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  1. Abdul Manan MM
    Accid Anal Prev, 2014 Sep;70:301-13.
    PMID: 24831271 DOI: 10.1016/j.aap.2014.04.009
    This paper uses data from an observational study, conducted at access points in straight sections of primary roads in Malaysia in 2012, to investigate the effects of motorcyclists' behavior and road environment attributes on the occurrence of serious traffic conflicts involving motorcyclists entering primary roads via access points. In order to handle the unobserved heterogeneity in the small sample data size, this study applies mixed effects logistic regression with multilevel bootstrapping. Two statistically significant models (Model 2 and Model 3) are produced, with 2 levels of random effect parameters, i.e. motorcyclists' attributes and behavior at Level 1, and road environment attributes at Level 2. Among all the road environment attributes tested, the traffic volume and the speed limit are found to be statistically significant, only contributing to 26-29% of the variations affecting the traffic conflict outcome. The implication is that 71-74% of the unmeasured or undescribed attributes and behavior of motorcyclists still have an importance in predicting the outcome: a serious traffic conflict. As for the fixed effect parameters, both models show that the risk of motorcyclists being involved in a serious traffic conflict is 2-4 times more likely if they accept a shorter gap to a single approaching vehicle (time lag <4s) and in between two vehicles (time gap <4s) when entering the primary road from the access point. A road environment factor, such as a narrow lane (seen in Model 2), and a behavioral factor, such as stopping at the stop line (seen in Model 3), also influence the occurrence of a serious traffic conflict compared to those entering into a wider lane road and without stopping at the stop line, respectively. A discussion of the possible reasons for this seemingly strange result, including a recommendation for further research, concludes the paper.
  2. Manan MM, Ali SM, Khan MA, Jafarian S
    Pak J Pharm Sci, 2015 Sep;28(5):1705-11.
    PMID: 26408891
    Out-of-pocket (OOP) payments may burden Methadone Maintenance Clinic patients. Since treatment is fully subsidized by the government, financial constraint might lead to patients being made to pay or be given incentive for inconvenience of therapy. This study thus evaluates the characteristic and commitment of methadone therapy patient's in terms of OOP cost, Willingness-To-Pay (WTP) and Willingness-To-Accept (WTA) concept. This survey utilizes the questionnaire by Boris ova & Goodman (2003) on the OOP, WTP and WTA. The forty adult patient's selected medical records from year 2009-2011 were from an urban government methadone clinic. Subject's selection was by convenient sampling based on the predetermined criteria. Most were male (95%) and Malay (60%) was the predominant group. Patients were group into three income groups; ≤ RM1000, ≥ RM1000 -≤ RM2000 and ≥ RM3000. The average OOP cost per month was RM391.30 (s.d RM337.50), which is about 35% of employed patient's monthly income. The wide variation could be attributed by high inter-individual and significant differences between patients in terms of transport, times taken to clinic, cost per trip and weekly household income (p=<0.05). Patients with income of less than RM1000 showed the highest tendency to pay for treatment, asked for the least money for inconvenience and many are unwilling to accept any payments. These findings showed that WTP and WTA is less of a concern for patients in the low-income group. To conclude, OOP payment is not a treatment barrier for most of the urban MMT patients.
  3. Rosli R, Ming LC, Abd Aziz N, Manan MM
    PLoS One, 2016;11(6):e0155385.
    PMID: 27249414 DOI: 10.1371/journal.pone.0155385
    BACKGROUND: Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups.

    METHODS: Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR.

    RESULTS: In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities.

    DISCUSSION: ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the ADRs manifesting in skin reactions. The majority of the ADR reports were received from nurses in the public sector, reporting ADRs associated with vaccine administration. The low fatality rate of ADR cases reported could potentially be caused by reporting bias due to the very low reporting percentage from the private healthcare institutions. This study indicates that ADR rates among Malaysian children are higher than in developed countries. Constant ADR reporting and monitoring, especially in respect to paediatric patients, should be undertaken to ensure their safety.

