Publications by authors named "Chuen Seng Tan"

183 Publications

Branched Chain Amino Acid Supplementation to a Hypocaloric Diet Does Not Affect Resting Metabolic Rate but Increases Postprandial Fat Oxidation Response in Overweight and Obese Adults after Weight Loss Intervention.

Nutrients 2021 Nov 26;13(12). Epub 2021 Nov 26.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117549, Singapore.

Background: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss intervention.

Methods: A total of 111 Chinese subjects comprising 55 males and 56 females aged 21 to 45 years old with BMI between 25 and 36 kg/m were randomized into three hypocaloric diet groups: (1) standard-protein (14%) with placebo (CT), (2) standard-protein with BCAA, and (3) high-protein (27%) with placebo. Indirect calorimetry was used to measure RMR, carbohydrate, and fat oxidation before and after 16 weeks of dietary intervention.

Results: RMR was reduced from 1600 ± 270 kcal/day to 1500 ± 264 kcal/day ( < 0.0005) after weight loss, but no significant differences in the change of RMR, respiratory quotient, and percentage of fat and carbohydrate oxidation were observed among the three diet groups. Subjects with BCAA supplementation had an increased postprandial fat ( = 0.021) and decreased postprandial carbohydrate ( = 0.044) oxidation responses compared to the CT group after dietary intervention.

Conclusions: BCAA-supplemented standard-protein diet did not significantly attenuate reduction of RMR compared to standard-protein and high-protein diets. However, the postprandial fat oxidation response increased after BCAA-supplemented weight loss intervention.
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http://dx.doi.org/10.3390/nu13124245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708242PMC
November 2021

Elucidating the role of a positive family history in differentiating between axial and peripheral spondyloarthritis: an ancillary analysis of the ASAS-PerSpA study.

Clin Exp Rheumatol 2021 Dec 10. Epub 2021 Dec 10.

Department of Rheumatology and Immunology, Singapore General Hospital; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore; and Duke-NUS Medical School, Singapore.

Objectives: Positive family history (PFH) of spondyloarthritis (SpA) is important in the diagnosis of SpA. However, the contribution of a PFH in differentiating the two SpA subtypes (axial and peripheral spondyloarthritis (pSpA)), in particular the importance of second-degree relative (SDR) has not been well-studied. We aimed to investigate whether PFH of radiographic axial spondyloarthritis (r-axSpA), psoriasis, uveitis, reactive arthritis and inflammatory bowel disease in first-degree relative (FDR) and second-degree relative (SDR) contributes to differentiation between axSpA and pSpA using the data from a multinational cohort study.

Methods: The ASAS-PerSpA study dataset was used to assess the effects of a PFH on differentiating between axSpA and pSpA via generalised structural equation modelling. Model building using backward selection was performed to obtain a final model. Direct, indirect and total effects of the path analysis were calculated.

Results: A total of 3803 patients were included: 2458 axSpA and 1345 pSpA patients. FDR (OR: 3.75, 95% CI: 2.86-4.91, p<0.001) and SDR (OR: 4.58, 95% CI: 3.19-6.59, p<0.001) with r-axSpA were positively associated while FDR (OR: 0.262, 95% CI: 0.207-0.331, p<0.001) and SDR (OR: 0.305, 95% CI: 0.221-0.420, p<0.001) with psoriasis were negatively associated with differentiating patients with axSpA from pSpA.

Conclusions: The presence of r-axSpA and psoriasis in FDR or SDR are useful in differentiating axSpA from pSpA. SDR with r-axSpA may contribute greater towards the differentiation than FDR. Clinicians should consider taking an extensive family history of SpA and their subtypes to better differentiate the subtypes within the SpA spectrum.
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December 2021

Dietary intake and associations with myopia in Singapore children.

Ophthalmic Physiol Opt 2021 Dec 3. Epub 2021 Dec 3.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Purpose: To evaluate associations of dietary factors with myopia, spherical equivalent refractive error (SE) and axial length (AL) in children at age 9 from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort.

Methods: We included 467 multi-ethnic children (933 eyes) who participated in the GUSTO prospective birth cohort and were delivered in two major hospitals in Singapore (2009-2010). At the 9-year visit, we assessed the 6-year incidence of myopia (between ages 3 to 9), cycloplegic SE and AL in children without myopia (SE ≤ -0.5 D in either eye) at the 3-year visit. Using a validated 112-item food frequency questionnaire, parents reported each child's average daily intake of dietary factors (nutrients and food groups) in the past month. Paired eyes were analysed using Generalised Estimating Equations with multivariable logistic or linear regression. Bonferroni corrections were applied, correcting for multiple comparisons between the 13 nutrients (p < 0.004) or 8 food groups (p < 0.006) and each outcome.

Results: In children aged 9 years (51.0% boys; 56.3% Chinese), the 6-year incidence of myopia was 35.5%. Overall, the mean (SD) SE and AL were -0.3 (1.7) D and 23.4 (1.0) mm, respectively. In multivariable regression, macronutrients or micronutrients were not associated with incident myopia (p ≥ 0.004 for all), adjusting for total energy, gender, ethnicity, time outdoors, near-work and the number of myopic parents (additionally child's height for outcome AL). Similarly, all food groups (including refined grains, sugar-sweetened beverages, protein foods, fruits and vegetables) were not associated with incident myopia (p ≥ 0.006 for all). Additionally, none of the nutrients (p ≥ 0.004 for all) or food groups (p ≥ 0.006 for all) were associated with SE or AL.

