Out of the Comfort Zone

Imagine the following experience: Your are a student nurse working with other health care providers in the obstetric unit of your facility. A fifteen-year-old Haitian girl, along with her grandmother, arrives seeking help because her two-day-old, eight-pound baby boy is having difficulty breathing..

Analysis of Patient Alarms in Adult Intensive Care Units

...Our study aims were pretty straight-forward. We concentrated quite a bit on arrhythmia alarms, which is a little different than the parameter alarms we\u27ve been talking about so far today. We decided we were going to assess the alarm prevalence of patient\u27s physiological monitor alarms. We\u27ll identify the alarm burden, analyze a select high priority number of arrhythmia alarms and determine patient characteristics that may be associated with the frequent alarms

Heart Rate Variability Measured Early in Patients with Evolving Acute Coronary Syndrome and 1-year Outcomes of Rehospitalization and Mortality

Objective: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS). Background: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established. Methods: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with �18 hours of sinus rhythm were selected for HRV analysis (number [N] �193). Time domain, frequency domain, and nonlinear HRV were examined. Survival analysis was performed. Results: During the 1-year follow-up, 94 patients were event-free, 82 were readmitted, and 17 died. HRV was altered in relation to outcomes. Predictors of rehospitalization included increased normalized high frequency power, decreased normalized low frequency power, and decreased low/high frequency ratio. Normalized high frequency �42 ms2 predicted rehospitalization while controlling for clinical variables (hazard ratio [HR] �2.3; 95% confidence interval [CI] �1.4–3.8, P�0.001). Variables significantly associated with death included natural logs of total power and ultra low frequency power. A model with ultra low frequency power �8 ms2 ( HR �3.8; 95% CI �1.5–10.1; P�0.007) and troponin �0.3 ng/mL (HR �4.0; 95% CI �1.3–12.1; P�0.016) revealed that each contributed independently in predicting mortality. Nonlinear HRV variables were significant predictors of both outcomes. Conclusion: HRV measured close to the ACS onset may assist in risk stratification. HRV cut-points may provide additional, incremental prognostic information to established assessment guidelines, and may be worthy of additional study

Heart Rate Variability Measurement and Clinical Depression in Acute Coronary Syndrome Patients: Narrative Review of Recent Literature

Aim: We aimed to explore links between heart rate variability (HRV) and clinical depression in patients with acute coronary syndrome (ACS), through a review of recent clinical research literature. Background: Patients with ACS are at risk for both cardiac autonomic dysfunction and clinical depression. Both conditions can negatively impact the ability to recover from an acute physiological insult, such as unstable angina or myocardial infarction, increasing the risk for adverse cardiovascular outcomes. HRV is recognized as a reflection of autonomic function. Methods: A narrative review was undertaken to evaluate state-of-the-art clinical research, using the PubMed database, January 2013. The search terms “heart rate variability” and “depression” were used in conjunction with “acute coronary syndrome”, “unstable angina”, or “myocardial infarction” to find clinical studies published within the past 10 years related to HRV and clinical depression, in patients with an ACS episode. Studies were included if HRV measurement and depression screening were undertaken during an ACS hospitalization or within 2 months of hospital discharge. Results: Nine clinical studies met the inclusion criteria. The studies’ results indicate that there may be a relationship between abnormal HRV and clinical depression when assessed early after an ACS event, offering the possibility that these risk factors play a modest role in patient outcomes. Conclusion: While a definitive conclusion about the relevance of HRV and clinical depression measurement in ACS patients would be premature, the literature suggests that these measures may provide additional information in risk assessment. Potential avenues for further research are proposed

Patient Characteristics Associated with False Arrhythmia Alarms in Intensive Care

