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   Table of Contents - Current issue
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November 2020
Volume 12 | Issue 6 (Supplement)
Page Nos. 657-934

Online since Thursday, November 5, 2020

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REVIEW ARTICLE  

Gender differences on methadone maintenance treatment outcome among patients with opioid use disorder: A systematic review p. 657
Mohemmad Redzuan Mohemmad Rizal, Amer Hayat Khan, Sabariah Noor Harun, Zaiton Saleh
DOI:10.4103/jpbs.JPBS_253_19  
Objectives: The objective of this study was to review the significant differences of MMT outcomes related to drug use behavior, health status, and social behavioral functioning between genders. Materials and Methods: A search of publication was conducted in PubMed/MEDLINE, Embase, CINAHL, PsycINFO, and Scopus database. Two reviewers independently screened the titles, abstracts, and keyword use for the search. Inclusion of studies was based on randomized controlled trials (RCTs) or observational studies that report the difference of opioid addiction treatment outcomes between genders. Any conflict between the two reviewers was resolved through discussion and consensus. The systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO with a registration number CRD42019116261. Results: A total of 25 studies were evaluated as part of qualitative synthesis. The review resulted in three main themes, which are (1) improving well-being and methadone-related outcome (five subthemes), (2) impact on social and behavioral (four subthemes), and (3) illicit drug use pattern–related behavior (four subthemes). Conclusion: This review will highlight how men and women differ in methadone treatment outcomes for further application and improvement in the clinical setting.
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RESEARCH ARTICLES Top

Plasma Concentrations of Pro-inflammatory Cytokine IL-6 and Antiinflammatory Cytokine IL-10 in Short- and Long-term Opioid Users with Noncancer Pain p. 663
Hussam Mizher, Che Suraya Zin, Abul Bashar Helal Uddin, Abdul Hadi Mohamed, Tan H Ling, Munira Izzat
DOI:10.4103/jpbs.JPBS_13_20  
Introduction: Little is known whether the duration of opioid use influences the concentrations of pro- and anti-inflammatory cytokines. Objectives: This study examined the plasma concentration of pro-inflammatory cytokine, interleukin 6 (IL-6), and anti-inflammatory cytokine, interleukin 10 (IL-10), in short-, and long-term opioid users with noncancer pain. Materials and Methods: Adult patients with opioid therapy for noncancer pain were recruited from pain clinics at two tertiary hospital settings in Malaysia between February 2016 and March 2017. They were stratified into short- or long-term users based on opioid prescriptions ≥ 90 days per year. A 10 mL blood sample was taken for the analysis of plasma concentrations of IL-6 and IL-10 and were quantified using a highly sensitive multiplex assay. Results: Of 38 patients recruited, 24% (n = 9/38) and 76% (n = 29/38) were respectively short- and long-term opioid users. Short-term use of opioid was associated with higher levels of IL-6 (mean ± SD, 173.9 ± 13.7 pg/mL) and IL-10 (50 ± 5.8 pg/mL), whereas long-term use of opioids was associated with lower levels (no significant difference) of both cytokines IL6 (125 ± 16.1 pg/mL) and IL10 (41.3 ± 6.7 pg/mL). There was strong correlation between IL-6 and IL-10 within the same group (r² = 0.72, P < 0.05) and (r² = 0.76, P < 0.05) for short- and long-term users, respectively. Conclusion: The duration of opioid use may modulate the level of pro-inflammatory cytokines in which it was higher in short-term use and lower in long-term use, but the effect of pain relief was similar as both cytokines were well correlated.
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A bibliometric analysis of opioid in Malaysia p. 667
Che Suraya Zin, Nor Asma Diyana Abdullah, Noorul Atiqah Ramli, Noorsyahiruh Khadir, Nor Shahfiza Zain, Nor Fatin Rosley, Siti Halimah Bux
DOI:10.4103/jpbs.JPBS_283_19  
Opioid analgesics have been widely used for the treatment of pain. In USA, it was reported an increase in opioid prescribing is parallel with the increase of opioid use disorders such as misuse, abuse, and opioids overdose-related death. Little is known about the opioid situation and its related research in Malaysia. Therefore, this bibliometric study provided an overview on the productivity of opioid research in Malaysia. All published articles on opioid research in Malaysia from 2006 to 2018 were included, where they were retrieved from online databases. Then, the data were analysed, presented and discussed using standard bibliometric indicators, such as growth of publications, number of citation journals, geographical distribution, and issues addressed in the publications. Total of 78 research articles on opioids published between 2006 and 2018 were identified. The relative growth rate (RGR) of publications during the study period was 12.24%. The most common issue studied was the methadone maintenance therapy. Most articles were published in the indexed journals (98.72%) and the predominant journal was the Drug and Alcohol Dependence (11.54%). The article on buprenorphine and naltrexone reported the highest citations of 85. It can be concluded that research evaluating opioids in pain management particularly in patients with non-cancer pain in Malaysia is limited and requires further exploration.
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ORIGINAL ARTICLES Top

The development and assessment of modified Fagerstrom test for nicotine dependence scale among Malaysian single electronic cigarette users p. 671
Aziz Ur Rahman, Mohamad Haniki Nik Mohamed, Shazia Jamshed, Syed Mahmood, Muhammad Ahsan Iftikhar Baig
DOI:10.4103/jpbs.JPBS_245_19  
Background: The Fagerstrom test for nicotine dependence (FTND) is the most widely used scale for assessing nicotine dependence on conventional tobacco cigarettes (TCGs). But the FTND does not evaluate the subject’s nicotine dependence to electronic cigarette (EC). Objective: The aim of this study was to develop and assess an equivalent modified FTND scale that measures the nicotine dependency via EC. Materials and Methods: The investigator developed the equivalent modified FTND scale that scores identical to the original scale, that is, 0–10. The developed scale piloted among 15 EC single users, that is, use only EC verified by carbon monoxide (CO) level of <8 ppm. The assessment of the scale was done among 69 EC single users and observed for 1 year to determine their nicotine status. Results: The modified scale revealed an acceptable Cronbach α value of 0.725. Further test–retest reliability of the scale showed a satisfactory Spearman’s rank correlation coefficient value of 0.730 (P > 0.05). A 1-year observation showed that of 69 single users, 11 single users completely stopped nicotine intake, 24 remained as EC single users, 15 shifted to dual-use, and 19 relapsed to TCG. Surprisingly, the EC users who completely stopped nicotine intake after 1 year had a low average nicotine dependence value of 3 that was measured by the modified FTND scale at the baseline. Conclusion: The modified FTND scale precisely identifies the physical dependence to nicotine via EC. Therefore, as per this study results the modified FTND scale can be applied in any EC-related studies to assess nicotine dependency via EC.
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Molecular docking study of naturally derived flavonoids with antiapoptotic BCL-2 and BCL-XL proteins toward ovarian cancer treatment p. 676
Mohd Faiz Abd Ghani, Rozana Othman, Noraziah Nordin
DOI:10.4103/jpbs.JPBS_272_19  
The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin–Bcl-xl protein complex (−8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from –8.0 to –8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin–Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers.
