Implementation of the European Society of Cardiology 0/3-hour accelerated diagnostic protocol, using high sensitive troponin T: a clinical practice evaluation of safety and effectiveness involving 3003 patients with suspected acute coronary syndrome.

BACKGROUND: There have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn). OBJECTIVE: To analyse the safety and effectiveness of early emergency department (ED) discharge following implementation of the European Society of Cardiology (ESC) 0/3-hour ADP for suspected acute coronary syndromes (ACS). METHOD: We prospectively studied 2 cohorts of consecutive suspected ACS presentations to ED before (n=1642) and after (n=1376, 2 centres) implementation of the ESC 0/3-hour ADP incorporating limit of detection rule out. Safety was defined by MACE (major adverse cardiac events) inclusive of type 1 myocardial infarction (MI) in patients discharged from ED, and clinical effectiveness by percentage ED discharge. Continuous variables and categorical data were evaluated by independent t-test and χ2 test, respectively. Time-to-event data were analysed as survival data and converted to Kaplan-Meier curves for interpretation. RESULTS: In the preimplementation period, there was a higher prevalence of MI. Discharge from ED increased by >100% (from 27.1% to 56.5% of the cohort) with no safety signal (MACE rate 4/444 (0.9%) vs 4/769 (0.52%), p=0.430 for the 2011 and 2018 cohort, respectively). This correlated with a marked reduction in length of stay overall but a more modest reduction for those discharged from ED (6 hours 10 min vs 5 hours 25 min, p<0.001) for the 2011 and 2018 cohort, respectively. There were improvements in presentation to blood draw (163-90 min, p<0.001). Time from presentation to first ECG actually increased (16.2 vs 31.2 min, p<0.001). Analysis of hs-cTn values and ECGs revealed a maximum ED discharge rate of 69%, by applying the 0/3-hour protocol, implying potential for increasing safe ED discharge. CONCLUSIONS: Implementation of an ADP with hs-cTn is safe and effective for early rule-out and discharge of suspected ACS but require considerable resources and education to optimise maximal patient flow.

Independent Predictors of Repeat Emergency Room Presentations: Insights from a Cohort of 1066 Consecutive Patients with Non-Cardiac Chest Pain Generating 4770 Repeat Presentations.

BACKGROUND AND IMPORTANCE: Chest pain (CP) is one of the most frequent presentations to the emergency department (ED), a large proportion of which is non-cardiac chest pain (NCCP). Repeat attendances to ED are common and impose considerable burden to overstretched departments. OBJECTIVE: Our aim was to determine drivers for repeat ED presentations using NCCP as the primary cause of index presentation. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study of 1066 consecutive presentations with NCCP to a major urban hospital ED in North England. Index of Multiple Deprivation (IMD), a postcode-derived validated index of deprivation, was computed. Charlson comorbidity index (CCI) was determined by reference to known comorbidity variables. Repeat presentation to ED to any national hospital was determined by a national linked database (population 53.5 million). Independent predictors of ED representation were computed using logistic regression analysis. RESULTS: Median age was 43 (IQR 28-59), and 50.8% were male. Furthermore, 27.8%, 8.1% and 3.8% suffered from chronic obstructive pulmonary disease (COPD), hypertension and diabetes mellitus, respectively. The most frequent diagnoses, using ICD-10 coding, were non-cardiac chest pain (55.1%), followed by respiratory conditions (14.7%). One-year incidence of adjudicated myocardial infarction, urgent or emergency coronary revascularisation and all-cause death was 0.6%, 2% and 5.3%, respectively. There was a total of 4770 ED repeat presentations 1 year prior to or following index presentation with NCCP in this cohort. Independent (multivariate) predictors for frequent re-presentation (defined as ≥2 representations) were a history of COPD (OR [odds ratio] 2.06, p = 0.001), previous MI (OR3.6, p = 0.020) and a Charlson comorbidity index ≥1 (OR 1.51, p = 0.030). The frequency of previous MI was low as only 3% had sustained a previous MI. CONCLUSIONS: This analysis indicates that COPD and complex health care needs (represented by high CCI), but not socio-economic deprivation, should be health policy targets for lessening repeat ED presentations. What is already known on this topic: Repeat presentations with non-ischaemic chest pain are common, placing a considerable burden on emergency departments. WHAT THIS STUDY ADDS: COPD and complex health care needs, denoted by Charlson comorbidity index, are implicated as drivers for repeat presentation to accident and emergency department. Socio-economic deprivation was not an independent predictor of re-presentation. How might this study affect research, practice, or policy: Community-based support for COPD and complex health care needs may reduce frequency of ED attendance.

