Δευτέρα, 9 Ιανουαρίου 2017

Impact of Race on Outcome of Patients Undergoing Rhythm Control of Atrial Fibrillation

Abstract

Racial disparities between African American (AA) and White patients have been documented in cardiovascular disease. We investigated whether these disparities exist in patients undergoing rhythm control for atrial fibrillation (AF). 5873 AF patients (241 AA) were followed to the endpoint of death, stroke, or AF recurrence. Invasive procedures for AF rhythm control were examined in both racial groups. Over a mean follow-up time of 40 months, AA patients had a higher adjusted risk of death [HR 1.39, 95% CI 1.00–1.92, p = 0.043] and stroke [HR 1.90, 95% CI 1.13–3.15, p = 0.013] but a lower risk of AF recurrence [HR 0.79, 95% CI 0.63–0.97, p = 0.026]. In addition, AA patients were less likely to undergo AF ablation (p = 0.006) or surgical maze (p = 0.032) procedures compared to White patients, possibly due to the lower rates of AF recurrence. Significant racial disparities exist in the management and outcomes of AA and White patients undergoing rhythm control management for AF.



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Quantification of postural stability in minimally disabled multiple sclerosis patients by means of dynamic posturography: an observational study

Multiple Sclerosis (MS) is a widespread progressive neurologic disease with consequent impairments in daily activities. Disorders of balance are frequent and equilibrium tests are potentially useful to quantif...

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Robot-aided developmental assessment of wrist proprioception in children

Several neurodevelopmental disorders and brain injuries in children have been associated with proprioceptive dysfunction that will negatively affect their movement. Unfortunately, there is lack of reliable and...

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Effects of stimulus mode and ambient temperature on cerebral responses to local thermal stimulation: An EEG study

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Publication date: Available online 10 January 2017
Source:International Journal of Psychophysiology
Author(s): Bin Lv, Chang Su, Lei Yang, Tongning Wu
The physiological responses to human thermal stimulation have been widely investigated, but most of them are mainly concerned about the whole body thermal stimulation. In this study, we investigated the effects of stimulus mode and ambient temperature on cerebral responses during local thermal stimulation on hand. The left hands were stimulated by metal thermostat based and thermostatic water based stimulators at different stimulated temperatures (38°C, 40°C, 42°C and 44°C) and different ambient temperatures (25°C and 32°C). EEG data were recorded over the whole brain during the experiments. Then the statistical comparisons were conducted on the EEG relative power among different experimental sessions. We observed that EEG activities were alternated between thermal stimulated periods and the baseline in all four frequency bands. And there was a higher percentage of delta band power in the right temporal and parietal regions under the ambient temperature of 32°C while compared to 25°C. In addition, the theta band activity under the metal based stimulation showed significantly higher EEG relative power than that under the water based stimulation over the whole brain. Compared with the water based stimulation, there was a lower EEG relative power of the beta band activity during the metal based stimulation in the bilateral frontal and right temporal regions. The experimental results suggested that the neural physiological responses in different EEG frequency bands were sensitive to different influence factors during the local hand thermal stimulation.



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Effects of exercise training on brain-derived neurotrophic factor in skeletal muscle and heart of rats post myocardial infarction

Abstract

Exercise training post myocardial infarction (MI) attenuates progressive left ventricle (LV) remodeling and dysfunction, but the peripheral stimuli induced by exercise which trigger these beneficial effects are still unclear. We investigated as possible mediators fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the skeletal muscle and heart. Male Wistar rats underwent either sham surgery or ligation of left descending coronary artery, and surviving MI rats were allocated to either sedentary (Sed-MI) or exercise group (ExT-MI). Exercise training was done for 4 weeks on a motor-driven treadmill. At the end, LV function was evaluated, and FNDC5 and BDNF mRNA and protein were assessed in soleus muscle, quadriceps, and non-, peri- and infarct areas of the LV. At 5 weeks post MI, FNDC5 mRNA was decreased in soleus muscle and all areas of the LV, but FNDC5 protein was increased in the soleus muscle and the infarct area. Mature BDNF (mBDNF) protein was decreased in the infarct area without change in mRNA. Exercise training attenuated the decrease in EF and the increase in LVEDP post MI. Exercise training had no effect on FNDC5 mRNA and protein, but increased mBDNF protein in soleus muscle, quadriceps and non-infarct area of the LV. mBDNF protein in the non-infarct area correlated positively with EF and inversely with LVEDP. In conclusion, mBDNF is induced by exercise training in skeletal muscle and non-infarct area of the LV, which may contribute to improvement of muscle dysfunction and cardiac function post MI.

