ResearchPad - pacemakers https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Is transjugular insertion of a temporary pacemaker a safe and effective approach?]]> https://www.researchpad.co/article/elastic_article_13814 Temporary pacemakers (TPMs) are usually inserted in an emergency situation. However, there are few reports available regarding which route of access is best or what the most preferred approach is currently in tertiary hospitals. This study aimed to compare procedure times, complication rates, and indications for temporary pacing between the transjugular and transfemoral approaches to TPM placement. We analyzed consecutive patients who underwent TPM placement. Indications; procedure times; and rates of complications including localized infection, any bleeding, and pacing wire repositioning rates were analyzed. A total of 732 patients (361 treated via the transjugular approach and 371 treated via the transfemoral approach) were included. Complete atrioventricular block was the most common cause of TPM placement in both groups, but sick sinus syndrome was especially common in the transjugular approach group. Separately, procedure time was significantly shorter in the transjugular approach group (9.0 ± 8.0 minutes vs. 11.9 ± 9.7 minutes; P < 0.001). Overall complication rates were not significantly different between the two groups, and longer duration of temporary pacing was a risk factor for repositioning. The risk of reposition was significantly increased when the temporary pacing was continued more than 5 days and 3 days in the transjugular approach group and the transfemoral approach group, respectively. The transjugular approach should be considered if the TPM is required for more than 3 days.

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<![CDATA[Population dynamics and entrainment of basal ganglia pacemakers are shaped by their dendritic arbors]]> https://www.researchpad.co/article/5c65dcf2d5eed0c484dec628

The theory of phase oscillators is an essential tool for understanding population dynamics of pacemaking neurons. GABAergic pacemakers in the substantia nigra pars reticulata (SNr), a main basal ganglia (BG) output nucleus, receive inputs from the direct and indirect pathways at distal and proximal regions of their dendritic arbors, respectively. We combine theory, optogenetic stimulation and electrophysiological experiments in acute brain slices to ask how dendritic properties impact the propensity of the various inputs, arriving at different locations along the dendrite, to recruit or entrain SNr pacemakers. By combining cable theory with sinusoidally-modulated optogenetic activation of either proximal somatodendritic regions or the entire somatodendritic arbor of SNr neurons, we construct an analytical model that accurately fits the empirically measured somatic current response to inputs arising from illuminating the soma and various portions of the dendritic field. We show that the extent of the dendritic tree that is illuminated generates measurable and systematic differences in the pacemaker’s phase response curve (PRC), causing a shift in its peak. Finally, we show that the divergent PRCs correctly predict differences in two major features of the collective dynamics of SNr neurons: the fidelity of population responses to sudden step-like changes in inputs; and the phase latency at which SNr neurons are entrained by rhythmic stimulation, which can occur in the BG under both physiological and pathophysiological conditions. Our novel method generates measurable and physiologically meaningful spatial effects, and provides the first empirical demonstration of how the collective responses of SNr pacemakers are determined by the transmission properties of their dendrites. SNr dendrites may serve to delay distal striatal inputs so that they impinge on the spike initiation zone simultaneously with pallidal and subthalamic inputs in order to guarantee a fair competition between the influence of the monosynaptic direct- and polysynaptic indirect pathways.

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<![CDATA[Cardiac implantable electronic device (CIED) infections are expensive and associated with prolonged hospitalisation: UK Retrospective Observational Study]]> https://www.researchpad.co/article/5c3667b4d5eed0c4841a612f

Background

There are limited reports outlining the financial cost of treating cardiac implantable electronic device (CIED) infection outside the United States. This study aimed to determine the average treatment cost of CIED infection in a large UK tertiary referral centre and compared costs of different treatment pathways that are recognised in the management of CIED infection (early versus delayed re-implantation).

Methods

We retrospectively analysed cost and length of stay (LOS) data for consecutive patients undergoing infected CIED extraction with cardiac resynchronization therapy (CRT-D [with defibrillator], CRT-P [with pacemaker]), implantable cardioverter-defibrillators (ICDs) and permanent pacemakers (PPMs).