Unstable angina in the context of high-sensitive troponins: Still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction.

BACKGROUND: Unstable angina (UA), considered historically a marker of high risk, has rarely been studied in the high sensitive troponin era. We sought to characterise this population and determine short- and medium-term outcomes for UA and compared this to both patients with musculoskeletal chest pain and adjudicated type 1 MI (NSTEMI). METHOD: We conducted a post-hoc analysis of 2 prospective cohort studies of suspected acute coronary syndrome in 2 hospitals in the northwest of England. (n = 3018) We used a dedicated symptom score to diagnose unstable angina. Type 1 MI (NSTEMI) was diagnosed by independent physician adjudication according to 3rd universal definition of MI. Follow-up was 100% complete for all patients to 1 year. RESULTS: 185 (6.1%) and 249 (8.3%) were adjudicated as suffering from UA and NSTEMI respectively. We restricted our analysis of UA to 158 (5.2%) patients with UA with high sensitive troponin T (Roche Elecsys) ≤14 ng/L (≤99th percentile). Compared to the NSTEMI population, the UA cohort were younger (59 vs 74, p < 0.002), had a lower incidence of hypertension (56.3% vs 69.1%, p = 0.009), had significantly lower composite risk scores and had fewer ECG abnormalities (ST depression >1 mm, 5.1% vs 15.6%, p = 0.001, T wave flattened, biphasic or inverted 24.1% vs 47.8%, p < 0.0001). Subsequent Type 1 MI to 30 days and 1 year in the UA cohort was 1.9% and 1.9% respectively compared to 0.8% and 2.4% in the index type 1 MI (NSTEMI cohort) respectively. However, compared to patients presenting with musculoskeletal chest pain (n = 468) there was a significantly greater incidence of subsequent MI and coronary revascularisation in patients with unstable angina. All cause death at 30 days and 1 year was 0.0% and 0.6% (n = 1) for UA patients and 2.8% (n = 7) and 16.1% (n = 40) for the NSTEMI cohort respectively. CONCLUSION: UA, defined objectively by a symptom score and absence of myocyte necrosis, is still prevalent as an entity, with a risk of subsequent MI and urgent or emergency coronary revascularisation. However, mortality is >10-fold lower when compared to NSTEMI, indicating a less severe pathology in terms of atherosclerosis or plaque burden, and implying the need for a different management strategy to that of NSTEMI.

The Impact of Frailty and Comorbidities on Heart Failure Outcomes.

Frailty is a multisystemic process leading to reduction of physiological reserve and a reduction in physical activity. Heart failure (HF) is recognised as a global cause of morbidity and mortality, increasing in prevalence over recent decades. Because of shared phenotypes and comorbidities, there is significant overlap and a bidirectional relationship, with frail patients being at increased risk of developing HF and vice versa. Despite this, frailty is not routinely assessed in patients with HF. Identification of these patients to direct multidisciplinary care is key, and the development of a frailty assessment tool validated in a large HF population is also an unmet need that would be of considerable benefit in directing multidisciplinary-team management. Non-pharmacological treatment should be included, as exercise and physical rehabilitation programmes offer dual benefit in frail HF patients, by treating both conditions simultaneously. The evidence for nutritional supplementation is mixed, but there is evidence that a personalised approach to nutritional support in frail HF patients can improve outcomes.

Acacia gums new fractions and sparkling base wines: How their biochemical and structural properties impact foamability?

Foam is the first attribute observed when sparkling wine is served. Bentonite is essentially used to flocculate particles in sparkling base wines but can impair their foamability. Gums from Acacia senegal and Acacia seyal improved the foamability of different bentonite-treated base wines. Our main goal was to see how the supplementation with new fractions separated from Acacia gums by Ion Exchange Chromatography affected foamability of sparkling base wines, deepening the relation between foam behavior and characteristics of wine and gums. High molar mass fractions increased the maximal foam height and the foam height during the stability period in, respectively, 11 out and 8 out of 16 cases (69% and 50%, respectively). The properties of the supplementing gums fractions obtained by IEC and, although to a minor extent, the wine characteristics, affected positively and/or negatively the foam behavior. Wine foamability also depended on the relationship between wine and gums fractions properties.

Improvement of the foamability of sparkling base wines by the addition of Acacia gums.

