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  1. Koh, P.S., Cha, K.H., Lucy, C., Rampal, S., Yoong, B.K.
    JUMMEC, 2012;15(2):1-7.
    MyJurnal
    BACKGROUND:
    Laparoscopic cholecystectomy, although is less invasive than open surgery, is not completely pain free. The use of local anaesthesia to relieve pain following this procedure is a common practice. However, it remains debatable whether a pre- or post-operative drug administration is more effective. Here, we investigated the role of preemptive local anaesthetic infiltration given pre- or post-incisional, in relieving the pain during laparoscopic surgery.

    METHODOLOGY:
    A randomized controlled trial was conducted with 96 patients receiving 0.5% Bupivacaine 100mg. Group A (n=48) received post-incisional skin infiltration whilst Group B (n=48) received pre-incisional infiltration. Incisional (somatic) and intra-abdominal (visceral) pain was assessed using Visual Analog Scale (VAS) at day 0, day 1 and day 7 post-operative days.

    RESULT:
    Baseline characteristics between the two groups were similar. Incisional pain was lower in Group B as compared to Group A at day 0 (P=0.03) and day 1 (P0.05).

    CONCLUSION:
    Administration of pre-incisional local anaesthesia offers better pre-emptive pain relief measure than post-incisional administration by reducing somatic and visceral pain in laparoscopic gall bladder surgery.
  2. Bandyopadhyay S, Lum LC, Kroeger A
    Trop Med Int Health, 2006 Aug;11(8):1238-55.
    PMID: 16903887 DOI: 10.1111/j.1365-3156.2006.01678.x
    BACKGROUND: The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported.
    OBJECTIVES: To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice.
    METHOD: Systematic literature review of post-1975 English-language publications on dengue classification.
    RESULTS: Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities.
    CONCLUSION: A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification.
  3. Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, Gan CS
    Pediatr Crit Care Med, 2011 Jan;12(1):e7-13.
    PMID: 20190672 DOI: 10.1097/PCC.0b013e3181d505f4
    To determine the factors that predict outcome of noninvasive ventilation (NIV) in critically ill children.
  4. Lum LC, Suaya JA, Tan LH, Sah BK, Shepard DS
    Am J Trop Med Hyg, 2008 Jun;78(6):862-7.
    PMID: 18541760
    Although the disease burden of dengue is increasing, the impact on the quality of life (QoL) has not been investigated. A study to determine the QoL of confirmed dengue patients using the EuroQol visual thermometer scale was carried out at the University Malaya Medical Center. Of the 207 participants, 40% were ambulatory and 60% were hospitalized. Of eight health domains, 6.2 and 5.0 domains were affected in the hospitalized and ambulatory cohorts, respectively (P < 0.001), with cognition and interpersonal activities affected most. All patients experienced a drastic decrease in their QoL from the onset of symptoms. The QoL deteriorated to the lowest point (40% of healthy status) between the third and seventh days of illness. The duration of impaired QoL (9 days for ambulatory or 13 days for hospitalized patients) was longer than the duration of fever (5 and 7 days, respectively). Symptomatic dengue has major effects on patients' health.

    Study site: e outpatient or inpatient care at the University Malaya Medical
    Center.
  5. Lum LC, Syed Omar SF, Sri La Sri Ponnampalavanar S, Tan LH, Sekaran SD, Kamarulzaman A
    PLoS Negl Trop Dis, 2015 Jun;9(6):e0003836.
    PMID: 26047325 DOI: 10.1371/journal.pntd.0003836
    INTRODUCTION: The increasing incidence of dengue among adults in Malaysia and other countries has important implications for health services. Before 2004, in order to cope with the surge in adult dengue admissions, each of the six medical wards in a university hospital took turns daily to admit and manage patients with dengue. Despite regular in-house training, the implementation of the WHO 1997 dengue case management guidelines by the multiple medical teams was piecemeal and resulted in high variability of care. A restructuring of adult dengue inpatient service in 2004 resulted in all patients being admitted to one ward under the care of the infectious disease unit. Hospital and Intensive Care Unit admission criteria, discharge criteria and clinical laboratory testing were maintained unchanged throughout the study period.