Results

Between January 2013 and March 2015, complete data was available for 84 patients (18 [21.4%] CRT-D, 24 [28.6%] ICDs and 42 [50.0%] PPMs). When all cases were considered the cost of infection ranged from £5,139 (PPM) to £24,318 (CRT-D). Considering different treatment strategies; 41 (48.8%) underwent CIED extraction and re-implantation during the same admission (early re-implant strategy (ER). 43 (51.2%) underwent extraction, but were then discharged home to be re-admitted for day-case re-implantation (delayed re-implant strategy (DR)). Median LOS was significantly shorter in DR compared to ER (5.0 vs. 18.0 days, p<0.001). The total cost of CIED infection episode was similar for both treatment strategies (median £14,241.48 vs. £14,741.70 including wearable defibrillator (Lifevest) and outpatient antibiotics costs, ER vs. DR; p = 0.491).

Conclusion

CIED infections are expensive and associated with significant health-economic burden. When all device types were considered, a DR strategy is associated with reduced LOS without an increased cost penalty.

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<![CDATA[Effect of increasing heart rate on finger photoplethysmography fitness index (PPGF) in subjects with implanted cardiac pacemakers]]> https://www.researchpad.co/article/5c084236d5eed0c484fcc339

Finger photoplethysmography (PPG) is a noninvasive method that measures blood volume changes in the finger. The PPG fitness index (PPGF) has been proposed as an index of vascular risk and vascular aging. The objectives of the study were to determine the effects of heart rate (HR) on the PPGF and to determine whether PPGF is influenced by blood pressure (BP) changes. Twenty subjects (78±8 years, 3 female) with permanent cardiac pacemakers or cardioverter defibrillators were prospectively recruited. HR was changed by pacing, in a random order from 60 to 100 bpm and in 10 bpm increments. At each paced HR, the PPGF was derived from a finger photoplethysmogram. Cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were derived from the finger arterial pressure waveform. Brachial blood pressure (BP) was measured by the oscillometric method. This study found that as HR was increased from 60 to 100 bpm, brachial diastolic BP, brachial mean BP and CO were significantly increased (p<0.01), whilst the PPGF and SV were significantly decreased (p<0.001). The effects of HR on the PPGF were influenced by BP, with a decreasing HR effect on the PPGF that resulted from a higher BP. In conclusion, HR was a significant confounder for PPGF and it must be taken into account in analyses of PPGF, when there are large changes or differences in the HR. The magnitude of this effect was BP dependent.

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<![CDATA[Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity]]> https://www.researchpad.co/article/5989dae7ab0ee8fa60bbe092

What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition.

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<![CDATA[One-Month Global Longitudinal Strain Identifies Patients Who Will Develop Pacing-Induced Left Ventricular Dysfunction over Time: The Pacing and Ventricular Dysfunction (PAVD) Study]]> https://www.researchpad.co/article/5989dad9ab0ee8fa60bb90ae

Background

Predicting which individuals will have a decline in left ventricular (LV) function after pacemaker implantation remains an important challenge. We investigated whether LV global longitudinal strain (GLS), measured by 2D speckle tracking strain echocardiography, can identify patients at risk of pacing-induced left ventricular dysfunction (PIVD) or pacing-induced cardiomyopathy (PICMP).

Methods

Fifty-five patients with atrioventricular block and preserved LV function underwent dual-chamber pacemaker implantation and were followed with serial transthoracic echocardiography for 12 months for the development of PIVD (defined as a reduction in LV ejection fraction (LVEF) ≥5 percentage points at 12 months) or PICMP (reduction in LVEF to <45%).

Results

At 12 months, 15 (27%) patients developed PIVD; of these, 4 patients developed PICMP. At one month, GLS was significantly lower in the 15 patients who subsequently developed PIVD, compared to those who did not (n = 40) (GLS -12.6 vs. -16.4 respectively; p = 0.022). When patients with PICMP were excluded, one month GLS was significantly reduced compared to baseline whereas LVEF was not. One-month GLS had high predictive accuracy for determining subsequent development of PIVD or PICMP (AUC = 0.80, optimal GLS threshold: <−14.5, sensitivity 82%, specificity 75%); and particularly PICMP (AUC = 0.86, optimal GLS threshold: <−13.5, sensitivity 100%, specificity 71%).

