Has thrombolysis lost its mojo?

This work addresses fundamental issues related to the structure and conditioning of linear time-delayed models of non-linear dynamics on an attractor. While this approach has been well-studied in the asymptotic sense (e.g., for an infinite number of delays), the non-asymptotic setting is not well-understood. First, we show that the minimal time-delays required for perfect signal recovery are solely determined by the sparsity in the Fourier spectrum for scalar systems. For the vector case, we provide a rank test and a geometric interpretation for the necessary and sufficient conditions for the existence of an accurate linear time delayed model. Furthermore, we prove that the output controllability index of a linear system induced by the Fourier spectrum serves as a tight upper bound on the minimal number of time delays required. An explicit expression for the exact linear model in the spectral domain is also provided. From a numerical perspective, the effect of the sampling rate and the number of time delays on numerical conditioning is examined. An upper bound on the condition number is derived, with the implication that conditioning can be improved with additional time delays and/or decreasing sampling rates. Moreover, it is explicitly shown that the underlying dynamics can be accurately recovered using only a partial period of the attractor. Our analysis is first validated in simple periodic and quasiperiodic systems, and sensitivity to noise is also investigated. Finally, issues and practical strategies of choosing time delays in large-scale chaotic systems are discussed and demonstrated on 3D turbulent Rayleigh-Bénard convection.

BackgroundCytomegalovirus (CMV) infection is common in immunocompetent patients in intensive care units (ICUs). However, whether CMV infection or CMV reactivation contributes to mortality of immunocompetent patients remains unclear.MethodsA literature search was conducted for relevant studies published before May 30, 2016. Studies reporting on CMV infection in immunocompetent patients in ICUs and containing 2 × 2 tables on CMV results and all-cause mortality were included.ResultsEighteen studies involving 2398 immunocompetent patients admitted to ICUs were included in the meta-analysis. The overall rate of CMV infection was 27% (95%CI 22–34%, I2 = 89%, n = 2398) and the CMV reactivation was 31% (95%CI 24–39%, I2 = 74%, n = 666). The odds ratio (OR) for all-cause mortality among patients with CMV infection, compared with those without infection, was 2.16 (95%CI 1.70–2.74, I2 = 10%, n = 2239). Moreover, upon exclusion of studies in which antiviral treatment was possibly or definitely provided to some patients, the association of mortality rate with CMV infection was also statistically significant (OR: 1.69, 95%CI 1.01–2.83, I2 = 37%, n = 912,). For CMV seropositive patients, the OR for mortality in patients with CMV reactivation as compared with patients without CMV reactivation was 1.72 (95%CI 1.04–2.85, I2 = 29%, n = 664). Patients with CMV infection required significantly longer mechanical ventilation (mean difference (MD): 9 days (95% CI 5–14, I2 = 81%, n = 875)) and longer duration of ICU stay (MD: 12 days (95% CI 7–17, I2 = 70%, n = 949)) than patients without CMV infection. When analysis was limited to detection in blood, CMV infection without antiviral drug treatment or reactivation was not significantly associated with higher mortality (OR: 1.69, 95%CI 0.81–3.54, I2 = 52%, n = 722; OR: 1.49, I2 = 63%, n = 469).ConclusionCritically ill patients without immunosuppression admitted to ICUs show a high rate of CMV infection. CMV infection during the natural unaltered course or reactivation in critically ill patients is associated with increased mortality, but have no effect on mortality when CMV in blood. More studies are needed to clarify the impact of CMV infection on clinical outcomes in those patients.

Stent retriever, contact aspiration, and combined treatment are crucial mechanical thrombectomy strategies for patients with acute ischemic stroke (AIS). The aim of this study was to compare and rank three different mechanical thrombectomy strategies for AIS due to large vessel occlusion by means of a Bayesian network meta-analysis. A systematic review and Bayesian network meta-analysis based on PRISMA guidelines. Relevant randomized controlled trials (RCTs) were identified in Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov from inception to 15 March 2022. We used random effect models to estimate corresponding odds ratios (ORs) and rank probabilities using pairwise and Bayesian network meta-analysis. We applied the grading of recommendations assessment, development, and evaluation (GRADE) methodology to rate the certainty of evidence. We identified 10 RCTs enrolling 2098 participants. As for modified Rankin Scale (mRS) 0-2, moderate certainty evidence established all mechanical thrombectomy strategies that were more effective than standard medical treatment [combined: log OR 0.9288, 95% credibility intervals (CrI) 0.1268-1.7246; contact aspiration: log OR 0.9507, 95% CrI 0.3361-1.5688; stent retriever: log OR 1.0919, 95% CrI 0.6127-1.5702]. The same applied to mRS 0-3 (combined: log OR 0.9603, 95% CrI 0.2122-1.7157; contact aspiration: log OR 0.7554, 95% CrI 0.1769-1.3279; stent retriever: log OR 1.0046, 95% CrI 0.6001-1.4789). Combined treatment was superior to stent retriever in substantial reperfusion (log OR 0.8921, 95% CrI 0.2105-1.5907, high certainty). Stent retriever had the highest probability of being optimal for mRS 0-2 and mRS 0-3. Standard medical treatment had the lowest risk of subarachnoid hemorrhage. For all other outcomes, combined treatment was most likely the best treatment. Our results indicated that, with the exception of functional outcome, combined treatment might be the outstanding strategy. Apart from subarachnoid hemorrhage, all three mechanical thrombectomy strategies proved better strategies than standard medical treatment. PROSPERO (CRD42022351878).

