Chronic Disease ; economics ; Cost of Illness ; Diabetes Mellitus ; drug therapy ; economics ; Global Health ; economics ; Humans ; Singapore

Pharmacogenomics (or pharmacogenetics), the study of the effects of genetic differences on a person’s response to drugs, can help in optimizing drug efficacy and minimizing adverse drug reactions. Interperson difference in drug metabolism is one of the important consequences of such genetic variation. This variation is determined in part by mutations in cytochrome P450 enzymes (CYPs). IMU is part of a major collaborative research project in the area of phamacogenetics and drug metabolism. Working together with USM and UiTM, our group has, since 2000, generated useful population database on genetic polymorphism of various CYP isoforms. We have successfully genotyped three major ethnic groups, Malay, Indian and Chinese for their allelic frequency of important isoforms. These include CYP2D6, CYP2C9, CYP2C8 and CYP2A6. Data generated so far collectively have contributed to our effort in mapping and constructing genomic database for Malaysian population. Since early 2002, our research has been focusing on developing in vitro methods in studying the functional consequences of genetic polymorphism of CYP enzymes. Using site-directed mutagenesis, CYP mutants, carrying nucleotide changes as reported in known alleles in human populations, were generated and expressed in E. coli system, and the expressed recombinant proteins were characterized using enzyme assays to determine the functional consequences of mutations. We have established a series of HPLC (high performance liquid chromatography)-based and fluorescence-based assays to investigate CYP activities. Assays that have been developed include tolbutamide methylhydroxylase, paclitaxel 6a-hydroxylase, dextromethorphan O-demethylation, testosterone 6b-hydroxylation and coumarin 7-hydroxylase assays. These assays serve as activity markers allowing comparison of catalytic activities of mutant proteins generated. Another focus of our work is to use the developed assays as a screening tool to investigate drug-herb interactions. This was achieved by co-incubation of herbal extracts and active constituents with the probe substrates in the assays followed by characterization of the kinetic behaviors of the enzymes involved using various pharmacokinetic parameters such as Km, Vmax, IC50 and Ki. This work is currently carried out with collaboration from the Institute for Medical Research (IMR) and is supported by MOSTI’s eScienceFund under RM9. It is envisaged that this screening work will give us insights on the potential of the commonly used herbs to cause pharmacokinetic interactions with other drug substrates, and allow us to elucidate the mechanisms involved in the interactions.

BACKGROUND: The ultrasound-guided oblique subcostal transversus abdominis plane (OSTAP) block provides a wider area of sensory block to the anterior abdominal wall than the classical posterior approach. We compared the intra-operative analgesic efficacy of OSTAP block with conventional intravenous (IV) morphine during laparoscopic cholecystectomy. METHODS: Forty adult patients undergoing laparoscopic cholecystectomy under standard general anesthesia, were randomly assigned for either bilateral OSTAP block using 1.5 mg/kg ropivacaine on each side (n = 20) or IV morphine 0.1 mg/kg (n = 20). The intra-operative pulse rate, systolic and diastolic blood pressure and mean arterial blood pressure were monitored every five minutes. Repetitive boluses of IV fentanyl 0.5 microg/kg were given as rescue analgesia when any of the above-mentioned parameters rose more than 15% from the baseline values. Time to extubation was documented. Additional boluses of IV morphine 0.05 mg/kg were administered in the recovery room if the recorded visual analogue score (VAS) was more than 4. Nausea and vomiting score, as well as sedation score were recorded. RESULTS: The morphine group required more rescue fentanyl as compared to the OSTAP block group but the difference was not significant statistically. Time to extubation was significantly shorter in the OSTAP block group (mean [SD] 10.4 [2.60] vs 12.4 [2.54] min; P = 0.021). Both methods provided excellent analgesia and did not differ in postoperative morphine requirements. No between-group differences in sedation score and incidence of nausea and vomiting were demonstrated. CONCLUSIONS: Ultrasound-guided OSTAP block has an important role as part of balanced anesthesia. It is as efficacious as IV morphine in providing effective analgesia during laparoscopic cholecystectomy.
Abdominal Wall ; Adult ; Amides ; Analgesia ; Anesthesia, General ; Arterial Pressure ; Balanced Anesthesia ; Blood Pressure ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Fentanyl ; Heart Rate ; Humans ; Incidence ; Morphine ; Nausea ; Prospective Studies ; Recovery Room ; Vomiting

Adult ; Anticarcinogenic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Disease Progression ; Female ; Humans ; Interdisciplinary Communication ; Neoplasm Staging ; Pregnancy ; Pregnancy Complications, Neoplastic ; drug therapy ; pathology ; Treatment Outcome

Aged ; Feasibility Studies ; Health Status ; Humans ; Mobile Applications ; Treatment Outcome

INTRODUCTIONAtherothrombosis is the leading cause of cardiovascular mortality. The Reduction of Atherothrombosis for Continued Health (REACH) Registry provided information on atherosclerosis risk factors and treatment. Singapore was one of the 44 participating countries in the REACH Registry. The objective of this study was to determine the atherosclerosis risk factor profile and treatment patterns in Singapore patients enrolled in the REACH Registry.