Conclusions

GLS is a novel predictor of decline in LV systolic function following pacemaker implantation, with the potential to identify patients at risk of PIVD before measurable changes in LVEF are apparent. GLS measured one month after implantation has high predictive accuracy for identifying patients who later develop PIVD or PICMP.

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<![CDATA[Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold]]> https://www.researchpad.co/article/5989da11ab0ee8fa60b79ca3

Arrhythmias in cardiac tissue are generally associated with irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. Recently, it was shown in simulations of two-dimensional (2D) discrete models of cardiac tissue that a wave crossing a fibrotic, heterogeneous region may produce reentry and transient or persistent ectopic activity provided the fraction of conducting connections is just above the percolation threshold. Here, we investigate the occurrence of these phenomena in three-dimensions by simulations of a discrete model representing a thin slab of cardiac tissue. This is motivated (i) by the necessity to study the relevance and properties of the percolation-related mechanism for the emergence of microreentries in three dimensions and (ii) by the fact that atrial tissue is quite thin in comparison with ventricular tissue. Here, we simplify the model by neglecting details of tissue anatomy, e. g. geometries of atria or ventricles and the anisotropy in the conductivity. Hence, our modeling study is confined to the investigation of the effect of the tissue thickness as well as to the comparison of the dynamics of electrical excitation in a 2D layer with the one in a 3D slab. Our results indicate a strong and non-trivial effect of the thickness even for thin tissue slabs on the probability of microreentries and ectopic beat generation. The strong correlation of the occurrence of microreentry with the percolation threshold reported earlier in 2D layers persists in 3D slabs. Finally, a qualitative agreement of 3D simulated electrograms in the fibrotic region with the experimentally observed complex fractional atrial electrograms (CFAE) as well as strong difference between simulated electrograms in 2D and 3D were found for the cases where reentry and ectopic activity were triggered by the micro-fibrotic region.

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<![CDATA[Travelling Wave Pulse Coupled Oscillator (TWPCO) Using a Self-Organizing Scheme for Energy-Efficient Wireless Sensor Networks]]> https://www.researchpad.co/article/5989d9e6ab0ee8fa60b6b70b

Recently, Pulse Coupled Oscillator (PCO)-based travelling waves have attracted substantial attention by researchers in wireless sensor network (WSN) synchronization. Because WSNs are generally artificial occurrences that mimic natural phenomena, the PCO utilizes firefly synchronization of attracting mating partners for modelling the WSN. However, given that sensor nodes are unable to receive messages while transmitting data packets (due to deafness), the PCO model may not be efficient for sensor network modelling. To overcome this limitation, this paper proposed a new scheme called the Travelling Wave Pulse Coupled Oscillator (TWPCO). For this, the study used a self-organizing scheme for energy-efficient WSNs that adopted travelling wave biologically inspired network systems based on phase locking of the PCO model to counteract deafness. From the simulation, it was found that the proposed TWPCO scheme attained a steady state after a number of cycles. It also showed superior performance compared to other mechanisms, with a reduction in the total energy consumption of 25%. The results showed that the performance improved by 13% in terms of data gathering. Based on the results, the proposed scheme avoids the deafness that occurs in the transmit state in WSNs and increases the data collection throughout the transmission states in WSNs.

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<![CDATA[Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1: A multicentre cohort follow-up study]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbf52

Objective

High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1).

Methods

117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months.

Results

Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score.

Conclusions

Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting.

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<![CDATA[Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart]]> https://www.researchpad.co/article/5989dae1ab0ee8fa60bbbfea

Purpose

Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth.

Methods

Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30 Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA.

