Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7 ,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. T o expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Problem: Emergency medical teams (EMTs) deployed to mass casualty incidents (MCIs) are required to work outside their usual settings and according to different principles, which may affect their performance and the survival of casualties. Prior to 2013, training offered to domestic EMTs was limited to ad hoc and infrequent simulation exercises. Context: Domestic EMTs are activated from public tertiary hospitals to provide pre-hospital medical support to the Singapore Civil Defence Force and establish a first-aid post (FAP) for triaging, stabilizing and treating casualties. These casualties are then evacuated to public hospitals for further management. Action: Recognizing the need for a more systematic approach to the training of domestic EMTs, the Disaster Medical Responder’s Course (the Course) was developed as a multi-institutional collaboration to equip EMT members attending a MCI with the necessary skills to perform effectively at the FAP. Outcome: The Course was first run in 2013 and is usually offered six to eight times a year. Since June 2019, a total of 414 health-care staff and allied health professionals have participated. There have been numerous revisions of the course content and delivery to reflect the latest concepts in operations and global best practice, as well as developments in educational methodologies. Discussion: Preparedness is crucial to optimize the survival and outcomes of casualties. The Course provides standardized training of domestic EMTs and plays a pivotal role in ensuring operational readiness for MCIs in Singapore.

INTRODUCTION: Pericardiocentesis is a potentially life-saving procedure. We compared two low-cost models-an agar-based model and a novel model, Centesys-in terms of ultrasound image quality and realism, effectiveness of the model, and learners' confidence and satisfaction after training. METHODS: In this pilot randomised 2x2 crossover trial stratified by physician seniority, participants were assigned to undergo pericardiocentesis training either with the agar-based or Centesys model first, followed by the other model. Participants were asked to rate their confidence in performing ultrasound-guided pericardiocentesis, clarity and realism of cardiac structures on ultrasound imaging, and satisfaction on a 7-point Likert scale before and after training with each model. RESULTS: Twenty participants with median postgraduate year of 4 (interquartile range [IQR] 3.75-6) years were recruited. Pre-training, participants rated themselves a median score of 2.5 (IQR 2-4) for level of confidence in performing pericardiocentesis, which improved to 5 (IQR 4-6) post-training with Centesys ( CONCLUSION Centesys achieved greater learner satisfaction as compared to the agar-based model, and was an effective tool for teaching ultrasound-guided pericardiocentesis and drain insertion.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Catheter-Related Infections ; diagnosis ; epidemiology ; Critical Care ; Cross Infection ; diagnosis ; epidemiology ; Electronic Health Records ; Hospitalization ; Hospitals ; Humans ; Intensive Care Units ; Length of Stay ; Singapore ; Urinary Catheterization ; adverse effects ; Urinary Tract Infections ; diagnosis ; epidemiology

INTRODUCTIONThe aim of this study was to determine the prevalence of hearing loss amongst the elderly population attending community services in Singapore. The usefulness of the Hearing Handicap Inventory for the Elderly Screening version (HHIE-S) in detecting hearing loss was also investigated.

MATERIALS AND METHODSPure-tone audiometry was carried out on a randomly recruited cohort of people (n = 338) over 60 years old and who were attending rehabilitation and social day care services for senior citizens at St Luke's Elder Care centres located throughout the city. Prior to the hearing test, subjects were administered the HHIE-S questionnaire, which was translated into the language they were most conversant in.

RESULTSThe study cohort showed mean pure-tone average at speech frequencies (0.5, 1, 2 and 4 kHz; 4-frequency average hearing level [4FA HL]) of the subjects' better hearing ear that has worsened with age. The percentage of the elderly with disabling hearing impairment (4FA >40 dB HL) was 9.1% (60 to 69 years old), 22.0% (70 to 79 years old), 35.7% (80 years old and above). Across all age groups, males had significantly poorer thresholds at 4 kHz than females. When adjusted for the demographic profile of the country, the prevalence of hearing loss (4FA >25 dB HL) and disabling hearing impairment (4FA >40 dB HL) amongst the elderly in Singapore was 63.7% and 16.2%, respectively. We estimate that there are currently 422,000 elderly with hearing loss greater than 25dB HL and over 100,000 elderly with disabling hearing loss of over 40 dB HL. Of subjects with a disabling hearing impairment, only 7.5% used hearing aids. The use of self-reporting HHIE-S showed poor sensitivity in detecting hearing loss of various severities amongst the elderly.

CONCLUSIONThese data provide estimates of the prevalence and severity of hearing loss in older persons in Singapore and suggest that more can be done to help the elderly recognise, acknowledge and address hearing loss in the country.