This article is protected by copyright. All rights reserved



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Resting-state EEG gamma power and theta–gamma coupling enhancement following high-frequency left dorsolateral prefrontal rTMS in patients with depression

Repetitive transcranial magnetic stimulation (rTMS), which increases cortical excitability in focused brain regions, has emerged as a safe and effective treatment for depression (Janicak et al., 2008; Hadley et al., 2011). Conventional rTMS protocols target the left dorsolateral prefrontal cortex (DLPFC) with high-frequency stimulation (George et al., 2010). However, the neurophysiological mechanisms underlying the therapeutic effects of rTMS are not well understood. One of the potential mechanisms of action of rTMS is the restoration of altered neuroplasticity in the etiopathogenic neural circuits associated with depression such as the left DLPFC (Hoogendam et al., 2010) to normal levels (Kuhn et al., 2016).

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How to use an metered-dose inhaler with closed-mouth technique

The Chronic Obstructive Pulmonary Disease Foundation demonstrates how to properly use a metered-dose inhaler with a closed-mouth technique.

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How to use an metered-dose inhaler with closed-mouth technique

The Chronic Obstructive Pulmonary Disease Foundation demonstrates how to properly use a metered-dose inhaler with a closed-mouth technique.

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How to use an metered-dose inhaler with closed-mouth technique

The Chronic Obstructive Pulmonary Disease Foundation demonstrates how to properly use a metered-dose inhaler with a closed-mouth technique.

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Prove It: Epinephrine may have a role during resuscitation from cardiac arrest

Engine 12 and Medic 20 respond to a reported cardiac arrest in a small office building. Medic 20 was already mobile in the district and arrives on the scene within about two minutes. One of the patient's co-workers is performing CPR but there was no AED in the office.

Paramedic Martin verifies pulselessness, activates the built-in metronome on the monitor and takes over chest compressions from the bystander. Paramedic Turner places defibrillation pads on the patient's chest and reviews the patient's ECG. After confirming ventricular fibrillation, Turner begins to charge the defibrillator but directs Martin to continue chest compressions. When the defibrillator is charged, Turner signals Martin to clear and then delivers the shock. Martin resumes chest compressions.

Turner prepares the bag mask device and begins to ventilate the patient using 100 percent oxygen. The crew from Engine 12 arrives and the firefighters take over CPR from the medics. Martin quickly establishes an intraosseous line. With 15 seconds to go before the next rhythm check, Martin decides to administer one milligram of epinephrine.

At the next rhythm check, the monitor continues to display ventricular fibrillation. During the subsequent resuscitation attempt, the patient received three additional shocks, 300 milligrams of amiodarone, and one additional milligram of epinephrine. The patient achieves ROSC, but does not regain consciousness. Martin successfully intubates the patient's trachea and transports without complications.

In the emergency department, Martin and Turner discuss the call. Both medics realize that epinephrine administered before the second shock is a violation of the agency's clinical treatment guidelines. They report the violation to the agency's medical director, who is on duty in the emergency department. She tells them not to worry about it and that the earlier administration of the epinephrine may have actually helped the patient to achieve ROSC in the field.

Study review

A research team composed entirely of paramedics investigated whether the timing of vasopressor administration affected the likelihood of adult patients achieving ROSC in the field following an episode of out-of-hospital cardiac arrest [1]. The team from Western Carolina University searched a statewide EMS database for patients 18 years of age or older who suffered a bystander-witnessed, but non-trauma related cardiac arrest and received paramedic administration of epinephrine, vasopressin or both. Patients were not eligible for inclusion if a member of the EMS response team witnessed the onset of the cardiac arrest, because the care received before the arrest could have biased the results.

