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1.
Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.
Song, HJJMD, Chia, AZQ, Tan, BKJ, Teo, CB, Lim, V, Chua, HR, Samuel, M, Kee, A
Journal of endocrinological investigation. 2023;46(2):235-259
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Plain language summary
Salt imbalances in individuals with Covid-19 are highly prevalent, however it is not fully understood if they determine whether a patient has a good or bad prognosis. This systematic review and meta-analysis of 28 observational studies aimed to determine the associations and prognostic value of different salt imbalances in individuals with Covid-19. The results showed that out of several salt imbalances analysed, high and low sodium levels and low calcium levels could predict poor outcomes in those with Covid-19. High sodium levels were particularly indicative, but this was not due to the relationship between high sodium and inflammation in the body and causal reasons remained undiscovered. It was concluded that sodium imbalances and low calcium levels were associated with poor clinical outcomes in individuals with Covid-19. This study could be used by healthcare professionals to understand that correcting these imbalances may be of benefit to individuals with Covid-19.
Abstract
PURPOSE Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.
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Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization.
Ullah, G, Nawaz, A, Latif, MS, Shah, KU, Ahmad, S, Javed, F, Alfatama, M, Abd Ghafar, SA, Lim, V
Gels (Basel, Switzerland). 2023;(1)
Abstract
Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.
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Vascular Protective Effect and Its Possible Mechanism of Action on Selected Active Phytocompounds: A Review.
Kamaruddin, NA, Hakim Abdullah, MN, Tan, JJ, Lim, V, Fong, LY, Abd Ghafar, SA, Yong, YK
Evidence-based complementary and alternative medicine : eCAM. 2022;:3311228
Abstract
Vascular endothelial dysfunction is characterized by an imbalance of vasodilation and vasoconstriction, deficiency of nitric oxide (NO) bioavailability and elevated reactive oxygen species (ROS), and proinflammatory factors. This dysfunction is a key to the early pathological development of major cardiovascular diseases including hypertension, atherosclerosis, and diabetes. Therefore, modulation of the vascular endothelium is considered an important therapeutic strategy to maintain the health of the cardiovascular system. Epidemiological studies have shown that regular consumption of medicinal plants, fruits, and vegetables promotes vascular health, lowering the risk of cardiovascular diseases. This is mainly attributed to the phytochemical compounds contained in these resources. Various databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched to identify studies demonstrating the vascular protective effects of phytochemical compounds. The literature had revealed abundant data on phytochemical compounds protecting and improving the vascular system. Of the numerous compounds reported, curcumin, resveratrol, cyanidin-3-glucoside, berberine, epigallocatechin-3-gallate, and quercetin are discussed in this review to provide recent information on their vascular protective mechanisms in vivo and in vitro. Phytochemical compounds are promising therapeutic agents for vascular dysfunction due to their antioxidative mechanisms. However, future human studies will be necessary to confirm the clinical effects of these vascular protective mechanisms.
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Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.
Priya, G, Bajaj, S, Kalra, B, Coetzee, A, Kalra, S, Dutta, D, Lim, V, Diwakar, H, Deshmukh, V, Mehta, R, et al
Journal of family medicine and primary care. 2021;(12):4350-4363
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Abstract
The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.
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The Urea-to-Creatinine Ratio Is Predictive of Worsening Kidney Function in Ambulatory Heart Failure Patients.
Sood, MM, Saeed, M, Lim, V, Cordova, F, Komenda, P, Malik, A, Rigatto, C, Shafer, LA, Tangri, N, Tappia, PS, et al
Journal of cardiac failure. 2015;(5):412-418
Abstract
BACKGROUND Changes in kidney function in heart failure patients convey important prognostic information. We investigated the association of the urea-to-creatinine (BUN/Cr) ratio, the fractional excretion of urea (FeUr), and the fractional excretion of sodium (FeNa) and subsequent declines in kidney function in ambulatory heart failure patients. METHODS AND RESULTS We prospectively enrolled adult patients with ejection fraction <40% at a multidisciplinary heart failure clinic and measured serial measurements of laboratory values from September 2008 to July 2011. The study outcome was changes in the estimated glomerular filtration rate (eGFR). In 138 patients contributing 10,350 patient-hours of follow-up, we found that participants with a decline of >25% in eGFR had higher mean BUN/Cr ratio (0.110 ± 0.043 vs 0.086 ± 0.026; P = .02) and no difference in the FeNa (1.81 vs 1.43; P = .2) or FeUr (32.3 vs 37.2; P = .9) compared with those with no change. There was an association of BUN/Cr ratio with the rate of change of eGFR (coefficient -25.67, 95% confidence interval [CI] -10.99 to -40.35; P < .0001). The BUN/Cr ratio was an independent predictor of eGFR drop >25% (odds ratio 1.19, 95% CI 1.07-1.32) and improved model discrimination (c-statistic increased from 0.624 to 0.693) and reclassification (net reclassification index 11.38% [P < .0001], integrated discrimination improvement 5.24% [P = .02]). CONCLUSIONS The BUN/Cr ratio is associated with worsening kidney function and adds incremental risk prediction information relative to traditional predictive measures in outpatients with heart failure at risk for worsening kidney disease.
