Thursday, June 07, 2007

Lit Bits: June 7, 2007

From the recent medical literature...

1. The risk for ACS associated with atrial fibrillation among ED patients with chest pain syndromes

Brown AM, et al. Amer J Emerg Med. 2007;25:523-528.

Objective: We sought to determine if atrial fibrillation is associated with an increased risk for an acute coronary syndrome (ACS) among emergency department (ED) patients with chest pain syndromes.

Methods: We performed a retrospective analysis of a prospectively collected database on ED patients with chest pain by selecting patients with atrial fibrillation and frequency-matched control subjects without atrial fibrillation. Measured outcomes were acute myocardial infarction (AMI), ACS, and unstable angina (UA). The relative risks of AMI, ACS, and UA associated with atrial fibrillation were calculated.

Results: One hundred forty patients with atrial fibrillation and 683 matched control subjects were identified. The rates of AMI for the atrial fibrillation and control groups were 11.4% and 10.8%, respectively; those of ACS were 27.9% and 26.7%, respectively; and those of UA were 16.4% and 15.8%, respectively. The relative risks of AMI and ACS did not increase in patients with atrial fibrillation: AMI, 1.05 (95% confidence interval [CI] = 0.63-1.75); ACS, 1.05 (95% CI = 0.78-1.40); and UA, 1.05 (95% CI = 0.6-1.7).

Conclusion: Among patients presenting to the ED with chest pain syndromes, atrial fibrillation is not associated with an increased risk for AMI, ACS, and UA.

2. Hospitalist Model May Reduce Costs Without Adversely Affecting Outcomes

Laurie Barclay, MD. May 25, 2007 (Dallas) — For patients with common inpatient diagnoses, the hospitalist model reduces length of stay and costs without adversely affecting mortality or readmission, according to a presentation by Peter K. Lindenauer, MD, MSc, medical director of clinical and quality informatics at Baystate Health and associate professor of medicine at Tufts University School of Medicine, in Springfield, Massachusetts, at Hospital Medicine 2007, the Society for Hospital Medicine annual meeting.

The hospitalist model, or designating specified physicians as hospitalists available to admit patients, was put forth a decade ago by Robert M. Wachter, MD, now a professor and associate chairman of medicine at the University of California, San Francisco (UCSF). Dr. Wachter was not involved with Dr. Lindenauer’s study, but was asked by Medscape to provide independent comment.

"Since I first described the hospitalist model in a 1996 New England Journal of Medicine article [335(7):514-7], the field has grown from a few hundred physicians to more than 20,000 today," said Dr. Wachter, who is also chief of the medical service at UCSF Medical Center. "This makes it the fastest growing physician specialty in the history of medicine. This remarkable growth has been fueled by studies that have shown that the model markedly improves efficiency without harming (and quite possibly improving) quality and medical education." However, Dr. Wachter noted that previous studies were criticized for being relatively small, mostly involving only a few hospitalists, with short follow-up and limited generalizability.

"The study by Lindenauer and colleagues is by far the largest study to date testing the following critical hypothesis: Do hospitalists improve value or quality/cost when compared with care delivered by nonhospitalist generalists?" Dr. Wachter said. "The strongly positive result is likely to further increase the diffusion of hospitalist programs. Importantly, despite impressive cost and length-of-stay savings, there was no evidence that there was any harm in quality, [with] stable mortality and readmission rates."

Dr. Lindenauer’s group performed a retrospective cohort study of 76,296 patients 18 years and older who were hospitalized at 1 of 45 US hospitals that used an expanded set of physician specialty codes, which included an option to categorize attending physicians as hospitalists.

The investigators reviewed the hospital records of patients discharged between September 1, 2002 and June 30, 2005 who had a primary diagnosis of pneumonia, heart failure, chest pain, ischemic stroke, urinary tract infection, acute exacerbation of chronic obstructive pulmonary disease, or acute myocardial infarction, and who were attended by a hospitalist, general internist, or family physician.

A series of multivariable models evaluated the independent effect of physician specialty on length of stay, cost, inpatient mortality, and readmission, after adjustment for patient age, sex, ethnicity, insurance, principal diagnosis, and comorbid conditions; hospital characteristics, including size, teaching status, location, and urban or rural setting; and physician’s annual case volume. Generalized estimating equation models accounted for a clustering of patients with physicians and a clustering of physicians within hospitals, and all models included an interaction term of physician specialty with principal diagnosis.

By specialty, the average number of patients with 1 of the 7 selected diagnoses cared for each year was 20 patients for the 971 family physicians, 30 patients for the 993 general internists, and 75 patients for the 284 hospitalists.

Compared with patients cared for by general internists, those cared for by hospitalists had a shorter length of stay (adjusted difference, -0.6 days; 95% confidence interval [CI], -0.7 to -0.5 days) and lower costs (adjusted difference, -$417; 95% CI, -$704 to -$131). However, inpatient mortality was similar in both groups (odds ratio [OR], 0.95; 95% CI, 0.85 to 1.05), as was 14-day readmission risk (OR, 0.98; 95% CI, 0.91 to 1.05).

Compared with patients cared for by family physicians, those cared for by hospitalists had a shorter length of stay (adjusted difference, -0.4 days; 95% CI, -0.6 to -0.3 days). However, both groups had similar costs (adjusted difference, $8; 95% CI, -$296 to $311), mortality (OR, 0.95; 95% CI, 0.83 to 1.07), and readmissions (OR, 0.95; 95% CI, 0.87 to 1.04).

