This study aimed to synthesize available evidence on the analgesic efficacy of buprenorphine in treating cancer pain and related adverse effects. We searched electronic databases for randomized controlled trials, assessing the efficacy of buprenorphine, regardless of delivery system. The primary endpoints were patient-reported 'pain intensity' and 'pain relief'. Statistical heterogeneity among included studies was assessed with the I (2) test. The summary relative risk (RR) and 95% CI were derived, if two or more studies reported the similar outcome. Sixteen RCTs (n = 1329) with buprenorphine were included: 8 transdermal (TD), 5 sublingual (SL), 2 intramuscular injection (IM) and 1 subcutaneous infusion (SC) studies; with both SL and IM routes being assessed in one study. Only a few studies reported the same outcome in a similar way, creating difficulty for pooling of the outcome data. Many studies had a high risk of bias. In 2 studies (n = 241), the 'global impression change' was significantly different between TD buprenorphine and the combined placebo and morphine (RR 1.35, 95% CI 1.14-1.59; I (2): 42%); the 'number-needed-to-treat' (NNT) was 4.9 (95% CI: 3.1-10.9). In 2 studies (n = 331), 'requirement for rescue SL buprenorphine' was comparable between TD buprenorphine and placebo (RR 1.25, 95% CI 0.71-2.18; I (2) : 40%). In 2 studies (n = 141), 'incidence of nausea' was less in TD buprenorphine (RR: 0.38, 95% CI: 0.2-0.71, I (2): 0%, NNT: 9.3, 5.6-28.5). Due to the small number of participants in a small number of studies, the results of the present review provide insufficient evidence to position adequately the use of buprenorphine in treatment of cancer pain. Large multicenter RCTs that compare TD buprenorphine with standard analgesic treatment is needed to position TD buprenorphine in the therapeutic armamentarium of cancer pain treatment.
Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.
Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.
The xenobiotic metabolizing enzymes N-acetyltransferases (NATs) are important for the biotransformation and/or bioactivation of drugs and carcinogens. NATs are coded for in humans by two distinct genes, designated NAT1 and NAT2. NAT1, which was originally thought to be monomorphic, was recently reported to exhibit variation in human populations. Recent studies suggested that a genetic polymorphism of NAT1 may be associated with colorectal cancer risk. The distributions of NAT1 allele and genotype frequencies in unrelated individuals among Indian (n = 140), Malay (n = 122) and Chinese (n = 181) populations in Singapore were characterized by polymerase chain reaction-restriction fragment length polymorphism and allele-specific-polymerase chain reaction. The allelic frequencies of NAT1*3, NAT1*4, NAT1*10 and NAT1*11 among Indians were 0.3, 0.51, 0.17 and 0.02, respectively. The corresponding NAT1 allelic frequencies in Malays were 0.29, 0.30, 0.39 and 0.02, respectively, and were similar to those in Chinese in the region. The allelic frequencies of NAT1*3, NAT1*4, NAT1*10 and NAT1*11 among Chinese were 0.33, 0.35, 0.30 and 0.02, respectively. These findings are of importance for the determination of cancer risk in these populations. In addition, nucleotide changes at positions 350-351 (GG to CC) and 497-499 (GGG to CCC) of the NAT1 gene were not found in the alleles of the populations studied.
This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia.The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable.Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%-35.8%) in 1996, 42.6% (37.5%-43.5%) in 2006, and 43.5% (40.4%-46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P