Conclusions: Our study findings of no significant association between specific nutrients or food groups and incident myopia or SE or AL suggest that diet may not be associated with myopia in children aged 9 years. Well-conducted prospective studies in other populations may clarify the association.
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http://dx.doi.org/10.1111/opo.12929DOI Listing
December 2021

Seeking healthcare services post-stroke: a qualitative descriptive study exploring family caregiver and stroke survivor perspectives in an asian setting.

BMC Neurol 2021 Nov 5;21(1):429. Epub 2021 Nov 5.

Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, 117549, Singapore, Singapore.

Aim: Exploration of the healthcare journey post-stroke is incomplete without acknowledging the crucial role of family caregivers. With limited literature documenting the role of caregivers in the healthcare journey post-stroke, we aimed to describe the healthcare experiences of family caregivers and stroke survivors across different caregiver identities in Singapore.

Methods: We conducted a qualitative descriptive study involving semi-structured interviews with transcripts analysed using thematic analysis. 26 stroke survivors and 35 family caregivers purposively sampled from multiple settings.

Results: Findings were summarized into seeking care and experience of healthcare encounters. Seeking care comprised of the following themes: factors influencing seeking care, decision to seek care and role of caregiver in seeking care. Experience of healthcare encounters comprised of the following themes: service around the patient, service with care and role of caregiver in healthcare encounters.

Conclusion: Multi-dimensional role of caregivers in healthcare experience emerged as a major finding. Unique to our Asian context, as per the participants' accounts, family caregivers seemed to be central in healthcare decision-making for stroke survivors, with adult-child caregivers commonly reported being engaged in collaborative decision-making. While spousal caregivers preferred a relational healthcare experience, adult-child caregivers preferred a transactional one. Practical implications include equipping caregivers with skillset to make healthcare decisions, provision of supportive decision-making environment for caregivers and reinforcing communication aspects in the medical, nursing and allied healthcare curriculum to improve healthcare experience.
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http://dx.doi.org/10.1186/s12883-021-02463-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569985PMC
November 2021

Support system diversity among family caregivers of stroke survivors: a qualitative study exploring Asian perspectives.

BMC Geriatr 2021 10 25;21(1):594. Epub 2021 Oct 25.

Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, Singapore, 117549, Singapore.

Background: Caregiving is a global phenomenon which is bound to increase in tandem with the aging population worldwide. Stroke is a condition common in older people that requires complex caregiving necessitating provision of adequate support to the caregivers. Past literature consists of limited accounts of types and organization of support arrangements needed by different caregivers. We aimed to describe the support system of caregivers of stroke survivors in Singapore, highlighting differences across the different caregiver identities (i.e. spouse, adult-child, etc.).

Methods: We conducted a qualitative descriptive study in the community setting involving 61 purposively sampled and recruited stroke survivors and caregivers. Semi-structured interviews were conducted, and transcripts were analysed using thematic analysis.

Results: Our findings were summarized across the following 4 themes: 1) cultural influence and caregiving; 2) caregiver support system with the following sub-themes: 2.1) dyadic caregiver support type, 2.2) extended caregiver support type, 2.3.) distributed caregiver support type and 2.4) empowering caregiver support type; 3) breaks in care of stroke survivor and 4) complex relationship dynamics. We operationalized the caregiver support system as comprising of type, people and activities that enable the caregiver to participate in caregiving activities sustainably. While spouse caregivers preferred dyadic and extended support systems positioning themselves in a more central caregiving role, adult-child caregivers preferred distributed support system involving family members with paid caregivers playing a more central role.

Conclusions: Our findings highlight caregiver identity as a surrogate for the differences in the caregiver support systems. Practical implications include imparting relationship-building skills to the stroke survivor-caregiver dyads to sustain dyadic support system and educating clinicians to include differences in caregiving arrangements of stroke survivors in practising family-centred care.
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http://dx.doi.org/10.1186/s12877-021-02557-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543837PMC
October 2021

Colorectal cancer incidence in a multi-ethnic population: Age-period-cohort analysis of trends in Singapore.

Cancer Epidemiol 2021 12 12;75:102046. Epub 2021 Oct 12.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.canep.2021.102046DOI Listing
December 2021

Audit and Comparison Between Radiographic Markers of Gaze Direction Using EOS Imaging - An Essential Step to Streamline Existing Methods.

Spine (Phila Pa 1976) 2021 Nov;46(22):E1202-E1210

Department of Orthopedic Surgery, National University of Singapore, Singapore.

Study Design: Retrospective cohort study on prospectively implemented EOS protocol.

Objective: This study aims to audit and compare existing radiological definitions of gaze direction-chin brow vertical angle (CBVA), McGregor slope (McGS), slope of line of sight (SLS), orbital-internal occipital protuberance (OIOP) slope angle, and Tangent to the hard palate (THP) in a neutral, healthy, and asymptomatic cohort.