"For 7 of the most common conditions seen on an inpatient medical service, when compared with care provided by general internists, the hospitalist model was associated with reductions in length of stay (0.6 days) and costs (~$400) without adversely affecting mortality or readmission," Dr. Lindenauer told Medscape. "When compared with care provided by family physicians, the hospitalist model was associated with reductions in length of stay (0.4 days), but similar costs, mortality, and readmission."

"The improved efficiency was observed at both teaching and nonteaching institutions," said Dr. Lindenauer. "These efficiency gains were only partially explained by the higher inpatient volumes of hospitalists compared with the 2 other physician groups. This suggests that the other aspects of the hospitalist model — such as their on-site and often 24-hour presence and the alignment of their incentives with those of the hospital — can result in greater efficiency."

According to Dr. Wachter, the major strengths of this study include size (many times larger than earlier studies), rigorous methodology, and multivariate analysis accounting for all the key variables. Limitations include lack of information concerning the way some physicians came to be coded as hospitalists, and difficulty in determining whether the source of the information was administrative data or clinical chart reviews.

"Overall, though, the methodology seems appropriate and strong, especially since the length-of-stay differences are so robust (approximately half a day) that they are unlikely to be explained by any subtle methodologic flaws," Dr. Wachter said. "Thousands of hospitals have chosen to provide financial support for hospitalists, in part because they believe that there will be a positive return on investment. This study provides the strongest evidence to date that this investment, which is more than $1.5 billion in the United States alone, is a wise one."

Recommendations for future research proposed by Dr. Wachter include determining the impact of hospitalists on process and outcome measures of quality, on patient satisfaction, and on trainee education. Factors making individual hospitalists, or groups of hospitalists, more or less effective in meeting their quality and efficiency goals should also be explored, as should outcomes associated with hospitalist comanagement of surgical patients.

"Based on these results, we believe that hospitalist programs will continue to be attractive to hospitals seeking ways of improving efficiency," Dr. Lindenauer concluded. "While our study provides valuable data on differences in costs and length of stay, future research is required to evaluate the impact of hospitalists on quality of care and patient satisfaction."

Hospital Medicine 2007: Abstract 40. Presented May 23-25, 2007.

Another abstract from the meeting: Medication Discrepancies in Sign-Outs among Hospitalists are Frequent and Potentially Harmful. See

3. The American Academy of Emergency Medicine Adopts an Official Position Statement on ED Boarding

On May 15, 2007, the American Academy of Emergency Medicine (AAEM) board of directors adopted an official position statement on the practice of boarding patients in the ED. In summary, AAEM urges hospitals to seek options other than ED boarding while waiting to admit patients and recommends that regulating agencies issue new rules that forbid the practice of boarding patients in the ED. Below is the position statement in its entirety.

AAEM Position Statement on ED Boarding

The practice of boarding patients in the ED is defined as holding admitted patients in the ED until a staffed, in-patient bed becomes available and this period usually lasts several hours (and sometimes days). Boarding is not in the best interest of the patient being boarded as it compromises their comfort, privacy and medical care. Boarding also delays the care of others, provokes ambulance diversion, and results in some patients leaving the waiting room before being seen by a physician. Boarding creates a significantly more stressful practice environment and contributes to professional dissatisfaction, burnout and high staff turnover. AAEM calls upon hospitals to seek options other than ED boarding to hold admitted patients. AAEM also calls upon regulating agencies to issue rules that forbid boarding.

4. Risk Factors Identified for Poor Short-Term Outcome in Acute Pediatric Asthma

News Author: Laurie Barclay, MD. May 25, 2007 — An observational cohort study of high-risk children with asthma, published in the May issue of the Annals of Allergy, Asthma & Immunology, helps identify more effective risk factors to screen and evaluate interventions at the time of emergency department (ED) treatment.

"Despite good initial treatment response, many children with acute asthma exacerbations have poor short-term outcomes," write Martha (Molly) W. Stevens, MD, MSCE, from the Medical College of Wisconsin, Children's Hospital of Wisconsin and Children's Research Institute, in Milwaukee, and colleagues. "Although many previous studies of pediatric asthma have attempted to find predictors of admission and relapse, none have specifically examined the ability to identify children at risk for these poor functional outcomes at the time of ED treatment for acute asthma. The aim of this study was to find predictors of poor outcome after ED care for acute asthma exacerbation and to develop and validate a model to identify patients at high risk for increased morbidity."

In this prospective cohort study of children treated for acute asthma at 2 pediatric EDs, poor 14-day outcome was defined as any of the following: asthma symptoms still above baseline at 14 days, child missed 5 or more days of school or daycare, caretaker missed 5 or more days of school or work, or unscheduled care or admission after the ED visit for worsening symptoms.

Of 1221 children enrolled, 852 were enrolled at the derivation site and 369 at the validation site. Five variables independently associated with poor outcome by logistic regression were used to create a simple linear score: wheezing 2 or more days before the visit, 3 or more acute outpatient asthma visits in the previous 12 months, home use of albuterol, history of severe persistent asthma, and fever at the ED visit.

Areas under the receiver operating characteristic curve were 0.66 for the derivation sample and 0.67 for the validation samples. Two or more features categorized high risk. For the derivation/validation samples, sensitivity was 0.67/0.62; specificity, 0.61/0.68; likelihood ratio, 1.7/1.9; pretest probability, 33%/47%; and posttest probability, 50%/62%, respectively.

