Effect of Transfusion Strategy in Acute Non-variceal Upper Gastrointestinal Bleeding: A Nationwide Study of 5861 Hospital Admissions in Denmark

Background

Acute non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of admissions as well as aggressive transfusion of blood products. Whether the transfusion strategy in NVUGIB impacts on hemostasis is unknown and constitutes the focus of this study.

Method

Retrospective analysis of all hospital admissions in Denmark between 2011 and 2013 where hemostatic endoscopic interventions in either the stomach or duodenum had been employed. Regression modeling was used to predict the effect of units transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets (PLT) on primary outcome 30-day mortality as well as secondary hemostasis-related outcomes and need for re-endoscopy and conversion to surgery. The model was corrected for confounders, including transfusion of other blood products (PRBC, FFP, and PLT, respectively), patient age as well as pre-existing medical conditions.

Results

5107 patients received 10783 therapeutic endoscopic interventions. Units of PRBC transfused were identified as a predictor of re-endoscopy, surgery, and 30-day mortality with odds ratio (OR) 1.08 (1.06–1.09, p < 0.01), 1.05 (1.03–1.07, p < 0.01), and 1.04 (1.01–1.06, p < 0.01), respectively. Units of FFP transfused were associated with a higher risk of surgery and 30-day mortality with OR 1.05 (1.02–1.08, p < 0.01) and 1.04 (1.02–1.07, p < 0.01), respectively. Units of PLTs transfused were independently associated with a reduction in risk of re-endoscopy 0.93 (0.87–0.98, p = 0.02). A high ratio of PRBC:FFP:PLT (1:1:1) was associated with reduced need for re-endoscopy OR 0.23 (0.06–0.67, p = 0.01) but increased mortality with OR 3.60 (1.34–11.38, p = 0.02).

Conclusion

PRBC transfusion was associated with adverse events, including 30-day mortality and failure of hemostasis. In contrast, transfusion of PLT was associated with a reduction in need for re-endoscopy.

     

Systematic review of cardiac output measurements by echocardiography vs. thermodilution: the techniques are not interchangeable

Purpose

Echocardiography is frequently used in the hemodynamic evaluation of critically ill patients, but inaccurate measurements may lead to wrong clinical decisions. The aim of our systematic review was to investigate the interchangeability of echocardiography with thermodilution technique in measuring cardiac output and its changes.

Methods

In August 2015 we systematically searched electronic databases and included studies investigating the echocardiographic measurement of cardiac output compared with thermodilution technique using the Bland–Altman method. Two authors independently reviewed the studies and extracted data on type of measurements, clinical setting and characteristics, and those of the Bland–Altman and trending ability analyses.

Results

We identified 13,834 citations and included 24 studies in the final analysis. The median number of participants was 32 (range 8–65). Most of the studies assessed left-sided heart structures and the majority had small bias, wide limits of agreement, and high percentage error between echocardiography and thermodilution. In only two of the 24 studies the precision of each technique (echocardiography and thermodilution) was assessed before comparing them. In the single study evaluating trending ability using valid methodology, agreement was observed between echocardiography and thermodilution in detecting the directional changes in cardiac output, but the magnitude of changes varied considerably.

Conclusions

The majority of studies comparing echocardiography with thermodilution were difficult to interpret, but current evidence does not support interchangeability between these techniques in measuring cardiac output. The techniques may be interchangeable in tracking directional changes in cardiac output, but this has to be confirmed in large high-quality studies.

     

Role of precise spike timing in coding of dynamic vibrissa stimuli in somatosensory thalamus

Rats discriminate texture by whisking their vibrissae across the surfaces of objects. This process induces corresponding vibrissa vibrations, which must be accurately represented by neurons in the somatosensory pathway. In this study, we investigated the neural code for vibrissa motion in the ventroposterior medial (VPm) nucleus of the thalamus by single-unit recording. We found that neurons conveyed a great deal of information (up to 77.9 bits/s) about vibrissa dynamics. The key was precise spike timing, which typically varied by less than a millisecond from trial to trial. The neural code was sparse, the average spike being remarkably informative (5.8 bits/spike). This implies that as few as four VPm spikes, coding independent information, might reliably differentiate between 10⁶ textures. To probe the mechanism of information transmission, we compared the role of time-varying firing rate to that of temporally correlated spike patterns in two ways: 93.9% of the information encoded by a neuron could be accounted for by a hypothetical neuron with the same time-dependent firing rate but no correlations between spikes; moreover, 93.4% of the information in the spike trains could be decoded even if temporal correlations were ignored. Taken together, these results suggest that the essence of the VPm code for vibrissa motion is firing rate modulation on a submillisecond timescale. The significance of such a code may be that it enables a small number of neurons, firing only few spikes, to convey distinctions between very many different textures to the barrel cortex.     

