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Lydia QN Liew,1 Lawrence SC Law,1 Edwin Seet,2 Fabio Di Piazza,3 Katherine E Liu,4 Ming Ann Sim,1 Vanessa TY Chua,1 Toby N Weingarten,5 Ashish K Khanna,6 Lian Kah Ti1,2 On behalf of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Investigators1National University Hospital, Singapore, Singapore; 2National University of Singapore, Yong Loo Lin School of Medicine, Singapore; 3Medtronic Core Clinical Solutions, Study and Scientific Solutions, Rome, Italy; 4Patient Monitoring Clinical Research, Medtronic, Minneapolis, MN, USA; 5Departments of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; 6Wake Forest School of Medicine, Winston-Salem, North Carolina, US & Outcomes Research Consortium, Cleveland, OH, USACorrespondence: Lian Kah Ti, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore, Tel +65 6779 5555, Email lian_kah_ti@nuhs.edu.sgPurpose: Postoperative monitoring of respiratory status on general care wards typically consists of intermittent checks of oxyhemoglobin saturation and respiratory rate, allowing substantial unmonitored time for severe opioid induced respiratory depression (RD) to develop unnoticed. Oxygen desaturation index (ODI) can be computed solely by continuous pulse oximetry monitoring. In this post-hoc analysis, we evaluate whether nocturnal ODI correlates with RD.Patients and Methods: The PRODIGY trial (NCT02811302) was a multinational study conducted where adult patients receiving parenteral opioids on the general care floor were continuously monitored by blinded pulse oximetry and capnography monitoring to detect episodes of RD. An RD episode was defined as: respiratory rate ≤ 5 breaths/min (bpm) for ≥ 3 minutes, oxygen saturation (SpO2) ≤ 85% for ≥ 3 minutes, end-tidal carbon dioxide (EtCO2) ≤ 15 or ≥ 60 mm Hg for ≥ 3 minutes, apnea episode lasting > 30 seconds, or any respiratory opioid-related adverse event. Data were used to calculate nocturnal (00:00 &boxh; 06:00) ODI4% based on desaturation episodes (4% decrease from mean oxyhemoglobin saturation in the past 120 seconds, lasting ≥ 10 seconds). Continuous monitoring began after a patient received parenteral opioids, allowing identification of potential RD and ODI4% episodes during opioid therapy. The average number of ODI4% episodes (≥ 1, ≥ 5, ≥ 10, ≥ 15 episodes/hour) were analyzed. Logistic regression and area under the receiver operating characteristic curve (AUC) were computed.Results: A final cohort of 1072 (out of 1335) patients had sufficient data, with 76% (N=817/1072) having ≥ 1 episode of ODI4%. Multivariable logistic regression showed that ODI4% was strongly associated with RD, with greater risk for higher ODI4% scores: ≥ 5 episodes/hour odds ratio 2.59 (95% CI 1.72– 3.89, p< 0.0001); ≥ 10 episodes/hour 3.39 (95% CI 1.80– 6.39, p=0.0002); ≥ 15 episodes/hour 4.71 (95% CI 1.93– 11.47, p=0.0006).There was no significant association between ODI4% and respiratory adverse events.Conclusion: Nocturnal ODI4% was highly correlated with RD among hospitalized patients receiving parenteral opioids. Patients with a high ODI4%, especially with ≥ 15 episodes/hour, are more likely to experience RD and should be evaluated for the need of closer monitoring after opioid administration.Keywords: opioids, oxygen desaturation index, respiratory depression, sleep apnea

Abstract Background The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. Methods Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. Results The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled ‘separation’, ‘different culture’, ‘other people’ and ‘work frustration’. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. Conclusion Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.

Abstract Background Pathogenic or regulatory effects of natural killer (NK) cells are implicated in many autoimmune diseases, but evidence in multiple sclerosis (MS) and its murine models remains equivocal. In an effort to illuminate this, we have here analysed expression of the prototypic NK cell marker, NCR1 (natural cytotoxicity triggering receptor; NKp46; CD335), an activating receptor expressed by virtually all NK cells and therefore considered a pan-marker for NK cells. The only definitive ligand of NCR1 is influenza haemagglutinin, though there are believed to be others. In this study, we investigated whether there were differences in NCR1+ cells in the peripheral blood of MS patients and whether NCR1+ cells are present in white matter lesions. Results We first investigated the expression of NCR1 on peripheral blood mononuclear cells and found no significant difference between healthy controls and MS patients. We then investigated mRNA levels in central nervous system (CNS) tissue from MS patients: NCR1 transcripts were increased more than 5 times in active disease lesions. However when we performed immunohistochemical staining of this tissue, few NCR1+ NK cells were identified. Rather, the major part of NCR1 expression was localised to astrocytes, and was considerably more pronounced in MS patients than controls. In order to further validate de novo expression of NCR1 in astrocytes, we used an in vitro staining of the human astrocytoma U251 cell line grown to model whether cell stress could be associated with expression of NCR1. We found up-regulation of NCR1 expression in U251 cells at both the mRNA and protein levels. Conclusions The data presented here show very limited expression of NCR1+ NK cells in MS lesions, the majority of NCR1 expression being accounted for by expression on astrocytes. This is compatible with a role of this cell-type and NCR1 ligand/receptor interactions in the innate immune response in the CNS in MS patients. This is the first report of NCR1 expression on astrocytes in MS tissue: it will now be important to unravel the nature of cellular interactions and signalling mediated through innate receptor expression on astrocytes.