Researchers measured time in one-minute intervals beginning when the 911 operators received the emergency call. Interval measurement ended when the patient received the first dose of a vasopressor. The researchers also measured a number of other variables in order to gain a better understanding of how prehospital factors influence outcomes in cardiac arrest. However, this study is about whether earlier administration of a vasopressor improves the odds of a patient achieving ROSC.

Results

During the six-month study period, EMS personnel in North Carolina attempted resuscitation in 3,263 cases. Of those, 2,141 were excluded from analysis for reasons such as being an unwitnessed arrest, a pediatric patient under the age of 18 years or because the arrest occurred as the result of trauma. This left 1,122 patients for inclusion in the final analysis.

All patients in the sample received some form of vasopressor during the resuscitation attempt. The overwhelming majority (81.5 percent) received epinephrine as the only vasopressor while 17.6 percent received both epinephrine and vasopressin. Less than 1 percent of the patient received vasopressin as the only vasopressor.

About 48 percent (n = 542) of the patients in the sample achieved transient or sustained ROSC. Not surprisingly, those patients were more likely to present in a shockable rhythm and less likely to be intubated in the field when compared to those who did not achieve ROSC. Paramedics established IV or IO access and administered a vasopressor significantly sooner in the group who achieved ROSC.

What is interesting is the relationship the researchers found between when paramedics administered the vasopressor and whether the patient achieved ROSC. Using a statistical process called logistic regression, researchers were able to isolate the effects that single variables have on the outcome of interest. In this analysis, researchers found that for every one-minute delay in vasopressor administration measured from the moment the 911 center received the emergency call, there was a 4 percent decrease in the odds of the patient achieving ROSC.

What this means for you

Animal studies have demonstrated improved short-term survival following the administration of intravenous epinephrine [2,3]. Unfortunately, clinical trials have not demonstrated improved long-term survival or neurologically favorable outcomes associated with the prehospital administration of epinephrine in patients who suffer out-of-hospital cardiac arrest [4-12].

One reason for the difference in effectiveness between animal studies and clinical trials may be related to how quickly after the onset of cardiac arrest rescuers administer the first dose of epinephrine. On average, time to first drug administration in animal studies is about 9.5 minutes, compared to 19.4 minutes for clinical trials [13]. Similarly, a systematic review of clinical studies between 1990 and 2005 found the time from dispatch to first drug administration ranges between 10 and 25 minutes, with an average of about 18 minutes [14].

Some have speculated the failure to demonstrate a survival advantage related to drug administration may actually be a reflection of this delay rather than the ineffectiveness of the drug action itself. This changes the question from "Does epinephrine administration improve the odds of survival" to "Does epinephrine only improve the odds of survival if given early"".

Retrospective analysis of large cardiac arrest registry in Japan (> 212,000 cases) found the adjusted odds of achieving neurologically intact survival increased by 39 percent when EMS personnel administered epinephrine early [15]. For that study, researchers defined early as drug administration within the first ten minutes after EMS personnel began chest compressions. Since the study did not consider EMS response time in the analysis, which is often around five to eight minutes, it is difficult to interpret the significance of the results.

Similarly, another study found a 92 percent increased odds of achieving ROSC if epinephrine was given within the first ten minutes measured from the moment the 911 center receives the call [16]. Advanced airway control procedures before epinephrine administration delayed the time to first drug administration and significantly reduced ROSC rates.

Although much of the delay to earlier drug administration by paramedics results from response intervals, together these studies suggest EMS agencies and medical directors must find ways to reduce or eliminate barriers to earlier drug administration once paramedics are on scene. One strategy may be for paramedics to use IO rather than IV access routes. An animal model suggests EMS personnel can administer epinephrine about 6 minutes sooner by using an IO rather than an IV [17].

