Displaying publications 1 - 20 of 35 in total

  1. Chow NK, Harun SN, Khan AH
    AIDS Care, 2021 Sep 20.
    PMID: 34543113 DOI: 10.1080/09540121.2021.1981220
    Sociodemographic status and medical problems were widely reported as the major factors in people living with HIV (PLHIV) with lower health-related quality of life (HRQoL). However, lifestyles and cultural changes are rarely studied. A multicentred cross-sectional study was conducted among 137 virally suppressed PLHIV on antiretroviral therapy (ART) in northern Malaysia by face-to-face interviews and World Health Organization Quality of Life (WHOQOL)-BREF questionnaire. It was to explore their health and socioeconomic status, lifestyles, and associations with different HRQoL domains. The result of multiple linear regression showed that smoking was a predominant risk factor of lower physical (beta coefficient (β): -5.82, 95% confidence interval (CI): -9.97 to -1.66; p = 0.006), social (β: -8.76, 95% CI: -15.12 to -2.40; p = 0.007), and environmental domain scores (β: -10.25, 95% CI: -15.21 to -5.30; p 
  2. Harun SN, Wainwright C, Klein K, Hennig S
    Paediatr Respir Rev, 2016 Sep;20:55-66.
    PMID: 27259460 DOI: 10.1016/j.prrv.2016.03.002
    A systematic review was performed (i) to describe the reported overall rate of progression of CF lung disease quantified as FEV1%predicted decline with age, (ii) to summarise identified influencing risk factors and (iii) to review methods used to analyse CF lung disease progression data. A search of publications providing FEV1%predicted values over age was conducted in PUBMED and EMBASE. Baseline and rate of FEV1%predicted decline were summarised overall and by identified risk factors. Thirty-nine studies were included and reported variable linear rates of lung function decline in patients with CF. The overall weighted mean FEV1%predicted over age was graphically summarised and showed a nonlinear, time-variant decline of lung function. Compared to their peers, Pseudomonas aeruginosa infection and pancreatic insufficiency were most commonly associated with lower baseline and more rapid FEV1%predicted declines respectively. Considering nonlinear models and drop-out in lung disease progression, analysis is lacking and more studies are warranted.
  3. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM
    Clin Nutr ESPEN, 2019 02;29:213-223.
    PMID: 30661689 DOI: 10.1016/j.clnesp.2018.10.002
    BACKGROUND: The contribution of dietary factors in the development and progression of pre-diabetes has been increasingly recognized. However, due to high variability in dietary habits measurement of dietary intake remains one of the most challenging tasks in this population. Food frequency questionnaire (FFQ) which investigates usual dietary intake can be used to identify frequent consumption of foods such as dietary fat, fiber, grains that are linked to the risk of pre-diabetes.

    METHOD: This systematic review was conducted to identify and describe FFQs that measure dietary intake of pre-diabetic patients and to examine their relative validity and reliability. The systematic search was done through electronic databases such as PubMed, CINAHL, PsycINFO, ProQuest and Scopus. Methodological quality of included studies and results of study outcome was also summarized in this review.

    RESULT: The search identified 445 papers, of which 18 studies reported 15 FFQs, met inclusion criteria. Most of the FFQs (n = 12) were semi-quantitative while three were frequency measures with portion size estimation of selected food items. Test-retest reliability of FFQ was reported in 7 (38.3%) studies with the correlation coefficient of 0.33-0.92. Relative validity of FFQ was reported in 16 (88.8%) studies with the range of correlation coefficient of 0.08-0.83. Dietary patterns rich in carbohydrate, fat, animal protein and n-3 fatty acids were associated with increased risk of pre-diabetes.

    CONCLUSION: No well-established disease-specific FFQ identified in the literature. Development of a valid, practical and reliable tool is needed for better understanding of the impact of diet in pre-diabetic population.