Abstract Background Since the 1991 Gulf War concerns have been raised about the effects of deployment to the Gulf War on veterans' health. Studies of the reproductive health of Gulf War veterans have reported varied findings. Methods We undertook a cross-sectional study of male Australian Gulf War veterans (n = 1,424) and a randomly sampled military comparison group (n = 1,548). The study was conducted from August 2000 to April 2002. A postal questionnaire included questions about difficulties achieving pregnancy, pregnancy outcomes including live births, stillbirths, miscarriages and terminations; and for all live births gestation, birth weight, sex, and any cancers, birth defects, chromosomal abnormalities or serious health problems. Results Male Gulf War veterans reported slightly increased risk of fertility difficulties following the Gulf War (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.0–1.8), but were more successful at subsequently fathering a child (OR 1.8; 95% CI 1.3–2.6). The study groups reported similar rates of pregnancies and live births. There was no increased risk in veterans of miscarriage, stillbirth, or terminations. Children of male Gulf War veterans born after the period of the Gulf War were not at greater risk of being born prematurely, having a low birth weight, or having a birth defect or chromosomal abnormality (OR 1.0; 95% CI 0.6–1.6). The numbers of cancers and deaths in children were too small to draw any firm conclusions. Conclusion The results of this study do not show an increased risk of adverse reproductive outcome in Australian male Gulf War veterans.

Abstract This paper investigates the dielectric properties and magnetic properties of epoxy composites with different amount of powdered iron phosphate glass (IPG) at 8.2 GHz to 12.4 GHz using microwave technique. IPG composed of 60P2O5-40Fe2O3 (mol%) was produced by conventional melt and quenching method and crushed into powder. The IPG powder was characterized using energy dispersive X-ray spectroscopy (EDS), particle size analyzer and powder X-ray diffraction (XRD). Different amount of IPG (10-70 wt%) were dispersed in the epoxy. The epoxy-IPG composites were characterized by their morphology, elemental composition and scattering parameters using scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS) and vector network analyzer (VNA), respectively. Reflection coefficient, |S11| increases whereas transmission coefficient, |S21| decreases with increasing IPG content in epoxy. Dielectric constant, εr' of epoxy-IPG composites were found increased with the IPG content from 3.33 to 4.69.

Introduction: The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored., Methods: We examined this in a Singaporean memory clinic cohort of 528 subjects (n = 300, CeVD; n = 167, incident cognitive decline) followed-up for 4 years., Results: Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .05). Sixteen diverse biological processes were implicated in cognitive decline. Ten proteins independently predicted incident dementia (q-value < .05). A unified prediction model combining plasma proteins with clinical risk factors increased the area under the curve for outcome prediction from 0.62 to 0.85. External validation in the cerebrospinal fluid proteome of an independent Caucasian cohort replicated four of the significantly predictive plasma markers for cognitive decline namely: GFAP, NEFL, AREG, and PPY., Discussion: The prognostic proteins prioritized in our study provide robust signals in two different biological matrices, representing potential mechanistic targets for dementia and cognitive decline., Highlights: A total of 1441 plasma proteins were profiled in a Singaporean memory clinic cohort. We report prognostic plasma protein signatures for cognitive decline and dementia. External validation was performed in the cerebrospinal fluid proteome of a Caucasian cohort. A concordant proteomic signature was identified across both biofluids and cohorts. Further studies are needed to explore the therapeutic implications of these proteins for dementia., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Brain serotonin dysregulation is associated with dementia and neuropsychiatric symptomology. However, the prognostic utility of circulating serotonin levels in detecting features of prodromal dementia including functional decline, cognitive impairment, mild behavioural impairment and brain atrophy remains unclear. In this prospective study of memory clinic subjects followed-up for ≤5 years, dementia-free subjects, classified as having no cognitive impairment or cognitive impairment, no dementia at baseline, underwent annual neuropsychological assessments including Montreal Cognitive Assessment, Global Cognition Z- scores and Clinical Dementia Rating Scale Global Scores (where a ≥ 0.5 increment from baseline denotes functional decline). Mild behavioural impairment was measured using baseline and annual Neuropsychiatric Inventory assessments, while brain atrophy was evaluated using cortical and medial temporal atrophy scores from baseline MRI scans. Baseline serum serotonin was then associated with the neuropsychological and neuroimaging measures cross-sectionally and longitudinally. Furthermore, associations of serum serotonin with cross-sectional brain atrophy scores were studied. Of the 191 elderly subjects included in the study, 63 (33.0%) had no cognitive impairment while 128 (67.0%) had cognitive impairment, no dementia. Fourteen subjects (9.0%) showed baseline mild behavioural impairment. Compared with the highest tertile, subjects within the lowest tertile of serotonin had greater Cortical Atrophy scores (adjusted odds ratio = 2.54, 95% confidence interval=1.22-5.30, P = 0.013). Serotonin levels were not significantly associated with cross-sectional neuropsychological or mild behavioural