In the present paper we perform, for the first time, an analysis of the average sensitivity of a coherent phase-sensitive optical time-domain reflectometer (phase-OTDR) with a semiconductor laser source to external actions. The sensitivity of this OTDR can be defined in a conventional manner via average SNR at its output, which in turn is defined by the average useful signal power and the average intensity noise power in the OTDR spatial channels in the bandwidth defined by the OTDR sampling frequency. The average intensity noise power is considered in detail in a previous paper. In the current paper we examine the average useful signal power at the output of a phase-OTDR.The analysis of the average useful signal power of a phase-OTDR is based on the study of a fiber scattered-light interferometer (FSLI) which is treated as a constituent part of a phase- OTDR. In the analysis, one of the conventional phase-OTDR schemes with a rectangular dual-pulse probe signal is considered. The FSLI which corresponds to this OTDR scheme has two scattering fiber segments with additional time delay, introduced between backscattered fields. The average useful signal power and the resulting average SNR at the output of this FSLI are determined by the degree of coherence of the semiconductor laser source, the length of the scattering fiber segments, and by the additional time delay between the scattering fiber segments. The average useful signal power characteristic of the corresponding phase-OTDR is determined by analogous parameters: the source coherence, the time durations of the parts constituting the dual-pulse, and the time interval which separates these parts.In the paper an expression for the average useful signal power of a phase-OTDR is theoretically derived and experimentally verified. Based on the found average useful signal power of a phase-OTDR and the average intensity noise power, derived in the previous paper, the average SNR of a phase-OTDR is defined. Setting the average signal SNR to 1, at a defined spectral band the minimum detectable external action amplitude for our particular phase-OTDR setup is determined. We also derive a simple relation for the average useful signal power and the average SNR which results when making the assumption that the laser source coherence is high. The results of the paper can serve as the basis for further development of the concept of phase-OTDR sensitivity.

This paper presents a Proportional Integral Derivative (PID) controller design with the presence of an uncertain internal gain and additional time delay in the forward path of a 300 kW Solid Oxide Fuel Cell-Gas Turbine (SOFC-GT). The outputs of the system are turbine speed and the fuel cell mass flow rate. A fixed set of proportional controller coefficients are determined to graphically develop an area of selection for the integral and derivative coefficients of the PID controller. The inputs to the power plant are the electric load and cold air valve. The decentralized controllers are applied to four sub-systems as a Single Input Single Output (SISO). The PID controller coefficients are selected from a singular matrix solution that stabilizes the system and satisfies the internal gain and time delay uncertainties. Two sub-systems are the transfer functions of the turbine speed over the electric load and the cold air valve. The other two sub-systems are the transfer functions of the fuel cell mass flow rate over the electric load and the cold air bypass valve. Multiple options for selecting PID controller coefficients are beneficial to the SOFC-GT plant due to the wide range of operations and internal uncertainty interactions. The specific internal time delay and gain margins increase the reliability and robustness of the SOFC-GT with multiple uncertain parameters.