    OBJECTIVES: To evaluate the impact of cohorting adult dengue patients on the quality of care and the clinical outcome in a university hospital in Malaysia.

    METHODS: A pre (2003) and post-intervention (2005-6) retrospective study was undertaken.

    INTERVENTION: Cohorting all dengue patients under the care of the Infectious Disease team in a designated ward in 2004.

    RESULTS: The number of patients enrolled was 352 in 2003, 785 in 2005 and 1158 in 2006. The evaluation and detection of haemorrhage remained high (>90%) and unchanged throughout the study period. The evaluation of plasma leakage increased from 35.4% pre-intervention to 78.8% post-intervention (p = <0.001) while its detection increased from 11.4% to 41.6% (p = <0.001). Examination for peripheral perfusion was undertaken in only 13.1% of patients pre-intervention, with a significant increase post-intervention, 18.6% and 34.2% respectively, p = <0.001. Pre-intervention, more patients had hypotension (21.5%) than detected peripheral hypoperfusion (11.4%), indicating that clinicians recognised shock only when patients developed hypotension. In contrast, post-intervention, clinicians recognised peripheral hypoperfusion as an early sign of shock. The highest haematocrit was significantly higher post-intervention but the lowest total white cell counts and platelet counts remained unchanged. A significant and progressive reduction in the use of platelet transfusions occurred, from 21.7% pre-intervention to 14.6% in 2005 and 5.2% in 2006 post-intervention, p<0.001. Likewise, the use of plasma transfusion decreased significantly from 6.1% pre-intervention to 4.0% and 1.6% in the post-intervention years of 2005 and 2006 respectively, p<0.001. The duration of intravenous fluid therapy decreased from 3 days pre-intervention to 2.5 days (p<0.001) post-intervention; the length of hospital stay reduced from 4 days pre- to 3 days (p<0.001) post-intervention and the rate of intensive care admission from 5.8% pre to 2.6% and 2.5% post-intervention, p = 0.005.

    CONCLUSION: Cohorting adult dengue patients under a dedicated and trained team of doctors and nurses led to a substantial improvement in quality of care and clinical outcome.

  6. Chew N, Noor Azhar AM, Bustam A, Azanan MS, Wang C, Lum LCS
    PLoS Negl Trop Dis, 2020 09;14(9):e0008562.
    PMID: 32881914 DOI: 10.1371/journal.pntd.0008562
    BACKGROUND: Dengue is a systemic and dynamic disease with symptoms ranging from undifferentiated fever to dengue shock syndrome. Assessment of patients' severity of dehydration is integral to appropriate care and management. Urine colour has been shown to have a high correlation with overall assessment of hydration status. This study tests the feasibility of measuring dehydration severity in dengue fever patients by comparing urine colour captured by mobile phone cameras to established laboratory parameters.

    METHODOLOGY/PRINCIPAL FINDINGS: Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients' clinical and laboratory hydration indices using Pearson's correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (β coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (β coefficient -2,946.255, p-value 0.007).

    CONCLUSIONS/SIGNIFICANCE: Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.

