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Leukotriene receptor antagonism may not be effective in atopic dermatitis treatment after all

Chin WK

J Clin Pharm Ther, 2018 Feb;43(1):159-162.
PMID: 29114905 DOI: 10.1111/jcpt.12648

WHAT IS KNOWN AND OBJECTIVE: Literature evidence suggests leukotriene involvement in the pathogenesis of atopic dermatitis. This article aimed to discuss whether the off-label use of montelukast, a leukotriene receptor antagonist, is justifiable for the treatment of atopic dermatitis.
COMMENT: Most non-randomized studies supported the use of montelukast for atopic dermatitis treatment. However, evidence from these studies should be interpreted with caution as it is relatively weak due to the absence of randomization, control groups and blinding processes, subjecting the results to high risk of selection and reporting biases. The inconsistent findings across RCTs may be related to the limited number of patients, nuances in study designs, varying severity of disease and the concomitant use of steroids in some of the studies.
WHAT IS NEW AND CONCLUSION: Current literature evidence is limited to rationally support the use of montelukast in atopic dermatitis treatment. For now, the conventional treatments should be preferred in the clinical setting.
A systematic review on the off-label use of montelukast in atopic dermatitis treatment

Chin WK, Lee SWH

Int J Clin Pharm, 2018 Oct;40(5):963-976.
PMID: 29777328 DOI: 10.1007/s11096-018-0655-3

Background Atopic dermatitis (AD) is the most common form of eczema. As leukotriene mediators are involved in the inflammatory phase of atopic dermatitis, montelukast has been suggested as a possible therapy. Aim of the review To evaluate the safety and efficacy of montelukast off-label use for the treatment atopic dermatitis. Method A search was performed from database inception until March 2018 in six electronic databases for randomized-controlled-trials examining the use of montelukast for AD. Results Among 301 articles screened, 11 studies met the inclusion criteria and were included in the review. The study populations consist of paediatric and adult subjects with moderate-to-severe AD. Montelukast use was shown to improve symptoms such as pruritus in four studies. Another 2 studies reported that montelukast could improve symptoms similar to the standard regimen of topical steroid and oral antihistamine. However, five studies reported that montelukast had no effects in symptoms alleviation. The use of montelukast was associated with a similar safety profile to placebo and well-tolerated with minimal adverse effects. Conclusion There is limited evidence to suggest that the off-label use of montelukast is effective in treating moderate-to-severe AD. Further research with larger study populations employing standardized endpoint measuring instrument is warranted to further investigate the off-label use of montelukast in AD treatment. Until then, the use of conventional treatments including optimal daily skin hydration should remain the mainstay in the management of atopic dermatitis. In fact, for moderate-to-severe condition, steroid sparing immune-suppressants should still be used clinically until more effective and safer alternative is discovered.
A proposal for a legally enforceable no-fault compensation framework for clinical trial-related injury in Malaysia

Chin WK, Thuraisingam AS, Kanagasabapathy S

Account Res, 2021 May 05.
PMID: 33857400 DOI: 10.1080/08989621.2021.1917397

Clinical trials play a critical role in the development of life-enhancing and life-sustaining biomedical advances. It is costly and, regardless of how well-designed and ethically conducted, there are always inherent uncertainties which subsequently expose human participants to the risk of injuries or even death. In Malaysia, compensation for clinical trial-related injury has not been incorporated into standard national regulations or policies. Therefore, when clinical trial-related injuries do occur, such participants cannot be compensated by researchers, and with the absence of specific statutory laws governing trial-related injury within the local legal framework, aggrieved parties need to seek legal redress and can only depend on the existing tort laws. To propose a viable compensation framework, the existing compensation regulations and policies implemented in India and South Africa are analyzed, and their best principles have been recommended. This study proposes the implementation of a no-fault compensation framework in Malaysia which should be disbursed efficiently at minimum administrative cost. This proposed approach should be mandated by the amendment of current laws governing biomedical research and, in the interim, should be adopted voluntarily by research sponsors, institutions and investigators conducting clinical trials in Malaysia.
The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis

Lee SWH, Ng KY, Chin WK

Sleep Med Rev, 2017 02;31:91-101.
PMID: 26944909 DOI: 10.1016/j.smrv.2016.02.001

Recent epidemiological studies have suggested that there is an association between glycemic control and sleep disturbances in patients with type 2 diabetes, but the extent is unclear. A systematic literature search was performed in nine electronic databases from inception until August 2015 without any language restriction. The search identified 20 studies (eight studies reporting duration of sleep and 15 studies evaluating sleep quality), and 15 were included in the meta-analysis. Short and long sleep durations were associated with an increased hemoglobin A1c (HbA1c) (weighted mean difference (WMD): 0.23% [0.10-0.36], short sleep; WMD: 0.13% [0.02-0.25], long sleep) compared to normal sleep, suggesting a U-shaped dose-response relationship. Similarly, poor sleep quality was associated with an increased HbA1c (WMD: 0.35% [0.12-0.58]). Results of this study suggest that amount of sleep as well as quality of sleep is important in the metabolic function of type 2 diabetes patients. Further studies are needed to identify for the potential causal role between sleep and altered glucose metabolism.
Purification of the extra-cellular domain of Nipah virus glycoprotein produced in Escherichia coli and possible application in diagnosis

Eshaghi M, Tan WS, Chin WK, Yusoff K

J Biotechnol, 2005 Mar 30;116(3):221-6.
PMID: 15707682

The glycoprotein (G) of Nipah virus (NiV) is important for virus infectivity and induction of the protective immunity. In this study, the extra-cellular domain of NiV G protein was fused with hexahistidine residues at its N-terminal end and expressed in Escherichia coli. The expression under transcriptional regulation of T7 promoter yielded insoluble protein aggregates in the form of inclusion bodies. The inclusion bodies were solubilized with 8 M urea and the protein was purified to homogeneity under denaturing conditions using nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. The denatured protein was renatured by gradual removal of the urea. Light scattering analysis of the purified protein showed primarily monodispersity. The purified protein showed significant reactivity with the antibodies present in the sera of NiV-infected swine, as demonstrated in Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Taken together, the data indicate the potential usefulness of the purified G protein for structural or functional studies and the development of immunoassay for detection of the NiV antibodies.