Friday, March 22, 2013

Lit Bits: March 22, 2013

From the recent medical literature...

1. Interpreting RBCs in LP: Distinguishing True SAH From Traumatic Tap 

Czuczman AD, et al. Acad Emerg Med. 2013;20:247-256.  

Objectives: The study purpose was to determine the optimal use of lumbar puncture (LP) red blood cell (RBC) counts to identify subarachnoid hemorrhage (SAH) when some blood remains in the final tube. 

Methods: A case series was performed at a tertiary emergency department (ED). Records of 4,496 consecutive adult patients billed for LPs between 2001 and 2009 were reviewed. Inclusion criteria were headache (HA), final tube RBCs ≥ 5, and neurovascular imaging within 2 weeks of the visit. Demographics, relevant history and physical examination components, LP results, and neuroimaging findings were recorded for 280 patients. True-positive (TP) and true-negative (TN) SAH were strictly defined. Primary outcomes were the areas under the receiver operating characteristic curves (AUC) for final tube RBC count, differential RBC count between the final and initial tubes, and absolute differential RBC count between the final and initial tubes divided by the mean RBC count of the two tubes (also called the percent change in RBC count). 

Results: There were 26 TP and 196 TN results; 58 patients were neither. The TP group consisted of 19 patients with visible or possible SAH on imaging (17 on noncontrast head computed tomography [CT; 12 definite and five possible] and two on magnetic resonance imaging), six with xanthochromia and a vascular lesion (aneurysm or arteriovenous malformation [AVM] greater than 2 mm), and one with xanthochromia and polymerase chain reaction (PCR)-positive meningitis. As a test for SAH, final tube RBC AUC was 0.85 (95% confidence interval [CI] = 0.80 to 0.91). Interval likelihood ratios (LRs) for final tube RBC count were LR 0 (95% CI = 0 to 0.3) for RBCs below 100, LR 1.6 (95% CI = 1.1 to 2.3) for RBCs between 100 and 10,000, and LR 6.3 (95% CI = 4.8 to 23.4) for RBCs above 10,000. Differential RBC count was not associated with SAH, with AUC 0.45 (95% CI = 0.31 to 0.60). However, the percent change in RBC count between the final and initial tubes had an AUC 0.84 (95% CI = 0.78 to 0.90), and the optimal test threshold for SAH was 0.63, with positive LR 3.6 (95% CI = 2.7 to 4.7) and negative LR 0.10 (95% CI = 0.03 to 0.4) for percent change less than 63% and  greater than 63%, respectively. This test added additional independent information to the final tube RBC count based on improved logistic regression model fit and discriminatory ability as measured by the LR test and c statistic, respectively. 

Conclusions: Final LP tube RBC count and the percent change in RBC count, but not the simple differential count between the final and initial tubes, were associated with SAH. In this sample, there were no patients with SAH who had RBCs below 100 in the final tube, and RBCs above 10,000 increased the odds of SAH by a factor of 6. 

2. Stress Testing Has Low Yield in Young Adults with Chest Pain  

Observation and further testing yielded few abnormal test results, and most were false-positive.  

Ely S, et al. J Emerg Med. 2013;44:306-312.  

Background: Determining which patients presenting to the Emergency Department (ED) require further work-up for acute coronary syndrome (ACS) can be difficult. The utility of routine observation for cardiac testing in low-risk young adult patients has been questioned.

Study Objectives: We investigated the rate of positive findings yielded by routine cardiac observation unit work-up in patients aged 40 years or younger. 

Methods: This was a retrospective observational cohort study of patients aged 18–40 years who were evaluated for ACS in an ED-based observation unit. Data were collected by trained abstractors from electronic medical records. 

Results: A total of 362 patients met inclusion criteria. Of those, 239 received stress testing, yielding five positive and nine indeterminate results. One other patient had acute troponin elevation while under observation. The positive stress test patients and troponin-elevated patient underwent cardiac angiography. Only one positive stress test patient showed significant coronary stenosis and received coronary interventions. In follow-up data, one patient had an adverse cardiac outcome within 1 year of index visit, but no coronary interventions. Thus, only 3 patients had adverse cardiac events, with only one patient warranting intervention discovered by observation unit stress testing and a second via serial cardiac markers. 

Conclusion: Routine observation of symptomatic young adults for ACS had low yield. Observation identified one patient with acute cardiac marker elevation and further stress testing identified only one patient with intervenable ACS, despite a high false-positive rate. This suggests that observation and stress testing should not be routinely performed in this demographic absent other high-risk features. 

J. Stephen Bohan, MD, MS, FACP, FACEP, Journal Watch, wrote: "It's unlikely that anyone would find it reasonable to stress test 250 individuals to find 1 who had cardiac disease, especially considering the cost and risk associated with testing." 

3. Single-operator Ultrasound-guided IV Placement by Emergency Nurses Reduces the Need for Physician Intervention in Patients with Difficult-to-establish IV Access

Weiner SG, et al. J Emerg Med. 2013; 653-660. 

Background: Emergency physicians (EPs) have become facile with ultrasound-guided intravenous line (USIV) placement in patients for whom access is difficult to achieve, though the procedure can distract the EP from other patient care activities. 

Objectives: We hypothesize that adequately trained Emergency Nurses (ENs) can effectively perform single-operator USIV placement with less physician intervention than is required with blind techniques. 

Methods: This was a prospective multicenter pilot study. Interested ENs received a 2-h tutorial from an experienced EP. Patients were eligible for inclusion if they had either two failed blind peripheral intravenous (i.v.) attempts, or if they reported or had a known history of difficult i.v. placement. Consenting patients were assigned to have either EN USIV placement or standard of care (SOC). 