An interesting proposition is whether alternative administration route might offer even greater time savings and clinical improvement. A pilot study of cardiac arrest using piglets weighing less than 6 kilograms found ROSC rates were not significantly different between the animals who received epinephrine via IM or IV routes [18]. However, both groups had significantly greater ROSC rates when compared to animals who received placebo. Although promising, this study was limited by two very important factors. First, the size of the piglets makes the results more applicable to children than to adults. Also, the researchers induced cardiac arrest in these animals by infusing a local anesthetic until the animal achieved cardiovascular collapse. This etiology is significantly different from factors that cause cardiac arrest in most human adults and children. However, if researchers could reproduce these results in asphyxial or other causes of arrest, it is reasonable to think strategies targeting early IM administration of epinephrine could further improve survival rates following cardiac arrest.

One of those strategies could be the development of an epinephrine auto injector containing a higher-dose than is currently available. These auto injectors could be placed with AEDs, making early administration possible by first responders and even bystanders.

Limitations of the present study

One significant limitation of the present study is the retrospective nature of the analysis. The lack of data control inherent with retrospective analysis always introduces the possibility that other unmeasured variables may explain the results. For example, the registry used in this study did not measure CPR quality, which includes significant predictors of survival such as chest compression fraction, depth, and rate. Any or all of those factors could have influenced the outcome of the study.

The accuracy of the registry data also represents a limitation to the study. There is no way to know whether the time points for first drug administration represent estimates made by the paramedics after the call was complete or whether they were recorded by a time keeper at the actual moment of drug administration in the field. One recent study comparing documentation of critical care interventions in a patient care record to time-stamped audio recordings of 192 patients who suffered an out-of-hospital cardiac arrest found a median difference of two minutes between when paramedics recorded completion of the intervention and when the intervention actually occurred [19].

Summary for EMS providers

This study found the odds of achieving ROSC decline by 4 percent for every 1-minute delay in vasopressor administration. This decline challenges EMS agencies to eliminate any factors that delay drug administration once paramedics arrive on the scene. What is significant about the present study is it is one of the first to measure the time to epinephrine administration as a continuous variable rather than simply a dichotomous variable (less than or more than ten minutes). This provides a clearer picture of the time-dependant nature of epinephrine administration and demonstrated that even within the first ten minutes, epinephrine should be given as early as possible.

References
1. Hubble, M. W., Johnson, C., Blackwelder, J., Collopy, K., Houston, S., Martin, M., Wilkes, D., & Wiser, J. (2015). Probability of return of spontaneous circulation as a function of timing of vasopressor administration in out-of-hospital cardiac arrest. Prehospital Emergency Care, 19(4), 457-463. doi:10.3109/10903127.2015.1005262

2. Palácio, M. Â., Paiva, E. F., Azevedo, L. C., & Timerman, A. (2013). Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo [Article in English, Portuguese]. Arquivos Brasileiros de Cardiologia, 101(6), 536-544. doi:10.5935/abc.20130213

3. Zuercher, M., Kern, K. B., Indik, J. H., Loedl, M., Hilwig, R. W., Ummenhofer, W., Berg, R. A., & Ewy, G. A. (2011). Epinephrine improves 24-hour survival in a swine model of prolonged ventricular fibrillation demonstrating that early intraosseous is superior to delayed intravenous administration. Anesthesia and Analgesia, 112(4), 884-890. doi:10.1213/ANE.0b013e31820dc9ec

4. Arrich, J., Sterz, F., Herkner, H., Testori, C., & Behringer, W. (2012). Total epinephrine dose during asystole and pulseless electrical activity cardiac arrests is associated with unfavourable functional outcome and increased in-hospital mortality. Resuscitation, 83(3), 333-337. doi:10.1016/j.resuscitation.2011.10.027

5. Hagihara, A., Hasegawa, M., Abe, T., Nagata, T., Wakata, Y., & Miyazaki, S. (2012). Prehospital epinephrine use and survival among patients with out-of- hospital cardiac arrest. Journal of the American Medical Association, 307(11), 1161–1168. doi:10.1001/ jama.2012.294

6. Holmberg, M., Holmberg, S., & Herlitz, J. (2002). Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden. Resuscitation, 54(1), 37–45. doi:10.1016/S0300-9572(02)00048-5

7. Jacobs, I. G., Finn, J. C., Jelinek, G. A., Oxer, H. F., & Thompson, P. L. (2011). Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomized double-blind placebo-controlled trial. Resuscitation, 82(9), 1138–1143. doi:10.1016/j.resuscitation.2011.06.029

