...patients undergoing TAVR have a hemostatic defect demonstrated by less thrombin generation and a significant prolongation of clotting time consistent with a differential risk of bleeding compared ...with patients undergoing PCI for AMI. ...patients with aortic stenosis are known to exhibit a bleeding defect related to von Willebrand’s factor, and this defect may have amplified differences between the groups in platelet-rich plasma; however, our results demonstrate an additional defect that was evident in platelet-poor plasma, suggesting a clotting defect independent of known platelet-mediated factors. PCI for Acute Myocardial Infarction (n = 55) TAVR (n = 29) p Value Baseline characteristics Age, yrs 77.67 ± 5.98 81 ± 7.07 0.007 Female 21 (38.2) 13 (44.8) 0.64 Diabetes mellitus 15 (29.0) 7 (24.0) 0.76 Hypertension 42 (76.0) 19 (66.0) 0.29 Body mass index, kg/m2 28.5 ± 4.9 27.9 ± 3.4 0.94 Peripheral arterial disease 5 (9.0) 7 (24.0) 0.09 Current smoking 7 (13.0) 0 (0.0) 0.09 Hemoglobin, baseline, g/dl 12.5 ± 2.0 12.5 ± 1.8 0.50 Baseline glomerular filtration rate, ml/min 72.2 ± 18.l2 68.4 ± 15.9 0.34 Baseline platelet count 211.1 ± 60.96 229.5 ± 64.4 0.20 Platelet-poor plasma Clot time, s 221.47 ± 49.62 258.31 ± 48.55 0.002 Max thrombin generation 407.69 ± 109.35 434.18 ± 96.71 0.27 Platelet-rich plasma Clot time, s 301.32 ± 65.72 481.17 ± 115.40 0.0001 Max thrombin generation 173.76 ± 55.39 140.11 ± 49.73 0.008 Table 1 Characteristics, Thrombin Generation, and Clotting Times for Patients With AMI and TAVR
Objectives
To assess closed‐loop communications (readback), a fundamental aspect of effective communication, among cardiovascular teams and assess improvement efforts.
Background
Effective ...communication within teams is essential to assure safety and optimal outcomes. Readback of verbal physician orders is a hospital and national requirement.
Methods
Single‐center observational study, where the readback responses to physician verbal orders in the catheterization laboratory were characterized over three distinct time intervals from 2015 to 2017. Performance feedback and focused education on the value of readbacks was provided to the teams in two waves, with subsequent remeasurement. Responses to verbal orders were characterized as complete (all important parameters of the order repeated for verification), partial, acknowledgement only, or no response. Changes in readback performance after quality interventions were assessed.
Results
During the first‐observational period of 101 cases, complete readback occurred in 195 of 515 (38%) medication orders and 136 of 235 (58%) equipment orders. After initial quality improvement efforts, 102 cases were observed. In these, 298 of 480 (62%) medication orders had complete readback, and 210 of 420 (50%) equipment orders had complete readback. After additional quality improvement efforts, 168 cases were observed. In these, 506 of 723 (70%) medication orders had complete readback, and 630 of 1,061 (59%) equipment orders had complete readback. Overall, medication order readback improved over time (correlation = 0.26 −0.30, −0.21; p < 0.001), but equipment order readback did not (correlation = 0.02 −0.07, 0.03; p = 0.44).
Conclusions
Closed‐loop communication of physician verbal orders was used infrequently in this medical team setting and proved difficult to fully improve. This is an important safety gap.