MATERIALS AND METHODSThe REACH Registry is an international prospective observational registry of subjects with or at risk for atherothrombosis. Patients aged 45 years or older with established vascular disease [coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial disease (PAD)] or 3 or more atherosclerosis risk factors were recruited between 2003 and 2004.

RESULTSA total of 881 patients (64.4% male) were recruited in Singapore by 63 physicians. The mean age was 64 +/- 9.8 years (range, 45 to 95). Seven hundred and one (79.6%) patients were symptomatic (CAD 430, CVD 321, PAD 72) while 180 (20.4%) patients had > or =3 risk factors. Approximately 13% of symptomatic patients had symptomatic polyvascular disease. There was a high proportion of diabetes mellitus (57%), hypertension (80.6%) and hypercholesterolemia (80.1%). A substantial proportion of symptomatic patients were current smokers (14.1%). Approximately half of the patients were either overweight or obese [abdominal obesity, 54.3%; body mass index (BMI) 23-27.5, 45.9%; BMI > or =27.5, 23.3%]. Patients were undertreated with antiplatelet agents (71.9% overall; range, 23.9% for > or =3 risk factors to 84.7% for PAD) and statins (76.2% overall; range, 73.6% for PAD to 82.1% for CAD). Risk factors remained suboptimally controlled with a significant proportion of patients with elevated blood pressure (59.4% for > or =3 risk factors and 48.6% for symptomatic patients), elevated cholesterol (40% for > or =3 risk factors and 24.4% for symptomatic patients) and elevated blood glucose (45% for > or =3 risk factors and 19.8% for symptomatic patients).

CONCLUSIONEstablished atherosclerosis risk factors are common in Singapore patients in the REACH Registry; and obesity is a major problem. Most of these risk factors remained suboptimally controlled.

Aged ; Atherosclerosis ; epidemiology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Registries ; Risk Factors ; Singapore ; epidemiology

The link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is well-established. In Singapore, there is an increasing prevalence of risk factors for ASCVD. Like many Asian countries, Singapore's population is rapidly ageing and increasingly sedentary, which predisposes individuals to chronic health problems. Current international and local guidelines recommend statin therapy for the primary and secondary prevention of ASCVD. However, despite the effectiveness of statin therapy, some studies have highlighted that Asian patients with cardiovascular disease are not achieving target lipid goals. Furthermore, it is widely believed that the responses of Asians (both patients and physicians) to statin therapy are different from those of their Western counterparts. Experts convened in 2014 to determine the impact of current guidelines on clinical practice in Singapore. This review summarises the key findings and recommendations of these guidelines, and presents key principles to aid clinicians to manage the cardiovascular risk of their patients more effectively.
Aging ; Atherosclerosis ; drug therapy ; Cardiology ; standards ; Cardiovascular Diseases ; drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Life Style ; Lipoproteins, LDL ; blood ; Practice Guidelines as Topic ; Risk Assessment ; Risk Factors ; Singapore

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Lipids to provide doctors and patients in Singapore with evidence-based treatment for lipids. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on Lipids, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.
Adult ; Cardiovascular Diseases ; complications ; therapy ; Child ; Coronary Artery Disease ; complications ; therapy ; Decision Support Systems, Clinical ; Dyslipidemias ; blood ; complications ; therapy ; Evidence-Based Medicine ; Female ; Humans ; Kidney Failure, Chronic ; complications ; therapy ; Life Style ; Lipids ; blood ; Lipoproteins, LDL ; blood ; Male ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Complications ; Risk Assessment ; Risk Factors ; Singapore

The aim of this Biologic Advisory Group (BAG) Malaysia consensus guideline is to provide clinicians managing cutaneous diseases with biologics relevant parameters to consider prior to initiating or stopping or continuing any biologic treatment in the current landscape of the COVID-19 pandemic. Besides reviewing the medical literatures on COVID-19 and evidences related to other human coronavirus or influenza, expert opinions and clinical experiences are shared and debated in formulation of this biologic consensus guideline.