Impact of standardized tobacco packaging on smoking-related behaviors and perceptions in Singapore.

INTRODUCTION: Singapore phased in standardized tobacco packaging on 1 July 2020 following a three-month grace period. This pre-post study evaluated its impacts on smoking-related behaviors and perceptions among adults who currently smoke. METHODS: Baseline and follow-up data were collected in a pre- and post-questionnaire from a cohort of 1873 Singaporean adults who were currently smoking at baseline. Baseline data were collected from December 2019 to May 2020, and follow-up data from July 2021 to September 2021. We used descriptive statistics and bivariate analyses to assess pre-post changes (Bhapkar's test, Wilcoxon signed rank test) and to identify characteristics of participants who had quit or cut down smoking at follow-up (Pearson's chi-squared, Fisher's exact test). RESULTS: At follow-up, 11.7% (n=220) had quit smoking. There was a higher proportion of those smoking non-daily (pre: 13.1%, post: 16.9%; p<0.001), and those intending to quit within the next year (pre: 14.8%, post: 17.5%; p<0.05) or six months (pre: 10.4%, post: 13.2%; p<0.01). Tobacco products were scored more negatively in relation to packaging, quality, satisfaction, value for money and overall appeal (scores pre: 15.9, post: 14.3; p<0.001), harmfulness (scores pre: 0.61, post: 0.54; p<0.05), noticing others smoking the same brand (scores pre: 1.92, post: 1.65; p<0.001), and considering quitting due to health warnings (scores pre: 0.81, post: 0.86, p<0.05). Fewer reported that some cigarette brands have higher prestige (pre: 58.0, post: 54.3%; p<0.01), and more reported using flavored cigarettes (pre: 42.2%, post: 60.1%; p<0.001) and e-cigarettes (pre: 4.2%, post: 6.1%; p<0.01). CONCLUSIONS: In Singapore, the changes observed before and after the implementation of standardized packaging suggest that it might be associated with quit-related outcomes, reduced tobacco product appeal, and increased effectiveness of graphic health warnings.

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.

Associations of childhood and current secondhand smoke exposure at home with current secondhand smoke exposure at work: A cross-sectional analysis of the Singapore multi-ethnic cohort.

INTRODUCTION: Relationships between secondhand smoke exposure (SHSE) in various temporal and physical settings are not fully studied despite its adverse impacts on human health, especially in multi-ethnic Asian populations. We investigated associations of childhood and current SHSE at home (SHSEhome) with current SHSE at work (SHSEwork) in Singapore and its relation to sources of daily smokers at home. METHODS: This cross-sectional study identified 925 healthy, never smoker working adults from the Singapore Multi-Ethnic Cohort (2004-2010). Firstly, the multiple logistic regression model estimated the adjusted odds ratios (AORs) of SHSEhome. Subsequently, sources of daily smokers entered through an additional model building process using the former as a base. RESULTS: Current adults (AOR=2.05; 95% CI: 1.28-3.29) and childhood SHSEhome (AOR=1.43; 95% CI: 0.93-2.19) had a positive and no association with current SHSEwork, respectively. These findings persisted when smoker identity-related variables entered the model: child (AOR=3.56; 95% CI: 1.19-10.64) for current daily smokers; father (AOR=2.30; 95% CI: 0.94-5.64) and sibling (AOR=2.97; 95% CI: 1.55-5.68) for childhood. Compared to no childhood SHSEhome, only those living with their fathers and siblings who smoked daily at home had significantly higher odds of reporting current SHSEwork (AOR=3.70; 95% CI: 1.88-7.30). CONCLUSIONS: Current SHSEhome was a risk factor for current SHSEwork, with risks elevated among those who smoke daily at home and living with their children. Childhood SHSEhome becomes a risk factor when daily household smokers include fathers and siblings. Deformalizing smoking could consider interpersonal dynamics of daily smokers at home with family members in different temporal settings, to reduce SHSEwork.

Association of Interleukin-6 and Interleukin-8 with Cognitive Decline in an Asian Memory Clinic Population.