  4. Manan MM, Ibrahim NA, Aziz NA, Zulkifly HH, Al-Worafi YM, Long CM
    Arch Med Sci, 2016 Jun 1;12(3):603-13.
    PMID: 27279855 DOI: 10.5114/aoms.2015.51208
    To identify and assess the characteristics, risk and outcome of neonates treated with empiric antibiotics for suspected early onset sepsis (EOS).
  5. Manan MM, Husin AR, Alkhoshaiban AS, Al-Worafi YM, Ming LC
    J Clin Diagn Res, 2014 Dec;8(12):JC05-9.
    PMID: 25653972 DOI: 10.7860/JCDR/2014/10481.5309
    Adherence to medications is an important factor that contributes to therapeutic success. With the current increase in the elderly population, information relating to adherence to treatment and quality of life (QoL) of diabetic elderly patients will help the healthcare provider to improve their treatment. Thus, this study aims to determine the factors affecting adherence to medications and the consequence of non adherence to QoL.
  6. Manan MM, Ali SM, Khan MA, Jafarian S, Hameed MA
    Pak J Pharm Sci, 2013 Jul;26(4):841-6.
    PMID: 23811468
    This study is an observational cross-sectional study aimed to examine the possible demographic and social characteristics of patients enrolled at the Methadone Maintenance Therapy Adherence Clinic (MMTAC) in Malaysia. Medical records from year 2009 - 2011 were Reviewed. Demographic, social characteristics and laboratory examinations such as age, gender, race, clinic attendances and urine analysis were recorded. Subjects were selected by means of convenient sampling but based on the specified inclusion and exclusion criteria. Data were analyzed by either Chi-square test, Fisher's exact test Mann-Whitney U-test, with the limit of significance was set at p < 0.05. Demographically, this study found that the ratio of Malays, Chinese and Indian enrolled to the MMTAC program is similar to the distribution of races in Malaysia. Their starting age for drug use was between 14-35 years and the age to enrolment between 30-58 years. Socially, many are unemployed, lowly educated and married. Most are drug users with a high percentage of HCV accompanied with impaired liver function. Retention rate was 87% but illicit drug use was at 57.50%. However, percentage of employment increased significantly after therapy. The study managed to identify several demographical and social distributions of patients attending the MMTAC. Although attendance rate was high, many were on illicit drug use. Nevertheless, employment rate improved significantly.
    Study site: government methadone clinic in Klang, Selangor, Malaysia
  7. Kamarudin NA, Manan MM, Zulkifly HH, Neoh CF, Ali SM, Ming LC
    Asia Pac J Clin Nutr, 2016;25(1):53-61.
    PMID: 26965762 DOI: 10.6133/apjcn.2016.25.2.02
    This study aimed to investigate the effects of parenteral nutrition (PN) administration of amino acids (AA) on physical changes among very low birth weight infants in a local hospital setting in Malaysia. A retrospective study was carried out at a hospital in Malaysia. Records of neonates prescribed PN in the neonatal unit in 2012 were screened for eligibility. A total of 199 premature neonates received PN support in the year 2012 and, of these, 100 fulfilled the inclusion criteria. The median value of AA intake on the first day of PN was 2.00 (<28 weeks group); 1.00 (28-31 weeks group) and 0.75 (>31 weeks group). Neonates in the <28 weeks group were more likely to receive AA at an earlier time and higher initial dose compared with the other age groups. The study also found that there was no statistically significant difference in the dose of AA on the first day of PN administration and that the significant variations in nutritional parameters among the subjects did not lead to differences in physical outcomes. This study identified that when PN is provided in the local hospital setting, it is likely that the current nutritional practices are inadequate to achieve the standard growth recommendations. Our findings call for a need to optimize AA and calorie intake since growth restriction is a morbidity which will affect the infants' growth and development. Current prescriptions for PN in this hospital need to be reviewed in order to improve patient outcomes.
  8. Jayasingh Chellammal HS, Veerachamy A, Ramachandran D, Gummadi SB, Manan MM, Yellu NR
    Biomed Pharmacother, 2019 Jan;109:1454-1461.
    PMID: 30551397 DOI: 10.1016/j.biopha.2018.10.189
    The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ(25-35) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days. Aβ(25-35) was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and step-down inhibitory tests were performed on the 27th day to determine the habituation memory, spatial learning, and short- and long-term memory, respectively. Acetylcholinesterase (AChE), Corticosterone, biogenic amines (serotonin and dopamine), tumour necrosis factor-α (TNF-α), and antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase and vitamin C were evaluated in brain homogenates after behavioural tests to ascertain the cognitive improvement through neuro-immune-endocrine modulation. The DAEA treatment with 25 mg/kg and 50 mg/kg resulted in significant (p < 0.001) improvement of habituation memory and step-down inhibitory avoidance task. In spatial learning, the cognitive improvement was significantly improved (p < 0.001) by reduction in escape latency. In the biochemical study, the significant (p < 0.001) reduction of AChE indicates the preeminent neuroprotection. Corticosterone and TNF-α were significantly (p < 0.01) reduced and biogenic amines were increased with antioxidant markers, which signify the potential influence of DAEA on neuroprotection. Our investigation revealed that the drug DAEA attenuates stress mediated through the HPA axis and regulates the neuroendocrine and neuroimmune function to improve the cognition. DAEA could be a potential lead candidate for the treatment of neurodegeneration.
  9. Bakrin FS, Makmor-Bakry M, Che Hon WH, Faizal SM, Manan MM, Ming LC
    Pharmacy (Basel), 2020 Dec 08;8(4).
    PMID: 33302438 DOI: 10.3390/pharmacy8040235
    INTRODUCTION: Drug utilization of analgesics in a private healthcare setting is useful to examine their prescribing patterns, especially the newer injectable cyclooxygenase (COX)-2 inhibitors (coxibs).

