A scoping review on the relationship between mental wellbeing and medical professionalism.

BACKGROUND: Mental wellbeing issues among medical students are common, and their relationship to medical professionalism is debated. Few studies have attempted to link such issues with undergraduate medical education. This review aimed to advance the knowledge on this matter by exploring the relationship between mental wellbeing and medical professionalism in undergraduate medical education. METHODS: We collected the literature about mental wellbeing and medical professionalism (published from 1 January 1986 to 31 March 2021) from the Web of Science, PubMed, Scopus and ScienceDirect databases using the search terms 'mental wellbeing' and 'medical professionalism'.We included all peer-reviewed articles in which mental wellbeing and medical professionalism in the undergraduate medical education context were the central topics regardless of the age range, nationality, race and gender of the participants. RESULTS: From the 13,076 Iinitially found articles, 16 were included. These 16 articles were from nine countries in four different continents, which all together helped us find answer to our research question using extracted points relating to the main study themes (mental wellbeing and medical professionalism). Under theme 1 (mental wellbeing), six subthemes emerged: burnout, stress, depression, disappointment, depersonalisation and conscientiousness. Theme 2 (medical professionalism), on the other hand, had five subthemes: empathy, academic performance, compassion, unprofessional behaviour and professionalism. A significant inverse association was found between empathy and burnout. Academic performance was also related to burnout. At the same time, empathy was found to have a varied association with stress. Moreover, compassion was found to alleviate burnout and nurture professional gratification. CONCLUSION: The medical professionalism attributes were found to deteriorate as the mental wellbeing issues grow. This can harm medical students' overall health, current learning abilities and future attitudes towards their patients. Explicit primary research is thus required to examine and intervene in the cause-effect relationship between medical professionalism and mental wellbeing.

Psychological Well-Being of Malaysian University Students during COVID-19 Pandemic: Do Religiosity and Religious Coping Matter?

The COVID-19 pandemic and the restrictions imposed that changed the teaching and learning activities may add a psychological impact to the existing academic stress faced by university students. Past studies have associated low levels of psychological disorder with high religiosity and positive religious coping (RC). This study aimed to determine the level of psychological disorder among university students in Malaysia during the COVID-19 pandemic and measure their association with religiosity and religious coping (RC). An online cross-sectional survey was conducted between March and June 2020 involving 450 students. The survey instruments consisted of sociodemographic proforma, Duke University Religious Index (DUREL) for religiosity, Brief RCOPE Scale for RC and General Health Questionnaire-12 (GHQ-12) for psychological disorder; 36% of the participants experienced psychological disorder. Younger age, being a Muslim, living in the Green/Yellow zone and higher negative RC were significantly associated with psychological disorder. Higher positive RC was found to be protective against psychological disorder. However, the level of religiosity had no significant association with psychological disorder. In conclusion, the level of psychological disorder among university students has been high during the pandemic. Measures and interventions focusing on positive RC and reducing negative RC are recommended to improve the psychological well-being.

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.

Validation of the Malay Version of Mini-IPIP among Substance Use Disorder Patients Attending Methadone Clinics in Malaysia.

There has been an increasing interest in personality study over the years. This has led to the necessity for personality measures with good psychometric properties. However, good personality measures are usually too cumbersome to apply in real practical settings due to their length. This study aims to validate a commonly used short personality measure of the Big Five model, i.e., Mini-IPIP (Mini International Personality Item Pool), which has never been validated and used in the substance abuse population in the local setting. The participants were 239 individuals attending one of the six methadone clinics in Malaysia. Structural analysis was conducted using confirmatory factor analysis. Results showed a good model fit for Mini-IPIP when item-parcelling and adding-in correlated uniqueness items were applied (fit indices: Comparative Fit Index = 0.949, Standardised Root Mean Residual = 0.044). Our study supported the five-factor solution for the Mini-IPIP. It is valid and reliable to be used among individuals with drug abuse in Malaysia.

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.

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.

A wavelet-based technique to predict treatment outcome for Major Depressive Disorder.

Treatment management for Major Depressive Disorder (MDD) has been challenging. However, electroencephalogram (EEG)-based predictions of antidepressant's treatment outcome may help during antidepressant's selection and ultimately improve the quality of life for MDD patients. In this study, a machine learning (ML) method involving pretreatment EEG data was proposed to perform such predictions for Selective Serotonin Reuptake Inhibitor (SSRIs). For this purpose, the acquisition of experimental data involved 34 MDD patients and 30 healthy controls. Consequently, a feature matrix was constructed involving time-frequency decomposition of EEG data based on wavelet transform (WT) analysis, termed as EEG data matrix. However, the resultant EEG data matrix had high dimensionality. Therefore, dimension reduction was performed based on a rank-based feature selection method according to a criterion, i.e., receiver operating characteristic (ROC). As a result, the most significant features were identified and further be utilized during the training and testing of a classification model, i.e., the logistic regression (LR) classifier. Finally, the LR model was validated with 100 iterations of 10-fold cross-validation (10-CV). The classification results were compared with short-time Fourier transform (STFT) analysis, and empirical mode decompositions (EMD). The wavelet features extracted from frontal and temporal EEG data were found statistically significant. In comparison with other time-frequency approaches such as the STFT and EMD, the WT analysis has shown highest classification accuracy, i.e., accuracy = 87.5%, sensitivity = 95%, and specificity = 80%. In conclusion, significant wavelet coefficients extracted from frontal and temporal pre-treatment EEG data involving delta and theta frequency bands may predict antidepressant's treatment outcome for the MDD patients.

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.

Emerging Drug Use Trends in Kelantan, Malaysia.

The primarily rural and agrarian Kelantan province of Malaysia has high rates of drug use and is characterized by unique sociocultural factors. Combining qualitative and ethnographic methods, we investigated drug use and treatment needs of people who use drugs (PWUD) in rural areas of Kelantan. In February 2014, field visits, participant observation, and focus group discussions (FGDs) with 27 active PWUD were conducted in rural areas surrounding the capital city of Kelantan. The findings indicate a high prevalence of opiate and amphetamine type stimulants (ATS) use in these areas. FGD participants reported initiating drug use at early ages due to peer influences, to relieve boredom, to cope with problems, and a high saturation of villages with other PWUD was reported as a major contributor to their own continued drug use. They reported a trend of drug use initiation at younger ages and increased drug use among females. Participants were interested in treatment; however, their limited knowledge about treatment options and perceived limited availability of services were barriers to treatment seeking. Easy access to drugs, primarily from Thailand and facilitated by the use of mobile phones, resulted in an expanding prevalence of drug use that underscores the need to bolster education and prevention efforts and accessibility of treatment services in Kelantan.

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.

EEG classification of physiological conditions in 2D/3D environments using neural network.

Higher classification accuracy is more desirable for brain computer interface (BCI) applications. The accuracy can be achieved by appropriate selection of relevant features. In this paper a new scheme is proposed based on six different nonlinear features. These features include Sample entropy (SampEn), Composite permutation entropy index (CPEI), Approximate entropy (ApEn), Fractal dimension (FD), Hurst exponent (H) and Hjorth parameters (complexity and mobility). These features are decision variables for classification of physiological conditions: Eyes Open (EO), Eyes Closed (EC), Game Playing 2D (GP2D), Game playing 3D active (GP3DA) and Game playing 3D passive (GP3DP). Results show that the scheme can successfully classify the conditions with an accuracy of 88.9%.