Study limitations include lack of validated instrument to measure functional outcome; lack of data on environmental factors or psychosocial factors; and predominantly poor, minority, urban populations in the northeastern United States seen at pediatric-specific facilities, which may limit generalizability.

"Information available at the ED visit was used to develop a simple risk score that identifies patients at high risk for poor outcome," the authors write. "The score would be useful in evaluating interventions to improve outcomes by allowing interventions to be targeted to a subgroup most likely to benefit."

The Maternal and Child Health Bureau Research Program supported this study.

Ann Allergy Asthma Immunol. 2007;98:432-439.

5. Prolonged QTc Is an Early Sign of Transmural Ischemia

Kenigsberg DK, et al. J Am Coll Cardiol. 2007;49:1299-1305.

Objectives: In order to more clearly understand the electrocardiographic manifestations of early transmural ischemia, we studied electrocardiograms (ECGs) in patients undergoing balloon angioplasty.

Background: Decisions regarding reperfusion strategies in patients with acute myocardial infarction rely largely on the presence of ST-segment elevation (STE) in the ECG, consequently with significant limitations. Studies of the "ischemic cascade" show that ST-segment changes occur well after the onset of wall motion abnormalities.

Methods: We prospectively analyzed ECGs obtained at 20-s intervals in 74 patients undergoing elective balloon angioplasty. The ECGs were analyzed using 3 methodologies. In 74 patients, the ST-segment, the T-wave, and the QT-interval were analyzed using the MUSE (General Electric HC, Menomonee Falls, Wisconsin) automated system (MUSE). Fifty patients were also analyzed using the Interval Editor automated system (IE; General Electric HC). In 20 patients, measurements were made manually.

Results: Transmural ischemia prolonged the QTc interval (using the Bazett’s formula) in 100% of patients. In all 74 patients analyzed with MUSE, QTc interval prolonged from 423 ± 25 ms to 455 ± 34 ms (p less than 0.001). In the 50 patients analyzed with IE, QTc interval prolonged in 50 of 50 (100%) patients (from 424 ± 27 ms to 458 ± 33 ms [p less than 0.001]). Mean time to maximal QTc interval prolongation, changes in T-wave polarity, 1 mm STE, and ST-segment depression (STD) were 22, 24, 29, and 35 s, respectively. Although QTc interval prolonged in 100% of patients, T-wave changes, STE, and STD (1 mm) occurred in 7%, 15%, and 7%, respectively.

Conclusions: The QTc interval prolongs in 100% of patients with early transmural ischemia. When compared with clinically accepted indexes of transmural ischemia (i.e., STD and STE [1 mm]) it is the earliest ECG abnormality.

6. Antibiotic Prescriptions for Viral URIs: We’re Making Progress!

Prescriptions decreased by 20% from 1993 through 2004.

Objectives: To examine antibiotic prescribing trends for U.S. emergency department (ED) visits with upper respiratory tract infections (URIs) between 1993 and 2004.

Methods: Data were compiled from the National Hospital Ambulatory Medical Care Survey (NHAMCS). URI visits were identified by using ICD-9-CM code 465.9, whereas antibiotics were identified using the National Drug Code Directory class Antimicrobials. A multivariate logistic regression model revealed sociodemographic and geographic factors that were independently associated with receipt of an antibiotic prescription for URIs.

Results: There were approximately 23.4 million ED visits diagnosed as URIs between 1993 and 2004. Although the proportion of URI diagnoses remained relatively stable (ptrend = 0.26), a significant decrease in provision of antibiotic prescriptions for URIs occurred during this 12-year period, from a maximum of 55% in 1993, to a minimum of 35% in 2004. Patients who were prescribed antibiotics were more likely to be white than African American and to have been treated in EDs located in the southern United States.

Conclusions: Antibiotic prescribing for URIs continues to decrease, a favorable trend that suggests that national efforts to reduce inappropriate antibiotic usage are having some success. Nevertheless, the frequency of antibiotic treatment for URI in the ED remains high (35%). Future efforts to reduce inappropriate antibiotic prescribing may focus on patients and physicians in southern U.S. EDs. Additional work is needed to address continued evidence of race-related disparities in care.

Vanderweil SG, et al. Acad Emerg Med. 2007;14:366-369.

7. Pediatric Procedural Sedation in Community EDs

Emergency physicians in community hospital settings provide safe and effective pediatric procedural sedation.

Most studies of pediatric procedural sedation have been conducted in university and tertiary-care pediatric settings. Little is known about this practice in community settings, where pediatric patient volume is typically lower. Researchers used data from the Procedural Sedation in the Community Emergency Department (ProSCED) registry, a database of consecutive emergency physician–directed procedural sedation cases, to describe practice patterns and associated outcomes. Fourteen community hospitals prospectively submitted data to the registry from January 2003 to March 2006 on forms required by the Joint Commission on Accreditation of Healthcare Organizations.

Of 1028 sedations, 341 (33%) were performed in patients younger than 21. The volume of pediatric cases varied by site, from 0.3 to 4.2 per month. Most patients (94%) were categorized as ASA class 1. The most common indications for sedation were laceration repair and joint relocation. Ketamine was the preferred medication (41%), followed by midazolam (32%). Medication use varied significantly according to age; for example, 90% of etomidate use and 80% of fentanyl use were in patients older than 8, whereas 80% of ketamine use was in children younger than 8. Two complications (0.6%) were reported, both in adolescents: one case of apnea after etomidate and fentanyl sedation that resolved with administration of naloxone and one case of hypoxia that resolved with supplemental oxygen. Overall, 99% of procedures were successful.

