5.9, -1.7), P<0.001] as well as Kangaroo mother care with Music therapy group [8.5 (3.2) vs. 11.5 (3.4), 95%CI (-5.1, -0.9), P=0.001] as compared to Control group. PIPP score was not significantly different between Control group and Music therapy group. CONCLUSIONS Kangaroo mother care with and without Music therapy (with expressed breast milk) significantly reduces pain on heel-prick as compared to expressed breast milk alone. Kangaroo mother care with expressed breast milk should be the first choice as a method for pain control in preterm neonates.
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Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve.
Williams, MC, Mirsadraee, S, Dweck, MR, Weir, NW, Fletcher, A, Lucatelli, C, MacGillivray, T, Golay, SK, Cruden, NL, Henriksen, PA, et al
European radiology. 2017;(3):1114-1124
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Abstract
OBJECTIVES Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS 51 patients (63 (61-65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by "snapshot" adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. RESULTS PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32-2.20) vs 3.11 (2.44-3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32-2.20) vs 3.12 (2.44-3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71-76) vs 86 (84-88) HU, P < 0.001 and 101 (96-106) vs 111 (107-114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. CONCLUSION CT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. KEY POINTS •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from "snapshot" imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with 15 O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.
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Randomised controlled trial of alternative messages to increase enrolment in a healthy food programme among individuals with diabetes.
Gopalan, A, Paramanund, J, Shaw, PA, Patel, D, Friedman, J, Brophy, C, Buttenheim, AM, Troxel, AB, Asch, DA, Volpp, KG
BMJ open. 2016;(11):e012009
Abstract
OBJECTIVES We compared the effectiveness of diabetes-focused messaging strategies at increasing enrolment in a healthy food programme among adults with diabetes. METHODS Vitality is a multifaceted wellness benefit available to members of Discovery Health, a South Africa-based health insurer. One of the largest Vitality programmes is HealthyFood (HF), an incentive-based programme designed to encourage healthier diets by providing up to 25% cashback on healthy food purchases. We randomised adults with type 2 diabetes to 1 of 5 arms: (1) control, (2) a diabetes-specific message, (3) a message with a recommendation of HF written from the perspective of a HF member with diabetes, (4) a message containing a physician's recommendation of HF, or (5) the diabetes-specific message from arm 2 paired with an 'enhanced active choice'(EAC). In an EAC, readers are asked to make an immediate choice (in this case, to enrol or not enrol); the pros and cons associated with the preferred and non-preferred options are highlighted. HF enrolment was assessed 1 month following the first emailed message. RESULTS We randomised 3906 members. After excluding those who enrolled in HF or departed from the Vitality programme before the first intervention email, 3665 (94%) were included in a modified intent-to-treat analysis. All 4 experimental arms had significantly higher HF enrolment rates compared with control (p<0.0001 for all comparisons). When comparing experimental arms, the diabetes-specific message with the EAC had a significantly higher enrolment rate (12.6%) than the diabetes-specific message alone (7.6%, p=0.0016). CONCLUSIONS Messages focused on diabetes were effective at increasing enrolment in a healthy food programme. The addition of a framed active choice to a message significantly raised enrolment rates in this population. These findings suggest that simple, low-cost interventions can enhance enrolment in health promoting programmes and also be pragmatically tested within those programmes. TRIAL REGISTRATION NUMBER NCT02462057.
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Effect of lowering the glycemic load with canola oil on glycemic control and cardiovascular risk factors: a randomized controlled trial.
Jenkins, DJ, Kendall, CW, Vuksan, V, Faulkner, D, Augustin, LS, Mitchell, S, Ireland, C, Srichaikul, K, Mirrahimi, A, Chiavaroli, L, et al
Diabetes care. 2014;(7):1806-14
Abstract
OBJECTIVE Despite their independent cardiovascular disease (CVD) advantages, effects of α-linolenic acid (ALA), monounsaturated fatty acid (MUFA), and low-glycemic-load (GL) diets have not been assessed in combination. We therefore determined the combined effect of ALA, MUFA, and low GL on glycemic control and CVD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS The study was a parallel design, randomized trial wherein each 3-month treatment was conducted in a Canadian academic center between March 2011 and September 2012 and involved 141 participants with type 2 diabetes (HbA1c 6.5%-8.5% [48-69 mmol/mol]) treated with oral antihyperglycemic agents. Participants were provided with dietary advice on either a low-GL diet with ALA and MUFA given as a canola oil-enriched bread supplement (31 g canola oil per 2,000 kcal) (test) or a whole-grain diet with a whole-wheat bread supplement (control). The primary outcome was HbA1c change. Secondary outcomes included calculated Framingham CVD risk score and reactive hyperemia index (RHI) ratio. RESULTS Seventy-nine percent of the test group and 90% of the control group completed the trial. The test diet reduction in HbA1c units of -0.47% (-5.15 mmol/mol) (95% CI -0.54% to -0.40% [-5.92 to -4.38 mmol/mol]) was greater than that for the control diet (-0.31% [-3.44 mmol/mol] [95% CI -0.38% to -0.25% (-4.17 to -2.71 mmol/mol)], P = 0.002), with the greatest benefit observed in those with higher systolic blood pressure (SBP). Greater reductions were seen in CVD risk score for the test diet, whereas the RHI ratio increased for the control diet. CONCLUSIONS A canola oil-enriched low-GL diet improved glycemic control in type 2 diabetes, particularly in participants with raised SBP, whereas whole grains improved vascular reactivity.
