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  1. Ng KT, Teoh WY
    Prehosp Disaster Med, 2019 Oct;34(5):532-539.
    PMID: 31455452 DOI: 10.1017/S1049023X19004758
    INTRODUCTION: Epinephrine has been recommended for out-of-hospital cardiac arrest (OHCA) resuscitation for nearly one century, but its efficacy and safety remain unclear in the literature. The primary aim of this review was to determine whether epinephrine increases the return of spontaneous circulation in OHCA patients.

    METHODS: A systematic review and meta-analysis were conducted using the following databases: MEDLINE, EMBASE, and CENTRAL, from their inception until October 2018. All the randomized controlled trials (RCTs) were included. Observational studies, case reports, case series, and non-systematic reviews were excluded.

    RESULTS: Two trials including 8,548 patients were eligible for inclusion in the data synthesis. In patients who received epinephrine during OHCA, the incidence of return of spontaneous circulation was increased, with an odds ratio (95%CI) of 4.25 (3.79-4.75), P

  2. Ng KT, Teoh WY, Khor AJ
    J Clin Anesth, 2020 Feb;59:74-81.
    PMID: 31279283 DOI: 10.1016/j.jclinane.2019.06.027
    OBJECTIVES: Melatonin is an endogenous hormone, which regulates circadian rhythms and promotes sleep. In recent years, several randomised controlled trials examining the prophylactic use of melatonin to prevent delirium were published with conflicting findings. The primary aim of this review was to determine the effect of melatonin on the incidence of delirium in hospitalised patients.

    DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from their inception until December 2018.

    REVIEW METHODS: All randomised clinical trials were included.

    RESULTS: Sixteen trials (1634 patients) were included in this meta-analysis. Incidence of delirium was not significantly lower in patients who received melatonin, with an odd ratio, OR (95%Cl) of 0.55 (0.24-1.26); ρ = 0.16, certainty of evidence = low, trial sequential analysis = inconclusive. However, patients who randomised to melatonin had a significantly shorter length of stay in intensive care units, with a mean difference, MD (95%CI) of -1.84 days (-2.46, -1.21); ρ 

