Publications by authors named "Luming Shi"

21 Publications

  • Page 1 of 1

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

Am J Trop Med Hyg 2021 Jun 15. Epub 2021 Jun 15.

Duke-NUS Medical School, Singapore.

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.
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http://dx.doi.org/10.4269/ajtmh.21-0299DOI Listing
June 2021

The Test of Infant Motor Performance (TIMP) in very low birth weight infants and outcome at two years of age.

J Perinatol 2021 Jun 14. Epub 2021 Jun 14.

Department of Child Development, KK Women's and Children's Hospital, Singapore, Singapore.

Objective: To evaluate TIMP in preterm very low birth weight (VLBW) infants, analyze risk factors, for atypical TIMP (aTIMP) scores, and explore TIMP's predictive relationship with Bayley-III at 2 years.

Method: A prospective study of 288 VLBW infants, with TIMP assessment between 34 weeks postmenstrual age and 16 weeks age, corrected for prematurity.

Result: aTIMP scores were observed in 58/288(20%) infants, whose mean birth weight (BW) and gestational age were 1122 ± 257 g and 29.2 ± 2.12 weeks respectively. Risk factors included BW < 750 g (OR 4.8, 95% CI 1.3-17.7) and 750-1000 g (OR 2.9, 95% CI 1.2-6.9), presence of necrotizing enterocolitis ≥ stage 2; or focal intestinal perforation (OR 4.6, 95% CI 1.4-14.4), periventricular leukomalacia (OR 22.4,95% CI 2.0-246.2), and need for intensive resuscitation at birth (OR 2.7, 95% CI 1.3-5.5). aTIMP scores correlated with Bayley-III Score <85 in motor and cognitive domains with high specificity (80-82%) and negative predictive value (85-94%).

Conclusion: Identification of the risk factors for aTIMP scores will enable targeted intervention to optimize resources and outcomes in VLBW infants.
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http://dx.doi.org/10.1038/s41372-021-01067-wDOI Listing
June 2021

Validation of "Care of the Dying Evaluation" in Emergency Medicine (CODE-EM): pilot phase of end-of-life management protocol offered within emergency room (EMPOWER) study.

Ann Palliat Med 2021 Jun 25;10(6):6145-6155. Epub 2021 May 25.

Emergency Medicine Department, National University Hospital, National University Health System, Singapore, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: An increasing number of patients who present to emergency departments are at their end-of-life phase and have significant palliative care needs such as in symptom control for pain and dyspnoea. Evaluating quality of care provided is imperative, yet there is no suitable tool validated in the emergency and Asian settings. We aim to examine the face and construct validity, and reliability of a newly developed questionnaire, Care of the Dying Evaluation - Emergency Medicine, for measuring the quality of end-of-life care in an Asian emergency context.

Methods: A mixed methods pilot study was conducted. Participants composed of the next-of-kin to thirty dying patients who presented to the emergency departments of three public hospitals in Singapore. Qualitative evaluation, using cognitive "think-aloud" interviews, and quantitative analysis were employed. Percentage agreement and κ statistic were measured to evaluate temporal stability of the questionnaire. Cronbach's α and item-total correlations were used to assess internal consistency within the constructs. Confirmatory factor analysis was performed for construct validity.

Results: All participants reported clear understanding of the questionnaire with no ambiguity; a minority felt the questions caused emotional distress (7/30, 23.3%). The questions showed moderate to good test-retest reliability. Internal consistencies within the constructs were good for "ENVIRONMENT" and "CARE", and moderate for "COMMUNICATION". Factor loadings range from 0.40 to 0.99.

Conclusions: The Care of the Dying Evaluation - Emergency Medicine questionnaire may be valid and reliable for use in an Asian emergency setting. Our prospective multicentre study using this evaluation tool may provide more insight on the quality of care rendered to dying patients and identify areas for improvement.

Trial Registration: ClinicalTrials.gov (NCT03906747).
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http://dx.doi.org/10.21037/apm-21-380DOI Listing
June 2021

Non-steroidal anti-inflammatory drugs (NSAIDs) for trigger finger.

Cochrane Database Syst Rev 2021 04 14;4:CD012789. Epub 2021 Apr 14.

Cochrane Singapore, Singapore, Singapore.

Background: Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs.

