Complementary and alternative medicines use among pediatric patients with epilepsy in a multiethnic community.

OBJECTIVE: Prior studies highlighted that patients on chronic medications who used complementary and alternative medicines (CAMs) did not share this information with their healthcare providers. Furthermore, there might be potential adverse interactions between CAMs and antiepileptic drug (AED) therapy. However, there are no studies that investigate the effect of religion or race on CAM use in a multiethnic community. Therefore, we aimed to investigate CAM usage among pediatric patients with epilepsy (PPE) and identify predictors of CAM usage in our multiethnic setting. METHODS: This was a cross-sectional study where caregivers of recruited at an outpatient epilepsy clinic between September 2013 and July 2014 completed a self-administered survey. Those who declined participation, lacked understanding of English or Mandarin, or missed the clinic appointments were excluded. Those caring for more than one patient participated only once. RESULTS: Of the 195 surveys collected, 178 were used for analysis. The PPE used an average of 1.50 AEDs (range: 0-4). Forty-nine (27.5%) caregivers reported giving CAMs to their PPE. Commonly used CAMs were multivitamins (44.4%), traditional herbs (42.2%), and acupuncture (17.4%). Multivitamins were mostly given by Christian/Catholic caregivers while Buddhist caregivers mostly gave traditional herbs or acupuncture. The majority of the CAM users were Chinese. Univariate analysis showed that caregivers with secondary school (high school) education were 3.52 times more likely to use CAMs compared to those with primary school (elementary school) education. CONCLUSIONS: While some caregivers gave CAMs to their PPE, they had various misconceptions and did not discuss the usage with their healthcare providers. We propose that the predictors identified in this study can help to identify potential CAM users. Healthcare providers should routinely probe about the usage of CAMs by PPE, and thereafter, the suitability of CAM use could be evaluated. The caregivers will benefit from open discussion with healthcare professionals on the safe use of AEDs with or without CAMs.

Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014.

BACKGROUND: The use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients. METHODS: AERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details. RESULTS: Fifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1-8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia. CONCLUSIONS: Drug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM.

Novel nanofiltration membranes consisting of a sulfonated pentablock copolymer rejection layer for heavy metal removal.

Facing stringent regulations on wastewater discharge containing heavy metal ions, various industries are demanding more efficient and effective treatment methods. Among the methods available, nanofiltration (NF) is a feasible and promising option. However, the development of new membrane materials is constantly required for the advancement of this technology. This is a report of the first attempt to develop a composite NF membrane comprising a molecularly designed pentablock copolymer selective layer for the removal of heavy metal ions. The resultant NF membrane has a mean effective pore diameter of 0.50 nm, a molecular weight cutoff of 255 Da, and a reasonably high pure water permeability (A) of 2.4 LMH/bar. The newly developed NF membrane can effectively remove heavy metal cations such as Pb(2+), Cd(2+), Zn(2+), and Ni(2+) with a rejection of >98.0%. On the other hand, the membrane also shows reasonably high rejections toward anions such as HAsO4(2-) (99.9%) and HCrO4(-) (92.3%). This performance can be attributed to (1) the pentablock copolymer's unique ability to form a continuous water transport passageway with a defined pore size and (2) the incorporation of polyethylenimine as a gutter layer between the selective layer and the substrate. To the best of our knowledge, this is the first reported NF membrane comprising this pentablock copolymer as the selective material. The promising preliminary results achieved in this study provide a useful platform for the development of new NF membranes for heavy metal removal.

Building a successful platform for interprofessional education for health professions in an Asian university.

Implementing Interprofessional Education (IPE) across health professions schools is challenging. Within an Asian context, academic staff at the National University of Singapore designed a platform to create a sustainable IPE effort. A two-pronged approach was developed to ensure adequate coverage of key concepts relating to IPE within each involved faculty. The Interprofessional Core Curricula (ICC) component ensures that each health profession student will be exposed to IPE concepts in their required curriculum. Interprofessional Enrichment Activities (IEA) incentivize further cross-faculty participation and progress within the IPE competency framework. Best practices and success factors were identified, while lessons learned led to further improvements. Adoption of this approach can help circumvent well-known barriers to implementation.

A simple method of microneedle array fabrication for transdermal drug delivery.