8. Koscik, C., Pinawin, A., McGovern, H., Allen, D., Media, D. E., Ferguson, T., Hopkins, W., Sawyer, K. N., Boura, J., & Swor, R. (2013). Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest. Resuscitation, 84(7), 915-920. doi:10.1016/j.resuscitation.2013.03.023

9. Machida, M., Miura, S., Matsuo, K., Ishikura, H., & Saku, K. (2012). Effect of intravenous adrenaline before arrival at the hospital in out-of-hospital cardiac arrest. Journal of Cardiology, 60(6), 503–507. doi:10.1016/j.jjcc.2012.07.001

10. Olasveengen, T. M., Wik, L., Sunde, K., & Steen, P. A. (2012). Outcome when adrenaline (epinephrine) was actually given vs not given—post hoc analysis of a randomized clinical trial. Resuscitation, 83(3), 327-332. doi:10.1016/j.resuscitation.2011.11.011

11. Ong, M. E., Tan, E. H., Ng, F. S., Panchalingham, A., Lim, S. H., Manning, P. G., Ong, V. Y. K., Lim, S. H. C., Yap, S., Tham, L. P., Ng, K. S., & Venkataraman, A. (2007). Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Annals of Emergency Medicine, 50(6), 635–642. doi:10.1016/j.annemergmed.2007.03.028

12. Tanaka, H., Takyu, H., Sagisaka, R., Ueta, H., Shirakawa, T., Kinoshi, T., Takahashi, H., Nakagawa, T., Shimazaki, S., Ong Eng Hock, M. (2016). Favorable neurological outcomes by early epinephrine administration within 19 minutes after emergency medical service call for out-of-hospital cardiac arrest patients. American Journal of Emergency Medicine, [Epub ahead of print]. doi:10.1016/j.ajem.2016.08.026

13. Reynolds, J. C., Rittenberger, J. C., & Menegazzi, J. J. (2007). Drug administration in animal studies of cardiac arrest does not reflect human clinical experience. Resuscitation, 74(1), 13–26. doi:10.1016/j.resuscitation.2006.10.032

14. Rittenberger, J. C., Bost, J. E., & Menegazzi, J. J. (2006). Time to give the first medication during resuscitation in out-of-hospital cardiac arrest. Resuscitation, 70(2), 201–206. doi:10.1016/j.resuscitation.2005.12.006

15. Nakahara, S., Tomio, J., Nishida, M., Morimura, N., Ichikawa, M., & Sakamoto, T. (2012). Association between timing of epinephrine administration and intact neurologic survival following out-of-hospital cardiac arrest in Japan: A population-based prospective observational study. Academic Emergency Medicine, 19(7), 782–792. doi:10.1111/j.1553-2712.2012.01387.x

16. Cantrell, C. L. Jr., Hubble, M. W., & Richards, M. E. (2013). Impact of delayed and infrequent administration of vasopressors on return of spontaneous circulation during out-of-hospital cardiac arrest. Prehospital Emergency Care, 17(1), 15-22. doi:10.3109/10903127.2012.702193

17. Mader, T. J., Coute, R. A., Kellogg, A. R., & Nathanson, B. H. (2016). Blinded evaluation of combination drug therapy for prolonged ventricular fibrillation using a swine model of sudden cardiac arrest. Prehospital Emergency Care, 20(3), 390-398. doi:10.3109/10903127.2015.1086848

18. Mauch, J., Ringer, S. K., Spielmann, N., & Weiss, M. (2013). Intravenous versus intramuscular epinephrine administration during cardiopulmonary resuscitation - a pilot study in piglets. Paediatric Anaesthesia, 23(10), 906-912. doi:10.1111/pan.12149

19. Frisch, A., Reynolds, J. C., Condle, J., Gruen, D., & Callaway, C. W. (2014). Documentation discrepancies of time-dependent critical events in out of hospital cardiac arrest. Resuscitation, 85(8), 1111–1114. doi:10.1016/j.resuscitation.2014.05.002



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Government, public has to stop treating EMS as a second class public safety

Field care and ambulance transport has a long history of volunteerism in the United States. For nearly a hundred years, citizens have stopped whatever they were doing and responded to calls for help from fellow community members. As modern emergency medical services has evolved, many rescue squads have tried to keep up with modernization efforts, purchasing new equipment, ambulances and upgrading the training of their personnel.

