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.
OBJECTIVES: The study aims to develop and validate scales (direct and indirect) based on a modified Theory of Planned Behavior (TPB) to measure factors associated with the provision of PCare for HDS users by Thai CPs.
METHOD: Item generation for the scales was based on the theoretical constructs of the modified TPB framework, literature review, and authors' previous qualitative study. Draft items were then subjected to content validity and face validity. Psychometric testing was carried out among CPs in Bangkok, Thailand. Refinement of the scales utilized factor analysis and validity was assessed using factor analysis and Rasch analysis. Internal consistency reliability and construct reliability were used to assess the scales' reliability.
RESULTS: Initially, the direct and indirect scales contained 15 and 28 items, respectively and were reduced to 12 and 16 items, after experts' review. Factor analysis further reduced the number of items of the indirect scale to 13. For both scales, confirmatory factor analysis showed model-data fit. Each construct of the direct scale was significant predictors of intention. Moreover, each construct of the direct scale correlated positively and significantly with the respective construct of the indirect scale, signifying concurrent validity. No misfit item was identified in the Rasch analysis and the majority of items were invariant across gender. Internal consistency reliability and construct reliability of the scales were acceptable.
CONCLUSION: This study presents the development and validation of theoretically-grounded scales to measure the factors associated with the provision of PCare for HDS users by Thai CPs.