OBJECTIVE: This study sought to detect CYP2B6 and OPRM1 variants and their genotypes, as major contributors to inter-variability in methadone responsiveness and methadone dose requirements.
METHODS: We carried out a prospective experimental one-phase pharmacogenetic study in four addiction clinics in Malaysia. Patients on stable methadone maintenance therapy were recruited. The prevalence of the CYP2B6 and OPRM1 polymorphisms was determined using a nested polymerase chain reaction (PCR), followed by genotyping. A two-step multiplex PCR method was developed to simultaneously detect the 26 SNPs in these two genes.
RESULTS: 120 males were recruited for this study. The patients were between 21and 59 years old, although the majority of the patients were in their 30s. C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1 were found to be polymorphic, and the allelic frequencies of each were calculated. We further detected eight new haplotypes.
CONCLUSION: C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1were found to be polymorphic. The new haplotypes may give a new insight on methadone clinics.
METHODS: A double-blind, multicenter randomized clinical trial was undertaken in four teaching hospitals in the North of Iraq and Al-Azhar University Hospital in Egypt, from March 2016 to May 2019. Group I (274 women) received 400 μg misoprostol and group II (249 women) received 800 μg misoprostol. Data regarding the time of placental separation and amount of vaginal blood loss were analyzed and proportions were compared between groups using Chi-squared test. Mean values were compared using the Student's t-test. The Mann-Whitney test was used to determine the median of vaginal blood loss.
RESULTS: The proportion of placental separation was 84.3% among women in group I and 86.7% of women in group II. The mean time of placental separation was 18.86 ± 234.2 and 17.86 ± 213.09 min in groups I and II, respectively (P
METHODS: A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed.
RESULT: The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses.
CONCLUSION: A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of Cervical Cancer cases and deaths. Using the saving money with 2-doses, more Cervical Cancers and deaths can be avoided.