The outermost layer of skin, stratum corneum, being lipophilic limits the passive transport of hydrophilic and large molecular weight drugs. Microfabrication technology has been adapted to fabricate micron scale needles, which are minimally invasive, yet able to deliver the drugs across this barrier layer. In this study, we fabricated microneedles from a biocompatible polymer, namely, poly (ethylene glycol) diacrylate. A simple lithographical approach was developed for microneedle array fabrication. Several factors including polymerization time, ultraviolet light intensity and distance from light source were studied for their effects on microneedle formation. The microneedle length and tip diameter can be controlled by varying these factors. The microneedles were shown to be able to penetrate cadaver pig skin. Model drug rhodamine B was encapsulated in the range of 50 µg to 450 µg per microneedle array. The fabricated microneedles containing rhodamine B increased the permeability by four times than the control. Altogether, we demonstrated that the microneedle arrays can be fabricated through a simple single-step process and needles were mechanically strong to penetrate skin, increasing the permeability of encapsulated drug through skin.

A Pilot Study on Pharmacists' Knowledge, Attitudes and Practices towards Medication Dysphagia via Asynchronous Online Focus Group Discussion.

Medication dysphagia (MD) refers to difficulty swallowing oral medications. To cope, patients may inappropriately modify or skip medications, leading to poorer outcomes. Little is known about healthcare professionals' (HCPs') perspectives in managing MD. This study investigated pharmacists' knowledge, attitudes, and practices (KAP) in caring for patients with MD. An asynchronous online focus group was pilot tested in seven pharmacists, with up to two questions posted daily on an online platform over 15 days. Thematic analysis of the transcripts revealed five interrelated themes: (1) knowledge about MD; (2) management of MD; (3) expectations of patient proactivity; (4) desire for objectivity; (5) professional roles. The findings provided insight into pharmacists' KAP and may be incorporated into a full-scale study involving various HCPs.

Development and validation of the INappropriate solid oral dosaGE form modification aSsessmenT (INGEST) Algorithm using data of patients with medication dysphagia from a neurology ward and nursing home in Singapore.

OBJECTIVES: This study aims to develop and validate a novel implicit tool to assist clinicians in resource-limited settings to promptly assess suitability for modification of solid oral dosage forms (SODFs) during medication prescribing, review and/or administration for patients with dysphagia. DESIGN: Literature review and a group discussion were conducted to elicit items for the construction of the INappropriate solid oral dosaGE form modification aSsessmenT (INGEST) algorithm. For its validation, inter-rater reliability among three independent users was evaluated. Accuracy of users' ratings was also evaluated against the screening results using the Don't Rush to Crush handbook. SETTING AND PARTICIPANTS: Three pharmacists were involved in the development and another three were involved in the validation of the INGEST algorithm using anonymised medication records of 50 patients in a nursing home and a hospital ward; only SODFs that were modified prior to administration were evaluated. RESULTS: Following literature review, considerations included by consensus in the INGEST algorithm were the presence of special coating or modified release characteristics of the SODF medications, hazardous nature and taste of the active ingredients, manufacturer's advice and use of tube feeding. Of the 381 SODF medications evaluated, 26 (6.8%) were identified by at least one pharmacist to be inappropriate for modification. Gwet's AC among the three pharmacists in identifying SODF medications inappropriate for modification was 0.75 (p<0.001, 95% CI 0.63 to 0.87), and 0.80 (p<0.001, 95% CI 0.71 to 0.89) in identifying SODF medications appropriate for modification, suggesting substantial inter-rater agreement. Overall accuracy of each pharmacist's ratings was high, ranging from 93.7% to 95.6%. CONCLUSIONS: The implicit INGEST algorithm has potential for use by clinicians in nursing home and hospital settings for determining suitability of SODF medications for modification. Further studies should be conducted to assess its external validity and utilisation in daily practice for improving clinical outcomes for patients with SODF dysphagia.

Development and characterization of skin permeation retardants and enhancers: a comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles.

Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly D,L lactide (PLA), poly D,L lactide co glycoside (PLGA), poly (N-isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy. It was found that ethyl cellulose microparticles had the highest drug encapsulation and minimal drug leakage during the 14 week storage period. The PNIPAM microparticles had the lowest drug encapsulation efficiency and a fast degradation rate. The PLGA microparticles exhibited a temperature dependent drug leakage. Permeation studies using a flow-through diffusion cell indicated that the polymer transition temperature (T(g)) may influence the skin permeation rate of levothyroxine. Polyesters (PLA and PLGA) and PNIPAM acted as a skin penetration retardant and caused skin accumulation of the drug. These microparticles have potential use in skin formulations containing sunscreens and other active ingredients that are meant to be concentrated on the skin surface. However, skin permeation was observed from EC microparticles, therefore such polymers may be used as carriers in transdermal formulations to help achieve therapeutic concentrations of the drug in the plasma.

Smart polymeric nanofibers for topical delivery of levothyroxine.

