Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. In 2018, the World Health Organization reported nearly 1.85 million new CRC cases and 0.88 million CRC-related deaths (Wong et al., 2019). Malaysia, together with China, Japan, Korea and Singapore, has recorded the highest 5-year prevalence of CRC (≥46.5 cases in 100,000) in Asia (Haggar and Boushey, 2009). It is well known that the prognosis of a CRC patient is strongly related to the stage at which the cancer is diagnosed. The 5-year survival rate of CRC is higher than 80% for stage 1 and 2, between 30 and 60% for stage 3, and lower than 10 % for stage 4 (Rashid et al., 2009). Although
Background Inflammatory bowel disease is an uncommon disease in developing nations whereby patient’s knowledge on the disease may be limited. The CCKNOW questionnaire, a widely known questionnaire to assess patient’s knowledge on the disease, may be too complex to comprehend for patients in developing countries. The aim of this study is to develop a new tool known as AIBDKQ questionnaire to evaluate the local inflammatory bowel disease patient’s knowledge. Methods This was a prospective study carried out in four phases. In phase 1, three gastroenterologists with expertise in IBD generated a total of 21 questions related to the general knowledge of the disease in the English language. Phase 2 involved content and face validity whereby the questions were further validated by other gastroenterologists. In phase 3, the validated questions were translated into three languages namely Malay, Mandarin and Tamil which are commonly used in Malaysia. In phase 4 (statistical validity), administration of the questionnaires to patients and hospital staff were conducted to assess the construct validity, discriminative ability, predictive validity and reliability of the questionnaires. Results A total of 21 questions were generated initially. Further evaluation indicated that 20 items had adequate kappa and content validity index for relevance (CVI: 0.714 to 1, Kapp: 0.645 to 1) and clarity (CVI: 0.714 to 1, Kapp: 0.645 to 1). The questionnaires in four languages were administered to 213 patients to assess the construct validity. Six items were removed (three for low communality, one for small loading factors, two for cross loading), resulting in 16 final questions. Assessment with 34 hospital staff involving nurses, doctors and clerks showed significant differences in knowledge between the groups (F = 14.007, p < 0.001) and were able to discriminate doctors from nurses and clerks. Another group of 18 hospital staff administered with AIBDKQ and CCKNOW questionnaires showed a Pearson’s correlation coefficient of 0.8 indicating strong correlation and concurrent predictive validity between the two questionnaires. Final assessment with 38 patients for reliability assessment revealed high intraclass correlation of the questionnaire among the four languages. Conclusions The AIBDKQ has an excellent discriminant ability and internal consistency with a strong correlation when compared to the standard CCKNOW questionnaire.
Background and AimsThiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 (NUDT15) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate the association of NUDT15 variants with leukopenia in a multiethnic population in Southeast Asia.MethodsPatients with a confirmed diagnosis of inflammatory bowel disease were recruited. We collected demographic and clinical characteristics and whole blood counts before and after initiating thiopurines. Thiopurine S-methyltransferase (TPMT) and NUDT15 genotypes were analyzed with the single nucleotide polymorphisms (SNPs) genotyping assay. Leukopenia was defined as a white blood cell (WBC) count < 3,000/μl.ResultsIn this study, 19 (18.6%) of the 102 patients who had adequate thiopurine therapy experienced leukopenia, 11 patients (57.9%) had NUDT15 c.415C > T variants, 2 patients (10.5%) had NUDT15 c.52G > A variants while one (5.3%) had a TPMT variation. Individually, NUDT15 c.415C > T had a sensitivity and specificity of 57.9% and 94.0% (odds ratio [OR] = 21.45, 95% CI 5.94–77.41, p < 0.001), respectively, for predicting thiopurine-induced leukopenia, while NUDT15 c.52G > A was only observed in patients with leukopenia. As compared with patients with wild-type NUDT15, both NUDT15 variations had a combined sensitivity and specificity of 68.4% and 94%, respectively (OR = 33.80, 95% CI 8.99–127.05, p < 0.001), for predicting thiopurine-induced leukopenia as well as a shorter onset to leukopenia (median onset [months] 2.0 vs. 5.5; p = 0.045). Sub-group analysis showed that both NUDT15 variations were strongly associated with leukopenia among the Chinese and Indians but not among the Malays.ConclusionNudix Hydroxylase 15 variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians.
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