Little is known about the within-person variability of different frailty instruments, their agreement over time, and whether use of repeat assessments could improve the strength of associations with adverse health outcomes. Repeat measurements recorded in 2010–2011 (Wave 1) and 2012 (Wave 2) from The Irish Longitudinal Study on Ageing (TILDA) were used to classify individuals with frailty using the frailty phenotype (FP) and frailty index (FI). Within-person variability and agreement of frailty classifications were assessed using ANOVA and kappa (K) statistics, respectively. Associations of each frailty measure (wave 1, wave 2, or mean of both waves) with risk of falls, hospitalisations and all-cause mortality were assessed using logistic regression. Among 7455 individuals (mean age 64.7 [SD 9.9] years), within-person SD was 0.664 units (95% CI 0.654–0.671) for FP and 2 health deficits (SD 0.050 [0.048–0.051]) for FI. Agreement of frailty was modest for both measures, but higher for FI (K 0.600 [0.584–0.615]) than FP (K 0.370 [0.348–0.401]). The odds ratios (ORs) for all-cause mortality were higher for frailty assessed using the mean of two versus single measurements for FI (ORs for mortality 3.5 [2.6–4.9] vs. 2.7 [1.9–3.4], respectively) and FP (ORs for mortality 6.9 [4.6–10.3] vs. 4.0 [2.8–5.635], respectively). Frailty scores based on single measurements had substantial within-person variability, but the agreement in classification of frailty was higher for FI than FP. Frailty assessed using the mean of two or more measurements recorded at separate visits was more strongly associated with adverse health outcomes than those recorded at a single visit.

Current rehabilitation guidelines for patients with post-COVID-19 condition (PCC) are primarily based on expert opinions and observational data, and there is an urgent need for evidence-based rehabilitation interventions to support patients with PCC. To synthesize the findings of existing studies that report on physical capacity (including functional exercise capacity, muscle function, dyspnea, and respiratory function) and quality of life outcomes following rehabilitation interventions in patients with PCC. A systematic electronic search was performed from January 2020 until February 2023, in MEDLINE, Scopus, CINAHL, and the Clinical Trials Registry. Key terms that were used to identify potentially relevant studies included long-covid, post-covid, sequelae, exercise therapy, rehabilitation, physical activity, physical therapy, and randomized controlled trial. This study included randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care, waiting list, or control in patients with PCC. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A pairwise bayesian random-effects meta-analysis was performed using vague prior distributions. Risk of bias was assessed using the Cochrane risk of bias tool version 2, and the certainty of evidence was evaluated using the GRADE system by 2 independent researchers. The primary outcome was functional exercise capacity, measured at the closest postintervention time point by the 6-minute walking test. Secondary outcomes were fatigue, lower limb muscle function, dyspnea, respiratory function, and quality of life. All outcomes were defined a priori. Continuous outcomes were reported as standardized mean differences (SMDs) with 95% credible intervals (CrIs) and binary outcomes were summarized as odds ratios with 95% CrIs. The between-trial heterogeneity was quantified using the between-study variance, τ2, and 95% CrIs. Of 1834 identified records, 1193 were screened, and 14 trials (1244 patients; 45% female participants; median [IQR] age, 50 [47 to 56] years) were included in the analyses. Rehabilitation interventions were associated with improvements in functional exercise capacity (SMD, -0.56; 95% CrI, -0.87 to -0.22) with moderate certainty in 7 trials (389 participants). These improvements had a 99% posterior probability of superiority when compared with current standard care. The value of τ2 (0.04; 95% CrI, 0.00 to 0.60) indicated low statistical heterogeneity. However, there was significant uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% CrI, 0.32 to 9.94). The findings of this systematic review and meta-analysis suggest that rehabilitation interventions are associated with improvements in functional exercise capacity, dyspnea, and quality of life, with a high probability of improvement compared with the current standard care; the certainty of evidence was moderate for functional exercise capacity and quality of life and low for other outcomes. Given the uncertainty surrounding the safety outcomes, additional trials with enhanced monitoring of adverse events are necessary.

Whose goals determine care?

Objective To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in...

The purpose of this study was to investigate whether sex disparity in cardiovascular outcomes exists in children who undergo cardiac surgery. Statewide hospital discharge data from California from 1995 to 1997 were used. Children <21 years old who had a procedure code (by ICD9-CM) that indicated cardiac surgery were selected. The outcome variable was binary, in-hospital death versus alive at discharge. Twenty-three surgical procedures were selected and adjusted for risk by procedure type. We used logistic regression analysis to evaluate the effect of sex on in-hospital mortality, controlling for age, race and ethnicity, type of insurance, home income, type of admission, date and month of surgery, hospital case volume, and type of procedure. There were 6593 cases of cardiac surgery, with 345 in-hospital deaths (mortality rate 5.23%). Crude mortality rates for males (4.98%) and females (5.54%) were not significantly different. However, fewer females were neonates, and females had more low-risk procedures than males. Multivariate logistic regression showed that females had a higher odds ratio (OR) for mortality than males (OR 1.51, P<0.01). The OR for mortality was 3.86 for neonates and 2.98 for infants compared with children aged > or =1 year. Low-volume hospitals had higher mortality rates than high-volume hospitals (OR 1.67, P<0.01). The risk-adjusted length of hospital stay and charges were similar between females and males. For children undergoing cardiac surgery, female sex was associated with 51% higher odds of death than male sex. The mechanism by which female sex acts as a risk factor requires further investigation.

