OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.
METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.
RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).
WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.
METHODS: This nested case-control study was performed by collecting data from 1 January 2015 to 30 June 2017. Univariable and multivariable logistic regressions were used to identify potential risk factors. The regression coefficients were converted into item scores by dividing each regression coefficient with the minimum coefficient in the model and rounding to the nearest integer. This value was then summed to the total score. The prediction power of the model was determined by the area under the receiver operating characteristic curve (AuROC).
RESULTS AND DISCUSSION: Six clinical risk factors, namely age ≥65 years, benzodiazepine use, history of a cerebrovascular accident, dose of hydrochlorothiazide ≥25 mg, female sex and statin use, were included in our ABCDF-S score. The model showed good power of prediction (AuROC 81.53%, 95% confidence interval [CI]: 78%-84%) and good calibration (Hosmer-Lemeshow X2 = 23.20; P = .39). The positive likelihood ratios of hyponatremia in patients with low risk (score ≤ 6) and high risk (score ≥ 8) were 0.26 (95% CI: 0.21-0.32) and 3.89 (95% CI: 3.11-4.86), respectively.
WHAT IS NEW AND CONCLUSION: The screening tool with six risk predictors provided a useful prediction index for thiazide-associated hyponatremia. However, further validation of the tool is warranted prior to its utilization in routine clinical practice.
METHODS: Six CADDs (three containing dobutamine 10 mg/mL in 0.9% sodium chloride and three containing dobutamine 10 mg/mL in 5% glucose) were prepared and stored at 4°C for 7 days, followed by 12 hours at 35°C and then for another 12 hours at 25°C. An aliquot (n = 3) was withdrawn aseptically at 0, 24, 48, 72, 96, 120, 144 and 168 hours when stored at 4°C, and at 0, 6 and 12 hours when stored at the other two temperatures. Each sample was analysed for dobutamine concentration using a stability-indicating high-performance liquid chromatography. All the samples were also evaluated for change in pH, colour and for particle content.
RESULTS AND DISCUSSION: No evidence of particle formation, colour or pH change was observed throughout the study period. Dobutamine, when admixed with 0.9% sodium chloride or 5% glucose, was found to be chemically stable for at least 168 hours at 4°C and for another 12 hours at 35°C and for another 12 hours at 25°C.
WHAT IS NEW AND CONCLUSIONS: Our findings will allow health professionals to provide a weekly supply of dobutamine-containing CADDs to patients for home infusions. Continuous infusion over a 24-hour period using one CADD per day will also decrease the number of exchanges required and thus reduce the risk of catheter-related bloodstream infections.
METHODS: Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database.
RESULTS AND DISCUSSIONS: A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%-99.1%), *1/*3 (2.3%-20.1%) and *3/*3 (0%-2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%-88.07%), *1/*2 (21.5%-86.46%), *1/*3 (0.8%-15.8%), *2/*2 (3.4%-14.5%), *2/*3 (0%-7.3%) and *3/*3 (0%-10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%-69.6%), *1/*1 (0%-61.21%) and *1/*10 (0%-62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%-71.4%), *1/*3 (16.0%-57.1%) and *1/*1 (0%-82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer).
WHAT IS NEW AND CONCLUSION: Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South-East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South-East Asian countries which will assist in establishing the databases for SEEA populations.
METHODS: We analysed the total visits and discharge rates during periods of using the nebulizer and current pMDI-VMMS methods. The acceptance of pMDI-VMMS by patients and assistant medical officers (AMOs) were assessed by questionnaire.
RESULTS AND DISCUSSION: We analysed 3184 ED visits and responses from 103 patients and 32 AMOs. The direct discharge rate was similar for both nebulizer (n = 2162, 92.5%) and pMDI-VMMS method (n = 768, 90.7%) (p-value = 0.120). Twenty-eight patients (27.2%) favoured the pMDI-VMMS over the nebulizer, whereas 36 patients (35.0%) had no preference for either method. Sixty-four patients (62.1%) felt that the current pMDI-VMMS method was better or at least as effective in relieving their symptoms as a nebulizer. The current method was favoured over the nebulizer by twenty-seven AMOs (84.4%). Twenty-eight (87.5%) AMOs suggested that the current method was more effective than the nebulizer.
WHAT IS NEW AND CONCLUSION: The bronchodilator delivered via pMDI-VMMS appeared to be comparable to nebulizer in treating mild to moderate asthma and COPD exacerbations in the outpatient ED. Most patients and AMOs accepted the use of pMDI-VMMS in the outpatient ED during the current COVID-19 pandemic. The Venturi mask modified spacer can be a cheap and effective alternative to the commercial spacer in a resource-limited situation.