Objectives: To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger.

Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions.

Selection Criteria: We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route.

Data Collection And Analysis: Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs).

Main Results: Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence).

Authors' Conclusions: For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.
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http://dx.doi.org/10.1002/14651858.CD012789.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094914PMC
April 2021

Academic school readiness in children born very preterm and associated risk factors.

Early Hum Dev 2021 Apr 15;155:105325. Epub 2021 Feb 15.

Department of Child Development, KK Women's and Children's Hospital, Bukit Timah Rd, 100, Singapore 229899, Singapore.

Background And Aims: Although the intelligence quotient (IQ) test is useful to assess general cognitive function, it may miss more specific and subtle deficits of learning, working memory, attention and executive function. This study aims to evaluate cognitive performance and academic school readiness (SR) concepts in preterm very low birth weight (PT/VLBW) children, compared to typically developing term controls and to evaluate factors affecting basic (SR) concepts in children with IQ>85.

Methods: A prospective cohort study of 123 PT/VLBW survivors with birth weights ≤1250 g and 74 term controls born between 2007 and 2009 in Singapore were assessed for school readiness using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Bracken School Readiness Assessment (BSRA-3) and Beery-Buktenica Developmental Test of Visual Motor Integration (VMI) at age 5.5 years. Social risk composite score (SRCS) was calculated based on ethnicity, parental education and family income and marital status. Uni- and multi-variable regressions were conducted to evaluate risk factors associated with poor academic SR in the entire cohort and in those with IQ >85.

Results: Mean gestational age and birth weight of the 123 PT/VLBW children were 27.8 (2.3) weeks and 939 (194) grams while that of the 74 term controls were 38.8 (1.2) weeks and 3165 (402) grams. PT/VLBW survivors had statistically significant lower full composite scores on WPPSI-III (97.0 vs 114), BSRA-3 (98.5 vs 112.3) and VMI (107.2 vs 112.9) compared to controls. The differences remained significant in preterm and children with higher SRCS even after adjustment.

Conclusions: Prematurity and high social composite risk scores were risk factors affecting academic SR and this difference persisted in PT/VLBW children with normal cognitive scores with IQ >85.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105325DOI Listing
April 2021

Is chemoprophylaxis required after total knee and total hip arthroplasty in the Asian population? A systematic review and network meta-analysis.

Thromb Res 2021 02 2;198:86-92. Epub 2020 Dec 2.

Department of Orthopaedic Surgery, Singapore General Hospital, Singapore.

Introduction: Although chemoprophylaxis against venous thromboembolism (VTE) after Total Joint Arthroplasty (TJA) is commonly practiced, epidemiology studies have shown Asians have a much lower incidence of VTE. The authors aim to investigate if chemoprophylaxis is really necessary in the Asian population undergoing TJA.

Material And Methods: Literature searched was conducted for randomized controlled trials or quasi-experimental studies investigating efficacy and/or safety of chemoprophylaxis for TJA without language restrictions. Network meta-analysis, comparing the incidence of 'VTE to be treated', 'VTE not to be treated', 'Minor bleeding', and 'Major bleeding' amongst the different interventions was performed using multivariate meta-regression model.

Results: 38 studies (11,769 patients) were included. Total incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) were 14.2% and 0.73% respectively. For outcome on efficiency, edoxaban, low-molecular-weight-heparin (LMWH), fondaparinux, and enoxaparin showed significantly lower Risk Ratio (RR) for 'VTE to be treated' compared to Control/Placebo. Although no interventions showed increased incidence of major bleeding, LMWH and fondaparinux showed higher RR for minor bleeding. Enoxaparin displayed the best efficacy and safety profile. Total incidence of symptomatic DVT in studies involving enoxaparin was 1.98% (1.07% in patients who received enoxaparin, 2.92% in Control/Placebo). Total incidence of proximal DVT was 2.93% (2.67% in patients who received enoxaparin, 3.11% in Control/Placebo).

Conclusion: Asian population has a much lower incidence of VTE events after TJA compared to the Western population. Although Enoxaparin is still efficacious in reducing symptomatic and proximal DVT after TJA, its benefit-to-risk ratio is much lower than described in the Western literature.
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http://dx.doi.org/10.1016/j.thromres.2020.11.033DOI Listing
February 2021

Sea-level rise and the emergence of a keystone grazer alter the geomorphic evolution and ecology of southeast US salt marshes.

