Browse publications by year: 2018

  1. Horn R, Heng C, Chea C, Sieng C, Louv C, Turton B, et al.
    Gerodontology, 2018 Mar;35(1):45-50.
    PMID: 29226455 DOI: 10.1111/ger.12315
    OBJECTIVE: Older adults (those above the age of 60) are an emerging demographic in Cambodia, and very little is understood about their oral health experiences, needs, perceptions and behaviours. The aim of this study was to explore the oral health experiences, practices and perceptions of a convenience sample of a small but diverse group of older adults in Cambodia.

    METHOD: A cross-sectional qualitative study in which focus group interviews were conducted by 5 trained senior Cambodian dental students. A convenience sample of 56 older adults and caregivers was recruited across urban, semi-urban and rural locations. Focus group conversations were recorded, transcribed and analysed thematically.

    RESULTS: The themes that emerged were around low expectations for both general health and oral health. A communal responsibility for health was expressed, and both money and transport were identified as key barriers to accessing care. Participants recognised that they had oral health problems, and acknowledged the impact of poor oral function on health and nutrition.

    CONCLUSION: This study is an important first step in better understanding the oral health experiences and perceptions of older people in Cambodia. Participants described the impacts of poor oral health as being important, even when compared with other general health conditions.

    MeSH terms: Aged; Attitude to Health*; Cambodia/epidemiology; Cross-Sectional Studies; Female; Humans; Interviews as Topic; Male; Middle Aged; Mouth Diseases/epidemiology; Oral Hygiene; Dental Care for Aged; Caregivers*; Focus Groups
  2. Vijay A, Earnshaw VA, Tee YC, Pillai V, White Hughto JM, Clark K, et al.
    LGBT Health, 2018 01;5(1):61-68.
    PMID: 29227183 DOI: 10.1089/lgbt.2017.0092
    PURPOSE: Transgender people are frequent targets of discrimination. Discrimination against transgender people in the context of healthcare can lead to poor health outcomes and facilitate the growth of health disparities. This study explores factors associated with medical doctors' intentions to discriminate against transgender people in Malaysia.

    METHODS: A total of 436 physicians at two major university medical centers in Kuala Lumpur, Malaysia, completed an online survey. Sociodemographic characteristics, stigma-related constructs, and intentions to discriminate against transgender people were measured. Bivariate and multivariate linear regression were used to evaluate independent covariates of discrimination intent.

    RESULTS: Medical doctors who felt more fearful of transgender people and more personal shame associated with transgender people expressed greater intention to discriminate against transgender people, whereas doctors who endorsed the belief that transgender people deserve good care reported lower discrimination intent. Stigma-related constructs accounted for 42% of the variance and 8% was accounted for by sociodemographic characteristics.

    CONCLUSIONS: Constructs associated with transgender stigma play an important role in medical doctors' intentions to discriminate against transgender patients. Development of interventions to improve medical doctors' knowledge about and attitudes toward transgender people are necessary to reduce discriminatory intent in healthcare settings.