  7. Lee WS, Wong SY, Wong SY, Koay ZL, Safuan NSK, Sam ZH, et al.
    Ann Acad Med Singap, 2021 Jul;50(7):580-582.
    PMID: 34342340 DOI: 10.47102/annals-acadmedsg.2020586
  8. Rosenberger KD, Alexander N, Martinez E, Lum LCS, Dempfle CE, Junghanss T, et al.
    PLoS Negl Trop Dis, 2020 Mar;14(3):e0008076.
    PMID: 32130212 DOI: 10.1371/journal.pntd.0008076
    Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.
  9. Suaya JA, Shepard DS, Siqueira JB, Martelli CT, Lum LC, Tan LH, et al.
    Am J Trop Med Hyg, 2009 May;80(5):846-55.
    PMID: 19407136
    Despite the growing worldwide burden of dengue fever, the global economic impact of dengue illness is poorly documented. Using a common protocol, we present the first multicountry estimates of the direct and indirect costs of dengue cases in eight American and Asian countries. We conducted prospective studies of the cost of dengue in five countries in the Americas (Brazil, El Salvador, Guatemala, Panama, and Venezuela) and three countries in Asia (Cambodia, Malaysia, and Thailand). All studies followed the same core protocol with interviews and medical record reviews. The study populations were patients treated in ambulatory and hospital settings with a clinical diagnosis of dengue. Most studies were performed in 2005. Costs are in 2005 international dollars (I$). We studied 1,695 patients (48% pediatric and 52% adult); none died. The average illness lasted 11.9 days for ambulatory patients and 11.0 days for hospitalized patients. Among hospitalized patients, students lost 5.6 days of school, whereas those working lost 9.9 work days per average dengue episode. Overall mean costs were I$514 and I$1,394 for an ambulatory and hospitalized case, respectively. With an annual average of 574,000 cases reported, the aggregate annual economic cost of dengue for the eight study countries is at least I$587 million. Preliminary adjustment for under-reporting could raise this total to $1.8 billion, and incorporating costs of dengue surveillance and vector control would raise the amount further. Dengue imposes substantial costs on both the health sector and the overall economy.
  10. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al.
    Clin Infect Dis, 2020 07 11;71(2):383-389.
    PMID: 31626692 DOI: 10.1093/cid/ciz850
    BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.

    METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.

    RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).

    CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.

    CLINICAL TRIALS REGISTRATION: NCT01030211.

  11. Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, et al.
    Lancet, 2017 Apr 22;389(10079):1611-1618.
    PMID: 28283286 DOI: 10.1016/S0140-6736(17)30269-6
    BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
    METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
    FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
    INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
    FUNDING: National Medical Research Council, Singapore.
    Study site: Hospitals, Singapore; University Malaya Medical Centre (UMMC). Kuala Lumpur, Malaysia
    Study protocol: https://clinicaltrials.gov/ct2/show/NCT01030211
  12. Mousa A, Al-Taiar A, Anstey NM, Badaut C, Barber BE, Bassat Q, et al.
    PLoS Med, 2020 10;17(10):e1003359.
    PMID: 33075101 DOI: 10.1371/journal.pmed.1003359
    BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM.

    METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify.

    CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.

  13. Omeyer LCM, Duncan EM, Abreo NAS, Acebes JMV, AngSinco-Jimenez LA, Anuar ST, et al.
    Sci Total Environ, 2023 May 20;874:162502.
    PMID: 36868274 DOI: 10.1016/j.scitotenv.2023.162502
    Southeast (SE) Asia is a highly biodiverse region, yet it is also estimated to cumulatively contribute a third of the total global marine plastic pollution. This threat is known to have adverse impacts on marine megafauna, however, understanding of its impacts has recently been highlighted as a priority for research in the region. To address this knowledge gap, a structured literature review was conducted for species of cartilaginous fishes, marine mammals, marine reptiles, and seabirds present in SE Asia, collating cases on a global scale to allow for comparison, coupled with a regional expert elicitation to gather additional published and grey literature cases which would have been omitted during the structured literature review. Of the 380 marine megafauna species present in SE Asia, but also studied elsewhere, we found that 9.1 % and 4.5 % of all publications documenting plastic entanglement (n = 55) and ingestion (n = 291) were conducted in SE Asian countries. At the species level, published cases of entanglement from SE Asian countries were available for 10 % or less of species within each taxonomic group. Additionally, published ingestion cases were available primarily for marine mammals and were lacking entirely for seabirds in the region. The regional expert elicitation led to entanglement and ingestion cases from SE Asian countries being documented in 10 and 15 additional species respectively, highlighting the utility of a broader approach to data synthesis. While the scale of the plastic pollution in SE Asia is of particular concern for marine ecosystems, knowledge of its interactions and impacts on marine megafauna lags behind other areas of the world, even after the inclusion of a regional expert elicitation. Additional funding to help collate baseline data are critically needed to inform policy and solutions towards limiting the interactions of marine megafauna and plastic pollution in SE Asia.
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