Results

Increasing distance from the pacing sites led to significant (p<0.01) attenuation of UEs (V-P = 7.0±0.5%; VP-P = 5.4±0.3% per cm). Attenuation of BE with distance was insignificant (Vp-p unfiltered  = 2.2±0.5%; filtered  = 1.7±1.4% per cm). Independent of pacing depth, significant (p<0.01) transmural electrophysiological gradients were observed, with highest amplitude occurring at epicardial layers for UE and endocardial layers for BE. Furthermore, during pacing, propagation was earlier at the epicardium than endocardial layer by 1.6±2.0 ms (UE) and 1.4±2.8 ms (BE) (all p>0.01) during endocardial stimulation, and 2.3±2.4 ms (UE) and 1.8±3.7 ms (BE) during epicardal stimulation (all p<0.01).

Conclusions

Electrogram amplitude is inversely proportional to propagation distance for unipolar modalities only, which affected V-P>VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient.

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<![CDATA[Emergent Network Topology within the Respiratory Rhythm-Generating Kernel Evolved In Silico]]> https://www.researchpad.co/article/5989dadbab0ee8fa60bb9bb4

We hypothesize that the network topology within the pre-Bötzinger Complex (preBötC), the mammalian respiratory rhythm generating kernel, is not random, but is optimized in the course of ontogeny/phylogeny so that the network produces respiratory rhythm efficiently and robustly. In the present study, we attempted to identify topology of synaptic connections among constituent neurons of the preBötC based on this hypothesis. To do this, we first developed an effective evolutionary algorithm for optimizing network topology of a neuronal network to exhibit a ‘desired characteristic’. Using this evolutionary algorithm, we iteratively evolved an in silico preBötC ‘model’ network with initial random connectivity to a network exhibiting optimized synchronous population bursts. The evolved ‘idealized’ network was then analyzed to gain insight into: (1) optimal network connectivity among different kinds of neurons—excitatory as well as inhibitory pacemakers, non-pacemakers and tonic neurons—within the preBötC, and (2) possible functional roles of inhibitory neurons within the preBötC in rhythm generation. Obtained results indicate that (1) synaptic distribution within excitatory subnetwork of the evolved model network illustrates skewed/heavy-tailed degree distribution, and (2) inhibitory subnetwork influences excitatory subnetwork primarily through non-tonic pacemaker inhibitory neurons. Further, since small-world (SW) network is generally associated with network synchronization phenomena and is suggested as a possible network structure within the preBötC, we compared the performance of SW network with that of the evolved model network. Results show that evolved network is better than SW network at exhibiting synchronous bursts.

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<![CDATA[Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be00b5

In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation.

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<![CDATA[Pattern Selection in Network of Coupled Multi-Scroll Attractors]]> https://www.researchpad.co/article/5989daaaab0ee8fa60ba8e71

Multi-scroll chaotic attractor makes the oscillator become more complex in dynamic behaviors. The collective behaviors of coupled oscillators with multi-scroll attractors are investigated in the regular network in two-dimensional array, which the local kinetics is described by an improved Chua circuit. A feasible scheme of negative feedback with diversity is imposed on the network to stabilize the spatial patterns. Firstly, the Chua circuit is improved by replacing the nonlinear term with Sine function to generate infinite aquariums so that multi-scroll chaotic attractors could be generated under appropriate parameters, which could be detected by calculating the Lyapunov exponent in the parameter region. Furthermore, negative feedback with different gains (D1, D2) is imposed on the local square center area A2 and outer area A1 of the network, it is found that spiral wave, target wave could be developed in the network under appropriate feedback gain with diversity and size of controlled area. Particularly, homogeneous state could be reached after synchronization by selecting appropriate feedback gain and controlled size in the network. Finally, the distribution for statistical factors of synchronization is calculated in the two-parameter space to understand the transition of pattern region. It is found that developed spiral waves, target waves often are associated with smaller factor of synchronization. These results show that emergence of sustained spiral wave and continuous target wave could be effective for further suppression of spatiotemporal chaos in network by generating stable pacemaker completely.

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<![CDATA[Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study]]> https://www.researchpad.co/article/5989db3eab0ee8fa60bd5afb

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.

