Summary Background Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate ...between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. Methods The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Findings Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15–24; 69 of 352 fetuses) for selective ultrasonography and 57% (51–62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4–3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk RR 1·60, 95% CI 1·22–2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction =0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9–8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2–34·0, p<0·0001). Interpretation Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. Funding National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare.
Abstract Purpose This study aimed to (1) document patterns of quadriceps muscle wasting in the first 10 days of admission and (2) determine the relationship between muscle ultrasonography and ...volitional measures. Materials and methods Twenty-two adults ventilated for more than 48 hours were included. Sequential quadriceps ultrasound images were obtained over the first 10 days and at awakening and intensive care unit (ICU) discharge. Muscle strength and function were assessed at awakening and ICU discharge. Results A total of 416 images were analyzed. There was a 30% reduction in vastus intermedius (VI) thickness, rectus femoris (RF) thickness, and cross-sectional area within 10 days of admission. Muscle echogenicity scores increased for both RF and VI muscles by + 12.7% and + 25.5%, respectively (suggesting deterioration in muscle quality). There was a strong association between function and VI thickness ( r = 0.82) and echogenicity ( r = − 0.77). There was a moderate association between function and RF cross-sectional area ( r = 0.71). Conclusions Muscle wasting occurs rapidly in the ICU setting. Ultrasonography is a useful surrogate measure for identifying future impairment. Vastus intermedius may be an important muscle to monitor in the future because it demonstrated the greatest change in muscle quality and had the strongest relationship to volitional measures.
Study objective We apply a previously described tool to forecast emergency department (ED) crowding at multiple institutions and assess its generalizability for predicting the near-future waiting ...count, occupancy level, and boarding count. Methods The ForecastED tool was validated with historical data from 5 institutions external to the development site. A sliding-window design separated the data for parameter estimation and forecast validation. Observations were sampled at consecutive 10-minute intervals during 12 months (n=52,560) at 4 sites and 10 months (n=44,064) at the fifth. Three outcome measures—the waiting count, occupancy level, and boarding count—were forecast 2, 4, 6, and 8 hours beyond each observation, and forecasts were compared with observed data at corresponding times. The reliability and calibration were measured following previously described methods. After linear calibration, the forecasting accuracy was measured with the median absolute error. Results The tool was successfully used for 5 different sites. Its forecasts were more reliable, better calibrated, and more accurate at 2 hours than at 8 hours. The reliability and calibration of the tool were similar between the original development site and external sites; the boarding count was an exception, which was less reliable at 4 of 5 sites. Some variability in accuracy existed among institutions; when forecasting 4 hours into the future, the median absolute error of the waiting count ranged between 0.6 and 3.1 patients, the median absolute error of the occupancy level ranged between 9.0% and 14.5% of beds, and the median absolute error of the boarding count ranged between 0.9 and 2.8 patients. Conclusion The ForecastED tool generated potentially useful forecasts of input and throughput measures of ED crowding at 5 external sites, without modifying the underlying assumptions. Noting the limitation that this was not a real-time validation, ongoing research will focus on integrating the tool with ED information systems.
Coronavirus disease 2019 continues to spread rapidly with high mortality. We performed metabolomics profiling of critically ill coronavirus disease 2019 patients to understand better the underlying ...pathologic processes and pathways, and to identify potential diagnostic/prognostic biomarkers.
Blood was collected at predetermined ICU days to measure the plasma concentrations of 162 metabolites using both direct injection-liquid chromatography-tandem mass spectrometry and proton nuclear magnetic resonance.
Tertiary-care ICU and academic laboratory.
Patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient tested positive (coronavirus disease 2019 positive).
None.
Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top-performing metabolites for identifying coronavirus disease 2019 positive patients from healthy control subjects and was dominated by increased kynurenine and decreased arginine, sarcosine, and lysophosphatidylcholines. Arginine/kynurenine ratio alone provided 100% classification accuracy between coronavirus disease 2019 positive patients and healthy control subjects (
= 0.0002). When comparing the metabolomes between coronavirus disease 2019 positive and coronavirus disease 2019 negative patients, kynurenine was the dominant metabolite and the arginine/kynurenine ratio provided 98% classification accuracy (
= 0.005). Feature selection identified creatinine as the top metabolite for predicting coronavirus disease 2019-associated mortality on both ICU days 1 and 3, and both creatinine and creatinine/arginine ratio accurately predicted coronavirus disease 2019-associated death with 100% accuracy (
= 0.01).
Metabolomics profiling with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 negative patients from coronavirus disease 2019 positive patients. Arginine/kynurenine ratio accurately identified coronavirus disease 2019 status, whereas creatinine/arginine ratio accurately predicted coronavirus disease 2019-associated death. Administration of tryptophan (kynurenine precursor), arginine, sarcosine, and/or lysophosphatidylcholines may be considered as potential adjunctive therapies.
Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to ...mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms.
Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells.
Tertiary care ICU and academic laboratory.
All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive.
None.
Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor (
< 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1;
< 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 (
< 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1-3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium.
Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.
Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only ...supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.
Daily blood inflammation profiling with immunoassays.
Tertiary care ICU and academic laboratory.
All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive).
None.
Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (
< 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1-3 (
< 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2-7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality.
While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.
Objective To investigate the optimum conduit for coronary targets other than the left anterior descending artery, we evaluated long-term patencies and clinical outcomes of the radial artery, right ...internal thoracic artery, and saphenous vein through the Radial Artery Patency and Clinical Outcomes trial. Methods As part of a 10-year prospective, randomized, single-center trial, patients undergoing primary coronary surgery were allocated to the radial artery (n = 198) or free right internal thoracic artery (n = 196) if aged less than 70 years (group 1), or radial artery (n = 113) or saphenous vein (n = 112) if aged at least 70 years (group 2). All patients received a left internal thoracic artery to the left anterior descending, and the randomized conduit was used to graft the second largest target. Protocol-directed angiography has been performed at randomly assigned intervals, weighted toward the end of the study period. Grafts are defined as failed if there was occlusion, string sign, or greater than 80% stenosis, independently reported by 3 assessors. Analysis is by intention to treat. Results At mean follow up of 5.5 years, protocol angiography has been performed in groups 1 and 2 in 237 and 113 patients, respectively. There are no significant differences within each group in preoperative comorbidity, age, or urgency. Patencies were similar for either of the 2 conduits in each group (log rank analysis, P = .06 and P = .54, respectively). The differences in estimated 5-year patencies were 6.6% (radial minus right internal thoracic artery) in group 1 and 2.9% (radial minus saphenous vein graft) in group 2. Conclusion At mean 5-year angiography in largely asymptomatic patients, the selection of arterial or venous conduit for the second graft has not significantly affected patency. This finding offers surgeons, for now, enhanced flexibility in planning revascularization.
Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been ...identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers.
Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins.
Tertiary care ICU and academic laboratory.
All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive).
None.
Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 CD83, family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0;
= 0.007).
Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality.
OBJECTIVES: To determine whether circulating markers of activated inflammation and hemostasis are associated with cognitive decline in older people.
DESIGN: Prospective cohort study (Edinburgh Artery ...Study).
SETTING: Eleven general practices in Edinburgh, Scotland.
PARTICIPANTS: A sample of 452 men and women followed for 16 years.
MEASUREMENTS: Biomarker data were collected in 1987/88, and cognitive assessment was first conducted in 1998/99, when the mean age of the sample ± standard deviation was 73.1±5.0), and subsequently in 2002/03. Information was obtained on verbal declarative memory (Wechsler Logical Memory Test (LMT)), nonverbal reasoning (Raven's Standard Progressive Matrices), verbal fluency (Verbal Fluency Test), information processing speed (Wechsler Digit Symbol Test), and a general cognitive factor representing the variance common to the individual test scores.
RESULTS: In age‐adjusted analyses, plasma fibrinogen, interleukin‐6 (IL‐6), and intercellular adhesion molecule 1 (ICAM‐1) were negatively associated with performance on all cognitive measures in 2002/03 except the LMT (correlation coefficients from −0.10 to −0.24). In multivariate analyses controlling for demographic characteristics, depression, and cardiovascular morbidity and risk factors, fibrinogen independently predicted 4‐year decline in nonverbal reasoning (P<.05). Also, when cognitive change was estimated from peak prior level, IL‐6 turned out to be inversely related to decline in information processing speed (P<.05). Similarly, ICAM‐1 was associated with a greater decline in general cognitive ability (P<.05) and nonverbal ability (P<.05).
CONCLUSION: Systemic markers of inflammation and hemostasis are associated with a progressive decline in general and specific cognitive abilities in older people, independent of major vascular comorbidity.
Abstract Background We sought to describe prevalence and care practices for patients experiencing prolonged mechanical ventilation (PMV), defined as ventilation for 21 or more consecutive days and ...medical stability. Methods We provided the survey to eligible units via secure Web link to a nominated unit champion from April to November 2012. Weekly telephone and e-mail reminders were sent for 6 weeks. Results Response rate was 215 (90%) of 238 units identifying 308 patients requiring PMV on the survey day occupying 11% of all Canadian ventilator-capable beds. Most units (81%) used individualized plans for both weaning and mobilization. Weaning and mobilization protocols were available in 48% and 38% of units, respectively. Of those units with protocols, only 25% reported weaning guidance specific to PMV, and 11% reported mobilization content for PMV. Only 30% of units used specialized mobility equipment. Most units referred to speech language pathologists (88%); use of communication technology was infrequent (11%). Only 29% routinely referred to psychiatry/psychology, and 17% had formal discharge follow-up services. Conclusions Prolonged mechanical ventilation patients occupied 11% of Canadian acute care ventilator bed capacity. Most units preferred an individualized approach to weaning and mobilization with considerable variation in weaning methods, protocol availability, access to specialized rehabilitation equipment, communication technology, psychiatry, and discharge follow-up.
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