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  1. Hamid N, Muhamad R, Kueh YC, Zahari Z, Mohamad Nor N, Abdullah N, et al.
    J Pharm Bioallied Sci, 2020 10 08;12(4):444-448.
    PMID: 33679091 DOI: 10.4103/jpbs.JPBS_265_19
    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.

  2. Tan SK, Sanmugam A, Danaee M, Ramanujam TM, Nallusamy MA, Zahari Z, et al.
    Sultan Qaboos Univ Med J, 2019 Nov;19(4):e352-e358.
    PMID: 31897319 DOI: 10.18295/squmj.2019.19.04.011
    Objectives: Transition of care (TOC) from paediatric to adult care is still at an early stage in Malaysia. This study aimed to explore current practices and perspectives regarding TOC among paediatric surgeons in Malaysia.

    Methods: This study was carried out between June and December 2017. All 48 paediatric surgeons currently working in Malaysia were invited to participate in a questionnaire-based survey to assess demographic characteristics and practices and perspectives regarding TOC.

    Results: A total of 38 paediatric surgeons participated in the survey (response rate: 79.2%). Overall, 97.4% did not have an organised TOC model in their institution, with most (65.8%) caring for paediatric patients with complex surgical conditions until adulthood. Although the majority (86.8%) felt that care should be transitioned to adult surgeons with appropriate credentials, most surgeons (84.2%) nevertheless preferred to be involved in the management of adolescent patients after transition. However, there was no consensus regarding the most suitable age to begin the transition. Years of experience as a paediatric surgeon and place of practice did not affect overall TOC practice scores (P >0.050 each). The presence of adult comorbidities was considered the most common reason to initiate TOC (81.6%), while the lack of TOC guidelines was perceived to be the greatest barrier (84.2%).

    Conclusion: This study provides a better understanding of TOC from the point of view of paediatric surgeons in Malaysia. However, further studies involving other stakeholders (i.e. patients and adult surgeons) are needed to help formulate a suitable and successful TOC model in this setting.

  3. Zainalabidin FA, Raimy N, Yaacob MH, Musbah A, Bathmanaban P, Ismail EA, et al.
    Trop Life Sci Res, 2015 Apr;26(1):1-8.
    PMID: 26019746 MyJurnal
    Helminthiasis due to strongyles such as Haemonchus contortus, coccidiosis caused by Eimeria sp. and blood parasite diseases such as theileriosis by Theileria sp. have been reported to cause severe morbidity and mortality annually in small ruminants in Malaysia. The aims of this study were to investigate the prevalence of helminthiasis, coccidiosis and theileriosis and to determine the packed cell volume (PCV) value of small ruminants in Perak, Malaysia. Blood and faecal samples were obtained from a total of 175 animals from 7 small ruminant farms in Kampar, Larut Matang and Selama, Kuala Kangsar and Manjung districts in Perak; the samples were examined for parasitic infestations from April to July 2011. The results of this study show that H. contortus was found in 152 (86.86%) animals, Eimeria sp. was found in 162 (92.57%) animals and the blood protozoa Theileria sp. was found in 25 (14.30%) animals. The PCV values of all of these animals were recorded between 7% and 44%. A total of 42 (24%) animals were anaemic, with a PCV of less than 21%. Continuous monitoring of small ruminant farms will provide important information for assisting farmers with managing the spread of parasitic infections and maintaining the productivity of animals.
  4. Zahari Z, Ishak A, Justine M
    J Back Musculoskelet Rehabil, 2020;33(2):245-254.
    PMID: 31356191 DOI: 10.3233/BMR-181305
    OBJECTIVES: This study aimed to gain an overview of patient education and the effects of patient education for older people with low back pain (LBP).

    METHODS: The search strategies were performed via EBSCO MEDLINE, EBSCO CINAHL, Science Direct, PubMed, and PEDro databases from 2006 to 2016. The keywords "patient education", "low back pain", "elderly", "older adults", "older persons" and "older people" were used during the literature search. Boolean operators were used to expand or limit the searching scope and manual exclusion was performed to choose articles eligible for this study.

    RESULTS: A total of 2799 articles were retrieved but only five articles were related with patient education for older people with LBP. Findings suggest that patient education for older people may differ in terms of its contents such as health education, self-management, video education, and postural education. The high methodological quality of the studies revealed that patient education showed improvement in terms of pain, disability and quality of life among older people with LBP.

    CONCLUSIONS: Patient education improved pain and had positive effects on disability and quality of life among older people with LBP. However, due to the limited number of RCTs more studies are needed to provide evidence for its effectiveness.