    MeSH terms: Adult; Attitude of Health Personnel*; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Physicians/psychology*; Prejudice; Socioeconomic Factors; Transsexualism/psychology; Intention*; Social Stigma*; Transgender Persons*
  3. Koh JEW, Ng EYK, Bhandary SV, Hagiwara Y, Laude A, Acharya UR
    Comput Biol Med, 2018 01 01;92:204-209.
    PMID: 29227822 DOI: 10.1016/j.compbiomed.2017.11.019
    Untreated age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma may lead to irreversible vision loss. Hence, it is essential to have regular eye screening to detect these eye diseases at an early stage and to offer treatment where appropriate. One of the simplest, non-invasive and cost-effective techniques to screen the eyes is by using fundus photo imaging. But, the manual evaluation of fundus images is tedious and challenging. Further, the diagnosis made by ophthalmologists may be subjective. Therefore, an objective and novel algorithm using the pyramid histogram of visual words (PHOW) and Fisher vectors is proposed for the classification of fundus images into their respective eye conditions (normal, AMD, DR, and glaucoma). The proposed algorithm extracts features which are represented as words. These features are built and encoded into a Fisher vector for classification using random forest classifier. This proposed algorithm is validated with both blindfold and ten-fold cross-validation techniques. An accuracy of 90.06% is achieved with the blindfold method, and highest accuracy of 96.79% is obtained with ten-fold cross-validation. The highest classification performance of our system shows the potential of deploying it in polyclinics to assist healthcare professionals in their initial diagnosis of the eye. Our developed system can reduce the workload of ophthalmologists significantly.
    MeSH terms: Algorithms; Diagnostic Techniques, Ophthalmological*; Fundus Oculi; Humans; Image Interpretation, Computer-Assisted/methods*
  4. Md Noh MSF, Abdul Rashid AM
    QJM, 2018 May 01;111(5):343.
    PMID: 29228291 DOI: 10.1093/qjmed/hcx240
  5. Loganathan T, Ng CW, Lee WS, Hutubessy RCW, Verguet S, Jit M
    Health Policy Plan, 2018 Mar 01;33(2):204-214.
    PMID: 29228339 DOI: 10.1093/heapol/czx166
    Cost-effectiveness thresholds (CETs) based on the Commission on Macroeconomics and Health (CMH) are extensively used in low- and middle-income countries (LMICs) lacking locally defined CETs. These thresholds were originally intended for global and regional prioritization, and do not reflect local context or affordability at the national level, so their value for informing resource allocation decisions has been questioned. Using these thresholds, rotavirus vaccines are widely regarded as cost-effective interventions in LMICs. However, high vaccine prices remain a barrier towards vaccine introduction. This study aims to evaluate the cost-effectiveness, affordability and threshold price of universal rotavirus vaccination at various CETs in Malaysia. Cost-effectiveness of Rotarix and RotaTeq were evaluated using a multi-cohort model. Pan American Health Organization Revolving Fund's vaccine prices were used as tender price, while the recommended retail price for Malaysia was used as market price. We estimate threshold prices defined as prices at which vaccination becomes cost-effective, at various CETs reflecting economic theories of human capital, societal willingness-to-pay and marginal productivity. A budget impact analysis compared programmatic costs with the healthcare budget. At tender prices, both vaccines were cost-saving. At market prices, cost-effectiveness differed with thresholds used. At market price, using 'CMH thresholds', Rotarix programmes were cost-effective and RotaTeq were not cost-effective from the healthcare provider's perspective, while both vaccines were cost-effective from the societal perspective. Using other CETs, both vaccines were not cost-effective at market price, from the healthcare provider's and societal perspectives. At tender and cost-effective prices, rotavirus vaccination cost ∼1 and 3% of the public health budget, respectively. Using locally defined thresholds, rotavirus vaccination is cost-effective at vaccine prices in line with international tenders, but not at market prices. Thresholds representing marginal productivity are likely to be lower than those reflecting human capital and individual preference measures, and may be useful in determining affordable vaccine prices.
