Factors affecting residents’ internal motivation, grit, and well-being

Abstract Background Residents completing competency-based medical education for postgraduate training face many challenging situations that may compromise their well-being or result in exhaustion or burnout. Factors described in self-determination theory and grit are important for residents’ achievement of learning outcomes and well-being. This study explored the relationships among internal motivation, grit, well-being, and related factors among non-Western Asian residents. Methods We conducted an explanatory sequential mixed-methods survey-based study to explore correlations among satisfaction with basic psychological needs, grit, and well-being from September to November 2021 among residents at Ramathibodi Hospital, Mahidol University, Thailand. Data were collected with the Basic Psychological Needs Scale, Short Grit Scale, and World Health Organization-Five Well-Being Index. Next, participants with the highest and lowest scores for each scale were purposively invited to participate in semi-structured interviews. Interview data underwent thematic analysis and data collection continued until saturation was reached. Results In total, 245 residents (51% major ward, 65% female) completed the survey. There were strong associations between internal motivation, grit, and well-being (r = 0.46–0.90). Female residents had higher autonomy and relatedness scores than males (p = 0.04 and p = 0.01, respectively), and residents with less family responsibility had higher relatedness scores than other residents (p = 0.01). Residents who got more sleep had higher autonomy, relatedness, and well-being scores than those that slept less (p  5 times/week had higher well-being scores than other residents (p < 0.01). Thirty residents completed interviews. The thematic analysis revealed internal motivation, grit, and well-being were promoted by a supportive learning environment, a well-designed curriculum, actions and personalities of faculty members, and good personal factors. Conclusion Internal motivation is significantly correlated with residents’ grit, well-being, gender, family burdens, exercise, and sleep hours. Priority should be given to promoting internal motivation, grit, and well-being among residents by enhancing a positive learning environment, creating well-designed curricula, fostering good characteristics and actions among faculty members, and supporting residents’ personal lives

Effect of genetic alterations of cytarabine-metabolizing enzymes in childhood acute lymphoblastic leukemia

BACKGROUND: Single nucleotide polymorphisms (SNPs) of deoxycytidine kinase (dCK) and cytidine deaminase (CDA) are known to alter their enzymatic activities, which affect the metabolism of cytarabine. Currently, treatment of childhood acute lymphoblastic leukemia (ALL) includes cytarabine, especially in high-risk patients. Therefore, we hypothesized that a genetic variation of dCK and CDA genes may influence the risk of cytarabine-related toxicities and early response to treatment. PATIENTS AND METHODS: We included children diagnosed with ALL and lymphoblastic lymphoma (LL) stage III and IV. The patients received a modified St Jude Total Therapy Study XV protocol. Cytarabine was used during induction remission (low-dose cytarabine) and reinduction II (high-dose cytarabine) phases. Genotyping of dCK -360C>G and -201C>T and CDA 79A>C and 208G>A was performed. Minimal residual disease (MRD) at the end of the induction phase was measured using flow cytometry. RESULTS: Ninety-four children with ALL (n=90) and LL (n=4) were analyzed. The median age at diagnosis was 5.8 years (range, 0.4-15 years). All four SNPs showed predominant wild type alleles. There was no CDA-208A allele in our population. Children with dCK-360G allele were at risk of mucositis after receiving low-dose cytarabine (OR=3.7; 95%CI, 1.2-11.3). Neither dCKnor CDA polymorphisms affected the MRD status at the end of induction phase. CONCLUSION: The dCK-360G allele was found to increase the risk of mucositis after exposure to low-dose cytarabine in childhood ALL therapy

Screening for ELANE, HAX1 and GFI1 gene mutations in children with neutropenia and clinical characterization of two novel mutations in ELANE gene

Abstract Background Congenital neutropenia is a rare disease. Recurrent infections since young age are the presentation. The most common mutation causing severe congenital neutropenia (SCN) and cyclic neutropenia (CyN) is the ELANE gene. The objectives of this study were to screen the three common genetic mutations of ELANE, HAX1 and GFI1 in children with chronic neutropenia and to describe the clinical characteristics of children who had the mutations. Methods Infants having ANC  1 year having ANC < 1,500/cu mm at least 3 times in 3 months were enrolled in the study. Patients who had acquired neutropenia due to infection, immune deficiency, or drugs were excluded. The ELANE gene was first studied; and if mutations were not identified, the HAX1 and GFI1 genes were further examined. Results A total of 60 patients were enrolled in the study. The median (range) age, ratio of female to male, ANC, and last follow-up age were 9.2 (0.5–45.2) months, 1:1.2, 248 (0–1,101) /cu mm, and 19.9 (3.5–202.3) months, respectively. Infections were noted in 67.3% of all patients. ELANE gene mutation was found in only four patients (6.7%), and the rest (56 patients) showed no mutations in the HAX1 and GFI1 genes. In patients without mutations, 66.0% had normal ANC during the follow-up, with a median (range) age for normal ANC of 19.8 (4.0–60.0) months. Two novel mutations p. Ala79del (c.234_236del) and p. Val197GlufsTer18 (c.589_590insAGGCCGGC) were identified, and they respectively cause SCN and CyN. Patients with the two novel mutations presented with several episodes of infection, including pneumonia, sepsis, abscess, otitis media, and gum infection. Conclusion The genetic screening for ELANE, HAX1, and GFI1 gene mutations in 60 patients with chronic neutropenia could identify four patients (6.7%) with ELANE gene mutation and two novel mutations, p. Ala79del in exon 3 and p. Val197GlufsTer18 in exon 4 causing SCN; and CyN, respectively