Abstract Background Sleep disturbance is bi-directionally related to mood de-stabilization in bipolar disorder (BD), and sleep quality differs in men and women. We aimed to determine whether ...perception of poor sleep quality would have a different effect on mood outcome in men versus women. Methods We assessed association between sleep quality (Pittsburgh Sleep Quality Index (PSQI)) at study intake and mood outcome over 2 years in subjects from the Prechter Longitudinal Study of Bipolar Disorder ( N =216; 29.6% males). The main outcome measure was the severity, variability, and frequency of mood episodes measured by self-report over 2 years of follow-up. Multivariable linear regression models stratified by sex examined the relationship between PSQI with mood outcomes, while age, stressful life events, mood state and neuroticism at baseline were controlled. Results In women, poor sleep quality at baseline predicted increased severity ( B =0.28, p <0.001) and frequency of episodes ( B =0.32, p <0.001) of depression, and poor sleep quality was a stronger predictor than baseline depression; poor sleep quality predicted increased severity ( B =0.19, p <0.05) and variability ( B =0.20, p <0.05) of mania, and frequency of mixed episodes ( B =0.27, p <0.01). In men, baseline depression and neuroticism were stronger predictors of mood outcome compared to poor sleep quality. Limitations We measured perception of sleep quality, but not objective changes in sleep. Conclusions In a longitudinal study of BD, women reported poorer perceived sleep quality than men, and poor sleep quality predicted worse mood outcome in BD. Clinicians should be sensitive to addressing sleep complaints in women with BD early in treatment to improve outcome in BD.
We propose the Philippine Eagle Optimization Algorithm (PEOA), which is a meta-heuristic and population-based search algorithm inspired by the territorial hunting behavior of the Philippine Eagle. ...From an initial random population of eagles in a given search space, the best eagle is selected and undergoes a local food search using the interior point method as its means of exploitation. The population is then divided into three subpopulations, and each subpopulation is assigned an operator which aids in the exploration. Once the respective operators are applied, the new eagles with improved function values replace the older ones. The best eagle of the population is then updated and conducts a local food search again. These steps are done iteratively, and the food searched by the final best eagle is the optimal solution of the search space. PEOA is tested on 20 optimization test functions with different modality, separability, and dimension properties. The performance of PEOA is compared to 13 other optimization algorithms. To further validate the effectiveness of PEOA, it is also applied to image reconstruction in electrical impedance tomography and parameter identification in a neutral delay differential equation model. Numerical results show that PEOA can obtain accurate solutions to various functions and problems. PEOA proves to be the most computationally inexpensive algorithm relative to the others examined, while also helping promote the critically endangered Philippine Eagle.
Urgent-start peritoneal dialysis (PD) in patients with newly diagnosed end-stage renal disease (ESRD) is a well-tolerated alternative to hemodialysis (HD). The primary aim of this study was to ...identify the demographic and clinical characteristics of ESRD patients, as well as the presurgical, surgical, and postsurgical factors associated with urgent-start PD complications.
A retrospective cross-sectional observational study was performed on 102 patients with ESRD who merited urgent-start PD from January 2015 to June 2019. The primary clinical outcome measures were catheter leakage, dysfunction, and peritonitis, whereas the secondary outcomes were catheter removal, repositioning, and death. Statistical inferences were made with the χ2 or Fisher’s exact test and independent samples t tests.
One hundred two subjects (65 men, 63.7%) 56.2 ± 15.1 years old were included in this study; 64 of the subjects had diabetes and hypertension (62.7%). Catheter leakage occurred in 8 patients (7.8%), catheter dysfunction in 27 patients (26.5%), and peritonitis in 14 patients (13.7%); meanwhile, catheter removal occurred in 6 patients (5.9%), catheter repositioning in 21 patients (20.6%), and death in 3 patients (2.9%). Peritonitis was associated with younger age (i.e., 47.0 ± 16.8 vs. 57.6 ± 14.4 years; P = 0.014; 95% confidence interval CI: 2.2–19.1; odds ratio OR 0.96; P = 0.018; 95% CI: 0.92–099), higher creatinine levels upon admission (i.e., 20.2 ± 9.8 vs. 14.1 ± 8.3; P = 0.014; 95% CI: −10.9 to −1.2), and heart failure (OR 4.79; P = 0.043; 95% CI: 1.05–21.88). Patients with abdominal hernia were 7.5 times more likely to have their catheter leak (OR 7.5; P = 0.036; 95% CI: 1.14–49.54). Catheter removal was associated with obesity (i.e., body mass index BMI of 31.6 ± 4.1 vs. 25.9 ± 4.9; P = 0.007; 95% CI: −9.8 to −1.6; OR 1.26; P = 0.013; 95% CI: 1.05–1.51) and Modification of Diet in Renal Disease glomerular filtration rate (MDRD-GFR) (i.e., 2.5 ± 0.6 vs. 3.7 ± 2.3; P = 0.003; 95% CI: 0.5–1.9).
