BackgroundMethadone is a synthetic opiate mu receptor agonist that is widely used to substitute for illicit opiates in the management of opiate dependence. It helps prevent opiate users from injecting and sharing needles which are vehicles for the spread of HIV and other blood borne viruses. This study has the objective of determining the utility of daily methadone dose to predict retention rates and re-injecting behaviour among opiate dependents.MethodsSubjects comprised opiate dependent individuals who met study criteria. They took methadone based on the Malaysian guidelines and were monitored according to the study protocols. At six months, data was collected for analyses. The sensitivity and specificity daily methadone doses to predict retention rates and re-injecting behaviour were evaluated.ResultsSixty-four patients volunteered to participate but only 35 (54.69%) remained active and 29 (45.31%) were inactive at 6 months of treatment. Higher doses were significantly correlated with retention rate (p < 0.0001) and re-injecting behaviour (p < 0.001). Of those retained, 80.0% were on 80 mg or more methadone per day doses with 20.0% on receiving 40 mg -79 mg.ConclusionsWe concluded that a daily dose of at least 40 mg was required to retain patients in treatment and to prevent re-injecting behaviour. A dose of at least 80 mg per day was associated with best results.

Medication non-adherence remains a significant barrier in achieving better health outcomes for patients with chronic diseases. Previous self-reported medication adherence tools were not developed in the context of the Malaysia population. The most commonly used tool, MMAS-8, is no longer economical because it requires a license and currently every form used is charged. Hence, there is a need to develop and validate a new medication adherence tool. The Malaysia Medication Adherence Assessment Tool (MyMAAT) was developed by a multidisciplinary team with expertise in medication adherence and health literacy. The face and content validities of the MyMAAT was established by a panel of experts. A total of 495 patients with type 2 diabetes were recruited from the Ministry of Health facilities consisting of five hospitals and five primary health clinics. A test-retest was conducted on 42 of the patients one week following their first data collection. Exploratory factor analysis was performed to evaluate the validity of the MyMAAT. The final item for MyMAAT was compared with SEAMS, HbA1c%, Medication Possession ratio (MPR) score, and pharmacist’s subjective assessment for its hypothesis testing validity. The MyMAAT-12 achieved acceptable internal consistency (Cronbach’s alpha = 0.910) and stable reliability as the test-retest score showed good to excellent correlation (Spearman’s rho = 0.96, p = 0.001). The MyMAAT has significant moderate association with SEAMS (Spearman’s rho = 0.44, p = < 0.001) and significant relationship with HbA1c (< 8% and ≥ 8%) (χ2(1) = 13.4, p < 0.001), MPR (χ2(1) = 13.6, p < 0.001) and pharmacist’s subjective assessment categories (χ2(1) = 31, p < 0.001). The sensitivity of MyMAAT-12, tested against HbA1c% was 72.9% while its specificity was 43%. This study demonstrates that the MyMAAT-12 together with other methods of assessment may make a better screening tool to identify patients who were non-adherence to their medications.

Background This systematic review and meta-analysis aimed to determine the effectiveness of olive leaf extract on cardiometabolic profiles among prehypertensive and hypertensive groups. Methodology The Cochrane central register of controlled trials, Medline (1966 to April week 1, 2020), Embase (1966 to April week 1, 2020) and trial registries for relevant randomized clinical trials were used. Published and unpublished randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the continuous outcomes and mean differences (MDs); both with 95% confidence intervals (CIs). The primary outcomes were changes in systolic and diastolic BP. The secondary outcomes were changes in lipid profile, glucose metabolism, inflammatory markers for CVD, kidney and liver functions safety parameters. We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence. Results Five trials were included involving 325 patients aged 18–80 years. Two trials involved high-income countries and three trials involved moderate-income countries. The analysis performed was based on three comparisons. No significant changes were found between systolic or diastolic blood pressure (BP) for the first comparison, 1,000 mg per day for a combined formulation of olive leaf extract versus a placebo. The second comparison, 500 mg per day of olive leaf extract versus placebo or no treatment, showed a significant reduction in systolic BP over a period of at least 8 weeks of follow up (MD −5.78 mmHg, 95% CI [−10.27 to −1.30]) and no significant changes on diastolic BP. The third comparison, 1,000 mg per day of olive leaf extract versus placebo shows no significant difference but an almost similar reduction in systolic BP (−11.5 mmHg in olive leaf extract and −13.7 mmHg in placebo, MD 2.2 mmHg, 95% CI [−0.43–4.83]) and diastolic BP (−4.8 mmHg in olive leaf extract and −6.4 mmHg in placebo, MD 1.60 mmHg, 95% CI [−0.13–3.33]). For secondary outcomes, 1,000 mg per day of olive leaf extract versus captopril showed a reduction in LDL (MD −6.00 mg/dl, 95% CI [−11.5 to −0.50]). The 500 mg per day olive leaf extract versus placebo showed a reduction in inflammatory markers for CVD IL-6 (MD −6.83 ng/L, 95% CI [−13.15 to −0.51]), IL-8 (MD −8.24 ng/L, 95% CI [−16.00 to −0.48) and TNF-alpha (MD −7.40 ng/L, 95% CI [−13.23 to −1.57]). Conclusions The results from this review suggest the reduction of systolic BP, LDL and inflammatory biomarkers, but it may not provide a robust conclusion regarding the effects of olive leaf extract on cardiometabolic profile due to the limited number of participants in the included trials. Review registrations PROSPERO CDR 42020181212.

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.

Aim. Poor sleep quality due to pain has been reported among opioid-dependent male patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of pain-sensitivity using cold pressor test (CPT) and the relationship between pain-sensitivity and sleep quality in this population. Methods. A total of 168 male participants were included into the study. Objective pain-tolerance was evaluated at 0 h and at 24 h after the first CPT. Malay version of the Pittsburgh Sleep Quality Index (PSQI) and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively. Results. The mean age of study participants was 37.22 (SD 6.20) years old. Mean daily methadone dose was 76.64 (SD 37.63) mg/day, mean global PSQI score was 5.47 (SD 2.74) and mean averaged SOWS score was 5.43 (SD 6.91). The averaged paintolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of participants were identified as pain-sensitive (averaged pain-tolerance time ≤37.53 s), and 36 (21.4%) participants were pain-tolerant (averaged pain-tolerance time >37.53 s). The pain-sensitive group reported poorer sleep quality with mean (SD) PSQI of 5.78 (2.80) compared with the pain-tolerant group with mean (SD) PSQI of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive group was found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant participants (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010). Conclusions. Majority of opioid-dependent male patients on methadone treatment are pain-sensitive with CPT. Poor sleep quality is associated with cold pressor pain-sensitivity. Pain and sleep complaints in this male population should not be overlooked.How to cite this article Zahari et al. (2015), Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment. PeerJ 3:e839; DOI 10.7717/peerj.839 Subjects

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N-Methyl-3, 4-methylenedioxyamphetamine (MDMA), or ecstasy is a recreational drug of abuse. It is a synthetic substance that affects the body's systems, which its mechanism of action and treatment should be more investigated. MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure. Only a few studies have been done regarding its treatment. Thus, the treatment of MDMA complications should be further explored mainly by targeting its mechanism of action in the neurotransmitter systems. Hence, this study presents a short review regarding the recent findings on the role of neurotransmitters to cause MDMA neurotoxicity. The results will be useful for future research in elucidating the potential treatment based on the targeted mechanisms to treat the neurotoxic effects of MDMA.