The effect of pre-endoscopy maltodextrin beverage on gastric residual volume and patient's well-being: a randomised controlled trial.

Prolonged fasting prior to oesophagogastroduodenoscopy (OGDS) could be noxious to patients' well-being. Strict fasting protocol has been used prior to OGDS with the concern of reduced visibility or suboptimal endoscopic assessment. Maltodextrin beverages were also commonly used as the pre-operative carbohydrate loading in enhanced recovery after surgery (ERAS) protocol. Our study aimed to look for the effects of maltodextrin beverage 2 h before OGDS on gastric residual volume and patient's well-being scores. This was a single-blinded, stratified randomised controlled trial, comparing control group (A, received 400 ml of plain water) and carbohydrate loading group (B, received 400 ml of Carborie). The primary objectives were to measure the gastric residual volume (GRV) and patient's well-being scores using visual analogue scale (VAS) scores for hunger, thirst, anxiety, tiredness and general discomfort. Of 80 randomised patients, 78 completed the study (38 received plain water and 40 Carborie). The median (IQR) GRV was not significantly different between group A and B (5.0 ml (20) vs 4.0 ml (19), p = 0.777). Both groups showed significant reduction in VAS scores in all five parameters (p ≤ 0.001). There were no complications attributed to endoscopy in either group. Pre-endoscopy maltodextrin beverage is as safe as clear water with improved patient's well-being in both groups.Clinical Trial Registration: NCT05106933.

Risk factors associated with low anterior resection syndrome: a cross-sectional study.

PURPOSE: Oncological outcomes following rectal cancer surgery have improved significantly over recent decades with lower recurrences and longer overall survival. However, many of the patients experienced low anterior resection syndrome (LARS). This study identified the prevalence and risk factors associated with the development of LARS. METHODS: This cross-sectional study involved patients who were diagnosed with rectal cancer and had undergone sphincter-preserving low anterior resection from January 2011 to December 2020. Upon clinic follow-up, patients were asked to complete an interviewed based questionnaire (LARS score) designed to assess bowel dysfunction after rectal cancer surgery. RESULTS: Out of 76 patients, 25 patients (32.9%) had major LARS, 10 patients (13.2%) had minor LARS, and 41 patients (53.9%) had no LARS. The height of tumor from anal verge showed an association with the development of major LARS (P=0.039). Those patients with less than 8 cm tumor from anal verge had an increased risk of LARS by 3 times compared to those with 8 cm and above (adjusted odds ratio, 3.11; 95% confidence interval, 1.06-9.13). CONCLUSION: Results from our study show that low tumor height was a significant risk factor that has a negative impact on bowel function after surgery. The high prevalence of LARS emphasizes the need for study regarding risk factors and the importance of understanding the pathophysiology of LARS, in order for us to improve patient bowel function and quality of life after rectal cancer surgery.

Conversion rate and risk factors of conversion to open in laparoscopic appendicectomy.

PURPOSE: Laparoscopic appendicectomy (LA) has several advantages over conventional open appendicectomy (OA). However, about 5% to 10% of LA patients still need to be converted to open surgery. Identifying risk factors that contribute to conversion to OA allows for early identification of patients who may benefit from primary OA. This study aimed to determine the conversion rate of LA to OA and to identify its associated risk factors among patients with acute or perforated appendicitis. METHODS: A retrospective review of medical records was performed among patients with acute or perforated appendicitis who underwent LA between December 2015 and January 2017. With the use of multivariable logistic regression analyses, the predictors of conversion from laparoscopic to OA were investigated. RESULTS: Out of 120 patients, 33 cases were converted to OA which gives a conversion rate of 27.5%. Among 33 patients who were converted to OA, 27 patients (81.8%) had perforated appendix, while in the LA group, perforated appendix cases consisted of 34.5% (P<0.001). Histopathology of the appendix was the predictor of conversion from LA to OA (adjusted odds ratio, 8.82; 95% confidence interval, 3.13-24.91; P<0.001). CONCLUSION: The result from our study shows that the overall conversion rate for the study period was high. Patients with perforated appendicitis had a higher risk of conversion to OA. Therefore, preoperative diagnosis of perforated appendicitis may be paramount in predicting conversion to OA.

An In vitro Study of Orthosiphon stamineus (Misai Kucing) Standardized Water Extract as a Chemolytic Agent in Urolithiasis.