    OBJECTIVES: To evaluate the utilization of coxibs and traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) indicated for postoperative orthopaedic pain control using defined daily dose (DDD) and ratio of use density to use rate (UD/UR).

    METHOD: A retrospective drug utilization review (DUR) of nonsteroidal anti-inflammatory drugs (NSAIDs) at an inpatient department of a private teaching hospital in Seremban, Malaysia was conducted. Patients' demographic characteristics, medications prescribed, clinical lab results, visual analogue scale (VAS) pain scores and length of hospital stay were documented. Orthopaedic surgeries, namely arthroscopy, reconstructive, and fracture fixation, were included. Stratified random sampling was used to select patients. Data were collected through patients' medical records. The DDD per 100 admissions and the indicator UD/UR were calculated with the World Health Organization's DDD as a benchmark. The inclusion criteria were patients undergoing orthopaedic surgery prescribed with coxibs (celecoxib capsules, etoricoxib tablets, parecoxib injections) and tNSAIDs (dexketoprofen injections, diclofenac sodium tablets). Data were analysed descriptively. This research was approved by the academic institution and the hospital research ethics committee.

    RESULT: A total of 195 records of patients who received NSAIDs were randomly selected among 1169 cases. In term of the types of orthopaedic surgery, the ratio of included records for arthroscopy:fracture fixation:reconstructive surgery was 55.4:35.9:8.7. Most of the inpatients had low rates of common comorbidities such as cardiovascular disease as supported by their baseline parameters. The majority were not prescribed with other concomitant prescriptions that could cause drug interaction (74.9%), or gastroprotective agents (77.4%). Overall, DDDs per 100 admissions for all NSAIDs were less than 100, except for parecoxib injections (389.23). The UD/UR for all NSAIDs were less than 100, except for etoricoxib tablets (105.75) and parecoxib injections (108.00).

