OBJECTIVE: To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance.
METHOD: The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific-High Resolution Melt (MS-HRM) analysis.
RESULTS: Both primers used to amplify promoter region from -333 to -223 and from -332 to -188 showed less than 10% methylation in all CML and normal samples. Consequently, there was no significant difference in SOCS1 promoter methylation level between IM resistant and IM good response patients.
CONCLUSION: SOCS1 promoter methylation level is not suitable to be used as one of the biomarkers for predicting the possibility of acquiring resistance among CML patients treated with IM.
Methods: A quantitative research was carried out using the methodology developed by the World Health Organization and Health Action International (WHO/HAI). The prices were compared with international reference prices (IRPs) to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used as the standard of the affordability for the medicines. In this study, ten medicines of the IHD were included. The data were collected from 10 private medicine outlets for both originator brand (OB) and lowest-priced generic brand (LPG) in Bangi, Selangor.
Results: From the results, the mean availability of OB and LPG were 30% and 42%, respectively. Final patient prices for LPG and OB were about 10.77 and 24.09 times their IRPs, respectively. Medicines that consumes more than a day's wage are considered unaffordable. Almost half of the IHD medications cost more than one day's wage. For example, the lowest paid unskilled government worker would need 1.4 days' wage for captopril, while 1.2 days' wage to purchase enalapril for LPG. Meanwhile, for OB, the costs rise to 3.4 days' wage for amlodipine and 3.3 days' wage for simvastatin.
Conclusion: The findings of this study emphasise the need of focusing and financing, particularly in the private sector, on making chronic disease medicines accessible. This requires multi-faceted interventions, as well as the review of policies and regulations.
OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.
METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.
RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.
CONCLUSIONS: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.
AIM: To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centers via a central standardised electronic data platform.
METHODS: Clinical, endoscopic and radiologic data at diagnosis from the registry were extracted between 1st January 1995 to 31st December 2019. Disease phenotypic characteristics were classified as per the Paris classification system.
RESULTS: There was a distinct rise in new PIBD cases: Nearly half (48.6%) of the cohort was diagnosed in the most recent 5 years (2015-2019). The ratio of Crohn's disease (CD):Ulcerative colitis (UC):IBD-Unclassified was 55.9%:38.3%:5.8%. The mean age was 9.07 years with a high proportion of very early onset IBD (VEO-IBD) (29.3%) and EO-IBD (52.7%). An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort (6.8%-9.0% Indians in census). Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease (P = 0.003). CD patients presented with significantly more constitutional symptoms (fever, anorexia, malaise/fatigue and muscle-wasting) than UC and higher inflammatory indices (higher C-reactive protein and lower albumin levels).
CONCLUSION: We observed a high incidence of VEO-IBD and an over-representation of the Indian ethnicity. South Asian CD patients were more likely to have symptomatic perianal disease.
METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income.
RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (β=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income.
CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.
MAIN METHODS: In silico approaches were utilized to characterize a set of 88 differentially expressed genes (DEGs) from intestinal cells of rat CMA model. Interaction networks were constructed for DEGs by GeneMANIA and hub genes as well as enriched clusters in the network were screened using GLay. Gene Ontology (GO) was used for enriching functions in each cluster.
KEY FINDINGS: Four gene hubs, i.e., trefoil factor 1, 5-hydroxytryptamine (serotonin) receptor 5a, solute carrier family 6 (neurotransmitter transporter), member 11, and glutamate receptor, ionotropic, n-methyl d-aspartate 2b, exhibiting the highest node degree were predicted. Six biologically related gene clusters were also predicted. Functional enrichment of GO terms predicted neurological processes such as neurological system process regulation and nerve impulse transmission which are related to negative and positive regulation of digestive system processes., intestinal motility and absorption and maintenance of gastrointestinal epithelium.
SIGNIFICANCE: The study predicted several important genomic pathways that potentially play significant roles in metabolic disruptions or compensatory adaptations of intestinal epithelium induced by CMA. The results provide a further insight into underlying molecular mechanisms associated with CMA.
METHODOLOGY: A prospective study was performed on children with diarrhoea of more than 14 days' duration who were managed at the Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur from 1 January 1996 to 31 December 1997.
RESULTS: Twenty-seven patients (14 boys and 13 girls) were studied. The median age of onset of diarrhoea was 6 months and the mean duration of symptoms before referral was 66.5 days. The underlying causes of diarrhoea were found to be: (i) prolonged diarrhoea due to well-defined entities (intestinal lymphangiectasia, two cases; congenital glucose-galactose malabsorption, one case; post-small bowel resection, one case; (ii) postenteritis diarrhoea (cow's milk protein intolerance, eight cases; secondary lactose intolerance, four cases; transient monosaccharide intolerance, one case; (iii) gastrointestinal infections (nontyphoid Salmonella gastroenteritis, three cases; trichuriasis, two cases; amoebiasis, one case; adenovirus, one case; (iv) cases in which a firm diagnosis could not be established (three cases). The mean duration of hospital admission was 63 days. Sixteen cases required a change in diet, while nine cases required total parenteral nutrition. One death occurred.
CONCLUSIONS: Chronic childhood diarrhoea in Malaysia had a variety of aetiologies. A specific diagnosis could be established in 90% of cases. Making a diagnosis was important because this led to appropriate therapy and a good outcome in 96% of cases.