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Fulltext Prevalence of pain and treatment outcomes among cancer patients in a Malaysian palliative care unit

Mejin M, Keowmani T, Rahman SA, Liew J, Lai J, Chua M, et al.

Pharm Pract (Granada), 2019 03 18;17(1):1397.
PMID: 31015879 DOI: 10.18549/PharmPract.2019.1.1397

Background: Pain remains one of the most common and debilitating symptoms of advanced cancer. To date, there is a lack of studies on pain and its treatment among Malaysian palliative care patients.
Objective: This study aimed to explore the prevalence of pain and its treatment outcomes among adult cancer patients admitted to a palliative care unit in Sabah, Malaysia.
Methods: Of 327 patients screened (01/09/15-31/12/17), 151 patients with assessed self-reported pain scores based on the numerical rating scale of 0-10 (current, worst and least pain within the past 24 hours) upon admission (baseline), 24, 48 and 72 hours post-admission and discharge were included. Pain severity and pain score reductions were analysed among those who experienced pain upon admission or in the past 24 hours. Treatment adequacy was measured by the Pain Management Index (PMI) among discharged patients. The PMI was constructed upon worst scores categorised as 0 (no pain), 1 (1-4, mild pain), 2 (5-6, moderate pain), or 3 (7-10, severe pain) which is then subtracted from the most potent level of prescribed analgesic drug scored as 0 (no analgesia), 1 (non-opioid), 2 (weak opioid) or 3 (strong opioid). PMI≥0 indicated adequate treatment.
Results: Upon admission, 61.1% [95%CI 0.54:0.69] of 151 patients presented with pain. Of 123 patients who experienced pain upon admission or in the past 24 hours, 82.1% had moderate to severe worst pain. Throughout patients' ward stay until discharge, there was an increased prescribing of analgesics and adjuvants compared to baseline, excluding weak opioids, with strong opioids as the mainstay treatment. For all pain score types (current, worst and least pain within the past 24 hours), means decreased at each time point (24, 48 and 72 hours post-admission and discharge) from baseline, with a significant decrease at 24 hours post-admission (p<0.001). Upon discharge (n=100), treatment adequacy significantly improved (PMI≥0 100% versus 68% upon admission, p<0.001).
Conclusions: Accounting for pain's dynamic nature, there was a high prevalence of pain among cancer patients in the palliative care unit. Continuous efforts incorporating comprehensive pain assessments, evidence-based treatments and patient education are necessary to provide adequate pain relief and end-of-life comfort care.
Fulltext Trends of platelet inhibition in different clopidogrel pretreatment patterns in malaysian patients undergoing elective percutaneous coronary intervention

Tiong WN, Mejin M, Fong AY, Wee CC, Lai LY, Hwang SS, et al.

Med J Malaysia, 2013 Aug;68(4):326-31.
PMID: 24145261 MyJurnal
CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention

Mejin M, Tiong WN, Lai LY, Tiong LL, Bujang AM, Hwang SS, et al.

Int J Clin Pharm, 2013 Aug;35(4):621-8.
PMID: 23661171 DOI: 10.1007/s11096-013-9783-y

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms are more common in Asian populations and have been associated with diminished antiplatelet response to clopidogrel. In this era of 'personalised medicine', combining genotyping and phenotyping as a strategy to personalise antiplatelet therapy warrants further exploration.
OBJECTIVE: This study aimed to investigate the prevalence and impact of CYP2C19*2, *3 and *17 genotypes on clopidogrel responsiveness in a multiethnic Malaysian population planned for percutaneous coronary intervention.
SETTING: Between October 2010 and March 2011, a total of 118 consecutive patients planned for percutaneous coronary intervention were enrolled in Sarawak General Hospital, Borneo. All patients received at least 75 mg aspirin daily for at least 2 days and 75 mg clopidogrel daily for at least 4 days prior to angiography.
METHOD: Genotyping for CYP2C19*2 (rs4244285, 681G > A), *3 (rs4986893, 636G > A) and *17 (rs11188072, -3402C > T) alleles were performed by polymerase chain reaction-restriction fragment linked polymorphism method. Whole blood ADP-induced platelet aggregation was assessed with multiple electrode platelet aggregometry (MEA) using the Multiplate Analyzer.
MAIN OUTCOME MEASURES: The distribution of CYP2C19*2, *3 and *17 among different ethnic groups and the association between genotype, clopidogrel responsiveness and clinical outcome were the main outcome measures.
RESULTS: The highest prevalence of poor metabolisers (carriers of at least one copy of the *2 or *3 allele) was among the Chinese (53.7 %), followed by the Malays (26.9 %), Ibans (16.4 %) and other races (3.0 %). Poor metabolisers (PMs) had the highest mean MEA (303.6 AU*min), followed by normal metabolisers (NMs) with 270.5 AU*min and extensive metabolisers (EMs) with 264.1 AU*min (p = 0.518). Among poor responders to clopidogrel, 65.2 % were PMs and NMs, respectively, whereas none were EMs (p = 0.350). Two cardiac-related deaths were reported.
CONCLUSION: There was a diverse inter-ethnic difference in the distribution of CYP2C19 polymorphism. The findings of this study echo that of other studies where genotype appears to have a limited impact on clopidogrel responsiveness and clinical outcome in low-risk patients.
Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa

Othman N, Pan L, Mejin M, Voong JC, Chai HB, Pannell CM, et al.