Topical administration of levothyroxine (T4) helps to reduces deposits of adipose tissue on skin. The question is whether topical application of T4 could lead to systemic effects. In the present study a series of nanofibrous membranes were electrospun into blends of poly vinyl alcohol (PVA) and poly-N-isopropylacrylamide (PNIPAM) to develop a sustained topical delivery of T4. The polymeric nanofiber mats were characterized by field emission scanning electron microscopy (FESEM) and fourier transform infrared (FTIR) spectroscopy. In vitro permeation of the drug from the polymeric nanofibers was studied using excised human skin and the permeation mechanism investigated using confocal microscopy. It was observed that polymeric nanofibers were able to sustain the penetration of T4 to the skin and help maintain the effective drug concentration in the skin layers for longer period of time. These formulations may have potential uses in topical skin products and can help to increase the accumulation of the active compound on the skin surface thus minimize the adverse side effects which may be caused by systemic absorption. This may result in great improvement in consumer compliance, avoid frequent dosing and enhance the therapeutic effectiveness.

Single and multi-layered nanofibers for rapid and controlled drug delivery.

This paper introduces a new delivery system for rapid and controlled drug release. Mixture of hydrophilic, (poly vinyl alcohol, PVA, and randomly methylated beta-cyclodextrin, RM beta-CD), and hydrophobic (poly D,L-lactide, PLA, and poly D,L-lactide-co-glycoside, PLGA) polymers were electrospun to make a multi-layered/multicomponent nanofiber mat. The release characteristics of the drug were modified using the layer by layer approach to help compensate the limitation of the individual materials. Incorporation of RM beta-CD to the PVA solution was able to significantly decrease the degradation rate of the resulting fiber mat from a few weeks to a few seconds. Hydrophilic polymer mat (PVA-RM beta-CD) can dissolve in the release media instantly and provide rapid release of the drug. This characteristic makes such carriers suitable as sublingual delivery systems in the treatment of acute disorders. Polyesters, PLA and PLGA, can control drug release via hydrolysis of the polymer and provide sustained and controlled release of the drug. Blends of these hydrophilic and hydrophobic polymers can effectively prolong drug release and decrease physiological toxicity resulting from fast release of drugs. These carriers may be suitable for the treatment of chronic disease where sustained release of the drug is required.

Novel vitamin and gold-loaded nanofiber facial mask for topical delivery.

L-ascorbic acid has been widely used in cosmetic and dermatological products because of its ability to scavenge free radicals and destroy oxidizing agents. However, it is chemically unstable and can easily be oxidized. The current cosmetic facial masks available in the market are pre-moistened, which means that the aqueous fluid content of the mask may oxidize some of the unstable active ingredients such as ascorbic acid. This work presents an anti-wrinkle nanofiber face mask containing ascorbic acid, retinoic acid, gold nanoparticles, and collagen. This novel face mask will only be wetted when applied to the skin, thus enhancing product stability. Once moistened, the content of the mask will gradually dissolve and release the active ingredients and ensure maximum skin penetration. The high surface area-to-volume ratio of the nanofiber mask will ensure maximum contact with the skin surface and help to enhance the skin permeation to restore its healthy appearance. Electrospun fiber mats may provide an attractive alternative to the commercial facial cotton masks.

Transdermal delivery of haloperidol by proniosomal formulations with non-ionic surfactants.

Proniosomal formulations with non-ionic surfactant were studied. The effect of hydrophilicity and hydrophobicity of one or two surfactants on drug solubility, proniosome surface structure and stability and skin permeation of haloperidol from different formulations were investigated. Haloperidol (HP) was entrapped in proniosomes with very high efficiency for all formulations. Stability studies performed at 4 degrees C and 25 degrees C for a period of 6 weeks did not reveal any significant drug leakage (p>0.05). Formulations with single surfactants were found to increase the skin permeation of HP more than formulations containing two surfactants. The number of carbons in the alkyl chain of the non-ionic surfactant influenced the in vitro permeation of HP though the epidermis and the skin permeation was increased with increase in hydrophilic-lipophilic balance (HLB) value of the surfactant. Interfacial tension and surfactant hydrophobicity appeared to be useful for elucidating mechanism of skin permeation and for comparing drug fluxes from different proniosomal formulations.

Impact of surface tension in pharmaceutical sciences.

Surface chemistry has a large influence in many industries. In the life sciences, surface area is gaining importance in the characterization of materials during their development, formulation and manufacturing. The chemical activity, adsorption, dissolution, and bioavailability of a drug may depend on the surface of the molecule. In order to meet manufacturing challenges and develop new and better performing products with improved qualities, knowledge of surface tension is of utmost importance. An attempt has been made in this paper to review the application of interfacial tension in the key domains of pharmaceutical applications.

