Informed consent in clinical practice: Old problems, new challenges.

Informed consent is a fundamental tenet of patient-centred clinical practice as it upholds the ethical principle of patient autonomy and promotes shared decision-making. In the medicolegal realm, failure to meet the accepted standards of consent can be considered as medical negligence which has both legal and professional implications. In general, valid consent requires three core components: (1) the presence of mental capacity - characterised by the patient's ability to comprehend, retain information, weigh options and communicate the decision, (2) adequate information disclosure - based on the 'reasonable physician' or 'reasonable patient' standards and (3) voluntariness in decision-making. Nonetheless, in real-world clinical settings, informed consent is not always optimally achieved, due to various patient, contextual and systemic factors. In this article, I herein discuss three major challenges to informed consent in clinical practice: (1) patient literacy and sociocultural factors, (2) psychiatric illnesses and elderly patients with cognitive impairment and (3) artificial intelligence in clinical care, and sought to offer practical mitigating strategies to address these barriers.

Drug-induced chylothorax as a rare pleural complication in dasatinib therapy for chronic myeloid leukaemia.

Chylothorax is a lymphatic chylous pleural effusion typically associated with traumatic (iatrogenic, non-iatrogenic) and non-traumatic (infections, malignancy, lymphatic disorders) aetiologies. Drug-induced chylothorax is uncommon and mostly reported in association with BCR-ABL tyrosine kinase inhibitor therapy.

Physicians, know thy patient.

Person-centered care is presently the standard healthcare model, which emphases shared clinical decision-making, patient autonomy and empowerment. However, many aspects of the modern-day clinical practice such as the increased reliance on medical technologies, artificial intelligence, and teleconsultation have significantly altered the quality of patient-physician communications. Moreover, many countries are facing an aging population with longer life expectancies but increasingly complex medical comorbidities, which, coupled with medical subspecialization and competing health systems, often lead to fragmentation of clinical care. In this article, I discuss what it truly means for a clinician to know a patient, which is, in fact, a highly intricate skill that is necessary to meet the high bar of person-centered care. I suggest that this can be achieved through the implementation of a holistic biopsychosocial model of clinical consultation at the physician level and fostering coordinated and continuity of care at the health systems level.

Mental health stigma in the medical profession: Where do we go from here?

Mental health conditions are highly prevalent among physicians with high rates of depression, anxiety, stress-related disorders, suicidal ideation and burnout reported among medical practitioners at all levels of training and practice. This phenomenon is in part contributed by a highly stressful clinical environment with an often suboptimal support system for doctors. Concerningly, there is hitherto a striking reluctance amongst medical trainees/practitioners to seek treatment/help for mental health-related conditions due to fear of associated stigma and negative career repercussions. In this article, we sought to raise awareness of the mental health stigma that has long been prevailing in the medical community, and review the key drivers of such stigma at the individual, community and organisational level. In general, drivers of mental health stigma in the medical profession include self-stigmatisation predisposed by physician personality and character traits, societal stereotypes about mental illness permeating through the medical community, and systemic constructs such as mandatory mental health declarations for medical licensure that perpetuate the unfortunate perception that mental illness appears synonymous with job impairment or incompetency. To destigmatise mental health issues in the medical profession, we herein propose multi-pronged strategies which can practically be implemented: 1) normalisation of mental health issues through open dialogue and sharing, 2) creating a supportive, "psychologically friendly" work environment through increased accessibility to workplace mental health support services, peer support systems, and reduction of psychiatric "name-calling" practices, and 3) reviewing systemic practices, in particular the mandatory mental health declarations for medical registration, that perpetuate mental health stigma.

Spotlighting 'Medical Collegiality'.

'Collegiality' comes from the Latin term 'Collegium', which essentially refers to a community of individuals bounded by their collective pursuit of a common goal. The concept has historical roots in both organised religion and academia, with its use subsequently extended to various industrial and corporate settings including healthcare. Nowadays, 'collegiality' has become a common buzzword adopted by the medical fraternity - often deemed as having a polite and respectful demeanour, maintaining cordial work relationships and being a team player who demonstrates willingness to help others and avoid speaking ill of fellow colleagues. While it is true that workplace incivility, aggression, bullying and verbal abuse are not uncommonly reported in highly stressful healthcare settings, which are concerning phenomena that should be addressed and prevented, the concept of 'medical collegiality' is, in reality, a rich and multi-faceted concept that is not limited to behavioural attributes, but extends to larger cultural principles and organisational constructs. In this article, we herein define 'medical collegiality' as 'a collective manifestation of respect, empathy and solidarity within the medical fraternity, driven by a common pursuit of clinical excellence in patient care, demonstrated through interpersonal/work relationships and organisational culture', by referencing historical origins of 'collegiality' in organised religion and academia. We further review the concept of 'medical collegiality' through three core lenses of cultural, behavioural and structural collegiality. Finally, we discuss the importance of medical collegiality for physician mental health and well-being, and quality of clinical care.

Learning during the pandemic: Perspectives of medical students in Singapore.

