ABSTRACT
Background and objective: No consensus exists as to the benefit of pleural drainage in mechanically ventilated patients with conflicting data concerning the effects on gas exchange. We ...determined the effects on gas exchange over a 48‐hour period of draining, by thoracocentesis, large volume pleural effusions.
Methods: A total of 15 thoracocenteses were performed in 10 mechanically ventilated patients with ultrasound evidence of pleural effusions predicted to be greater than 800 mL in volume. Gas exchange, mixed expired CO2, dynamic lung compliance, ventilator settings before procedure and at 30 min, 4, 8, 24 and 48 h were determined. Data were analysed using paired t‐tests and repeated‐measure anova.
Results: Following thoracocentesis there was a 40% increase in the PaO2 from 82.0 ± 10.6 mm Hg to 115.2 ± 31.1 mm Hg (P < 0.05) with a 34% increase in the P:F ratio from 168.9 ± 55.9 mm Hg to 237.8 ± 72.6 mm Hg (P < 0.05). These effects were maintained for a period of 48 h. There was a correlation between the amount of fluid drained and the effects on oxygenation with an increase in the PaO2 of 4 mm Hg for each 100 mL of pleural fluid drained. A‐a gradients continued to improve over the course of the study together with a reduction in the dead space fraction and improved dynamic compliance.
Conclusions: Drainage of large pleural effusions in mechanically ventilated patients leads to a significant improvement in gas exchange, and these effects are sustained for 48 h after the procedure supporting a role in the discontinuation of mechanical ventilation.
For patients requiring mechanical ventilation for greater than 72 h, the drainage of large volume pleural effusions led to a 40% improvement in the PaO2 and a 34% improvement in the PaO2/FiO2 (P:F) ratio within 30 min. The effects on the P:F ratio were maintained for 48 h after the procedure. Similar improvements were seen in A‐a gradient, dead space fraction, ventilatory support and dynamic compliance. These improvements suggest that drainage of large effusions facilitate weaning from mechanical ventilation.
Kinematics of Complex-Valued Time Series Rubin-Delanchy, P.; Walden, A.T.
IEEE transactions on signal processing,
09/2008, Letnik:
56, Številka:
9
Journal Article
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Odprti dostop
The contribution to a stationary complex-valued time series at a single frequency magnitude takes the form of a random ellipse, and its properties such as aspect ratio (which includes rotational ...direction) and orientation are of great interest in science. A case when both the aspect ratio and orientation are fixed is found, and their variability, in general, results from the additional influence of an orthogonal ellipse. It is shown how a magnitude squared coherence coefficient controls both the relative influences of these components and the variation of both the orientation and aspect ratio of the resultant ellipse. Realizations of random ellipses are recovered very accurately from simulated time series. The mean orientation of the random ellipse is formally derived.
Several guidelines recommend hypothermia for comatose patients who have had a cardiac arrest outside hospital. Jerry Nolan and Jasmeet Soar (doi:10.1136/bmj.d5830) believe the data support this ...advice, but Andrew Walden, Niklas Nielsen, and Matt Wise question the quality of the evidence
Perioperative myocardial injury (PMI) is common in elective inpatient abdominal surgery and correlates with mortality risk. Simple measures for reducing PMI in this cohort are needed. This study ...evaluated whether remote ischemic preconditioning (RIPC) could reduce PMI in elective inpatient abdominal surgery.
This was a double-blind, sham-controlled trial with 1:1 parallel randomization. PMI was defined as any post-operative serum troponin T (hs-TNT) > 14 ng/L. Eighty-four participants were randomized to receiving RIPC (5 min of upper arm ischemia followed by 5 min reperfusion, for three cycles) or a sham-treatment immediately prior to surgery. The primary outcome was mean peak post-operative troponin in patients with PMI, and secondary outcomes included mean hs-TnT at individual timepoints, post-operative hs-TnT area under the curve (AUC), cardiovascular events and mortality. Predictors of PMI were also collected. Follow up was to 1 year.
PMI was observed in 21% of participants. RIPC did not significantly influence the mean peak post-operative hs-TnT concentration in these patients (RIPC 25.65 ng/L SD 9.33, sham-RIPC 23.91 SD 13.2, mean difference 1.73 ng/L, 95% confidence interval - 9.7 to 13.1 ng/L, P = 0.753). The treatment did not influence any secondary outcome with the pre-determined definition of PMI. Redefining PMI as > 5 ng/L in line with recent data revealed a non-significant lower incidence in the RIPC cohort (68% vs 81%, P = 0.211), and significantly lower early hs-TnT release (12 h time-point, RIPC 5.5 ng/L SD 5.5 vs sham 9.1 ng/L SD 8.2, P = 0.03).
RIPC did not at reduce the incidence or severity of PMI in these general surgical patients using pre-determined definitions. PMI is nonetheless common and effective cardioprotective strategies are required.
This trial was registered with Clinicaltrials.gov, NCT01850927 , 5th July 2013.
This paper proposes a frequency domain approach to test the hypothesis that a stationary complex-valued vector time series is proper, i.e., for testing whether the vector time series is uncorrelated ...with its complex conjugate. If the hypothesis is rejected, frequency bands causing the rejection will be identified and might usefully be related to known properties of the physical processes. The test needs the associated spectral matrix that can be estimated by multitaper methods by using, say, K tapers. Standard asymptotic distributions for the test statistic are of no use since they would require K → ∞, but, as K increases so does resolution bandwidth that causes spectral blurring. In many analyses, K is necessarily kept small, and hence our efforts are directed at practical and accurate methodology for hypothesis testing for small K. Our generalized likelihood ratio statistic combined with exact cumulant matching gives very accurate rejection percentages. We also prove that the statistic on which the test is based is comprised of canonical coherencies arising from our complex-valued vector time series. Frequency specific tests are combined by using multiple hypothesis testing to give an overall test. Our methodology is demonstrated on ocean current data collected at different depths in the Labrador Sea. Overall, this paper extends results on propriety testing for complex-valued vectors to the complex-valued vector time series setting.
An algorithm is proposed for the simulation of improper (noncircular) complex-valued second-order stationary stochastic processes having specified second-order properties. Three examples are given. ...Generated processes are shown to obey necessary distributional properties.
In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.
This randomised, controlled, ...open-label, platform trial (Randomised Evaluation of COVID-19 Therapy RECOVERY), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001).
In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
IMPORTANCE: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. OBJECTIVE: To determine whether hydrocortisone improves outcome for patients with severe ...COVID-19. DESIGN, SETTING, AND PARTICIPANTS: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. INTERVENTIONS: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). MAIN OUTCOMES AND MEASURES: The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). RESULTS: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707
On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization ...titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
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•Large reduction in Omicron neutralization titers, ameliorated by the 3rd booster vaccine•Failure of many potent mAbs to neutralize Omicron•Complex pattern of mutations balances ACE2 binding and antibody escape•Omicron RBD is structurally similar but the most antigenically distant variant
A comprehensive analysis of sera from vaccinees, convalescent patients previously infected by multiple variants, and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction in the ability to neutralize the SARS-CoV-2 Omicron variant, which seems to ameliorate with a third vaccine dose. Structural analyses of the Omicron RBD suggest that selective pressure balances key changes that increase affinity for ACE2 with other changes in the receptor-binding motif that disfavor ACE2 binding but facilitate immune escape.
AbstractObjectiveTo develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).DesignProspective observational cohort ...study.SettingInternational Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium—ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020.ParticipantsAdults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.Main outcome measureIn-hospital mortality.Results35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).ConclusionsAn easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.Study registrationISRCTN66726260
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