Proc Natl Acad Sci U S A 2020 07 13;117(30):17891-17902. Epub 2020 Jul 13.

Department of Environmental Engineering Sciences, Engineering School of Sustainable Infrastructure and Environment, University of Florida, Gainesville, FL 32611.

Keystone species have large ecological effects relative to their abundance and have been identified in many ecosystems. However, global change is pervasively altering environmental conditions, potentially elevating new species to keystone roles. Here, we reveal that a historically innocuous grazer-the marsh crab -is rapidly reshaping the geomorphic evolution and ecological organization of southeastern US salt marshes now burdened by rising sea levels. Our analyses indicate that sea-level rise in recent decades has widely outpaced marsh vertical accretion, increasing tidal submergence of marsh surfaces, particularly where creeks exhibit morphologies that are unable to efficiently drain adjacent marsh platforms. In these increasingly submerged areas, cordgrass decreases belowground root:rhizome ratios, causing substrate hardness to decrease to within the optimal range for burrowing. Together, these bio-physical changes provoke to aggregate in high-density grazing and burrowing fronts at the heads of tidal creeks (hereafter, creekheads). Aerial-image analyses reveal that resulting "grazed" creekheads increased in prevalence from 10 ± 2% to 29 ± 5% over the past <25 y and, by tripling creek-incision rates relative to nongrazed creekheads, have increased marsh-landscape drainage density by 8 to 35% across the region. Field experiments further demonstrate that grazed creekheads, through their removal of vegetation that otherwise obstructs predator access, enhance the vulnerability of macrobenthic invertebrates to predation and strongly reduce secondary production across adjacent marsh platforms. Thus, sea-level rise is creating conditions within which functions as a keystone species that is driving dynamic, landscape-scale changes in salt-marsh geomorphic evolution, spatial organization, and species interactions.
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http://dx.doi.org/10.1073/pnas.1917869117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395507PMC
July 2020

End-of-life management protocol offered within emergency room (EMPOWER): study protocol for a multicentre study.

BMJ Open 2020 04 28;10(4):e036598. Epub 2020 Apr 28.

Emergency Medicine Department, National University Hospital, National University Health System, Singapore.

Background: Patients at their end-of-life (EOL) phase frequently visit the emergency department (ED) due to their symptoms, yet the environment and physicians in ED are not traditionally equipped or trained to provide palliative care. This multicentre study aims to measure the current quality of EOL care in ED to identify gaps, formulate improvements and implement the improved EOL care protocol. We shall also evaluate healthcare resource utilisation and its associated costs.

Methods And Analysis: This study employs a quasiexperimental interrupted time series design using both qualitative and quantitative methods, involving the EDs of three tertiary hospitals in Singapore, over a period of 3 years. There are five phases in this study: (1) retrospective chart reviews of patients who died within 5 days of ED attendance; (2) pilot phase to validate the CODE questionnaire in the local context; (3) preimplementation phase; (4) focus group discussions (FGDs); and (5) postimplementation phase. In the prospective cohort, patients who are actively dying or have high likelihood of mortality this admission, and whose goal of care is palliation, will be eligible for inclusion. At least 140 patients will be recruited for each preimplementation and postimplementation phase. There will be face-to-face interviews with patients' family members, review of medical records and self-administered staff survey to evaluate existing knowledge and confidence. The FGDs will involve hospital and community healthcare providers. Data obtained from the retrospective cohort, preimplementation phase and FGDs will be used to guide prospective improvement and protocol changes. Patient, family and staff relevant outcomes from these changes will be measured using time series regression.

Ethics And Dissemination: The study protocol has been reviewed and ethics approval obtained from the National Healthcare Group Domain Specific Review Board, Singapore. The results from this study will be actively disseminated through manuscript publications and conference presentations.

Trial Registration Number: NCT03906747.
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http://dx.doi.org/10.1136/bmjopen-2019-036598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213875PMC
April 2020

Tropical cyclone rainbands can trigger meteotsunamis.

Nat Commun 2020 02 3;11(1):678. Epub 2020 Feb 3.

US Geological Survey, Woods Hole Coastal and Marine Science Center, Woods Hole, MA, 02543, USA.