Results: Fifty patients were enrolled, of which 29 were assigned to USIV and 21 to SOC. There were no significant differences in age, race, gender, or reason for inclusion. Physicians were called to assist in 11/21 (52.4%) of SOC cases and 7/29 (24.1%) of USIV cases (p = 0.04). Mean time to i.v. placement (USIV 27.6 vs. SOC 26.4 minutes, p = 0.88) and the number of skin punctures (USIV 2.0 vs. SOC 2.1, p = 0.70) were not significantly different. Patient satisfaction was higher in the USIV group, though the difference did not reach statistical significance (USIV 86.2% vs. SOC 63.2%, p = 0.06). Patient perception of pain on a 10-point scale was also similar (USIV 4.9 vs. SOC 5.5, p = 0.50). 

Conclusions; ENs performing single-operator USIV placement in patients with difficult-to-establish i.v. access reduces the need for EP intervention. 

4. Patients Not Always Told About CT Risks 

By Cole Petrochko, Staff Writer, MedPage Today. March 05, 2013 

Physicians often don't communicate the risks of CT studies to patients undergoing the scans and usually leave patients out of the decision-making process, researchers found. A survey of patients receiving outpatient CT scans showed that only 35% said they had discussed risks associated with the test with a healthcare professional, according to Tanner Caverly, MD, of the University of Colorado in Aurora, and colleagues. In addition, 62% said they thought the final decision to undergo the procedure was up to their doctors, the authors wrote online in the March 4 issue of JAMA Internal Medicine. 

They noted that "up to one in three imaging tests in the U.S. are ordered in situations when the expected benefits do not sufficiently exceed the risks," adding that "clinicians are not well informed about the risks of medical imaging." They also wrote that prior research has shown that fully informed patients tend to ask for fewer tests and less aggressive care. 

Caverly and colleagues studied the frequency of risk communication among patients undergoing CT studies through a survey issued to a sample of 271 patients at the Denver Veterans Affairs Medical Center. Participants were mostly older than 50 (86%), male (92%), and had undergone a prior CT scan (92%). More than one-third had received more than five CT scans (38%). 

The survey included questions on patient demographics, presence of risk communication, preference for more information, and knowledge of potential harms. The response rate was 94.8%. 

Respondents were grouped as having basic knowledge about the hazards of the procedure -- that CT scan was associated with higher radiation exposure than a chest x-ray -- and those without that basic knowledge, as well as into groups who did and did not have a discussion with a healthcare professional about the risks and benefits of CT scan. The rate of patients who said they knew the radiation exposure in CT scan was higher than chest x-ray was 63%. The rate of patients who said they did not have a risk-benefit discussion was 65%. 

Only 17% reported all of the following before having the CT scan:
·         Having a shared final decision
·         Discussing the potential benefits with the healthcare provider
·         Talking about the potential risks with the healthcare provider 

Finally, less than 1% of patients could correctly identify the relative amount of radiation exposure the scan exposed them to (0.4%). "Those who reported discussing both risks and benefits with their healthcare provider were no more likely to know that CT was associated with more radiation than chest x-ray than were respondents not reporting a risk-benefit discussion," the authors wrote. 

In an accompanying editorial, Patrick O'Malley, MD, MPH, of Walter Reed Army Medical Center in Washington, D.C., noted that if healthcare professionals likely do not understand the risks associated with a test, it cannot be expected that patients will understand those risks either. 

He suggested that "much work needs to be done" to educate physicians on the magnitude of radiation exposure and associated risks involved in "commonly used CT scans" so that patients can fully understand the risks of a procedure they may undertake through a discussion that "assures patient understanding of the risks" and "should be part of every discussion surrounding the decision to image." 

The researchers noted that their study was limited by use of a single center and a population of mostly older patients, meaning results may not be generalizable. 

5. Watching CPR Helps Ease Family's Grief 

By Nancy Walsh, Staff Writer, MedPage Today. March 13, 2013 

The proportion of family members with PTSD 3 months after the resuscitative attempt was lower among those in an intervention group routinely offered the opportunity to be present than for controls who were not directly invited (27% versus 37%), according to Frederic Adnet, MD, PhD, of Hôpital Avicenne in Bobigny, France, and colleagues. 

The odds ratio for PTSD after not witnessing the CPR process was 1.7 (95% CI 1.2 to 2.5, P=0.004), the researchers reported in the March 14 issue of the New England Journal of Medicine. 

Whether or not witnessing CPR on a family member who experienced cardiac arrest at home is beneficial or harmful has been controversial ever since the topic was first addressed 25 years ago. 

Some have argued that being present would be associated with an increased emotional burden and other difficulties, not only for the family but also for the emergency medical services team, yet the sole randomized trial looking at this was stopped prematurely because of apparent benefits for families. Despite the lack of evidence, international guidelines today favor family presence during CPR. 

To address the ongoing controversy, Adnet and colleagues conducted a prospective study in which eight EMS units routinely asked family members if they wanted to witness their attempts to resuscitate the patient, explaining the process in a structured fashion. In seven control units, the medical team did not systematically invite family members to witness the resuscitation attempt. 

Three months later, the researchers contacted the 570 family members, interviewing them about PTSD symptoms on the Impact of Event Scale, and about other symptoms on the Hospital Anxiety and Depression Scale. 

A single family member was used for each patient in the analysis, with 266 in the intervention group and 304 in the control group. 

A total of 79% of family members in the intervention group chose to be present, compared with 43% of controls. 