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Healthcare professional attitude and social support: how do they affect the self-esteem of physically disabled people? p. 681
Farhana Fakhira Ismail, Zaswiza Mohamed Noor, Siti Mariam Muda, Norny Syafinaz Ab Rahman
DOI:10.4103/jpbs.JPBS_383_19  
Context: The attitude of healthcare professionals and social supports give big influence toward self-esteem of physically disabled people. Aims: To explore how impairments could affect the self-esteem of physically disabled people and how healthcare professionals and social support boost their self-esteem. Materials and Methods: This study was conducted qualitatively whereby face-to-face interviews were conducted among 10 participants with physical disabilities. Participants were recruited from two rehabilitation centres in Kuantan, namely Community-based rehabilitation and rehabilitation, occupational therapy, and physiotherapy of public hospital in Kuantan. Interviews were conducted using the developed interview guide that explored on the disabled peoples’ self-esteem and motivation, feelings toward attitude of the healthcare professionals, and satisfaction toward the physical, services, and social support from the healthcare professionals. Thematic analysis was done to identify the themes emerged from the interview transcripts. Results: Five males and five females with age ranging from 31 to 58 years were interviewed. Five are still working or studying post impairments. Participants claimed being low self-esteem resulted from negative perception from the society, issue of rejection, being discriminated, and difficulty in getting support from the society. Most of the participants asserted that they gained their motivation and self-esteem due to the continuous support from various groups, such as their spouses, family members, colleagues, employers, and healthcare professionals. Conclusions: Despite heavy workload and stressful working environment, positive attitude showed by the healthcare professionals is highly praised. Hence, this will indirectly improve the self-esteem, motivation, and rehabilitation progress of physically disabled people.
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Exploring medications for hypertension advertised online: A qualitative study in Indonesia p. 691
Riana Rahmawati
DOI:10.4103/jpbs.JPBS_259_19  
Introduction: Patients with hypertension often self-medicate and are increasingly purchasing their medications online. This study aimed to identify the medications and products used for hypertension offered by Indonesian online marketplaces and the availability of prescription-only antihypertensive medication on these platforms. Materials and Methods: This qualitative document analysis comprehensively assessed three online marketplaces in Indonesia in May 2019. Five top products in each online marketplace were identified and reviewed. An in-depth analysis was performed to obtain detailed information about the products (e.g., ingredients), indications, and customers’ comments. Selected antihypertensive medications (captopril, amlodipine, and valsartan) were searched for. The data were analyzed thematically. Results: The search results showed that more than 5000 products were available in each online marketplace and that all of the top products offered in these platforms were traditional medicines. Some products specifically claimed to be effective for lowering blood pressure (e.g., “the solution for hypertension without complications”). Morinda citrifolia (noni) and Allium sativum (garlic) were ingredients found in all three platforms, mainly in combination with other herbal medicines. The prescription-only antihypertensive medications offered and could be purchased through online marketplaces reviewed. However, information about dosage forms, indications, side effects, and contraindications of these medications was rarely provided on these platforms. Conclusion: Indonesian online marketplaces provide a wide range of products for the treatment of hypertension, particularly traditional medicines. Given the increasing trends of online shopping, providing objective and adequate information for customers is essential. Regulations for the purchase of prescription-only medicines, such as antihypertensive medications, should be strengthened.
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Cross-sectional Retrospective Study on Paracetamol Post Infants’ Vaccination in Malaysia p. 696
Nurain Suleiman, Siti Hadijah Shamsudin, Razman Mohd Rus, Shamsul Draman
DOI:10.4103/jpbs.JPBS_255_19  
Introduction: Practice of dispensing paracetamol (PCM) in post infants’ vaccination remains debatable in Malaysia as the administration of PCM postvaccination in infants was found to cause the vaccine to be less effective, thus requiring appropriate regulation measures. Objective: This research aimed to investigate the prevalence of adverse events following immunization (AEFI) with/without PCM to be prescribed post infants’ vaccination in Malaysia (possible associated factors: age, types and stages of vaccination, concomitant vaccines and drugs, and/vitamins). Materials and Methods: A retrospective cross-sectional study was conducted from 2011 to 2017. The AEFI was extracted from Quests 2, 3, and 3+ System of National Pharmaceutical Regulatory Agency (NPRA). The population of vaccinated infants was obtained from the Ministry of Health (MOH) Malaysia official website. The AEFI data were further categorized into (i) AEFI with possibility for PCM to be prescribed, and (ii) AEFI with no possibility for PCM to be prescribed. The data were analyzed using Microsoft Excel 2013, Portland, USA simple and multiple logistic regression tests, Statistical Package for the Social Sciences (SPSS) software programme, version 22.0 (IBM), New York, USA. Result: Various AEFI cases (359 infants) were reported. DTaP/Hib/IPV and measles–mumps–rubella (MMR) showed higher prevalence of AEFI with/without PCM to be prescribed post infants’ vaccination cases per 100,000 population (2.07 and 2.21, respectively) than other types of vaccinations. DTaP/Hib/IPV (2 months) vaccination showed the highest value (3.00) among other age groups. Backward elimination presented DTaP/Hib/IPV (3–4 months) (95%CI; 0.231, 0.899%; P = 0.023) was the possible associated factor. Hepatitis B (1–5 months), DTaP/Hib/IPV (3–4 months), DTaP/Hib/IPV (5–12 months), concomitant vaccines as well as concomitant drugs and/ vitamins were the identified potential cofounders. Conclusion: Prescribing and dispensing of PCM post infants’ vaccination may be confined to DTaP/Hib/IPV (2–4 months) and 12 months MMR groups.
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Screening of electrospray-operating parameters in the production of alginate–royal jelly microbeads using factorial design p. 703
Mohd Rus Shaiqah, Haris Muhammad Salahuddin, Abu Yazid Anis Afiful Huda, Mohamad Izzuddin, Noor Ismadi Muhammad Nur Shafiq, Mohd Azlan Nur Hakimah, Rahman Siti Radziah, Abd Almonem Doolaanea, Adina Anugerah Budipratama
DOI:10.4103/jpbs.JPBS_249_19  
Introduction: Royal jelly (RJ) has been consumed as food or as a supplement because of its high nutritional and medicinal values. A fresh harvested RJ is yellowish to whitish in color and contains proteins, free amino acids, lipids, vitamins, and sugar. Without proper storage conditions, such as at 4°C, the color of RJ changes to much darker yellow and produces a rancid smell. To prolong its shelf life, RJ is usually mixed with honey. Alginate, a natural and edible polymer derived from seaweed, is commonly used to encapsulate drugs and food due to its ability to form gels by reacting with divalent cations. However, there is a lack of research on the microencapsulation of RJ in alginate using electrospray. The electrospray technique has the advantage in producing consistent size and shape of alginate microbeads under optimum parameters. Aim: This research aimed to optimize electrospray-operating parameters in producing alginate–RJ microbeads. Materials and Methods: Optimization of alginate–RJ microbeads electrospray parameters was carried out using 24 factorial design with three center points (19 runs). The studied parameters were flow rate, high voltage, nozzle size, and tip-to-collector distance, whereas the responses were particle size, particle size distribution, and sphericity factor. The responses of each run were analyzed using Design-Expert software. Results: Nozzle size is a significant parameter that influences the particle size. Flow rate is a significant parameter influencing the sphericity factor. Conclusion: Screening of the electrospray-operating parameters paves the way in determining the significant parameters and their design space to produce consistent alginate–RJ microbeads.