Summary Of Background Data: The ability to accurately define direction of gaze is the first step when striving for horizontal gaze restoration in any affected individual with rigid sagittal deformity. Yet, the radiological definition of gaze direction remains poorly standardized.

Methods: Hundred healthy subjects who could achieve horizontal gaze underwent whole-body standing EOS radiographs taken under a strictly standardized protocol. Radiographic measurements of global spinal sagittal parameters and surrogate measures of horizontal gaze were analyzed and compared.

Results: The mean age was 45 ± 15.9 years, with a balanced male-to-female-ratio. Their C7 SVA was -7.7 mm ± 24.8 mm, PI was 51.0o ± 11.4o, PI-LL was -0.9o ± 13.0o and T1-slope was 21.2o ± 9.2o. Measured horizontal gaze parameters were as follows: CBVA (1.07o ± 5.48o), McGS (-3.23o ± 5.63o), SLS (0.45o ± 5.34o), OIOP (5.03o ± 4.66o), THP (-0.17o ± 6.27o). CBVA correlated strongly with McGS (r = 0.679, P < 0.001), SLS (r = 0.592, P < 0.001), OIOP (r = 0.697, P < 0.001), and THP (r = -0.504, P < 0.001). OIOP had the lowest variance amongst all parameters and showed less variability compared to CBVA (SD 4.66 Var 21.69 vs. SD 5.48 Var 30.08, P = .012). Multivariate analysis showed that C2-7 angle was the only parameter found to be associated with OIOP values (P = 0.006).

Conclusion: OIOP is the least variable, and most robust radiological method in determining gaze direction. It uses easily recognizable anatomical landmarks and an angular criterion, which makes it advantageous both with x-rays or slot scanners.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004213DOI Listing
November 2021

Behavioral impact of national health campaigns on healthy lifestyle practices among young adults in Singapore: a cross-sectional study.

BMC Public Health 2021 08 30;21(1):1601. Epub 2021 Aug 30.

Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 1E Kent Ridge Road, NUHS Tower Block Level 11, Singapore, 119228, Singapore.

Background: National health campaigns are often used to improve lifestyle behaviors in the general population. However, evidence specifically in the young adult population is scarce. Given the general deterioration of healthy lifestyle practices from adolescence to young adulthood, it is imperative to study this age group. This study aimed to investigate the behavioral impact of a national health campaign in Singapore on the lifestyle practices of young adults, and whether sex or full-time working and schooling status affected lifestyle practices.

Methods: A total of 594 Singaporean respondents aged 18-39 years old were interviewed via a cross-sectional study in December 2019. Lifestyle practices assessed were diet, exercise, alcohol consumption, current tobacco use, and participation in health screening programs. Other factors investigated included exposure to the national health campaign "War on Diabetes" (WoD), sex, ethnicity, and working/schooling status. Multivariable modified Breslow-Cox proportional hazards models were used to estimate prevalence risk ratios (PRRs) as measures for the associations in this study, after adjusting for potential confounders.

Results: Exposure to the WoD campaign had a significant association with meeting dietary recommendations (PRR = 1.6, 95% CI: 1.0-2.5, p = 0.037), participation in screening (PRR = 1.2, 95% CI: 1.0-1.5, p = 0.028), and current tobacco use (PRR = 0.5, 95% CI: 0.3-0.8, p = 0.003). Males were significantly more likely to meet exercise recommendations (PRR = 2.0, 95% CI: 1.5-2.7, p < 0.001), currently use tobacco (PRR = 3.9, 95% CI: 2.2-6.9, p < 0.001), and consume alcohol excessively (PRR = 1.5, 95% CI: 1.0-2.3, p = 0.046), as compared to females. Working young adults were significantly less likely to meet exercise recommendations (PRR = 0.7, 95% CI: 0.5-0.9, p = 0.019) but significantly more likely to be current tobacco users (PRR = 1.8, 95% CI: 1.1-3.1, p = 0.024), as compared to those who were in school.

Conclusions: While this paper affirms that national health campaigns have significant beneficial associations in diet, health screenings and current tobacco use, policymakers should acknowledge that young adults are an age group with different influences that impact their healthy lifestyle habits. Specific interventions that target these subgroups may be required for better health outcomes. Future studies should evaluate other socio-environmental factors that could play a role in modifying the effect of health campaigns among young adults.
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http://dx.doi.org/10.1186/s12889-021-11628-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404369PMC
August 2021

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.

Crit Care 2021 08 12;25(1):292. Epub 2021 Aug 12.

Adult Intensive Care Services, Prince Charles Hospital, Brisbane, QLD, Australia.

Background: Prone positioning (PP) improves oxygenation and respiratory mechanics and is associated with lower mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS). Despite this, some patients develop refractory hypoxemia and hypercapnia requiring venovenous extracorporeal membrane oxygenation (VV ECMO) support and are usually cared for in supine position. The physiologic and outcome benefits of routine PP of patients during VV ECMO remains unclear. Hence, we conducted the systematic review and meta-analysis to evaluate the outcome benefits of PP for patients with ARDS being treated with VV ECMO.