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<![CDATA[Insights into the Problem of Alarm Fatigue with Physiologic Monitor Devices: A Comprehensive Observational Study of Consecutive Intensive Care Unit Patients]]> https://www.researchpad.co/article/5989d9efab0ee8fa60b6ddaf

Purpose

Physiologic monitors are plagued with alarms that create a cacophony of sounds and visual alerts causing “alarm fatigue” which creates an unsafe patient environment because a life-threatening event may be missed in this milieu of sensory overload. Using a state-of-the-art technology acquisition infrastructure, all monitor data including 7 ECG leads, all pressure, SpO2, and respiration waveforms as well as user settings and alarms were stored on 461 adults treated in intensive care units. Using a well-defined alarm annotation protocol, nurse scientists with 95% inter-rater reliability annotated 12,671 arrhythmia alarms.

Results

A total of 2,558,760 unique alarms occurred in the 31-day study period: arrhythmia, 1,154,201; parameter, 612,927; technical, 791,632. There were 381,560 audible alarms for an audible alarm burden of 187/bed/day. 88.8% of the 12,671 annotated arrhythmia alarms were false positives. Conditions causing excessive alarms included inappropriate alarm settings, persistent atrial fibrillation, and non-actionable events such as PVC's and brief spikes in ST segments. Low amplitude QRS complexes in some, but not all available ECG leads caused undercounting and false arrhythmia alarms. Wide QRS complexes due to bundle branch block or ventricular pacemaker rhythm caused false alarms. 93% of the 168 true ventricular tachycardia alarms were not sustained long enough to warrant treatment.

Discussion

The excessive number of physiologic monitor alarms is a complex interplay of inappropriate user settings, patient conditions, and algorithm deficiencies. Device solutions should focus on use of all available ECG leads to identify non-artifact leads and leads with adequate QRS amplitude. Devices should provide prompts to aide in more appropriate tailoring of alarm settings to individual patients. Atrial fibrillation alarms should be limited to new onset and termination of the arrhythmia and delays for ST-segment and other parameter alarms should be configurable. Because computer devices are more reliable than humans, an opportunity exists to improve physiologic monitoring and reduce alarm fatigue.

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<![CDATA[A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia]]> https://www.researchpad.co/article/5989da02ab0ee8fa60b74a1e

Background

Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.

Methods

A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.

Results

Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.

Conclusions

A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique.

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<![CDATA[No Evidence for Ionotropic Pheromone Transduction in the Hawkmoth Manduca sexta]]> https://www.researchpad.co/article/5989d9d4ab0ee8fa60b6552f

Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

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<![CDATA[A Statistical Framework to Identify Deviation from Time Linearity in Epigenetic Aging]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f914

In multiple studies DNA methylation has proven to be an accurate biomarker of age. To develop these biomarkers, the methylation of multiple CpG sites is typically linearly combined to predict chronological age. By contrast, in this study we apply the Universal PaceMaker (UPM) model to investigate changes in DNA methylation during aging. The UPM was initially developed to study rate acceleration/deceleration in sequence evolution. Rather than identifying which linear combinations of sites predicts age, the UPM models the rates of change of multiple CpG sites, as well as their starting methylation levels, and estimates the age of each individual to optimize the model fit. We refer to the estimated age as the “epigenetic age”, which is in contrast to the known chronological age of each individual. We construct a statistical framework and devise an algorithm to determine whether a genomic pacemaker is in effect (i.e rates of change vary with age). The decision is made by comparing two competing likelihood based models, the molecular clock (MC) and UPM. For the molecular clock model, we use the known chronological age of each individual and fit the methylation rates at multiple sites, and express the problem as a linear least squares and solve it in polynomial time. For the UPM case, the search space is larger as we are fitting both the epigenetic age of each individual as well as the rates for each site, yet we succeed to reduce the problem to the space of individuals and polynomial in the more significant space—the methylated sites. We first tested our algorithm on simulated data to elucidate the factors affecting the identification of the pacemaker model. We find that, provided with enough data, our algorithm is capable of identifying a pacemaker even when a weak signal is present in the data. Based on these results, we applied our method to DNA methylation data from human blood from individuals of various ages. Although the improvement in variance across sites between the UPM and MC was small, the results suggest that the existence of a pacemaker is highly significant. The PaceMaker results also suggest a decay in the rate of change in DNA methylation with age.

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