Comment: These results from a community setting add to the literature from pediatric tertiary settings that show that EPs perform pediatric procedural sedation safely. The reliability of the findings is strengthened by the fact that clinicians could not exclude cases from the registry since data were collected as part of a JCAHO-mandated hospital performance improvement program.

— Jill M. Baren, MD, MBE, FACEP, FAAP. Published in Journal Watch Emergency Medicine May 25, 2007. Citation: Sacchetti A et al. Pediatric procedural sedation in the community emergency department: Results from the ProSCED registry. Pediatr Emerg Care 2007 Apr; 23:218-22.

8. ALS May (or May Not) Improve Survival in Respiratory Distress: High cost, small benefit

To determine whether the introduction of advanced life support (ALS) services improves survival in patients with out-of-hospital respiratory distress, researchers conducted a before-and-after controlled study. They enrolled approximately 4000 patients in 15 cities in Ontario during each of two 6-month study periods: In the first period, care was delivered by basic life support crews; in the second period, ALS services were available from "advanced care" paramedics who had 24 weeks of skills training in endotracheal intubation and intravenous administration of medications.

ALS crews responded to 57% of patients in the second period. During this period, 15% of all patients received IV medications, fewer than 3% received bag mask ventilation, and fewer than 2% underwent endotracheal intubation. Administration of medications for symptom relief (most often salbutamol) increased markedly between periods, from 16% to 59%. Mortality before hospital discharge (the primary outcome measure) decreased significantly, from 14.3% to 12.4%, but the absolute difference of 1.9% was less than the 2.0% difference that the investigators had predefined as being clinically important. Mortality in the emergency department did not change, however, and the entire mortality benefit was attributable to a reduction in inhospital death.

Comment: Given the low rate of ALS interventions (administration of medications for symptom relief was not considered an ALS intervention), that they had a significant effect on mortality is unlikely. Although the authors did not calculate cost per life year saved, it is likely to be high, considering the costs of 24 weeks of training and continuous skill maintenance. The finding that only 80 patients were intubated during a 6-month period in 15 cities suggests that intubation skills would be difficult to maintain even with training. This study did not show a clear cause-and-effect relation between the introduction of ALS and reduced mortality, and, therefore, EMS directors and public health officials might have reason to initiate further studies to determine exactly what benefits derive from complex and expensive prehospital ALS systems.

— J. Stephen Bohan, MD, MS, FACP, FACEP. Published in Journal Watch Emergency Medicine May 23, 2007. Citation: Stiell IG et al. Advanced life support for out-of-hospital respiratory distress. N Engl J Med 2007 May 24; 356:2156-64.

9. American Academy of Neurology Issues Lyme Disease Guidelines

The American Academy of Neurology last week published new evidence-based guidelines on the treatment of nervous system Lyme disease and post-Lyme syndrome. The Infectious Diseases Society of America has endorsed these guidelines, which focus on different treatments for different types of neurologic symptoms. Key recommendations include:

--Parenteral ceftriaxone, cefotaxime, or penicillin G are "probably safe and effective" options to treat meningitis or CSF pleocytosis.

--In the absence of severe (brain or spinal cord) involvement, oral doxycycline is "probably safe and effective." When doxycycline is contraindicated, alternatives are amoxicillin and cefuroxime axetil, but data to support these treatments are lacking.

--The highest level of evidence supports a recommendation against prolonged antibiotic courses for post-Lyme syndrome; symptomatic management is recommended instead.

--Two weeks of antibiotic treatment are recommended to eradicate neuroborreliosis.

--The data on the use of corticosteroids in patients with neuroborreliosis are limited and show no clear benefit or harm.

The guidelines also specify recommended doses of each antibiotic for adults and for children.

AAN guidelines published in Neurology (Free PDF):

10. Mirror, Mirror on the Wall: An International Update on the Comparative Performance of American Health Care

The U.S. health system is the most expensive in the world, but comparative analyses consistently show the United States underperforms relative to other countries on most dimensions of performance. This report, which includes information from primary care physicians about their medical practices and views of their countries' health systems, confirms the patient survey findings discussed in previous editions of Mirror, Mirror. It also includes information on health care outcomes that were featured in the U.S. health system scorecard issued by the Commonwealth Fund Commission on a High Performance Health System.

Among the six nations studied—Australia, Canada, Germany, New Zealand, the United Kingdom, and the United States—the U.S. ranks last, as it did in the 2006 and 2004 editions of Mirror, Mirror. Most troubling, the U.S. fails to achieve better health outcomes than the other countries, and as shown in the earlier editions, the U.S. is last on dimensions of access, patient safety, efficiency, and equity. The 2007 edition includes data from the six countries and incorporates patients' and physicians' survey results on care experiences and ratings on various dimensions of care.

The most notable way the U.S. differs from other countries is the absence of universal health insurance coverage. Other nations ensure the accessibility of care through universal health insurance systems and through better ties between patients and the physician practices that serve as their long-term "medical home." It is not surprising, therefore, that the U.S. substantially underperforms other countries on measures of access to care and equity in health care between populations with above-average and below average incomes.

With the inclusion of physician survey data in the analysis, it is also apparent that the U.S. is lagging in adoption of information technology and national policies that promote quality improvement. The U.S. can learn from what physicians and patients have to say about practices that can lead to better management of chronic conditions and better coordination of care. Information systems in countries like Germany, New Zealand, and the U.K. enhance the ability of physicians to monitor chronic conditions and medication use.
These countries also routinely employ non-physician clinicians such as nurses to assist with managing patients with chronic diseases.