In sparkling wine, foam characteristics are one of the major attributes. The foam quality depends on wine components. Bentonite is added to the base wine to facilitate the riddling process, but causes a loss of foamability. Acacia gum can be used as additive in wine. We have studied if the addition of Acacia senegal gum (AsenG), Acacia seyal gum (AseyG) and different AsenG fractions could improve the foamability of different base wines treated with bentonite. The foamability differs depending on the gum or the gum fraction treatment but also on the wine, being these differences linked to some aspects of their respective compositions and molecular parameters. AsenG and AseyG increase the foamability (by Mosalux - sparging procedure), respectively, in five and seven out of eight base wines treated with bentonite. Therefore, AsenG and AseyG are potential treatments increasing the foamability of these wines.

Impact of Botrytis cinerea Contamination on the Characteristics and Foamability of Yeast Macromolecules Released during the Alcoholic Fermentation of a Model Grape Juice.

Botrytis cinerea is a fungal pathogen responsible for the decrease in foamability of sparkling wines. The proteolysis of must proteins originating from botrytized grapes is well known, but far less information is available concerning the effect of grape juice contamination by Botrytis. The impact from Botrytis on the biochemical and physico-chemical characteristics of proteins released from Saccharomyces during alcoholic fermentation remains elusive. To address this lack of knowledge, a model grape juice was inoculated with three enological yeasts with or without the Botrytis culture supernatant. Size exclusion chromatography coupled to multi-angle light scattering (SEC-MALLS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques (AgNO3 and periodic acid Schiff staining) was used in the study. When Botrytis enzymes were present, a significant degradation of the higher and medium MW molecules released by Saccharomyces was observed during alcoholic fermentation whilst the lower MW fraction increased. For the three yeast strains studied, the results clearly showed a strong decrease in the wine foamability when synthetic musts were inoculated with 5% (v/v) of Botrytis culture due to fungus proteases.

Influence of Grape Berry Maturity on Juice and Base Wine Composition and Foaming Properties of Sparkling Wines from the Champagne Region.

In sparkling wine cool-climate regions like Champagne, it is sometimes necessary to pick the healthy grape clusters that have a relatively low maturity level to avoid the deleterious effects of Botrytis cinerea. In such conditions, we know that classical oenological parameters (sugars, pH, total acidity) may change but there is little information concerning the impact of grape berry maturity on wine proteins and foaming properties. Therefore, healthy grapes (Chardonnay and Pinot meunier) in 2015 and 2016 were picked at different maturity levels within the range of common industrial maturity for potential alcohol content 8⁻11% v/v in the Champagne region. Base wine protein content and foamability, and oenological parameters in grape juice and their corresponding base wines, were investigated. The results showed that base wine protein contents (analyzed by the Bradford method and by electrophoresis) and foamability were higher when the grapes were riper. The Pearson's correlation test found significant positive correlations (r = 0.890⁻0.997, p < 0.05) between Chardonnay grape berry maturity degree (MD) and base wine foamability in both vintages. Strong correlations between MD and most of the oenological parameters in grape juice and base wine were also found for the two cultivars. Under the premise of guaranteed grape health, delaying harvest date is an oenological decision capable of improving base wine protein content and foamability.

Effect of grape juice press fractioning on polysaccharide and oligosaccharide compositions of Pinot meunier and Chardonnay Champagne base wines.

Press fractioning is an important step in the production of sparkling base wines to segregate the grape juices with different qualities. Grape juice fractions were collected during the pressing cycle at industrial and laboratory scales. The Pinot meunier and Chardonnay Champagne base wines obtained from the free-run juice and the squeezed juices exhibited strong differences from the beginning to the last step of pressing cycle for numerous enological parameters. Significant changes in polysaccharide (PS) and oligosaccharide (OS) base wine composition and concentration were found as the pressing cycle progressed. During the pressing cycle, the total PS concentration decreased by 31% (from 244 to 167mg/L) and 32% (from 201 to 136mg/L) in the Pinot meunier and Chardonnay wines respectively. The wine OS amounts varied between 97 and 139mg/L. The polysaccharide rich in arabinose and galactose (39-54%) and mannoproteins (38-55%) were the major PS in the base wines.

Comparison of two artificial tear formulations using aberrometry.

