Warfarin versus direct oral anticoagulants in South Asian octogenarians: a retrospective review.

To investigate the efficacy and safety outcomes of warfarin and direct oral anticoagulants in Asian octogenarians. A retrospective study was undertaken in 270 patients aged 80 years old and above, between 15 July 2015 and 21 December 2017, prescribed oral anticoagulation (OAC) with warfarin or direct oral anticoagulant (DOAC). Data collection included demographics, bleeding events, cessation of anticoagulation, mortality and hospital utilization up to 2 years post prescription. Thrombotic and embolic events within 30 days of anticoagulation cessation were reviewed. Data was analysed according to initial prescription of either warfarin or DOAC. There were 134 patients on warfarin and 136 patients on DOAC, of which majority of them were on anticoagulation for atrial fibrillation. In the warfarin group, there was a higher rate of minor bleeding events leading to permanent cessation (12.7 vs. 2.9%, P  = 0.035) compared with DOAC. Mortality rate at 2 years was higher in the warfarin group than DOAC (40.3 vs. 28.7%, P  = 0.044). There was no difference in major bleeding events, risk of gastrointestinal bleed or ICH between the two groups. There was no difference in rate of thrombotic and embolic events after cessation of anticoagulation and hospital utilization over 2 years was similar in both groups. In Asian octogenarians on anticoagulation, DOAC appears to have benefit over warfarin in terms of minor bleeding risk and mortality.

Paroxysmal hemicrania masquerading as a stroke in an elderly gentleman: case report.

BACKGROUND: Paroxysmal hemicrania has not been associated with ipsilateral weakness, loss of sensation and Horner's syndrome. This report is the first of its kind documented in literature. CASE PRESENTATION: This was an elderly, sixty-five-year-old Chinese male who presented with a headache fulfilling criteria of paroxysmal hemicrania and was found to have signs of ipsilateral conjunctival injection, Horner's syndrome, weakness and loss of sensation; with resolution of the patient's physical signs after relief of the headache. Brain magnetic resonance imaging did not show any strokes or other headache mimics. The patient had a marked response to indomethacin and a decrease of headache intensity and frequency with indomethacin prophylaxis. CONCLUSIONS: Paroxysmal hemicrania has joined the list of stroke chameleons and that it would be one of the differentials in a patient with hemiplegia, hemisensory loss, autonomic signs and severe headache. It suggests that paroxysmal hemicrania in the elderly present atypically.

Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever. METHODS: To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21-65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01619969. FINDINGS: We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (-1·86, SD 1·07) than in the placebo group (-1·64, 0·75), but the difference was non-significant (-0·22, 90% CI -0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16-26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups. INTERPRETATION: Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue. FUNDING: STOP Dengue Translational Clinical Research.

Epidemiology and control of chikungunya fever in Singapore.

OBJECTIVES: We conducted an epidemiological review of the chikungunya fever situation in Singapore and described the measures taken to prevent the chikungunya virus from becoming entrenched in the tropical city-state. METHODS: All laboratory-confirmed cases and outbreak investigation reports maintained by the Communicable Diseases Division, Ministry of Health, and Aedes mosquito surveillance data obtained by the National Environment Agency during the period 2006 and 2009 were reviewed and analysed. RESULTS: Sporadic cases were imported into Singapore until the first local transmission occurred in an urban area where Aedes aegypti was the predominant vector. Subsequent introduction of a mutant viral strain (A226V) in early 2008 resulted in the rapid spread to suburban and rural areas where Aedes albopictus was the primary vector. 1072 cases including 812 (75.7%) indigenous cases were reported. The main sources of importation were India and Malaysia. Foreign contract workers were identified as high-risk for indigenous infections. CONCLUSIONS: The disease was successfully brought under control through aggressive vector control measures directed at A. albopictus. Although the incidence has sharply declined since January 2009, a high degree of vigilance is maintained to prevent a recurrence of epidemic transmission which can occur even with a well-established nationwide mosquito control programme.

Outbreak of novel influenza A (H1N1-2009) linked to a dance club.

INTRODUCTION: This paper describes the epidemiology and control of a community outbreak of novel influenza A (H1N1-2009) originating from a dance club in Singapore between June and July 2009. MATERIALS AND METHODS: Cases of novel influenza A (H1N1-2009) were confirmed using in-house probe-based real-time polymerase chain reaction (PCR). Contact tracing teams from the Singapore Ministry of Health obtained epidemiological information from all cases via telephone. RESULTS: A total of 48 cases were identified in this outbreak, of which 36 (75%) cases were patrons and dance club staff, and 12 (25%) cases were household members and social contacts. Mathematical modelling showed that this outbreak had a reproductive number of 1.9 to 2.1, which was similar to values calculated from outbreaks in naïve populations in other countries. CONCLUSION: This transmission risk occurred within an enclosed space with patrons engaged in intimate social activities, suggesting that dance clubs are places conducive for the spread of the virus.