At the 3-month interview, a total of 17% of family members declined to participate further because of emotional distress. This included five in the intervention group and 20 controls (P=0.007). Only 4% of patients survived for a month or longer following CPR. In an analysis that excluded these patients, whose family members might be experiencing less grief, the greater likelihood of PTSD at 3 months was still higher in the control group (P=0.009). 

Symptoms of anxiety were more common in the control group than in the intervention group overall (23% versus 15%, P less than 0.001), and also as reported by individual family members (24% versus 16%, P less than 0.001). There was no significant difference between the intervention and control groups in the proportion of family members who reported symptoms of depression, although more individual members who did not witness the CPR reported symptoms of depression (26% versus 15%, P=0.009). 

Another concern the researchers addressed was whether family members would become disruptive while witnessing the resuscitation, but this occurred in fewer than 1% of cases. A total of 12% of those who were not present said they wished they had been, while only 3% of those who were present regretted it (P less than 0.001). 

The median level of stress reported by the medical team during CPR was 5 on a visual analog scale of 100 points. No family members claimed damages or pursued lawsuits during a mean follow-up period of almost 2 years. 

"Many medical team members are reluctant to permit the presence of family members during resuscitation because of fear of medicolegal conflicts," Adnet and colleagues noted. "Although our sample size is small and the medicolegal culture may be different in France than elsewhere, our findings should help allay physicians' medicolegal concerns," they wrote. 

A possible limitation of the study was its exclusion of resuscitative attempts taking place in the hospital, and further work will be needed to establish the generalizability of these findings to other settings. 

"This study provides useful data that will advance debate surrounding family-witnessed resuscitation," observed Daniel B. Kramer, MD, and Susan L. Mitchell, MD, of Harvard University in an accompanying editorial. "Most notably, when offered the choice to witness resuscitative efforts, most relatives opted to do so, and having that choice improved mental health outcomes, with no evidence of harm to any stakeholders," Kramer and Mitchell wrote. "Future studies should aim to improve our understanding of why this choice may reduce the suffering of family members and whether such an approach could be implemented in practice in a safe and cost-effective manner," they advised. 

See also (Pros and Cons of) Family Presence during Cardiac Resuscitation. N Engl J Med 2013; 368:1060-1062  

6. Head CT Not Useful for Evaluating Acute Dizziness in the ED 

Magnetic resonance imaging has a higher diagnostic yield.  

In a retrospective chart review, investigators determined the diagnostic yield (acute and subacute findings) of head computed tomography (CT) in 448 adult patients who presented to a single urban academic emergency department (ED) with acute dizziness (vertigo, lightheadedness, disequilibrium, presyncope). 

The overall diagnostic yield of head CT was 2.2%, with emergent findings detected on only 1.6% of the scans. Of the 448 patients, 104 underwent follow-up imaging, most often with magnetic resonance imaging or angiography (MRI/A; 78.7%). Seventeen patients (13%) had findings on follow-up imaging that changed or confirmed the diagnosis; most of the changes in diagnosis were ischemic stroke that was not identified on initial CT. MRI was the follow-up modality that most often led to a change in diagnosis (16% of the time). 

Comment: These findings are consistent with the recommendation from the American College of Radiology and American College of Emergency Physicians that head CT be used in the evaluation of acute dizziness only when hemorrhage is the suspected cause. When an intracranial cause of dizziness is suspected (unless the patient presents with trauma or severe headache suspicious for hemorrhage), MRI is the test of choice. 

— Richard D. Zane, MD, FAAEM. Published in Journal Watch Emergency Medicine March 15, 2013. Citation: Lawhn-Heath C et al. Utility of head CT in the evaluation of vertigo/dizziness in the emergency department. Emerg Radiol 2013 Jan; 20:45. ( 

7. Incremental Value of Objective Cardiac Testing in Addition to Physician Impression and Serial Contemporary Troponin Measurements in Women 

Diercks DB, et al. Acad Emerg Med. 2013;265-270. 

Objectives: Guidelines recommend that patients presenting to the emergency department (ED) with chest pain who are at low risk for acute coronary syndrome (ACS) receive an objective cardiac evaluation with a stress test or coronary imaging. It is uncertain whether all women derive benefit from this process. The study aim was to determine the incremental value of objective cardiac testing after serial cardiac markers and physician risk assessment. 

Methods: Women enrolled in the 18-site Myeloperoxidase in the Diagnosis of Acute Coronary Syndrome (MIDAS) study had serial troponin I measured at time 0 and 90 minutes and physician risk assessment for the presence of ACS. Risk estimates obtained at the time of ED evaluation were dichotomized as high or non–high risk. The primary outcome was the composite of acute myocardial infarction (AMI) or revascularization at 30 days. Logistic regression with receiver operator characteristic (ROC) curves and net reclassification index were used to determine the diagnostic accuracy for the composite outcome of 30-day MI or revascularization for two models: 1) troponin I results and physician risk assessment alone and 2) troponin I results, physician risk assessment, and objective cardiac testing. 

Results: A total of 460 women with a median age 58 years (interquartile range [IQR] = 48.5 to 68 years) were included, and 32 (6.9%) experienced AMI or revascularization by 30 days. Comparison of the area under the ROC curves (AUC) showed that the addition of objective cardiac testing to the combination of troponin I results and physician risk assessment did not significantly improve prediction of 30-day AMI or revascularization (AUC = 0.85 vs. 0.89; p = 0.053). Using a threshold of 1%, net reclassification index showed that the addition of objective cardiac testing to troponin I results and physician risk assessment worsened the prediction for 30-day AMI and revascularization. All of the reclassified patients were false positives, with nine (2.1%) patients incorrectly reclassified from less than 1% risk to ≥1% risk of 30-day AMI or revascularization. 

