Outcomes after off-pump coronary bypass surgery

The complications associated with in coronary artery bypass surgery (CABG) using cardiopulmonary bypass (CPB) have led to a renewed interest in coronary bypass surgery on the beating heart. The primary objective of the Octopus Study was to compare cognitive outcome between patients randomized to off-pump or on-pump CABG. In chapter 2, the literature suggesting that CABG may impair cognitive function is systematically reviewed and chapter 3 describes in detail the rationale and design of the Octopus Study. In chapter 4, the cerebral outcome and quality of life after off-pump and on-pump CABG are presented. From March 1998 through August 2000, 281 patients were enrolled. At 3 and 12 months after surgery, there was no difference in quality of life between the two groups. At 3 months, cognitive decline (or stroke) occurred in 21% in the off-pump group and 29% in the on-pump group (relative risk 0.65; 95% CI 0.36-1.16; p=0.15). At 12 months, cognitive decline occurred in 31% in the off-pump group and 34% in the on-pump group (relative risk 0.88; 95% CI 0.52-1.49; p=0.69). Chapter 5 is a prediction study on cognitive outcome. The previously identified determinants of cognitive outcome were no predictor of cognitive outcome in the present patient sample. The only variables that were significantly associated with cognitive outcome after 3 months, were measures of cognitive outcome 4 days after surgery. In chapter 6 measures of early clinical outcome after off-pump and on-pump CABG are compared. Completeness of revascularization was similar in both groups. Blood products were needed during 3% of the off-pump procedures and 13% of the on-pump procedures (p<0.01). Release of creatine kinase muscle-brain isoenzyme was 41% less in the off-pump group (p<0.01). Off-pump patients were discharged 1 day earlier. At 1 month, operative mortality was zero in both groups, and quality of life had improved similarly. In chapter 7, a comparison of cardiac outcome and cost-effectiveness one year after off-pump and on-pump CABG is reported. One year survival free from stroke, myocardial infarction and coronary re-intervention was 88.0% after off-pump surgery and 90.6% after on-pump surgery (p=0.48). Survival free from angina was 89.3% vs 89.0% (p=0.93). Graft patency, determined in a randomized subset of patients, was 91% after off-pump and 93% after on-pump surgery (p=0.65). Off-pump surgery reduced costs by $2,329 (13.1$ 15,479 vs $ 17,808 p<0.01). Quality adjusted life years (0.82 vs 0.83; p=0.74) and event free survival years (1.02 vs 1.03; p=0.23) did not differ. Finally, Chapter 8 comprises a general discussion of the Octopus Study. It is concluded that in selected patients, off-pump CABG is safe and yields a cardiac outcome that is comparable to that of on-pump CABG. Avoiding CPB is cost-effective and slightly decreases the need for blood transfusion, but other clinically relevant benefits of off-pump CABG are not established yet. Patients undergoing off-pump CABG have better cognitive outcome at 3 months after surgery, but the effect is of limited size

The impact of textual elements on the comprehensibility of drug label instructions (DLIs):A systematic review

IntroductionCorrect interpretation of drug labels instructions (DLIs) is needed for safe use and better adherence to prescribed drugs. DLIs are often too difficult for patients, especially for those with limited health literacy. What is yet unknown, is how specific textual elements in DLIs (e.g., the presentation of numbers, or use of medical jargon) and patients' health literacy skills are related to the comprehension of DLIs. In order to provide concrete directions for health professionals on how to optimize drug prescriptions, we performed a systematic review to summarize the available research findings on which textual elements facilitate or hinder the correct interpretation of DLIs in relation to patients' health literacy.MethodA systematic search was performed in PubMed, EMBASE, PsychINFO, and Smartcat (until April 2019) to identify studies investigating textual elements that facilitate or hinder the correct interpretation of DLIs in relation to patients' health literacy.ResultsA total of 434 studies were identified of which 28 studies met our inclusion criteria. We found that textual elements contributing to the correct interpretation of DLIs were: using explicit time periods in dosage instructions, using plain language, presenting numbers in a numerical format, and providing DLIs in patients' native language. Multistep instructions per instruction line, using abbreviations and medical jargon seem to hinder the correct interpretation of DLIs. Although health literacy was taken into account in a majority of the studies, none of them assessed the effectiveness of specific textual elements on patients' comprehensibility of DLIs.ConclusionBased on our findings, we provide an overview of textual elements that contribute to the correct interpretation of DLIs. Optimizing the textual instruction on drug labels may increase the safety and adherence to prescribed drugs, taking into account that a significant proportion of patients has low health literacy

Stress-related psychopathology after cardiac surgery and intensive care treatment