BACKGROUND: This study investigates the effect of artificial tears of different viscosities on aberrations of healthy eyes. METHODS: We recruited subjects from the student population of the Northeastern State University Oklahoma College of Optometry. Using the Complete Ophthalmic Analysis System (COAS), aberrometry measurements were taken every second for 60 seconds with a blink every 10 seconds. We made measurements of the naked eye, then after instillation of TheraTears non-preserved drops, and after instillation of SystanePF, a more viscous formulation. Zernike coefficients up to the sixth order were recorded and analysed. We evaluated changes in spherical and astigmatic dioptric powers and coma-like, spherical aberration-like and total higher-order aberration (HOA) RMS values as a function of time. RESULTS: Both drops yielded significantly higher values than the naked eye for HOA RMS and cylindrical power as well as a hyperopic shift in spherical equivalent (p < 0.001,paired t-test). SystanePF, the more viscous tear, showed significantly higher values than TheraTears in HOA RMS and cylinder in all inter-blink periods (p < 0.001, paired t-test). CONCLUSIONS: This study shows artificial tears can have a measurable and significant impact on aberrations of healthy eyes. This effect is sustained for at least one minute and its magnitude appears to be related to the viscosity of the tear formulation.

Influence of the epicanthal fold on the perceived direction of gaze.

PURPOSE: Judged direction of gaze from straight and turned heads is known to be biased from its true direction. We have tested the additional influence of epicanthal folds on the perceived direction of gaze. METHODS: Western observers (U.S. residents of Western appearance) and Eastern observers (native Japanese) judged the direction of gaze from cathode ray tube-imaged heads with and without epicanthal folds (Japanese vs. Western models) when the heads, both straight and turned, gazed in different lateral directions. RESULTS: When the gazers' heads were straight and gave eye contact, both Western and Eastern observers judged the gaze to be giving eye contact. However, with straight heads and gaze to the side, epicanthal folds produced significant differences in the judged direction of gaze. Observers judged the right and left eyes to be gazing in nearly the same direction when the gazer had the eye appearance that the observers were used to viewing within their own country, but in very different directions when the gazer had eyes typical of the other country. When the gazers' heads were turned, the Western and Eastern observers judged the direction of gaze of the Western gazer's right and left eyes similarly, but both judged large differences in direction of gaze between right and left eyes for the Eastern gazer. CONCLUSION: Direction of gaze from eyes that have epicanthal folds is judged very differently than gaze from eyes that do not have epicanthal folds. This difference is sensitive to the cultural experience of the observers.

Normal-eye Zernike coefficients and root-mean-square wavefront errors.

PURPOSE: To compare aberrometry measurements from multiple sites and compute mean Zernike coefficients and root-mean-square (RMS) values for the entire data pool to serve as a reference set for normal, healthy adult eyes. SETTING: Northeastern State University, Tahlequah, Oklahoma, USA. METHODS: Data were collected from 10 laboratories that measured higher-order aberrations (HOAs) in normal, healthy adult eyes using Shack-Hartmann aberrometry (2560 eyes of 1433 subjects). Signed Zernike coefficients were scaled to pupil diameters of 6.0 mm, 5.0 mm, 4.0 mm, and 3.0 mm and corrected to a common wavelength of 550 nm. The mean signed and absolute Zernike coefficients across data sets were compared. Then, the following were computed: overall mean values for signed and absolute Zernike coefficients; polar Zernike magnitudes and RMS values for coma-like aberrations (Z(3)(+/-1) and Z(5)(+/-1) combined); spherical-like aberrations (Z(4)(0) and Z(6)(0) combined); and 3rd-, 4th-, 5th-, and 6th-order, and higher-order aberrations (orders 3 to 6). RESULTS: The different data sets showed good agreement for Zernike coefficients values across most higher-order modes, with greater variability for Z(4)(0) and Z(3)(-1). The most prominent modes and their mean absolute values (6.0-mm pupil) were, respectively, Z(3)(-1) and 0.14 microm, Z(4)(0) and 0.13 microm, and Z(3)(-3) and 0.11 microm. The mean total higher-order RMS was 0.33 microm. CONCLUSIONS: There was a general consensus for the magnitude of HOAs expected in normal adult human eyes. At least 90% of the sample had aberrations less than double the mean values reported here. These values can serve as a set of reference norms.

Evaluation of a clinical aberrometer for lower-order accuracy and repeatability, higher-order repeatability, and instrument myopia.