Conclusions: In the era of contemporary troponin assays, objective cardiac testing after an ED clinician risk assessment of non–high risk and negative troponin I results at 0 and 90 minutes does not improve the prediction of 30-day AMI or revascularization in women presenting with chest pain or other symptoms of cardiac ischemia. 

8. Prehospital ECG Provides Important Information  

In this Canadian study, some cases of STEMI, ST-segment depression, and arrhythmia were seen on prehospital ECGs but not on initial emergency department ECGs.  

Boothroyd LJ et al. Prehosp Emerg Care. Epub 2013 Feb 15 

Background. The prehospital electrocardiogram (ECG) allows earlier identification of acute ST-segment elevation myocardial infarction (STEMI). Its utility for detection of other acute cardiac events, as well as for transient ST-segment abnormalities no longer present when the first hospital ECG is performed, is not well characterized.  

Objective. We sought to examine whether the prehospital ECG adds supplemental information to the first ECG obtained in hospital, by comparing data on possible cardiac ischemia and arrhythmias provided by the two ECGs, in ambulance patients later diagnosed as having cardiac disorders, including STEMI.  

Methods. Ambulance personnel acquired 12-lead ECGs for patients suspected of having an acute ischemic event, prior to transport to hospital. The first emergency department 12-lead ECG was provided by medical records at the receiving hospital, and the principal hospital diagnosis for the event was extracted from chart data. Two cardiologists, blinded to the hospital diagnosis, provided their consensus interpretation of 1,209 pairs of ECGs, noting the presence or absence of specific abnormalities on each tracing.  

Results. Among the 82 patients who had an eventual hospital diagnosis of STEMI, the study cardiologists identified 71 with ST-segment elevations on the ECGs they examined. The vast majority of these (97%) were observed on both ECGs, but the prehospital ECG showed ST-segment elevation for two additional patients (3%). No additional instances were seen only on the hospital ECG. Among the 116 patients with a hospital diagnosis of non–ST-segment elevation myocardial infarction (NSTEMI), the cardiologists identified 36 with ST-segment depressions: 28 (78%) of these were present on both ECGs, seven (19%) only on the prehospital ECG, and one (3%) only on the hospital ECG. Among the 567 patients with any cardiac hospital diagnosis, the cardiologists identified 87 with arrhythmias: 73 (84%) on both ECGs, 12 (14%) only on the prehospital ECG, and two (2%) only on the hospital ECG.  

Conclusions. Beyond identifying ST-segment elevation earlier, prehospital ECGs detect important transient abnormalities, information not otherwise available from the first emergency department ECG. These data can expedite diagnosis and clinical management decisions among patients suspected of having an acute cardiac event. The prehospital ECG should be fully integrated into emergency medicine practice.  

9. ACEP Focus On 

Each "Focus On" article has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). The American College of Emergency Physicians is accredited by the ACCME to provide continuing medical education for physicians. The American College of Emergency Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1 CreditTM and 1 ACEP Category I credit. 

Focus On: Chemical Restraint in the ED
December, 2012  

Focus On: Ultrasound-Guided Paracentesis
November, 2012  

Focus On: Bedside Ultrasound Assessment of Left Ventricular Function
October, 2012  

Focus On: Hypertensive Emergency
September, 2012  

Focus On: Focused Renal Ultrasonography
August, 2012  

Focus On: Pediatric Hip Ultrasound
July, 2012 

Link to each of these reviews:  

10. Steroids Trim Pneumonia Hospital Stays, Mortality Unchanged 

Diedtra Henderson. Medscape Medical News. Mar 07, 2013 

Giving steroids to adults who were hospitalized for community-acquired pneumonia (CAP) shortened their hospital stays but had no effect on mortality or on how much time patients spent in the intensive care unit, according to a meta-analysis. 

Majid Shafiq, MD, formerly from the Mayo Clinic College of Medicine in Rochester, Minnesota, and now at Johns Hopkins University, Baltimore, Maryland, and colleagues report their findings in the February issue of the Journal of Hospital Medicine. 

CAP is the most common lower respiratory tract infection among adults in the United States. In addition, pneumonia is the most common reason for patients to be admitted to hospitals from the emergency department, with hospital mortality rates ranging from 5% to 18%, yet consensus guidelines are neutral about using steroids in CAP because of unconvincing clinical trial efficacy data. 

Therefore, Dr. Shafiq and colleagues examined how steroids affected the health of adult patients with CAP by conducting a meta-analysis of 8 randomized controlled trials published before July 2011. The trials included a total of 1119 patients. The mean ages in 7 of the trials ranged from 60 to 80 years; the mean age in the intervention group of the eighth study was 31.7 years. The patients taking steroids used low doses: less than 2 mg/kg/day of methylprednisolone or an equivalent. 

"Although adjunctive steroid therapy had no effect on hospital mortality or [intensive care unit] length of stay, it was associated with reduced hospital length of stay," Dr. Shafiq and colleagues report (relative risk [RR], −1.21 days; 95% confidence interval [CI], −2.12 to −0.29 days). In addition, the authors found that "steroid use was associated with lower incidence of delayed shock (ie, shock occurring after enrollment (RR: 0.12 [95% CI: 0.03 to 0.41]) and lower incidence of persistent chest x-ray abnormalities at 1 week (RR: 0.13 [95% CI: 0.06 to 0.27])." 

Study limitations included the moderate quality of the evidence; variations in the patients' baseline illness severity and comorbidities and the length of follow-up; and considerable variation in steroid therapy regimes. The authors recommend that more robust clinical trials be conducted with tighter controls, such as standardized steroid doses, concurrent measurement of inflammatory markers, and accurate measurement of secondary outcomes of interest. 