Hydrogen sulfide regulates intracellular pH in rat primary cultured glia cells.

Intracellular pH (pH(i)) plays an important role in the regulation of central nervous system function. In the present study, we examined whether hydrogen sulfide (H(2)S), a recently recognized neuromodulator, regulates pH(i) in rat primary cultured glia cells. pH(i) was measured with a fluorescent sensitive dye, BCECF-AM. Activities of Cl(-)/HCO(3)(-) exchanger and Na(+)/H(+) exchanger were examined by assessing their capacities to load or extrude H(+) upon NH(4)Cl pulse load. We found that NaHS, a H(2)S donor, decreased pH(i) in a concentration-dependent manner ranging from 10 to 200muM in the primary cultured microglia. Blockade of the Cl(-)/HCO(3)(-) exchanger with, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or Na(+)/H(+) exchanger with 5-N-methyl-N-isobutylamiloride (MIA) significantly attenuated the pH(i)-lowering effect of NaHS. Moreover, NaHS significantly increased the activity of Cl(-)/HCO(3)(-) exchanger but inhibited that of Na(+)/H(+) exchanger. The pH regulatory effect of H(2)S was also observed in primary cultured astrocytes, but not in SH-SY5Y neuronal cells. In conclusion, we found for the first time that H(2)S induced intracellular acidification in glia cells via regulation of the activities of Cl(-)/HCO(3)(-) exchanger and Na(+)/H(+) exchanger. The present study may provide new evidence for H(2)S to serve as a neuromodulator and offer a potential approach for the treatment of neurological diseases.

Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells.

Hydrogen sulfide (H(2)S) is now known as a new biological mediator. In the present study, the effects of H(2)S on intracellular calcium ([Ca(2+)](i)) in neuronal SH-SY5Y cells was investigated. In SH-SY5Y neuronal cells, NaHS, a H(2)S donor, concentration-dependently increased [Ca(2+)](i). The H(2)S-induced Ca(2+) elevation was significantly attenuated by EGTA-treated calcium-free Krebs' solution. This elevation was also reduced by antagonists of L-type (verapamil and nifedipine), T-type (mibefradil) calcium channels and N-methyl-d-aspartate receptor (MK-801, AP-5 and ifenprodil). A 90% reduction in H(2)S-induced [Ca(2+)](i) elevation was found in cells pretreated with combination of all three kinds of inhibitors. Depletion of intracellular Ca(2+) store with thapsigargin or cyclopiazonic acid or blockade of ryanodine receptor with ruthenium red significantly attenuated the effect of H(2)S on [Ca(2+)](i). Inhibition of protein kinase A (PKA), phospholipase C (PLC) and protein kinase C (PKC) suppressed the H(2)S-elevated [Ca(2+)](i), suggesting that H(2)S may regulate [Ca(2+)](i) via both PKA and PLC/PKC pathways. In conclusion, it was found in this study that H(2)S increased [Ca(2+)](i) in SH-SY5Y neuronal cells by increasing Ca(2+) influx via plasma membrane and in turn releasing calcium from intracellular calcium store. The findings in the present study provide the direct evidence that H(2)S may serve as a neuromodulator.

Hydrogen sulfide: a novel signaling molecule in the central nervous system.

Hydrogen sulfide is an endogenously produced gas in the central nervous system and has been touted as the body's third gaseous signaling molecule after nitric oxide and carbon monoxide. A review of the current understanding of hydrogen sulfide is necessary in view of the current plethora of research in this area. The aim of this review is to present the current understanding of H(2)S as a signaling molecule in the central nervous system (CNS). This objective is achieved by discussing the involvement of H(2)S in the regulation of (1) intracellular signaling molecules such as protein kinase A, receptor tyrosine kinases, mitogen kinases and oxidative stress signaling, (2) ion channels such as calcium (L-type, T-type and intracellular stores), potassium (K(ATP) and small conductance channels) and cystic fibrosis transmembrane conductance regulator chloride channels, (3) the release and function of neurotransmitters such as gamma-aminobutyric acid, N-methyl-D-aspartate, glutamate and catecholamines. The role of H(2)S as an important mediator in a myriad of neural functions inclusive of neuroprotection is also discussed throughout the review.

Entomologic and virologic investigation of Chikungunya, Singapore.

Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas.