Abdul Aziz Baba

Prevalence and associated factors of stress, anxiety and depression among prospective medical students

Many studies have reported that the prevalence of psychological distress among medical students during medical training was high. However, there are very few studies exploring on the psychological health of prospective medical students. This study aimed to determine the prevalence and associated factors for stress, anxiety and depression symptoms among the prospective medical students. A cross-sectional study was done on two cohorts of applicants to a public medical school. A total of 839 applicants were invited to participate in the study. The 21-item Depression Anxiety Stress Scale was administered to the applicants after they completed interviews. A total of 743 (92.2%) applicants took part in the study. The prevalence of moderate to extremely severe level of stress, anxiety and depression were 3.6%, 54.5% and 1.9%, respectively. Stress was significantly associated with extra-curricular activity (p<0.001) and race (p<0.001). Anxiety was associated with extra-curricular activity (p<0.001), race (p<0.001), mother education level (p=0.002) and CGPA group (p=0.034). Depression was associated with academic performance in class (p<0.001) and race (p=0.004). Prevalence of stress and depression among entering medical students was low; however prevalence of anxiety was high which could be due to worry about the interviews to enter medical course. The associated factors of psychological distress among prospective medical students were related to academic, non-academic, parent education and cultural backgrounds.

The impact of medical education on psychological health of students: a cohort study.

Many studies have shown that the prevalence of psychological distress among medical students during medical training is higher than that in general population. A few studies have shown that the prevalence of psychological distress among medical students before the onset of medical training was similar to general population. This study aimed to investigate psychological health of medical students before and during medical training. A one-year prospective study was done on successful applicants who undergo the first year of medical training for 2010/2011 academic session. The stress, anxiety and depression were measured by the DASS-21 at five intervals; during interview (Time 0), two months (Time 1), four months (Time 2), six months (Time 3) and final examination (Time 4) of the first year medical training. The prevalence of unfavourable stress, anxiety and depression before the onset of medical training was 4.1%, 55.6% and 1.8%, respectively. The prevalence of unfavourable stress during medical training ranged between 11.8% and 19.9%. The prevalence of anxiety during medical training ranged between 41.1% and 56.7%. The prevalence of depression during medical training ranged between 12% and 30%. Mean scores of stress and depression before (Time 0) and during medical training (Time 1–4) were significantly different (p < 0.001). The prevalence and level of unfavourable stress and depression during medical training were significantly higher than before the onset medical training. This study supports views that medical training is not an optimal environment to psychological health of medical students.

Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients

The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.

A comparison between infrared tympanic thermometry, oral and axilla with rectal thermometry in neutropenic adults

BACKGROUND This study assessed the agreement between infrared tympanic membrane (TM), axillary, corrected axillary (+0.5 degrees C), oral, and corrected oral (+0.3 degrees C) to rectal thermometry as reference standard in neutropenic adults. The sensitivity and specificity of the mentioned thermometries in detecting rectal fever (> or =38 degrees C) were also analysed. METHOD This is a comparative diagnostic test study. A total of 400 sets of blinded simultaneous temperature readings were measured from 21 haemato-oncology in-patients with neutropenia following chemotherapy. Three-hundred sets were then randomly sampled. Agreements were analysed using random two-way intraclass correlation (ICC). Sensitivity and specificity were analysed using contingency 2x2 table. FINDINGS Both right and left TM thermometry have good correlation with rectal thermometry; 0.810 (95% CI, 0.748-0.855) and 0.770 (95% CI, 0.713-0.815) respectively. Axilla thermometry has weak agreement (ICC 0.486 (95% CI, 0.118-0.689)) with rectal thermometry. The sensitivity (sn) and specificity (sp) in detecting rectal fever (> or =38 degrees C) were: right TM (sn) 0.712 (95% CI, 0.586-0.814), (sp) 0.957 (95% CI, 0.920-0.978); oral (sn) 0.561 (95% CI, 0.433-0.681), (sp) 0.983 (95% CI, 0.954-0.995); and axilla (sn) 0.348 (95% CI, 0.238-0.477), (sp) 0.996 (95% CI, 0.973-0.999). INTERPRETATION Single tympanic membrane thermometry is in good agreement with rectal thermometry. It is more sensitive than oral or axillary thermometry in detecting rectal fever.