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Research on nonsteroidal anti-inflammatory drugs in Malaysia: A bibliometric analysis p. 707
Che Suraya Zin, Norzaini Ros Nozid, Amalia Athirah Razak, Siti Nuraisyah Hashim, Nur Aimi Mazlan, Norhayati Daud, Siti Halimah Bux
DOI:10.4103/jpbs.JPBS_282_19  
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common analgesics used for pain relief. Adverse effects of NSAIDs range from gastrointestinal tract disturbances to increased risk of bleeding, renal injury, and myocardial infarction. In Malaysia, the research productivity of NSAIDs is not well explored. Objective: This study examined research productivity of NSAIDs in Malaysia. Materials and Methods: This bibliometric study included all published research articles on NSAIDs from 1979 to 2018, which were conducted in Malaysia. The search databases such as Google Scholar, PubMed, ScienceDirect, and Scopus were used. Search terms included NSAIDs and specific drug names such as ibuprofen, celecoxib, and naproxen. Growth of publication, authorship pattern, citation analysis, journal index, type of studies, and geographical distribution of institutions publishing articles on NSAIDs were measured. Results: Overall, 111 articles were retrieved from 1979 to 2018. The annual productivity of articles throughout the study fluctuated in which the highest productivity was in 2018, 12.61% (n = 14). Majority of articles were multiple authored, 99.10% (n = 109), and University of Science Malaysia (USM) produced the highest number of articles (30 articles). Most of the articles were International Scientific Indexing-indexed, 52.25% (n = 58), and the main issue studied in most of the articles was the drug formulation of NSAIDs. Conclusion: The growth of NSAID research in Malaysia was slow, and the majority of research involved laboratory studies. Clinical studies evaluating the clinical outcomes of NSAIDs in patients, particularly using large healthcare databases are still lacking.
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Evaluation of antinociceptive profile of chalcone derivative (3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (DMPF-1) in vivo p. 711
Noor Azlina Abu Bakar, Mohd Roslan Sulaiman, Nordin Lajis, Mohd Nadeem Akhtar, Azam Shah Mohamad
DOI:10.4103/jpbs.JPBS_344_19  
Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties. Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivoMaterials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets. Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test. Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.
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Perceived safety and effectiveness of electronic cigarettes among Malaysian adults and public support for regulations p. 718
Samsul Draman, Norny Syafinaz Ab Rahman, Mohamad Haniki Nik Mohamed, Jamalludin Ab Rahman, Mira Kartiwi
DOI:10.4103/jpbs.JPBS_384_19  
Context: Electronic cigarettes have been used as a harm reduction method toward tobacco cessation. Malaysian government has enforced a strict policy to regulate the sale of electronic cigarette products because its liquid contains nicotine. Aims: This study aimed to explore the general public’s perception toward electronic cigarette use. Public support toward electronic cigarette regulation was also examined. Settings and Design: This was a Malaysian population-based survey. Materials and Methods: Data were obtained from the National E-Cigarette Survey (NECS) 2016, which used a multistage stratified cluster sampling household survey representing all Malaysian adults aged 18 years old. A cross-sectional survey was conducted among a total of 4288 adults. Statistical Analysis Used: Descriptive and logistic regression analysis. Results: Majority were aged 25–44 years old (44%), completed at least secondary education (69%), of Malay ethnicity (73%), and married (68%). Majority (88.1%) have never used electronic cigarette. A quarter (25.5%) perceived electronic cigarette helps people quit cigarette smoking, whereas 20.3% perceived electronic cigarette helps people to maintain cigarette abstinence. Approximately 85% believed that electronic cigarette use does not help in improving breathing and coughing. Majority (91.8%) disagreed that electronic cigarettes should be allowed in places where tobacco smoking is banned. Thus, 63.4% agreed that electronic cigarette should be banned completely rather than regulated. Conclusion: Majority of general public had negative perception about electronic cigarette use.
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Comparison of the clinical outcomes between short-term and long-term opioid users with noncancer pain at pain clinics p. 728
Asween R Sani, Che Suraya Zin
DOI:10.4103/jpbs.JPBS_284_19  
Introduction: The clinical use of opioids for long-term for noncancer pain indications remains a controversy. More studies are needed for evidence-based guidelines in noncancer pain management involving opioids. The primary objective of this study was to investigate the clinical outcomes of the short-term and long-term opioid use among patients with noncancer pain. Materials and Methods: This is a retrospective cross-sectional study where patients (aged ≥18 years) with noncancer pain treated with opioids were recruited from three pain clinics in Malaysia. Data on patients’ opioid use were collected from prescription records. The individual days covered with opioids per patient were calculated and based on this, patients were classified as short-term (<90 days) or long-term (≥90 days) opioid user. Outcome measures included pain intensity and pain interference with daily activities assessed by Brief Pain Inventory – Short Form (BPI-SF), health-related quality of life (HRQoL) assessed by 36-Item Short Form Health Survey version 2 (SF-36v2). These measures were compared between short-term and long-term opioid users. Results: Of the 61 noncancer pain patients recruited, 49.2% (n = 30/61) were short-term and 50.8% (n = 31/61) were long-term opioid users. There were no statistically significant differences in the mean scores of pain intensity, pain interference with daily activities, and HRQoL between short-term and long-term opioid users in this study. Conclusion: Findings of this study imply that long-term opioid therapy does not provide significant pain relief or improvement in patients’ functional capability and HRQoL in noncancer pain patients. Future prospective studies with larger sample sizes are needed to support the findings of this study.