BACKGROUND: Refractive surgery has stimulated the development of aberrometers, which are instruments that measure higher-order aberrations. The purpose of this study was to test one clinical aberrometer, the Complete Ophthalmic Analysis System (COAS), for its accuracy, repeatability, and instrument myopia for measuring sphere and astigmatism and its repeatability for measuring higher-order aberrations. METHODS: Aberrations of 56 normal eyes (28 subjects) were measured with and without cycloplegia using a COAS, a conventional autorefractor and by subjective refraction. We evaluated lower-order accuracy (sphere and astigmatism) of the COAS and autorefractor by comparing that data with that of subjective refraction. We also tested COAS lower- and higher-order repeatability for 5 measurements taken in less than 1 minute. We evaluated instrument myopia by comparing cycloplegic and noncycloplegic measurements of the same eye. Data were analyzed for a 5.0-mm-diameter pupil. RESULTS: Mean COAS spherical error was between -0.1 and +0.4 diopters (D), depending on cycloplegia and the kind of sphere power computation selected. Cylinder power errors were less than 0.1 D. COAS repeatability coefficients were better than 0.25 D, and instrument myopia was less than 0.4 D. These were comparable with those of autorefraction. Higher-order repeatability was sufficient to allow reliable measurement of normal third-order aberrations and spherical aberration. CONCLUSIONS: Accuracy, repeatability, and instrument myopia of the COAS are similar to those of a conventional autorefractor. Accuracy and repeatability are also similar to those of subjective refraction. Like an autorefractor, the COAS provides instantaneous, objective measurements of sphere and astigmatism, but it also measures higher-order aberrations. We found that it is capable of reliably measuring problematic higher-order aberrations and is therefore a valuable asset for modern clinical eye care.

Measurement of refractive errors in young myopes using the COAS Shack-Hartmann aberrometer.

PURPOSE: To evaluate the Complete Ophthalmic Analysis System (COAS; WaveFront Science) for accuracy, repeatability, and instrument myopia when measuring myopic refractive errors. METHODS: We measured the refractive errors of 20 myopic subjects (+0.25 to -10 D sphere; 0 to -1.75 D cylinder) with a COAS, a phoropter, and a Nidek ARK-2000 autorefractor. Measurements were made for right and left eyes, with and without cycloplegia, and data were analyzed for large and small pupils. We used the phoropter refraction as our estimate of the true refractive error, so accuracy was defined as the difference between phoropter refraction and that of the COAS and autorefractor. Differences and means were computed using power vectors, and accuracy was summarized in terms of mean vector and mean spherocylindrical power errors. To assess repeatability, we computed the mean vector deviation for each of five measurements from the mean power vector and computed a coefficient of repeatability. Instrument myopia was defined as the difference between cycloplegic and noncycloplegic refractions for the same eyes. RESULTS: Without cycloplegia, both the COAS and autorefractor had mean power vector errors of 0.3 to 0.4 D. Cycloplegia improved autorefractor accuracy by 0.1 D, but COAS accuracy remained the same. For large pupils, COAS accuracy was best when Zernike mode Z4(0) (primary spherical aberration) was included in the computation of sphere power. COAS repeatability was slightly better than autorefraction repeatability. Mean instrument myopia for the COAS was not significantly different from zero. CONCLUSIONS: When measuring myopes, COAS accuracy, repeatability, and instrument myopia were similar to those of the autorefractor. Error margins for both were better than the accuracy of subjective refraction. We conclude that in addition to its capability to measure higher-order aberrations, the COAS can be used as a reliable, accurate autorefractor.

Videokeratoscope-line-of-sight misalignment and its effect on measurements of corneal and internal ocular aberrations.

A growing number of research laboratories are using the new technologies of videokeratoscopy and Shack-Hartmann aberrometry, in combination, to study the optical structure of the human eye. A potential source of error arises, however, because the two instruments are designed to measure the human eye along different reference axes. The Shack-Hartmann aberrometer is usually aligned coaxially with the line of sight, but videokeratoscopes usually are not. Thus far, corneal optics research has not adequately addressed the problem of videokeratoscope-line-of-sight misalignment and its effect on the computation of corneal and internal ocular aberrations. We measured corneal, ocular, and internal aberrations for three normal human eyes, developed a method to compensate for videokeratoscope-line-of-sight misalignment, and analyzed the importance of compensating for the misalignment. Our results show that when the value of angle lambda (the angle between the line of sight and the pupillary axis) is larger than 2 degrees-3 degrees, the misalignment, if ignored, can lead to incorrect estimates of corneal and internal aberrations as well as the corneal/internal aberration balance.