OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.
METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.
RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).
CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.
METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.
RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.
CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.
METHODS: RNA was isolated from peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls) were assessed using the Affymetrix array. We also collected expression data from 447 patients with other cancers (201 patients) and non-cancer conditions (246 patients). Multivariate logistic regression analysis was used to obtain biomarker signatures differentiating NPC samples from controls and other diseases. Differences were also analysed within a subset (n=28) of a pre-intervention case cohort of patients whom we followed post-treatment.
RESULTS: A blood-based gene expression signature composed of three genes - LDLRAP1, PHF20, and LUC7L3 - is able to differentiate NPC from various other diseases and from unaffected controls with significant accuracy (area under the receiver operating characteristic curve of over 0.90). By subdividing our NPC cohort according to the degree of patient response to treatment we have been able to identify a blood gene signature that may be able to guide the selection of treatment.
CONCLUSION: We have identified a blood-based gene signature that accurately distinguished NPC patients from controls and from patients with other diseases. The genes in the signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of the head and neck, tumour-associated antigens, and/or cellular signalling. We have also identified blood-based biomarkers that are (potentially) able to predict those patients who are more likely to respond to treatment for NPC. These findings have significant clinical implications for optimizing NPC therapy.
OBJECTIVE: This study aimed to determine the survival rate of breast cancer among the women of Malaysia and characteristics of the survivors.
METHOD: A retrospective cohort study was conducted on secondary data obtained from the Breast Cancer Registry and medical records of breast cancer patients admitted to Hospital Kuala Lumpur from 2005 to 2009. Survival data were validated with National Birth and Death Registry. Statistical analysis applied logistic regression, the Cox proportional hazard model, the Kaplan-Meier method and log rank test.
RESULTS: A total of 868 women were diagnosed with breast cancer between January 2005 and December 2009, comprising 58%, 25% and 17% Malays, Chinese and Indians, respectively. The overall survival rate was 43.5% (CI 0.573-0.597), with Chinese, Indians and Malays having 5 year survival rates of 48.2% (CI 0.444-0.520), 47.2% (CI 0.432-0.512) and 39.7% (CI 0.373-0.421), respectively (p<0.05). The survival rate was lower as the stages increased, with the late stages were mostly seen among the Malays (46%), followed by Chinese (36%) and Indians (34%). Size of tumor>3.0cm; lymph node involvement, ERPR, and HER 2 status, delayed presentation and involvement of both breasts were among other factors that were associated with poor survival.
CONCLUSIONS: The overall survival rate of Malaysian women with breast cancer was lower than the western figures with Malays having the lowest because they presented at late stage, after a long duration of symptoms, had larger tumor size, and had more lymph nodes affected. There is an urgent need to conduct studies on why there is delay in diagnosis and treatment of breast cancer women in Malaysia.
METHODS: Data are obtained from the Malaysia Non-Communicable Disease Surveillance-1. Logistic regressions are conducted using a multiracial (Malay, Chinese, Indian and other ethnic groups) sample of 2,447 observations to examine the factors affecting individual decisions to consume FV on a daily basis.
RESULTS: Based on the binary outcomes of whether individuals consumed FV daily, results indicate that work hours, education, age ethnicity, income, gender, smoking status, and location of residence are significantly correlated with daily fruit consumption. Daily vegetable consumption is significantly correlated with income, gender, health condition, and location of residence.
CONCLUSIONS: Our results imply the need for programs to educate and motivate consumers to make healthier dietary choices. Interventions to increase FV consumption by changing behaviors should be considered, as should those that increase public awareness of the dietary benefits of FV. These intervention programs should be targeted at and tailored toward individuals who are less educated, younger, less affluent, males, smokers, and metropolitan dwellers.
METHODS: Researchers developed 6 culturally relevant disease scenarios varying from low to high medical seriousness. Quota samples of approximately 290 middle-aged urban residents in Australia, China, Malaysia, India, South Korea, Thailand, and the USA completed an online survey that examined desired levels of FI and identified individual difference predictors in each country. All reliability coefficients were acceptable. Regression models met standard assumptions.
RESULTS: The strongest finding across all 7 countries was that those who desired higher self-involvement (SI) in medical decision making also wanted lower FI. On the other hand, respondents who valued relational-interdependence tended to want their families involved - a key finding in 5 of 7 countries. In addition, in 4 of 7 countries, respondents who valued social hierarchy desired higher FI. Other antecedents were less consistent.
CONCLUSION: These results suggest that it is important for health providers to avoid East-West cultural stereotypes. There are meaningful numbers of patients in all 7 countries who want to be individually involved and those individuals tend to prefer lower FI. On the other hand, more interdependent patients are likely to want families involved in many of the countries studied. Thus, individual differences within culture appear to be important in predicting whether a patient desires FI. For this reason, avoiding culture-based assumptions about desired FI during medical decision making is central to providing more effective patient centered care.
RESEARCH DESIGN AND METHODS: Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, ≥150 to <300, ≥300 to <450, and ≥450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model.
RESULTS: During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (≥450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40; P for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; P for trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86; P for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; P for trend = 0.38).
CONCLUSIONS: Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.
METHODS: Men from Dolakha, Nepal, who had ever migrated outside of Nepal for work were interviewed on their experiences, from predeparture to return (n=194). Forced labour was assessed among those who returned within the past 10 years (n=140) using the International Labour Organization's forced labour dimensions: (1) unfree recruitment; (2) work and life under duress; and (3) impossibility to leave employer. Forced labour is positive if any one of the dimensions is positive.
RESULTS: Participants had worked in India (34%), Malaysia (34%) and the Gulf Cooperation Council countries (29%), working in factories (29%), as labourers/porters (15%) or in skilled employment (12%). Among more recent returnees (n=140), 44% experienced unfree recruitment, 71% work and life under duress and 14% impossibility to leave employer. Overall, 73% experienced forced labour during their most recent labour migration.Forced labour was more prevalent among those who had taken loans for their migration (PR 1.23) and slightly less prevalent among those who had migrated more than once (PR 0.87); however the proportion of those who experienced forced labour was still high (67%). Age, destination and duration of stay were associated with only certain dimensions of forced labour.
CONCLUSION: Forced labour experiences were common during recruitment and at destination. Migrant workers need better advice on assessing agencies and brokers, and on accessing services at destinations. As labour migration from Nepal is not likely to reduce in the near future, interventions and policies at both source and destinations need to better address the challenges migrants face so they can achieve safer outcomes.