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Gel potential of red onion (Allium cepa L.) ethanol extract as antifungal cause tinea pedis p. 733
Erza Genatrika, Elza Sundhani, Mayang I Oktaviana
DOI:10.4103/jpbs.JPBS_256_19  
Introduction: Tinea pedis is a dermatophyte infection of human feet, especially between the fingers and soles of the feet. Tinea pedis is caused by a fungal infection of Trichophyton rubrum. Red onion is one of the spices that has been widely known by the community and used as a traditional medicine in the prevention of fungus. The objective of this research was to determine the antifungal activity of gel produced from an extract of red onion on T. rubrum. Materials and Methods: The gel was formulated with various concentration of red onion, FI with a concentration of extract (5%), F2 (7.5%). and F3 (12.5%). Each formula tested the physical characteristics and antifungal activity toward T. rubrum. The antifungal activity was determined by the agar well-diffusion method using Saboround Dextrose Agar plates. Furthermore, the antifungal activities were assessed by the presence or absence of inhibition zones after the plates were incubated at 28oC for 7 days. Results: F3 has the greatest inhibitory power than F1 and F2 (P < 0.05). Then, F3 has the same inhibitory power as a positive control (P > 0.05). Discussion: All gel understudy at various concentrations of red onion was formulated in gel-exhibited antifungal activity. Antifungal activity of red onion occurred because it contained allicin. Therefore, the researchers can use these gels as a natural antifungal in the healing of tinea pedis caused by T. rubrum. Conclusion: The gel from an extract of red onion showed significant antifungal activity against T. rubrum.
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Intraperitoneal antibiotic utilization among continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis at a tertiary hospital setting in Malaysia p. 737
Mastura Ahmad, Che Suraya Zin, Ab Fatah Ab Rahman
DOI:10.4103/jpbs.JPBS_298_19  
Introduction: Patients receiving continuous ambulatory peritoneal dialysis (CAPD) are commonly associated with peritonitis. However, little is known about the utilization of antibiotics for the treatment of peritonitis in these patients. Objectives: This study aimed to evaluate the patterns of intraperitoneal (IP) antibiotic utilization for the treatment of peritonitis in CAPD patients. Materials and Methods: This is a retrospective study conducted at a tertiary hospital setting in Malaysia. Medical records of CAPD patients who were diagnosed with peritonitis and registered with National Kidney Registry from 2013 to 2018 were reviewed. Types of antibiotics used and its dose and duration were recorded and reported using the anatomical therapeutic chemical/defined daily dose (ATC/DDD) system. Results: A total of 105 peritonitis episodes were recorded from 72 patients. The most common first-line empirical antibiotic combinations used were ceftazidime/cefazolin (40%, n = 42), followed by cefepime/cefazolin (30.5%, n = 32) and ceftazidime/cloxacillin (25.7%, n = 27). The definitive therapy for culture-proven CAPD-related peritonitis (CAPD-P) showed that vancomycin was the most frequently prescribed antibiotic (31.7%, n = 26/82), followed by amikacin (14.6%, n = 12/82), meropenem (11%, n = 9/82) and ampicillin (11%, n = 9/82). Ciprofloxacin was among the least prescribed definitive antibiotics for CAPD-P (2.4%, n = 2/82) but the DDD/100 patient-days estimates showed that it had the highest therapeutic intensity. Conclusion: There are various IP antibiotics used for CAPD-P and the most common empirical therapy was the combination of ceftazidime and cefazolin while vancomycin is predominantly used for definitive therapy. Future studies to evaluate the clinical outcomes of the antibiotic use should be conducted to have a better insight on the efficacy of the peritonitis treatment.
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Formulation of effervescent granule from robusta green coffee bean ethanolic extract (Coffea canephora) p. 743
Hilda Maysarah, Irma Sari, Meutia Faradilla, Kevin Kwok
DOI:10.4103/jpbs.JPBS_258_19  
Introduction: Robusta coffee (Coffea canephora) is one of the many crops cultivated in Aceh, and at present is only being used as a drink. Research has shown the potential of many pharmacological uses for coffee, including its use as a remedy to treat diabetes. Effervescent granules are one of the oral dosage forms that can not only mask the unpleasant taste of bioactive substances, but also have a high aesthetic value and can contain relatively large doses of bioactive substances. Previous research has shown that ethanolic extract of robusta green coffee beans at 100 mg/kg body weight (BW) rat yielded the highest percentage of glucose reduction. On the basis of that research, the dosage was used in this study to be formulated into effervescent granule. Aims: This study aimed to find the best formulation of effervescent granules preparation using various concentrations of effervescent salt that meets the general requirements of effervescent dosage forms. The concentrations of citric acid, tartaric acid, and sodium bicarbonate used in sequence were 7.35%, 14.7%, and 25% (F1); 8.08%, 16.17%, and 27.5% (F2); and 8.82%, 17.64%, and 30% (F3), respectively. Robusta green coffee beans were extracted using the maceration method. Results: Secondary metabolite screening of extract showed that it contained alkaloid, saponin, phenolic, and flavonoid metabolites. Effervescent granules were evaluated and F1 and F2 did not qualify the flowability standard of the granules, whereas F3 qualified in all the evaluation standards. Conclusion: On the basis of these results, F3 produced the best effervescent granules that met the general standards of the effervescent dosage forms.
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The prevalence of prescribing medications associated with geriatric syndromes among discharged elderly patients p. 747
Muhammad Eid Akkawi, Nor Hidayah Mohd Taufek, Azfar Diyana Abdul Hadi, Nik Nur Nadia Fatin Nik Lah
DOI:10.4103/jpbs.JPBS_305_19  
Introduction: A geriatric syndrome is a group of signs and symptoms that occur in older people and do not fit into a discrete disease. Several medications were reported to be associated with the incidence of geriatric syndromes. Objective: The objective of this study was to investigate the prevalence and pattern of medications associated with geriatric syndromes (MAGSs) among the discharged elderly patients (≥65 years old). Materials and Methods: This is a cross-sectional study that was conducted at a Malaysian teaching hospital from October to December 2018. The discharge medications of geriatric patients were reviewed to identify MAGSs using Beers criteria, Lexicomp drug information handbook, and the United States Food and Drug Administration (USFDA) drug inserts. Chi-square test was used to compare MAGS prescribed between categories. Spearman’s rank-order correlation was used to test the correlation between the presence of MAGS and the number of discharge medications. A binomial logistic regression was applied to determine the predictors of prescribing MAGSs. Results: A total of 400 patients (mean ± standard deviation [SD] age, 72.0 ± 5.0 years) were included, and 45.3% of them were females. The most common diseases were hypertension followed by diabetes mellitus. The mean ± SD number of discharge medications per patient was 4.2 ± 2.5. The MAGSs were prescribed in 51.7% of the patients, and 54 patients were discharged with more than one MAGSs. The most commonly prescribed MAGSs were opioid analgesics, vasodilators, and β-blockers, which are associated with falls, depression, and delirium. Polypharmacy was found in 138 patients, and it was significantly associated with the presence of MAGSs (P < 0.001). No significant differences were found in prescribing MAGSs based on the patients’ gender, race, and age. Conclusion: The prescribing of MAGSs occurred in half of the discharged elderly patients. Physicians should be aware of the medications that are associated with special side effects in the elderly patients, and should switch to safer alternatives when possible.
