Pharmacotherapy for Venous Thromboprophylaxis following Total Hip or Knee Arthroplasty: A Systematic Review and Network Meta-analysis.

The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Preoperative anemia and anemia treatment in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: We aimed to conduct a systematic review and meta-analysis to assess the effects of anemia and anemia severity on patient outcomes in cardiac surgery and determine whether preoperative treatments confer postoperative benefit. SOURCE: We searched four international databases for observational and randomized studies published until 1 October 2022. Study quality was assessed via Newcastle-Ottawa scores and the Cochrane Risk-of-Bias 2 tool and certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations approach. We conducted random-effects meta-analyses for our primary outcome of mortality, for secondary outcomes including length of stay (LOS) in the hospital and intensive care unit, and for postsurgical complications. As part of a secondary analysis, we analyzed short-term preoperative anemia treatments and conducted trial sequential analysis of randomized trials to assess the efficacy of these treatment programs. PRINCIPAL FINDINGS: We included 35 studies (159,025 patients) in our primary meta-analysis. Preoperative anemia was associated with increased mortality (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.2 to 2.9; P < 0.001, high certainty). Study-level meta-regression revealed lower hemoglobin levels and studies with lower proportions of male patients to be associated with increased risk of mortality. Preoperative anemia was also associated with an increase in LOS and postsurgical complications. Our secondary analysis (seven studies, 1,012 patients) revealed short-term preoperative anemia treatments did not significantly reduce mortality (OR, 1.1; 95% CI, 0.65 to 1.9; P = 0.69). Trial sequential analysis suggested that there was insufficient evidence to conclude if treatment programs yield any benefit or harm. CONCLUSIONS: Preoperative anemia is associated with mortality and morbidity after cardiac surgery. More research is warranted to test the efficacy of current anemia treatment programs. STUDY REGISTRATION: PROSPERO (CRD42022319431); first submitted 17 April 2023.

RéSUMé: OBJECTIF: Notre objectif était de mener une revue systématique et une méta-analyse pour évaluer les effets de l'anémie et de la gravité de l'anémie sur les devenirs des patient·es en chirurgie cardiaque et déterminer si les traitements préopératoires conféraient un bénéfice postopératoire. SOURCES: Nous avons réalisé des recherches dans quatre bases de données internationales pour en extraire des études observationnelles et randomisées publiées jusqu'au 1er octobre 2022. La qualité des études a été évaluée à l'aide des scores de Newcastle-Ottawa et de l'outil Cochrane 2 sur le risque de biais, et la certitude des données probantes a été évaluée selon l'approche GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Nous avons réalisé des méta-analyses à effets aléatoires pour notre critère d'évaluation principal de mortalité, pour les critères d'évaluation secondaires, notamment la durée du séjour à l'hôpital et à l'unité de soins intensifs, et pour les complications postopératoires. Dans le cadre d'une analyse secondaire, nous avons examiné les traitements préopératoires de l'anémie à court terme et effectué une analyse séquentielle d'études randomisées afin d'évaluer l'efficacité de ces modalités de traitement. CONSTATATIONS PRINCIPALES: Nous avons inclus 35 études portant sur 159 025 patient·es dans notre méta-analyse. L'anémie préopératoire était associée à une augmentation de la mortalité (rapport de cotes [RC], 2,5; intervalle de confiance [IC] à 95 %, 2,2 à 2,9; P < 0,001, certitude élevée). La méta-régression au niveau de l'étude a révélé que des taux d'hémoglobine plus faibles et des études avec des proportions plus faibles de patients masculins étaient associées à un risque accru de mortalité. L'anémie préopératoire était également associée à une augmentation de la durée de séjour et des complications postopératoires. Notre analyse secondaire (sept études, 1012 patient·es) a révélé que les traitements préopératoires de l'anémie à court terme ne réduisaient pas significativement la mortalité (RC, 1,1; IC 95 %, 0,65 à 1,9; P = 0,69). L'analyse séquentielle des études a suggéré qu'il n'y avait pas suffisamment de données probantes pour conclure si les modalités de traitement entraînaient un bénéfice ou un préjudice. CONCLUSION: L'anémie préopératoire est associée à la mortalité et à la morbidité après une chirurgie cardiaque. D'autres recherches sont justifiées pour tester l'efficacité des programmes actuels de traitement de l'anémie. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022319431); première soumission le 17 avril 2023.