"In conclusion, although evidence suggests that adjunctive steroid therapy is associated with reduced hospital length of stay, the data are not strong enough to recommend routine use of steroids among all adults hospitalized with CAP," the authors write. "However, considering that there was no increase in mortality or hospital length of stay with steroid use, it is reasonable to continue steroids if warranted for treatment of underlying comorbid conditions." 

J Hosp Med. 2013;8:68-75. Abstract:  

11. The NNT: Quick summaries of evidence-based medicine. 

From their webpage: “We are a group of physicians that have developed a framework and rating system to evaluate therapies based on their patient-important benefits and harms as well as a system to evaluate diagnostics by patient sign, symptom, lab test or study. 

“We only use the highest quality, evidence-based studies (frequently, but not always Cochrane Reviews), and we accept no outside funding or advertisements.”

This is an excellent resource:   

Here are the latest blog entries:
·         Heart Diets, Heart Numbers, and Truth That Lasts
·         Delusions of Benefit in the International Stroke Trial
·         Drugs, Data, and Deception: A True Story (on Statins)
·         Introducing: The Modern H&P 

12. Dabigatran and Postmarketing Reports of Bleeding 

Southworth MR, et al. N Engl J Med. March 13, 2013; online first DOI: 10.1056/NEJMp1302834 

In the months following the approval of the oral anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) in October 2010, the Food and Drug Administration (FDA) received through the FDA Adverse Event Reporting System (FAERS) many reports of serious and fatal bleeding events associated with use of the drug. Because dabigatran is an anticoagulant, reports of bleeding were anticipated, but the rate of reported incidents was unusually high and was greater than the concurrent rate of reported bleeding incidents with warfarin, which had been the anticoagulant of choice for nearly 60 years before dabigatran was approved. In contrast, the controlled trial that supported the approval of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RE-LY]), which compared warfarin with dabigatran in patients with nonvalvular atrial fibrillation,1 showed that the two drugs conferred a similar risk of bleeding. 

The postmarketing reports of bleeding with dabigatran led to discussions in medical publications as well as the mainstream media about the agency's approval of the drug. Many of these discussions cited the large numbers of reports of bleeding events in FAERS as a reason to question the benefit–risk profile of dabigatran as described in its labeling. But important factors that could have affected reporting rates, such as the novelty of dabigatran (relative to the well-established warfarin) and the coverage of novel drugs in the media, which can greatly influence how and when adverse events are reported, were not generally considered. 

The RE-LY trial enrolled patients with nonvalvular atrial fibrillation and at least one risk factor for stroke. Dabigatran at a dose of 150 mg twice daily was shown to be superior to warfarin for reducing the combined rate of stroke and systemic embolism (1.1 vs. 1.7 per 100 patient-years) among these patients. Dabigatran resulted in a lower rate of both thrombotic and hemorrhagic strokes than warfarin, and the mortality rate was lower in the dabigatran group than in the warfarin group (3.6 vs. 4.1 per 100 patient-years). The level of the primary risk, bleeding, was similar among the patients who received dabigatran at a dose of 150 mg and those who received warfarin (for major bleeding, the rates were 3.3 and 3.6 per 100 patient-years, respectively). (Major bleeding in the RE-LY study was defined as a reduction in hemoglobin concentration of at least 2 g per deciliter, the need to transfuse at least 2 units of blood or packed cells, or symptomatic bleeding in a critical area or organ.) Although major gastrointestinal bleeding events were more frequent in the dabigatran group than in the warfarin group (1.6 vs. 1.1 per 100 patient-years), the rate of intracranial bleeding events was lower for dabigatran than for warfarin (0.3 vs. 0.8 per 100 patient-years). The superiority of dabigatran (at the 150-mg dose) over warfarin for reducing the rates of stroke and systemic embolism with a similar rate of clinically significant bleeding led to FDA approval of dabigatran. 

Because the RE-LY trial had clearly shown that bleeding was a serious side effect of dabigatran, it was expected that bleeding events would be reported after the product was approved, but the number of reports was sufficiently high to prompt the FDA to initiate a review of the spontaneous reports received by FAERS. We were concerned that postmarketing use of dabigatran might be different from its use in the RE-LY trial (e.g., different patient populations, dosing, concomitant medications, and degree of renal impairment) or that adjustments for renal function had not been made correctly. 

As is often the case with spontaneous reports, the reports of bleeding generally did not include information on patients' risk factors, age, renal function, or cause of death. In a small number of cases, the dabigatran dose had not been reduced for a patient who had impaired renal function. Overall, however, the case review did not identify any unrecognized risk factors for bleeding, and there was generally no indication that dabigatran was not being used in accordance with its labeled directions…. 

…We believe that the large number of reported cases of bleeding associated with dabigatran provides a salient example of stimulated reporting. In this case, such reporting provided a distorted estimate of the comparative bleeding rates associated with dabigatran and warfarin in clinical practice. The Mini-Sentinel assessment suggests that bleeding rates associated with dabigatran are not higher than those with warfarin, a finding that is consistent with the results of RE-LY. 

Although some have noted the lack of an available reversal agent for the anticoagulant effects of dabigatran as an important limitation of its use, data from RE-LY are reassuring with respect to bleeding. We believe that dabigatran provides an important health benefit when used as directed. Further analysis of the Mini-Sentinel and other claims databases is ongoing, as is routine postmarketing surveillance through FAERS. 

The remainder of the essay (free for now):  

13. How Quickly Do Germs Spread in the Office?  

Betty Ann Bowser. PBS News. HEALTH. March 7, 2013  

We've all done it. Come to work when we're sick.  