Methods: After registration with PROSPERO (CRD42020199723), MEDLINE, EMBASE, Scopus and Cochrane databases were searched for relevant studies that reported PP in more than 10 adult patients supported with VV ECMO from origin to 1 March 2021. Studies were reviewed for quality using appropriate Joanna Briggs Institute (JBI) checklists, and certainty of evidence was assessed using the GRADE approach. The random-effects model (DerSimonian and Laird) was used. The primary outcome of interest was cumulative survival. Secondary outcomes were intensive care unit length of stay (ICU LOS) and ECMO duration. Changes in arterial blood gas (ABG) values, ventilator mechanics and complication rates were also studied.

Results: Of 812 potentially relevant publications, 12 studies (640 patients) met our inclusion criteria. Due to overlapping study populations, 11 studies were included in the final meta-analysis. Cumulative survival in patients that underwent PP was 57% (95% CI 41.9-71.4, high certainty). Patients that underwent PP had longer ICU LOS (+ 14.5 days, 95% CI 3.4-25.7, p = 0.01) and ECMO duration (+ 9.6 days, 95% CI 5.5-13.7, p < 0.0001). After PP, patients had significantly higher PaO/FiO ratio, lower PaCO and reduced ventilator driving pressure, and no major complications were reported.

Conclusions: PP during VV ECMO appears safe with a cumulative survival of 57% and may result in longer ECMO runs and ICU LOS. However, evidence from appropriately designed randomized trials is needed prior to widespread adoption of PP on VV ECMO.
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http://dx.doi.org/10.1186/s13054-021-03723-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358249PMC
August 2021

Venoarterial extracorporeal membrane oxygenation as mechanical circulatory support in adult septic shock: a systematic review and meta-analysis with individual participant data meta-regression analysis.

Crit Care 2021 07 14;25(1):246. Epub 2021 Jul 14.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival.

Methods: We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted.

Data Synthesis: We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%-72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%-60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%-73.0%) and North America (45.5%, 95%-CI: 16.7%-75.8%). GRADE assessment indicated high certainty of evidence for pooled survival.

Conclusions: When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.
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http://dx.doi.org/10.1186/s13054-021-03668-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278703PMC
July 2021

Near work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium.

Acta Ophthalmol 2021 Jun 17. Epub 2021 Jun 17.

Singapore Eye Research Institute, Singapore, Singapore.

Purpose: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC).

Methods: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL.

Results: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83).

Conclusion: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.
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http://dx.doi.org/10.1111/aos.14942DOI Listing
June 2021

An open source tool to compute measures of inpatient glycemic control: translating from healthcare analytics research to clinical quality improvement.

JAMIA Open 2021 Apr 16;4(2):ooab033. Epub 2021 Jun 16.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Objectives: The objective of this study is to facilitate monitoring of the quality of inpatient glycemic control by providing an open-source tool to compute glucometrics. To allay regulatory and privacy concerns, the tool is usable locally; no data are uploaded to the internet.

Materials And Methods: We extended code, initially developed for healthcare analytics research, to serve the clinical need for quality monitoring of diabetes. We built an application, with a graphical interface, which can be run locally without any internet connection.

Results: We verified that our code produced results identical to prior work in glucometrics. We extended the prior work by including additional metrics and by providing user customizability. The software has been used at an academic healthcare institution.

Conclusion: We successfully translated code used for research methods into an open source, user-friendly tool which hospitals may use to expedite quality measure computation for the management of inpatients with diabetes.
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http://dx.doi.org/10.1093/jamiaopen/ooab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206397PMC
April 2021

Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

Crit Care 2021 06 14;25(1):211. Epub 2021 Jun 14.

Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Background: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research.

Methods: We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO.

Results: We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7-40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common.

Conclusion: The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.
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http://dx.doi.org/10.1186/s13054-021-03634-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201440PMC
June 2021

The Effects of Mean of Visit-to-Visit Blood Pressure on Incident Brain Vascular Lesions and Functional-Cognitive Decline.

J Alzheimers Dis 2021 ;82(2):561-573

Memory Aging and Cognition Centre, National University Health System, Singapore.

Background: Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear.

Objective: To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up.

Methods: 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline.

Results: Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline.

Conclusion: These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD.
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http://dx.doi.org/10.3233/JAD-210188DOI Listing
September 2021

Facilitators of and barriers to implementing a traditional Chinese medicine collaborative model of care for axial spondyloarthritis: a qualitative study.

Acupunct Med 2021 Dec 28;39(6):629-636. Epub 2021 May 28.

Program in Health Systems and Services Research, Duke-NUS Medical School, Singapore.

Background: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC.

Methods: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis.

Results: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important 'facilitators' and 'barriers'. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians' skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM.

Conclusion: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC.

Trial Registration Number: NCT03420404 (ClinicalTrials.gov).
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http://dx.doi.org/10.1177/09645284211009543DOI Listing
December 2021

Severe COVID-19 and coagulopathy: A systematic review and meta-analysis.

Ann Acad Med Singap 2021 04;50(4):325-335

Cardiothoracic Intensive Care Unit, National University Heart Centre, National University Hospital, Singapore.

Introduction: Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.

Methods: We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.

Results: Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.

Conclusion: Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.
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April 2021

Number of daily measurements needed to estimate habitual step count levels using wrist-worn trackers and smartphones in 212,048 adults.

Sci Rep 2021 05 5;11(1):9633. Epub 2021 May 5.

Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building (Block MD1), 12 Science Drive 2, #09-01v, Singapore, 117549, Singapore.

Daily step count is a readily accessible physical activity measure inversely related to many important health outcomes. However, its day-to-day variability is not clear, especially when measured by recent mobile devices. This study investigates number of measurement days required to reliably estimate the weekly and monthly levels of daily step count in adults using wrist-worn fitness trackers and smartphones. Data were from a 5-month physical activity program in Singapore. The 5-month period was divided into 22 weekly and 5 monthly time windows. For each time window, we leveraged data sampling procedures and estimated the minimum number of measurement days needed to achieve reliable mean daily step count with intraclass correlation coefficients (ICC) above 80%. The ICCs were derived using linear mixed effect models. We examined both simple random and random consecutive measurement days and conducted subgroup analysis by participant characteristics and tracking devices. Analysis of weekly and monthly step count included 212,048 and 112,865 adults, respectively. Fewer simple random measurement days are needed than random consecutive days for weekly time windows (mean 2.5, SD 0.5 vs mean 2.7, SD 0.5; p-value = 0.025). Similarly, monthly time windows require fewer measurements of simple random days than random consecutive days (mean 3.4, SD 0.5 vs mean 4.4, SD 0.5; p-value = 0.025). Younger participants and those tracking steps via smartphones consistently required more days. Being obese was associated with more measurement days for weekly time windows. In sum, to obtain reliable daily step count level, we recommend at least 3 measurement days for weekly and 5 days for monthly time window in adults. Fewer days could be considered for adults age 60+ years, while more days are required when tracking daily step via smartphones.
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http://dx.doi.org/10.1038/s41598-021-89141-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100112PMC
May 2021

Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10 year observational study in Singapore.

Diabetologia 2021 07 22;64(7):1538-1549. Epub 2021 Apr 22.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Republic of Singapore.

Aims/hypothesis: Diabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population.

Methods: This was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation.

Results: Between 2007 and 2017, of the 156,593 individuals with incident type 2 diabetes, 20,744 developed a DRLEC, of whom 1208 underwent amputation. Age- and sex-standardised incidence of first DRLEC and first amputation was 28.29/1000 person-years of diabetes and 8.18/1000 person-years of DRLEC, respectively. Incidence of both was highest in individuals of Malay ethnicity (DRLEC, 36.09/1000 person-years of diabetes; amputation, 12.96/1000 person-years of DRLEC). Median time from diabetes diagnosis in the public healthcare system to first DRLEC was 30.5 months for those without subsequent amputation and 10.9 months for those with subsequent amputation. Median time from DRLEC to first amputation was 2.3 months. Older age (p < 0.001), male sex (p < 0.001), Malay ethnicity (p < 0.001), Indian ethnicity (p = 0.014), chronic comorbidities (nephropathy [p < 0.001], heart disease [p < 0.001], stroke [p < 0.001], retinopathy [p < 0.001], neuropathy [p < 0.001]), poorer or missing HbA (p < 0.001), lower (p < 0.001) or missing (p = 0.002) eGFR, greater or missing BMI (p < 0.001), missing LDL-cholesterol (p < 0.001) at diagnosis, and ever-smoking (p < 0.001) were associated with higher hazard of DRLEC. Retinopathy (p < 0.001), peripheral vascular disease (p < 0.001), poorer HbA (p < 0.001), higher (p = 0.009) or missing (p < 0.001) LDL-cholesterol and missing BMI (p = 0.008) were associated with higher hazard of amputation in those with DRLEC. Indian ethnicity (p = 0.007) was associated with significantly lower hazard of amputation.

Conclusions/interpretation: This study has revealed important ethnic differences in risk of diabetes-related lower limb complications, with Malays most likely to progress to DRLEC. Greater research efforts are needed to understand the aetiopathological and sociocultural processes that contribute to the higher risk of lower extremity complications among these ethnic groups.
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http://dx.doi.org/10.1007/s00125-021-05441-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187215PMC
July 2021

Association of time outdoors and patterns of light exposure with myopia in children.

Br J Ophthalmol 2021 Apr 15. Epub 2021 Apr 15.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background/aims: To evaluate the association of reported time outdoors and light exposure patterns with myopia among children aged 9 years from the Growing Up in Singapore Towards Healthy Outcomes birth cohort.

Methods: We assessed reported time outdoors (min/day), light exposure patterns and outdoor activities of children aged 9 years (n=483) with a questionnaire, the FitSight watch and a 7-day activity diary. Light levels, the duration, timing and frequency of light exposure were assessed. Cycloplegic spherical equivalent (SE), myopia (SE≤-0.5 D) and axial length (AL) of paired eyes were analysed using generalised estimating equations.

Results: In this study, 483 (966 eyes) multiethnic children (50.0% boys, 59.8% Chinese, 42.2% myopic) were included. Reported time outdoors (mean±SD) was 100±93 min/day, and average light levels were 458±228 lux. Of the total duration children spent at light levels of ≥1000 lux (37±19 min/day), 76% were spent below 5000 lux. Peak light exposure occurred at mid-day. Children had 1.7±1.0 light exposure episodes/day. Common outdoor activities were walks, neighbourhood play and swimming. Greater reported time outdoors was associated with lower odds of myopia (OR=0.82, 95% CI 0.70 to 0.95/hour increase daily; p=0.009). Light levels, timing and frequency of light exposures were not associated with myopia, SE or AL (p>0.05).

