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  1. Premakumar CM, Turner MA, Morgan C
    Nutr Rev, 2019 12 01;77(12):878-889.
    PMID: 31504841 DOI: 10.1093/nutrit/nuz049
    CONTEXT: Very preterm neonates (VPNs) are unable to digest breast milk and therefore rely on parenteral nutrition (PN) formulations. This systematic review was prepared following PRISMA-P 2015 guidelines. For the purpose of this review, desirable mean plasma arginine concentration is defined as ≥80 micromoles/L.

    OBJECTIVE: The review was performed to answer the following research question: "In VPNs, are high amounts of arginine in PN, compared with low amounts of arginine, associated with appropriate circulating concentrations of arginine?" Therefore, the aims were to 1) quantify the relationship between parenteral arginine intakes and plasma arginine concentrations in PN-dependent VPNs; 2) identify any features of study design that affect this relationship; and 3) estimate the target parenteral arginine dose to achieve desirable preterm plasma arginine concentrations.

    DATA SOURCES: The PubMed, Scopus, Web of Science, and Cochrane databases were searched regardless of study design; review articles were not included.

    DATA EXTRACTION: Only articles that discussed amino acid (AA) intake and measured plasma AA profile post PN in VPNs were included. Data were obtained using a data extraction checklist that was devised for the purpose of this review.

    DATA ANALYSIS: Twelve articles met the inclusion criteria. The dose-concentration relationship of arginine content (%) and absolute arginine intake (mg/(kg × d)) with plasma arginine concentrations showed a significant positive correlation (P < 0.001).

    CONCLUSION: Future studies using AA solutions with arginine content of 17%-20% and protein intakes of 3.5-4.0 g/kg per day may be needed to achieve higher plasma arginine concentrations.

  2. Abdul Hadi NN, Premakumar CM, Mohamed Shah N
    Med J Malaysia, 2022 Jan;77(1):26-32.
    PMID: 35086991
    INTRODUCTION: Parental attitudes can have a significant impact on the use of medicines in children. This study aimed to investigate parental attitudes towards medicines used in children in Malaysia and the sociodemographic factors associated with it.

    MATERIALS AND METHODS: A cross-sectional study using convenience sampling was conducted among 230 parents with children aged 12 years and below in Malaysia. Data were collected between November 2020 and January 2021 through online platforms.

    RESULTS: The majority of respondents were mothers (67.8%) and aged between 40-49 years (43.0%). The results showed that antipyretics were the most commonly used medicines followed by cough and cold medicines, antibiotics, and analgesics. The results further revealed that parents have neutral attitudes toward the use of medicines in children (69.90 ± 12.12 from a total score of 105), and mothers and younger parents having a significantly more positive attitude than fathers and older parents, respectively (p < 0.05).

    CONCLUSION: This study provided insights into the types of medicines commonly used in children and parental attitudes towards medicines used in children in Malaysia.

  3. Hon MY, Chua XY, Premakumar CM, Mohamed Shah N
    Int J Clin Pharm, 2020 Jun;42(3):948-955.
    PMID: 32356248 DOI: 10.1007/s11096-020-01045-w
    Background Drug-related problems are relatively common among hospitalised patients and may be detrimental to patients and even increase healthcare costs. Characterising drug-related problems allows remedial actions to be in place to minimise the frequency and ensure higher medication safety for the patients involved. Currently, the incidence of drug-related problems among hospitalised paediatric patients in Malaysia is unknown. Objective To determine the incidence, types and intervention acceptance, as well as the risk factors associated with drug-related problems in a Malaysian general paediatric ward. Setting General paediatric ward in Universiti Kebangsaan Malaysia Medical Centre. Method A cross-sectional observational study was conducted from March to May 2019. Data were collected from patients' medical charts, clinical notes and medical records for problem identification based on the modified Pharmaceutical Care Network Europe (PCNE) classification V 8.02. The incidence, types, causes and intervention acceptance as well as the risk factors were assessed. Main outcome measure Drug-related problems based on the modified PCNE classification V 8.02. Results In total, 225 paediatric patients with a total of 694 prescriptions were included in this study. The incidence of drug-related problems was 52.9% (198 prescriptions with problems in 119 patients). The main types of problems were treatment safety (68 prescriptions, 34.3%), incomplete prescription (56 prescriptions, 28.3%) and un-optimised drug treatment (35 prescriptions, 17.7%). The main causes for the problems were necessary information not provided (n = 63, 30.1%), inappropriate dose selection (n = 47, 22.5%) and medication served without a valid prescription (n = 40, 19.1%). Of the 143 interventions proposed to prescribers by the pharmacist, 117 (81.8%) were accepted. The number of prescriptions was found to be the only risk factor associated with DRPs (odds ratio, 1.91; 95% confidence interval, 1.54-2.38; p 
  4. Kan E, Mustafa S, Chong WW, Premakumar CM, Mohamed Shah N
    Patient Prefer Adherence, 2020;14:1411-1419.
    PMID: 32848370 DOI: 10.2147/PPA.S255289
    Context: Pain is a common and distressing symptom among cancer patients. Opioid analgesics are the mainstay of cancer pain management, and adequate adherence plays an important role in achieving good pain control.

    Purpose: To determine the level of adherence to opioid analgesics in patients with cancer pain and to identify factors that may influence the adherence.

    Patient and Methods: This was a cross-sectional study conducted from March to June 2018 at two tertiary care hospitals in Malaysia. Study instruments consisted of a set of validated questionnaires; the Medication Compliance Questionnaire, Brief Pain Inventory and Pain Opioid Analgesic Beliefs─Cancer scale.