Background: Orthosiphon stamineus was reported to have diuretic effects in experimental rats, and this leads to inhibition of kidney stones through the abundant levels of minerals and flavonoids in it. This study aimed to determine the in vitro effects of O. stamineus water extract as a potential chemolytic agent in urolithiasis. Materials and Methods: In this prospective experiment, a total of 15 stone samples collected from patients who underwent stone extraction were used in each concentration (4 mg/ml, 2 mg/ml, and 1 mg/ml) of the O. stamineus extract and control solution. The effects of pH change in the chemolysis of the stones were assessed using the O. stamineus extract 4 mg/ml under pH 7 and 8. Results: The percentage weight reduction of calcium oxalate stone was highest in the 4 mg/ml concentration. O. stamineus extract 4 mg/ml showed a better effect in terms of chemolytic action on calcium oxalate stone than the potassium citrate solution (70% vs. 41%). Regarding the calcium oxalate stone, the percentage weight reduction has shown about 70% in the pH 5, 48% in pH 7, and <10% in pH 8. The percentage weight reduction of uric acid stone was determined as 47%, 11%, and 14% for pH 5, 7, and 8, respectively. The percentage weight reduction of combination stone was 40%, 60%, and 80% in the pH 5, pH 7, and pH 8, respectively. Data analysis showed that the percentage weight reduction of combination stone was significantly different between acidic, neutral, and alkaline conditions (P = 0.027). Conclusions: In this in vitro study, we are able to show that O. stamineus water extract do have some dissolving capability of urinary stones.

A cross sectional study on assessing the knowledge, attitude and perception towards allergic reactions of paracetamol in Malaysia.

Recent years, the prevalence of paracetamol allergy becomes great concerns. However, data on knowledge, attitude and perception towards allergic reactions of paracetamol are lacking. This study aimed to investigate knowledge, attitude, and perception towards allergic reactions of paracetamol (KAP-ARP). A cross-sectional survey was conducted using a validated self-administered questionnaire around Pasar Siti Khadijah, Kelantan from February 2016 to January 2017 among the general population. A total of 177 respondents participated in this study. The mean percentage scores for knowledge, attitude and perception towards allergic reactions of paracetamol were 31.7% (SD 23.6), 53.1% (SD 19.2) and 53.3% (SD 23.9), respectively. This study revealed that respondents demonstrated a poor level of knowledge, a fair level of attitude and negative perception towards allergic reactions of paracetamol. These results may lay a basis for conducting a study of knowledge, attitude and perception towards allergic reactions among general population in other different setting or around Malaysia.

The Use of M2-Pyruvate Kinase as a Stool Biomarker for Detection of Colorectal Cancer in Tertiary Teaching Hospital: A Comparative Study.

PURPOSE: Guaiac fecal occult blood test (gFOBT) has been the standard for colorectal screening but it has low sensitivity and specificity. This study evaluated the use of fecal tumor M2-pyruvate kinase (M2-PK) for detection of colorectal cancer and to compare with the current surveillance tool; gFOBT in symptomatic adult subjects underwent colonoscopy. METHODS: Stool samples were collected prospectively from symptomatic adults who had elective colonoscopy from September 2014 to January 2016 and were analyzed with the ScheBo M2-PK Quick test and laboratory detection of fecal hemoglobin. RESULTS: The results were correlated to the colonoscopy findings and/or histopathology report. Eighty-five subjects (age of 56.8 ± 15.3 years [mean ± standard deviation]) were recruited with a total of 17 colorectal cancer (20.0%) and 10 colorectal adenoma patients (11.8%). The sensitivity of M2-PK test in colorectal cancer detection was higher than gFOBT (100% vs. 64.7%). M2-PK test had a lower specificity when compared to gFOBT (72.5% vs. 88.2%) in colorectal cancer detection. The positive and negative predictive values were 47.2% and 100% for M2-PK test and 57.9% and 90.9% for gFOBT. CONCLUSION: Fecal M2-PK Quick test has a high sensitivity for detection of colorectal cancer when compared to gFOBT, making it the potential choice for colorectal tumor screening biomarker in the future.

Predictors of early postoperative hypocalcemia after total parathyroidectomy in renal hyperparathyroidism.