BCR-ABL kinase domain mutations, including 2 novel mutations in imatinib resistant Malaysian chronic myeloid leukemia patients—Frequency and clinical outcome

Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine kinase inhibitor (TKI) has resulted in its use as the frontline therapy for chronic myeloid leukemia (CML) across the world. Although high response rates are observed in CML patients who receive IM treatment, a significant number of patients develop resistance to IM. Resistance to IM in patients has been associated with a heterogeneous array of mechanisms of which point mutations within the ABL tyrosine kinase domain (TKD) are the frequently documented. The types and frequencies of mutations reported in different population studies have shown wide variability. We screened 125 Malaysian CML patients on IM therapy who showed either TKI refractory or resistance to IM to investigate the frequency and pattern of BCR-ABL kinase domain mutations among Malaysian CML patients undergoing IM therapy and to determine the clinical significance. Mutational screening using denaturing high performance liquid chromatography (dHPLC) followed by DNA sequencing was performed on 125 IM resistant Malaysian CML patients. Mutations were detected in 28 patients (22.4%). Fifteen different types of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G, N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were identified, with T315I as the predominant type of mutation. The data generated from clinical and molecular parameters studied were correlated with the survival of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer prognosis compared to those without mutation. Interestingly, when the prognostic impact of the observed mutations was compared inter-individually, E355G and Y253H mutations were associated with more adverse prognosis and shorter survival (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart from those mutations occurring in the three crucial regions (catalytic domain, P-loop and activation-loop), other rare mutations also may have high impact in the development of resistance and adverse prognosis. Presence of mutations in different regions of BCR-ABL TKD leads to different levels of resistance and early detection of emerging mutant clones may help in decision making for alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis associated with acquired TKI resistance. Identification of these KD mutations is essential in order to direct alternative treatments in such CML patients.

HOXA4 Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673–12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.

Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCR-ABL kinase domain mutations using dHPLC followed by sequencing, and also status of BCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5%). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCR-ABL independent pathways. Different mutations confer different levels of resistance and, therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.

Clinical impact of ABCC1 and ABCC2 genotypes and haplotypes in mediating imatinib resistance among chronic myeloid leukaemia patients

The introduction and success of imatinib mesylate (IM) has brought about a paradigm shift in chronic myeloid leukaemia (CML) treatment. However, despite the high efficacy of IM, clinical resistance develops due to a heterogeneous array of mechanisms. Pharmacogenetic variability as a result of genetic polymorphisms could be one of the most important factors influencing resistance to IM. The aim of this study was to investigate the association between genetic variations in drug efflux transporter ABCC1 (MRP1) and ABCC2 (MRP2) genes and response to IM in patients with CML.

The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions

The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women.

P-1408 - Prevalence and associated factors of stress, anxiety and depression among entering medical students

Introduction Many studies have shown that the prevalence of psychological distress among medical students during medical training is high. However, there are few studies explore on the psychological health of medical students prior to the medical training. Objectives To determine the prevalence and associated factors of entering medical students had significant stress, anxiety and depression symptoms prior to medical course. Aims This study was an attempt to explore the psychological health aspects of entering medical students prior to medical training. Methods A cross-sectional study was done on two cohorts of applicants to a medical school. A total of 839 applicants were invited to participate in the study. The DASS-21 was administered to them after they completed interviews to measure stress, anxiety and depression level. Moderate to extremely severe levels of stress, anxiety and depression were considered as significant levels. Results A total of 743 (92.2%) applicants took part in the study. Approximately 26 (3.6%) experienced stress, 400 (54.5%) experienced anxiety, and 14 (1.9%) experienced depression. Stress associated with entry qualification, previous academic performance, race, involvement in extra-curricular activities, and parent education levels. Anxiety associated with parent concern about religion education, entry qualification, extra-curricular activities, previous academic performance, race and mother education level. Depression associated with parent concern about friends, entry qualification, extra-curricular activities, previous academic performance and race. Conclusion The prevalence of stress and depression among entering medical students was low prior to medical training. Its associated factors seem to be related to academic, parent and student personal backgrounds.