    Results: A total of 134 patients participated in this study. The patients' adherence scores ranged from 52-100%. Factors with a moderate, statistically significant negative correlation with adherence were negative effect beliefs (rs= -0.53, p<0.001), pain endurance beliefs (rs = -0.49, p<0.001) and the use of aqueous morphine (rs = -0.26, p=0.002). A multiple linear regression model on these predictors resulted in a final model which accounted for 47.0% of the total variance in adherence (R2 = 0.47, F (7, 126) = 15.75, p<0.001). After controlling for other variables, negative effect beliefs were the strongest contributor to the model (β = -0.39, p<0.001) and uniquely explained 12.3% of the total variance.

    Conclusion: The overall adherence to opioid analgesics among Malaysian patients with cancer pain was good. Negative effects beliefs regarding cancer pain and opioids strongly predicted adherence.

  5. Henry Basil J, Premakumar CM, Mhd Ali A, Mohd Tahir NA, Mohamed Shah N
    Drug Saf, 2022 Dec;45(12):1457-1476.
    PMID: 36192535 DOI: 10.1007/s40264-022-01236-6
    INTRODUCTION: Neonates are at greater risk of preventable adverse drug events as compared to children and adults.

    OBJECTIVE: This study aimed to estimate and critically appraise the evidence on the prevalence, causes and severity of medication administration errors (MAEs) amongst neonates in Neonatal Intensive Care Units (NICUs).

    METHODS: A systematic review and meta-analysis was conducted by searching nine electronic databases and the grey literature for studies, without language and publication date restrictions. The pooled prevalence of MAEs was estimated using a random-effects model. Data on error causation were synthesised using Reason's model of accident causation.

    RESULTS: Twenty unique studies were included. Amongst direct observation studies reporting total opportunity for errors as the denominator for MAEs, the pooled prevalence was 59.3% (95% confidence interval [CI] 35.4-81.3, I2 = 99.5%). Whereas, the non-direct observation studies reporting medication error reports as the denominator yielded a pooled prevalence of 64.8% (95% CI 46.6-81.1, I2 = 98.2%). The common reported causes were error-provoking environments (five studies), while active failures were reported by three studies. Only three studies examined the severity of MAEs, and each utilised a different method of assessment.

    CONCLUSIONS: This is the first comprehensive systematic review and meta-analysis estimating the prevalence, causes and severity of MAEs amongst neonates. There is a need to improve the quality and reporting of studies to produce a better estimate of the prevalence of MAEs amongst neonates. Important targets such as wrong administration-technique, wrong drug-preparation and wrong time errors have been identified to guide the implementation of remedial measures.

  6. Henry Basil J, Premakumar CM, Mhd Ali A, Mohd Tahir NA, Seman Z, Mohamed Shah N
    BMJ Paediatr Open, 2023 Feb;7(1).
    PMID: 36754439 DOI: 10.1136/bmjpo-2022-001765
    INTRODUCTION: Medication administration errors (MAEs) are the most common type of medication error. Furthermore, they are more common among neonates as compared with adults. MAEs can result in severe patient harm, subsequently causing a significant economic burden to the healthcare system. Targeting and prioritising neonates at high risk of MAEs is crucial in reducing MAEs. To the best of our knowledge, there is no predictive risk score available for the identification of neonates at risk of MAEs. Therefore, this study aims to develop and validate a risk prediction model to identify neonates at risk of MAEs.

    METHODS AND ANALYSIS: This is a prospective direct observational study that will be conducted in five neonatal intensive care units. A minimum sample size of 820 drug preparations and administrations will be observed. Data including patient characteristics, drug preparation-related and administration-related information and other procedures will be recorded. After each round of observation, the observers will compare his/her observations with the prescriber's medication order, hospital policies and manufacturer's recommendations to determine whether MAE has occurred. To ensure reliability, the error identification will be independently performed by two clinical pharmacists after the completion of data collection for all study sites. Any disagreements will be discussed with the research team for consensus. To reduce overfitting and improve the quality of risk predictions, we have prespecified a priori the analytical plan, that is, prespecifying the candidate predictor variables, handling missing data and validation of the developed model. The model's performance will also be assessed. Finally, various modes of presentation formats such as a simplified scoring tool or web-based electronic risk calculators will be considered.

  7. Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM
    Front Pharmacol, 2022;13:820969.
    PMID: 35140617 DOI: 10.3389/fphar.2022.820969
    Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy. Genistein belongs to the flavonoid family, in the subgroup of isoflavones. It is a phytoestrogen that is mainly derived from legumes. It is a naturally occurring chemical constituent with a similar chemical structure to mammalian estrogens. It is claimed to exert many beneficial effects on health, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties. In the past, numerous in vitro and in vivo studies have been conducted to investigate the anti-inflammatory potential of genistein. Henceforth, this review aims to summarize the anti-inflammatory properties of genistein linking with the signaling pathways and mediators that are involved in the inflammatory response as well as its toxicity profile. The current outcomes are analysed to highlight the prospect as a lead compound for drug discovery. Data was collected using PubMed, ScienceDirect, SpringerLink and Scopus databases. Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokines and reactive oxygen species (ROS). A comprehensive assessment of the mechanism of action in anti-inflammatory effects of genistein is included. However, evidence for the pharmacological effects is still lacking. Further studies using various animal models to assess pharmacological effects such as toxicity, pharmacokinetics, pharmacodynamics, and bioavailability studies are required before clinical studies can be conducted. This review will highlight the potential use of genistein as a lead compound for future drug development as an anti-inflammatory agent.
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