Peritonitis was associated with younger age, higher creatinine levels upon admission, and heart failure; meanwhile, catheter removal was linked to obesity and lower glomerular filtration rate. Compared with previous reports, our study included patients in which PD was initiated shortly after catheter insertion, making the intervention a true urgent-start PD. This study contributes to the existing urgent-start PD literature by providing evidence that urgent-start PD with catheter opening within 72 hours has limited complications, making it a relatively safe option.
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Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute ...COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.
The most commonly used markers to assess complement activation are split products that are produced through activation of all three pathways and are located downstream of C3. In contrast, C4d derives ...from the cleavage of C4 and indicates either classical (CP) or lectin pathway (LP) activation. Although C4d is perfectly able to distinguish between CP/LP and alternative pathway (AP) activation, no well-established markers are available to differentiate between early CP and LP activation. Active enzymes of both pathways (C1s/C1r for the CP, MASP-1/MASP-2 for the LP) are regulated by C1 esterase inhibitor (C1-INH) through the formation of covalent complexes. Aim of this study was to develop validated immunoassays detecting C1s/C1-INH and MASP-1/C1-INH complex levels. Measurement of the complexes reveals information about the involvement of the respective pathways in complement-mediated diseases. Two sandwich ELISAs detecting C1s/C1-INH and MASP-1/C1-INH complex were developed and tested thoroughly, and it was investigated whether C1s/C1-INH and MASP-1/C1-INH complexes could serve as markers for either early CP or LP activation. In addition, a reference range for these complexes in healthy adults was defined, and the assays were clinically validated utilizing samples of 414 COVID-19 patients and 96 healthy controls. The immunoassays can reliably measure C1s/C1-INH and MASP-1/C1-INH complex concentrations in EDTA plasma from healthy and diseased individuals. Both complex levels are increased in serum when activated with zymosan, making them suitable markers for early classical and early lectin pathway activation. Furthermore, measurements of C1-INH complexes in 96 healthy adults showed normally distributed C1s/C1-INH complex levels with a physiological concentration of 1846 ± 1060 ng/mL (mean ± 2SD) and right-skewed distribution of MASP-1/C1-INH complex levels with a median concentration of 36.9 (13.18 - 87.89) ng/mL (2.5-97.5 percentile range), while levels of both complexes were increased in COVID-19 patients (p<0.0001). The newly developed assays measure C1-INH complex levels in an accurate way. C1s/C1-INH and MASP-1/C1-INH complexes are suitable markers to assess early classical and lectin pathway activation. An initial reference range was set and first studies showed that these markers have added value for investigating and unraveling complement activation in human disease.
Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses ...and sibling comparisons to clarify the direction of this relationship.
Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons).
ADHD and PTSD had consistent rg (rg range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10−5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10−4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53).
Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.
IMMUNEPOTENT CRP is a dialyzable leukocyte extract obtained from bovine spleen with immunomodulatory and antitumour properties; therefore, when administrated as an adjuvant therapy for cancer ...patients, it has increased their survival and quality of life. The bioavailability of any orally administered compound can be reduced due to gastrointestinal enzymes. In this study, we evaluated if IMMUNEPOTENT CRP is resistant to the treatment with different enzymes (proteases, nucleases, polysaccharide-degrading enzymes or lipase), using as parameters for biological activity measurement its in vitro antitumour and antioxidant properties and in vivo the antitumour effect of IMMUNEPOTENT CRP treated with proteinase K. In conclusion, we consider necessary to include the antioxidant and cytotoxic activity on the MCF-7 cancer cell line as parameters for the quantitative determination of biological activity or potency tests for batch release. Additionally, the results showed that different enzymatic treatments do not affect the antitumour and antioxidant activities of IMMUNEPOTENT CRP in vitro, suggesting that this product can be administered orally without any loss of biological activity. Furthermore, IMMUNEPOTENT CRP treatment with proteinase K increases the antitumour activity in vivo.
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