We know we're not doing our fellow workers any favors by exposing them to whatever we've got, but pressure to get our jobs done almost always trumps common sense. 

Well, now there is research to back up what common sense has been telling us all along: It's a bad idea. Environmental microbiologist Kelly Reynolds at the University of Arizona in Tucson noticed the trend in her own office. As winter wore on, more and more of her colleagues started feeling ill. "So we asked the obvious question: how well do germs spread if one person comes to work sick?" she said. 

So Reynolds and her team launched a study in one of the University of Arizona offices involving a typical cast of winter characters: several dozen coworkers in good health and one "sick" colleague carrying a virus mimicking the flu. 

Within four hours, more than 50 percent of surfaces and employees were contaminated with the virus. Pretty startling stuff. 

We spoke with Reynolds recently to learn more about her experiment... 

14. A randomized open-label study of sodium valproate vs sumatriptan and metoclopramide for prolonged migraine headache 

Bakhshayesh B, et al. Amer J Emerg Med. 2013;31:540-544.   

Objective: The objective of this study is to compare the efficacy and tolerability of intravenous valproic acid (iVPA) with intramuscular metoclopramide + subcutaneous (SQ) sumatriptan for prolonged acute migraine. 

Background: Intravenous valproic acid has been explored as a possible treatment of acute migraine. Sumatriptan and newer generation triptans are also effective for migraine. However, iVPA has not yet been compared with triptans in head-to-head studies. 

Methods: Patients presenting with moderate to severe intensity migraine without aura were randomized to receive either 400 mg of iVPA or 10 mg intramuscular metoclopramide + 6 mg SQ sumatriptan (30 patients in each study arm). The severity of headache and other associated symptoms such as photophobia and phonophobia were assessed at baseline and after 20 minutes and 1, 2, 4, and 24 hours. The primary end point was to compare the efficacy of the 2 study treatments in relieving headache from moderate-severe to none-mild and of other associated symptoms within a period of 24 hours. 

Results: Pain relief from severe or moderate to mild or none was obtained in 53.3% of subjects in the iVPA arm and 23.3% in the metoclopramide + sumatriptan arm at 1 hour following treatment (P = .033), whereas 60% and 30% reported pain relief at 2 hour (P = .037). There was no other significant difference in alleviation of associated migraine symptoms between the 2 arms. No serious adverse effects were noted. 

Conclusion: Treatment with iVPA was more effective than metoclopramide + SQ sumatriptan during the first 2 hours in patients with a prolonged migraine. 

15. Decreasing Hospital LOS for Bronchiolitis by Using an Observation Unit and Home Oxygen Therapy  

Sandweiss DR, et al. JAMA Pediatr. 2013;():1-7. doi:10.1001/jamapediatrics.2013.1435.  Published online March 11, 2013. 

Importance  Pediatric observation units (OUs) offer the opportunity to safely and efficiently care for common illnesses previously cared for in an inpatient setting. Home oxygen therapy (HOT) has been used to facilitate hospital discharge in patients with hypoxic bronchiolitis. It is unknown how implementation of a hospitalwide bronchiolitis treatment protocol promoting OU-HOT would affect hospital length of stay (LOS). 

Objective  To test the hypothesis that using OU-HOT for bronchiolitis would decrease LOS. 

Design and Setting  Retrospective cohort study at Primary Children's Medical Center, Salt Lake City, Utah. 

Participants  Uncomplicated bronchiolitis patients younger than 2 years admitted during the winter seasons of 2005 through 2011. 

Interventions  Implementation of a new bronchiolitis care process encouraging use of an OU-HOT protocol. 

Main Outcome Measures  Mean hospital LOS, discharge within 24 hours, emergency department (ED) bronchiolitis admission rates and ED revisit/readmission rates, and inflation-adjusted cost. 

Results  A total of 692 patients with bronchiolitis from the 2010-2011 bronchiolitis season were compared with 725 patients from the 2009-2010 season. Implementation of an OU-HOT protocol was associated with a 22.1% decrease in mean LOS (63.3 hours vs 49.3 hours, P less than .001). Although LOS decreased during all 6 winter seasons, linear regression and linear quantile regression analyses for the 2005-2011 LOS data demonstrated a significant acceleration in the LOS decrease for the 2010-2011 season after implementation of the OU-HOT protocol. Discharges within 24 hours increased from 20.0% to 38.4% (P less than .001), with no difference in ED bronchiolitis admission or ED revisit/readmission rates. After implementation of the OU-HOT protocol, the total cost per admitted case decreased by 25.4% ($4800 vs $3582, P less than .001). 

Conclusions and Relevance  Implementation of an OU-HOT protocol for patients with bronchiolitis safely reduces hospital LOS with significant cost savings. Although widespread implementation has the potential for dramatic cost savings nationally, further studies assessing overall health care use and cost, including the impact on families and outpatient practices, are needed. 

16. Viewpoint: Myths about ‘Inappropriate’ ED Visits 

Smulowitz PB et al. EM News. 2013;35:3,18.  

The recent Washington State Medicaid proposal to deny payment for patients' use of EDs for a “non-emergency” reminds us of the first “ER abuser” one of us saw as a resident. He had the characteristics typically described in “inappropriate” users of the ED: It was his second visit in three days for a vague complaint of trouble breathing. He seemed anxious, demanding immediate attention despite his stable appearance. He was impoverished, presumably uninsured or on Medicaid. And he was not cooperative, refusing to hold still for a blood draw. 

And then he died, sustaining a cardiac arrest from which he could not be resuscitated. Absent an autopsy, the presumed diagnosis was pulmonary embolism, missed on his previous visit. 