The COVID-19 pandemic has significantly disrupted medical education, particularly affecting clinical-year students. Educational institutions often had to halt, shorten or impose significant restrictions on their hospital rotations due to strict infection control and social-distancing guidelines implemented in tertiary healthcare institutions, as well as manpower and logistical constraints amid the pandemic. Thus, distance-based learning platforms such as online lectures and case-based teaching were increasingly adopted in place of bedside and face-to-face tutorials. While interactive virtual case-based discussions are generally useful in imparting clinical reasoning skills to medical students, they are unfortunately not able to fully replicate the experience of clerking, examining and managing real patients in the wards, which is a quintessential process towards building clinical acumen and attaining core clinical competencies. Therefore, for final year medical students who are preparing for their Bachelor of Medicine and Bachelor of Surgery (MBBS) examinations, many are naturally concerned by how learning in this "new normal" may affect their ability to make the transition to become competent junior doctors. As such, we seek to share our learning experiences as the first batch of medical students to have completed our entire final year of clinical education amid the COVID-19 pandemic, and offer 4 practical suggestions to future batches of students on how to adapt and optimise clinical learning under these circumstances: actively engaging in virtual learning, making the most of every clinical encounter, learning how to construct peer teaching/practice sessions, and maintaining physical and psychological well-being.

Development, internal validation and calibration of a risk score to predict survival in patients with EGFR-mutant non-small cell lung cancer.

AIMS: EGFR tyrosine kinase inhibitors (TKIs) are first-line molecularly targeted therapies in patients with advanced non-small cell lung cancer (NSCLC) who carry sensitising EGFR mutations, due to its superior survival outcomes compared with conventional chemotherapy regimens. In this study, we sought to identify clinical, immune and biochemical variables with prognostic significance in this patient subgroup and incorporate them into a nomogram-based risk score. METHODS: A total of 199 patients with EGFR mutation-positive, advanced NSCLC (defined as stage IV at initial diagnosis or incurable disease recurrence) treated with first-line EGFR TKI therapy were retrospectively profiled. Univariable and multivariable survival analyses were conducted, with variables from the multivariable model with the highest Harrell's Concordance (C) Index selected for inclusion in the subsequent survival nomogram. Internal validation and internal calibration of our prognostic nomogram were also performed. RESULTS: Serum lactate dehydrogenase (LDH) and lung/pleural metastasis were independent predictors of unfavourable overall survival in all three multivariable models. A survival nomogram was generated based on the multivariable model with the highest Harrell's C Index, incorporating the following 11 variables: white cell count, haemoglobin, LDH, neutrophil/lymphocyte ratio, ethnicity (Chinese vs non-Chinese), Karnofsky-Performance Status (score of '90-100' or '70-80' vs '0-60'), Charlson Comorbidity Index (≥3, or 2, or 1 vs 0), neurological symptoms, brain, lung/pleural and adrenal metastases. CONCLUSION: We identified serum LDH as an independent predictor of unfavourable clinical outcomes in patients with advanced, EGFR mutation-positive NSCLC. We further developed a robust nomogram-based risk score that incorporates clinical, biochemical and immune variables that can provide more targeted prognostication and management in this patient subgroup.

Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation.

BACKGROUND: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. CASE PRESENTATION: The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell transplant from her mother with normal RUNX1 profile. Comprehensive genomic analyses were performed at diagnosis, post-chemotherapy and post-transplant. A total of 8 mutations (RUNX1, GATA2, DNMT3A, BCORL1, BCOR, 2 PHF6 and CDKN2A) were identified in the pre-induction sample, of which 5 remained (RUNX1, DNMT3A, BCORL1, BCOR and 1 out of 2 PHF6) in the post-treatment sample and none were present post-transplant. In brief, the 3 mutations which were lost along with the leukemic cells at complete morphological remission were most likely acquired leukemic driver mutations that were responsible for the AML transformation from a pre-leukemic germline RUNX1-mutated state. On the contrary, the 5 mutations that persisted post-treatment, including the germline RUNX1 mutation, were likely to be part of the preleukemic clone. CONCLUSION: Further studies are necessary to assess the prevalence of these preleukemic and secondary mutations in the larger FPD/AML patient cohort and establish their prognostic significance. Given the molecular heterogeneity of FPD/AML and other AML subtypes, a better understanding of mutational classes and their involvement in AML pathogenesis can improve risk stratification of patients for more effective and targeted therapy.

Identifying large indels in targeted next generation sequencing assays for myeloid neoplasms: a cautionary tale of the ZRSR1 pseudogene.

Targeted next generation sequencing platforms have been increasingly utilised for identification of novel mutations in myeloid neoplasms, such as acute myeloid leukaemia (AML), and hold great promise for use in routine clinical diagnostics. In this study, we evaluated the utility of an open source variant caller in detecting large indels in a targeted sequencing of AML samples. While we found that this bioinformatics pipeline has the potential to accurately capture large indels (>20 bp) in patient samples, we highlighted the pitfall of a confounding ZRSR1 pseudogene that led to an erroneous ZRSR2 variant call. We further discuss possible clinical implications of the ZRSR1 pseudogene in myeloid neoplasms based on its molecular features. Knowledge of the confounding ZRSR1 pseudogene in ZRSR2 sequencing assays could be particularly important in AML diagnostics because the detection of ZRSR2 in AML patients is highly specific for an s-AML diagnosis.