But times have changed since the mid-20th century. With most towns being bedroom communities for business and manufacturing hubs, the idea of one working within a couple of miles of the ambulance station has become an anachronism. Even if it were true, most people are unable to leave their jobs at a moment's notice and be gone for a couple of hours or more.

The experience of this Connecticut town is nothing new. Volunteerism in EMS has been on the decline since the late 1970s. Numerous news articles have reported on the difficulty of getting crews to emergency medical calls, often having to send the neighboring jurisdictions' units to the incident. Dispatchers often joke about "Bermuda Triangles," where a call for ambulance response will be sent from one squad to the next, in the hopes that at some point a unit will respond.

You would think that such a situation would be not tolerated by the community. Most citizens expect that if they are having a heart attack or were hit by a car, that an ambulance would arrive at their scene within just a few minutes. Scores of reality and fictional television shows have created that expectation of immediate response. The fact is, in many parts of this country, that simply doesn't exist.

Public doesn't know EMS reality

In fact, that idyllic vision of dedicated community-based medical responders hasn't existed for decades in many communities. It makes me wonder why that's the case. Such a situation would seem to result in some demand by the citizenry to local officials to modernize and improve their medical response system. If only the citizens and elected officials knew more about EMS.

And that's the issue. Most folks don't realize how fragile their EMS system is from personnel departures, funding losses and inadequate reimbursement for patient transport. I don't blame them for being ignorant — most people will live their entire lives without ever having to ride in the back of an ambulance. All they see is a unit roll by them a couple of times a year, with lights flashing and sirens blaring, and believe that they are safe.

When the annual fund drive occurs, many people will throw a few dollars into the bucket or boot. Some even tolerate a tax assessment for public safety, believing that all of those efforts provide them the best medical care and transportation system. With a few exceptions, that's hardly the truth.

Maintaining a social club

That's because in many cases, volunteer squads are really social clubs. Members with similar interests get together and spend their time building a common understanding among each other. They become friends, know each other's families and consider themselves as a big family. Clubs are the epitome of how humans socially engage with one another outside of biological family units.

It's a wonderful system until the social club begins to reinforce malignancy. As volunteerism decays, rather than coming up with solutions that benefit the community, squads try to preserve the past and protect what they have. We'll get more volunteers. We'll incentivize shift staffing. We'll lower the training standard. We'll do anything to keep what we have.

The idea that nothing else will work in their region is refuted by the many EMS systems that have transitioned to combination or career systems. This is where local government officials must work hand-in-hand with failing EMS agencies and develop a long-term solution that works for them. It often means to stop thinking provincially, that every town is its own fiefdom. County and regional systems work well, reducing administrative overhead while providing a stable number of responding units. Whether it's publicly funded, privately contracted or a combination of the two is not relevant. The fact is that an EMS agency needs to be and can be held accountable for its efforts is critical.

I began my career as a volunteer almost 35 years ago. I appreciated and am quite fond of the time I spent volunteering in the community. As I matured in the profession, it became increasingly apparent that I had to move on, in order to remain competent and keep up with the changes in the industry. Volunteer EMS needs to do the same. I agree that in some places in the country, having volunteers is needed because of sheer necessity. But that applies only to very few systems. Most squads must take a hard, long look at what is best for their communities and take steps to strengthen their part of the public safety net.



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Is some EMS better than no EMS?

Volunteer EMS agencies can be the best option for 911 services in many areas, but response must be guaranteed

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Frequent Flyers: If Calvin grew up to become a paramedic

See all of Lenwood Brown's comics.



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Government, public has to stop treating EMS as a second class public safety

Field care and ambulance transport has a long history of volunteerism in the United States. For nearly a hundred years, citizens have stopped whatever they were doing and responded to calls for help from fellow community members. As modern emergency medical services has evolved, many rescue squads have tried to keep up with modernization efforts, purchasing new equipment, ambulances and upgrading the training of their personnel.