Growing from Our Roots: Strategies for Developing Culturally Grounded Health Promotion Interventions in American Indian,Alaska Native,and Native Hawaiian Communities

Given the paucity of empirically based health promotion interventions designed by and for American Indian, Alaska Native, and Native Hawaiian (i.e., Native) communities, researchers and partnering communities have had to rely on the adaptation of evidence-based interventions (EBIs) designed for non-Native populations, a decidedly sub-optimal approach. Native communities have called for development of Indigenous health promotion programs in which their cultural worldviews and protocols are prioritized in the design, development, testing, and implementation. There is limited information regarding how Native communities and scholars have successfully collaborated to design and implement culturally based prevention efforts “from the ground up.” Drawing on five diverse community-based Native health intervention studies, we describe strategies for designing and implementing culturally grounded models of health promotion developed in partnership with Native communities. Additionally, we highlight indigenist worldviews and protocols that undergird Native health interventions with an emphasis on the incorporation of (1) original instructions, (2) relational restoration, (3) narrative-[em]bodied transformation, and (4) indigenist community-based participatory research (ICBPR) processes. Finally, we demonstrate how culturally grounded interventions can improve population health when they prioritize local Indigenous knowledge and health-positive messages for individual to multi-level community interventions.

     

Characteristics of staff–child interaction in 1–3-year-olds’ risky play in early childhood education and care

Despite increased interest in children’s risk-taking in play, little is known of this aspect considering children under three years. Therefore, this study aimed to investigate the concept of scaffolding to potentially describe patterns in staff–child interaction in 1–3-year-olds’ risky play. Empirical data were taken from an exploratory study, executed as a focused ethnography with multiple data collecting techniques, resulting in a sample of 198 instances of risky play. Findings indicate that scaffolding is a pertinent theoretical foundation for describing high-quality staff–child interaction in risky play, leading to increased opportunities for developmentally appropriate stimulation. Of the 171 instances where staff were present, staff did not interact at all in 70 of the instances (41%). Staff–child interaction, directly related to children’s risky play, occurred in the remaining 101 instances. Of these 101 instances, ‘Scaffolding’- and ‘Non-scaffolding’-interaction were observed in 78% and 22% of the instances, respectively. Implications are discussed.     

The effect of activated protein C on plasma cytokine levels in a porcine model of acute endotoxemia

Objective To assess the anti-inflammatory effects of recombinant human activated protein C (rhAPC) in a porcine model of acute endotoxemia. Design and setting Animal randomized controlled study at the Laboratory of Clinical Institute, Aarhus University Hospital. Subjects Eighteen female landrace pigs (30 kg). Interventions By pairwise randomization, pigs were given either LPS or LPS and rhAPC. Both groups received a stepwise increasing LPS infusion for 30 min; whereafter the infusion continued at a lower rate (300 min LPS in both groups). The LPS+rhAPC group received rhAPC (100 μg/kg per hour) 15 min before the LPS infusion began and throughout the trial period. Results While rhAPC showed no modifying effects on peak plasma levels of pro- or anti-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10), TNF-α and IL-10 peaked significantly later in the rhAPC-treated animals. The profibrinolytic effects of rhAPC were confirmed by decreased plasminogen activator inhibitor 1 levels, while no differences were found in other coagulation markers, hemodynamic, metabolic, or leukocyte data between the two groups. Conclusions We found no significant effect of rhAPC on plasma levels of either pro- or anti-inflammatory cytokines in this porcine model of acute endotoxemia. However, TNF-α and IL-10 peaked significantly later in the rhAPC-treated animals.     

Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination

Background

The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination.

Methods

We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS.

Results

A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center.

Conclusions

Time to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.

     

Coronary sinus cannulation with a steerable catheter during biventricular device implantation

Objectives. To determine whether a steerable catheter with electrogram guidance (CS-assist group) could facilitate access to the coronary sinus (CS) during cardiac resynchronization therapy (CRT) implantation. Design. Consecutive patients who underwent CRT implantation were recruited prospectively into the CS-assist group (n = 81) and compared with those using conventional techniques without an electrogram guidance (conventional group, n = 101). Results. The CS cannulation success rate was clearly greater in the CS-assist group (100%) than that in the conventional group (95%, p < 0.05), with significantly shorter mean procedure time (52.6 ± 20.6 min vs. 73.2 ± 40.9 min, p < 0.01) and fluoroscopy time (3.6 ± 3.2 min vs. 14.2 ± 20.4 min, p < 0.01). In the five CS cannulation failure cases, mean procedure time (144.0 ± 37.0 min) and fluoroscopy time (57.8 ± 24.8 min) were significantly longer than those in the other patients (61.2 ± 32.3 and 8.2 ± 13.6 min, respectively, n = 177, both p < 0.01). Conclusions. Using the steerable catheter with real-time electrogram guidance, location of and access to the CS is more rapid and successful, which may improve the success of the CRT implantation and may give significant time savings.     

CYP2C19*17 increases clopidogrel‐mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel

The aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open‐label two‐phase cross‐over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi‐Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and its metabolites cycloguanil and 4‐chlorphenylbiguanide (4‐CPB) were determined in 29 of 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant correlations were found between the area under the time–concentration curve (AUC_0–∞) of CAMD and both the absolute ADP‐induced P2Y₁₂ receptor‐activated platelet aggregation (r = ?0.60, P = 0.0007) and the percentage inhibition of aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the absolute ADP‐induced P2Y₁₂ receptor‐activated platelet aggregation, exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4‐CPB exhibited any significant differences among the genotype groups. In conclusion, carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet aggregation, but do not have significantly lower absolute P2Y₁₂ receptor‐activated platelet aggregation or higher exposure to the active metabolite after a single oral administration of 600 mg clopidogrel.