Postoperative cognitive dysfunction (POCD) is common in elderly patients after noncardiac surgery, but the consequences are unknown. The authors' aim was to determine the effects of POCD on long-term ...prognosis.
This was an observational study of Danish patients enrolled in two multicenter studies of POCD between November 1994 and October 2000. The cohort was followed up from the date of surgery until August 2007. Cognitive function was assessed by a neuropsychological test battery at three time points: before, at 1 week after, and at 3 months after noncardiac surgery. Data on survival, labor market attachment, and social transfer payments were obtained from administrative databases. The Cox proportional hazards regression model was used to compute relative risk estimates for mortality and disability, and the relative prevalence of time on social transfer payments was assessed by Poisson regression.
A total of 701 patients were followed up for a median of 8.5 yr (interquartile range, 5.3-11.4 yr). POCD at 3 months, but not at 1 week, was associated with increased mortality (hazard ratio, 1.63 95% confidence interval, 1.11-2.38; P = 0.01, adjusted for sex, age, and cancer). The risk of leaving the labor market prematurely because of disability or voluntary early retirement was higher among patients with 1-week POCD (hazard ratio, 2.26 1.24-4.12; P = 0.01). Patients with POCD at 1 week received social transfer payments for a longer proportion of observation time (prevalence ratio, 1.45 1.03-2.04; P = 0.03).
Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market prematurely, and dependency on social transfer payments.
Objectives This study sought to perform an indirect comparison analysis of dabigatran etexilate (2 doses), rivaroxaban, and apixaban for their relative efficacy and safety against each other. ...Background Data for warfarin compared against the new oral anticoagulants (OACs) in large phase III clinical trials of stroke prevention in atrial fibrillation (AF) are now available for the oral direct thrombin inhibitor, dabigatran etexilate, in 2 doses (150 mg twice daily BID, 110 mg BID), and the oral Factor Xa inhibitors, rivaroxaban and apixaban. A “head-to-head” direct comparison of drugs is the standard method for comparing different treatments, but in the absence of such head-to-head direct comparisons, another alternative to assess the relative effect of different treatment interventions would be to perform indirect comparisons, using a common comparator. Nonetheless, any inter-trial comparison is always fraught with major difficulties, and an indirect comparison analysis has many limitations, especially with the inter-trial population differences and thus, should not be overinterpreted. Methods Indirect comparison analysis was performed using data from the published trials. Results There was a significantly lower risk of stroke and systemic embolism (by 26%) for dabigatran (150 mg BID) compared with rivaroxaban, as well as hemorrhagic stroke and nondisabling stroke. There were no significant differences for apixaban versus dabigatran (both doses) or rivaroxaban; or rivaroxaban versus dabigatran 110 mg BID in preventing stroke and systemic embolism. For ischemic stroke, there were no significant differences between the new OACs. Major bleeding was significantly lower with apixaban compared with dabigatran 150 mg BID (by 26%) and rivaroxaban (by 34%), but not significantly different from dabigatran 110 mg BID. There were no significant differences between apixaban and dabigatran 110 mg BID in safety endpoints. Apixaban also had lower major or clinically relevant bleeding (by 34%) compared with rivaroxaban. When compared with rivaroxaban, dabigatran 110 mg BID was associated with less major bleeding (by 23%) and intracranial bleeding (by 54%). There were no significant differences in myocardial infarction events between the dabigatran (both doses) and apixaban. Conclusions Notwithstanding the limitations of an indirect comparison study, we found no profound significant differences in efficacy between apixaban and dabigatran etexilate (both doses) or rivaroxaban. Dabigatran 150 mg BID was superior to rivaroxaban for some efficacy endpoints, whereas major bleeding was significantly lower with dabigatran 110 mg BID or apixaban. Only a head-to-head direct comparison of the different new OACs would fully answer the question of efficacy/safety differences between the new drugs for stroke prevention in AF.
Background
Available evidence on the effects of a high fraction of inspired oxygen (FIO2) of 60% to 90% compared with a routine fraction of inspired oxygen of 30% to 40%, during anaesthesia and ...surgery, on mortality and surgical site infection has been inconclusive. Previous trials and meta‐analyses have led to different conclusions on whether a high fraction of supplemental inspired oxygen during anaesthesia may decrease or increase mortality and surgical site infections in surgical patients.
Objectives
To assess the benefits and harms of an FIO2 equal to or greater than 60% compared with a control FIO2 at or below 40% in the perioperative setting in terms of mortality, surgical site infection, respiratory insufficiency, serious adverse events and length of stay during the index admission for adult surgical patients.
