Primecuts – This Week In The Journals

October 25, 2016

depressionBy Danielle Brewington MD, MS

Peer Reviewed 

As October draws to a close, the presidential debates have wrapped up and most people are bracing until the end of the political season. Many of the revelations in politics this week have left the entire nation depressed, so first up for discussion this week is an article about how to predict if anti-depressants will work in patients presenting with MDD.

fMRI and History Predict Anti-Depressant Effectiveness1

Researchers have shown that the amygdala plays an important role in depression in animal and human models. There is also evidence that early life stress (ELS) can predict who is likely to develop depressive symptoms. ELS is also known to have an impact on the amygdala. While the reciprocal relationship between ELS and amygdala abnormalities and the role it plays in developing depression has been investigated, these factors have never been used to predict clinical outcomes in response to anti-depressant therapy. This week in Proceedings of the National Academy of Sciences, researchers evaluated the combined predictive capability of ELS and fMRI.

Neuro-imaging and ELS history was gathered on 70 patients who presented with Major Depressive Disorder. The patients were evaluated based on previous amygdala studies that focused on enhancement on fMRI to happy or fearful images. ELS history was used to categorize the patients into low, moderate, or high stress groups. The patients and their medication was followed until they achieved remission or the end of the study was reached.

The results demonstrated that combining fMRI data from happy and fearful responses along with ELS data was highly predictive of which patients would experience MDD remission on anti-depressant therapy with 89% sensitivity and 88% specificity. History gathering and fMRI are tools that are available to physicians and could be utilized by psychiatrists as well as those considering a referral to psychiatrists, since many primary care physicians are often first line responders for initial presentations of MDD.

Platelet transfusions in GI Bleeders on Dual Anti-platelet Therapy2

Anti-platelet therapy has had a tremendous impact on cardiac events in patient with heart disease. Gastrointestinal bleed (GIB) is a known potentially fatal side effect of mono and dual antiplatelet therapy. Since platelets are permanently inactivated by aspirin and clopidogrel, an option to combat this risk in a bleeding patient is platelet transfusion. While this is a good idea in theory, the outcomes of platelet infusions in this population have not previously been studied.

A new retrospective case-control study, in Clinical Gastroenterology and Hepatology, examined 204 patients admitted for GI bleed while on single or dual anti-platelet therapy. The intent of the study was to determine if platelets contributed the theoretical benefit in preventing rebleeds behind the American Society for Gastrointestinal Endoscopy recommendation. Importantly, the researchers also investigated obvious potential sequelae in this population including myocardial infarction (MI), mortality, length of stay, and major adverse cardiovascular events (MACE). Cases and controls were matched based on sex, age, and G.I. bleed location. Of note, all patients had to have a platelet count greater than 100,000 to rule out platelet infusion indicated for thrombocytopenia.

Their results showed that patients who received platelet transfusions had increased rebleeding rather than decreased, 14% in cases compared to 8% in controls. Predictably, thrombotic outcomes (MACE, MI) were increased after receiving platelets. Secondary to these issues, mortality and length of stay were also increased. The researchers unexpectedly found that deaths were more likely due to GIB rather than cardiac events, contrary to previously published data. While the researchers attempted to control for confounders, there is one important consideration. It appears that platelets were given to patients who presented with more severe initial GI bleeds, which may have put them at higher risk from the outset. Due to a lack of evidence of any benefit from platelet transfusions, the authors recommend a more conservative approach to patient presenting with GIB on anti-platelet therapy that includes early endoscopy with source control and PPIs as needed.

Clinical Importance of Short Episodes of Afib and Atach 3

Patients with implanted cardiac devices (ICDs or pacemakers) trigger their devices, causing them at a minimum to document electrical activity and at most deliver electricity to normalize the rhythm. Due to the high volume of data generated by these devices, researchers have previously boot-strapped the results by arbitrarily setting time limits to identify true arrhythmias (usually >5 min was deemed likely to be true arrhythmia). The issue with this method is the high-false positive rate in addition to lack of evaluation of clinical importance of events lasting less than the arbitrary minimum. A new study published in Circulation investigates this previously ignored set of events to determine their clinical importance.

The RATE researchers collected all device data for over 5000 patients in a prospective study over 2 years. Extensive demographic data and prospective clinical events were collected for all patients. All device ECG recordings were evaluated by physicians for a subset of patients including a 600 patient random sample in addition to selected “case-patients” (556 patients total who experienced symptomatic atrial arrhythmias, heart failure, stroke or TIA, syncope, and death.) and their matched controls (1112 total). Interestingly the researchers were not concerned with timing of captured atrial fibrillation or atrial tachycardia (AF/AT), but instead by the length of diagnosed arrhythmia on the device recording. As such, “short AF/AT” was on average 10-12 seconds and terminated within the recording strip, and “long AF/AT” had no time limit but was defined as unremitting past the end of the recording.

The end result was a comparison of groups with recorded AF/AT that was much shorter than previously studied groups. Interestingly the data showed that short AF/AT had no significant impact on adverse events, hospitalization for AF or heart failure, stroke, and all-cause mortality. Long AF/AT was associated with hospitalization for AF (OR 2.78, P=.032 in pacemaker group; OR 6.57, p=.0001 in ICD group), all adverse events (OR 1.65, p=.005 in pacemaker group), and all-cause mortality (OR 1.86, p=.009) but not with stroke or hospitalization for heart failure. Of note, 50% of patients in the random sample experienced at least one episode of AF/AT during the follow-up period, which was twice the rate that was expected based on Framingham study data. These results are especially useful to physicians practicing in hospitals that may be evaluating patients on telemetry for the first time. This study provides evidence that patients with short episodes of AF/AT are not a cause for concern. Furthermore, there is a lack of evidence that long AF/AT was associated with stroke in this population. This data calls into question the practice of placing all patients with AF/AT on anticoagulation. The greatest limitation of this study is the incomplete picture provided about the long AF/AT group. While it is clear that their episodes did not self-terminate within a single device recording, it is impossible to know the average length of their episodes and whether they cross the previously studied 5 minute threshold that has been shown to be associated with elevated risk. The most important conclusions from this study are about the short AF/AT group which are not at elevated risk for clinical events nor do they have an elevated risk of progressing to long AF/AT.

