PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

Background: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.publishersversionPeer reviewe

Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery

Publisher Copyright: © 2015 Ozolina et al.Background: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. Methods: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. Results: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. Conclusions: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.publishersversionPeer reviewe

Family members' experience with in-hospital health care after severe traumatic brain injury : a national multicentre study.

Background Family member’s experience and satisfaction of health care in the acute care and in-patient rehabilitation are important indicators of the quality of health care services provided to patients with severe traumatic brain injury (TBI). The objective was to assess family members’ experience of the health care provided in-hospital to patients with severe TBI, to relate experiences to family member and patient demographics, patients’ function and rehabilitation pathways. Methods Prospective national multicentre study of 122 family members of patients with severe TBI. The family experience of care questionnaire in severe traumatic brain injury (FECQ-TBI) was applied. Independent sample t-tests or analysis of variance (ANOVA) were used to compare the means between 2 or more groups. Paired samples t-tests were used to investigate differences between experience in the acute and rehabilitation phases. Results Best family members` experience were found regarding information during the acute phase, poorest scores were related to discharge. A significantly better care experience was reported in the acute phase compared with the rehabilitation phase (p &lt; 0.05). Worst family members` experience was related to information about consequences of the injury. Patient’s dependency level (p &lt; 0.05) and transferral to non-specialized rehabilitation were related to a worse family members` experience (p &lt; 0.01). Conclusions This study underscores the need of better information to family members of patients with severe TBI in the rehabilitation as well as the discharge phase. The results may be important to improve the services provided to family members and individuals with severe TBI

Epidural anesthesia and postoperative analgesia with ropivacaine and fentanyl in off-pump coronary artery bypass grafting: a randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Our aim was to assess the efficacy of thoracic epidural anesthesia (EA) followed by postoperative epidural infusion (EI) and patient-controlled epidural analgesia (PCEA) with ropivacaine/fentanyl in off-pump coronary artery bypass grafting (OPCAB).</p> <p>Methods</p> <p>In a prospective study, 93 patients were scheduled for OPCAB under propofol/fentanyl anesthesia and randomized to three postoperative analgesia regimens aiming at a visual analog scale (VAS) score < 30 mm at rest. The control group (n = 31) received intravenous fentanyl 10 μg/ml postoperatively 3-8 mL/h. After placement of an epidural catheter at the level of Th₂-Th₄before OPCAB, a thoracic EI group (n = 31) received EA intraoperatively with ropivacaine 0.75% 1 mg/kg and fentanyl 1 μg/kg followed by continuous EI of ropivacaine 0.2% 3-8 mL/h and fentanyl 2 μg/mL postoperatively. The PCEA group (n = 31), in addition to EA and EI, received PCEA (ropivacaine/fentanyl bolus 1 mL, lock-out interval 12 min) postoperatively. Hemodynamics and blood gases were measured throughout 24 h after OPCAB.</p> <p>Results</p> <p>During OPCAB, EA decreased arterial pressure transiently, counteracted changes in global ejection fraction and accumulation of extravascular lung water, and reduced the consumption of propofol by 15%, fentanyl by 50% and nitroglycerin by a 7-fold, but increased the requirements in colloids and vasopressors by 2- and 3-fold, respectively (<it>P </it>< 0.05). After OPCAB, PCEA increased PaO₂/FiO₂at 18 h and decreased the duration of mechanical ventilation by 32% compared with the control group (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>In OPCAB, EA with ropivacaine/fentanyl decreases arterial pressure transiently, optimizes myocardial performance and influences the perioperative fluid and vasoactive therapy. Postoperative EI combined with PCEA improves lung function and reduces time to extubation.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01384175">NCT01384175</a></p

Rasch analysis of the Psychiatric Out-Patient Experiences Questionnaire (POPEQ)