We looked at various outcomes, conducted subgroup and sensitivity analyses, examined the role of bias and applied trial sequential analysis (TSA) to examine the level of evidence supporting or refuting a high FIO2 during surgery, anaesthesia and recovery.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS, International Web of Science, the Latin American and Caribbean Health Science Information Database (LILACS), advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to February 2014. We checked the references of included trials and reviews for unidentified relevant trials and reran the searches in March 2015. We will consider two studies of interest when we update the review.
Selection criteria
We included randomized clinical trials that compared a high fraction of inspired oxygen with a routine fraction of inspired oxygen during anaesthesia, surgery and recovery in individuals 18 years of age or older.
Data collection and analysis
Two review authors extracted data independently. We conducted random‐effects and fixed‐effect meta‐analyses, and for dichotomous outcomes, we calculated risk ratios (RRs). We used published data and data obtained by contacting trial authors.
To minimize the risk of systematic error, we assessed the risk of bias of the included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta‐analyses, we applied trial sequential analyses. We used Grades of Recommendation, Assessment, Development and Evaluation (GRADE) to assess the quality of the evidence.
Main results
We included 28 randomized clinical trials (9330 participants); in the 21 trials reporting relevant outcomes for this review, 7597 participants were randomly assigned to a high fraction of inspired oxygen versus a routine fraction of inspired oxygen.
In trials with an overall low risk of bias, a high fraction of inspired oxygen compared with a routine fraction of inspired oxygen was not associated with all‐cause mortality (random‐effects model: RR 1.12, 95% confidence interval (CI) 0.93 to 1.36; GRADE: low quality) within the longest follow‐up and within 30 days of follow‐up (Peto odds ratio (OR) 0.99, 95% CI 0.61 to 1.60; GRADE: low quality). In a trial sequential analysis, the required information size was not reached and the analysis could not refute a 20% increase in mortality. Similarly, when all trials were included, a high fraction of inspired oxygen was not associated with all‐cause mortality to the longest follow‐up (RR 1.07, 95% CI 0.87 to 1.33) or within 30 days of follow‐up (Peto OR 0.83, 95% CI 0.54 to 1.29), both of very low quality according to GRADE. Neither was a high fraction of inspired oxygen associated with the risk of surgical site infection in trials with low risk of bias (RR 0.86, 95% CI 0.63 to 1.17; GRADE: low quality) or in all trials (RR 0.87, 95% CI 0.71 to 1.07; GRADE: low quality). A high fraction of inspired oxygen was not associated with respiratory insufficiency (RR 1.25, 95% CI 0.79 to 1.99), serious adverse events (RR 0.96, 95% CI 0.65 to 1.43) or length of stay (mean difference ‐0.06 days, 95% CI ‐0.44 to 0.32 days).
In subgroup analyses of nine trials using preoperative antibiotics, a high fraction of inspired oxygen was associated with a decrease in surgical site infections (RR 0.76, 95% CI 0.60 to 0.97; GRADE: very low quality); a similar effect was noted in the five trials adequately blinded for the outcome assessment (RR 0.79, 95% CI 0.66 to 0.96; GRADE: very low quality). We did not observe an effect of a high fraction of inspired oxygen on surgical site infections in any other subgroup analyses.
Authors' conclusions
As the risk of adverse events, including mortality, may be increased by a fraction of inspired oxygen of 60% or higher, and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60% or higher on surgical site infection, our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery. Given the risk of attrition and outcome reporting bias, as well as other weaknesses in the available evidence, further randomized clinical trials with low risk of bias in all bias domains, including a large sample size and long‐term follow‐up, are warranted.
In this article, we investigate the jointly optimized resource allocation with hybrid multiple access in energy-efficient industrial Internet of Things (IIoT), where some devices (e.g., those for ...critical control devices) have higher transmission priority and stable energy supply while some devices (e.g., those for comprehensive sensors) may not. We consider a system model supporting wireless powered IIoT devices, with certain user terminal as a potential relay for the transmission between a hybrid access point and another user terminal. Constrained by the limited energy storage, the user needs to harvest energy before relaying and only the harvested energy is utilized for the following transmission. We propose a collaborative orthogonal and nonorthogonal multiple access protocol where two cooperation schemes with and without decoding the relay message are applied. Jointly considering time sharing in the transmission process, power splitting for simultaneous wireless information and power transfer, and transmit power allocation at the cooperative user, the achievable rate regions under the Rayleigh fading channel model are derived. Based on which, an optimization problem on resource allocation strategies is formulated and discussed. Both analytical and numerical results are provided, illustrating the impact of user geometry on the achievable rates as well as the optimal resource allocation with different cooperative strategies applied in different use cases. Aiming to enhance resource utilization, energy-efficient cooperation enables the combination of various transmission modes and networking classes in large scale networks, as well as a better use of ambient radio frequency signals for wireless powered transmissions.