J Nat Prod, 2016 Apr 22;79(4):784-91.
PMID: 26974604 DOI: 10.1021/acs.jnatprod.5b00810

Four new 2,3-secodammarane triterpenoids, stellatonins A-D (3-6), together with a new 3,4-secodammarane triterpenoid, stellatonin E (7), and the known silvestrol (1), 5‴-episilvestrol (2), and β-sitosterol, were isolated from a methanol extract of the stems of Aglaia stellatopilosa through bioassay-guided fractionation. The structures of the new compounds were elucidated using spectroscopic and chemical methods. The compounds were evaluated for their cytotoxic activity against three human cancer cell lines and for their antimicrobial activity using a microtiter plate assay against a panel of Gram-positive and Gram-negative bacteria and fungi.
Photodynamic activity of plant extracts from Sarawak, Borneo

Jong WW, Tan PJ, Kamarulzaman FA, Mejin M, Lim D, Ang I, et al.

Chem Biodivers, 2013 Aug;10(8):1475-86.
PMID: 23939795 DOI: 10.1002/cbdv.201200303

Photodynamic therapy (PDT) is a medical treatment that involves the irradiation of an administered photosensitizing drug with light of a particular wavelength to activate the photosensitizer to kill abnormal cells. To date, only a small number of photosensitizers have been clinically approved for PDT, and researchers continue to look for new molecules that have more desirable properties for clinical applications. Natural products have long been important sources of pharmaceuticals, and there is a great potential for discovery of novel chemotypes from under-explored biodiversities in the world. The objective of this study is to mine the terrestrial plants in Sarawak, Borneo Island, for new photosensitizers for PDT. In a screening program from 2004 to 2008, we prepared and studied 2,400 extracts from 888 plants for their photosensitizing activities. This report details the bioprospecting process, preparation and testing of extracts, analysis of the active samples, fractionation of four samples, and isolation and characterization of photosensitizers.
Association of CYP2C19*2 polymorphism with clopidogrel response and 1-year major adverse cardiovascular events in a multiethnic population with drug-eluting stents

Tan SSN, Fong AYY, Mejin M, Gerunsin J, Kong KL, Chin FYY, et al.

Pharmacogenomics, 2017 08;18(13):1225-1239.
PMID: 28745576 DOI: 10.2217/pgs-2017-0078

BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE).
AIM OF THE STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE.
MATERIALS & METHODS: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx.
RESULTS: A total of 42.0% carried ≥1 CYP2C19*2 allele. Prevalences of aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and 19.8% respectively. In multivariate ana-lysis, clopidogrel HPR was found to be an independent predictor for 1-year MACE (adj HR: 3.48, p = 0.022 ).
CONCLUSION: Having clopidogrel HPR could be a potentially modifiable risk factor guided by phenotyping.
Prognostic Implications of Dual Platelet Reactivity Testing in Acute Coronary Syndrome

de Carvalho LP, Fong A, Troughton R, Yan BP, Chin CT, Poh SC, et al.

Thromb. Haemost., 2018 02;118(2):415-426.
PMID: 29443374 DOI: 10.1160/TH17-08-0564

Studies on platelet reactivity (PR) testing commonly test PR only after percutaneous coronary intervention (PCI) has been performed. There are few data on pre- and post-PCI testing. Data on simultaneous testing of aspirin and adenosine diphosphate antagonist response are conflicting. We investigated the prognostic value of combined serial assessments of high on-aspirin PR (HASPR) and high on-adenosine diphosphate receptor antagonist PR (HADPR) in patients with acute coronary syndrome (ACS). HASPR and HADPR were assessed in 928 ACS patients before (initial test) and 24 hours after (final test) coronary angiography, with or without revascularization. Patients with HASPR on the initial test, compared with those without, had significantly higher intraprocedural thrombotic events (IPTE) (8.6 vs. 1.2%, p ≤ 0.001) and higher 30-day major adverse cardiovascular and cerebrovascular events (MACCE; 5.2 vs. 2.3%, p = 0.05), but not 12-month MACCE (13.0 vs. 15.1%, p = 0.50). Patients with initial HADPR, compared with those without, had significantly higher IPTE (4.4 vs. 0.9%, p = 0.004), but not 30-day (3.5 vs. 2.3%, p = 0.32) or 12-month MACCE (14.0 vs. 12.5%, p = 0.54). The c-statistic of the Global Registry of Acute Coronary Events (GRACE) score alone, GRACE score + ASPR test and GRACE score + ADPR test for discriminating 30-day MACCE was 0.649, 0.803 and 0.757, respectively. Final ADPR was associated with 30-day MACCE among patients with intermediate-to-high GRACE score (adjusted odds ratio [OR]: 4.50, 95% confidence interval [CI]: 1.14-17.66), but not low GRACE score (adjusted OR: 1.19, 95% CI: 0.13-10.79). In conclusion, both HASPR and HADPR predict ischaemic events in ACS. This predictive utility is time-dependent and risk-dependent.