  3. Teoh WY, Wahab NA, Sim KS
    Nucleosides Nucleotides Nucleic Acids, 2017 Apr 03;36(4):243-255.
    PMID: 28323520 DOI: 10.1080/15257770.2016.1268693
    This study aims to investigate the mechanisms associated with the antiproliferation effect of guanosine on human colon carcinoma HCT 116 cells. In this study, guanosine induced more drastic cell cycle arrest effect than cell death effect on HCT 116 cells. The cell cycle arrest effect of guanosine on HCT 116 cells appeared to be associated with the increased activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, p38 and JNK. The decrease of AMP-activated protein kinase (AMPK) activation and cyclin D1 expression was also involved. Thus, the antiproliferation of colon cancer cells of guanosine could be mediated by the disruption of MAPK and AMPK pathways.
  4. Yap AC, Teoh WY, Chan KG, Sim KS, Choo YM
    Nat Prod Res, 2015;29(8):722-6.
    PMID: 25427277 DOI: 10.1080/14786419.2014.983507
    Enterobacter cloacae is a versatile bacterial species inhabiting a wide variety of niches and is capable of metabolising a wide variety of substances as energy resources. The fermentation culture of this bacterial species has successfully yielded one new compound, Rimboxa (1) and three known compounds, i.e. indole-3-carboxaldehyde (2), indole-3-acetic acid (3) and 3,4-di-t-butylaniline (4). Rimboxa (1) is shown to possess the 1,2-oxathiolane core structure. 3,4-Di-t-butylaniline (4) is isolated for the first time from a natural resource. These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods, and were subjected to cytotoxicity evaluations.
  5. Teoh WY, Tan HP, Ling SK, Abdul Wahab N, Sim KS
    Nat Prod Res, 2016;30(4):448-51.
    PMID: 25738869 DOI: 10.1080/14786419.2015.1017726
    Gynura bicolor (Compositae) is a popular vegetable in Asia and believed to confer a wide range of benefits including anti-cancer. Our previous findings showed that the ethyl acetate extract of G. bicolor possessed cytotoxicity and induced apoptotic and necrotic cell death in human colon carcinoma cells (HCT 116). A combination of column chromatography had been used to purify chemical constituents from the ethyl acetate and water extract of G. bicolor leaves. Eight chemical constituents 5-p-trans-coumaroylquinic acid (I), 4-hydroxybenzoic acid (II), rutin (III), kampferol-3-O-rutinoside (IV), 3,5-dicaffeoylquinic acid (V), kampferol-3-O-glucoside (VI), guanosine (VII) and chlorogenic acid (VIII) were isolated from G. bicolor grown in Malaysia. To our best knowledge, all chemical constituents were isolated for the first time from G. bicolor leaves except rutin (III). 3,5-dicaffeoylquinic acid (V), guanosine (VII) and chlorogenic acid (VIII) demonstrated selective cytotoxicity (selective index>3) against HCT 116 cancer cells compared to CCD-18Co human normal colon cells.
  6. Chew ST, Lo KM, Lee SK, Heng MP, Teoh WY, Sim KS, et al.
    Eur J Med Chem, 2014 Apr 9;76:397-407.
    PMID: 24602785 DOI: 10.1016/j.ejmech.2014.02.049
    Four new copper(II) complexes containing phosphonium substituted hydrazone (L) with the formulations [CuL]Cl(3), [Cu(phen)L]Cl(4), [Cu(bpy)L]Cl(5), [Cu(dbpy)L]Cl(6), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bipyridine; dbpy = 5,5'-dimethyl-2,2'-bipyridine) have been synthesized. The compounds were characterized by elemental analysis, spectroscopic methods and in the case of crystalline products by X-ray crystallography. The cytotoxicity and topoisomerase I (topo I) inhibition activities of these compounds were studied. It is noteworthy that the addition of N,N-ligands to the copper(II) complex lead to the enhancement in the cytotoxicity of the compounds, especially against human prostate adenocarcinoma cell line (PC-3). Complex 4 exhibits the highest activity against PC-3 with the IC₅₀ value of 3.2 μΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.
  7. Sim DS, Teoh WY, Sim KS, Lim SH, Thomas NF, Low YY, et al.
    J Nat Prod, 2016 Apr 22;79(4):1048-55.
    PMID: 26918761 DOI: 10.1021/acs.jnatprod.5b01117
    Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells.
  8. Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.
    PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095
    Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
  9. Ng KT, Sarode D, Lai YS, Teoh WY, Wang CY
    Paediatr Anaesth, 2019 12;29(12):1163-1172.
    PMID: 31587414 DOI: 10.1111/pan.13752
    BACKGROUND: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings.

    AIMS: To investigate the effect of ketamine on emergence agitation in children.

    METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.

    RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm.

    CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials.

    PROSPERO REGISTRATION: CRD42019131865.

  10. Ng KT, Yap JLL, Izham IN, Teoh WY, Kwok PE, Koh WJ
    Eur J Anaesthesiol, 2020 Mar;37(3):212-223.
    PMID: 31977626 DOI: 10.1097/EJA.0000000000001164
    BACKGROUND: Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain.

    OBJECTIVES: The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery.

    DESIGN: Systematic review and meta-analysis with trial sequential analysis.

    DATA SOURCES: MEDLINE, EMBASE, CENTRAL from their inception until January 2019.

    ELIGIBILITY CRITERIA: All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded.

    RESULTS: Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of -5.6 mg (-7.54 to -3.66, P 

  11. Ng KT, Lee ZX, Ang E, Teoh WY, Wang CY
    J Clin Anesth, 2020 Jun;62:109731.
    PMID: 31986433 DOI: 10.1016/j.jclinane.2020.109731
    OBJECTIVES: The repetitive hypoxic and hypercapnia events of obstructive sleep apnea (OSA) are believed to adversely affect cardiopulmonary function, which make them vulnerable to a higher incidence of postoperative complications. The primary aim of this systematic review and meta-analysis was to examine the association of OSA and the composite endpoints of postoperative cardiac or cerebrovascular complications in adult undergoing non-cardiac surgery.

    DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from its inception until May 2019.

    REVIEW METHODS: All observational studies were included.

    RESULTS: Twenty-two studies (n = 3,033,814; 184,968 OSA vs 2,848,846 non-OSA) were included for quantitative meta-analysis. In non-cardiac surgery, OSA was significantly associated with a higher incidence of the composite endpoints of postoperative cardiac or cerebrovascular complications (odd ratio: 1.44, 95%CI: 1.17 to 1.78, ρ = 0.007, trial sequential analysis = conclusive; certainty of evidence = very low). In comparison to non-OSA, OSA patients were reported to have nearly 2.5-fold risk of developing pulmonary complications (odd ratio: 2.52, 95%CI: 1.92 to 3.31, ρ 

  12. Chew WZ, Teoh WY, Sivanesan N, Loh PS, Shariffuddin II, Ti LK, et al.
    J Cardiothorac Vasc Anesth, 2022 Dec;36(12):4449-4459.
    PMID: 36038444 DOI: 10.1053/j.jvca.2022.07.004
    OBJECTIVE: To examine the effect of bispectral index (BIS)-guided anesthesia on the incidence of postoperative delirium (POD) in elderly patients undergoing surgery.

    DESIGN: A systematic review, meta-analysis, and trial sequential analysis (TSA).

    SETTING: In the operating room, postoperative anesthesia care units (PACU), and ward.

    PARTICIPANTS: Elderly patients (>60 years old) undergoing surgery.

    INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until December 2020 for randomized controlled trials comparing BIS and usual care or blinded BIS.

    MEASUREMENTS AND MAIN RESULTS: Ten trials (N = 3,891) were included for quantitative meta-analysis. In comparison to the control group, there was no significant difference in the incidence of POD in elderly patients randomized to BIS-guided anesthesia (odds ratio [OR] 0.71, 95% CI 0.47-1.08, I2 = 76%, p = 0.11, level of evidence = very low, TSA = inconclusive). The authors' review demonstrated that elderly patients with BIS-guided anesthesia were significantly associated with a lower incidence of postoperative cognitive dysfunction (POCD) (OR 0.64, 95% CI 0.46-0.88, p = 0.006), extubation time (mean difference [MD] -3.38 minutes, 95% CI -4.38 to -2.39, p < 0.00001), time to eye opening (MD -2.17 minutes, 95% CI -4.21 to -0.14, p = 0.04), and time to discharge from the PACU (MD -10.77 minutes, 95% CI -11.31 to - 10.23, p < 0.00001).

    CONCLUSION: The authors' meta-analysis demonstrated that BIS-guided anesthesia was not associated with a reduced incidence of POD, but it was associated with a reduced incidence of POCD and improved recovery parameters.

  13. Ng KT, Lim WE, Teoh WY, Shariffuddin II, Ti LK, Abidin MFBZ
    J Anesth, 2024 Feb;38(1):65-76.
    PMID: 38019351 DOI: 10.1007/s00540-023-03281-6
    PURPOSE: Midline approach of spinal anesthesia has been widely used for patients undergoing surgical procedures. However, it might not be effective for obstetric patients and elderly with degenerative spine changes. Primary objective was to examine the success rate at the first attempt between the paramedian and midline spinal anesthesia in adults undergoing surgery.

    METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting date until February 2023. Randomized clinical trials (RCTs) comparing the paramedian versus midline approach of spinal anesthesia were included. The primary outcome was the success rate at the first attempt of spinal anesthesia.

    RESULTS: Our review included 36 RCTs (n = 5379). Compared to the midline approach, paramedian approach may increase success rate at the first attempt but the evidence is very uncertain (OR: 0.47, 95% CI 0.27-0.82, ρ = 0.007, level of evidence:very low). Our pooled data indicates that the paramedian approach likely reduced incidence of post-spinal headache (OR: 2.07, 95% CI 1.51-2.84, ρ 

  14. Teoh WY, Sim KS, Moses Richardson JS, Abdul Wahab N, Hoe SZ
    PMID: 24369485 DOI: 10.1155/2013/958407
    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
  15. Chua EX, Wong ZZ, Hasan MS, Atan R, Yunos NM, Yip HW, et al.
    Braz J Anesthesiol, 2022;72(6):780-789.
    PMID: 35809681 DOI: 10.1016/j.bjane.2022.06.007
    BACKGROUND: The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients.