  4. Harun SN, Hanafiah MM, Aziz NIHA
    Environ Manage, 2021 Jan;67(1):146-161.
    PMID: 33001258 DOI: 10.1007/s00267-020-01365-7
    This study aims to assess the environmental impacts of conventional and organic rice cultivations and proposes a sustainable conceptual framework of rice farming based on the life cycle assessment (LCA) approach. A cradle-to-gate LCA was performed by using the ReCiPe 2016 method and SimaPro 8.5 software. The functional unit was one ton of rice grains harvested. Primary data were obtained from the farmer, while secondary data were collected from Ecoinvent 3.0, the Agri Footprint 3.0 database and the literature. The total characterization factors for global warming potential (GWP), water consumption potential (WCP) and fossil fuel depletion potential (FFP) were 457.89 kg CO2-eq, 98.18 m3 and 84.56 kg oil-eq, respectively, at the midpoint level for conventional rice, while the impacts for organic rice were 140.55 kg CO2-eq, 29.45 m3 and 22.25 kg oil-eq, respectively. At the endpoint level, the total characterization factors for human health damage (HH), ecosystem damage (ED) and resource availability (RA) for conventional rice were 9.63 × 10-4 DALY, 5.54 × 10-6 species.year and 30.98 Dollar, respectively, while for organic rice, the impacts were 2.60 × 10-4 DALY, 2.28 × 10-6 species.year and 8.44 Dollar, respectively. Rice cultivation impacted the environment, particularly in relation to three impact categories: GWP, WCP and FFP. The cultivation phase of rice production was the main contributor to environmental impacts due to the production and application of fertilizer and pesticides. It can be concluded that the application of LCA in agricultural sector is able to provide information and responses for policy makers in understanding the potential environmental impacts at various spatial levels.
  5. Albitar O, Harun SN, Ahmad SNA, Sheikh Ghadzi SM
    Pharmaceutics, 2021 Jul 22;13(8).
    PMID: 34452082 DOI: 10.3390/pharmaceutics13081121
    Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients' medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan-Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93-0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97-7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01-1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.
  6. Siddiqui S, Zainal H, Harun SN, Ghadzi SMS
    Clin Nutr ESPEN, 2020 10;39:165-172.
    PMID: 32859312 DOI: 10.1016/j.clnesp.2020.06.022
    BACKGROUND: Diabetes mellitus is a leading cause of preventable deaths and becomes a major public health concern in Malaysia. Multiple studies have reported the association between diet quality and glycemic parameters among known diabetic subjects. Its influence in individuals with borderline diabetes (i.e. pre-diabetes) or unknown diabetes is still unclear.

    OBJECTIVE: The objective of this study was to assess the association between diet quality evaluated by healthy eating index (HEI) with the glucose outcome in individuals with distinct diabetes progression stages, as well as to identify causal factors in relation to their diabetes status.

    METHOD: A cross-sectional study was conducted at clinical care setting in Universiti Sains Malaysia (USM) between October 2018-March 2019. Normoglycemic controls (n = 47), at-risk of pre-diabetes (n = 58), pre-diabetes (n = 24) as well as individuals with undiagnosed diabetes (n = 18) were queried about their habitual diet by using Food Frequency Questionnaire (FFQ). Correlation analyses were performed to examine the relationship between HEI score and 1) Fasting plasma glucose (FPG) 2) postprandial blood glucose (2-HPP) and glycosylated hemoglobin (HbA1c). Multinomial regression was performed to identify predictors associated with diabetes status of study participants.