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Rapid discrimination of halal and non-halal pharmaceutical excipients by Fourier transform infrared spectroscopy and chemometrics p. 752
Nurul F A Razak, Roziah H Abd Karim, Jamia A Jamal, Mazlina M Said
DOI:10.4103/jpbs.JPBS_364_19  
Introduction: The appendage of “halal” to a product is not just a guarantee that the product is permitted for Muslims, but it has also become favorable lifestyle choice globally. However, the expansion of halal pharmaceutical market was hindered by lack of global halal standards for pharmaceutical ingredients and product integrity analytical methodology. Objective: This work aimed to explore the possibility of using Fourier-transform infrared (FTIR) spectroscopy and chemometrics to develop multivariate models to authenticate the “halal-ity” of pharmaceutical excipients with controversial halal status (e.g., magnesium stearate). Materials and Methods: The FTIR spectral fingerprints of the substance were used to build principal component analysis (PCA) models. The effects of different spectral pretreatment processes such as auto-scaling, baseline correction, standard normal variate (SNV), first, and second derivatives were evaluated. The optimization of the model performance was established to ensure the sensitivity, specificity, and accuracy of the predicted models. Results: Significant peaks corresponding to the properties of the compound were identified. For both bovine and plant-derived magnesium stearate, the peaks associated can be seen within the regions 2900 cm-1 (C–H), 2800 cm-1 (CH3), 1700 cm-1 (C=O), and 1000–1300 cm-1 (C–O). There was not much difference observed in the FTIR raw spectra of the samples from both sources. The quality and accuracy of the classification models by PCA and soft independent modeling classification analogy (SIMCA) have shown to improve using spectra optimized by first derivative followed by SNV smoothing. Conclusion: This rapid and cost-effective technique has the potential to be expanded as an authentication strategy for halal pharmaceuticals.
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Medication adherence assessment among patients with type 2 diabetes mellitus treated polytherapy in indonesian community health center: A cross sectional-study p. 758
Nora Wulandari, Maifitrianti Maifitrianti, Faridlatul Hasanah, Sri Atika, Risa Dini Putri
DOI:10.4103/jpbs.JPBS_257_19  
Background: Type 2 diabetes mellitus (T2DM) is a chronic disease where most of the patients usually need polytherapy. This could affect their medication adherence (MA). However, other complex factors may also associate with MA, which are important to identify. Aim: The purpose of this study was to evaluate the MA of patients with T2DM who received polytherapy and to identify other factors that can affect the MA. Materials and Methods: This was a cross-sectional study conducted in seven community health centers in Jakarta with HbA1C representing their MA level. Poor controlled blood glucose with Hemoglobin A1C (HbA1C) of ≥7% is indicated to have low MA. All characteristics were collected to identify factors that are potentially associated with low MA. The univariate analysis tests were used to analyze factors that potentially associate with low MA. Multiple logistic regression analysis was performed in the factors to find their relationship with low MA. Results: The study obtained 143 patients with a female dominance (67.8%) and mean ± standard deviation (SD) age of 59.53 ± 9.251 years. Approximately 75.5% of the patients had low MA (HbA1C ≥ 7). Univariate analysis found that duration of T2DM significantly (P = 0.047) related to MA, where patients with T2DM of less than or equal to 5 years tended to have low MA. Logistic regression showed that patients with T2DM less than or equal to 5 years (P = 0.015, odds ratio = 1.206, 95% confidence interval = 1.216–8.014) were associated with low MA. Conclusion: Patients with the duration of T2DM less than or equal to 5 years surprisingly were susceptible to have low MA. Low MA was not affected by polytherapy.
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Docking study on anti-HIV-1 activity of secondary metabolites from Zingiberaceae plants p. 763
Muhammad Sulaiman Zubair, Saipul Maulana, Agustinus Widodo, Alwiyah Mukaddas, Ramadanil Pitopang
DOI:10.4103/jpbs.JPBS_261_19  
Introduction: Human immunodeficiency virus type-1 (HIV-1) that causes acquired immunodeficiency syndrome (AIDS) has become a worldwide health problem today. There are approximately 30 anti-HIV-1 drugs that have been used in the treatment of AIDS. However, effective anti HIV-1 agents with less side affect and high inhibition potency are still in demand. Objective: The objective of this study was to identify the potential compounds from Zingiberaceae plants that might be active as anti-HIV-1 by molecular docking. Materials and Methods: Molecular docking simulation was performed by using AutoDock 4.2 on Linux operation system. Docking protocol was validated by using root mean square deviation (RMSD) value using redocking and cross-docking methods. The reported metabolites from Zingiberaceae plants were docked on HIV-1 protease, integrase, and reverse transcriptase protein enzymes. Results: The docking result showed that the genera of Zingiber, Etlingera, Alpinia, Hedychium, and Boesenbergia have potential metabolites that inhibit HIV protease, integrase, and reverse transcriptase enzymes by possessing lower docking energy than native ligand of amprenavir, raltegravir, and nevirapine. Among the metabolites, noralpindenoside B and alpindenoside A from Alpinia densespicata inhibited protease enzymes with the lowest docking energy of -18.02 and -17.90 kcal/mol, respectively. Meanwhile, panduratin E from Boesenbergia pandurata Roxb. and 5α,8α-epidioxyergosta-6,22-dien-3β-ol from Etlingera elatior showed the lowest docking energy on integrase protein with docking energy of -11.97 and -11.41 kcal/mol, respectively. Pahangensin A from Alpinia pahangensis Ridley showed the lowest docking energy on reverse transcriptase enzyme with docking energy of -13.76 kcal/mol. Conclusion: The docking molecular study has identified the possible potential compounds from Zingiberaceae plants that might be used for anti-HIV-1 treatment. So, this study suggested further isolation and purification of the predicted compounds.
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Clinacanthus nutans standardized fraction arrested SiHa cells at G1/S and induced apoptosis via upregulation of p53 p. 768
Nik Aina Syazana Nik Zainuddin, Hussin Muhammad, Nik Fakhuruddin Nik Hassan, Nor Hayati Othman, Yusmazura Zakaria
DOI:10.4103/jpbs.JPBS_262_19  
Introduction: Cervical cancer is a leading cause of death in women. Current cancer treatment comes with side effects. Clinacanthus nutans has been known traditionally to treat cancer. This study was aimed to characterize C. nutans standardized fraction (SF1) and to investigate its anticancer mechanism against SiHa cells. Materials and Methods: SF1 was produced by optimized methodology for bioassay-guided fractionation. Fourier transform infrared (FTIR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS) were carried out to characterize the SF1. SF1 was screened for cytotoxicity activity toward HeLa, SiHa, and normal cells (NIH) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The anticancer mechanism of SF1 was evaluated toward SiHa cells, which showed highest cytotoxicity toward SF1 treatment. The mechanism includes cell cycle progression and protein expression, which was detected using specific antibody-conjugated fluorescent dye, p53-FITC, by flow cytometry. Results: Major constituents of SF1 were alkaloids with amines as functional group. SF1 showed highest cytotoxic activity against SiHa (half-maximal inhibitory concentration [IC50] < 10 µg/mL) compared to HeLa cells. Cytoselectivity of SF1 was observed with no IC50 detected on normal NIH cells. On flow cytometry analysis, SF1 was able to induce apoptosis on SiHa cells by arresting cell cycle at G1/S and upregulation of p53 protein. Conclusion: SF1 showed anticancer activity by inducing apoptosis through arrested G1/S cell cycle checkpoint–mediated mitochondrial pathway.