    MeSH terms: Child, Preschool; Cost-Benefit Analysis*; Costs and Cost Analysis/economics*; Decision Making*; Developing Countries/economics; Female; Humans; Infant; Infant, Newborn; Malaysia; Male; Rotavirus Infections/economics; Rotavirus Infections/immunology; Vaccination/economics; Models, Statistical; Rotavirus Vaccines/administration & dosage; Rotavirus Vaccines/economics*
  6. Rasib SZM, Ahmad Z, Khan A, Akil HM, Othman MBH, Hamid ZAA, et al.
    Int J Biol Macromol, 2018 Mar;108:367-375.
    PMID: 29222015 DOI: 10.1016/j.ijbiomac.2017.12.021
    In this study, chitosan-poly(methacrylic acid-co-N-isopropylacrylamide) [chitosan-p(MAA-co-NIPAM)] hydrogels were synthesized by emulsion polymerization. In order to be used as a carrier for drug delivery systems, the hydrogels had to be biocompatible, biodegradable and multi-responsive. The polymerization was performed by copolymerize MAA and NIPAM with chitosan polymer to produce a chitosan-based hydrogel. Due to instability during synthesis and complexity of components to produce the hydrogel, further study at different times of reaction is important to observe the synthesis process, the effect of end product on swelling behaviour and the most important is to find the best way to control the hydrogel synthesis in order to have an optimal swelling behaviour for drug release application. Studied by using Fourier transform infra-red (FTIR) spectroscopy found that, the synthesized was successfully produced stable chitosan-based hydrogel with PNIPAM continuously covered the outer surface of hydrogel which influenced much on the stability during synthesis. The chitosan and PMAA increased the zeta potential of the hydrogel and the chitosan capable to control shrinkage above human body temperature. The chitosan-p(MAA-co-NIPAM) hydrogels also responses to pH and temperature thus improved the ability to performance as a drug carrier.
    MeSH terms: Acrylic Resins/chemistry; Hydrogen-Ion Concentration*; Methacrylates/chemistry; Polymers/chemistry; Temperature*; Spectroscopy, Fourier Transform Infrared; Hydrogels/chemical synthesis; Hydrogels/chemistry*; Chitosan/chemistry*; Chemistry Techniques, Synthetic*; Carbon-13 Magnetic Resonance Spectroscopy
  7. Amal MNA, Zarif ST, Suhaiba MS, Aidil MRM, Shaqinah NN, Zamri-Saad M, et al.
    Microb Pathog, 2018 01;114:251-254.
    PMID: 29217326 DOI: 10.1016/j.micpath.2017.11.069
    This study describes the susceptibility of different fish gender following acute Streptococcus agalactiae infection by using Javanese medaka Oryzias javanicus as test fish. The fish were grouped into four groups, which were: (1) all-male; (2) all-female; (3) mixed-gender (1 male: 1 female ratio); and (4) control non-infected (1 male: 1 female ratio). The fish in group 1, 2 and 3 were intraperitoneally exposed to 5.4 × 108 CFU/mL of S. agalactiae, while for group 4, the fish were exposed using sterile broth. The main clinical signs and histopathological changes of infected Javanese medaka were commonly observed in S. agalactiae infected fishes. However, no difference on clinical signs and histopathological changes of fish in group 1, 2 and 3 were noticed. The Javanese medaka mortality in group 1, 2 and 3 were observed from 4 h post infection (hpi) to 6 hpi, with the cumulative mortality from 3% to 30%. Then, the mortality increased at 12 hpi, with the range from 53% to 80%. However, 100% of the infected fish dead at 24 hpi. No clinical sign, histopathological change and fish mortality recorded in group 4. Generally, the clinical signs, mortality patterns, cumulative mortality and histopathological changes of Javanese medaka infected by S. agalactiae did not show any difference between the all-male, all-female and mixed-gender groups. This indicates that the susceptibility of fish to S. agalactiae infection is not influenced by their gender.
    MeSH terms: Animals; Brain/pathology; Disease Models, Animal; Female; Fish Diseases/microbiology*; Fish Diseases/pathology; Fishes/microbiology*; Kidney/pathology; Liver/pathology; Male; Mortality; Oryzias/microbiology*; Sex Factors; Streptococcal Infections/microbiology*; Streptococcal Infections/pathology; Streptococcal Infections/veterinary*; Streptococcus agalactiae/pathogenicity*
  8. Garba B, Bahaman AR, Bejo SK, Zakaria Z, Mutalib AR, Bande F
    Acta Trop, 2018 Feb;178:242-247.
    PMID: 29217379 DOI: 10.1016/j.actatropica.2017.12.010
    INTRODUCTION: Leptospirosis is a zoonotic disease caused by a diverse pathogenic leptospira species and serovars. The disease is transmitted directly following contact with infected urine and other body fluids or indirectly after contact with water or soil contaminated with infected urine.