Tropical cyclones are one of the most destructive natural hazards and much of the damage and casualties they cause are flood-related. Accurate characterization and prediction of total water levels during extreme storms is necessary to minimize coastal impacts. While meteotsunamis are known to influence water levels and to produce severe consequences, their impacts during tropical cyclones are underappreciated. This study demonstrates that meteotsunami waves commonly occur during tropical cyclones, and that they can contribute significantly to total water levels. We use an idealized coupled ocean-atmosphere-wave numerical model to analyze tropical cyclone-induced meteotsunami generation and propagation mechanisms. We show that the most extreme meteotsunami events are triggered by inherent features of the structure of tropical cyclones: inner and outer spiral rainbands. While outer distant spiral rainbands produce single-peak meteotsunami waves, inner spiral rainbands trigger longer lasting wave trains on the front side of the tropical cyclones.
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http://dx.doi.org/10.1038/s41467-020-14423-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997351PMC
February 2020

The safest and most efficacious route of tranexamic acid administration in total joint arthroplasty: A systematic review and network meta-analysis.

Thromb Res 2019 Apr 11;176:61-66. Epub 2019 Feb 11.

Department of Orthopaedic Surgery, Singapore General Hospital, Singapore.

Introduction: Blood loss in Total Joint Arthroplasty can be significant and often under-estimated. This study aims to investigate the safety and efficacy of different routes of tranexamic acid (TXA) administration in reducing blood transfusion after Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). The secondary aim is to find the safest and most efficacious route and dose of TXA.

Material And Methods: PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, and OpenGrey were systemically searched for randomised controlled trials investigating the efficacy and/or safety of TXA for THA and/or TKA. Network meta-analysis, comparing the number of transfusion and deep vein thrombosis (DVT) among different interventions, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach.

Results: 211 publications (20,639 individuals) were included. For outcome of transfusion, all interventions showed significantly lower transfusion rates compared to placebo. When compared to placebo, TXA via intra-venous and topical showed statistically significant lowest risk ratio (RR = 0.11, 95CI: 0.03, 0.41). For safety, TXA via topical showed relatively lowest risk ratio (RR = 0.75, 95CI 0.44, 1.30). TXA via topical and intra-articular had the highest but statistically insignificant RR (RR = 1.10, 95%CI: 0.51, 2.38). Therefore, current studies did not reveal any significant safety issue in using TXA.

Conclusion: All forms of TXA administration showed significantly lower transfusion rate compared to control. There is a trend towards better efficacy with intra-venous and topical. In patients with higher risk of thrombosis, physicians may consider topical alone for its best safety profile.
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http://dx.doi.org/10.1016/j.thromres.2019.02.006DOI Listing
April 2019

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis.

United European Gastroenterol J 2018 Nov 20;6(9):1294-1306. Epub 2018 Apr 20.

Department of Pathophysiology, University of Leuven, Leuven, Belgium.

Background: Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests.

Aim: This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors.

Methods: Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied.

Results: Fifteen studies ( = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99).

Conclusions: Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.
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http://dx.doi.org/10.1177/2050640618772787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206531PMC
November 2018

Factors affecting neurodevelopmental outcome at 2 years in very preterm infants below 1250 grams: a prospective study.

J Perinatol 2018 08 1;38(8):1093-1100. Epub 2018 Jun 1.

Department of Child Development, KK Women's and Children's Hospital, Singapore, Singapore.

Objective: To evaluate the neurodevelopmental outcomes of preterm very-low birth weight (PT/VLBW) infants at 2 years and identify risk factors associated with significant developmental delay or neurodevelopmental impairment (NDI).

Study Design: We evaluated 165 PT/VLBW infants born between January 2010 and December 2011, using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). NDI was defined as the presence of neurosensory impairment or significant delay with Bayley-III score < 70 in any domain and risk factors for delay/NDI were assessed using logistic regressions.

