INTRODUCTION: Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit. METHODS: This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m², and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test. RESULTS: A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE. CONCLUSION Serum NGAL identifies AKI and predicts three-month mortality.
Humans ; Lipocalin-2 ; Prospective Studies ; Lipocalins ; Proto-Oncogene Proteins ; Acute-Phase Proteins ; Biomarkers ; Acute Kidney Injury/diagnosis* ; Emergency Service, Hospital ; Predictive Value of Tests

Cytochrome P4502J2 (CYP2J2) metabolizes arachidonic acid (AA) to cardioprotective epoxyeicosatrienoic acids (EETs). Dronedarone, an antiarrhythmic drug prescribed for treatment of atrial fibrillation (AF) induces cardiac adverse effects (AEs) with poorly understood mechanisms. We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly, disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment. In this study, we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs. We first synthesized a deuterated analogue of dronedarone (termed poyendarone) and demonstrated that it neither inactivates CYP2J2, disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro. Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration. Next, we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat (BTB) variability reflective of proarrhythmic phenotype. In contrast, poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity. Importantly, poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF, while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk. Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.

Asian People ; Humans ; Prevalence ; Stereotyping

INTRODUCTION: A voluntary cerebral palsy (CP) registry was established in 2017 to describe the clinical characteristics and functional outcomes of CP in Singapore. METHODS: People with CP born after 1994 were recruited through KK Women's and Children's Hospital, National University Hospital and Cerebral Palsy Alliance Singapore. Patient-reported basic demographics, service utilisation and quality of life measures were collected with standardised questionnaires. Clinical information was obtained through hospital medical records. RESULTS: Between 1 September 2017 and 31 March 2020, 151 participants were recruited. A majority (n=135, 89%) acquired CP in the pre/perinatal period, where prematurity (n=102, 76%) and the need for emergency caesarean section (n=68, 50%) were leading risk factors. Sixteen (11%) of the total participants had post-neonatally acquired CP. For predominant CP motor types, 109 (72%) had a spastic motor type; 32% with spastic mono/hemiplegia, 41% diplegia, 6% triplegia and 21% quadriplegia. The remaining (42, 27.8%) had dyskinetic CP. Sixty-eight (45.0%) participants suffered significant functional impairment (Gross Motor Functional Classification System levels IV-V). Most participants (n=102, 67.5%) required frequent medical follow-up (≥4 times a year). CONCLUSION Optimisation of pre- and perinatal care to prevent and manage prematurity could reduce the burden of CP and their overall healthcare utilisation.

OBJECTIVE: In Singapore, the use of traditional Chinese medicine (TCM) alongside Western medicine (WM) is common. There are risks of adverse herb-drug interactions when taken concurrently. Current literature suggests that TCM use is not regularly reported to WM doctors in Singapore, but the underlying reasons are not understood. METHODS: A cross-sectional study was conducted across Singapore by administering questionnaires to TCM-using patients and WM-practising general practitioners (GPs). The questionnaire examined the following themes: (1) demographics and TCM use pattern; (2) respondents' (patients and GPs) knowledge and beliefs about TCM and the factors influencing the discussion of TCM during the WM consultation; and (3) respondents' qualitative suggestions to increase disclosure rate. RESULTS: A total of 484 patients and 334 GPs were surveyed. Factors associated with patients' initiation of TCM discussion include length of consultation (odds ratio [OR]: 2.1; P < 0.001), comfort level in discussing TCM (OR: 1.6; P < 0.001) and belief in importance of discussion (OR: 1.4; P = 0.017). Doctor's initiation of discussion (74%) was the top patient-ranked factor influencing their discussion of TCM. For doctors, knowledge of TCM indications (OR: 2.2; P < 0.001), belief in importance of discussion (OR: 2.1; P < 0.001) and comfort level in discussing TCM (OR: 1.9; P = 0.001) were associated with their initiation of TCM use discussion. Possible WM-TCM interactions (58%) was the top doctor-ranked factor influencing their discussion of TCM. CONCLUSION The discussion of TCM in a WM setting is multifactorial. Interventions include doctors' active screening for TCM use in patients and equipping doctors with TCM knowledge. Improving communication between patients and doctors is key to avoiding harmful herb-drug interactions.