Ecological momentary assessment of digital food and beverage marketing exposure and impact in young adults: A feasibility study.

Unhealthy food marketing is contributing to the obesity epidemic, but real-time insights into the mechanisms of this relationship are under-studied. Digital marketing is growing and following food and beverage (F&B) brands on social media is common, but measurement of exposure and impact of such marketing presents novel challenges. Thus, this study aimed to evaluate the feasibility of collecting data on exposure and impact of digital F&B marketing (DFM) using a smartphone-based ecological momentary assessment (EMA) methodology. We hypothesized that DFM-induced food cravings would vary based on whether (or not) participants engaged with F&B brands online. Participants were Singapore residents (n = 95, 21-40 years), recruited via telephone from an existing cohort. Participants were asked to upload screenshots of all sightings of online F&B marketing messages for seven days, and answer in-app contextual questions about sightings including whether any cravings were induced. Participants provided a total of 1310 uploads (median 9 per participant, Q1-Q3: 4-21) of F&B marketing messages, 27% of which were provided on Day 1, significantly more than on other days (P < 0.001). Followers of food/beverage brands on social media encountered 25.6 percentage points (95% CI 11.4, 39.7) more marketing messages that induced cravings than participants who were not followers. University education was also associated with more (18.1 percentage points; 95% CI 3.1, 33.1) encounters with marketing messages that induced cravings. It was practical and acceptable to participants to gather insights into digital F&B marketing exposure and impact using EMA in young adults, although a shorter study period is recommended in future studies. Followers of food and beverage brands on social media appear to be more prone to experience cravings after exposure to digital F&B marketing.

Physical Activity Trends Among Adults in a National Mobile Health Program: A Population-Based Cohort Study of 411,528 Adults.

Physical inactivity is a global public health challenge, and effective, large-scale interventions are needed. We examined the effectiveness of a population-wide mobile health (mHealth) intervention in Singapore, National Steps Challenge Season 3 (NSC3) and 2 booster challenges (Personal Pledge and Corporate Challenge). The study includes 411,528 participants. We used regression discontinuity design and difference-in-difference with fixed-effects regression to examine the association of NSC3 and the additional booster challenges on daily step counts. Participants tended to be female (58.5%), with an average age of 41.5 years (standard deviation, 13.9) and body mass index (weight (kg)/height (m)2) of 23.8 (standard deviation, 4.5). We observed that NSC3 was associated with a mean increase of 1,437 steps (95% confidence interval (CI): 1,408, 1,467) per day. Enrollments in Personal Pledge and Corporate Challenge were associated with additional mean increases of 1,172 (95% CI: 1,123, 1,222) and 896 (95% CI: 862, 930) steps per day, respectively. For NSC3, the associated mean increase in the step counts across different sex and age groups varied, with greater increases for female participants and those in the oldest age group. We provide real-world evidence suggesting that NSC3 was associated with improvements in participants' step counts. Results suggest NSC3 is an effective and appealing population-wide mHealth physical activity intervention.

Association between nutrition and cognition in a multi-ethnic cohort from Singapore.

BACKGROUND: Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-aged and older adults of different ethnicities (Chinese, Malay, Indian) in Singapore. METHODS: This cross-sectional study (n = 3138; mean age: 50.4 ± 9.8, 58.4% women) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire was converted into AHEI-2010 scores. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired or not, using cut-offs of ≥ 24, 26 or 28 for no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates. RESULTS: A total of 988 (31.5%) participants had cognitive impairment. Higher AHEI-2010 scores were significantly associated with higher MMSE scores [ß = 0.44; 95% confidence interval (CI) 0.22-0.67 highest vs. lowest quartile; p-trend < 0.001] and lower odds of cognitive impairment [OR 0.69; 95% CI 0.54-0.88; p-trend = 0.01] after adjusting for all the covariates. No significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment. CONCLUSION: Healthier dietary patterns were associated with better cognitive function in middle-aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.

