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Chen C.L.H.,National University of Singapore | Venketasubramanian N.,Raffles Hospital | Lee C.F.,Singapore Clinical Research Institute | Wong K.S.L.,Chinese University of Hong Kong | Bousser M.-G.,Lariboisiere University Hospital
Stroke | Year: 2013

BACKGROUND AND PURPOSE - Early vascular events are an important cause of morbidity and mortality in the first 3 months after a stroke. We aimed to investigate the effects of MLC601 on the occurrence of early vascular events within 3 months of stroke onset. METHODS - Post hoc analysis was performed on data from subjects included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study, a randomized, placebo-controlled, double-blinded trial that compared MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate severity in the preceding 72 hours. Early vascular events were defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death occurring within 3 months of stroke onset. RESULTS - The frequency of early vascular events during the 3-month follow-up was significantly less in the MLC601 group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk difference=-2.7%; 95% confidence interval, -5.1% to -0.4%; P=0.025) without an increase in nonvascular deaths. Kaplan-Meier survival analysis showed a difference in the risk of vascular outcomes between the 2 groups as early as the first month after stroke (Log-rank P=0.024; hazard ratio, 0.51; 95% confidence interval, 0.28-0.93). CONCLUSIONS - Treatment with MLC601 was associated with reduced early vascular events among subjects in the CHIMES study. The mechanisms for this effect require further study. © 2013 American Heart Association, Inc.


Tan D.,Raffles Hospital | Tan D.,SGP General Hospital | Chng W.J.,National University of Singapore | Chou T.,Niigata Cancer Center Hospital | And 6 more authors.
The Lancet Oncology | Year: 2013

Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia. © 2013 Elsevier Ltd.


Tan D.,Raffles Hospital | Tan D.,Singapore General Hospital | Tan S.Y.,Singapore General Hospital | Tan S.Y.,National University of Singapore | And 7 more authors.
The Lancet Oncology | Year: 2013

Treatment of B-cell non-Hodgkin lymphomas has undergone substantial developments in the past 10 years. The introduction of rituximab has greatly improved survival outcomes in patients. Clinical practice guidelines based on current evidence have been developed to provide recommendations for standard treatment approaches. However, guidelines do not take into account resource limitations in resource-poor countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs between Asian countries can hinder the delivery of optimum care to patients with lymphoma in Asia. We outline guidelines appropriate to different levels of health-care resources and expertise, aiming to provide advice on diagnosis and treatment, unify interpretation of results, and allow the design of future studies in Asia. In this resource-adapted consensus, we summarise recommendations for diagnosis, staging, risk stratification, and treatment of common B-cell non-Hodgkin lymphomas in Asia. © 2013 Elsevier Ltd.


Navarro J.C.,University of Santo Tomas of Philippines | Baroque A.C.,University of Santo Tomas of Philippines | Lokin J.K.,University of Santo Tomas of Philippines | Venketasubramanian N.,Raffles Hospital | Venketasubramanian N.,National University of Singapore
International Journal of Stroke | Year: 2014

Stroke is the Philippines' second leading cause of death. It has a prevalence of 0·9%; ischemic stroke comprises 70% while hemorrhagic stroke comprises 30%. Age-adjusted hypertension prevalence is 20·6%, diabetes 6·0%, dyslipidemia 72·0%, smoking 31%, and obesity 4·9%. The neurologist-to-patient ratio is 1:330·000, with 67% of neurologists practicing in urban centers. Health care is largely private and the cost is borne out-of-pocket by patients and their families. Challenges include delivering adequate support to the rural communities and to the underprivileged sectors. © 2014 World Stroke Organization.


Xu X.,National University of Singapore | Hilal S.,National University of Singapore | Collinson S.L.,National University of Singapore | Yi Chong E.J.,National University of Singapore | And 4 more authors.
Stroke | Year: 2015

Background and Purpose-The present study sought to examine the association between the burden of cerebrovascular disease (CeVD) as assessed by multimodal magnetic resonance imaging and neurocognitive function. Methods-Cognitively impaired patients and controls were tested on an extensive neuropsychological battery and underwent multimodal brain magnetic resonance imaging. CeVD markers determined from magnetic resonance imaging included the presence of multiple lacunes, multiple cerebral microbleeds, and moderate or severe white matter hyperintensities as markers for small-vessel disease and cortical stroke and intracranial stenosis as markers for large-vessel disease. A weighted CeVD burden score was constructed, and its association with global and domain-specific cognitive performance was investigated. Results-A total of 305 cases and 94 controls were included in the analysis. A graded association of CeVD burden with neurocognitive function was found. Moreover, a clear threshold of CeVD burden was associated with severe impairment. White matter hyperintensities was associated with global neurocognitive deficits, whereas microbleeds were associated with domain-specific impairments. Conclusions-The weighted CeVD burden score comprising markers of both small-and large-vessel diseases were associated with deficits in both global and domain-specific neurocognitive function. Additional studies are needed to validate the use of this CeVD burden score for the prediction of dementia. © 2015 American Heart Association, Inc.