PURPOSE: Patients with secondary hyperparathyroidism are at high risk for developing postoperative hypocalcemia. However, there are limited data regarding predictors of postoperative hypocalcemia in renal failure patient with secondary hyperparathyroidism. This study aimed to determine the clinical presentations of renal hyperparathyroidism and the predictors of early postoperative hypocalcemia after total parathyroidectomy. METHODS: Data of patients with renal hyperparathyroidism who underwent total parathyroidectomy between January 2007 to December 2014 were reviewed retrospectively. Patients were divided into 2 cohort groups according to their serum calcium levels within 24 hours of parathyroidectomy: the hypocalcemia group (calcium levels of 2 mmol/L or less), and the normocalcemia group (calcium levels more than 2 mmol/L). With the use of multivariable logistic regression analyses, the predictors of early postoperative hypocalcemia after total parathyroidectomy in patients with renal hyperparathyroidism were investigated. RESULTS: Among 68 patients, 56 patients (82.4%) were symptomatic preoperatively. Fifty patients (73.5%) presented with bone pain and 14 patients (20.6%) had muscle weakness. Early postoperative hypocalcemia occurred in 25 patients (36.8%). Preoperative alkaline phosphatase level was the predictor of early postoperative hypocalcemia (adjusted odds ratio, 1.004; 95% confidence interval, 1.001-1.006; P = 0.002). CONCLUSION: Results from our study show that most of the patients with renal hyperparathyroidism were symptomatic preoperatively and the most common clinical presentations were bone pain and muscle weakness. The significant predictor of early postoperative hypocalcemia after total parathyroidectomy was the preoperative alkaline phosphatase levels.

Development and Validation of a Questionnaire on Knowledge, Attitude, and Perception Towards Allergic Reactions of Paracetamol.

INTRODUCTION: National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia has received 1018 adverse drug reaction reports related to paracetamol with 1972 adverse events from the year 2000 to February 2015. Serious skin reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, and acute generalized exanthematous pustulosis may develop as a result of allergic reactions of paracetamol. This study aimed to develop and validate a questionnaire regarding Knowledge, Attitude, and Perception towards Allergic Reactions of Paracetamol (KAP-ARP) among the general population. MATERIALS AND METHODS: Content and face validity of the KAP-ARP were determined by four experts and 20 respondents, respectively. A questionnaire with 36 items, consisting of 16 Knowledge, 9 Attitude, and 11 Perception items, was distributed to 177 respondents. Exploratory factor analysis (EFA) was performed for construct validity. Cronbach's alpha was used to determine the reliability of the questionnaire. RESULTS: EFA constructed 13 Knowledge, 8 Attitude, and 8 Perception items. The final KAP-ARP questionnaire is reliable based on its internal consistency reliability (Knowledge: α = 0.78; Attitude: α = 0.63; Perception: α = 0.70). CONCLUSION: A valid and reliable questionnaire that is useful for measuring KAP-ARP among the general population has been developed.

Translation of the Revised Dyadic Adjustment Scale (RDAS) into the Malay Language and Its Psychometric Qualities among Healthy Married Malay Women.

BACKGROUND: In Malaysia, the problem of marital distress is fast becoming an important public health concern. A major shortcoming is inadequate marital evaluation. There are, however, very few localized instruments for married women in Malaysia. The objective of this study was to translate the original version of the Revised Dyadic Adjustment Scale (RDAS) and to evaluate for its psychometric properties. Multiple aspects of validity and reliability were also assessed. MATERIALS AND METHODS: The questionnaire was first translated into the Malay language (RDAS-M). In this cross-sectional study, healthy married Malay women in Kota Bharu, Kelantan, were recruited from January to April 2018. Participants were asked to complete the RDAS-M that consists of three domains, that is, dyadic consensus, dyadic satisfaction, and dyadic cohesion with a total of 14 items. The concept, content, and construct validity using exploratory factor analysis (EFA) and reliability of the RDAS-M were assessed. RESULTS: Of the 164 recruited participants, 150 consented to participate. The mean age of the participants was 34.1 years (standard deviation [SD], 9.5 years), ranging from 20 to 57 years. All 14 items were considered comprehensible by more than 95% of the subjects. Based on EFA, total variance extracted was 69.08%, and the original three factors were retained. The Malay version of the RDAS was valid based on factor loadings for dyadic consensus, dyadic satisfaction, and dyadic cohesion, which ranged from 0.64 to 0.80, 0.79 to 0.98, and 0.37 to 0.78, respectively. The internal consistency was good with coefficient α of 0.87 for dyadic consensus, 0.93 for dyadic satisfaction, and 0.78 for dyadic cohesion. CONCLUSIONS: The Malay version of the RDAS is easy to understand, and is a reliable and valid instrument for married women. It is also comparable with the original version of the RDAS in terms of structure and psychometric properties.

Influence of DRD2 Polymorphisms on the Clinical Outcomes of Opioiddependent Patients on Methadone Maintenance Therapy.

INTRODUCTION: Dopamine receptor D2 (DRD2) is one of the dopamine receptors that have been studied in relation to opioid dependence. It is possible, therefore, that DRD2 gene (DRD2) polymorphisms influence treatment outcomes of patients with opioid dependence. The objective of this study was to investigate the influence of DRD2 polymorphisms on the clinical outcomes of opioid-dependent patients on methadone maintenance therapy (MMT). MATERIALS AND METHODS: Patients with opioid dependence (n = 148) were recruited from MMT clinics. Pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality were assessed using cold pressor test (CPT), Subjective Opiate Withdrawal Scale (SOWS-M), and Pittsburgh Sleep Quality Index (PSQI)-Malay, respectively. Deoxyribonucleic acid (DNA) was extracted from whole blood, and then was used for genotyping of Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms. RESULTS: Among 148 patients, 8.1% (n = 12), 60.8% (n = 90), 27.7% (n = 41), and 29.1% (n = 43) had at least one risk allele for Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms, respectively. There were no significant differences in pain responses (pain threshold, tolerance, and intensity), SOWS, and PSQI scores between DRD2 polymorphisms. CONCLUSION: The common DRD2 polymorphisms are not associated with pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality in patients with opioid dependence on MMT. However, this may be unique for Malays. Additional research should focus on investigating these findings in larger samples and different ethnicity.

Postoperative major surgery patients developing silent deep vein thrombosis: A prospective observational study.

Surgical patients are at high risk for developing deep vein thrombosis (DVT). There are many reports concerning DVT, but little is known about silent deep vein thrombosis (sDVT). This study aimed to determine the incidence of sDVT. Secondary objective is to identify the associated factors for the use of DVT prophylaxis and Caprini risk scores among major surgery patients. This prospective observational study involved postoperative surgical patients who are at risk of developing sDVT. The Caprini risk-assessment scores were calculated, and each subject had a preoperative and postoperative compression ultrasound complemented by duplex venous ultrasonography of deep venous system. No patient from the study experienced sDVT. There were significant associations between Caprini risk score group (odds ratio, 8.16; 95% confidence interval [CI], 1.01-68.74; P = .016) and the use of central venous catheter (odds ratio, 6.34; 95% CI, 1.62-24.80; P = .008) with DVT prophylaxis. Interestingly, the use of central venous catheter resulted in more than four-point increment of Caprini risk scores (mean increment, 4.19; 95% CI, 3.16-5.21; P < .001). Besides that, age was also significantly associated with Caprini risk scores (ß coefficient, 0.06; 95% CI, 0.02-0.11). Result from our study shows that the sDVT was nonexistent in this study setting. High-Caprini risk score group and the presence of central venous catheter were the significant predictor factors for the use of DVT prophylaxis. Significant predictor factors for Caprini risk scores were age and the presence of central venous catheter.

Relationship between Serum Methadone Concentration and Cold Pressor Pain Sensitivity in Patients Undergoing Methadone Maintenance Therapy.