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Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism.
Lim, V, Guo, Q, Grant, CS, Thompson, GB, Richards, ML, Farley, DR, Young, WF
The Journal of clinical endocrinology and metabolism. 2014;(8):2712-9
Abstract
CONTEXT The accurate distinction between unilateral and bilateral adrenal disease in patients with primary aldosteronism (PA) guides surgical management. Adrenal venous sampling (AVS), the criterion standard localization procedure, is not readily available at many centers throughout the world. OBJECTIVE The objective of the study was to determine factors most consistent with surgically curable PA. DESIGN This was a retrospective observational study. SETTING The study was conducted at the Mayo Clinic (Rochester, Minnesota), a tertiary referral center. PATIENTS All patients who underwent unilateral adrenalectomy for treatment of PA between January 1993 and December 2011 participated in the study. INTERVENTION The intervention in the study was unilateral adrenalectomy. MAIN OUTCOME MEASURES Variables associated with the prediction of unilateral disease were measured. RESULTS Over 19 years, 263 patients underwent unilateral adrenalectomy for the treatment of PA. Long-term postoperative follow-up was obtained in 143 patients (54.4%). The overall effective cure rate of PA was 95.5% in those patients sent for adrenalectomy for presumptive unilateral disease. In patients with cured PA, defined as the resolution of autonomous aldosterone secretion, hypertension was cured in 53 (41.7%) and improved in 59 (46.5%) patients. PA was not cured with unilateral adrenalectomy in six patients (4.2%). Adrenal imaging and AVS were concordant to the surgically documented side in 58.6% and 97.1% of the patients, respectively. Although there was no statistically significant difference in mean age between the inaccurate vs the accurate adrenal imaging group, we found that the minimum age in the former was 35.1 years. CONCLUSIONS Using adrenal imaging and AVS, the effective surgical cure rate for PA was 95.5%. Although the overall accuracy of computed tomography and magnetic resonance imaging in detecting unilateral adrenal disease was poor at 58.6%, adrenal imaging performed well in those patients younger than 35 years of age.
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Two-year-plus follow-up of a paclitaxel-eluting stent in de novo coronary narrowings (TAXUS I).
Grube, E, Silber, S, Hauptmann, KE, Buellesfeld, L, Mueller, R, Lim, V, Gerckens, U, Russell, ME
The American journal of cardiology. 2005;(1):79-82
Abstract
Early results with polymer-based paclitaxel-eluting stents have shown significant improvements in the clinical and angiographic parameters of restenosis, as well as excellent safety outcomes. However, the duration of these beneficial effects is unknown. Therefore, the clinical outcomes of the TAXUS I study population were evaluated at 2- and 3-year follow-up. In TAXUS I, 61 patients with single, focal coronary lesions were randomly assigned to receive either a paclitaxel-eluting TAXUS stent (n = 31) or a bare metal control stent (n = 30). Low rates of composite major adverse cardiac events (MACEs) reported at 1-year follow-up (3.2% TAXUS vs 10.0% control) were maintained at 2 and 3 years, with no additional MACEs in either treatment group 1 year after implantation. The single target vessel revascularization in the TAXUS group was remote from the target lesion in contrast to 3 target lesion revascularizations in the control group.
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Physical Activity in the Prevention of Atherosclerotic Coronary Heart Disease.
Thompson, PD, Lim, V
Current treatment options in cardiovascular medicine. 2003;(4):279-285
Abstract
There are compelling epidemiologic and clinical data demonstrating that regular physical activity reduces the incidence of atherosclerotic vascular disease. The hypothesis that exercise decreases atherosclerotic coronary heart disease has never been directly tested in a randomized, controlled clinical trial. Nevertheless, there are sufficient data to recommend that adults should routinely engage in moderately vigorous physical activity. Exercise training also improves multiple atherosclerotic cardiovascular risk factors, including low levels of high-density lipoprotein cholesterol, blood triglycerides, blood pressure, glucose intolerance, insulin resistance, and obesity. Some of this effect attributed to exercise training is actually an acute effect of recent exercise and not a chronic metabolic adaptation. There are multiple randomized controlled clinical trials of exercise training in patients with established coronary artery disease enrolled in cardiac rehabilitation programs. These results demonstrate that exercise training reduces total cardiovascular mortality in patients with established coronary heart disease. The evidence cited above supports the recommendation that all stable adults should participate daily in a minimum of 30 minutes of moderately vigorous physical activity. Less activity than this is probably beneficial, whereas more activity is probably more beneficial.