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Evaluation and comparison of Trachyspermum ammi seed extract for its anti-inflammatory effect p. 777
Adeel Aslam, Ahmed Nokhala, Sohaib Peerzada, Shoaib Ahmed, Tanveer Khan, Mohammad Jamshed Siddiqui
DOI:10.4103/jpbs.JPBS_243_19  
Aims and Objectives: The present study was aimed to evaluate the antiinflammatory effect of different seed extracts of Trachyspermum ammi at different doses. Materials and Methods: Three different seed extracts were prepared through Soxhlet extraction method by using n-hexane, chloroform and methanol solvents. Acute toxicity test performed at dose of 400 mg/ kg, 800 mg/kg, 1600 mg/kg and 3200 mg/kg. Two different strengths of seed extracts (minimum therapeutic dose of 500 mg/kg and maximum therapeutic dose of 1000 mg/kg) were given to Wistar rats to measure anti-inflammatory activity through Carrageenan induced paw edema method. Results: The standard drug diclofenac sodium was (percentage of inhibition of paw edema 29.68%) more effective as compared to test drug. When efficacy of all extracts compared with each other, n-hexane extract showed more anti-inflammatory effect (percentage inhibition of paw edema 22.21%) at maximum effective dose 1000 mg/kg. Conclusion: Seed extracts of T. ammi showed anti-inflammatory activity by potentiating the neurotransmission of GABA and also by repression glutamate receptor.
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Assessing adherence and persistence to non-vitamin K antagonist oral anticoagulants (NOACs) among patients with atrial fibrillation in tertiary-care referral centers in Malaysia p. 781
Mohammed A Kubas, Fatiha Hana Shabaruddin, Wardati Mazlan-Kepli, Nirmala Jagan, Sahimi Mohamed, Nor Ilyani Mohamed Nazar, Che Suraya Zin
DOI:10.4103/jpbs.JPBS_381_19  
Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran and rivaroxaban, are now available for stroke prevention in patients with atrial fibrillation (AF) and are often clinically preferred over vitamin K antagonists (VKAs), such as warfarin. Data describing adherence and persistence to NOACs in real-life clinical practice in Malaysia are scarce. This study aimed to assess adherence and persistence to NOACs in patients with AF in two tertiary-care referral centers: Hospital Kuala Lumpur (HKL) and Hospital Serdang (HSDG). Materials and Methods: This was a retrospective cohort study that included all patients with AF who were treated with NOACs (dabigatran or rivaroxaban) in HKL and HSDG. Data were obtained from medical records and pharmacy databases. Adherence was assessed using proportion of days covered (PDC) over a 1-year duration. High adherence was defined as PDC ≥80%. A gap of >60 days between two consecutive refills was used to define non-persistence. Result: There were 281 patients who met the inclusion criteria, with 54.1% (n = 152) male. There were 75.1% (n = 211) patients on dabigatran and others on rivaroxaban. Only 66.9% (n = 188) of patients achieved high adherence with PDC ≥80% and 69.8% (n = 196) were persistence with >60-day gap over 12 months. Adherence and persistence were both influenced by treatment center, whereas polypharmacy only influenced adherence. Conclusion: Overall adherence and persistence to NOACs were suboptimal and varied between treatment centers, potentially due to institution-specific administrative and clinical practice differences. Clinical care and outcomes can potentially be optimized by identifying factors affecting adherence and persistence and by implementing interventions to improving them.
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Influence of DRD2 polymorphisms on the clinical outcomes of opioiddependent patients on methadone maintenance therapy p. 787
Zalina Zahari, Chee Siong Lee, Muslih Abdulkarim Ibrahim, Nurfadhlina Musa, Mohd Azhar Mohd Yasin, Yeong Yeh Lee, Soo Choon Tan, Nasir Mohamad, Rusli Ismail
DOI:10.4103/jpbs.JPBS_248_19  
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.
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Knowledge, perception, and antibiotic prescribing practice in the intensive care unit: Findings from the malaysian public setting p. 804
Muhammad Azrai Rozali, Norny Syafinaz Abd Rahman, Helmi Sulaiman, Azrin Nurul Abd Rahman, Nadia Atiya, Wan Rahiza Wan Mat, Mohd Fadhil Jamaluddin, Muhd Zulfakar Mazlan, Mohd Basri Mat Nor, Mohd Shahnaz Hasan, Mohd Hafiz Abdul-Aziz
DOI:10.4103/jpbs.JPBS_266_19  
Introduction: Approach to managing infection in the intensive care unit (ICU) often varies between institutions and not many readily adapt to available local guidelines despite it was constructed to suite local clinical scenario. Malaysia already has two published guidelines on managing infection in the ICU but data on its compliance are largely unknown. Objectives: A cross-sectional survey was carried out and sent to a total of 868 specialists working primarily in the ICU. The aim of this study was to explore knowledge, perception, and the antibiotic prescribing practice among specialists and advanced trainees in Malaysian ICU. Materials and Methods: A cross-sectional survey was used, consisted of three sections: knowledge, perception, and antibiotic prescribing practice in ICU. Three case vignettes on hospital-acquired pneumonia (HAP), infected necrotizing pancreatitis (INP), and catheter-related bloodstream infection (CRBSI) were used to explore antibiotic prescribing practice. Results: A total of 868 eligible subjects were approached with 104 responded to the survey. Three hundred eighty-nine antibiotics were chosen from seven different classes in the case vignettes. All respondents acknowledged the importance of pharmacokinetic/pharmacodynamic (PK/PD) in antibiotic optimization and majority (97.2%) perceived that current dosing is inadequate to achieve optimal PK/PD target in ICU patients. Majority (85.6%) believed that antibiotic dose should be streamlined to the organisms’ minimum inhibitory concentration (MIC). In terms of knowledge, only 64.4% provided the correct correlations between antibiotics and their respective PK/PD targets. Compliance rates in terms of antibiotic choices were at 79.8%, 77.8%, and 27.9% for HAI, INP, and CRBSI, respectively. Conclusion: Malaysian physicians are receptive to use PK/PD approach to optimize antibiotic dosing in ICU patients. Nonetheless, there are still gaps in the knowledge of antibiotic PK/PD as well as its application in the critically ill, especially for β-lactams.