The area where the U.S. health care system performs best is preventive care, an area that has been monitored closely for over a decade by managed care plans. Nonetheless, the U.S.
scores particularly poorly on its ability to promote healthy lives, and on the provision of care that is safe and coordinated, as well as accessible, efficient, and equitable.

For all countries, responses indicate room for improvement. Yet, the other five countries spend considerably less on health care per person and as a percent of gross domestic product than does the United States. These findings indicate that, from the perspectives of both physicians and patients, the U.S. health care system could do much better in achieving better value for the nation's substantial investment in health.


11. Outlook Poor After Resuscitation of In-Hospital Cardiac Arrest

NEW YORK (Reuters Health) May 31 - Many patients have limited long-term survival after successful resuscitation following in-hospital cardiac arrest. However, those who receive internal cardioverter-defibrillators (ICDs) have a significant advantage, researchers report in the May issue of the American Heart Journal.

"Post-in-hospital cardiac arrest patients who survive to be discharged from the hospital have abysmal subsequent survival," lead investigator Dr. Heather L. Bloom of the Atlanta VA Medical Center, told Reuter Health.

"The clinical implications," she added, "are that we need to be looking beyond survival to discharge as an end point for resuscitation trials, to truly impact survival in this patient population."

Dr. Bloom and colleagues retrospectively studied data on 732 patients her hospital who had in-hospital cardiac arrest between 1995 and2 004.

In total, 49 patients (6%) survived to discharge. The chances of survival were increase in patients using beta-blockers, angiotensin-converting enzyme inhibitors, and antiarrhythmics at the time of arrest. Conversely, older age and comorbidities were associated with reduced survival. The 1-year survival rate after discharge was 68%. At 3 years, this had fallen to 41% overall. However, in the 9 patients with ICDs, the 3-year survival rate was 77%.

"The small subgroup of patients who received ICDs did extremely well post-discharge," Dr. Bloom said. "This suggests that these patients, who have often been felt to be 'too sick' to receive ICDs, may, in fact, benefit quite."

Am J Heart 2007;153:831-836.

12. FAST Trial Shows No Benefit of Factor VII in Treatment of ICH

May 31 2007 (Glasgow) — Despite promising early results suggesting recombinant activated factor VII (rFVIIa, Novo Nordisk, Denmark) may be effective in the treatment of intracerebral hemorrhage (ICH), new research shows the drug, which is currently the only available agent for the treatment of ICH, stops bleeding but does not improve clinical outcomes.

However, even in light of these disappointing phase 3 results, experts say this may not be the end of the road for rFVIIa as a viable treatment for ICH.

Here at the 16th European Stroke Conference, researchers presented the results of the Factor Seven for Acute Hemorrhagic Stroke (FAST) study, which showed a reduction in bleeding but absolutely no difference in the study's primary end point, which was rates of poor outcomes, defined as death or severe disability at 90 days, among patients taking rFVIIa compared with placebo.

In the earlier, phase 2 study, published in 2005 (Mayer SA et al. N Engl J Med. 2005;352:777-785), researchers studied 3 doses (40, 80 and 160 µg/kg) of the drug and found a 50% relative reduction in ICH volume growth compared with placebo.

Shock and Disappointment

Furthermore, they found mortality across all 3 rFVIIa dose groups was 18%, vs 29% in the placebo group, a finding that was statistically significant. In addition to a reduction in mortality, phase 2 study results also showed a dose-related increase in the proportion of patients who survived with no disability at 90 days. "Even though the study was not powered to detect clinical end points, these results were statistically significant and led us, with great enthusiasm, to proceed with [phase 3 of] the FAST trial," said principal investigator Stephan Mayer, MD, from Columbia University, in New York.

However, the investigators' enthusiasm was soon quashed when FAST's phase 3 results came to light. "Initially, we were shocked and disappointed. We couldn't understand how the hemostatic effect that we observed in the first trial remained but the clinical effect completely disappeared," Dr. Mayer told Medscape.

The randomized, placebo-controlled, multicenter, multinational trial compared 20 µg/kg or 80 µg/kg of rFVIIa with placebo in 821 patients with ICH at 180 sites. Patients were eligible for the study if they were 18 years or older and diagnosed within 3 hours of symptom onset by CT scan. Patients were randomized to 1 of 3 study groups. Treatment was then administered within 1 hour of baseline scan. The trial's main outcome was the proportion of patients who died or had severe disability graded as 5 or 6 on the modified Rankin Scale (mRS) at 90 days.

Best Hope

However, he added, the investigators still have not defined an optimal responder group to serve as a cohort for future research. In addition, he said, the pharmaceutical company that manufacturers rFVIIa and has sponsored both trials is suspending further ICH research until further notice.

Nevertheless, Dr. Mayer said, the scientific community is "firmly in favor" of proceeding with further research into rFVIIa and ICH. "It is still our best hope of coming up with something that will help at least some of these patients, where mortality runs between 30% and 40%."

Bo Norrving, MD, PhD, from Lund University Hospital, in Sweden, agreed and said it is "highly plausible" that patient selection will be important in influencing outcomes of rFVIIa in ICH. "This is a very important question to explore. We definitely need better treatment in the acute phase of intracerebral hemorrhage, and if we can better target the patient population factor VII may offer that potential," he told Medscape.