    OBJECTIVES: While a wide range of domestic and wild animals are known to be reservoirs of the disease, occupation, international travel and recreation are beginning to assume a center stage in the transmission of the disease. The objective of this study is to review available literatures to determine the extent to which these aforementioned risk factors aid the transmission, increase incidence and outbreak of leptospirosis in Malaysia.

    STUDY DESIGN: The review was conducted based on prevalence, incidence, and outbreak cases of leptospirosis among human and susceptible animals predisposed to several of the risk factors identified in Malaysia.

    METHODS: Literature searchers and reviews were conducted based on articles published in citation index journals, Malaysian ministry of health reports, periodicals as well as reliable newspapers articles and online media platforms. In each case, the newspapers and online media reports were supported by press briefings by officials of the ministry of health and other agencies responsible.

    RESULTS: The disease is endemic in Malaysia, and this was attributed to the large number of reservoir animals, suitable humid and moist environment for proliferation as well as abundant forest resources. Over 30 different serovars have been detected in Malaysia in different domestic and wild animal species. This, in addition to the frequency of flooding which has increased in recent years, and has helped increase the risk of human exposure. Occupation, recreation, flooding and rodent population were all identified as an important source and cause of the disease within the study population.

    CONCLUSION: There is an urgent need for the government and other stakeholders to intensify efforts to control the spread of the disease, especially as it greatly affect human health and the tourism industry which is an important component of the Malaysian economy. The risk of infection can be minimized by creating awareness on the source and mode of transmission of the disease, including the use of protective clothing and avoiding swimming in contaminated waters. Moreover, improved diagnostics can also help reduce the suffering and mortalities that follow infection after exposure to infection source.

    MeSH terms: Animals; Animals, Domestic; Animals, Wild; Body Fluids; Disease Outbreaks; Government; Humans; Leptospira; Leptospirosis; Malaysia; Occupations; Protective Clothing; Recreation; Risk Factors; Rodentia; Soil; Swimming; Water; Zoonoses; Incidence; Prevalence; Cell Proliferation; Floods; Serogroup; Forests
  9. Takaoka H, Srisuka W, Maleewong W, Saeung A
    Acta Trop, 2018 Feb;178:281-289.
    PMID: 29217382 DOI: 10.1016/j.actatropica.2017.12.009
    A faunistic survey of black flies in Shan State, central Myanmar, was carried out in 2013. A total of 16 species were collected, of which 13 species are newly recorded from Myanmar. Among 13 newly recorded species, S. (S.) chiangmaiense Takaoka & Suzuki varied in the number of pupal gill filaments from eight to 10. This survey increases the number of species of black flies from Myanmar from 8 to 23. They are classified in five subgenera of the genus Simulium: one in Asiosimulium, seven in Gomphostilbia, one in Montisimulium, two in Nevermannia and 12 in Simulium.
    MeSH terms: Animals; Myanmar; Female; Larva/classification; Male; Pupa/classification; Simuliidae/anatomy & histology*; Simuliidae/classification*; Simuliidae/physiology; Species Specificity; Animal Distribution
  10. Guérin C, Beuret P, Constantin JM, Bellani G, Garcia-Olivares P, Roca O, et al.
    Intensive Care Med, 2018 01;44(1):22-37.
    PMID: 29218379 DOI: 10.1007/s00134-017-4996-5
    INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

    AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

    METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).

    RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

    CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

    MeSH terms: Aged; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Positive-Pressure Respiration*; Prospective Studies; Prone Position*
  11. Thukral V, Varshney B, Ramly RB, Ponia SS, Mishra SK, Olsen CM, et al.
    Virus Genes, 2018 Apr;54(2):199-214.
    PMID: 29218433 DOI: 10.1007/s11262-017-1526-z
    The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of Orthomyxoviridae family. It encodes at least 10 proteins from eight negative-strand RNA segments. Since ISAV belongs to the same virus family as Influenza A virus, with similarities in protein functions, they may hence be characterised by analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in interferon antagonism and RNA-binding functions. In this study, we investigated the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium transient suppression assay in stably silenced transgenic Nicotiana xanthi. In addition, s8ORF2 was identified as a novel interactor with SsMov10, a key molecule responsible for RISC assembly and maturation in the RNAi pathway. This study thus sheds light on a novel route undertaken by viral proteins in promoting viral growth, using the host RNAi machinery.
    MeSH terms: Animals; Protein Binding; Salmon*; RNA-Binding Proteins/metabolism*; Viral Nonstructural Proteins/metabolism*; Fish Proteins/metabolism*; RNA Interference; Isavirus/immunology; Isavirus/physiology*; Host-Pathogen Interactions*; Immune Evasion*
  12. Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA
    Parasitol Res, 2018 Jan;117(1):265-271.
    PMID: 29218442 DOI: 10.1007/s00436-017-5701-x
    Infectious diseases are the leading cause of morbidity and mortality, killing more than 15 million people worldwide. This is despite our advances in antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising technology to enhance drug efficacy and formation of effective vehicles for drug delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes), and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were synthesized successfully and characterized by ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba castellanii belonging to the T4 genotype using amoebicidal assay and host cell cytotoxicity assay. Viability assays revealed that silver nanoparticles conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited significant antiamoebic properties compared with drugs alone or AgNPs alone (P 
    MeSH terms: Amebiasis/drug therapy*; Amebiasis/parasitology; Amebicides/pharmacology*; Amebicides/chemistry; Amphotericin B/pharmacology*; Amphotericin B/chemistry; Humans; Nystatin/pharmacology*; Nystatin/chemistry; Silver/chemistry; Spectrophotometry, Ultraviolet; Fluconazole/pharmacology*; Fluconazole/chemistry; Spectroscopy, Fourier Transform Infrared; Microscopy, Atomic Force; Acanthamoeba castellanii/drug effects; Acanthamoeba castellanii/genetics; Metal Nanoparticles/chemistry*
  13. Zulkipli AF, Islam T, Mohd Taib NA, Dahlui M, Bhoo-Pathy N, Al-Sadat N, et al.
    Integr Cancer Ther, 2018 06;17(2):312-321.
    PMID: 29218996 DOI: 10.1177/1534735417745248
    BACKGROUND: The use of complementary and alternative medicine (CAM) has increased and little is known on CAM use during the initial period. Therefore, the aim was to determine prevalence of CAM use among newly diagnosed breast cancer patients prior to seeking conventional treatment.