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Time to treatment initiation and retrospective analysis of antiretroviral therapy outcomes among HIV-positive methadone maintenance therapy clients in primary health-care centers, Kuantan, Pahang p. 810
Aida Roziana Ramlan, Nor Ilyani Mohamed Nazar, Afidalina Tumian, Norny Syafinaz Ab Rahman, Dzawani Mohamad, Mat Sharil Abdul Talib, Khairul Faizan M Zakaria, Muhammad Azzim Izuddin, Nadia Akmal Zainal Abidin, Syarifah Syafiqah T Syed Manso, Wan Nur Khairiyah Wan Hassan
DOI:10.4103/jpbs.JPBS_3_20  
Introduction: Methadone maintenance therapy (MMT) program helped to improve access to antiretroviral therapy (ART) among people who inject drugs (PWID) with human immunodeficiency virus (HIV). However, the time to treatment initiation (TTI) and outcomes of ART intervention in this population have scarcely been analyzed. Objectives: The aim of this study was to analyze the TTI and outcomes of ART among MMT clients in primary health-care centers in Kuantan, Pahang. Materials and Methods: This was a retrospective evaluation of MMT clients from 2006 to 2019. The TTI was calculated from the day of MMT enrolment to ART initiation. The trends of CD4 counts and viral loads were descriptively evaluated. Cox proportional hazard model was used to analyze the survival and treatment retention rate. Results: A total of 67 MMT clients from six primary health-care centers were HIV-positive, of which 37 clients were started on ART. The mean TTI of ART was 27 months. The clients who were given ART had a mean CD4 count of 119 cells/mm3 at baseline and increased to 219 cells/mm3 after 6 months of ART. Only two patients (5.4%) in the ART subgroup had an unsuppressed viral load. The initiation of ART had reduced the risk of death by 72.8% (hazard ratio = 0.27, P = 0.024), and they are 13.1 times more likely to remain in treatment (P < 0.01). Conclusion: The TTI of ART was delayed in this population. MMT clients who were given ART have better CD4 and viral load outcomes, helped reduced death risk and showed higher retention rates in MMT program.
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Development of nanoemulsion-based hydrogel containing andrographolide: physical properties and stability evaluation p. 816
Oktavia Indrati, Ronny Martien, Abdul Rohman, Akhmad Kharis Nugroho
DOI:10.4103/jpbs.JPBS_174_20  
Introduction: Andrographolide is a compound that shows various pharmacological activities, which can be applied topically or orally. Nanoemulsion can improve drug solubility and stability, but has limitations for topical application. Incorporation of nanoemulsion into hydrogel can increase the viscosity of the system which can prolong the drug residence time. The aim of this study was to develop andrographolide nanoemulsion-based hydrogel for topical application. Method: Andrographolide nanoemulsion was prepared using Capryol 90 as the oil, Kolliphor RH 40 as the surfactant, and propylene glycol as the cosurfactant. Droplet size and polydispersity index of the nanoemulsions were evaluated using particle size analyzer. D-optimal mixture design was employed to generate the total number of runs (formulation), and obtain the optimum formulation. Fourteen formulations of nanoemulsion-based hydrogel were prepared by incorporating nanoemulsion into the hydrogel base (1:1). Carbopol was employed as the gelling agent, whereas other excipients including propylene glycol, oleic acid, triethanolamine, methylparaben, and propylparaben were also added to produce hydrogel base. Nanoemulsion-based hydrogel was evaluated for its pH, viscosity, and physical appearance (after 8 weeks of storage). Results: The result revealed that nanoemulsion-based hydrogel containing 34.65% of carbopol, 1.35% of triethanolamine, and 9% of propylene glycol was selected as an optimum formulation which shows acceptable pH, viscosity, and physical appearance. This optimum nanoemulsion-based hydrogel has pH of 6.50 ± 0.02, and 2492.33 ± 36.91 cP of viscosity with milky white color, and smooth homogeneous texture. Conclusion: This study suggested that andrographolide can be successfully formulated into an acceptable nanoemulsion-based hydrogel.
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The COPD (chronic obstructive pulmonary disease) assessment test: Assessment of therapeutic outcomes of patients at private hospitals in yogyakarta p. 821
Chynthia Pradiftha Sari, Suci Hanifah, Rosdiana Rosdiana, Yuni Anisa
DOI:10.4103/jpbs.JPBS_302_19  
Introduction: Chronic obstruction pulmonary disease (COPD) is a chronic airflow disorder along with decreasing health status. COPD assessment test (CAT) is commonly used to assess the health status of patients and their medical results. The aim of this study was to assess the therapeutic outcomes in patients with COPD using CAT in private hospitals in Yogyakarta. Materials and Methods: This was a cross-sectional study involving 156 patients, aged >40 years who had completed the CAT questionnaire. CAT scores were categorized into four groups and consisted of eight items: cough, phlegm, chest tightness, breathlessness going up hills/stairs, activity limitations at home, confidence leaving home, sleep, and energy. The four categories were successful therapy (CAT scores <10), moderately successful CAT 10–19), less successful (CAT scores 20–30), and unsuccessful (CAT score >30). The study was conducted from April to August 2018 at two Private Hospitals in Yogyakarta followed by descriptive-analytical data processing and chi-square analysis. Results: The therapeutic outcomes of COPD were 30.13% successful (CAT score: <10), 60.26% moderately successful (CAT score: 10–19), 9.62% less successful (CAT score: 20–30), and there were no patients with unsuccessful therapy. The majority of patients had moderate airflow severity. Exacerbation condition, severity level, and type of therapy showed a significant result (P < 0.05) toward therapy results with COPD measurement, and from eight CAT items, it was identified that 37.8% of respondents had breathlessness going up hills/stairs. Conclusion: CAT can assess the therapeutic outcomes and COPD patient’s health status with moderately successful therapy (CAT score 10–19) in more than sixty percent of respondents.
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Striatum hyperactivity triggers relapse to morphine and methamphetamine (polydrug) dependence in mice p. 826
Nur Syafinaz Wasli, Irna Elina Ridzwan, Marwan Saad Azzubaidi, Abdul Razak Kasmuri, Qamar Uddin Ahmed, Long Chiau Ming, Nornisah Mohamed, Syed Mohd Syahmi Syd Mohmad Faudzi
DOI:10.4103/jpbs.JPBS_379_19  
Introduction: κ-opioid receptor (KOPr) system has been linked to relapse to many substances, especially opioids. Positive responses were recently reported in morphine and methamphetamine (polydrug)-dependent mice treated with buprenorphine and naltrexone, a functional κ antagonist. Objectives: This study aimed to determine the specific brain region that is responsive to KOPr treatment following polydrug dependence. Materials and Methods: The polydrug-dependent mice model was developed using conditioned place preference (CPP) method. Following successful withdrawal phase, the mice were treated with 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone. Four brain regions (hippocampus, prefrontal cortex, amygdala, and striatum) were investigated using immunohistochemistry technique. This is to quantify the changes in KOPr expression in each major brain region that was primarily involved in addiction neurocircuits of many substances. Unpaired Student’s t test was used to analyze all results, where P < 0.05 is considered significant. Results: The results showed that treatment with buprenorphine and naltrexone successfully attenuated relapse in 60% of mice (n = 14). A significant upregulation of KOPr was detected in striatum at the end of post-withdrawal phase (P < 0.01, n = 12). This treatment successfully suppressed KOPr in striatum (P < 0.001, n = 12), which supports the positive results seen in the CPP setting. No significant changes were observed in other brain regions studied. Conclusion: The hyperactivity of striatum suggests that the affected brain region following KOPr antagonist treatment is the region that primarily controls the drug rewarding activity, in which nucleus accumbens is located. This indicates that manipulation of KOPr system is one of the potential targets to treat morphine- or methamphetamine-dependence problem.