Evaluating the Effects of Rewards and Schedule Length on Response Rates to Ecological Momentary Assessment Surveys: Randomized Controlled Trials.

BACKGROUND: Ecological momentary assessments (EMAs) are short, repeated surveys designed to collect information on experiences in real-time, real-life contexts. Embedding periodic bursts of EMAs within cohort studies enables the study of experiences on multiple timescales and could greatly enhance the accuracy of self-reported information. However, the burden on participants may be high and should be minimized to optimize EMA response rates. OBJECTIVE: We aimed to evaluate the effects of study design features on EMA response rates. METHODS: Embedded within an ongoing cohort study (Health@NUS), 3 bursts of EMAs were implemented over a 7-month period (April to October 2021). The response rate (percentage of completed EMA surveys from all sent EMA surveys; 30-42 individual EMA surveys sent/burst) for each burst was examined. Following a low response rate in burst 1, changes were made to the subsequent implementation strategy (SMS text message announcements instead of emails). In addition, 2 consecutive randomized controlled trials were conducted to evaluate the efficacy of 4 different reward structures (with fixed and bonus components) and 2 different schedule lengths (7 or 14 d) on changes to the EMA response rate. Analyses were conducted from 2021 to 2022 using ANOVA and analysis of covariance to examine group differences and mixed models to assess changes across all 3 bursts. RESULTS: Participants (N=384) were university students (n=232, 60.4% female; mean age 23, SD 1.3 y) in Singapore. Changing the reward structure did not significantly change the response rate (F3,380=1.75; P=.16). Changing the schedule length did significantly change the response rate (F1,382=6.23; P=.01); the response rate was higher for the longer schedule (14 d; mean 48.34%, SD 33.17%) than the shorter schedule (7 d; mean 38.52%, SD 33.44%). The average response rate was higher in burst 2 and burst 3 (mean 50.56, SD 33.61 and mean 48.34, SD 33.17, respectively) than in burst 1 (mean 25.78, SD 30.12), and the difference was statistically significant (F2,766=93.83; P<.001). CONCLUSIONS: Small changes to the implementation strategy (SMS text messages instead of emails) may have contributed to increasing the response rate over time. Changing the available rewards did not lead to a significant difference in the response rate, whereas changing the schedule length did lead to a significant difference in the response rate. Our study provides novel insights on how to implement EMA surveys in ongoing cohort studies. This knowledge is essential for conducting high-quality studies using EMA surveys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/ct2/show/NCT05154227.

Extracorporeal membrane oxygenation in patients with hematologic malignancies: a systematic review and meta-analysis.

Hematological malignancies (HM) have been, until recently, viewed as contraindications to extracorporeal membrane oxygenation (ECMO) due to bleeding and infectious complications. However, conflicting literature regarding whether ECMO should be used for patients with HM still exists. We conducted a random effects meta-analysis to investigate the outcomes of patients with HM on ECMO. We searched Medline, Embase, Scopus, and Cochrane through 10 October 2021. Risk of bias and certainty of evidence were assessed using the JBI checklists and GRADE approach respectively. Thirteen observational studies (422 patients with HM, 9778 controls without HM) were included. The pooled in-hospital mortality for patients with HM and those with hematopoietic stem cell transplants for HM indications needing ECMO were 79.1% (95%CI: 70.2-86.9%) and 87.7% (95%CI: 80.4-93.8%), respectively. Subgroup analyses found that mortality was higher in adults than children (85.1% vs 67.9%, pinteraction = 0.003), and in Asia compared to North America and Europe (93.8% vs 69.6%, pinteraction < 0.001). Pooled ECMO duration was 10.0 days (95%CI: 7.5-12.5); pooled ICU and hospital lengths of stay were 19.8 days (95%CI: 12.4-27.3) and 43.9 days (95%CI: 29.4-58.4) respectively. Age (regression coefficient [B]: 0.008, 95%CI: 0.003-0.014), proportion of males (B: 1.799, 95%CI: 0.079-3.519), and ECMO duration (B: - 0.022, 95%CI: - 0.043 to - 0.001) were significantly associated with higher mortality. In-hospital mortality of patients with HM who needed ECMO was 79.1%, with better outcomes in children, and in North America and Europe. ECMO should not be regarded as routine support therapy in these patients but can be carefully considered on a case-by-case basis.