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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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Efficacy comparison of levocetirizine vs montelukast in ragweed sensitized patients.
Patel, P, Patel, D
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2008;(3):287-94
Abstract
BACKGROUND To date, no adequate data are available on direct comparison of the efficacy of levocetirizine, a recently approved histamine1-antihistamine, with that of a leukotriene antagonist in the treatment of seasonal allergic rhinitis (SAR) symptoms. OBJECTIVE To compare the efficacy of therapeutic doses of 5 mg of levocetirizine and 10 mg of montelukast in ragweed sensitized patients. METHODS A randomized, double-blind, placebo-controlled, parallel-group study was conducted between July and October 2006. Symptomatic patients with SAR were exposed to ragweed pollen under controlled conditions in an environmental exposure chamber for 4 to 5 hours after treatment with 5 mg of levocetirizine, 10 mg of montelukast, or matched placebo on 2 consecutive days. The mean change from baseline in pollen-induced rhinitis symptoms, expressed as a major symptoms complex (MSC) score (sum of scores for rhinorrhea, itchy nose, sniffles, nose blows, sneezes, and watery eyes), in period 1 (first 5 hours after first drug intake) was the primary efficacy outcome. RESULTS A total of 611 patients were screened, of whom 403 were randomized to receive treatment (102 placebo, 152 levocetirizine, and 149 montelukast). The MSC score in period 1 was progressively decreased to a significantly greater extent in the levocetirizine group compared with the montelukast and placebo groups (adjusted mean differences, -2.18 [95% confidence interval, -3.35 to -1.01; P < .001] and -2.22 [95% confidence interval, -3.51 to -0.92; P < .001] for levocetirizine vs montelukast and vs placebo, respectively). The effect of 10 mg of montelukast was not significantly different compared with placebo. Levocetirizine also achieved a significantly faster onset of action within 2.5 hours of administration. Both products were well tolerated. CONCLUSIONS This study in an environmental exposure chamber confirms the therapeutic efficacy of 5 mg of levocetirizine in improving symptoms of SAR, which was superior to 10 mg of montelukast.
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A randomized prospective trial comparing different regimens of oral sodium phosphate and polyethylene glycol-based lavage solution in the preparation of patients for colonoscopy.
Rostom, A, Jolicoeur, E, Dubé, C, Grégoire, S, Patel, D, Saloojee, N, Lowe, C
Gastrointestinal endoscopy. 2006;(4):544-52
Abstract
BACKGROUND Regulatory agencies have warned clinicians regarding the risk of electrolyte abnormalities if more than two 45-mL bottles of oral sodium phosphate (NaP) solution are administered within a 24-hour period. OBJECTIVE To compare the efficacy, safety, and tolerability of different regimens of oral NaP and polyethylene glycol (PEG). DESIGN Randomized controlled trial. SETTING Teaching hospital outpatient endoscopy clinic. PATIENTS Two hundred outpatients without comorbidities who underwent routine colonoscopy. INTERVENTIONS Two bottles of NaP, 6, 12, or 24 hours apart; or 4 L PEG. MAIN OUTCOME MEASUREMENTS Bowel preparation quality, patient tolerability, and electrolyte changes. RESULTS The 12- and 24-hour NaP achieved better cleansing than the 6-hour NaP or PEG. Only 8.5% and 8.3% of patients in the 24- and 12-hour NaP had poor preparations, respectively, compared with 15.6% and 23.4% in the 6-hour NaP and PEG, respectively. The poorer preparation scores with PEG were partly because of a greater amount of colonic fluid. There were no relevant electrolyte changes with PEG, whereas hypokalemia, hypocalcemia, or hyperphosphatemia developed in 5% to 57% of patients on NaP. All regimens were poorly tolerated by patients. LIMITATIONS The study was likely underpowered to detect small group differences in electrolytes. CONCLUSIONS A 24- or 12-hour NaP bowel preparation strategy was more effective than NaP 6 hours apart or PEG. PEG use is associated with more residual colonic fluid but represents an alternative to NaP in some clinical situations.