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Effect of non-hydrogen peroxide on antibacterial activity of Malaysian Meliponini honey against Staphylococcus aureus p. 831
Fatima Ibrahim Jibril, Abu Bakar Mohd Hilmi, Sani Aliyu
DOI:10.4103/jpbs.JPBS_280_19  
Introduction: Stingless bee is an insect that belongs to the family Apidae. Its name is based on its disability of stinging. It has a high product of Meliponini honey and propolis by which are commonly referred to as stingless bee honey and stingless bee propolis. Meliponini honey is one of the crucial natural sources and has the potential to kill infectious microorganisms. Previous studies have proved that the antibacterial activity of natural honey was an effect of hydrogen peroxide, a substance contained in the honey. However, these claims were contradicting with too many studies. Objective: Therefore, this study aimed to identify the antibacterial activity of Malaysian Meliponini honey which contained non-hydrogen peroxide against Staphylococcus aureus, an opportunistic microbial. Materials and Methods: Meliponini honey was used as an antibacterial agent for the treatment of S. aureus in agar well diffusion assay. An amplex red hydrogen peroxide kit was used to identify the hydrogen peroxide in the honey sample. Meanwhile, non-hydrogen peroxide activity was performed by using honey-catalase treated. Results: For the first time, we found that hydrogen peroxide was absent in all Meliponini honey samples. Meliponini honey has higher antibacterial activity (13.30 ± 0.56 mm) compared to Apis honey (9.03 ± 0.22 mm) in agar well diffusion assay. Discussion: Non-hydrogen peroxide in Meliponini honey is a bioactive compound and beneficial to kill the microbial infection. Conclusion: Antibacterial activity of Malaysian Meliponini honey is directly contributed by non-hydrogen peroxide.
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Docking studies and molecular dynamics simulation of Ipomoea batatas L. leaves compounds as lipoxygenase (LOX) inhibitor p. 836
Yeni Yeni, Supandi Supandi, Lusi P Dwita, Suswandari Suswandari, Maizatul S Shaharun, Nonni S Sambudi
DOI:10.4103/jpbs.JPBS_103_20  
Background: Inflammatory mediators produced by cyclooxygenase (COX) and lipoxygenase (LOX) pathways are responsible for many human diseases, such as cancer, arthritis, and neurological disorders. Flavonoid-containing plants, such as Ipomoea batatas leaves, have shown potential anti-inflammatory activity. Objectives: This study aimed to predict the actions of 10 compounds in I. batatas leaves, which are YGM–0a [cyanidin 3–0–sophoroside–5–0–glucosede], YGM–0f [cyanidin 3–O–(2–0–(6–0–(E)–p–coumaroyl–β–D–glucopyranosyl)–β–D–glucopyranoside)–5–0–β–D–glucopyranoside], YGM–1a [cyanidin 3–(6,6′–caffeylp–hydroxybenzoylsophoroside) –5–glucoside], YGM–1b [cyanidin 3–(6,6′–dicaffeylsophor-oside)–5–glucoside], YGM–2 [cyanidin 3–(6–caffeylsophoroside)–5–glucoside], YGM–3 [cyanidin 3–(6,6′–caffeyl-ferulylsophoroside)–5–glucoside], YGM–4b [peonidin 3–(6,6′–dicaffeylsophoroside)–5– glucoside], YGM–5a [peonidin 3–(6,6′–caffeylphydroxybenzo-ylsophoroside)–5–gluco-side], YGM–5b [cyanidin 3–6–caffeylsophoroside)–5–glucosede], and YGM–6 [peonidin 3–(6,6′–caffeylferulylsophoroside)–5–glucoside] as LOX inhibitors, and also predict the stability of ligand–LOX complex. Materials and Methods: The compounds were screened through docking studies using PLANTS. Also, the molecular dynamics simulation was conducted using GROMACS at 310K. Results: The results showed that the most significant binding affinity toward LOX was shown by YGM–0a and YGM–0a, and the LOX complex in molecular dynamics simulation showed stability for 20 ns. Conclusion: Based on Docking Studies and Molecular Dynamics Simulation of I. Batatas Leaves compounds, YGM-0a was shown to be the most probable LOX inhibitor.
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Prescribing of nonsteroidal anti-inflammatory drugs, tramadol, and opioids in children: Patterns of its utilization p. 841
Che Suraya Zin
DOI:10.4103/jpbs.JPBS_251_19  
Background: Analgesic is commonly used in children but little is known about its patterns of utilization. This study explored the patterns of analgesic prescribing in children. Materials and Methods: This cross-sectional study used prescription databases of tertiary hospital settings in Malaysia from 2010 to 2016. Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged <18 years were included. Number of annual patients and prescriptions were measured and analyzed using Stata v15. Results: During a 7-year study period, a total of 5040 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 2460 pediatric patients (81.8% NSAIDs patients, 17.9% tramadol patients, and 0.3% opioid patients). Ibuprofen was the primary analgesic in young children less than 12 years old (≤2 years old [y.o.] [75%], 3–5 y.o. [85%], and 6–12 y.o. [56.3%]). However, there was a wide range of analgesics used in older children (>12 y.o.) with the majority for naproxen (13–15 y.o. (28.2%) and 16–17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12–15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16–17 y.o. Conclusion: Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol.
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Ten years of strong opioid analgesics consumption in Malaysia and other Southeast Asian countries p. 846
Che Suraya Zin
DOI:10.4103/jpbs.JPBS_252_19  
Background: It was reported that opioid consumption in developing countries was stagnated or decreased, but precise data on the consumption are unclear. This study examined the trends and patterns of opioid consumption in Malaysia and other four Southeast Asian countries. Materials and Methods: Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) was used for calculating the annual amount of opioid use. Results: The total consumption of five strong opioids was increased in all five Southeast Asian countries during a 10-year study period. Malaysia was recorded with the largest increase of the opioid consumption (993.18%), followed by Indonesia (530.34%), Vietnam (170.17%), Singapore (116.16%), and Thailand (104.66%). Malaysia also had the highest total strong opioid consumption (11.2 DDD/1000 inhabitants/day), primarily for methadone. Among the opioids used for pain management, fentanyl was primarily used in Malaysia and Singapore but the greatest increase in these two countries was for oxycodone. Fentanyl was also primarily used in Indonesia while morphine was predominantly used in Thailand and Vietnam. Conclusion: Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain.
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Symposium - ICPRP 2019-era of Big Data Highly accessed article p. 852

DOI:10.4103/JPBS.JPBS_237_19  
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