  5. Zulkifli MF, Md Hashim MN, Zahari Z, Wong MP, Syed Abd Aziz SH, Yahya MM, et al.
    Sci Rep, 2023 Nov 16;13(1):20078.
    PMID: 37973795 DOI: 10.1038/s41598-023-47357-5
    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.
  6. Che Alhadi S, Wan Zain WZ, Zahari Z, Md Hashim MN, Syed Abd Aziz SH, Zakaria Z, et al.
    Ann Coloproctol, 2020 Dec;36(6):409-414.
    PMID: 32972105 DOI: 10.3393/ac.2020.08.27
    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.

  7. Zahari Z, Lee CS, Ibrahim MA, Musa N, Yasin MA, Lee YY, et al.
    Pain Ther, 2015 Dec;4(2):179-96.
    PMID: 26581429 DOI: 10.1007/s40122-015-0041-y
    We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy.
  8. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Pain Ther, 2016 Jun;5(1):43-54.
    PMID: 26792136 DOI: 10.1007/s40122-016-0044-3
    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.
    KEYWORDS: AC/AG diplotype; Male patients; Methadone; Methadone maintenance therapy; OPRM1; Opioid dependence; Opioid receptor; Opioid receptor, mu 1 gene; Pittsburgh Sleep Quality Index; Sleep quality
  9. Mohd Tan A, Zahari Z, Bukry SA
    Med J Malaysia, 2024 Mar;79(Suppl 1):197-202.
    PMID: 38555905
    INTRODUCTION: The ankles and feet of footballers are the most commonly affected areas by acute and chronic injuries, especially sprains. The durability of changes in motor control for the sprained injury strongly suggests that central motor commands have been reorganized and restructured involving the sensorimotor system. Indirectly, providing strength training improves muscular strength and benefits cardiometabolic health, coordination, sensorimotor, and motor performance. Thus, this study aimed to identify the effects of strengthening exercises on motor control among footballers with sprained ankles.

    MATERIALS AND METHODS: This scoping review selected studies published from January 2002 to November 2022. The articles were searched through PubMed Central, BMJ Journal, Science Direct, and Scopus using "motor control", "ankle sprain" and "strengthening exercise" as the keywords. After finding the articles, the information extracted included author, year of publication, country, objective, type of study, and motor control analysis summary. The literature search strategy used Preferred Reporting Items for Systematic Review and a meta-analysis (PRISMA) where studies that are related to strengthening exercise and motor control were selected.

    RESULTS: From the initial search, 50 articles were found. After processing, only ten articles were further reviewed. The findings demonstrated strengthening exercises provide changes in neurophysiological parameters with motor performance, improved motor control, strength, balance, pain, and functional movement in footballers with sprained ankles.

    CONCLUSION: This review suggests the application of strengthening exercise interventions not only improves motor control, but strength, balance, pain, and functional performance among footballers with sprained ankles.

  10. Nah SA, Sanmugam A, Singaravel S, Zahari Z, Aziz DA
    J Pediatr Surg, 2023 Feb;58(2):299-304.
    PMID: 36404187 DOI: 10.1016/j.jpedsurg.2022.10.032
    BACKGROUND: A shortage of specialist paediatric surgeons in Malaysia led to establishment of a national postgraduate training programme in 2004. We aimed to identify sociodemographic factors impacting training experience, and to define pressure points during training to inform targeted trainee support strategies.

    METHODS: We conducted an anonymized online survey in June 2021 on all programme graduates. Participants were asked for sociodemographic data, both current and during training. Likert scale responses were required for questions regarding adequacy of support received for family, health and personal issues during training. A free text response question soliciting suggestions for programme improvement was included. Data are reported as median (range). Chi-square/Fisher's exact tests for categorical variables and Mann-Whitney U tests for continuous variables were used, with p<0.05 significance.

    RESULTS: Of 53 eligible participants, 52 (98%) responded, 24 (46%) were female. Marital status was similar between genders at entry, but female trainees were more likely to be unmarried on exit (p = 0.001), and less likely to have children while training (p = 0.017). Of the 6 female and 18 male trainees who had children while training, women were more likely to take parental leave (p = 0.01). The majority felt advice given regarding parental leave and managing training while having children were poor. In thematic analysis of free text answers, lack of hands-on experience was the most common concern.

    CONCLUSION: Factors related to marriage and parenthood significantly associate with gender amongst trainees in Malaysia despite both genders being well represented. Concerns regarding adequacy of hands-on training highlight the need for educational innovations such as simulation models.

    LEVEL OF STUDY: Level III.

  11. Zahari Z, Inrahim MA, Tan SC, Mohamad N, Ismail R
    Turk J Med Sci, 2016 Dec 20;46(6):1743-1748.
    PMID: 28081321 DOI: 10.3906/sag-1507-132
    BACKGROUND/AIM: Sleep disturbances may contribute to poor treatment outcomes in opioid-dependent patients. The extent to which the sleep profiles of opioid-dependent patients differ from those of the general Malaysian population is not documented. This study compared opioid-naive subjects and opioid-dependent patients on methadone maintenance therapy (MMT) in terms of their sleep quality.

    MATERIALS AND METHODS: Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI).

    RESULTS: The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030].

    CONCLUSION: This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.

  12. Lim SL, Wan Zain WZ, Zahari Z, Zakaria AD, Hashim MNM, Wong MP, et al.
    Ann Coloproctol, 2023 Oct;39(5):427-434.
    PMID: 35655395 DOI: 10.3393/ac.2022.00227.0032
    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.

  13. Zainal Zahari Z, Rosnina Y, Wahid H, Yap KC, Jainudeen MR
    Anim. Reprod. Sci., 2005 Feb;85(3-4):327-35.
    PMID: 15581515
    The Sumatran rhinoceros (Dicerorhinus sumatrensis) is on the verge of extinction in Malaysia. At the Sumatran rhinoceros Conservation Centre in Sungai Dusun, the reproductive behaviour of two female and two male rhinoceroses were studied for 8-10 months during attempts to breed them in captivity. Due to the paucity of scientific information on the reproductive biology of the Sumatran rhinoceros, this study was conducted to obtain information on the reproductive behaviour of this species. The male rhino was introduced to a female rhino in the morning for 1-2 h daily in order to observe for behavioural oestrus. Observations were made on the signs of oestrus and mating behaviour. Oestrus was determined by receptivity towards the male and lasted about 24 h. Common signs of oestrus were an increase in frequency of urine spraying, tail raising or swinging, anogenital and other contacts. Although the males exhibited mounting, the inability of the male to achieve intromission was poor. The study demonstrated that the pattern of courtship and copulation of the captive Sumatran rhinos were comparable with those of other rhino species, reported previously by other scientists and flehmen reflex was also exhibited by the male Sumatran rhinos. In a captive breeding programme, it is recommended that only an oestral female is introduced into a male enclosure due to the male solitary behaviour and to avoid serious injuries inflicted onto the females.
  14. Zahari Z, Siong LC, Musa N, Mohd Yasin MA, Choon TS, Mohamad N, et al.
    Pak J Pharm Sci, 2016 Jan;29(1):239-46.
    PMID: 26826835
    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.
  15. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Iran J Pharm Res, 2018;17(Suppl):8-16.
    PMID: 29796025
    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.
    Study site: Psychiatric Clinic, Hospital Universiti Sains Malaysia (HUSM); Psychiatric Clinic, Hospital Raja Perempuan Zainab II; and eight other government MMT clinics in Kelantan, Malaysia
  16. Zahari Z, Lee CS, Tan SC, Mohamad N, Lee YY, Ismail R
    PeerJ, 2015;3:e839.
    PMID: 25870765 DOI: 10.7717/peerj.839
    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 pain-tolerance 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.
    Study site: Hospital Universiti Sains Malaysia (HUSM) and other MMT clinics (Kota Bharu, Pasir Mas, Pasir Puteh and Bachok), Kelantan, Malaysia
  17. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Drug Alcohol Depend, 2016 08 01;165:143-50.
    PMID: 27289271 DOI: 10.1016/j.drugalcdep.2016.05.028
    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.

  18. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Am J Drug Alcohol Abuse, 2016 09;42(5):587-596.
    PMID: 27284701 DOI: 10.3109/00952990.2016.1172078
    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-1mg-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.
    Study site: Psychiatric Clinic, Hospital Universiti Sains Malaysia (HUSM), and other MMT clinics in Kelantan,
    Malaysia
  19. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Pain Pract, 2017 09;17(7):930-940.
    PMID: 27996183 DOI: 10.1111/papr.12546
    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.

  20. Tan PG, Ab Hadi IS, Zahari Z, Yahya MM, Wan Zain WZ, Wong MP, et al.
    Ann Surg Treat Res, 2020 Jan;98(1):1-6.
    PMID: 31909044 DOI: 10.4174/astr.2020.98.1.1
    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.

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