    RESULT: Overall, diet quality of study participants was unsatisfactory with the mean score of 58.05 ± 9.07 that need improvement. Total HEI score was negatively correlated with the 2-HPP levels in pre-diabetic patients (r = - 0.45, p = 0.05). No significant association was revealed between glycemic parameters and total HEI score among other groups. Age, body mass index (BMI), triglycerides and female gender were positively correlated with the risk of pre-diabetes, at-risk of pre-diabetes and undiagnosed diabetes (p 

  7. Harun SN, Wainwright CE, Grimwood K, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 02;74(2):125-131.
    PMID: 30275132 DOI: 10.1136/thoraxjnl-2018-211550
    BACKGROUND: The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.
    AIMS: To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables.
    METHODS: A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV1% predicted measurements at age 5 years from the ACFBAL study and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis Data Registry.
    RESULTS: Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV1% predicted at age 5 years or FEV1% predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population.
    CONCLUSION: In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function decline between ages 5 years and 14 years.
  8. Rehman AU, Hassali MAA, Muhammad SA, Harun SN, Shah S, Abbas S
    Eur J Health Econ, 2020 Mar;21(2):181-194.
    PMID: 31564007 DOI: 10.1007/s10198-019-01119-1
    OBJECTIVES: To find the economic burden of COPD and to identify the key cost drivers in the management of COPD patients across different European countries.

    BACKGROUND: COPD is a major cause of mortality and morbidity and is associated with considerable economic burden on the individual and society. It limits the daily activities and working ability of the patients.

    METHODOLOGY: We conducted a systematic search of PUBMED, SCIENCE DIRECT, Cochrane CENTRAL, SCOPUS, Google Scholar and SAGE Premier Databases to find scientific research articles evaluating the cost of COPD management from patient and societal perspective.

    RESULTS: Estimated per patient per year direct cost in Norway, Denmark, Germany, Italy, Sweden, Greece, Belgium, and Serbia was €10,701, €9580, €7847, €7448, €7045, €2896, €1963, and €2047, respectively. Annual per patient cost of work productivity loss was highest in Germany as €5735 and lowest in Greece as €998. It was estimated as €4824, €2033 and €1298 in Bulgaria, Denmark and Sweden, respectively. Several factors found associated with increasing cost of COPD management that include but not limited to late diagnosis, severity of disease, frequency of exacerbation, hospital readmissions, non-adherence to the therapy and exposure to COPD risk factors.

    CONCLUSION: Minimizing the COPD exacerbations and controlling the worsening of symptoms may potentially reduce the cost of COPD management at any stage.

  9. Harun SN, Holford NHG, Grimwood K, Wainwright CE, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 08;74(8):740-748.
    PMID: 31203197 DOI: 10.1136/thoraxjnl-2018-211548
    BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.

    AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.

    METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.

    RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.

    CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

  10. Harun SN, Ahmad H, Lim HN, Chia SL, Gill MR
    Pharmaceutics, 2021 Jan 24;13(2).
    PMID: 33498795 DOI: 10.3390/pharmaceutics13020150
    The ruthenium polypyridyl complex [Ru(dppz)2PIP]2+ (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C16) as the template. Optimization of the synthesis conditions by Box-Behnken design (BBD) generated MSNs with high surface area response at 833.9 m2g-1. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC50) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period.
  11. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM, Ghafoor S
    Diabetes Metab Syndr, 2020 07 08;14(5):1243-1252.
    PMID: 32688241 DOI: 10.1016/j.dsx.2020.06.069
    BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking.

    AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders.

    METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables.

    RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders.

    CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

  12. Albitar O, Ballouze R, Harun SN, Mohamed Noor DA, Sheikh Ghadzi SM
    J Clin Pharmacol, 2020 11;60(11):1474-1482.
    PMID: 32557653 DOI: 10.1002/jcph.1670
    Cyclosporine is a primary drug in transplant immunosuppression regimens. It has a narrow therapeutic index and variable pharmacokinetic behavior. This study aimed to develop a population pharmacokinetic model of cyclosporine in Malaysian renal transplant recipients as well as to evaluate the performances of different methodsfor handling missing doses. A total of 2804 concentrationts predose and 2 hours after doses were collected retrospectively from 113 renal transplant patients on cyclosporine in Penang General Hospital. Model structure and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling software. Missing doses were handled using different methods to evaluate their performance. Covariate analysis was performed using stepwise forward addition (P < .05) followed by backward elimination (P < .001). Prediction-corrected visual predictive check and sampling-importance resampling methods were used to validate the final model. A 1-compartment model with first-order absorption and elimination best fitted the data. All methods to handle missing doses performed well with the missing dose method being superior to other methods and thus was applied in the final model. Cyclosporine clearance (CL/F) was estimated as 15.1 L/h, and volume of distribution (V/F) was 108 L. Postoperative time, sex, and calcium channel blockers were identified as significant covariates on CL/F, whereas sex and cholesterol level were identified as significant covariates on V/F. This is the first population pharmacokinetic model developed in Malaysian renal transplant patients using a large sample with an evaluation of different methods to handle missing doses in less informative conventional therapeutic drug-monitoring data.
  13. Daud NAA, Mohiuddin SG, Ong YP, Yusof F, Yusoff F, Harun SN, et al.
    J Pharm Bioallied Sci, 2021 05 26;13(2):230-237.
    PMID: 34349484 DOI: 10.4103/jpbs.JPBS_542_20
    Background: Metformin has been added in the Malaysian clinical practice guideline (CPG) as one of the first-line options in the management of gestational diabetes mellitus (GDM); however, the uptake on this practice among healthcare professionals is unknown.

    Objective: The objective of the study is to determine the awareness, attitude, and practice and their predictors on the use of metformin for GDM among healthcare professionals in Malaysia.

    Materials and Methods: This was a multicenter, cross-sectional study in three tertiary hospitals in Malaysia. Medical doctors and pharmacists working in several departments were invited to participate in a survey using self-administered questionnaires.

    Results: From 350 questionnaires distributed, 225 were completed by medical doctors (43.1%), pharmacists (40.4%), and specialists (7.5%). Less than 30% of them were aware on the option of using metformin as one of the first-line agents in GDM. Education level, department, and profession were found to be associated with the awareness level (P = 0.016, P = 0.004, and P = 0.001, respectively). 70.2% of the respondents showed a positive attitude toward metformin use in GDM. Only 64 (28.4%) of the respondents have prescribed/dispensed metformin for GDM before, although more than half will consider doing so in the future. Having postgraduate qualifications increased the likelihood of having a good awareness (odds ratio [OR]: 2.44, 95% confidence interval [CI] 1.23-4.85) and to consider prescribing/dispensing metformin for GDM patients (OR: 2.27, 95% CI 1.08-4.78).

    Conclusion: Despite a positive attitude toward metformin use in GDM among healthcare professionals in Malaysia, their awareness level on this practice was low as they currently prefer the use of insulin over metformin.

  14. Gill MR, Harun SN, Halder S, Boghozian RA, Ramadan K, Ahmad H, et al.
    Sci Rep, 2016 08 25;6:31973.
    PMID: 27558808 DOI: 10.1038/srep31973
    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.
  15. Harun SN, Nordin SA, Gani SSA, Shamsuddin AF, Basri M, Basri HB
    Int J Nanomedicine, 2018;13:2571-2584.
    PMID: 29731632 DOI: 10.2147/IJN.S151788
    Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.

    Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.

    Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
    , prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
    , prolonged half-life, and lower clearance as compared to free cefuroxime solution.

    Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

  16. Albitar O, Harun SN, Zainal H, Ibrahim B, Sheikh Ghadzi SM
    Biomed Res Int, 2020;2020:9872936.
    PMID: 31998804 DOI: 10.1155/2020/9872936
    Background and Objective: Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models.

    Methods: A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded.

    Results: Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models.

    Conclusions: Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.

  17. Rehman AU, Hassali MAA, Harun SN, Abbas S, Muneswarao J, Ali IABH, et al.
    Health Qual Life Outcomes, 2020 May 13;18(1):138.
    PMID: 32404113 DOI: 10.1186/s12955-020-01393-1
    BACKGROUND: Cultural differences affect the administration and results of health status questionnaires. "Cross cultural adaptation" ensures retention of psychometric properties such as validity and reliability at an item and/or scale level.