Infrared authentication of ginseng species: the use of the 2-6PC rule.

The quality of herbal products is important for ensuring efficacy and consumer safety. Traditional methods of authenticating herbs like ginseng via their morphology are hardly reliable. Different chemical constituents in herbs like ginseng tend to exhibit characteristic IR fingerprints that enable their identification. We previously introduced an IR-based protocol known as the "2-6PC rule" to categorize and identify ginseng and its products, as well as distinguishing it from morphological fakes. Here, we describe the use of this rule as a rapid and effective means of analyzing the IR spectral fingerprints of the biologically active components of ginseng, as well as distinguishing among its species. Our results show that Panax ginseng, P. quinquefolius, and P. notoginseng can be differentiated from each other. Our results also indicate the presence of starch, carbohydrates, calcium oxalate, and ginsenosides Re and Rg1 in commercial ginseng roots sold in Singapore. This work effectively demonstrates the usefulness of the 2-6PC rule as a rapid screening tool in the authentication of ginseng species.

A Point Prevalence Study of Antimicrobial Use and Practice Among Nursing Homes in Singapore.

BACKGROUND: Inappropriate antimicrobial use is a major cause for the development of antimicrobial resistance in nursing homes (NHs); however, little is known about antimicrobial use at NHs in Singapore compared with NHs in other countries. OBJECTIVES: The aim of this study was to determine the prevalence, practice and challenges of antimicrobial prescribing in Singapore NHs compared with those in other countries. METHODS: A point prevalence survey (PPS) was conducted from August to October 2017. Data on antimicrobial use and the quality of documentation were retrieved from medical and/or medication records of NH residents. Informed consent was obtained from the NH management. RESULTS: Nine of 73 NHs in Singapore, with a total of 1760 residents, participated in the PPS. The prevalence of oral antibiotic and topical antimicrobial use was 2% and 11%, respectively, and the worldwide point prevalence of antimicrobial prescribing in NHs ranged from 1-17% (median 8%). The key challenges identified locally were different from those of overseas NHs, including incomplete documentation of antimicrobial duration and indication of use, as well as the high prevalence of topical antimicrobial use. CONCLUSIONS: The prevalence of oral antibiotic use in NHs in Singapore was lower, while topical antimicrobial use was higher, compared with NHs in other countries. Variability in antimicrobial prescribing and challenges in practice among local and overseas NHs implied that a comprehensive PPS could be beneficial to aid in the design of effective and practicable antimicrobial stewardship strategies appropriate for the NH.

Spontaneous cutaneous adverse drug reaction reports-An analysis of a 10-year dataset in Singapore.

We analyzed the spontaneous adverse event database in Singapore to determine the types of cutaneous adverse drug reactions (CADRs) and causative drugs reported. We selected 10 CADRs-of-interest, and identified the suspected drugs and the characteristics of the at-risk population. ADR reports received from 2006 to 2015 of the system organ class "Skin and Appendages Disorders" were analyzed based on patient demographics, the types of CADRs, suspected drugs, outcome, and latency period. Of the 104 372 reports analyzed, 56.2% involved females and 72.5% involved Chinese patients. The mean age was 41.1 years old. The top CADRs reported were rash (including nonspecified rash, follicular rash, maculopapular rash, and vesicular rash) (67.2%) and angioedema (13.9%). The drugs frequently associated with the CADRs-of-interest include nonsteroidal antiinflammatory drugs and antibiotics with angioedema, iohexol with urticaria, and antiepileptics and allopurinol with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). A subgroup analysis based on age, sex, and race on the 10 CADRs-of-interest showed the following trends in reporting: Alopecia (reported more in females), drug hypersensitivity syndrome (more in males), angioedema (more in younger patients), and photosensitivity (more in older patients). In general, the racial distribution across each CADR-of-interest was consistent with that of Singapore's population, with slight deviations observed for SJS/TEN, photosensitivity and skin discoloration. We analyzed CADR reports from Singapore over 10 years, and identified the types of CADRs reported, and their associated drugs, latency periods and patient characteristics. Such information could add value to healthcare professionals as they assess CADR cases and evaluate suspected drugs.

Association between access to health-promoting facilities and participation in cardiovascular disease (CVD) risk screening among populations with low socioeconomic status (SES) in Singapore.