Association of Arterial Spin Labeling Parameters With Cognitive Decline, Vascular Events, and Mortality in a Memory-Clinic Sample.

BACKGROUND: Cognitive decline in older adults has been attributed to reduced cerebral blood flow (CBF). Recently, the spatial coefficient of variation (sCoV) of ASL has been proposed as a proxy marker of cerebrovascular insufficiency. We investigated the association between baseline ASL parameters with cognitive decline, incident cerebrovascular disease, and risk of vascular events and mortality. DESIGN, SETTING, AND PARTICIPANTS: About 368 memory-clinic patients underwent three-annual neuropsychological assessments and brain MRI scans at baseline and follow-up. MRIs were graded for white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), cortical infarcts, and intracranial stenosis. Baseline gray (GM) and white matter (WM) CBF and GM-sCoV were obtained with ExploreASL from 2D-EPI pseudo-continuous ASL images. Cognitive assessment was done using a validated neuropsychological battery. Data on incident vascular events (heart disease, stroke, transient ischemic attack) and mortality were obtained. RESULTS: Higher baseline GM-sCoV was associated with decline in the memory domain over 3 years of follow-up. Furthermore, higher GM-sCoV was associated with a decline in the memory domain only in participants without dementia. Higher baseline GM-sCoV was associated with progression of WMH and incident CMBs. During a mean follow-up of 3 years, 29 (7.8%) participants developed vascular events and 18 (4.8%) died. Participants with higher baseline mean GM-sCoV were at increased risk of vascular events. CONCLUSIONS: Higher baseline GM-sCoV of ASL was associated with a decline in memory and risk of cerebrovascular disease and vascular events, suggesting that cerebrovascular insufficiency may contribute to accelerated cognitive decline and worse clinical outcomes in memory clinic participants.

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

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.

Effects of neighborhood features on healthy aging in place: the composition and context of urban parks and traditional local coffeeshops in Singapore.

BACKGROUND: Healthy aging in place is affected by what the neighborhood provides for older adults. The mixed-methods ethnographic study explored the built environmental and contextual effects of urban parks and traditional local coffeeshops (kopitiam) on health practices among older adults in Singapore. METHODS: A door-to-door survey with 497 older adults from 32 residential blocks in a public housing town assessed exercise and smoking. The walking distances from the residential blocks to the facilities were calculated. Regression analysis examined the associations between the distance and rates of exercise and smoking. Ethnographic assessment data contextualized the quantitative findings. RESULTS: Older adults' exercise was associated with proximity to an urban park but not traditional local coffeeshops. High rates of smoking were clustered in the housing blocks close to the coffeeshops, which provided casual drinking places with smoking tables. The proximity to the coffeeshops was significantly associated with increased smoking and decreased exercise. A walking distance of 200 m to the park and coffeeshops was found to discriminate the outcomes. CONCLUSIONS: The findings suggested that walking distances of a few blocks influenced health behaviors among older adults. Their smoking habits appeared to be maintained through environmental features and cultural norms attached to the coffeeshops. Policy of urban planning and redevelopment for the aging population needs to consider the socioecology of healthy aging in place.

Dietary intake and associations with myopia in Singapore children.

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.

Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10 year observational study in 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 HbA1c (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 HbA1c (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.

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.

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.

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

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 (ß = -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.

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

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.

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

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.

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

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 PaO2/FiO2 ratio, lower PaCO2 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.

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.

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.

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

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.