BACKGROUND: Neuroinflammation has been postulated to play an important role in cognitive impairment, cognitive decline, and dementia. Inflammatory biomarkers such as interleukin-6 (IL-6) and IL-8 are found to be associated with the neuro-inflammatory process and worse cognitive function. However, it is unknown whether these interleukins are associated with long-term cognitive function. OBJECTIVE: To investigate the association of baseline IL-6 and IL-8 with cognitive function at baseline as well as its association with cognitive decline over five-year follow-up. METHODS: 387 patients were recruited from an ongoing memory clinic-based study who underwent comprehensive physical, medical, neuropsychological and blood assessments together with brain MRI. IL-6 and IL-8 were measured using LUMINEX assays. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network neuropsychological battery was used to assess cognitive decline across multiple domains. RESULTS: Among the 387 (mean age = 72.9 years and 53.7% males) participants, 322 had at least two follow-up assessments and were included in the longitudinal analysis. Negative linear trend associations were found between tertiles of IL-8 with baseline global cognition (p-trend< 0.001), attention (p-trend = 0.005), executive function (p-trend< 0.001), and visuospatial function (p-trend = 0.002) domains. No association was found between baseline IL-8 and cognitive decline. IL-6 was not associated with both baseline and follow-up cognition. CONCLUSION: IL-8 was associated with worse cognition especially in attention, executive function, and visuospatial function, suggesting the role of neuroinflammation in cognitive impairment. Hence, blood inflammatory biomarkers may be useful indicators in identifying patients at risk of cognitive impairment and warrant consideration for inclusion in treatment trials.

The Use of Extracorporeal Membrane Oxygenation for Burns: A Systematic Review and Meta-Analysis.

Burns are among the leading causes of trauma worldwide, and acute respiratory distress syndrome (ARDS) is a common cause of death in burn patients. Some patients develop hypoxemia refractory to conventional therapies and may be initiated on extracorporeal membrane oxygenation (ECMO) as rescue therapy. We conducted a meta-analysis for studies reporting on survival rates of patients receiving ECMO for burns or inhalation injuries, which was the primary outcome. Secondary outcomes included the hospital and intensive care unit length of stay and duration of ECMO. Random-effects (DerSimonian and Laird) were conducted. The pooled survival from 10 studies was 53.6% (95% confidence interval [CI]: 37.6-69.2%, high certainty). Survival was significantly associated with age (regression coefficient [B]: -0.0088, 95% CI: -0.0155 to -0.0021, p = 0.011) and the proportion of male patients (B: -1.0137 95% CI: -1.9695 to -0.0580, p = 0.038). Patients were cannulated on ECMO for a mean of 8.4 days (95% CI: 6.1-10.7) and remained in the ICU for a mean of 40.4 days (95% CI: 11.4-69.3). Mean hospital length of stay was 45.4 days (95% CI: 31.7-59.0). In conclusion, patients with burn and inhalation injuries who develop ARDS refractory to conservative management have a survival rate of 54% when placed on ECMO.

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.

Determinants of Hardcore Smoking in a MULTI-ETHNIC Study of Cigarette Smokers in Singapore.

Smokers who are resistant to quitting are not well studied in Asia, particularly in multi-ethnic populations. We compared the characteristics of hardcore smokers in Singapore, a multi-ethnic Asian population, with other daily smokers, and investigated the role of ethnicity as an effect modifier on identified determinants, including cigarette flavor preferences, using cross-sectional data from Singapore Smokers' Survey (n = 1,501). Multivariable logistic regression was used to assess the association. 22.8% of adult daily smokers were hardcore smokers. Novel findings on hardcore smokers' preference for regular flavored cigarettes (AOR = 1.54; 95%CI: 1.14, 2.07) suggest there is room for interventions among hardcore smokers through regulation of cigarette flavors and nicotine content. Although ethnicity was not a significant factor, it was an effect modifier with peers' disapproval of smoking (p-value for interaction = 0.024), significantly lowering odds of Malays being hardcore smokers (stratified odds ratio, AOR stratified, Malay = 0.35; CI: 0.17, 0.71), but not Chinese (AOR stratified, Chinese = 1.27; CI: 0.70, 2.42) and Indian smokers (AOR stratified, Indian = 0.62; CI: 0.18, 2.28), suggesting that smoking cessation policies utilizing social norm change strategies may be more effective when tailored to the differing roles of peer norms among different ethnic groups, in Singapore and other multi-ethnic Asian populations.

Handgrip Strength and Cognitive Performance in a Multiethnic Cohort in Singapore.