Chu H.P.,Raffles Hospital | Logarajah V.,KK Womens and Childrens Hospital | Tan N.,KK Womens and Childrens Hospital | Phua K.B.,KK Womens and Childrens Hospital
Singapore Medical Journal | Year: 2013

Introduction This study examined the characteristics and trends in the incidence of inflammatory bowel disease (IBD) among children in Singapore. Methods We retrospectively reviewed all patients under 18 years diagnosed with IBD over a 14-year period. Information on demographics, disease presentation, laboratory findings, radiological investigations, and endoscopic and histological findings were obtained from the patients' medical records. Results 32 patients were diagnosed with IBD, 30 of whom had Crohn's disease and 2 had ulcerative colitis. The incidence of IBD rose from an initial rate of 2.2 per 100,000 patients in the year 2000 to a peak of 11.4 patients per 100,000 patients by 2008. Median age of onset of symptoms was 10.5 years. There were more boys (63%) than girls in the group and a higher representation of Indians (34.4%). The most common presenting symptoms were abdominal pain (87.5%), diarrhoea (75.0%) and weight loss (71.9%). Extraintestinal manifestations such as fever and arthralgia were found in over 50% of patients. The most common physical findings were perianal abnormalities (56.3%), mouth ulcers (37.5%) and growth failure (15.6%). Abnormal laboratory findings such as low albumin, raised erythrocyte sedimentation rate, anaemia, thrombocytosis and high C-reactive protein were found in nearly half of the patients. Endoscopic and histological findings showed that a majority of patients (90.6%) also had evidence of inflammation in the upper gastrointestinal tract. Conclusion Paediatric IBD is on the rise. The higher occurrence in Indians, earlier onset and more florid presentation may suggest different genetic and environmental influences specific to Asian children.


Bathla G.,University of Iowa | Hegde A.,Raffles Hospital
Clinical Radiology | Year: 2016

Lymphoma may arise within the central nervous system (CNS), known as primary CNS lymphoma (PCNSL) or may involve the CNS secondary to systemic disease. Clinical features are non-specific. A provisional diagnosis of PCNSL can be made on imaging, potentially changing the management algorithm from neurosurgical resection to biopsy. PCNSL in immunocompetent patients generally presents late, is solid, is bright on diffusion weighted imaging and shows uniform enhancement. Contiguity with a cerebrospinal fluid (CSF) surface and perivascular enhancement are useful clues. Immunocompromised patients, on the other hand, present earlier and often have multiple, necrotic, haemorrhagic lesions with irregular or rim enhancement. Secondary CNS involvement predominantly affects the leptomeninges. This review illustrates the varied imaging features of CNS lymphoma, atypical presentations, and differential diagnoses. © 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.


Macleod D.B.,Duke University | Habib A.S.,Duke University | Ikeda K.,Duke University | Spyker D.A.,Alexza Pharmaceuticals Inc. | And 3 more authors.
Anesthesia and Analgesia | Year: 2012

BACKGROUND: Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato® Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (≥98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption.METHODS: We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 μg and inhaled fentanyl 25 μg on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 μg). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect.RESULTS: In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations.CONCLUSIONS: This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration. Copyright © 2012 International Anesthesia Research Society.


Anil G.,Singapore General Hospital | Anil G.,Changi General Hospital | Tay K.-H.,Singapore General Hospital | Howe T.-C.,Raffles Hospital | Tan B.-S.,Singapore General Hospital
CardioVascular and Interventional Radiology | Year: 2011

This study reviews our experience with dynamic computed tomographic angiography (CTA) as an imaging modality in the evaluation of popliteal artery entrapment syndrome (PAES). Eight patients with surgically proven PAES were included in this study. Dynamic CTA studies performed with the feet in neutral and plantar flexed positions were reviewed for the detailed anatomy of the region and to define the location and extent of the stenosis, occlusions and collateral circulation. These findings were compared with intraoperative observations. CTA provided adequate angiographic and anatomic information required to arrive at the diagnosis and make a surgical decision. Thirteen limbs were affected in eight patients. There was popliteal artery occlusion in four limbs, stenosis at rest that was accentuated on stress imaging in two limbs, and patent popliteal artery with marked stenosis on stress imaging in seven limbs. Long-segment stenosis was seen in functional entrapment compared to short-segment stenosis in anatomic PAES. Anteroposterior compression of the popliteal artery in anatomic PAES unlike the side-to-side compression in functional PAES was a unique observation in this study. The CTA and surgical characterisation and classification of PAES matched in all the patients, except for misinterpretation of compressing fibrous bands as accessory slips of muscles in three limbs. In conclusion, dynamic CTA is a robust diagnostic tool that provides clinically relevant information and serves as a rapidly performed and easily available "one-stop-shop" imaging modality in the management of PAES. © 2010 Springer Science+Business Media, LLC.


Zhang J.,Zhengzhou University | Ho K.-Y.,Raffles Hospital | Wang Y.,Zhengzhou University
British Journal of Anaesthesia | Year: 2011

Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966-2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of ≥300 mg, there was a reduction of 8.8 mg [weighted mean difference (WMD)]. At pregabalin doses <300 mg, cumulative opioid consumption was even lower (WMD, -13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting [risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56-0.95]. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95-5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery. © The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

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