    OBJECTIVE: To develop a Malaysian version of St George's respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia.

    METHODOLOGY: SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated.

    RESULTS: The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, - 0.82, 0.72 and - 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = - 0.35 to r = - 0.87. The MCID was reported as 5.07 (- 2.54-12.67).

    CONCLUSION: The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.

  18. Chow NK, Harun SN, Wong EJ, Low LL, Sheikh Ghadzi SM, Khan AH
    Br J Clin Pharmacol, 2021 10;87(10):3756-3765.
    PMID: 33608883 DOI: 10.1111/bcp.14783
    AIMS: Efavirenz is still widely used as the preferred first-line antiretroviral agent in middle- and low-income countries, including Malaysia. The efavirenz population pharmacokinetic profile among HIV-positive smokers is still unknown. We aimed to assess the association of smoking with efavirenz and the differences in HIV clinical outcomes.

    METHODS: A total of 154 stable HIV-positive patients on efavirenz in northern Malaysia were recruited with a sparse sampling for this multicentre prospective cohort study. The association between smoking and efavirenz pharmacokinetic parameters was determined using the nonlinear mixed-effect model. A mixture model of clearance was adopted to describe the metaboliser status because genetic data are unavailable. The effect of smoking on HIV clinical markers (CD4, CD4/CD8 ratio and viral blips) for at least 2 years after the antiretroviral initiation was also investigated.

    RESULTS: Our data were best fitted with a 1-compartment mixture model with first-order absorption without lag time. Smoking significantly associated with higher clearance (β = 1.39; 95% confidence interval: 1.07 to 1.91), while weight affected both clearance and volume. From the mixture model, 20% of patients were in the slow clearance group, which mimic the genotype distribution of slow metaboliser. An efavirenz dose reduction is not recommended for smokers ≥60 kg with normal metabolism rate. Smoking significantly associated with slower normalisation of CD4 and CD4/CD8 ratio.

    CONCLUSIONS: HIV-positive smokers presented with significantly higher efavirenz clearance and unfavourable clinical outcomes. Close monitoring of adherence and clinical response among smokers is warranted.

  19. Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, et al.
    J Psychoactive Drugs, 2018 03 20;50(3):266-274.
    PMID: 29558272 DOI: 10.1080/02791072.2018.1443234
    Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p 
  20. Yaghi AR, Shaheed HS, Harun SN, Hyder Ali IA, Khan AH
    Adv Respir Med, 2022 Nov 14;90(6):467-482.
    PMID: 36412638 DOI: 10.3390/arm90060054
    BACKGROUND: Multidrug resistance TB (MDR-TB) has emerged as a public health issue worldwide, and the mortality rate is worrying. Therefore, this study was conducted to investigate the factors related to MDR-TB occurrence and the survival experience of TB patients.

    METHODS: A retrospective cohort study was conducted at Hospital Pulau Pinang in Malaysia. Medical records of active TB patients from 2014-2018 were reviewed. Cox regression was used to identify the factors associated with MDR-TB development and mortality among TB patients.

    RESULTS: The patients had a mean age of 48.84 ± 16.713 years, and a majority of the Chinese race (46.4%). Out of 351 TB patients, 325 (92.6%) were drug-susceptible TB, and 26 (7.4%) were diagnosed with MDR-TB. Among drug-susceptible TB patients, 245 (75.4%) achieved successful outcomes, and 73 (22.5%) passed away. In multivariable Cox regression, drug addiction, levels of white blood cells, urea, platelets, and albumin were significantly associated with death. Relapsed TB, alcohol consumption, and being single were significant risk factors for MDR-TB development.

    CONCLUSION: Patients achieved a success rate of 75.4%, which is encouraging but still far below the WHO target (at least an 85% success rate) and has room for further improvement.

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