impairment scores (all P > 0.05). Of the 181 subjects with longitudinal cognitive follow-up (median duration 60.0 months), 56 (30.9%) developed functional decline, while incident mild behavioural impairment occurred in 26/119 (21.8%) subjects. Compared with the highest tertile, lower serotonin levels were associated with higher hazards of functional decline (lowest tertile: adjusted hazards ratio = 2.15, 95% confidence interval = 1.04-4.44, P = 0.039), and incident mild behavioural impairment (lowest tertile: adjusted hazards ratio = 3.82, 95% confidence interval = 1.13-12.87, P = 0.031, middle tertile: adjusted hazards ratio = 3.56, 95% confidence interval =1.05-12.15, P = 0.042). The association between the lowest serotonin tertile and functional decline was mediated via its effect on incident mild behavioural impairment (adjusted odds ratio = 3.96, 95% confidence interval = 1.15-13.61, P = 0.029). In conclusion, low circulating serotonin may be associated with cortical atrophy at baseline, as well as act as an early prognostic marker for functional decline and mild behavioural impairment in elderly, dementia-free subjects., Competing Interests: The authors have no competing interests., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Acute kidney injury (AKI) within the intensive care unit (ICU) is common but evidence is limited on longer-term renal outcomes. We aimed to model the trend of kidney function in ICU survivors using estimated glomerular filtration rate (eGFR), comparing those with and without AKI, and investigate potential risk factors associated with eGFR decline., Methods: This observational cohort study included all patients aged 16 or older admitted to two general adult ICUs in Scotland between 1st July 2015 and 30th June 2018 who survived to 30 days following hospital discharge. Baseline serum creatinine and subsequent values were used to identify patients with AKI and calculate eGFR following hospital discharge. Mixed effects modelling was used to control for repeated measures and to allow inclusion of several exploratory variables., Results: 3649 patients were included, with 1252 (34%) experiencing in-ICU AKI. Patients were followed up for up to 2000 days with a median 21 eGFR measurements. eGFR declined at a rate of -1.9 ml/min/1.73m 2 /year ( p- value < 0.001) in the overall ICU survivor cohort. Patients with AKI experienced an accelerated rate of post-ICU eGFR decline of -2.0 ml/min/1.73m 2 /year compared to a rate of -1.83 ml/min/1.73m 2 /year in patients who did not experience AKI ( p- value 0.007). Pre-existing diabetes or liver disease and in-ICU vasopressor support were associated with accelerated eGFR decline regardless of AKI experience., Conclusions: ICU survivors experienced a decline in kidney function beyond that which would be expected regardless of in-ICU AKI. Long-term follow-up is warranted in ICU survivors to monitor kidney function and reduce morbidity and mortality., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PM reports lecture honoraria from Astrazeneca, Pharmacomsos, Astellas, GSK and Boehringer Ingelheim outside the submitted work. The authors declare no other potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2024.)

Preoperative biofluid biomarkers reflecting pathophysiological, neuronal injury, and inflammation as well as those for Alzheimer's disease (AD) may be valuable tools for the risk stratification of perioperative neurocognitive disorders (PNDs) in older adults. We summarized current evidence relating these preoperative biomarkers to PND beyond 7 days, in older surgical participants aged ≥60 years. Studies that evaluated the association of preoperative biomarkers with cognitive decline as an outcome, beyond 7 days, were identified through searches of 6 databases and 3 trial registries to 17 January 2024. Preclinical studies, intracranial surgical, or studies with participants aged <60 years were excluded. Studies varied widely in the assessment of PND, so a wide range of cognitive outcomes was accepted, including those using the term postoperative cognitive dysfunction (POCD) to define cognitive decline. The pooled incidence of POCD utilizing a binary cognitive outcome was summarized. Fifteen studies involving 2103 participants were included. Marked heterogeneity was evident in the cognitive outcome metrics, assessment timeframes, limiting a quantitative synthesis. Of the 9 studies using binarized cognitive outcomes, the incidence of POCD was 23.4% (95% confidence interval [CI], 6.6-46.2) at <3 months, 11.4% (95% CI, 8.1-15.0) at 3 to <12 months, and 6.9% (95% CI, 1.9-14.5) at ≥12 months postoperatively. Of the 15 studies, 9 described blood-based biomarkers, 4 described cerebrospinal fluid (CSF) biomarkers, and 2 measured both blood and CSF markers. The biomarkers evaluated reflected the pathogenic indicators neuronal injury (9 studies), inflammation (5 studies) and of amyloid (5 studies), and Tau (1 study). The studies included were of medium to high quality. Evidence was the most promising for amyloid biomarkers, with 4 of 5 included studies demonstrating associations of lower preoperative biofluid amyloid biomarker levels with increased risk of POCD. In conclusion, preoperative biofluid amyloid biomarkers may hold potential utility for the prediction of POCD, although current evidence remains limited. Other potential preoperative biomarkers for POCD included p-Tau181 and Neurofilament Light, however small sample sizes, study heterogeneity, and conflicting results limited conclusions drawn. Standardized cognitive outcome metrics and common assessment timeframes are additionally required in future studies to ascertain the prognostic utility of these biomarkers for POCD., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Background: The association between platelet endothelial cell adhesion molecule-1 (PECAM-1) with cerebral small-vessel disease and cognition in dementia-free subjects remains uninvestigated., Methods and Results: A prospective cohort of dementia-free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice-yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM-1 levels with cerebral small-vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM-1 levels were 0.790 (interquartile range, 0.645-0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM-1 tertile had greater cross-sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67-9.01]; P =0.023), age-related white matter change scores (β=1.39 [95% CI, 0.12-2.67]; P =0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19-5.62]; P =0.016). Of the 204 participants with follow-up data (median, 60.0 [interquartile range, 60.0-60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM-1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35-15.13]; P =0.024; second tertile: AHR, 3.28 [95% CI, 1.02-10.60]; P =0.047). The lowest PECAM-1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06-8.24]; P =0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05-4.65]; P =0.036), and decline in executive function (β=-0.45 [95% CI, -0.76 to -0.14]; P =0.004), and Montreal Cognitive Assessment (β=-1.32 [95% CI, -2.30 to -0.35]; P =0.008) scores., Conclusions: In dementia-free subjects, lower circulating PECAM-1 levels are associated with greater cerebral small-vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

Purpose: Oxygen delivery (DO 2 ) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO 2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO 2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO 2 ) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO 2 trend., Methods: Our algorithm was built systematically with 4 components - machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO 2 presentation using a graphic-user interface. Hb readings were validated., Results: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO 2 trends and AKI were studied., Conclusion: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO 2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO 2 thresholds and optimizing DO 2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery., (© 2024. The Author(s).)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Objective: Studies investigating associations between maternal epidural analgesia (MEA) and autism spectrum disorder (ASD) in the offspring are conflicting and lack prospective neurobehavioral follow-up assessments for autistic traits. We aim to prospectively investigate associations between MEA and autistic traits in the offspring., Design: Prospective neurobehavioral observational cohort study., Setting: Singaporean tertiary healthcare institutions., Patients: Participants recruited were singleton non-IVF children, >36 weeks gestation, delivered via normal vaginal delivery by mothers >18 years of age, delivered in Singapore from June 2009-September 2010 and followed up over 7 years., Interventions: Exposure to maternal epidural analgesia during delivery., Measurements: The primary outcome is an abnormal Social Responsiveness Scale (SRS) T score at 7 years (≥60 points). Secondary outcomes include the diagnosis of ASD and abnormal scores for autistic traits assessed via a neurobehavioral battery comprising: CBCL (child behavioural checklist), Q-CHAT (Quantitative Checklist for Autism in Toddlers), and Bayley-III. Multivariable analyses adjusting for maternal and offspring characteristics were performed., Main Results: 704 out of 769 mother-child dyads recruited fulfilled the criteria for analysis. 365/704 mothers received MEA. The incidence of an abnormal SRS score at 7 years in offspring exposed to MEA was 19.9%, and 26.1% in non-exposed offspring (p = 0.154). Multivariable analysis did not demonstrate a significant association between MEA and abnormal SRS scores at 7 years (O.R.0.726, 95% C·I. 0.394-1.34, p = 0.305). After adjustment for maternal and fetal demographics, exposure to MEA was not significantly associated with an abnormal screen in all other tests for autistic traits. The clinical incidence of ASD was 1.76% in children without exposure to MEA, and 2.32% in children with MEA exposure (p = 0.506)., Conclusions: MEA is not significantly associated with the development of ASD and autistic traits in offspring, assessed over 7 years. Results should be taken into perspective given our wide confidence intervals and small cohort size., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Opioid-induced respiratory depression (OIRD) is common on the medical and surgical wards and is associated with increased morbidity and health care costs. While previous studies have investigated risk factors for OIRD, the role of race remains unclear. We aim to investigate the association between race and OIRD occurrence on the medical/surgical ward., Methods: This is a post hoc analysis of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial; a prospective multinational observational blinded study of 1335 general ward patients who received parenteral opioids and underwent blinded capnography and oximetry monitoring to identify OIRD episodes. For this study, demographic and perioperative data, including race and comorbidities, were analyzed and assessed for potential associations with OIRD. Univariable χ 2 and Mann-Whitney U tests were used. Stepwise selection of all baseline and demographic characteristics was used in the multivariable logistic regression analysis., Results: A total of 1253 patients had sufficient racial data (317 Asian, 158 Black, 736 White, and 42 other races) for inclusion. The incidence of OIRD was 60% in Asians (N = 190/317), 25% in Blacks (N = 40/158), 43% in Whites (N = 316/736), and 45% (N = 19/42) in other races. Baseline characteristics varied significantly: Asians were older, more opioid naïve, and had higher opioid requirements, while Blacks had higher incidences of heart failure, obesity, and smoking. Stepwise multivariable logistic regression revealed that Asians had increased risk of OIRD compared to Blacks (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.54-4.04; P = .0002) and Whites (OR, 1.38; 95% CI, 1.01-1.87; P = .0432). Whites had a higher risk of OIRD compared to Blacks (OR, 1.81; 95% CI, 1.18-2.78; P = .0067). The model's area under the curve was 0.760 (95% CI, 0.733-0.787), with a Hosmer-Lemeshow goodness-of-fit test P value of .23., Conclusions: This post hoc analysis of PRODIGY found a novel association between Asian race and increased OIRD incidence. Further study is required to elucidate its underlying mechanisms and develop targeted care pathways to reduce OIRD in susceptible populations., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Given the rising prevalence of antiplatelet therapy, rapid preoperative identification of patients with bleeding diathesis is necessary for the guidance of blood product administration. This is especially relevant in neurosurgery for intracranial hemorrhage (ICH), where indiscriminate transfusions may lead to further hemorrhagic or thromboembolic injury. Point-of-care (POC) testing of platelet function is a promising solution to this dilemma, as it has been proven effective in cardiac surgery. However, to date, POC platelet function testing in neurosurgery has not been extensively evaluated. This systematic review appraises the use of POC platelet function test (PFT) in emergency neurosurgery in terms of its impact on patient outcomes.A comprehensive search was conducted on four electronic databases (Pubmed, MEDLINE, Embase, and Cochrane) for relevant English language articles from their respective inceptions until 1 June 2022. We included all randomized controlled trials and cohort studies that met the following inclusion criteria: (i) involved adult patients undergoing neurosurgery for ICH; (ii) evaluated platelet function via POC PFT; (iii) reported a change in perioperative blood loss; and/or (iv) reported data on treatment-related adverse events and mortality. Assessment of study quality was conducted using the Newcastle Ottawa Quality Assessment Scale for Cohort Studies and Case-Control Studies, and the JBI Critical Appraisal Checklist for Case Series.The search yielded 2,835 studies, of which seven observational studies comprising 849 patients met the inclusion criteria for this review. Overall, there is evidence that the use of POC PFT to assess bleeding risk reduced bleeding events, thromboembolic adverse outcomes, and the length of hospitalization. However, there is currently insufficient evidence to suggest that using POC PFT improves blood product use, functional outcomes or mortality., (© 2022. The Author(s).)

Objectives: Our study aims to investigate the safety and efficiency of the Codonics Safe Label System (SLS) in a prospective simulation study., Methods: Three sets of simulated experiments involving 82 anesthetists were carried out on patient simulator mannequins. The primary outcome assessed through the simulated experiments was the effectiveness of the SLS in avoiding vial swap errors. Secondary outcomes analyzed included the efficacy of the SLS in preventing syringe swap and the difference in time taken to prepare standardized drugs as compared with conventional methods., Results: The SLS was associated with a significant reduction in all 4 stages of vial swap error. The incidence of wrong ampoule breakage was significantly lower in the SLS group compared with the conventional group (12.1% versus 38.5%, P = 0.007). The number of staff who drew the wrong ampoule was similarly lower in the SLS group compared with the conventional group (4.9% versus 33.3%, P = 0.001). The proportions of staff who eventually wrongly labeled the loaded syringe were 0% in the SLS group and 17.9% in the conventional group (P = 0.005).Drug preparation time was longer for the SLS group than for the conventional group (239.6 ± 45.9 versus 160.3 ± 46.5 seconds, P < 0.001).There was no significant difference in the incidence of syringe swap with the use of the SLS., Conclusions: The use of the SLS is effective in reducing vial swap error, but not syringe swap errors, and is associated with increased time taken for anesthetic drug preparation., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Adverse events (AEs) remain a challenge in tertiary healthcare with incidence rates of 4% to 14%, where half are potentially preventable. Reported patient safety strategies rarely involve changing the practices of an entire academic institution and maintaining sustainability. We hypothesize that implementing an effective patient safety strategy (PSS) improves hospital-wide AE rates, cost avoidance, and patient safety culture., Methods: A 3-stage hospital-wide PSS was implemented from 2012 to 2016, involving a top-down, bottom-up approach in a 1171-bed academic institution. The primary outcome was the incidence, preventability, and severity of hospital-wide AEs, calculated through the Institute of Healthcare Improvement, Global Trigger Tool method (incidence), National Coordinating Council for Medication Error Reporting and Prevention tool (severity), and a preventability decision algorithm (preventability). Secondary outcomes include hospital-wide cost savings and patient safety climate survey results., Results: A total of 15,120 random chart reviews were performed across 430,868 admissions from 2012 to 2018. Overall, AE rates decreased from 11.6% to 5.4% (R2 = 0.71, P = 0.017). The incidence of preventable AEs declined from 5.7% to 2.0% (R2 = 0.80, P = 0.006). The severity of AEs reduced, with the proportion of category G, H, and I AEs decreasing from 8.4% (2012) to 2.6% (2018). A