Dr. Norrving pointed out that a much higher proportion of ICH patients come to the hospital much more rapidly than their counterparts with ischemic stroke. "If we have something effective to offer them at a very early stage, we have the opportunity to dramatically improve outcomes," he said.

16th European Stroke Conference: Large Clinical Trials 1/Abstract 1. May 29 – June 1, 2007.

13. Accelerated Diagnostic Protocol Effective for Transient Ischemic Attack

By Will Boggs, MD. NEW YORK (Reuters Health) May 30 - An emergency department (ED) accelerated diagnostic protocol for transient ischemic attack (TIA) is more efficient and less costly than traditional inpatient admission, according to a report in the May 8th Annals of Emergency Medicine.

"If a hospital is willing to commit resources to this accelerated approach, then it can be a win-win for everybody," Dr. Michael A. Ross from William Beaumont Hospital, Royal Oak, Michigan told Reuters Health. "Patients are diagnosed sooner, overcrowded hospitals keep inpatient beds open, and doctors are less likely to miss serious disease since the work up is more easily completed."

Dr. Ross and associates investigated whether treatment of TIA patients using an accelerated diagnostic protocol in the ED was associated with a decrease in the index visit length of stay and with comparable clinical outcomes relative to traditional inpatient care.

The initial ED evaluation included a history and physical, an ECG, cardiac monitoring, a panel of lab tests, and a head CT. Patients also underwent carotid Doppler imaging, 2-dimensional echocardiography, serial nursing "neurochecks," and a neurology consultation.

Most patients (85%) randomized to the accelerated diagnostic protocol were discharged from the ED, the authors report, and the median length of stay was significantly shorter for the accelerated diagnostic protocol patients (25.6 hours) than for patients admitted to hospital (61.2 hours).

Accelerated diagnostic protocol admissions were for clinical events, not for carotid stenosis, major arrhythmia, or echocardiographic findings, the results indicate. The median length of stay for these patients was 100.5 hours.

Median total direct costs for the index visit were significantly lower for the accelerated diagnostic protocol patients ($864) than for the inpatient group ($1528), the researchers note, as were the median 90-day total direct costs ($890 versus $1547, respectively). The median 90-day cost of admitted accelerated diagnostic protocol patients was $2737.

There were no deaths or adverse events during the study period attributable to the use of the accelerated diagnostic protocol, the report indicates.

"This study suggests that shorter periods of observation, coupled with appropriate patient selection and active testing, may be adequate to identify TIA patients who develop early adverse neurologic outcomes," the authors write. "TIA patients need follow-up with their primary care physician or neurologist," Dr. Ross said. "This is part of the TIA protocol. These patients are at increased risk of stroke and major cardiac events in the near future. Their risk profile must be actively managed as outpatients."

Ann Emerg Med 2007.

14. AHA Announces Mission: Lifeline, a New Initiative to Improve Systems of Care for STEMI Patients

from Heartwire — a professional news service of WebMD. May 31, 2007 (Dallas, TX) – The American Heart Association (AHA) today announced the launch of a community-based initiative aimed at activating the critical chain of events necessary for opening blocked arteries [1]. The new plan, known as Mission: Lifeline, is aimed at providing better diagnosis and appropriate transport and ensuring proper care of patients with ST-segment elevation MI (STEMI).

Announcing the initiative, Dr Alice Jacobs (Boston University School of Medicine, Boston, MA), who led the work group addressing the issue of STEMI systems of care this past year, told the media that Mission: Lifeline is grounded in the stark reality of the current treatment--thrombolytic therapy or PCI--of these patients.

"Despite the proven benefits of quickly restoring blood flow to the heart muscle during a heart attack with either therapy, 30% of STEMI patients do not receive the treatment available," said Jacobs. "In addition, approximately 20% of patients are not candidates for the clot-lysing therapy, most often due to a bleeding risk. Of these patients, 70% do not receive angioplasty, even though it is the only way to open the artery. We know that among patients who receive either therapy in the United States, less than half are treated within the recommended time frames after arriving at the hospital."

The new initiative is based on the findings of experts and stakeholders who convened last year to develop a plan for improving care for STEMI, and these findings and recommendations appear online today in Circulation.

All the stakeholders are involved

Speaking during a briefing for the media, Jacobs pointed out that primary PCI, when performed in STEMI patients in a timely manner by healthcare providers at experienced medical centers, is superior to thrombolytic therapy in reducing death and complications following MI, even when patients need to be transferred to hospitals equipped to perform PCI. Clot-busting therapy, however, is the mainstay of treatment because it is more widely available, she said. These realities, said Jacobs, fueled the work of individuals and organizations that have come together to launch the Mission: Lifeline initiative.

In March 2007, the AHA brought together patients, doctors, nurses, hospitals, emergency medical service (EMS) personnel, payers, and policy makers to review the current system of care for STEMI patients, to develop an ideal implementation system, and to identify gaps and barriers between the current and ideal system.

"For patients with STEMI, saving time saves lives," said Jacobs. "Getting STEMI patients the timely care they need involves a series of events that must flow seamlessly to be most effective."

The process, explained Jacobs, begins with educating patients to signs and symptoms of an MI, which are subtler than the public realizes, and the importance of activating EMS by calling 911 for hospital transport. More than half of STEMI patients drive themselves to the hospital or are driven by family and friends, a mistake that often results in delays in diagnosis and treatment that trained EMS personnel could provide. In addition, improving EMS diagnosis of STEMI before hospital arrival is critical to acquire, interpret, and transmit information from the 12-lead ECG. The catheterization lab could then be activated by EMS personnel from the field or by emergency physicians at the hospital who receive the ECG, said Jacobs.