    METHODS: This is a cross-sectional study involved interviewing newly diagnosed breast cancer patients in the University Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible respondents were interviewedduring a routine clinical visit.

    RESULTS: A total of 400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary supplementation (n = 107, 77.0%) was the most frequently used type of CAM, followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their doctors. Most of them used remedies based on the recommendation of family and friends. Malay ethnicity and patients with 3 or more comorbidities were more likely to use CAM.

    CONCLUSION: There is substantial use of CAM among breast cancer patients in UMMC prior to seeking hospital treatment, and the most popular CAM modality is dietary supplements. Since, the majority of CAM users do not disclose the use of CAM to their physicians, therefore health care providers should ensure that those patients who are likely to use CAM are appropriately counseled and advised.

    MeSH terms: Complementary Therapies/methods; Breast Neoplasms/drug therapy*; Cross-Sectional Studies; Female; Humans; Malaysia; Medicine, Chinese Traditional/methods; Middle Aged; Surveys and Questionnaires; Prevalence
  14. AlMatar M, Makky EA, Var I, Koksal F
    Curr Drug Deliv, 2018;15(4):470-484.
    PMID: 29219055 DOI: 10.2174/1567201815666171207163504
    BACKGROUND: Until recently, one of the main reasons for mortality has been infectious diseases, and bacteria that are drug-resistant have emerged as a result of the wide application, as well as the misuse of antibacterial medications. Having multidrug-resistance, bacteria present a great problem for the efficient management of bacterial infections and this challenge has resulted in the creation of other means of dealing with bacterial diseases. Of late, metallic nanoparticles (NPs), employed as antibacterial agents, have the potential for use against resistance to bacterial drugs.

    OBJECTIVE: The mechanisms of bacterial resistance are described in this review and this is followed by an outline of the features and uses of metallic NPs as antibiotic agents to address bacteria that are antibiotic- sensitive and resistant. Additionally, a general impression of metallic NPs as antibiofilm bactericidal agents is presented.

    CONCLUSION: Biofilms and bacterial strains that are resistant to antibiotics present a grave public health challenge and this has enhanced the need to develop new bactericidal agents. Therefore, nanomaterials are considered as a potential platform for managing bacterial infections.

    MeSH terms: Anti-Infective Agents/administration & dosage; Anti-Infective Agents/therapeutic use; Drug Carriers/pharmacology; Drug Carriers/therapeutic use*; Humans; Biofilms/drug effects*; Drug Resistance, Multiple, Bacterial/drug effects*; Metal Nanoparticles/administration & dosage*; Metal Nanoparticles/adverse effects; Metal Nanoparticles/therapeutic use*
  15. Mohd-Tahir NA, Li SC
    Epilepsy Res, 2018 01;139:113-122.
    PMID: 29220742 DOI: 10.1016/j.eplepsyres.2017.11.007
    AIM: This study conducted a systematic review evaluating the effectiveness of newer antiepileptic drugs (AEDs) (namely, lamotrigine, levetiracetam, topiramate, vigabatrin, zonisamide, oxcarbazepine, perampanel, gabapentin, and stiripentol) as add-on for treatment of focal epilepsy in children.

    METHODS: Articles were retrieved from EMBASE, Medline and Cochrane Library from inception to January 2016. Treatment outcomes were analysed based on responder, seizure-free, withdrawal and adverse event rates. Quality of each study was also assessed.

    RESULTS: Twelve articles fulfilled the inclusion criteria. Heterogeneity and quality of the included studies were considered acceptable. Overall, newer AEDs as adjunct therapy in children with inadequate control of focal seizure showed a trend of better seizure outcomes. The pooled ORs for responder, seizure-free and withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69 (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively higher than placebo (OR:1.64, 95%CI:1.13, 2.39).

    CONCLUSION: In our updated review, newer AEDs as adjunct therapy for focal epilepsy in children have trends of better effectiveness compared to placebo. Newer AEDs are associated with statistically more children with >50% seizure reduction, and a trend of better seizure freedom. Their tolerability would also be considered acceptable with the observed low withdrawal rate. However, the relative lack of well-conducted RCTs evaluating their effectiveness against other active AED treatment in children would not facilitate evidence-based practice. This highlights the knowledge gap and the need for more well-conducted RCTs against active treatments to ascertain the long term effectiveness and the role of newer AEDs in managing epilepsy in children.

    MeSH terms: Adolescent; Anticonvulsants/therapeutic use*; Child; Child, Preschool; Epilepsies, Partial/drug therapy*; Humans; Infant
  16. Valli H, Ahmad S, Sriharan S, Dean LD, Grace AA, Jeevaratnam K, et al.
    Clin Exp Pharmacol Physiol, 2018 03;45(3):278-292.
    PMID: 29027245 DOI: 10.1111/1440-1681.12870
    Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na+ current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na+ currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20.23 ± 1.48 (17) and -29.8 ± 2.4 (10) pA/μm2 (mean ± SEM [n]). Challenge by 8-CPT (1 μmol/L) reduced these currents to -11.21 ± 0.91 (12) (P  .05). Assessment of the inactivation that followed by applying subsequent steps to a fixed voltage 100 mV positive to resting potential gave concordant results. Half-maximal inactivation voltages and steepness factors, and time constants for Na+ current recovery from inactivation in double-pulse experiments, were similar through all the pharmacological conditions. Intracellular sharp microelectrode membrane potential recordings in intact Langendorff-perfused preparations demonstrated concordant variations in maximum rates of atrial and ventricular action potential upstroke, (dV/dt)max . We thus demonstrate an acute, reversible, Na+ channel inhibition offering a possible mechanism for previously reported pro-arrhythmic slowing of AP propagation following modifications of Ca2+ homeostasis, complementing earlier findings from chronic alterations in Ca2+ homeostasis in genetically-modified RyR2-P2328S hearts.
    MeSH terms: Action Potentials; Cyclic AMP/analogs & derivatives*; Cyclic AMP/pharmacology; Animals; Calcium/metabolism; Dantrolene/administration & dosage; Dantrolene/pharmacology*; Gene Expression Regulation/drug effects; Heart/physiology; Mice, Inbred C57BL; Microelectrodes; Muscle Relaxants, Central/pharmacology*; Sodium Channels; Patch-Clamp Techniques; Ryanodine Receptor Calcium Release Channel/genetics; Ryanodine Receptor Calcium Release Channel/metabolism*; Guanine Nucleotide Exchange Factors/metabolism*; Myocytes, Cardiac/drug effects*; Myocytes, Cardiac/metabolism; Mice
  17. Hui CK, Hui NK
    Gut Liver, 2018 May 15;12(3):288-296.
    PMID: 29212311 DOI: 10.5009/gnl17056
    Background/Aims: The epidemiology of eosinophilic gastroenteritis remains unclear. We aim to determine the prevalence of eosinophilic gastroenteritis in patients with lower abdominal symptoms.

    Methods: In a prospective study, colonoscopy was performed on 2,469 consecutive patients. Biopsies were taken from the terminal ileum and ascending, transverse, descending and sigmoid colon in all patients.

    Results: Sixty-four of the 2,469 patients (2.6%) had eosinophilic gastroenteritis. Only five of the 64 patients (7.8%) with eosinophilic gastroenteritis had endoscopic mucosal abnormalities during colonoscopy. Six of these 64 patients (9.4%) had severe disease at presentation, and seven of these 64 patients (10.9%) required systemic steroid treatment. An elevated absolute peripheral eosinophil count was independently associated with severe disease at presentation (4/6 [66.7%] vs 3/58 [5.2%], p=0.005; odds ratio [OR], 25.320; 95% confidence interval [CI], 2.628 to 243.910), and severe disease at the time of presentation was independently associated with the use of systemic steroid treatment (6/7 [85.7%] vs 0/57 [0%], p=0.008; OR, 18.021; 95% CI, 2.163 to 150.152).