To investigate the association between markers of acute endothelial glycocalyx degradation, inflammation, coagulopathy, and mortality after trauma.
Hyperinflammation and acute coagulopathy of trauma ...predict increased mortality. High catecholamine levels can directly damage the endothelium and may be associated with enhanced endothelial glycocalyx degradation, evidenced by high circulating syndecan-1.
Prospective cohort study of trauma patients admitted to a Level 1 Trauma Centre in 2003 to 2005. Seventy-five patients were selected blindly post hoc from 3 predefined injury severity score (ISS) groups (<16, 16-27, >27). In all patients, we measured 17 markers of glycocalyx degradation, inflammation, tissue and endothelial damage, natural anticoagulation, and fibrinolysis (syndecan-1, IL-6, IL-10, histone-complexed DNA fragments, high-mobility group box 1 (HMGB1), thrombomodulin, von Willebrand factor, intercellular adhesion molecule-1, E-selectin, protein C, tissue factor pathway inhibitor (TFPI), antithrombin, D-dimer, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), soluble uPA receptor, and plasminogen activator inhibitor-1), hematology, coagulation, catecholamines, and assessed 30-day mortality. Variables were compared in patients stratified according to syndecan-1 median.
Patients with high circulating syndecan-1 had higher catecholamines, IL-6, IL-10, histone-complexed DNA fragments, HMGB1, thrombomodulin, D-dimer, tPA, uPA (all P < 0.05), and 3-fold increased mortality (42% vs. 14%, P = 0.006) despite comparable ISS (P = 0.351). Only in patients with high glycocalyx degradation was higher ISS correlated with higher adrenaline, IL-6, histone-complexed DNA fragments, HMGB1, thrombomodulin, and APTT, lower protein C (all P < 0.05), unchanged TFPI and blunted D-dimer response (P < 0.001) because D-dimer was profoundly increased even at low ISS. After adjusting for age and ISS, syndecan-1 was an independent predictor of mortality (OR: 1.01 95%CI, 1.00-1.02; P = 0.043).
In trauma patients, high circulating syndecan-1, a marker of endothelial glycocalyx degradation, is associated with inflammation, coagulopathy and increased mortality.
Among older men in Denmark, the incidence of death from any cause at a median follow-up of 5.6 years was not significantly lower among those randomly invited to undergo screening for subclinical ...cardiovascular disease.
BACKGROUND:Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent ...strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients.
METHODS:In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70–80 mm Hg) or lower (40–50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min·m. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging–evaluated total number of new ischemic lesions.
RESULTS:Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (P=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm (interquartile range, 0–118 mm; range, 0–25 261 mm) in the low-target group versus 29 mm (interquartile range, 0–143 mm; range, 0–22 116 mm) in the high-target group (median difference estimate, 0; 95% confidence interval, −25 to 0.028; P=0.99), as was the secondary outcome of number of new lesions (1 interquartile range, 0–2; range, 0–24 versus 1 interquartile range, 0–2; range, 0–29 respectively; median difference estimate, 0; 95% confidence interval, 0–0; P=0.71). No significant difference was observed in frequency of severe adverse events.
CONCLUSIONS:Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02185885.
Objective
Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described ...this systemic‐to‐brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short‐ and long‐term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.
Methods
Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using 11CPBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.
Results
Patients showed a global downregulation of gray matter 11CPBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS‐induced release of the proinflammatory marker tumor necrosis factor‐α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in 11CPBR28 distribution volume. Change in Stroop Color‐Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in 11CPBR28 binding (p = 0.027).
Interpretation
This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572–582
IMPORTANCE: The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years doubled, diabetes, stroke/transient ischemic attack/thromboembolism doubled, vascular disease prior ...myocardial infarction, peripheral artery disease, or aortic plaque, age 65-75 years, sex category female) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear. OBJECTIVE: To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF. DESIGN, SETTING, AND POPULATION: Nationwide prospective cohort study using Danish registries, including 42 987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012. EXPOSURES: Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death. MAIN OUTCOMES AND MEASURES: Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis. RESULTS: In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n = 977), 9.9% (n = 3187), and 21.8% (n = 6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall P<.001 for interaction). C statistics and negative predictive values indicate that the CHA2DS2-VASc score performed modestly in this HF population with and without AF (for ischemic stroke, 1-year C statistics, 0.67 95% CI, 0.65-0.68 and 0.64 95% CI, 0.61-0.67, respectively; 1-year negative predictive values, 92% 95% CI, 91%-93% and 91% 95% CI, 88%-95%, respectively). CONCLUSIONS AND RELEVANCE: Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.
BACKGROUND:Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the ...association between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins.
METHODS:Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not.
RESULTS:Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, −0.27; 95% CI, −0.48 to −0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, −0.18 to 0.87).
CONCLUSIONS:A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.
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