For patients arriving at non-PCI hospitals, they would remain on the stretcher with EMS personnel in attendance until a decision is made about transferring them to a PCI-capable hospital. For STEMI patients who drive themselves to a non-PCI hospital, transfer to a PCI-capable hospital should take the same urgency as a 911 call, said Jacobs.

Other steps include working with payers and policy makers to ensure systems are in place for proper reimbursement and accountability protocols. A STEMI Center Certification Program with criteria for STEMI referral and receiving hospitals is also in the works. Existing regional STEMI systems of care have been implemented in Minnesota, North Carolina, and Boston, and these have served as models for Mission: Lifeline. California, Texas, and Florida are also participating in pilot programs.

Dr Tim Henry (Minneapolis Heart Institute Foundation, MN), who also spoke during the media briefing, provided information on the STEMI system of care experience in Minnesota, the largest reported experiences designed to integrate the care at non-PCI hospitals (STEMI referral) with a regional PCI-capable hospital (STEMI-receiving). A key component of their program is that emergency room physicians, or EMS personnel in some situations, can activate the system with a phone call. Using a standardized protocol, the median door-to-balloon times from the community STEMI-referral hospitals to balloon inflation in the STEMI-receiving hospital were 96 minutes in areas 60 miles from the referring hospital and 118 minutes from centers as far as 210 miles away. "If done in standardized manner, patients can be transferred and treated in a timely manner," said Henry.

The full cost of implementing the STEMI system of care, said Jacobs, has not been assessed. The writing group noted that the system is implemented and funded at the community level, although the AHA will work with various agencies to provide expertise and to support training. The continued operation of referring hospitals, they added, is critical, and the AHA hopes Mission: Lifeline can foster a system where both the referring and receiving STEMI hospitals remain viable.

Jacobs AK, et al. Development of systems of care for ST-elevation myocardial infarction patients. Circulation 2007; OI:10.1161/CIRCULATIONAHA.107.184043. Available (full-text free) at:

15. Aggressive Care Might Delay Recovery From Whiplash

News Author: Laurie Barclay, MD. May 29, 2007 — Increased intensity of care by a general practitioner or chiropractor is associated with slower recovery for patients with soft tissue injuries such as whiplash, according to the results of a study published in the May 25 Early View issue and June print issue of Arthritis & Rheumatism.

"Although there are few effective treatments for whiplash, a growing body of evidence suggests that the delivery of intensive health care shortly after the injury may lead to iatrogenic disability," write Pierre Côté, DC, PhD, from the University of Toronto and the Toronto Western Research Institute and Rehabilitations Solutions in Ontario, Canada, and colleagues. "The objective of our analysis was to test whether the association between early patterns of care and time to recovery reported by Côté et al in a cohort of patients compensated under no-fault insurance is reproducible in an independent cohort of patients with whiplash compensated under tort insurance."

The study cohort consisted of 1693 adults in Saskatchewan who sustained whiplash injuries between July 1, 1994, and December 31, 1994. The investigators studied 8 initial patterns of care that integrated type of provider (general practitioners, chiropractors, and specialists) and number of visits (low vs high utilization), using Cox models to estimate the association between patterns of care and time to recovery while controlling for injury severity and other confounders.

Even after controlling for important prognostic factors, patients in the low-utilization general practitioner group and those in the general medical group had the fastest recovery. Compared with the low-utilization general practitioner group, the high-utilization chiropractic group had a 1-year rate of recovery that was 25% slower (adjusted hazard rate ratio [HRR], 0.75; 95% confidence interval [CI], 0.54 - 1.04), the low-utilization general practitioner plus chiropractic group had a rate that was 26% slower (HRR, 0.74; 95% CI, 0.60 - 0.93), and the high-utilization general practitioner plus chiropractic combined group had a rate that was 36% slower (HRR, 0.64; 95% CI, 0.50 - 0.83).

"The observation that intensive health care utilization early after a whiplash injury is associated with slower recovery was reproduced in an independent cohort of patients," the authors write. "The results add to the body of evidence suggesting that early aggressive treatment of whiplash injuries does not promote faster recovery. In particular, the combination of chiropractic and general practitioner care significantly reduces the rate of recovery."

Study limitations include possible residual confounding by indication.

"Our research complements the findings of randomized clinical trials suggesting that early minimal care that promotes activation improves prognosis," the authors conclude. "Future research should include the design of pragmatic randomized trials to test the effectiveness of various patterns of care in the community. These trials are essential to understand the influence of health care provision in preventing or facilitating disability."

Arthritis Rheum. 2007;57:861-868.

16. Unnecessary, Inappropriate ER Visits Hard to Determine

Source: AMA Member Communications

In a news analysis, the UPI (5/19, Pierce) reported that although "health-care reformers say the U.S. can save a lot of money by reducing unnecessary emergency-room visits," two studies presented at the Society for Academic Emergency Medicine Annual Meeting "found that it is difficult to define what an 'unnecessary' or 'avoidable' ER visit is, and reducing those visits may not actually save a lot of money."