Using sevoflurane for pediatric anesthesia plays a pivotal role in surgeries. Emergence agitation (EA) is a major adverse event accompanied with pediatric anesthesia. Other anesthetic adjuvants can be combined with sevoflurane in clinical practices for different purposes. However, it is uncertain that such a practice may have substantial influence on the risk of EA. We conducted a literature search in online databases, including PubMed, Embase, Cochrane Library, and Clinical Trials. Key data were extracted from eligible randomized control trials (RCTs). Both pairwise and network meta-analysis (NMA) were conducted for synthesizing data from eligible studies. The relative risk of EA was assessed using the odds ratios (ORs) and their corresponding 95% confidence intervals (CI) or credible intervals (CrI). Ranking scheme based on the surface under the cumulative ranking curve (SUCRA) values was produced. Several key assumptions of NMA such as heterogeneity, degree of consistence, and publication bias were validated by different statistical or graphical approaches. Evidence from 67 randomized control trials was synthesized. The relative risk of EA associated with eight anesthetic adjuvants was analyzed, including ketamine, propofol, dexmedetomidine, clonidine, midazolam, fentanyl, remifentanil, and sufentanil. Patients with the following anesthetic adjuvants appeared to have significantly reduced risk of EA in relation to those with placebo: dexmedetomidine (OR=0.18, 95% CrI 0.12-0.25), fentanyl (OR=0.19, 95% CrI 0.12-0.30), sufentanil (OR=0.20, 95% CrI 0.08-0.50), ketamine (OR=0.21, 95% CrI 0.13-0.34), clonidine (OR=0.25, 95% CrI 0.14-0.46), propofol (OR=0.32, 95% CrI 0.18-0.56), midazolam (OR=0.46, 95% CrI 0.27-0.77), and remifentanil (OR=0.29, 95% CrI 0.13-0.68). The SUCRA values for each anesthetic adjuvant were: dexmedetomidine (73.65%), fentanyl (68.04%), sufentanil (60.81%), ketamine (59.99%), clonidine (47.74%), remifentanil (40.15%), propofol (33.23%), midazolam (16.33%), and placebo (0.06%). Incorporating anesthetic adjuvants particularly dexmedetomidine into sevoflurane appeared to be significantly associated with a decreased risk of EA in pediatric anesthesia.

The paper shows, with the help of numerical simulation and hardware experiments, that the tracking response of a NLA-based second order PLL would be affected in the presence of additional loop time delay. The inclusion of a phase modulator in the system structure can reduce the adverse effects to some extent, but the design parameters should have to be properly chosen to get a stable system.

Background:The National Trauma Data Bank (NTDB) is plagued by the problem of missing physiological data. The Glasgow Coma Scale score, Respiratory Rate and Systolic Blood Pressure are an essential part of risk adjustment strategies for trauma system evaluation and clinical research. Missing data on these variables may compromise the feasibility and the validity of trauma group comparisons.Aims:To evaluate the validity of Multiple Imputation (MI) for completing missing physiological data in the National Trauma Data Bank (NTDB), by assessing the impact of MI on 1) frequency distributions, 2) associations with mortality, and 3) risk adjustment.Methods:Analyses were based on 170,956 NTDB observations with complete physiological data (observed data set). Missing physiological data were artificially imposed on this data set and then imputed using MI (MI data set). To assess the impact of MI on risk adjustment, 100 pairs of hospitals were randomly selected with replacement and compared using adjusted Odds Ratios (OR) of mortality. OR generated by the observed data set were then compared to those generated by the MI data set.Results:Frequency distributions and associations with mortality were preserved following MI. The median absolute difference between adjusted OR of mortality generated by the observed data set and by the MI data set was 3.6% (inter-quartile range: 2.4%-6.1%).Conclusions:This study suggests that, provided it is implemented with care, MI of missing physiological data in the NTDB leads to valid frequency distributions, preserves associations with mortality, and does not compromise risk adjustment in inter-hospital comparisons of mortality.

BackgroundShivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering.ObjectiveWe performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD.MethodsThis review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc.ResultsTwenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10–0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18–32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09–0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14–5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result.ConclusionIT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.

Neoadjuvant therapy in triple-negative breast cancer: A systematic review and network meta-analysis