Results: Median Bayley-III composite scores in the cognitive, language and motor domains were 95, 89 and 94, respectively. NDI was present in 20% of the children, with 5-18% having significant delay in either cognitive, language or motor domain, seven (4%) children had cerebral palsy, three (2%) were deaf and none were blind. Regression models identified significant positive associations of delayed cognitive skills with male gender (Odds ratio (OR) 22.4, 95% confidence interval (CI) 1.5-341.1; P = 0.025), lack of anntenatal steroids (ANS) (OR 41.5, 95% CI 3.5-485.7; P = 0.003), and hypotension needing inotropes (OR 36.0, 95% CI 2.6-506.0; P = 0.008); delayed language skills with lower maternal education (OR 3.8, 95% CI 1.4-10.3; P = 0.10), lack of ANS (OR 2.8, 95% CI 1.1-7.4; P = 0.04), and 5 minute Apgar Score ≤ 5 (OR 7.4, 95% CI 1.4-38.4; P = 0.017) and delayed motor skills with chronic lung disease at 36 weeks (OR 38.3, 95% CI 2.4-603.4; P = 0.010). NDI was associated with lack of ANS (OR 2.91, 95% CI 1.21-7.00; P = 0.02) and use of postnatal steroids (OR 3.36, 95% CI 1.07-10.54; P = 0.0374).

Conclusion: Risk factors for both NDI and individual domain delay were identified and will be helpful in planning of specific and targeted early intervention services.
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http://dx.doi.org/10.1038/s41372-018-0138-3DOI Listing
August 2018

Expressing diagnostic test performance, whose perspective - God's or Man's?

Int J Cardiol 2018 09 19;267:215-216. Epub 2018 May 19.

Singapore Clinical Research Institute, Singapore; Duke-NUS Medical University, Singapore.

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http://dx.doi.org/10.1016/j.ijcard.2018.05.067DOI Listing
September 2018

Nutritional intake and growth velocity in preterm extremely low-birthweight infants in Asia: Are we doing enough?

J Paediatr Child Health 2017 Dec 18;53(12):1199-1207. Epub 2017 Aug 18.

Department of Neonatology, KK Women's and Children's Hospital, Singapore.

Aim: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile.

Methods: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model. Univariable analysis was applied to identify the potential risk factors associated with poor GV at day 28 and at discharge from hospital.

Results: The median GV from birth to day 28 was 9.84 g/kg/day and 11.87 g/kg/day for GV from birth to discharge. Increased protein and energy intake was associated with higher GV at discharge. Hypotension needing inotropes, necrotising enterocolitis (NEC), patent ductus arteriosus and chronic lung disease were significantly associated with reduced GV at discharge. Infants with NEC, hypotension needing inotropes and sepsis took a significantly longer time to achieve full enteral nutrition. A longer time to attain full enteral feeds was associated with slower GV at discharge. Small-for-gestational-age babies increased from 22% at birth to 66.6% at discharge.

Conclusions: GV at discharge was positively correlated with increasing protein and energy intake in the first 28 days and adversely affected by the presence of neonatal morbidities. There was strong evidence of extra-uterine growth restriction, with the majority of preterm ELBW infants having lower z scores at discharge compared to at birth.
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http://dx.doi.org/10.1111/jpc.13630DOI Listing
December 2017

Effects of Aortic Valve Replacement on Severe Aortic Stenosis and Preserved Systolic Function: Systematic Review and Network Meta-analysis.

Sci Rep 2017 07 11;7(1):5092. Epub 2017 Jul 11.

Duke-NUS Medical School, Singapore, Singapore.

The survival benefits of aortic valve replacement (AVR) in the different flow-gradient states of severe aortic stenosis (AS) is not known. A comprehensive search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were conducted to identify studies that investigated the prognosis of severe AS (effective orifice area ≤1.0 cm) and left ventricular ejection fraction ≥50%. Severe AS was stratified by mean pressure gradient [threshold of 40 mmHg; high-gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35 ml/m; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted to assess all-cause mortality among each AS sub-type with rate ratio (RR) reported. The effects of AVR on prognosis were examined using network meta-regression. In the pooled analysis (15 studies and 9,737 patients), LF states (both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88; 95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS; and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR 1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred different survival benefits: it was most effective in NFHG (RR /RR : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR /RR : 1.19; 95% CI: 0.74-1.94).
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http://dx.doi.org/10.1038/s41598-017-05021-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505951PMC
July 2017

Combined diagnostic performance of coronary computed tomography angiography and computed tomography derived fractional flow reserve for the evaluation of myocardial ischemia: A meta-analysis.