    METHODS: Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded.

    RESULTS: Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low).

    CONCLUSION: Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

  16. Chua EX, Zahir SMISM, Ng KT, Teoh WY, Hasan MS, Ruslan SRB, et al.
    J Clin Anesth, 2021 Nov;74:110406.
    PMID: 34182261 DOI: 10.1016/j.jclinane.2021.110406
    STUDY OBJECTIVE: To review the effects of prone position and supine position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19).

    DESIGN: Systematic review and meta-analysis of non-randomized trials.

    PATIENTS: Databases of EMBASE, MEDLINE and CENTRAL were systematically searched from its inception until March 2021.

    INTERVENTIONS: COVID-19 patients being positioned in the prone position either whilst awake or mechanically ventilated.

    MEASUREMENTS: Primary outcomes were oxygenation parameters (PaO₂/FiO₂ ratio, PaCO₂, SpO₂). Secondary outcomes included the rate of intubation and mortality rate.

    RESULTS: Thirty-five studies (n = 1712 patients) were included in this review. In comparison to the supine group, prone position significantly improved the PaO₂/FiO₂ ratio (study = 13, patients = 1002, Mean difference, MD 52.15, 95% CI 37.08 to 67.22; p 

  17. Teoh WY, Tan TG, Ng KT, Ong KX, Chan XL, Hung Tsan SE, et al.
    Ann Surg, 2021 Apr 01;273(4):676-683.
    PMID: 32282377 DOI: 10.1097/SLA.0000000000003896
    OBJECTIVES: Perioperative bleeding remains a major concern to all clinicians caring for perioperative patients. Due to the theoretical risk of thromboembolic events associated with tranexamic acid (TXA) when administered intravenously, topical route of TXA has been extensively studied, but its safety and efficacy profile remain unclear in the literature. The primary aim of this review was to assess the effect of topical TXA on incidence of blood transfusion and mortality in adults undergoing surgery.

    DATA SOURCES: EMBASE, MEDLINE, CENTRAL, and ISI Web of Science were systematically searched from their inception until May 31, 2019.

    REVIEW METHODS: Parallel-arm randomized controlled trials were included.

    RESULTS: Seventy-one trials (7539 participants: orthopedics 5450 vs nonorthopedics 1909) were included for quantitative meta-analysis. In comparison to placebo, topical TXA significantly reduced intraoperative blood loss [mean difference (MD) -36.83 mL, 95% confidence interval (CI) -54.77 to -18.88, P < 0.001], total blood loss (MD -319.55 mL, 95% CI -387.42 to -251.69, P < 0.001), and incidence of blood transfusion [odds ratio (OR) 0.30, 95% CI 0.26-0.34, P < 0.001]. Patients who received topical TXA were associated with a shorter length of hospital stay (MD -0.28 days, 95% CI -0.47 to -0.08, P = 0.006). No adverse events associated with the use of topical TXA were observed, namely mortality (OR 0.78, 95% CI 0.45-1.36, P = 0.39), pulmonary embolism (OR 0.73, 95% CI 0.27-1.93, P = 0.52), deep vein thrombosis (OR 1.07, 95% CI 0.65-1.77, P = 0.79), myocardial infarction (OR 0.79, 95% CI 0.21-2.99, P = 0.73), and stroke (OR 0.85, 95% CI 0.28-2.57, P = 0.77). Of all included studies, the risk of bias assessment was "low" for 20 studies, "unclear" for 26 studies and "high" for 25 studies.

    CONCLUSIONS: In the meta-analysis of 71 trials (7539 patients), topical TXA reduced the incidence of blood transfusion without any notable adverse events associated with TXA in adults undergoing surgery.

    PROSPERO: CRD 42018111762.

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