Conclusion: Reported time outdoors, light levels and number of light exposure episodes were low among Singaporean children aged 9 years. Reported time outdoors was protective against myopia but not light levels or specific light measures. A multipronged approach to increase time outdoors is recommended in the combat against the myopia epidemic.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318918DOI Listing
April 2021

Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore.

BMC Fam Pract 2021 04 14;22(1):74. Epub 2021 Apr 14.

Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, Singapore, 117549, Singapore.

Background: Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke.

Method: Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0-3 months (early) and 4-12 months (late) post-stroke.

Results: For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits.

Conclusion: We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.
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http://dx.doi.org/10.1186/s12875-021-01405-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048235PMC
April 2021

Rapid Myopic Progression in Childhood Is Associated With Teenage High Myopia.

Invest Ophthalmol Vis Sci 2021 04;62(4):17

Singapore Eye Research Institute, Singapore.

Purpose: The purpose of this study was to evaluate the association of childhood progression of spherical equivalent (SE) with high myopia (HM) in teenagers in the Singapore Cohort of Risk factors for Myopia (SCORM).

Methods: We included 928 SCORM children followed over a mean follow-up of 6.9 ± 1.0 years from baseline (6-11 years old) until their teenage years (12-19 years old). Cycloplegic autorefraction and axial length (AL) measurements were performed yearly. The outcomes in teenagers were HM (SE ≤ -5 diopter [D)], AL ≥ 25 mm, SE and AL. Three-year SE and AL progression in childhood and baseline SE and AL with outcomes were evaluated using multivariable logistic or linear regression models, with predictive performance of risk factors assessed using the area under the curve (AUC).

Results: At the last visit, 9.8% of teenagers developed HM and 22.7% developed AL ≥ 25 mm. In multivariate regression analyses, every -0.3 D/year increase in 3-year SE progression and every 0.2 mm/year increase in 3-year AL progression were associated with a -1.14 D greater teenage SE and 0.52 mm greater teenage AL (P values < 0.001). The AUC (95% confidence interval [CI]) of a combination of 3-year SE progression and baseline SE for teenage HM was 0.97 (95% CI = 0.95 - 0.98). The AUC of 3-year AL progression and baseline AL for teenage AL ≥ 25 mm was 0.91 (95% CI = 0.89 - 0.94).

Conclusions: Three-year myopia progression in childhood combined with baseline SE or AL were good predictors of teenage HM. Clinicians may use this combination of factors to guide timing of interventions, potentially reducing the risk of HM later in life.
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http://dx.doi.org/10.1167/iovs.62.4.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054625PMC
April 2021

Lifetime Prevalence and Correlates of Schizophrenia and Other Psychotic Disorders in Singapore.

Front Psychiatry 2021 11;12:650674. Epub 2021 Mar 11.

Research Division, Institute of Mental Health, Singapore, Singapore.

The current study aimed to establish the lifetime prevalence of schizophrenia and other psychotic disorders, its sociodemographic correlates and association with physical disorders using data from the Singapore Mental Health Study (SMHS 2016). A two-phase design comprising population-level screening of psychotic symptoms using the World Health Organization Composite International Diagnostic Interview version 3.0 psychosis screen followed by clinical reappraisal based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were used to establish the prevalence. A total of 6,126 respondents completed the first phase of the study, giving a response rate of 69.5%. 5.2% ( = 326) of respondents endorsed at least one symptom in the psychosis screen. After the phase two clinical reappraisal interviews and adjusting for false-negative rate, the corrected prevalence of schizophrenia and other psychotic disorders was 2.3% (95% CI: 2.3-2.3%). The odds of having DSM-IV schizophrenia and other psychotic disorders was significantly higher among those of Malay ethnicity (OR = 3.9, 95% CI 1.4-11.0), and those who were unemployed (OR = 4.3, 95% CI 1.2-15.9). 80.4% of those with a psychotic disorder had consulted a doctor or a mental health professional for their symptoms. Our results indicate that approximately 2.3% of Singapore's community-dwelling adult population had a lifetime diagnosis of schizophrenia and other psychotic disorders. While the treatment gap of the disorder was relatively small, the severe nature of the disorder emphasizes the need for continued outreach and early diagnosis and treatment.
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http://dx.doi.org/10.3389/fpsyt.2021.650674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991584PMC
March 2021

Population segmentation of type 2 diabetes mellitus patients and its clinical applications - a scoping review.

BMC Med Res Methodol 2021 03 11;21(1):49. Epub 2021 Mar 11.

SingHealth Regional Health System PULSES Centre, Singapore Health Services, Outram Rd, Singapore, 169608, Singapore.

Background: Population segmentation permits the division of a heterogeneous population into relatively homogenous subgroups. This scoping review aims to summarize the clinical applications of data driven and expert driven population segmentation among Type 2 diabetes mellitus (T2DM) patients.