Int J Cardiol 2017 Jun 22;236:100-106. Epub 2017 Feb 22.

National Heart Center Singapore, Singapore; Duke-NUS Medical School, Singapore. Electronic address:

Background: To evaluate the combined diagnostic accuracy of coronary computed tomography angiography (CCTA) and computed tomography derived fractional flow reserve (FFRct) in patients with suspected or known coronary artery disease (CAD).

Methods: PubMed, The Cochrane library, Embase and OpenGray were searched to identify studies comparing diagnostic accuracy of CCTA and FFRct. Diagnostic test measurements of FFRct were either extracted directly from the published papers or calculated from provided information. Bivariate models were conducted to synthesize the diagnostic performance of combined CCTA and FFRct at both "per-vessel" and "per-patient" levels.

Results: 7 articles were included for analysis. The combined diagnostic outcomes from "both positive" strategy, i.e. a subject was considered as "positive" only when both CCTA and FFRct were "positive", demonstrated relative high specificity (per-vessel: 0.91; per-patient: 0.81), high positive likelihood ratio (LR+, per-vessel: 7.93; per-patient: 4.26), high negative likelihood ratio (LR-, per-vessel: 0.30; per patient: 0.24) and high accuracy (per-vessel: 0.91; per-patient: 0.81) while "either positive" strategy, i.e. a subject was considered as "positive" when either CCTA or FFRct was "positive", demonstrated relative high sensitivity (per-vessel: 0.97; per-patient: 0.98), low LR+ (per-vessel: 1.50; per-patient: 1.17), low LR- (per-vessel: 0.07; per-patient: 0.09) and low accuracy (per-vessel: 0.57; per-patient: 0.54).

Conclusion: "Both positive" strategy showed better diagnostic performance to rule in patients with non-significant stenosis compared to "either positive" strategy, as it efficiently reduces the proportion of testing false positive subjects.
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http://dx.doi.org/10.1016/j.ijcard.2017.02.053DOI Listing
June 2017

Prospective evaluation of the Ages and Stages Questionnaire 3rd Edition in very-low-birthweight infants.

Dev Med Child Neurol 2017 05 24;59(5):484-489. Epub 2016 Nov 24.

Department of Neonatology, KK Women's and Children's Hospital, Singapore.

Aim: To evaluate the predictive and concurrent diagnostic agreement of the Ages and Stages Questionnaire 3rd Edition (ASQ-3) with the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) in infants born preterm and very-low-birthweight (PT/VLBW; ≤1250g).

Method: We evaluated 141 PT/VLBW infants (68 males, 73 females) born at the KK Women's and Children's Hospital between January 2010 and December 2011, to determine predictive and concurrent diagnostic agreement between the ASQ-3 at 9, 12, 18, and 24 months corrected age and Bayley-III at 24 months. Cut-offs on the ASQ-3 at 24 months were estimated by receiver operating characteristic curves.

Results: Sixty (43%) and 25 (18%) failed in any domain of the ASQ-3 and Bayley-III (<70) respectively. A negative predictive value (NPV) >98% was achieved for the motor domain from 9 months, and >90% for the communication domain and the overall results at 24 months. Optimal referral ASQ-3 score at 24 months to achieve 100% NPV was 243.

Interpretation: In PT/VLBW infants, ASQ-3 screening at 24 months can reduce the need for costly psychometric assessments in children with normal results. Clinicians can be assured of normal motor development at 9 months using the ASQ-3, but should continue to screen children on other domains.
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http://dx.doi.org/10.1111/dmcn.13307DOI Listing
May 2017

Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria.

Hepatology 2015 Jan 29;61(1):227-37. Epub 2014 May 29.

Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore; Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.

Unlabelled: Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations.

Conclusion: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.
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http://dx.doi.org/10.1002/hep.27135DOI Listing
January 2015

Use of tissue sealants in face-lifts: a metaanalysis.

Aesthetic Plast Surg 2009 May 17;33(3):336-9. Epub 2008 Dec 17.

Department of Plastic, Reconstructive and Aesthetic Surgery, Kandang Kerbau Women's and Children's Hospital, Singapore, Singapore.

Background: This review sought to determine the efficacy of tissue sealants such as fibrin tissue adhesives and platelet-rich plasma in reducing postoperative drainage, ecchymosis, and edema after face-lift surgery.