Introduction A high rate of false arrhythmia alarms in the intensive care unit (ICU) leads to alarm fatigue, the condition of desensitization and potentially inappropriate silencing of alarms due to frequent invalid and nonactionable alarms, often referred to as false alarms. Objective The aim of this study was to identify patient characteristics, such as gender, age, body mass index, and diagnosis associated with frequent false arrhythmia alarms in the ICU. Methods This descriptive, observational study prospectively enrolled patients who were consecutively admitted to one of five adult ICUs (77 beds) at an urban medical center over a period of 31 days in 2013. All monitor alarms and continuous waveforms were stored on a secure server. Nurse scientists with expertise in cardiac monitoring used a standardized protocol to annotate six clinically important types of arrhythmia alarms (asystole, pause, ventricular fibrillation, ventricular tachycardia, accelerated ventricular rhythm, and ventricular bradycardia) as true or false. Total monitoring time for each patient was measured, and the number of false alarms per hour was calculated for these six alarm types. Medical records were examined to acquire data on patient characteristics. Results A total of 461 unique patients (mean age =60±17 years) were enrolled, generating a total of 2,558,760 alarms, including all levels of arrhythmia, parameter, and technical alarms. There were 48,404 hours of patient monitoring time, and an average overall alarm rate of 52 alarms/hour. Investigators annotated 12,671 arrhythmia alarms; 11,345 (89.5%) were determined to be false. Two hundred and fifty patients (54%) generated at least one of the six annotated alarm types. Two patients generated 6,940 arrhythmia alarms (55%). The number of false alarms per monitored hour for patients’ annotated arrhythmia alarms ranged from 0.0 to 7.7, and the duration of these false alarms per hour ranged from 0.0 to 158.8 seconds. Patient characteristics were compared in relation to 1) the number and 2) the duration of false arrhythmia alarms per 24-hour period, using nonparametric statistics to minimize the influence of outliers. Among the significant associations were the following: age ≥60 years (P=0.013; P=0.034), confused mental status (P\u3c0.001 for both comparisons), cardiovascular diagnoses (P\u3c0.001 for both comparisons), electrocardiographic (ECG) features, such as wide ECG waveforms that correspond to ventricular depolarization known as QRS complex due to bundle branch block (BBB) (P=0.003; P=0.004) or ventricular paced rhythm (P=0.002 for both comparisons), respiratory diagnoses (P=0.004 for both comparisons), and support with mechanical ventilation, including those with primary diagnoses other than respiratory ones (P\u3c0.001 for both comparisons). Conclusion Patients likely to trigger a higher number of false arrhythmia alarms may be those with older age, confusion, cardiovascular diagnoses, and ECG features that indicate BBB or ventricular pacing, respiratory diagnoses, and mechanical ventilatory support. Algorithm improvements could focus on better noise reduction (eg, motion artifact with confused state) and distinguishing BBB and paced rhythms from ventricular arrhythmias. Increasing awareness of patient conditions that apparently trigger a higher rate of false arrhythmia alarms may be useful for reducing unnecessary noise and improving alarm management

NOD/SCID-GAMMA Mice Are an Ideal Strain to Assess the Efficacy of Therapeutic Agents Used in the Treatment of Myeloma Bone Disease

Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7–8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti-myeloma therapies, particularly those targeting myeloma bone disease

Resting state connectivity correlates with drug and placebo response in fibromyalgia patients

AbstractFibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response.We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition.15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex.This study indicates that ACC–IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response

Genome-wide analyses of Liberibacter species provides insights into evolution, phylogenetic relationships, and virulence factors.

'Candidatus Liberibacter' species are insect-transmitted, phloem-limited α-Proteobacteria in the order of Rhizobiales. The citrus industry is facing significant challenges due to huanglongbing, associated with infection from 'Candidatus Liberibacter asiaticus' (Las). In order to gain greater insight into 'Ca. Liberibacter' biology and genetic diversity, we have performed genome sequencing and comparative analyses of diverse 'Ca. Liberibacter' species, including those that can infect citrus. Our phylogenetic analysis differentiates 'Ca. Liberibacter' species and Rhizobiales in separate clades and suggests stepwise evolution from a common ancestor splitting first into nonpathogenic Liberibacter crescens followed by diversification of pathogenic 'Ca. Liberibacter' species. Further analysis of Las genomes from different geographical locations revealed diversity among isolates from the United States. Our phylogenetic study also indicates multiple Las introduction events in California and spread of the pathogen from Florida to Texas. Texan Las isolates were closely related, while Florida and Asian isolates exhibited the most genetic variation. We have identified conserved Sec translocon (SEC)-dependent effectors likely involved in bacterial survival and virulence of Las and analysed their expression in their plant host (citrus) and insect vector (Diaphorina citri). Individual SEC-dependent effectors exhibited differential expression patterns between host and vector, indicating that Las uses its effector repertoire to differentially modulate diverse organisms. Collectively, this work provides insights into the evolution of 'Ca. Liberibacter' species, the introduction of Las in the United States and identifies promising Las targets for disease management

Altered fMRI restingâ state connectivity in individuals with fibromyalgia on acute pain stimulation

BackgroundFibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain.MethodsIn this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Restingâ state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex.ResultsAcute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain.ConclusionsThese data reporting changes in restingâ state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain.What does this study/add?In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/1/ejp832_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/2/ejp832.pd

Detailed study of BBN implications of neutrino oscillation generated neutrino asymmetries in some four neutrino models

We re-examine the evolution of neutrino asymmetries in several four neutrino models. The first case involves the direct creation of $L_{\nu_e}$ by $\nu_e \leftrightarrow \nu_s$ oscillations. In the second case, we consider the mass hierarchy $m_{\nu_\tau} \gg m_{\nu_\mu}, m_{\nu_e}, m_{\nu_s}$ where $\nu_\tau \leftrightarrow \nu_s$ oscillations generate a large $L_{\nu_\tau}$ and some of this asymmetry is converted into $L_{\nu_e}$ by $\nu_{\tau} \leftrightarrow \nu_{e}$ oscillations. We estimate the implications for BBN for a range of cosmologically interesting $\delta m^2$ values. The present paper improves on previous published work by taking into account the finite repopulation rate and the time dependence of the distortions to the neutrino momentum distributions. The treatment of chemical decoupling is also improved.Comment: Expanded discussion on the sign of the neutrino asymmetr