But times have changed since the mid-20th century. With most towns being bedroom communities for business and manufacturing hubs, the idea of one working within a couple of miles of the ambulance station has become an anachronism. Even if it were true, most people are unable to leave their jobs at a moment's notice and be gone for a couple of hours or more.

The experience of this Connecticut town is nothing new. Volunteerism in EMS has been on the decline since the late 1970s. Numerous news articles have reported on the difficulty of getting crews to emergency medical calls, often having to send the neighboring jurisdictions' units to the incident. Dispatchers often joke about "Bermuda Triangles," where a call for ambulance response will be sent from one squad to the next, in the hopes that at some point a unit will respond.

You would think that such a situation would be not tolerated by the community. Most citizens expect that if they are having a heart attack or were hit by a car, that an ambulance would arrive at their scene within just a few minutes. Scores of reality and fictional television shows have created that expectation of immediate response. The fact is, in many parts of this country, that simply doesn't exist.

Public doesn't know EMS reality

In fact, that idyllic vision of dedicated community-based medical responders hasn't existed for decades in many communities. It makes me wonder why that's the case. Such a situation would seem to result in some demand by the citizenry to local officials to modernize and improve their medical response system. If only the citizens and elected officials knew more about EMS.

And that's the issue. Most folks don't realize how fragile their EMS system is from personnel departures, funding losses and inadequate reimbursement for patient transport. I don't blame them for being ignorant — most people will live their entire lives without ever having to ride in the back of an ambulance. All they see is a unit roll by them a couple of times a year, with lights flashing and sirens blaring, and believe that they are safe.

When the annual fund drive occurs, many people will throw a few dollars into the bucket or boot. Some even tolerate a tax assessment for public safety, believing that all of those efforts provide them the best medical care and transportation system. With a few exceptions, that's hardly the truth.

Maintaining a social club

That's because in many cases, volunteer squads are really social clubs. Members with similar interests get together and spend their time building a common understanding among each other. They become friends, know each other's families and consider themselves as a big family. Clubs are the epitome of how humans socially engage with one another outside of biological family units.

It's a wonderful system until the social club begins to reinforce malignancy. As volunteerism decays, rather than coming up with solutions that benefit the community, squads try to preserve the past and protect what they have. We'll get more volunteers. We'll incentivize shift staffing. We'll lower the training standard. We'll do anything to keep what we have.

The idea that nothing else will work in their region is refuted by the many EMS systems that have transitioned to combination or career systems. This is where local government officials must work hand-in-hand with failing EMS agencies and develop a long-term solution that works for them. It often means to stop thinking provincially, that every town is its own fiefdom. County and regional systems work well, reducing administrative overhead while providing a stable number of responding units. Whether it's publicly funded, privately contracted or a combination of the two is not relevant. The fact is that an EMS agency needs to be and can be held accountable for its efforts is critical.

I began my career as a volunteer almost 35 years ago. I appreciated and am quite fond of the time I spent volunteering in the community. As I matured in the profession, it became increasingly apparent that I had to move on, in order to remain competent and keep up with the changes in the industry. Volunteer EMS needs to do the same. I agree that in some places in the country, having volunteers is needed because of sheer necessity. But that applies only to very few systems. Most squads must take a hard, long look at what is best for their communities and take steps to strengthen their part of the public safety net.



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Role of Nhp6 and Hmo1 in SWI/SNF occupancy and nucleosome landscape at gene regulatory regions