Methods: The electronic databases MEDLINE (1966-May 2007) and EMBASE (1974-May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for human studies, randomized controlled trials, controlled clinical trials, metaanalyses, and reviews of randomized controlled trials using the key words "fibrin tissue adhesive," "tissue sealant," "platelet-rich plasma," "face-lift," "rhytidoplasty," "rhytidectomy," and "facial plastic surgery." The search yielded 10 articles, only 3 of which met our inclusion criteria. The three studies were within-patient comparisons (patients acted as their own controls).

Results: Although not statistically significant, the pooled results showed a strong trend toward reduction in postoperative drainage at 24 h and ecchymosis with the use of tissue sealants compared with the control arm of the study. No difference in outcomes was observed between the tissue sealant and control arms of the study in terms of postoperative edema measurement.

Conclusion: There was no statistically significant benefit from the use of tissue sealants in face-lift surgery. However, tissue sealants may be useful for patients at a high risk for hematoma and ecchymosis formation.
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http://dx.doi.org/10.1007/s00266-008-9280-1DOI Listing
May 2009

Interventions for the management of oral submucous fibrosis.

Cochrane Database Syst Rev 2008 Oct 8(4):CD007156. Epub 2008 Oct 8.

UKCC (Bahrain Branch), Ministry of Health, Bahrain, Box 25438, Awali, Bahrain.

Background: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity which is more commonly found in patients in the Asian subcontinent and the Far East. It is characterised by the progressive build up of constricting bands of collagen in the cheeks and adjacent structures of the mouth which can severely restrict mouth opening and tongue movement and cause problems with speech and swallowing.

Objectives: To assess the effectiveness of interventions for the management of pain and restricted jaw opening or movement occurring as a result of oral submucous fibrosis.

Search Strategy: We searched the Cochrane Oral Health Group's Trials Register to July 2008; CENTRAL (The Cochrane Library 2008, Issue 2); MEDLINE (from 1950 to July 2008); EMBASE (from 1980 to July 2008) and IndMED on 18th November 2007. There were no language restrictions.

Selection Criteria: Randomised controlled trials comparing surgical interventions, systemic or topical medicines or other interventions to manage the symptoms of oral submucous fibrosis.

Data Collection And Analysis: Two authors independently assessed trial quality and extracted trial data. Disagreements were resolved by consultation with a third author. Attempts were made to contact study authors where necessary for clarification and for additional information.

Main Results: Two trials, involving 87 participants, evaluated lycopene in conjunction with intralesional injections of a steroid, and pentoxifylline in combination with mouth stretching exercises and heat. Only two of the primary but none of the secondary outcomes of this review were considered in these trials and provided a limited amount of unreliable data. The data in one trial were based on inadequately defined evaluations of outcomes, and in the other trial are likely to be skewed due to a substantial number of withdrawals and therefore were not entered into the RevMan analyses. There were no reports of toxicity to the interventions but some side effects, which were mostly gastric irritation to pentoxifylline, were noted.

Authors' Conclusions: The lack of reliable evidence for the effectiveness of any specific interventions for the management of oral submucous fibrosis is illustrated by the paucity, and poor methodological quality, of trials retrieved for this review.
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http://dx.doi.org/10.1002/14651858.CD007156.pub2DOI Listing
October 2008

Electrical impedance tomography based on sensitivity theorem with singular value decomposition.

Conf Proc IEEE Eng Med Biol Soc 2005;2005:1488-91

School of Communication and Information Engineering, Shanghai University, Shanghai 200072, P.R.China. Phone: 8621-56333213; Fax: 8621-56336908; e-mail: P.M. Yan:

In electrical impedance tomography (EIT), distribution of internal resistivity of an unknown object is estimated using measured boundary voltage induced by different current patterns. In this paper singular value decomposition is modified with a threshold to be used in the sensitivity theorem for reconstruction of EIT images. Two different parameters are added to the singular values according to a threshold. The method has a major impact on efficient solution of EIT to achieve improved image resolution. Computer simulation and experiments indicate that this method performs better than the previous truncated SVD without using the threshold in terms of reconstructed image resolution.
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http://dx.doi.org/10.1109/IEMBS.2005.1616713DOI Listing
October 2012
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