Methods: The literature search was conducted in Medline®, Embase®, Scopus® and PsycInfo®. Articles which utilized expert-based or data-driven population segmentation methodologies for evaluation of outcomes among T2DM patients were included. Population segmentation variables were grouped into five domains (socio-demographic, diabetes related, non-diabetes medical related, psychiatric / psychological and health system related variables). A framework for PopulAtion Segmentation Study design for T2DM patients (PASS-T2DM) was proposed.

Results: Of 155,124 articles screened, 148 articles were included. Expert driven population segmentation approach was most commonly used, of which judgemental splitting was the main strategy employed (n = 111, 75.0%). Cluster based analyses (n = 37, 25.0%) was the main data driven population segmentation strategies utilized. Socio-demographic (n = 66, 44.6%), diabetes related (n = 54, 36.5%) and non-diabetes medical related (n = 18, 12.2%) were the most used domains. Specifically, patients' race, age, Hba1c related parameters and depression / anxiety related variables were most frequently used. Health grouping/profiling (n = 71, 48%), assessment of diabetes related complications (n = 57, 38.5%) and non-diabetes metabolic derangements (n = 42, 28.4%) were the most frequent population segmentation objectives of the studies.

Conclusions: Population segmentation has a wide range of clinical applications for evaluating clinical outcomes among T2DM patients. More studies are required to identify the optimal set of population segmentation framework for T2DM patients.
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http://dx.doi.org/10.1186/s12874-021-01209-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953703PMC
March 2021

The effect of intracranial stenosis on cognitive decline in a memory clinic cohort.

Eur J Neurol 2021 06 18;28(6):1829-1839. Epub 2021 Mar 18.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore City, Singapore.

Background And Purpose: Intracranial stenosis (ICS) is a risk factor for cognitive impairment and dementia in cross-sectional studies. However, data examining the effect of ICS on cognitive decline are limited. We investigated the effect of ICS on cognition over a period of 3 years in a memory clinic cohort.

Methods: Patients were recruited from the National University Hospital in Singapore. Data were collected using a standardised questionnaire, physical examination, and 3-T magnetic resonance imaging (MRI) at baseline. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any intracranial vessel. Cognition was measured at baseline and annually for 3 years using the Mini-Mental State Examination, the Montreal Cognitive Assessment, and a detailed neuropsychological test battery. The association between ICS and cognitive decline was analysed using generalised estimating equations.

Results: A total of 364 patients were included in the analysis. The mean (±SD) age was 71.9 (±8.0) years, and 164 (45.1%) patients were male. A total of 66 (18.1%) patients had ICS. ICS was associated with worse executive function (β = -0.37, 95% confidence interval = -0.68 to -0.05, p = 0.022) and modified the effect of follow-up time on memory (p = 0.005) and visuomotor speed (p = 0.047). These results remained significant after controlling for demographics, overall diagnosis, cardiovascular risk factors, and MRI markers of cerebrovascular disease.

Conclusions: Intracranial stenosis was independently associated with worse executive function across all time points, and cognitive decline in memory and visuomotor speed over 3 years of follow-up. This suggests that ICS may be a useful indicator of vascular brain damage leading to cognitive decline and may warrant consideration of antiatherosclerotic treatment in clinical trials.
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http://dx.doi.org/10.1111/ene.14788DOI Listing
June 2021

A New Procedure to Assess When Estimates from the Cumulative Link Model Can Be Interpreted as Differences for Ordinal Scales in Quality of Life Studies.

Clin Epidemiol 2021 4;13:53-65. Epub 2021 Feb 4.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Purpose: Assessing the clinical importance of an exposure effect on a quality of life (QoL) score often requires quantifying the effect in terms of a difference in scores. Using the linear regression model (LRM) for this purpose assumes the ordinal score is a proxy for an underlying continuous variable, but the analysis offers no assessment for the validity of the assumption. We propose an approach that assesses the proxy assumption and estimates the exposure effect by using the cumulative link model (CLM).

Patients And Methods: CLM is a well-established regression model that assumes an ordinal score is an ordered category generated from applying thresholds to a latent continuous variable. Our approach assesses the proxy assumption by testing whether these thresholds are equidistant. We compared the performance of CLM and LRM using simulated ordinal data and illustrated their application to the effect of time since diagnosis on five subscales of fatigue among breast cancer survivors measured using the Multidimensional Fatigue Inventory.

Results: CLM had good performance in estimating the difference in means with simulated ordinal data satisfying the proxy assumption, even when the outcome had only a few categories. When the proxy assumption was inadequate, both the CLM and LRM had biased estimates with poor coverage. The proxy assumption was appropriate for four of the five subscales in our real data application to fatigue scores, which highlighted the importance of assessing the proxy assumption to avoid reporting invalid estimates in terms of the difference in scores.

Conclusion: The proxy assumption is critical to the interpretation of the exposure effect on the difference in mean QoL scores. CLM offers a valid test for the presence of an association, a method for assessing the proxy assumption, and when the assumption is adequate, an assessment for clinical significance using the difference in means.
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http://dx.doi.org/10.2147/CLEP.S288801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869833PMC
February 2021

Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.

J Nutr 2021 04;151(4):911-920

Clinical Nutrition Research Center, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore.

Background: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss.

Objective: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity.

Methods: A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group.

Results: The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period.