BACKGROUND: Handgrip strength (HGS) is an important marker of frailty but there is limited research on lifestyle and vascular determinants of HGS and its relationship with cognitive impairment. OBJECTIVE: To identify determinants of HGS and the association of HGS with cognitive impairment in a multiethnic cohort from Singapore. METHODS: This study (n = 2,109, median [Q1, Q3] age: 53 [48, 60] years, 59.6% women) was based on cross-sectional data from Singapore Multi-Ethnic Cohort. HGS was collected using hand-held Electronic Dynamometer. The potential determinants of HGS included age, sex, ethnicity, smoking, physical activity, serum cholesterol and history of hypertension, diabetes, and stroke. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analyzed as both continuous and binary outcome (cognitively impaired [scores < 26] and cognitively normal [scores≥26]). RESULTS: In total, 239 (11.3%) participants were cognitively impaired. Older age, female sex, Malay or Indian compared with Chinese ethnicity, and diabetes history were associated with decreased HGS, whereas higher education, higher body mass index, and more physical activity were associated with higher HGS. Higher HGS was associated with higher MMSE scores (ß: 0.34, 95% CI: 0.20, 0.49) and 37% lower odds of cognitive impairment (OR: 0.63, 95% CI: 0.49-0.82). These associations were significantly stronger in participants who were older (50-90 years), female, of Malay and Indian ethnicity (compared with Chinese), and less educated. CONCLUSION: In this multi-ethnic Asian population, demographics, vascular risk factors, and lifestyle behaviors were associated with HGS. Additionally, higher HGS was associated with substantially better cognitive function, which association was modified by age, sex, ethnicity, and education level.

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.

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

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.

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.

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.

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.

Vascular Complications of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Regression Analysis.

OBJECTIVES: Perform a systematic review and meta-analysis of vascular complications associated with extracorporeal membrane oxygenation and identify prognostic and predictive factors. DATA SOURCES: Systematic search for publications reporting vascular complications on extracorporeal membrane oxygenation, published from 1972 to January 31, 2020, was conducted via PubMed, Scopus, and Embase. STUDY SELECTION: Of 4,076 references screened, 47 studies with 6,583 patients were included in final analyses. Studies with fewer than 10 patients were excluded. DATA EXTRACTION: Relevant data, including demographics, comorbidities, extracorporeal membrane oxygenation and cannulation characteristics, occurrence rates of early and late vascular complications, patient outcomes, and use of distal perfusion cannula, were extracted from selected articles into an excel sheet specifically designed for this review. DATA SYNTHESIS: Random-effects meta-analyses and meta-regression analyses were undertaken. Overall pooled estimate of vascular complications in our meta-analysis was 29.5% (95% CI, 23.6-35.9%). Two-thousand three-hundred forty-seven vascular complications in 6,124 venoarterial extracorporeal membrane oxygenation patients compared with 95 in 459 venovenous extracorporeal membrane oxygenation patients (odds ratio, 2.35; 95% CI, 1.87-2.96; p < 0.0001) were analyzed. Successful weaning off extracorporeal membrane oxygenation occurred in 60.6% of pooled patients; 46.2% were eventually discharged. Pooled prevalences of vascular complications like significant bleeding, limb ischemia, and cannula site bleeding were 15.4% (95% CI, 8.6-23.7%), 12.6% (95% CI, 10.0-15.5%), and 12.6% (95% CI, 9.6-18.5%), respectively. Meta-analysis showed that the use of distal perfusion cannula was associated with lower odds of limb ischemia (odds ratio, 1.93; 95% CI, 1.17-2.47; p = 0.03) Meta-regression showed that male sex, smoking, advanced age, and comorbidities contributed to higher in-hospital mortality, while distal perfusion cannula was protective. CONCLUSIONS: Nearly a third of patients on extracorporeal membrane oxygenation develop vascular complications; elderly males with comorbidities appear vulnerable. The use of distal perfusion cannulas caused significant reduction in limb ischemia and mortality.

Robust estimation of the effect of an exposure on the change in a continuous outcome.