All experienced emergency physicians have similar stories of patients who on first assessment did not seem to have an emergency condition but who turned out to have a life-threatening problem. Every shift we work, we treat many patients with seemingly minor complaints, each of whom might have a life-threatening emergency that can only be ruled out through a thorough evaluation. How do we reconcile the inconsistency between our daily experience and the common wisdom of policy-makers that widespread “ER abuse” for non-emergency conditions threatens the financial viability of our medical care system, compromises continuity of care, and causes ED crowding? And, for those of us whose EDs serve many patients who end up not requiring high-acuity care, how do we deal with our own burnout? 

Five common misunderstandings about ED use require understanding of the literature. 

Is there a lot of “inappropriate,” “non-emergency,” or “avoidable” ED use? Different studies have reported the proportion of ED visits that are “inappropriate” as anywhere from 11 percent to 82 percent. These inconsistencies largely reflect the lack of any validated measure of “appropriateness.” (Ann Emerg Med 2001;37[6]:629.) We cannot study its frequency without a measure of inappropriateness. 

What about “appropriateness” from the patient perspective? Patients who use the ED usually go there for two reasons: lack of access to other providers (80%) and perception of the seriousness of the medical problem (66%). (National Center for Health Statistics, May 2012.) It is difficult to argue that these are “inappropriate” reasons for ED use. 

Does ED use disrupt continuity of care? Many frequent ED users also have frequent visits to their primary care physicians. These high utilizers of overall health care services suffer from poor physical or mental health. (Ann Emerg Med 2006;48[1]:1.) Their chronic illnesses — not their ED use — are what make it challenging to coordinate their care. That said, many of the care coordination challenges need to be dealt with better. Improving the coordination of care for patients seen in the ED calls for new models of team-based care. It will be one of our biggest challenges, yet it may also provide one of the greatest sources of satisfaction in the years to come. 

Is the ED costly? It is the charge for ED care that is so substantial, not the cost. Like many parts of the medical care delivery system, EDs cost-shift, charging more for lower intensity visits to be able to afford the resources needed for the most seriously ill and injured patients. But ED care accounts for only two to four percent of total U.S. medical expenditures. The major cost drivers of medical spending are in-patient care (29%), office-based care (24%), and prescription drugs (20%). Put simply, policy changes that led to a three percent drop in these costs would save more money than eliminating half the charges for ED care. 

Does “inappropriate ED use” cause ED crowding? The “input” side of ED use has little to do with ED crowding. Rather, the major contributor is “output,” the time it takes to move admitted patients out of the ED into an inpatient bed. (Ann Emerg Med 2003;42[2]:173.) Many EDs' biggest challenge is the loss of beds because they are boarding psychiatric patients. Even if we could figure out ahead of time which discharged patients didn't need to be in the ED, we wouldn't make a dent in the problem of crowding. 

Is ED “overuse” easy to fix? Health care organizations have tried a variety of strategies to reduce ED utilization, with mixed results. Creating barriers to emergen cy medical care through triage or preauthorization requirements carries risks. The most effective strategies have been higher copayments and the extension of primary care availability. 

We still don't know, however, what level of copayments is safe, and evidence suggests that lower-income patients may be placed at higher risk by such copayments. (Health Serv Res 2008;43[2]:515.) Moreover, the reasons people use EDs for care are complex and not likely to be “fixed” by any single organizational strategy. One possibility for the long term is that the move toward Accountable Care Organizations will redirect our focus on improving overall health for populations. The consequence of this is that better health (and improved value) will be the main outcome measure, not a single data point like “inappropriate” use of the ED. 

I know what to say to policy-makers, but what do I tell my colleagues and myself when we are being hammered by Medicaid patients with toothaches? Difficult as it may be during a busy shift, try not to blame the victim. Instead, think about how current patterns of ED use present opportunity for solutions. Three percent of Medicaid and five percent of uninsured ED visits in Oregon are primarily for dental conditions. Let's advocate for safety-net dental clinics! 

A tenfold variation exists between the different communities in Oregon Health Plan enrollees' ED utilization rates. (Med Care 2009;47[1]:15.) What can we learn from the low-use communities? Philadelphia Medicaid enrollees whose primary care providers have 12 or more evening hours a week use EDs 20 percent less than enrollees whose primary care physicians lack evening hours. (Med Care Aug 2005;43[8]:792.) How can we incentivize providers to expand hours? 

We emergency physicians see the successes — and failures — of the entire health care system, and we — like no others — are in a position to advocate for our patients and to fix the system. 

17. Unusual Headache Syndromes 

Queiroz LP. Headache. 2013;53(1):12-22.  

Objective/Background.—Some headache syndromes have few cases reported in the literature. Their clinical characteristics, pathogenesis, and treatment may have not been completely defined. They may not actually be uncommon but rather under-recognized and/or underreported. 

Methods.—A literature review of unusual headache syndromes, searching PubMed and ISI Web of Knowledge, was performed. After deciding which disorders to study, relevant publications in scientific journals, including original articles, reviews, meeting abstracts, and letters or correspondences to the editors were searched. 

Findings.—This paper reviewed the clinical characteristics, the pathogenesis, the diagnosis, and the treatment of five interesting and unusual headache syndromes: exploding head syndrome, red ear syndrome, neck-tongue syndrome, nummular headache, and cardiac cephalgia. 

Conclusions.—Recognizing some unusual headaches, either primary or secondary, may be a challenge for many non-headache specialist physicians. It is important to study them because the correct diagnosis may result in specific treatments that may improve the quality of life of these patients, and this can even be life saving. 