Conclusions: BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.
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http://dx.doi.org/10.1093/jn/nxaa414DOI Listing
April 2021

Concurrent Use of Renal Replacement Therapy during Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Jan 11;10(2). Epub 2021 Jan 11.

Cardiothoracic Intensive Care Unit, National University Heart Centre, National University Hospital, Singapore 119228, Singapore.

Patients supported with extracorporeal membrane oxygenation (ECMO) often receive renal replacement therapy (RRT). We conducted this systematic review and meta-analysis (between January 2000 and September 2020) to assess outcomes in patients who received RRT on ECMO. Random-effects meta-analyses were performed using R 3.6.1 and certainty of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was pooled mortality. The duration of ECMO support and ICU/hospital lengths of stay were also investigated. Meta-regression analyses identified factors associated with mortality. A total of 5896 adult patients (from 24 observational studies and 1 randomised controlled trial) were included in this review. Overall pooled mortality due to concurrent use of RRT while on ECMO from observational studies was 63.0% (95% CI: 56.0-69.6%). In patients receiving RRT, mortality decreased by 20% in the last five years; the mean duration of ECMO support and ICU and hospital lengths of stay were 9.33 days (95% CI: 7.74-10.92), 15.76 days (95% CI: 12.83-18.69) and 28.47 days (95% CI: 22.13-34.81), respectively, with an 81% increased risk of death (RR: 1.81, 95% CI: 1.56-2.08, < 0.001). RRT on ECMO was associated with higher mortality rates and a longer ICU/hospital stay compared to those without RRT. Future research should focus on minimizing renal dysfunction in ECMO patients and define the optimal timing of RRT initiation.
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http://dx.doi.org/10.3390/jcm10020241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827381PMC
January 2021

Annual Myopia Progression and Subsequent 2-Year Myopia Progression in Singaporean Children.

Transl Vis Sci Technol 2020 12 7;9(13):12. Epub 2020 Dec 7.

Singapore Eye Research Institute, Singapore.

Purpose: To investigate the association between 1-year myopia progression and subsequent 2-year myopia progression among myopic children in the Singapore Cohort Study of the Risk Factors for Myopia.

Methods: This retrospective analysis included 618 myopic children (329 male), 7 to 9 years of age (mean age, 8.0 ± 0.8) at baseline with at least two annual follow-up visits. Cycloplegic autorefraction was performed at every visit. Receiver operating characteristic (ROC) curves from multiple logistic regressions were derived for future fast 2-year myopia progression.

Results: Children with slow progression during the first year (slower than -0.50 diopter [D]/y) had the slowest mean subsequent 2-year myopia progression (-0.41 ± 0.33 D/y), whereas children with fast progression (faster than -1.25 D/y) in year 1 had the fastest mean subsequent 2-year myopia progression (-0.82 ± 0.30 D/y) ( for trend < 0.001). Year 1 myopia progression had the highest area under the curve (AUC) for predicting fast subsequent 2-year myopia progression (AUC = 0.77; 95% confidence interval [CI], 0.73-0.80) compared to baseline spherical equivalent (AUC = 0.70; 95% CI, 0.66-0.74) or age of myopia onset (AUC = 0.66; 95% CI, 0.61-0.70) after adjusting for confounders. Age at baseline alone had an AUC of 0.65 (95% CI, 0.61-0.69).

Conclusions: One-year myopia progression and age at baseline were associated with subsequent 2-year myopia progression in children 7 to 9 years of age.

Translational Relevance: Myopia progression and age at baseline may be considered by eye care practitioners as two of several factors that may be associated with future myopia progression in children.
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http://dx.doi.org/10.1167/tvst.9.13.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726587PMC
December 2020

Evaluating the effectiveness of a multi-faceted inpatient diabetes management program among hospitalised patients with diabetes mellitus.

Clin Diabetes Endocrinol 2020 Nov 5;6(1):21. Epub 2020 Nov 5.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Background: Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs.

Methods: We designed a multi-faceted intervention program with the aim of reducing inpatient hypoglycemia and hyperglycemia. This was implemented over seven phases between September 2013 to January 2016, and covered all the non-critical care wards in a tertiary hospital. The program represented a pragmatic approach that leveraged on existing resources and infrastructure within the hospital. We calculated glucometric outcomes in June to August 2016 and compared them with those in June to August 2013 to assess the overall effectiveness of the program. We used regression models with generalised estimating equations to adjust for potential confounders and account for correlations of repeated outcomes within patients and admissions.

Results: We observed significant reductions in patient-days affected by hypoglycemia (any glucose reading < 4 mmol/L: OR = 0.71, 95% CI: 0.61 to 0.83, p <  0.001), and hyperglycemia (any glucose reading > 14 mmol/L: OR = 0.84, 95% CI: 0.71 to 0.99, p = 0.041). Similar findings were observed for admission-level hypoglycemia and hyperglycemia. Further analyses suggested that these reductions started to occur four to 6 months post-implementation.

Conclusions: Our program was associated with sustained improvements in clinically relevant outcomes. Our described intervention could be feasibly implemented by other secondary and tertiary care hospitals by leveraging on existing infrastructure and work force.
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http://dx.doi.org/10.1186/s40842-020-00107-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643419PMC
November 2020
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