Hyperalgesia is a common clinical phenomenon among opioid dependent patients on methadone maintenance therapy (MMT) and it may be associated with undertreated pain and/or therapeutic failure. This study aimed to investigate association between serum methadone concentration (SMC) and cold pressor pain responses. Cold pressor pain responses in 147 opioid dependent patients on MMT were assessed using cold pressor test (CPT) at 0 h and at 2, 4, 8, 12, and 24 h after the dose intake. Blood samples were collected at 24 h after the dose. Serum methadone concentrations were measured using the Methadone ELISA kit and classified into two categories: < 400 ng/mL and ≥ 400 ng/mL. Eighty-eight patients (59.9%) had trough concentrations of < 400 ng/mL and 40.1% had trough concentrations of ≥ 400 ng/mL. There were significant effects of SMC on the cold pressor pain threshold (p = 0.019). Patients with concentrations < 400 ng/mL had significantly higher (almost 60% higher) cold pressor pain threshold (adjusted mean (95% CI) = 30.15 (24.29, 36.01) s) compared to those with concentrations of ≥ 400 ng/mL (18.93 (11.77, 26.08) seconds). There was also a 20% difference in pain tolerance, and 6% difference in cold pressor pain intensity score, neither of which were significant statistically (p > 0.05). Our results suggest an association of trough methadone concentration with the cold pressor pain threshold among opioid dependent patients on MMT. It would be useful to study the mechanisms underlying this association to help managing pain in such a population.

Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

ABSTRACT O sistema opioidérgico envolve a regulação do sono e da vigília. É possível, portanto, que os polimorfismos genéticos no OPRM1 influenciem na qualidade do sono. Este estudo investigou a associação de polimorfismos do OPRM1 com a qualidade subjetiva do sono entre indivíduos sem tratamento prévio com opióides. Este estudo observacional de corte transversal envolveu 161 homens que nunca haviam se tornado opióides (média de idade = 27,74 anos; variação: 18 a 63 anos). A qualidade subjetiva do sono foi avaliada com a versão traduzida e validada em malaio do Índice de Qualidade do Sono de Pittsburgh (PSQI). O DNA foi extraído do sangue total e submetido à reação em cadeia da polimerase (PCR) para dois polimorfismos OPRM1 (118A> G e IVS2 + 691G> C). Sujeitos combinados com 118A e IVS2 + 691Galelos (haplótipo AC) apresentaram escores significativamente mais baixos do PSQI [média (DP) = 4,29 (1,76)] em comparação àqueles sem o haplótipo [4,99 (2,50)] (p = 0,004). Por outro lado, os indivíduos com genótipo heterozigótico combinado (GC / AG diplotipo) apresentaram escores significativamente mais altos do PSQI em comparação àqueles sem o diplótipo [6,04 (2,48) vs 4,54 (2,22), p = 0,004]. Em indivíduos sem tratamento prévio com opiáceos, o haplótipo AC e o diplótipo GC / AG para os polimorfismos 118A> G e IVS2 + 691G> C do OPRM1 estão associados a uma melhor e pior qualidade do sono, respectivamente.

ABCB1 Polymorphisms and Cold Pressor Pain Responses: Opioid-Dependent Patients on Methadone Maintenance Therapy.

BACKGROUND: Methadone is a substrate of the P-glycoprotein efflux transporter, which is encoded by ABCB1 (MDR1), and thus, ABCB1 polymorphisms may influence the transport of methadone at the blood-brain barrier, affecting its adverse effects. OBJECTIVES: This study investigated the association between ABCB1 polymorphisms and cold pressor pain responses among opioid-dependent patients on methadone maintenance therapy (MMT). METHODS: Malay male opioid-dependent patients receiving MMT (n = 148) were recruited. Cold pressor pain responses (pain threshold, pain tolerance, and pain intensity) were measured at 0, 2, 4, 8, 12, and 24 hours post-methadone dose. DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms including 1236C>T (rs1128503), 2677G>T/A (rs2032582), and 3435C>T (rs1045642) using the allelic discrimination real-time polymerase chain reaction. Repeated-measure analysis of variance between-group analysis was used to compare the three cold pressor pain responses and ABCB1 polymorphisms (1236C>T, 2677G>T/A, and 3435C>T) according to genotypes and allelic additive models, genotype dominant and recessive models, haplotypes, and diplotypes. RESULTS: Patients with 2677 GG or 2677G allele had the lowest pain threshold compared with 2677G>T/A genotypes or alleles (p = .007 and .002, respectively). Haplotype analysis showed a significant association between ABCB1 haplotypes and pain threshold (p = .02). Patients with 2677G allele had the lowest pain tolerance compared to those with 2677T and 2677A alleles (2677G < 2677T < 2677A allele carriers; p = .05). In terms of pain intensity scores, patients with 2677 GG or 2677G allele had the highest scores compared to other 2677G>T/A genotypes or alleles (p = .04 and .008, respectively). Haplotype analysis revealed a significant difference between patients with CGC haplotype and those without this haplotype (p = .02). DISCUSSION: To the best of our knowledge, this study provides the first evidence that ABCB1 polymorphisms are associated with cold pressor pain responses among Malay male patients with opioid dependence on MMT. The results may provide an initial prediction on heightened pain sensitivity or hyperalgesia for individuals who are carriers of the ABCB1 polymorphisms.

Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid-naive Malay Males.

BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction. RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype. CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.

Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT).

BACKGROUND: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations. OBJECTIVE: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT). METHODS: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit. RESULTS: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml-1 mg-1, respectively; p = 0.033]. CONCLUSION: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.

Relationship between CYP2B6*6 and cold pressor pain sensitivity in opioid dependent patients on methadone maintenance therapy (MMT).

BACKGROUND: CYP2B6 polymorphisms contribute to inter-individual variations in pharmacokinetics of methadone. Increased pain sensitivity is frequently reported by opioid dependent patients on methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in CYP2B6, which affects the metabolism of methadone, influence pain sensitivity among patients on MMT. This study investigated CYP2B6 polymorphisms and pain sensitivity in this group. METHODS: The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping. RESULTS: Of the 148 subjects, 77 (52.0%) were carriers of CYP2B6*6 allele. CYP2B6*6 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B6*6 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B6*6 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352). CONCLUSION: Our study indicates that the CYP2B6*6 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B6*6 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.

Comparison of Pain Tolerance between Opioid Dependent Patients on Methadone Maintenance Therapy (MMT) and Opioid Naive Individuals.

PURPOSE: This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects. METHODS: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose. RESULTS: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016). CONCLUSIONS: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.

Report: Demographic profiles and sleep quality among patients on methadone maintenance therapy (MMT) in Malaysia.

Poor sleep quality was frequently reported by opioid dependence patients during methadone maintenance therapy (MMT). The study investigated a sample of patients on MMT to investigate the severity and prevalence of sleep problems in MMT patients. We evaluated sleep quality and disturbances of 119 Malay male patients from MMT clinics in Kelantan, Malaysia between March and July 2013 using the Pittsburgh Sleep Quality Index (PSQI)-Malay version. Patients' demographic, clinical data, past drug history and methadone treatment variables were recorded. Patients averaged 37.5 years of age (SD 6.79) and their mean age of first time illicit drug use was 19.3 years (SD 4.48). Their mean age of entering MMT was 34.7 years (SD 6.92) and the mean duration in MMT was 2.8 years (SD 2.13). The mean current daily dosage of methadone was 77.8 mg (SD 39.47) and ranged from 20 to 360 mg. The mean global PSQI score was 5.6 (SD 2.79) and 43.7% patients were identified as 'poor sleepers' (global PSQI scores >5). This study confirms the poor overall sleep quality among patients on MMT. The prevalence and severity of sleep problems in MMT patients should not be underestimated.

The AC/AG Diplotype for the 118A>G and IVS2 + 691G>C Polymorphisms of OPRM1 Gene is Associated with Sleep Quality Among Opioid-Dependent Patients on Methadone Maintenance Therapy.

INTRODUCTION: Methadone is a full agonist of the opioid receptor mu 1 which is encoded by the OPRM1 gene. Sleep disorders were frequently reported by opioid-dependent patients during methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality among patients on MMT. This study investigated the association of OPRM1 polymorphisms with sleep quality among opioid-dependent patients on MMT. METHODS: The sleep quality of 165 male opioid-dependent patients receiving MMT was evaluated using the Pittsburgh Sleep Quality Index (PSQI). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR) genotyping. RESULTS: Patients with IVS2 + 691 CC genotype had higher PSQI scores [mean (SD) = 5.73 (2.89)] compared to those without the IVS2 + 691 CC genotype (IVS2 + 691 GG/GC genotype) [4.92 (2.31)], but the difference did not reach statistical significance (p = 0.081). Patients with combined 118 AA genotype and IVS2 + 691 GC genotype (AC/AG diplotype) had significantly lower PSQI scores [mean (SD) = 4.25 (2.27)] compared to those without the diplotype [5.68 (2.77)] (p = 0.018). CONCLUSION: Our study indicates that the AC/AG diplotype for the 118A>G and IVS2 + 691G>C polymorphisms of OPRM1 gene is associated with better sleep quality among males with opioid dependence on MMT.