BACKGROUND: The change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model misspecifications, which are commonly addressed by applying monotonic transformations (e.g., Box-Cox transformation) to the outcomes. However, transforming the outcomes complicates the data analysis, especially when variable selection is involved. We propose a robust alternative through a novel application of the conditional probit (cprobit) model. METHODS: The cprobit model analyzes the ordered outcomes within each subject, making the estimate invariant to monotonic transformation on the outcome. By scaling the estimate from the cprobit model, we obtain the exposure effect on the change in the observed or Box-Cox transformed outcome, pending the adequacy of the normality assumption on the raw or transformed scale. RESULTS: Using simulated data, we demonstrated a similar good performance of the cprobit model and REM with and without transformation, except for some bias from both methods when the Box-Cox transformation was applied to scenarios with small sample size and strong effects. Only the cprobit model was robust to skewed subject-specific intercept terms when a Box-Cox transformation was used. Using two real datasets from the breast cancer and inpatient glycemic variability studies which utilize electronic medical records, we illustrated the application of our proposed robust approach as a seamless three-step workflow that facilitates the use of Box-Cox transformation to address non-normality with a common underlying model. CONCLUSIONS: The cprobit model provides a seamless and robust inference on the change in continuous outcomes, and its three-step workflow is implemented in an R package for easy accessibility.

The Association Between Psychological Resilience and Physical Function Among Older Adults With Hip Fracture Surgery.

OBJECTIVES: To examine the associations of prefracture psychological resilience and prefracture general mental health with physical function among older adults with hip fracture surgery. DESIGN: Single-center observational study. INTERVENTION: None. SETTING AND PARTICIPANTS: Patients aged ≥50 years who underwent first hip fracture surgery between January 2017 and December 2017 (N = 152). METHODS: We used data collected prospectively from the hospital's hip fracture registry. We performed generalized estimating equations to examine the associations of prefracture psychological resilience (10-item Connor-Davidson Resilience Scale) and prefracture general mental health (Short Form-36 mental health subscale) with physical function (Short Form-36 physical functioning subscale) at 4 time points-prefracture (based on recall), and 1.5, 3, and 6 months after surgery. RESULTS: Prefracture psychological resilience had an association with physical function; a 1-unit increase in psychological resilience score was associated with 1.15 units [95% confidence interval (CI) 0.71, 1.59] higher physical function score across 4 time points. In contrast, the association between general mental health and physical function varied over time; a 1-unit increase in general mental health score was associated with 0.42 units (95% CI 0.18, 0.66) higher physical function score at prefracture, 0.02 units (95% CI -0.18, 0.22) lower at 1.5 months, 0.23 units (95% CI -0.03, 0.49) higher at 3 months, and 0.39 units (95% CI 0.09, 0.68) higher at 6 months after surgery. CONCLUSIONS AND IMPLICATIONS: Psychological resilience is associated with physical function among older adults with hip fracture surgery, independent from general mental health. Our findings suggest the potential for interventions targeting psychological resilience for these patients and call for more studies on psychological factors affecting physical function recovery after hip fracture surgery.

Ovarian Cancer Incidence in the Multi-Ethnic Asian City-State of Singapore 1968-2012.

PURPOSE: We investigate ovarian cancer incidence between 1968 and 2012 in Singapore, a multiethnic Asian city state. METHODS: Aggregated data of ovarian epithelial cancer numbers and estimated person-years from 1968 to 2012 were obtained from Singapore Cancer Registry. Age-Period-Cohort modelling was performed. RESULTS: The age-standardised incidence rate of ovarian cancer increased from 5.8 to 12.5 per 100,000 per year between 1968 and 2012, while the age-standardised mortality rate has remained stable. This increase was higher among Malays (5.1 to 14.0 per 100,000 per year), compared to Chinese and Indians.  Serous carcinoma showed the greatest increase in incidence from 0.4 to 3.4 per 100,000 per year.  Period effects were seen in the ovarian cancer incidence trend in Chinese women, but not Malay and Indian women. Clear cell and mucinous carcinoma subtypes were more common in Chinese than in Malay and Indian women. Stage at diagnosis for the years 2003-2010 differed by subtype, and the majority of patients with serous carcinomas presented at a later stage compared to those with clear cell or mucinous carcinomas. CONCLUSION: Ovarian cancer incidence rates have doubled in 40 years in Singapore. There were ethnic differences in incidence rates and ovarian cancer subtypes.

Stroke Factors Associated with Thrombolysis Use in Hospitals in Singapore and US: A Cross-Registry Comparative Study.