total of 15,960 hospital-wide patient safety climate surveys were administered from 2011 to 2016, demonstrating an improvement in hospital-wide percentage positive patient safety grade from 46.5% pre-PSS to 58.3% post-PSS implementation. This was accompanied by an 82% increase in voluntary event reporting, and cost savings of 20,600 bed-days and U.S. $29.2 million upon completion of stage 3 (2012-2016)., Conclusions: The hospital-wide PSS resulted in significant improvements in the incidence and severity of AEs, healthcare cost savings, and patient safety culture, demonstrating sustainability for 7 years., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute kidney injury is common in the surgical intensive care unit (ICU). It is associated with poor patient outcomes and high healthcare resource usage. This study's primary objective is to help identify which ICU patients are at high risk for acute kidney injury. Its secondary objective is to examine the effect of acute kidney injury on a patient's prognosis during and after the ICU admission., Methods: A retrospective cohort of patients admitted to a Singaporean surgical ICU between 2015 to 2017 was collated. Patients undergoing chronic dialysis were excluded. The outcomes were occurrence of ICU acute kidney injury, hospital mortality and one-year mortality. Predictors were identified using decision tree algorithms. Confirmatory analysis was performed using a generalized structural equation model., Results: A total of 201/940 (21.4%) patients suffered acute kidney injury in the ICU. Low ICU haemoglobin levels, low ICU bicarbonate levels, ICU sepsis, low pre-ICU estimated glomerular filtration rate (eGFR) and congestive heart failure was associated with the occurrence of ICU acute kidney injury. Acute kidney injury, together with old age (> 70 years), and low pre-ICU eGFR, was associated with hospital mortality, and one-year mortality. ICU haemoglobin level was discretized into 3 risk categories for acute kidney injury: high risk (haemoglobin ≤9.7 g/dL), moderate risk (haemoglobin between 9.8-12 g/dL), and low risk (haemoglobin > 12 g/dL)., Conclusion: The occurrence of acute kidney injury is common in the surgical ICU. It is associated with a higher risk for hospital and one-year mortality. These results, in particular the identified haemoglobin thresholds, are relevant for stratifying a patient's acute kidney injury risk.

Background: The acute medical unit (AMU) provides early specialist care to emergency department patients before inpatient admission. The workflows and skills for successful AMU nursing comprise a hybrid of internal and emergency medicine., Purpose: To understand nursing work dynamics in the AMU., Methods: AMU at a 1,250-bed tertiary academic center in Singapore with 14,000 ED presentations monthly. Retrospective mixed methods study using focus group discussions and surveys. Fifteen nurses across three focus group discussions. Thirty-two physicians and 54 nurses responded to a validated questionnaire., Findings: Focus group discussions transcripts content analyzed by two researchers. Survey items factor analyzed and attitudinal differences between AMU physicians and nurses, and among nurses compared using Student's t- and one-way ANOVA tests., Discussion: AMU nursing staff faced obstacles of inadequate patient information, emergency department onboarding, unbalanced workload, and coworker conflicts, which led to them to develop processes and checklists to manage patient information, patient expectations, and teamwork., Conclusion: AMU nursing requires a combination of specialist internal medicine and emergency medicine skills. Training should familiarize nurse workforce with managing patient expectations and multidisciplinary teamwork., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiac surgery induces a significant inflammatory hypermetabolic stress response, resulting in postoperative hyperglycemia in both preoperatively diabetic and nondiabetic patients. Such postoperative hyperglycemia has been associated with adverse outcomes in surgery and postsurgical recovery. Yet, while diabetes is a known risk factor for postoperative hyperglycemia, predictors of postoperative hyperglycemia among nondiabetics in the local Southeast Asian population remain unknown.We aim to investigate the predictors and outcomes associated with hyperglycemia after cardiac surgery among nondiabetics in the local Southeast Asian population. We analyzed data from 1602 nondiabetic adult patients undergoing elective cardiac surgery, from 2008 to 2010 at the 2 main heart centers in Singapore.Nondiabetic patients who developed postoperative hyperglycemia tended to be women, older, more obese, and hypertensive. Higher body mass index (BMI), age, aortic cross-clamp time, and blood transfusion were identified as independent risk factors of postoperative hyperglycemia. Postoperative hyperglycemia was also significantly associated with postoperative cardiac arrhythmias (26.9% vs 15.0%, P < .001), acute kidney injury (30.0% vs 20.1%, P < .001), longer intensive care unit (ICU) stay (46.7 ± 104.1 vs 37.2 ± 76.6 hours, P = .044) and longer hospitalization (11.5 ± 12.2 vs 9.6 ± 8.0 days, P < .001).Our study identified aortic cross-clamp time and blood transfusion as independent risk factors of postoperative hyperglycemia after cardiac surgery in nondiabetics. Similar to other studies, higher BMI and age were independent risk factors for postoperative hyperglycemia. Postoperative hyperglycemia was also associated with adverse perioperative outcomes and should thereby be avoided by treating modifiable risk factors identified in this study including reducing blood transfusion and aortic cross-clamp time. Our findings contribute to early risk stratification of nondiabetic patients who are at increased risk of postoperative hyperglycemia.