Objective: Cardiac surgery patients are at risk for psychopathology. Symptoms of post-traumatic stress disorder (PTSD) and depression occur in 10–20% of these patients and affect their quality of life. The aim of this study was to assess factors associated with psychopathology after cardiac surgery. Methods: We followed participants of the multi-center randomized clinical trial Dexamethasone for Cardiac Surgery (DECS), on a single, intravenous dose of dexamethasone (1 mg/kg) or placebo during cardiac surgery, using validated questionnaires to assess PTSD and depressive symptoms after 1.5 to 4 years, as well as childhood trauma, trait anxiety, pre-existing psychopathology, and substance use. Saliva was used for genotyping of the hypothalamic-pituitary-adrenal-axis (HPA axis) glucocorticoid receptor gene. Linear backward regression analysis was performed with these factors, including pre-specified interaction terms of dexamethasone with sex and genotype. Results: Complete data was available for 90% of cases (n = 1111). The model including trait anxiety and the [dexamethasone x female sex] interaction explained 57% of variance in PTSD symptoms (Model fit F (2;4.817)=643.043, p<.001; R2=0 0.57). Similar explained variance was seen for depressive symptoms, where age, trait anxiety and the [dexamethasone x female sex] interaction provided the optimal model (Model fit F (3;4.261)=435,960, p<.001; R2=0.58). Limitations: In this study psychopathology was assessed through validated questionnaires. Variability in data collection detail was present. Conclusion: This study suggests that the occurrence of psychopathology after cardiac surgery is influenced by higher trait anxiety. Female cardiac surgery patients may benefit from intra-operative dexamethasone administration

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control:a randomized controlled trial

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC₁₅). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC₁₅ 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC₁₅ 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006

Особенности личности страдающих гашишной зависимостью мужчин

Рассмотрен личностный профиль мужчин, страдающих гашишной зависимостью. Показано, что длительное употребление наркотика ведет к формированию шизотипической личности.The personality profile of men with hashish addiction is described. Prolonged use of drugs is shown to cause formation of schizothymic personality

Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function

Background-Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation. Methods and Results-Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3(mut); n = 17), mutation negative HCM patients without an identified sarcomere mutation (HCM(mn); n = 11), and nonfailing donors (n = 12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3(mut) by 33 +/- 5%, and similar in HCM(mn) compared with donor. cMyBP-C phosphory Conclusions-Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression. (Circ Heart Fail. 2012; 5: 36-46.

Framework to Support the Process of Decision-Making on Life-Sustaining Treatments in the ICU: Results of a Delphi Study

Objectives: To develop a consensus framework that can guide the process of decision-making on continuing or limiting life-sustaining treatments in ICU patients, using evidence-based items, supported by caregivers, patients, and surrogate decision makers from multiple countries. Design: A three-round web-based international Delphi consensus study with a priori consensus definition was conducted with experts from 13 countries. Participants reviewed items of the decision-making process on a seven-point Likert scale or with open-ended questions. Questions concerned terminology, content, and timing of decision-making steps. The summarized results (including mean scores) and expert suggestions were presented in the subsequent round for review. Setting: Web-based surveys of international participants representing ICU physicians, nurses, former ICU patients, and surrogate decision makers. Patients: Not applicable. Interventions: Not applicable. Measurements and Main Results: In three rounds, respectively, 28, 28, and 27 (of 33 invited) physicians together with 12, 10, and seven (of 19 invited) nurses participated. Patients and surrogates were involved in round one and 12 of 27 responded. Caregivers were mostly working in university affiliated hospitals in Northern Europe. During the Delphi process, most items were modified in order to reach consensus. Seven items lacked consensus after three rounds. The final consensus framework comprises the content and timing of four elements; three elements focused on caregiver-surrogate communication (admission meeting, follow-up meeting, goals-of-care meeting); and one element (weekly time-out meeting) focused on assessing preferences, prognosis, and proportionality of ICU treatment among professionals. Conclusions: Physicians, nurses, patients, and surrogates generated a consensus-based framework to guide the process of decision-making on continuing or limiting life-sustaining treatments in the ICU. Early, frequent, and scheduled family meetings combined with a repeated multidisciplinary time-out meeting may support decisions in relation to patient preferences, prognosis, and proportionality

Complement C5 contributes to brain injury after subarachnoid hemorrhage

Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH

Quantum Experimental Data in Psychology and Economics

We prove a theorem which shows that a collection of experimental data of probabilistic weights related to decisions with respect to situations and their disjunction cannot be modeled within a classical probabilistic weight structure in case the experimental data contain the effect referred to as the 'disjunction effect' in psychology. We identify different experimental situations in psychology, more specifically in concept theory and in decision theory, and in economics (namely situations where Savage's Sure-Thing Principle is violated) where the disjunction effect appears and we point out the common nature of the effect. We analyze how our theorem constitutes a no-go theorem for classical probabilistic weight structures for common experimental data when the disjunction effect is affecting the values of these data. We put forward a simple geometric criterion that reveals the non classicality of the considered probabilistic weights and we illustrate our geometrical criterion by means of experimentally measured membership weights of items with respect to pairs of concepts and their disjunctions. The violation of the classical probabilistic weight structure is very analogous to the violation of the well-known Bell inequalities studied in quantum mechanics. The no-go theorem we prove in the present article with respect to the collection of experimental data we consider has a status analogous to the well known no-go theorems for hidden variable theories in quantum mechanics with respect to experimental data obtained in quantum laboratories. For this reason our analysis puts forward a strong argument in favor of the validity of using a quantum formalism for modeling the considered psychological experimental data as considered in this paper.Comment: 15 pages, 4 figure