18. Treating Cirrhotics: What's the NNT?  

David H. Newman, MD. EP Monthly. February 18, 2013 

Q: Does it help to use prophylactic antibiotics during management of gastrointestinal bleeding in cirrhotic patients?

A: Yes!  (by Daniel P. Runde, MD) 

Take Home Message: Antibiotics for cirrhotics with upper GI bleeding appear to save lives by reducing infections. 

Q: Do somatostatin analogues drugs improve survival or reduce morbidity during acute variceal bleeding? 

A: NO!  (by Lucy Willis, MD) 

Take Home Message: Somatostatin analogues like octreotide did not reduce morbidity or mortality in randomized trials of patients with variceal bleeding. 

19. Recognition of Psychogenic Non-epileptic Seizures: A Curable Neurophobia? 

O'Sullivan SS, et al. J Neurol Neurosurg Psychiatry. 2013;84(2):228-231.  

Background Diagnosing psychogenic non-epileptic seizures (PNES) remains challenging. The majority of 'PNES status' cases are likely to be seen in the emergency department or similar non-specialised units, where patients are initially assessed and managed by physicians of varying expertise in neurology. 

Methods 216 participants including medical students and doctors of all grades from a wide range of medical disciplines were shown video recordings of six patients with PNES and six other patients with convulsive epileptic seizures (ES). Participants were asked to choose between PNES and ES as a diagnosis and to rate their confidence in each diagnosis, both before and after a 15-minute teaching presentation on PNES and ES. 

Results Pre-teaching sensitivity for diagnosing PNES was 0.77, specificity 0.55. The positive predictive value (PPV) of diagnosing PNES was 0.63, and was 0.7 for ES. Diagnostic accuracy increased with increasing clinical grades (p=0.022), as did clinical confidence (p less than 0.0005). Clinical accuracy and clinical confidence increased post-teaching (p less than 0.0005). Sensitivity for diagnosing PNES post-teaching improved to 0.88, specificity to 0.67. The PPV of diagnosing PNES increased to 0.72, and to 0.84 for ES. 

Conclusions Diagnosing PNES can be improved by clinical experience in neurology and focussed teaching interventions. 

20. Study Criticizes Policy Penalizing Nonemergency ED Visits 

Robert Lowes, Medscape Medical News. Mar 19, 2013 

In an effort to control Medicaid costs, some state legislators have wanted to deny or limit payment for emergency department (ED) visits if a later discharge diagnosis indicated the problem was a nonemergency that could have been handled in a physician's office. 

Good luck making that work, says a new study published in the Journal of the American Medical Association (JAMA). Lead author Maria Raven, MD, MPH, and colleagues write that in ED visits later deemed to be primary care treatable based on the discharge diagnosis, patients presented the same chief complaints given by the vast majority of all ED patients. 

In other words, clinicians can't accurately predict an ED discharge diagnosis based on the chief complaint at the time of the visit. Initially, true emergencies and nonemergencies look an awful lot alike. 

Remainder of the essay:  

21. Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study 

Rosenson J, et al. J Emerg Med. 2013;44: 592-598.e2 

Background: Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. 

Objective: We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. 

Methods: This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). 

Results: There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4–32). There were no differences in adverse events. 

Conclusions: A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. 

22. FYIs 

A. Azithromycin Poses Fatal Cardiac Risk, FDA Warns 

Robert Lowes. Medscape Medical News. Mar 12, 2013 

The popular antibiotic azithromycin (Zithromax and Zmax, Pfizer) poses the risk for a potentially fatal irregular heart rhythm, which therefore warrants careful screening of patients for this drug, the US Food and Drug Administration (FDA) announced today. 

The macrolide-class antibiotic can cause abnormal changes in the electrical activity of the heart that may prolong the QT interval and trigger a rare, associated arrhythmia called torsades de pointes. 

The FDA stated that patients at risk for this azithromycin-induced arrhythmia include those who already have a prolonged QT interval, low blood levels of potassium or magnesium, and an abnormally slow heart rate, or who take drugs to treat arrhythmias. Elderly patients and patients with cardiac disease also may be more susceptible to the arrhythmogenic effects of the antibiotic. 

The agency advised clinicians to put the cardiac risk for azithromycin in an "appropriate context," because other antibiotics in the macrolide class as well as nonmacrolides such as fluoroquinolones can prolong the heart's QT interval. 

The FDA safety announcement about azithromycin follows a review of a study conducted by Pfizer on the antibiotic's effect on cardiac electrical activity and another study published in the New England Journal of Medicine in May 2012. The study reported that patients receiving a 5-day course of azithromycin had a small, increased risk for sudden cardiac death compared with those who received amoxicillin or no antibiotics. The FDA said at the time that it would review these findings.

The agency has updated the label of azithromycin to warn of the risk for QT interval prolongation and torsades de pointes. 

More information about today's drug safety communication is available on the FDA Web site:  

B. Hardening of the arteries an ancient disease 

Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern humans raises the possibility of a more basic predisposition to the disease.  

C. CDC: Norovirus is top cause of acute gastroenteritis in young children 

An estimated 1 million medical visits by U.S. children younger than age 5 every year are attributed to norovirus infection, exceeding for the first time visits linked to rotovirus, CDC researchers said. They reported that the annual cost of norovirus-related acute gastroenteritis was $273 million. 

D. Surgery is not routinely needed for presumed symptomatic meniscal tears in patients with knee osteoarthritis 

E. Drug for Severe Sepsis Not a Life Saver   

Eritoran, a novel agent that blocks inflammatory reactions to the major endotoxin from gram-negative bacteria, doesn’t help save lives in severe sepsis, the ACCESS trial showed.