BACKGROUND: Low socioeconomic status (SES) is a barrier for cardiovascular disease (CVD) risk screening and a determinant of poor CVD outcomes. This study examined the associations between access to health-promoting facilities and participation in a CVD risk screening program among populations with low SES residing in public rental flats in Singapore. METHODS: Data from Health Mapping Exercises conducted from 2013 to 2015 were obtained, and screening participation rates of 66 blocks were calculated. Negative binomial regression was used to test for associations between distances to four nearest facilities (i.e., subsidized private clinics, healthy eateries, public polyclinics, and parks) and block participation rate in CVD screening. We also investigated potential heterogeneity in the association across regions with an interaction term between distance to each facility and region. RESULTS: The analysis consisted of 2069 participants. The associations were only evident in the North/North-East region for subsidized private clinic and park. Specifically, increasing distance to the nearest subsidized private clinic and park was significantly associated with lower [incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.80-0.98] and higher (IRR = 1.93, 95%CI: 1.15-3.25) screening participation rates respectively. CONCLUSIONS: Our findings could potentially inform the planning of future door-to-door screenings in urban settings for optimal prioritization of resources. To increase participation rates in low SES populations, accessibility to subsidized private clinics and parks in a high population density region should be considered.

Efficient intracellular delivery of functional proteins using cationic polymer core/shell nanoparticles.

Cationic core/shell nanoparticles self-assembled from biodegradable, cationic and amphiphilic copolymer poly{N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS-co-CES), were fabricated and employed to deliver lectin A-chain, an anticancer glycoprotein. Lectin A-chain was efficiently bound onto the surfaces of the nanoparticles at high mass ratios of nanoparticles to lectin A-chain. The nanoparticle/lectin A-chain complexes had an average size of approximately 150 nm with zeta potential of about +30 mV at the mass ratio of 50 or above while the BioPorter/lectin A-chain complexes had a larger particle size and relatively lower zeta potential (150 nm vs. 455 nm; +30 mV vs. +20 mV). Therefore, the cellular uptake of nanoparticle/lectin A-chain complexes was much greater than that of BioPorter/lectin A-chain complexes. The results obtained from cytotoxicity tests show that lectin A-chain delivered by the nanoparticles was significantly more toxic against MDA-MB-231, HeLa, HepG2 and 4T1 cell lines when compared to BioPorter, and IC50 of lectin A-chain delivered by the nanoparticles was 0.2, 0.5, 10 and 50 mg/l, respectively, while that of lectin A-chain delivered by BioPorter was higher than 100 mg/l in all cell lines tested. These nano-sized particles may provide an efficient approach for intracellular delivery of biologically active proteins.

High-affinity sulfonated materials with transition metal counterions for enhanced protein separation in dual-layer hollow fiber membrane chromatography.

High-affinity membrane materials have been successfully synthesized through a combination of the polymer sulfonation reaction with transition metal counterion exchange treatment. This type of promising materials were embodied for the first time with the aid of dual-layer hollow fiber technology for protein separation. Three types of immobilized metal affinity membranes (Cu(2+), Ni(2+) and Zn(2+) forms) were developed in this work and they all exhibited enhanced protein separation performance compared to the as-spun hollow fiber in H(+) form due to the strong affinity between transition metal counterions and target protein molecules. Ultimately, the high-purity target protein (>99%, w/w) could be achieved via the membrane in Cu(2+) form.

Physicochemical effects of terpenes on organogel for transdermal drug delivery.

It is accepted that terpenes are effective penetration enhancers to promote the passage of drugs or chemicals through the human skin barrier. However the physical and chemical changes of a pharmaceutical vehicle induced by the incorporation of terpenes have not been explored. Thus, this study examines the effects of three terpenes (linalool, cineole, limonene) on the rheology and chemical stability of an organogel composed of dibutyllauroylglutamide (GP1) and propylene glycol (PG). At a given GP1 concentration, oxygen-containing linalool and cineole decreased gel moduli (elastic and viscous) and brittleness, and the reverse was obtained for hydrocarbon limonene. Probably, linalool and cineole interfered with hydrogen bonding between GP1 molecules while limonene could have initiated a phase separation-mediated gelation, changing the gel morphology. Microcalorimetry detected minute heat endotherms for gels (with and without terpenes) subjected to accelerated heat testing. These heat changes could arise from a small degree of structural disruption of the gel network. Heat endotherms normalized with respect to GP1 content were used to assess gel chemical stability. Although the terpenes altered rheology, they did not significantly affect the chemical stability of the gels. This is the first in the literature that reports the effect of penetration enhancers, such as terpenes, on the physical, rheological and chemical characteristics of a model pharmaceutical formulation for topical and transdermal drug delivery.