INTRODUCTIONEnterovirus infections in childhood can be associated with significant neurological morbidity. This study aimed to describe the prevalence and range of neurological manifestations, determine the clinical characteristics and assess differences in clinical outcomes for Singaporean children diagnosed with enterovirus infections.

METHODSIn this single-centre, case-control study, clinical data was collected retrospectively from patients admitted to National University Hospital, Singapore, from August 2007 to October 2011 and diagnosed with enterovirus infection, based on the enterovirus polymerase chain reaction test, or cultures from throat and rectal swabs or cerebrospinal fluid samples. The occurrence of neurological manifestations was reviewed and clinical outcomes were assessed.

RESULTSA total of 48 patients (age range: six days-17.8 years) were included in the study. Neurological manifestations were seen in 75.0% of patients, 63.9% of whom presented with aseptic meningitis. Other neurological manifestations included encephalitis, acute cerebellitis, transverse myelitis and autonomic dysfunction. The incidence of neurological manifestations was significantly higher in patients aged > 1 year as compared to younger patients (p = 0.043). In patients without neurological manifestations, a significantly higher proportion presented with hand, foot and mouth disease and poor feeding. Long-term neurological sequelae were seen in 16.7% of patients with neurological manifestations.

CONCLUSIONA wide spectrum of neurological manifestations resulting in a relatively low incidence of long-term neurological sequelae was observed in our study of Singaporean children with enterovirus infections. As some of these neurological morbidities were severe, careful evaluation of children with neurological involvement is therefore necessary.

Adult ; Extracorporeal Membrane Oxygenation ; methods ; Female ; Humans ; Near Drowning ; complications ; diagnostic imaging ; therapy ; Neuroimaging ; Treatment Outcome

Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/β-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/β-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/β-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of β-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced β-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of β-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.
Bone Morphogenetic Protein 2 ; physiology ; Cell Differentiation ; physiology ; Dental Pulp ; cytology ; Humans ; MAP Kinase Signaling System ; Wnt Proteins ; metabolism ; beta Catenin ; metabolism

INTRODUCTIONThis study aimed to examine the impact of housemanship and cohort effect on the perceptions of what constitutes a "role model physician" between 2 cohorts of medical students.

MATERIALS & METHODSFinal year medical students of the Yong Loo Lin School of Medicine, National University of Singapore, from the classes of 2005 (pre- and post-housemanship) and class of 2009 (pre-housemanship) responded to an anonymous 25-statement questionnaire reflecting Fones et al's 25-item characterisation of a "role model" doctor. Qualitative data was also collected on student's perceived qualities of a role model doctor.

RESULTSFor the 2005 cohort pre- and post-housemanship, only 3 of the 25 items had increased in importance post-housemanship. However, when comparing the 2005 and 2009 cohorts pre-housemanship, the latter cohort placed significantly greater importance on 12 of the 25 items. Willingness to teach was identified via qualitative analysis as a new important quality of a role model doctor for medical students.

CONCLUSIONThe importance placed on characteristics of "role model" physicians were relatively unchanged by housemanship within the same cohort but increased with time between 2 cohorts 5 years apart. This suggests that professional standards of an "ideal" doctor expected and aspired to by medical students may not be eroding as feared by the medical profession and society.

Attitude of Health Personnel ; Humans ; Mentors ; Physician's Role ; Physicians ; standards ; Singapore ; Students, Medical ; psychology ; Surveys and Questionnaires

Adaptation, Psychological ; Humans ; Interdisciplinary Communication ; Male ; Muscular Dystrophy, Duchenne ; therapy ; Patients ; psychology ; Singapore