Objective: Postoperative hyperglycemia is a known risk factor for adverse outcomes following cardiac surgery. Therefore, the authors investigated the association between ethnicity and postoperative hyperglycemia in a Southeast Asian multiethnic population undergoing cardiac surgery., Design: Perioperative data were analyzed prospectively., Setting: Perioperative data were obtained from 2008 to 2010 at the 2 main heart centers in Singapore., Participants: Data from 911 adult patients were collected., Interventions: All patients underwent elective cardiac surgery., Measurements and Main Results: Perioperative variables, genetic associations, and outcomes of hyperglycemic versus normoglycemic patients were compared. Of the 911 patients analyzed, 47.7% (n = 435) were diabetic and 77.7% (n = 708) had postoperative hyperglycemia. Patients with postoperative hyperglycemia after cardiac surgery were more likely to have diabetes; be female, older, and more obese; and have hypertension and renal impairment. Patients of Indian ethnicity had a significantly higher incidence of postoperative hyperglycemia (86.7%, p = 0.043), as compared to Malays (79.1%) and Chinese (75.9%). Ethnicity was identified as an independent risk factor for postoperative hyperglycemia, with Indians having a significantly higher risk than Chinese (OR 2.115, p = 0.015). Although Indian ethnicity was associated with the presence of angiotensin-converting enzyme D allele (65.7%, p = 0.044), no genetic associations with postoperative hyperglycemia were identified. Postoperative hyperglycemia also was associated significantly with poorer outcomes of longer high-dependency unit stay and new-onset cardiac arrhythmias., Conclusion: The authors' findings demonstrated Indian ethnicity as an independent risk factor of postoperative hyperglycemia, likely due to insulin resistance and exaggerated hyperglycemic stress response, emphasizing the need for ethnic-based data unique to each population group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery associated with increased morbidity and mortality. Although sustained hyperglycemia is a known risk factor of AF and poor ICU outcomes, emerging in-vitro studies reveal acute glycemic fluctuations to be an additional independent predictor of AF. The effect of acute glycemic fluctuations on the incidence of POAF in the clinical setting remains unclear. We aim to investigate the effect of the magnitude of acute perioperative glycemic fluctuations on the incidence of POAF in a multi-ethnic Southeast-Asian population., Methods: We obtained data from1743 patients who underwent elective CABG in a tertiary heart centre from 2009-2011. Patients were kept to a tight baseline glycemic control in accordance with hospital protocol. The magnitude of the difference between the highest and lowest perioperative glucose levels up till the first 48 postoperative hours was employed as a measure of glycemic fluctuation. Patients were divided into 4 groups for analysis based on the magnitude of glycemic fluctuation:A)0-2mmol/L(N = 147); B)>2-4mmol/L(N = 426); C)>4-6mmol/L(N = 513); D)>6mmol/L(N = 657).Our primary outcome was the incidence of POAF. Secondary outcomes included ICU and 30-day mortality and length of stay., Results: The overall incidence of POAF was 14.7%. This increased as the magnitude of glycemic fluctuation increased, and was statistically highest in Group D(16.4%) as compared with the other 3 sub-groups. Multivariate logistic regression revealed the magnitude of perioperative glycemic fluctuation to be an independent risk factor of POAF(O.R.1.06, 95% C.I.1.01-1.11, p = 0.014).ICU length of stay was statistically highest in Group D(63.1 hours, p = < .001). However, ICU and 30 day mortality rates were similar among the 4 groups., Conclusion: Increased magnitudes of acute perioperative glycemic fluctuations are associated with a significantly increased risk of POAF and length of ICU stay; and should therefore be minimised but balanced against the risks of hypoglycemia so as to avoid POAF and optimise patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

Aim: Thermoregulatory stability and monitoring are crucial in neonatal care. However, the current standard of temperature measurement using Axillary Thermometry (AT) poses multiple limitations. Temporal Artery Thermometry (TT) is a promising new method, which thus begs the question: Can TT replace AT in neonates? Previous studies reveal conflicting results, with none involving a Southeast-Asian multi-ethnic neonatal population under different environments., Methods: A 6-month prospective comparative study involving neonates managed in a tertiary neonatal centre. Subjects were divided into 4 groups based on the required nursing environment: A) Room air B) Phototherapy C) Radiant warmers D) Incubators. Six hundred and sixty-one paired TT and AT temperature readings were obtained, with concurrent FLACC scoring to evaluate the discomfort associated with each thermometry method., Results: TT readings were higher than AT in all groups. The mean temperature difference between both methods (TT-AT) was lowest in Group A (0.10 ± 0.19°C), followed by Groups B (0.50 ± 0.33°C), C (0.97 ± 0.76°C) and D (1.15 ± 0.57°C) respectively. Bland-Altman analysis revealed good clinical agreement (± 0.5°C) between both methods in Group A (7-0.27,0.47). However, Groups B (-0.14,1.13), C (-0.51,2.45) and D (0.03,2.27) showed poor agreement. Multiple GEE analysis revealed Malay ethnicity to be an additional predictor of decreased TT-AT ( β = -0.13, p = 0.012). Compared to TT, AT was associated with higher discomfort levels (p <0.001)., Conclusions: Given the good agreement and increased comfort with TT use, our study confirms that TT is comparable to AT for neonates nursed in room air. TT is therefore recommended for the temperature screening and monitoring of neonates nursed on ambient air. Its use in other environments and factors predictive of comparability of both methods requires further study., (© 2016 The Authors. Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Acute kidney injury (AKI) is a common complication after cardiac surgery. Recent studies have revealed emerging associations between the magnitude of acute glycemic fluctuations and intensive care unit (ICU) mortality rates. However, the effect of acute glycemic fluctuations on the development of postoperative AKI remains unclear. Thus, we aim to investigate the effect of the magnitude of acute perioperative glycemic fluctuations on the incidence of postoperative AKI.We conducted a prospective cohort study by prospectively obtaining data from all patients who underwent elective coronary artery bypass grafting in a tertiary heart institution from 2009 to 2011. The magnitude of the difference between the highest and lowest perioperative glucose levels within 48 hr was calculated as a measure of perioperative glycemic fluctuation. Patients were divided into 4 groups for analysis based on the magnitude of perioperative glycemic fluctuation-A: 0 to 2 mmol/L; B: >2 to 4 mmol/L; C: >4 to 6 mmol/L; and D: >6 mmol/L. We analyzed the incidence of postoperative AKI, ICU mortality and ICU length of stay as primary and secondary outcomes, respectively. Both univariate and multivariate analyses were used.We analyzed data from 1386 patients. The overall incidence of AKI was 29.9% and increased with wider glycemic fluctuation. The incidence of AKI was statistically highest in Group D (38.3%), followed by Groups C (28.6%), B (21.7%), and A (17.4%), respectively (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.001). A similar trend was observed among both diabetics and nondiabetics (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.001 and P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.002, respectively). Multivariate logistic regression showed the magnitude of perioperative glycemic fluctuations to be an independent risk factor in the development of AKI (P < 0.001, odds ratio 1.180, 95% confidence interval 1.116-1.247). ICU length of stay was statistically highest in Group D (58.3[REPLACEMENT CHARACTER]hr) compared with Groups C (44.5[REPLACEMENT CHARACTER]hr), B (37.3[REPLACEMENT CHARACTER]hr), and A (32.8[REPLACEMENT CHARACTER]hr, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.003). ICU mortality rate was comparable among all 4 groups (P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.172).Wide acute perioperative glycemic fluctuations should be avoided as they are associated with a significantly increased risk of AKI and ICU length of stay in both the diabetics and the nondiabetics.

Oxygen is the commonest drug prescribed in hospitals. The inhaled concentration is altered by the administered oxygen flow rate, the characteristics of the delivery device and the patient's respiratory pattern. Using healthy volunteers we measured the inspired oxygen concentration achieved with different devices both at rest and when the breathing pattern of respiratory failure was simulated by binding the subjects' chests until the forced expiratory volume in 1 s was reduced by > 50% and the respiratory rate was > 25 breaths.min(-1). With this respiratory pattern, there was a statistically significant fall in F(I)o(2) while administering oxygen via a Hudson mask at 4 l.min(-1) (23.8% (95% CI 17.4-30.3%) reduction), 12 l.min(-1), humidified (17.8% (95% CI 8.8-26.7%) reduction) and 24 l.min(-1), humidified (12.2% (95% CI 5.0-19.3%) reduction). There was no statistically significant change with a nonrebreathing (reservoir) mask at 15 and 110 l.min(-1) or with a Vapotherm 2000i at 40 l.min(-1), humidified, via nasal prongs. We conclude that the F(I)o(2) delivered by high flow devices is unaffected when the breathing pattern of respiratory failure is simulated. The F(I)o(2) achieved at rest by a nonrebreathing mask (0.68) is less than that often quoted in the literature.

A cross-sectional study of 63 current and former aluminum potroom workers and 37 comparison workers was conducted to evaluate for evidence of neurological dysfunction, including tremor from long-term exposures to aluminum using sensitive quantitative measures of arm/hand and leg tremor. Signs of upper extremity tremor were also evaluated by neurological examination and compared with the quantitative measures of arm/hand tremor. Both arm/hand and leg tremor were measured using fatiguing test conditions, but no statistically significant differences due to exposure to aluminum were present between the potroom workers and the comparison workers. The neurological examination also showed no statistically significant differences between the groups on the evaluation of signs of tremor. These results do not support the findings of Best-Pettersen et al., who reported evidence of increased tremor in aluminum workers using the static steadiness test in the Halstead-Reitan battery. Differences between the studies that may have contributed to the contrasting results are discussed. In addition, techniques are presented for using microcomputer-controlled devices to evaluate tremor in both the visible (1-6 Hz) and nonvisible (7-18 Hz) frequencies of the tremor spectrum.