BACKGROUND AND OBJECTIVES: This paper aims to describe and compare the characteristics of 2 stroke populations in Singapore and in St. Louis, USA, and to document thrombolysis rates and contrast factors associated with its uptake in both populations. METHODS: The stroke populations described were from the Singapore Stroke Registry (SSR) in -Singapore and the Cognitive Rehabilitation Research Group Stroke Registry (CRRGSR) in St. Louis, MO, USA. The registries were compared in terms of demographics and stroke risk factor history. Logistic regression was used to determine factors associated with thrombolysis uptake. RESULTS: A total of 39,323 and 8,106 episodes were recorded in SSR and CRRGSR, respectively, from 2005 to 2012. Compared to CRRGSR, patients in SSR were older, male, and from the ethnic majority. Thrombolysis rates in SSR and CRRGSR were 2.5 and 8.2%, respectively, for the study period. History of ischemic heart disease or atrial fibrillation was associated with increased uptake in both populations, while history of stroke was associated with lower uptake. For SSR, younger age and males were associated with increased uptake, while having a history of smoking or diabetes was associated with decreased uptake. For CRRGSR, ethnic minority status was associated with decreased uptake. CONCLUSIONS: The comparison of stroke populations in Singapore and St Louis revealed distinct differences in clinicodemographics of the 2 groups. Thrombolysis uptake was driven by nonethnicity demographics in Singapore. Ethnicity was the only demographic driver of uptake in the CRRGSR population, highlighting the need to target ethnic minorities in increasing access to thrombolysis.

Extracorporeal Membrane Oxygenation for Severe Adenoviral Pneumonia in Neonatal, Pediatric, and Adult Patients.

OBJECTIVES: We examined data on patients with severe adenoviral pneumonia from the international registry of the Extracorporeal Life Support Organization to identify risk factors for mortality in patients receiving extracorporeal membrane oxygenation. DESIGN: Retrospective analysis. SETTING: International Registry of Extracorporeal Life Support Organization. PATIENTS: We collected de-identified data on all patients with adenoviral pneumonia who needed extracorporeal membrane oxygenation from 1992 to 2016 using International Classification of Diseases, 9th Edition, criteria. INTERVENTIONS: Our primary outcome measure was in-hospital mortality. We also collected data on demographics, preextracorporeal membrane oxygenation ventilator settings, biochemical variables, extracorporeal membrane oxygenation mode, duration, and complications. Initial bivariate analysis assessed potential associations between mortality and various preextracorporeal membrane oxygenation variables as well as extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis that identified predictors of mortality. MEASUREMENTS AND RESULTS: There were 542 patients with adenoviral pneumonia who were supported with extracorporeal membrane oxygenation. Overall mortality was 58% (307/529 patients) (neonates 86.4% [108/125 patients], children 49% [158/327 patients], and adults 49% [41/83 patients]). Multivariate regression identified hypercapnia (PCO2 > 45.7; odds ratio > 3.2; p < 0.001), immunosuppression (odds ratio, 4.44; 95% CI, 1.69-11.61; p = 0.002] and lack of pharmacologic paralysis (odds ratio, 0.30; 95% CI, 0.16-0.57; p < 0.001] as significant preextracorporeal membrane oxygenation factors for mortality. Neonatal patients had significantly higher mortality than pediatric or adult patients (odds ratio, 10.9; 95% CI, 3.2-37.3; p < 0.001). The presence of renal (odds ratio, 4.4; 95% CI, 2.5-7.7; p < 0.001), neurologic (odds ratio, 2.5; 95% CI, 1.2-5.1; p = 0.014), hemorrhagic (odds ratio, 2.2; 95% CI, 1.2-4.0; p = 0.014), or cardiovascular complications (odds ratio, 2.4; 95% CI, 1.3-4.6; p = 0.006) was associated with higher mortality on extracorporeal membrane oxygenation. CONCLUSIONS: Patients with adenoviral pneumonia supported on extracorporeal membrane oxygenation had mortality of 58% over a 25-year-old period. We identified risk factors both before and during extracorporeal membrane oxygenation which were associated with higher mortality. Mortality in neonatal patients was particularly high.

Serial Quantification of Urinary Protein Biomarkers to Predict Drug-induced Acute Kidney Injury.

BACKGROUND: Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. METHODS: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. RESULTS: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. CONCLUSION: Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.