    Conclusions: The prevalence of eosinophilic gastroenteritis is common, and patients usually present normal-appearing mucosa on colonoscopy. Those with severe disease at presentation usually have a raised absolute peripheral eosinophil count and should be commenced on systemic steroids as an initial therapy.

    MeSH terms: Acetates/administration & dosage; Adolescent; Adult; Anti-Inflammatory Agents/administration & dosage; Colonoscopy/methods; Drug Therapy, Combination; Enteritis/complications; Enteritis/epidemiology; Enteritis/therapy*; Eosinophilia/complications; Eosinophilia/epidemiology; Eosinophilia/therapy*; Female; Gastric Mucosa; Gastritis/complications; Gastritis/epidemiology; Gastritis/therapy*; Humans; Ketotifen/administration & dosage; Male; Middle Aged; Prednisolone/administration & dosage; Prospective Studies; Quinolines/administration & dosage; Colon, Sigmoid; Abdominal Pain/etiology; Prevalence; Treatment Outcome; Colon, Descending; Young Adult; Republic of Korea/epidemiology
  18. Gan ST, Wong WC, Wong CK, Soh AC, Kilian A, Low EL, et al.
    J Appl Genet, 2018 Feb;59(1):23-34.
    PMID: 29214520 DOI: 10.1007/s13353-017-0420-7
    Oil palm (Elaeis guineensis Jacq.) is an outbreeding perennial tree crop with long breeding cycles, typically 12 years. Molecular marker technologies can greatly improve the breeding efficiency of oil palm. This study reports the first use of the DArTseq platform to genotype two closely related self-pollinated oil palm populations, namely AA0768 and AA0769 with 48 and 58 progeny respectively. Genetic maps were constructed using the DArT and SNP markers generated in combination with anchor SSR markers. Both maps consisted of 16 major independent linkage groups (2n = 2× = 32) with 1399 and 1466 mapped markers for the AA0768 and AA0769 populations, respectively, including the morphological trait "shell-thickness" (Sh). The map lengths were 1873.7 and 1720.6 cM with an average marker density of 1.34 and 1.17 cM, respectively. The integrated map was 1803.1 cM long with 2066 mapped markers and average marker density of 0.87 cM. A total of 82% of the DArTseq marker sequence tags identified a single site in the published genome sequence, suggesting preferential targeting of gene-rich regions by DArTseq markers. Map integration of higher density focused around the Sh region identified closely linked markers to the Sh, with D.15322 marker 0.24 cM away from the morphological trait and 5071 bp from the transcriptional start of the published SHELL gene. Identification of the Sh marker demonstrates the robustness of using the DArTseq platform to generate high density genetic maps of oil palm with good genome coverage. Both genetic maps and integrated maps will be useful for quantitative trait loci analysis of important yield traits as well as potentially assisting the anchoring of genetic maps to genomic sequences.
    MeSH terms: Plant Breeding; Chromosome Mapping*; Genetic Markers; Genotype; Genetic Linkage*; Microsatellite Repeats; Polymorphism, Single Nucleotide*; Arecaceae/genetics*; Quantitative Trait Loci
  19. Ruttala HB, Ramasamy T, Madeshwaran T, Hiep TT, Kandasamy U, Oh KT, et al.
    Arch Pharm Res, 2018 Feb;41(2):111-129.
    PMID: 29214601 DOI: 10.1007/s12272-017-0995-x
    The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.
    MeSH terms: Animals; Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/metabolism; Drug Carriers/administration & dosage; Drug Carriers/metabolism; Humans; Neoplasms/drug therapy; Neoplasms/metabolism; Drug Delivery Systems/methods; Drug Delivery Systems/trends*; Nanomedicine/methods; Nanomedicine/trends*; Nanoparticles/administration & dosage*; Nanoparticles/metabolism
  20. Tsai JJ, Wu T, Leung H, Desudchit T, Tiamkao S, Lim KS, et al.
    Acta Neurol. Scand., 2018 Apr;137(4):378-391.
    PMID: 29214650 DOI: 10.1111/ane.12879
    Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.
    MeSH terms: Adolescent; Adult; Aged; Anticonvulsants/therapeutic use*; Female; Humans; Male; Pyridones/therapeutic use*; Seizures/drug therapy*; Treatment Outcome; Receptors, AMPA/antagonists & inhibitors*
External Links