In the first study, researchers "examined Oregon emergency-room data before and after significant cuts in 2003 to the state's Medicaid program." While they found "a significant increase in emergency-room visits from uninsured patients, they were unable to easily divide them into categories of non-emergency, emergency, emergencies that could have been avoided with timely primary care and emergencies that could be treated if timely primary care were available." Another study "suggests there is little money to be saved from cracking down on unnecessary emergency-room visits. During the same time period in Oregon, only 6.8 percent of Medicaid dollars were spent on emergency care, and four out of five beneficiaries never went to the emergency room at all." Eileen Moore, director of the Health Rights Project at the Georgetown University School of Medicine, told the UPI, that the "causes of patients seeking primary care in emergency departments may also range beyond simple lack of affordability. Transportation, safety concerns and work schedules also play a role -- even for patients that are insured."

Cyrus Shahpar & Brian Potts, Managing Editors, CAL/AAEM News Service.

The CAL/AAEM Archives are available at:

17. Recommendations Issued for Acute Pancreatitis

News Author: Laurie Barclay, MD. June 4, 2007 — A review in the May 15 issue of American Family Physician highlights the best practices for diagnosing and treating acute pancreatitis, defined as a reversible inflammatory process of the pancreas.

Full-text (free):

18. Glucagon for the Relief of Esophageal Food Impaction: Does it really work?

Al-Haddad M, et al. Dig Dis Sci. 2006;51:1930-3.

We sought to evaluate our experience with glucagon used in the emergency department setting to relieve esophageal food impaction (EFI). We reviewed the records of patients with food impaction who received glucagon between January 1998 and May 2003 and recorded patient demographics, medical history, symptoms following glucagon administration, and endoscopic findings. There were 92 episodes of food impaction in 85 patients.

Thirty-three percent of the episodes resulted in resolution of symptoms following a dose of glucagon. Sixty-seven percent had symptoms of food impaction after glucagon and underwent upper endoscopy in the emergency room. Only previous solid food dysphagia was positively associated with response to glucagon. Patients who received glucagon plus a benzodiazepine were more likely to have resolution of the EFI. In our experience, glucagon appears to relieve food impaction in one third of patients treated. This result is comparable to previously published data examining glucagon and placebo. The lack of advantage over placebo questions the practice of glucagon administration for EFI.

19. Sodium Thiosulfate or Hydroxocobalamin for the Empiric Treatment of Cyanide Poisoning?

Hall AH, et al. Ann Emerg Med. 2007;49:806-813.

Cyanide poisoning must be seriously considered in victims of smoke inhalation from enclosed space fires; it is also a credible terrorism threat agent. The treatment of cyanide poisoning is empiric because laboratory confirmation can take hours or days. Empiric treatment requires a safe and effective antidote that can be rapidly administered by either out-of-hospital or emergency department personnel. Among several cyanide antidotes available, sodium thiosulfate and hydroxocobalamin have been proposed for use in these circumstances. The evidence available to assess either sodium thiosulfate or hydroxocobalamin is incomplete.

According to recent safety and efficacy studies in animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an appropriate antidote for empiric treatment of smoke inhalation and other suspected cyanide poisoning victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium thiosulfate may be too slow for it to be the only cyanide antidote for emergency use. Hydroxocobalamin is being developed for potential introduction in the United States and may represent a new option for emergency personnel in cases of suspected or confirmed cyanide poisoning in the out-of-hospital setting.

Full-text pdf (free as of June 5):

20. Boxed Warning Issued for MRI Contrast Agents

The FDA is mandating boxed warnings on gadolinium-based MRI contrast agents.

The agency says that patients with severe renal insufficiency who are exposed to the agents are at risk for developing nephrogenic systemic fibrosis, a life-threatening disease that can cause thickening and hardening of the skin, connective tissues, and other organs. Also at risk are patients with chronic liver disease, or with just-transplanted livers, who have any level of renal insufficiency. Several cases of gadolinium-associated fibrosis were reported in February in MMWR.

The FDA advises that physicians should check their patients' renal status before exposure to gadolinium-based agents.

FDA announcement (Free):

21. Prevention of awakening signs after rapid-sequence intubation: a randomized study

Morgan Jaffrelot M, et al. Amer J Emerg Med; 2007;25:529-534.

Background: This study aimed to establish the incidence of signs of inadequate sedation after rapid-sequence intubation (RSI) and to determine whether a supplementary bolus of induction agent decreases these signs.

Methods: A randomized, double-blind trial design was used. Patients were randomly assigned to 1 of 2 treatments: RSI plus etomidate bolus followed by continuous sedative infusion (ETO group) or RSI plus placebo followed by continuous sedative infusion (placebo group). The primary outcome measure was a composite sedation score measured 6 minutes after induction. The components of the score were the Ramsay sedation score, the presence of cough or pulling at endotracheal (ET) tube, jaw relaxation, motor activity, and eye opening. The total score (0-10) was the sum of the 5 components.

Results: There were 21 patients in the ETO group and 20 patients in the placebo group. The percentage of patients presenting with at least 1 sign of awareness was 43% in the ETO group and 65% in the placebo group (P = .16) 6 minutes after induction. The sedation score was significantly higher at 6 minutes in the placebo group compared with the ETO group (2.4 ± 2.9 vs 0.9 ± 1.4; P less than .05). The use of additional sedative drugs during the observation period was 43% (9/21) in the ETO group compared with 55% (11/20) in the placebo group (P = .44).

Conclusions: This study demonstrated that some patients have signs of inadequate sedation after RSI. These signs may be partially prevented by a supplementary dose of an induction agent but other supplementary sedation seems necessary.