    DISCUSSION: As per guidelines, the majority (96.9%) received other analgesics to ensure a multimodal approach was carried out to control pain. From the UD/UR results, the arthroscopy surgery was probably the most appropriate in terms of NSAID utilization.

    CONCLUSION: The prescribing pattern of NSAIDs except parecoxib was appropriate based on adverse effect and concurrent medication profile. The findings of this DUR provide insight for a low-risk patient population at a private specialized teaching hospital on the recommended use of NSAIDs for postoperative orthopaedic pain control.

  10. Rosli R, Dali AF, Abd Aziz N, Abdullah AH, Ming LC, Manan MM
    Front Pharmacol, 2017;8:27.
    PMID: 28228724 DOI: 10.3389/fphar.2017.00027
    Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized neonates. The present review reveals that neonates are exposed to a high number of drugs and various methods are used to report drug consumption in this age group. The best measure of drug consumption to quantify prevalence of drug use in neonates remains to be identified and additional research in this area is warranted.
  11. Shamsuddin S, Akkawi ME, Zaidi ST, Ming LC, Manan MM
    Int J Infect Dis, 2016 Nov;52:16-22.
    PMID: 27639454 DOI: 10.1016/j.ijid.2016.09.013
    OBJECTIVES: To examine the appropriateness of antibiotics prescribed for acute infection based on the Malaysian national antibiotic guidelines and the defined daily dose (DDD) system of the World Health Organization (WHO). This study also aimed to describe the factors influencing the drug use pattern and to investigate the procurement patterns of antibiotics in the primary healthcare setting.
    METHODS: A retrospective cohort follow-up study of randomly selected patients from all patients who received any antibiotic between January and December 2013 was conducted at three primary healthcare clinics in Selangor State of Malaysia. For each patient, the following information was recorded: name of the antibiotic, frequency and dose, and Anatomical Therapeutic Chemical (ATC) group. The defined daily dose per 1000 inhabitants per day was calculated for each antibiotic. The national antibiotic guidelines were used to assess the appropriateness of each antibiotic prescription.
    RESULTS: A total of 735 patients were included in the study. The five most used antibiotics were amoxicillin (1.36g, 35.2%), cloxacillin (0.68g, 26.3%), erythromycin (0.32g, 22.3%), bacampicillin (0.13g, 7.2%), and cephalexin (0.11g, 6.9%). Respiratory tract infections were the most commonly treated infections, and the doctors' preferred antibiotic for the treatment of these infections was amoxicillin. More than 18% of all amoxicillin prescriptions were deemed inappropriate according to the national antibiotic guidelines. In terms of procurement costs, USD 88885 was spent in 2011, USD 219402 in 2012, and USD 233034 in 2013 at the three primary healthcare clinics, an average of USD 180440 per year for the three clinics.
    CONCLUSIONS: This study reports the antibiotic usage at three primary healthcare clinics in Klang Province. The most prescribed antibiotic was amoxicillin in capsules (250mg), which was mainly prescribed for respiratory infections. Although the national antibiotic guidelines state that amoxicillin is a preferred drug for acute bacterial rhinosinusitis, this drug is also being prescribed for other disease conditions, such as acute pharyngitis and acute tonsillitis. This result shows that current practice is not following the current antibiotic guidelines, which state that phenoxypenicillin should be the preferred drug.
    KEYWORDS: Antibiotic guideline; Defined daily dose; Drug utilization study; Prescribing pattern; Upper respiratory tract infection
    Study site: Klinik Kesihatan Anika, Klinik Kesihatan Pandamaran, Klinik Kesihatan Bukit Kuda, Kelang, Selangor, Malaysia
  12. Rosli R, Dali AF, Aziz NA, Ming LC, Manan MM
    Front Pharmacol, 2017;8:30.
    PMID: 28239351 DOI: 10.3389/fphar.2017.00030
    Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children.
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