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Prognostic value of cardiac biomarkers in COVID-19 infection.
Sheth, A, Modi, M, Dawson, D, Dominic, P
Scientific reports. 2021;(1):4930
Abstract
Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. PubMed, Embase and Web of Science were searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.57, 95% CI 0.43-0.70, p < 0.001). Additionally, BNP levels were also significantly higher in patients who died or were critically ill (WMD 0.45, 95% CI - 0.21-0.69, p < 0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26-35.1, p = 0.03). A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.79, 95% CI 0.25-1.33, p = 0.004). Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.
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Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.
Abbara, A, Eng, PC, Phylactou, M, Clarke, SA, Richardson, R, Sykes, CM, Phumsatitpong, C, Mills, E, Modi, M, Izzi-Engbeaya, C, et al
The Journal of clinical investigation. 2020;(12):6739-6753
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Abstract
BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.
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Early Aggressive Enteral Feeding in Neonates Weighing 750-1250 Grams: A Randomized Controlled Trial.
Modi, M, Ramji, S, Jain, A, Kumar, P, Gupta, N
Indian pediatrics. 2019;(4):294-298
Abstract
BACKGROUND In preterm neonates, enteral feeding is advanced slowly, considering the risk of necrotizing enterocolitis. Prolonged intravenous alimentation in these neonates, however, may increase the risk of sepsis-related morbidity and mortality, particularly in low resource settings. OBJECTIVES Objective of this was study to evaluate impact of aggressive enteral feeding on mortality and morbidities among preterm neonates. DESIGN Randomized controlled trial. PARTICIPANTS Neonates with birthweight 750-1250 g. INTERVENTIONS 131 preterm neonates with birth weight 750-1250 g, admitted to neonatal intensive care unit between April 2012 and June 2014, were randomized to aggressive feeding or conservative feeding regimen. OUTCOMES The primary outcome of the study was all-cause mortality during hospital stay. The secondary outcomes included proportion of sepsis (blood culture proven), necrotizing enterocolitis, feed intolerance, survival without major morbidity at discharge, time to reach full enteral feed (180 mL/kg/d), duration of hospitalization, and average daily weight gain (g/kg). RESULTS All-cause mortality was 33.3% in aggressive regimen and 43.1% in conservative regimen, [RR (95%) CI 0.77 (0.49, 1.20)]. Neonates with aggressive feeding regimen reached full enteral feed earlier; median (IQR) 7 (6, 8) days compared to conservative regimen, 10 (9, 14) days; P <0.001. There was no difference in culture positive sepsis rate, survival without major morbidities, feed intolerance, necrotizing enterocolitis, duration of hospitalization and average daily weight gain. CONCLUSIONS In neonates with birth weight 750-1250 g, early aggressive feeding regimen is feasible but not associated with significant reduction in all-cause mortality, culture positive sepsis or survival without major morbidities during hospital stay. Neonates with aggressive regimen have fewer days on IV fluids and reach full feed earlier.
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Effect of Vitamin D and calcium supplementation on ischaemic stroke outcome: a randomised controlled open-label trial.
Gupta, A, Prabhakar, S, Modi, M, Bhadada, SK, Kalaivani, M, Lal, V, Khurana, D
International journal of clinical practice. 2016;(9):764-70
Abstract
BACKGROUND AND AIMS Vitamin D deficiency is a common problem in stroke survivors. Observational studies have reported an association of low vitamin D levels with greater stroke severity, poststroke mortality and functional disability. Randomised clinical trials are lacking. We sought to assess the effect of calcium and vitamin D supplementation in ischaemic stroke survivors with vitamin D deficiency/insufficiency on disability/mortality outcomes. METHODS In this randomised controlled open-label trial, 73 patients of acute ischaemic stroke were screened for serum 25 hydroxy Vitamin D (25(OH)D) levels. A total of 53 patients with baseline 25(OH)D <75 nmol/L were randomised into two arms. One received vitamin D and calcium supplementation along with usual care (n=25) and the other received usual care alone (n=28). Primary outcome was the proportion of patients achieving a good outcome [modified Rankin Scale score 0-2] at 6 months and all cause mortality at 6 months. RESULTS The age (mean±SD) of participants was 60.4±11.3 years, 69.8% were males. The proportion of patients achieving good outcome was higher in the intervention arm (Adjusted OR 1.9, 95% CI 0.6-6.4; P=.31). The survival probability was greater in the intervention arm (83.8%, CI 62.4-93.6) as compared with the control arm (59.5%, CI 38.8-75.2; P=.049) with adjusted Hazard ratio (HR) of 0.26 (95% CI 0.08-0.9; P=.03). CONCLUSIONS This is the first randomised controlled study assessing the effect of vitamin D and calcium supplementation on ischaemic stroke outcomes and points towards a potential benefit. Findings need to be validated by a larger trial.
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Abdominal circumference or gastric residual volume as measure of feed intolerance in VLBW infants.
Kaur, A, Kler, N, Saluja, S, Modi, M, Soni, A, Thakur, A, Garg, P
Journal of pediatric gastroenterology and nutrition. 2015;(2):259-63
Abstract
BACKGROUND The aim of the study was to compare prefeed abdominal circumference (AC) and gastric residual volume (GRV) as a measure of feed intolerance in very-low-birth-weight infants (VLBW). METHODS Eighty VLBW infants were randomized to 2 groups; feed intolerance was monitored by measuring either GRV group or prefeed AC group. The primary outcome was time to full enteral feeds (180 mL · kg · day). Other main outcome measures were feed interruption days, duration of parenteral nutrition, incidence of culture positive sepsis, necrotizing enterocolitis, mortality, and duration of hospital stay. RESULTS The median (interquartile range) time to achieve full feeds was 10 (9-13) versus 14 (12-17.5) days in AC and GRV groups, respectively (P < 0.001). Infants in AC group had fewer feed interruption days (0 [0-2] vs 2.0 [1, 5], P < 0.001) and shorter duration of parenteral nutrition (P < 0.001). The incidence of culture-positive sepsis in AC and GRV groups was 17.5% and 30 %, respectively (P = 0.18). Duration of hospital stay and mortality were comparable in both the groups. CONCLUSIONS Prefeed AC as a measure of feed intolerance in VLBW infants may shorten the time taken to achieve full feeds.
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Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration.
, , Apte, RS, Modi, M, Masonson, H, Patel, M, Whitfield, L, Adamis, AP
Ophthalmology. 2007;(9):1702-12
Abstract
OBJECTIVE To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received pegaptanib sodium. INTERVENTION Subjects were randomized to receive intravitreous pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antipegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of pegaptanib plasma concentrations. RESULTS No antipegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology. CONCLUSIONS At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.