Publication date: Available online 9 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Matias I. Hepp, Michaela Smolle, Cristian Gidi, Roberto Amigo, Nicole Valenzuela, Axel Arriagada, Alejandro Maureira, Madelaine M. Gogol, Marcela Torrejón, Jerry L. Workman, José L. Gutiérrez
Diverse chromatin modifiers are involved in regulation of gene expression at the level of transcriptional regulation. Among these modifiers are ATP-dependent chromatin remodelers, where the SWI/SNF complex is the founding member. It has been observed that High Mobility Group (HMG) proteins can influence the activity of a number of these chromatin remodelers. In this context, we have previously demonstrated that the yeast HMG proteins Nhp6 and Hmo1 can stimulate SWI/SNF activity. Here, we studied the genome-wide binding patterns of Nhp6, Hmo1 and the SWI/SNF complex, finding that most of gene promoters presenting high occupancy of this complex also display high enrichment of these HMG proteins. Using deletion mutant strains we demonstrate that binding of SWI/SNF is significantly reduced at numerous genomic locations by deletion of NHP6 and/or deletion of HMO1. Moreover, alterations in the nucleosome landscape take place at gene promoters undergoing reduced SWI/SNF binding. Additional analyses show that these effects also correlate with alterations in transcriptional activity. Our results suggest that, besides the ability to stimulate SWI/SNF activity, these HMG proteins are able to assist the loading of this complex onto gene regulatory regions.

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Chromatin Dynamics Regulate Mesenchymal Stem Cell Lineage Specification and Differentiation to Osteogenesis

Publication date: Available online 8 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Hai Wu, Jonathan A.R. Gordon, Troy W. Whitfield, Phillip W.L. Tai, Andre J. van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian
Multipotent mesenchymal stromal cells (MSCs) are critical for regeneration of multiple tissues. Epigenetic mechanisms are fundamental regulators of lineage specification and cell fate, and as such, we addressed the question of which epigenetic modifications characterize the transition of nascent MSCs to a tissue specific MSC-derived phenotype. By profiling the temporal changes of seven histone marks correlated to gene expression during proliferation, early commitment, matrix deposition, and mineralization stages, we identified distinct epigenetic mechanisms that regulate transcriptional programs necessary for tissue-specific phenotype development. Patterns of stage-specific enrichment of histone modifications revealed distinct modes of repression and activation of gene expression that would not be detected using single endpoint analysis. We discovered that at commitment, H3K27me3 is removed from genes that are upregulated and is not acquired on downregulated genes. Additionally, we found that the absence of H3K4me3 modification at promoters defined a subset of osteoblast-specific upregulated genes, indicating acquisition of acetyl modifications drive activation of these genes. Significantly, loss or gain of H3K36me3 was the primary predictor of dynamic changes in temporal gene expression. Using unsupervised pattern discovery analysis the signature of osteogenic-related histone modifications identified novel functional cis regulatory modules associated with enhancer regions that control tissue-specific genes. Our work provides a cornerstone to understand the epigenetic regulation of transcriptional programs that are important for MSC lineage commitment and lineage, as well as insights to facilitate MSC-based therapeutic interventions.



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Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia

Abstract

POP1 is a large protein common to the RNase-MRP and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8 s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals demonstrate the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

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Resting-state EEG gamma power and theta–gamma coupling enhancement following high-frequency left dorsolateral prefrontal rTMS in patients with depression

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Publication date: Available online 9 January 2017
Source:Clinical Neurophysiology
Author(s): Yoshihiro Noda, Reza Zomorrodi, Takashi Saeki, Tarek K. Rajji, Daniel M. Blumberger, Zafiris J. Daskalakis, Motoaki Nakamura
ObjectiveWe aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression.MethodsThirty one patients diagnosed with depression included in the present study. Resting-state gamma power and theta–gamma coupling (TGC) were calculated before and after a course of rTMS. We explored the relationship among gamma power, TGC, and clinical/cognitive outcomes as measured with the Hamilton Rating Scale for Depression (HAM-D17), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST).ResultsFollowing rTMS, depressed patients demonstrated significant increases of resting gamma power at the F3 and F4 electrode sites and resting TGC at the C3 and T3 electrode sites. Furthermore, the increased gamma power at the F3 electrode site was significantly correlated with improved score on the HAM-D17 and BDI, while the increased TGC at the C3 electrode site was significantly correlated with reduced number of errors on the WCST.ConclusionThus, resting-state gamma power and TGC may represent potential biomarkers of depression associated with therapeutic effects of rTMS.SignificanceResting-state EEG may provide potential biomarkers related to therapeutic effects of rTMS.



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