Neurostimulation for Central Sleep Apnea 4

Central sleep apnea, similar to obstructive sleep apnea, is associated with adverse cardiac outcomes, such as ischemia and arrythmias. There is little data for using continuous positive pressure therapy in central sleep apnea, which is most often associated with heart failure. Central sleep apnea is an independent condition that affects quality of life measures, but hasn’t been considered as a separate condition to treat. The researchers in a new Lancet article set out to evaluate an alternative therapy to reduce apneic episodes due to central sleep apnea in a randomized trial. 

In total, 151 patients were randomized to either a control or device group. All patients completed a sleep study and were required to have 20 apneic events per hour and less than 20% obstructive apneic index to participate. Neurostimulators were implanted in the device group and turned on after one month. The devices were designed to cause gradual diaphragm contraction, simulating normal breathing rather than hiccup-style gasps. The stimulators were automatically activated at a scheduled time each night when the patient was sleeping and in a reclined positioned, which was determined by sensors in the device.

The goal of the study was to evaluate the effectiveness of the device in achieving a 50% or greater reduction in apnea-hypopnic index (episodes per hour) at 6 months compared to initial polysomnography. In the device group, 51% of patients achieved a 50% or greater reduction in API compared to 11% in the control group. Patients also experienced significantly improved rates of oxygen desaturation, REM sleep, and daytime sleepiness. There was a 97% success rate of device placement on the first attempt with 91% experiencing no serious adverse events after 12 months. Since the device is implanted this therapy may be an option for central sleep apnea that is limited by adherence and discomfort.

Mini-cuts:

An egg a day may actually keep stroke away.5An analysis of studies between 1982 and 2014 of over 500,000 people showed eggs, commonly thought to be an unhealthy source of cholesterol, actually reduce stroke risk by 12% and have no impact on coronary heart disease. Congruently, recent guidelines have dropped recommendations to avoid dietary cholesterol and instead now focus on dietary fat.

If you’ve added a fitness tracker to your health regimen, the data says it probably isn’t helping.6

A 2 year randomized study of 470 young adults showed that a diet and exercise program plus electronic fitness trackers resulted in less weight loss than the diet and exercise program alone.

Thinking of extubating that PACU patient overnight, new data says it’s better to wait.7A study of over 97,000 intubated adults across 165 ICUs demonstrated that overnight extubations are associated with increased mortality and reintubation. Overnight extubation was more likely to be tried in patients admitted from the operating room or PACU.

Culture negative sepsis is on the rise and that’s bad news for patients.8 The rate of culture negative severe sepsis increased 28% (43.5% up from 33.9%) from 2000-2010. This diagnosis is an independent predictor of death with a 75% excess risk of death compared to culture positive severe sepsis.

Dr. Danielle Brewington is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Neha Jindal, internal medicine resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References 

  1. Goldstein-Piekarski AN, Korgaonkar MS, Green E, et al. Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. Proceedings of the National Academy of Sciences. October 2016:201606671. doi:10.1073/pnas.1606671113.  http://www.pnas.org/content/113/42/11955
  2. Zakko L, Rustagi T, Douglas M, Laine L. No Benefit From Platelet Transfusion for Gastrointestinal Bleeding in Patients Taking Antiplatelet Agents. Clinical Gastroenterology and Hepatology. July 2016. doi:10.1016/j.cgh.2016.07.017.  http://www.sciencedirect.com/science/article/pii/S1542356516304384
  3. Swiryn S, Orlov MV, Benditt DG, et al. Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population: Results from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes. Circulation. 2016;134(16):1130-1140. doi:10.1161/CIRCULATIONAHA.115.020252.http://circ.ahajournals.org/content/134/16/1130
  4. Costanzo MR, Ponikowski P, Javaheri S, et al. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet. 2016;388(10048):974-982. doi:10.1016/S0140-6736(16)30961-8.  http://www.sciencedirect.com/science/article/pii/S0140673616309618
  5. Alexander DD, Miller PE, Vargas AJ. Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke. Journal of the …. 2016:1-13. doi:10.1080/07315724.2016.1152928. http://www.tandfonline.com/doi/abs/10.1080/07315724.2016.1152928
  6. Jakicic JM, Davis KK, Rogers RJ, et al. Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss. JAMA. 2016;316(11):1161. doi:10.1001/jama.2016.12858.  http://jamanetwork.com/journals/jama/fullarticle/2553448
  7. Gershengorn HB, Scales DC, Kramer A, Wunsch H. Association Between Overnight Extubations and Outcomes in the Intensive Care Unit. JAMA Internal Medicine. September 2016. doi:10.1001/jamainternmed.2016.5258. http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2547203
  8. Gupta S, Sakhuja A, Kumar G, McGrath E, Nanchal RS, Kashani KB. Culture Negative Severe Sepsis – Nationwide Trends and Outcomes. Chest. September 2016. doi:10.1016/j.chest.2016.08.1460. http://www.sciencedirect.com/science/article/pii/S0012369216589569

 

 

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