<p>Abstract</p> <p>Background</p> <p>The Psychiatric Out-Patient Experiences Questionnaire (POPEQ) is an 11-item core measure of psychiatric out-patients experiences of the perceived outcome of the treatment, the quality of interaction with the clinician, and the quality of information provision. The POPEQ was found to have evidence for reliability and validity following the application of classical test theory but has not previously been assessed by Rasch analysis.</p> <p>Methods</p> <p>Two national postal surveys of psychiatric outpatients took place in Norway in 2004 and 2007. The performance of the POPEQ, including item functioning and differential item functioning, was assessed by Rasch analysis. Principal component analysis of item residuals was used to assess the presence of subdimensions.</p> <p>Results</p> <p>6,677 (43.3%) and 11,085 (35.2%) psychiatric out patients responded to the questionnaire in 2004 and 2007, respectively. All items in the scale were retained after the Rasch analysis. The resulting scale had reasonably good fit to the Rasch model. The items performed the same for the two survey years and there was no differential item functioning relating to patient characteristics. Principal component analysis of the residuals confirmed that the measure to a high degree is unidimensional. However, the data also reflects three potential subscales, each relating to one of the three included aspects of health care.</p> <p>Conclusions</p> <p>The POPEQ had excellent psychometric properties and Rasch analysis further supported the construct validity of the scale by also identifying the three subdimensions originally included as components in the instrument development. The 11-item instrument is recommended in future research on psychiatric out-patient experiences. Future development may lead to the construction of more precise measures of the three subdomains that the POPEQ is based on.</p

Addressing preference heterogeneity in public health policy by combining Cluster Analysis and Multi-Criteria Decision Analysis: Proof of Method.

The use of subgroups based on biological-clinical and socio-demographic variables to deal with population heterogeneity is well-established in public policy. The use of subgroups based on preferences is rare, except when religion based, and controversial. If it were decided to treat subgroup preferences as valid determinants of public policy, a transparent analytical procedure is needed. In this proof of method study we show how public preferences could be incorporated into policy decisions in a way that respects both the multi-criterial nature of those decisions, and the heterogeneity of the population in relation to the importance assigned to relevant criteria. It involves combining Cluster Analysis (CA), to generate the subgroup sets of preferences, with Multi-Criteria Decision Analysis (MCDA), to provide the policy framework into which the clustered preferences are entered. We employ three techniques of CA to demonstrate that not only do different techniques produce different clusters, but that choosing among techniques (as well as developing the MCDA structure) is an important task to be undertaken in implementing the approach outlined in any specific policy context. Data for the illustrative, not substantive, application are from a Randomized Controlled Trial of online decision aids for Australian men aged 40-69 years considering Prostate-specific Antigen testing for prostate cancer. We show that such analyses can provide policy-makers with insights into the criterion-specific needs of different subgroups. Implementing CA and MCDA in combination to assist in the development of policies on important health and community issues such as drug coverage, reimbursement, and screening programs, poses major challenges -conceptual, methodological, ethical-political, and practical - but most are exposed by the techniques, not created by them

Changes in Body Weight and Psychotropic Drugs: A Systematic Synthesis of the Literature

<div><h3>Introduction</h3><p>Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.</p> <h3>Objective</h3><p>To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.</p> <h3>Methodology and Results</h3><p>We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs.</p> <h3>Conclusion</h3><p>Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.</p> </div

Controversial treatment of a victim of severe head injury complicated by septic shock and acute respiratory distress syndrome

Anniken Haavind1, Olav Hevr&amp;oslash;y1, Rune Hennig2,3, Lars Bjertnaes1,31Division of Intensive Care Medicine, Department of Anesthesiology; 2Department of Neurosurgery, University Hospital of North Norway; 3Department of Clinical Medicine (neurosurgery and anesthesiology), Faculty of Health Sciences, University of Troms&amp;oslash;, Troms&amp;oslash;, NorwayAbstract: Pneumonia, severe sepsis, and acute respiratory distress syndrome (ARDS) are frequent complications after head trauma. Recombinant human activated protein C (APC) reportedly improves circulation and respiration in severe sepsis, but is contraindicated after head injury because of increased risk of intracranial bleeding. A 21-year-old man with severe head injury after a car accident was endotracheally intubated, mechanically ventilated, and hemodynamically stabilized before transfer to our university hospital. His condition became complicated with pneumonia, septic shock, ARDS, coagulation dysfunction, and renal failure. In spite of intensive therapy, oxygenation and arterial blood pressure fell to critically low values. Simultaneously, his intracranial pressure peaked and his pupils dilated, displaying no reflexes to light. His antibiotic regimen was changed and ventilation was altered to high frequency oscillations, and despite being ethically problematic, we added APC to his treatment. The patient recovered with modest neurological sequelae.Keywords: activated protein C, acute respiratory distress syndrome, septic shock, severe head injury&amp;nbsp