Lit Bits: November 28, 2008

From the recent medical literature...

1. Specialists Identify Clinical Features to Avoid TIA Misdiagnosis

Allison Gandey. November 21, 2008 — Neurologists are proposing 3 clinical features to help clinicians diagnose difficult-to-assess transient ischemic attacks (TIAs). In a study to be published in the December print issue of Cerebrovascular Diseases and published in the November 4 Online First issue, researchers report that only 40% of cases in the emergency department are true TIAs.

"There are not a lot of objective findings on which to base a diagnosis and this can be exceedingly challenging. Neurologists should be involved in the diagnosis," lead author Shyam Prabhakaran, MD, MS, from Rush University Medical Center in Chicago, Illinois, told Medscape Neurology & Neurosurgery.

To help bridge this gap, Dr. Prabhakaran's team developed a list of bedside clinical features designed to help clinicians in training, nonneurologists, and less experienced neurologists more accurately distinguish TIAs from nonischemic causes.

They identified 3 clinical characteristics:

Gradual symptom onset.
History of unexplained transient neurologic attacks.
Presence of nonspecific symptoms.

"Speed of onset, we found, was the strongest indicator of a TIA," Dr. Prabhakaran added in a news release. "I typically ask my patients if their symptoms came on like lightning — within seconds," he said. "With other neurological problems that can mimic a TIA — migraines or seizures — for example, symptoms take more than a minute to manifest."

The research team examined the records of 100 emergency department patients diagnosed with TIA and admitted for further evaluation.

After inpatient evaluation and review, final diagnoses were made by 2 neurologists. Of the 100 patients, 40 were confirmed to have TIA and 60 nonischemic transient neurologic attacks.

Table. Independent Predictors of Nonischemic Transient Neurologic Attacks
Characteristic Odds Ratio P Value
Gradual symptom onset 6.7 .002
History of unexplained attacks 10.6 .031
Presence of nonspecific symptoms 4.2 .008

"These data imply that without expert neurologic evaluation, a significant overestimation of the true prevalence and incidence of TIA is likely," the researchers write.

They also point to several limitations to their work, including the fact that it is a hospital-based study and is not generalizable to outpatient referral or a community setting. Also, because no gold standard exists to improve diagnostic accuracy for TIA, the final diagnosis can be questioned.

Still, investigators report that their 3 clinical features correctly classified 79% of study participants. These data may be useful in the education of clinicians and may help better triage patients in the emergency department, they note.

"It's important not to miss a diagnosis of TIA as these can be harbingers of stroke and patients need to be treated," Dr. Prabhakaran added. "But at the same time, we don't want to overdiagnose TIAs either. Overdiagnosis subjects patients to the risks of unnecessary and potentially dangerous medications and tests and leaves their actual condition untreated or inadequately managed."

The researchers have disclosed no relevant financial relationships.

Cerebrovasc Dis 2008;26:630-635.

2. In-Patient Hallway Boarding Lowers Mortality in Emergency Department Patients

Vicki Gerson. From American College of Emergency Physicians (ACEP) 2008 Scientific Assembly

October 30, 2008 (Chicago, Illinois) — Patients in the emergency department who are admitted to the hospital and wait for an available bed in an in-patient hallway instead of being "boarded" in the emergency department have no medical complications.

The number one challenge in hospital emergency departments is overcrowding. "There is a 26% increase in demand for emergency room care, while throughout the country, 425 emergency departments have closed," coauthor Adam Singer, MD, professor and vice chair for research at Stony Brook University Medical Center, Stony Brook, New York, told Medscape Emergency Medicine.

Dr. Singer and colleagues noted the consequences of overcrowding in emergency departments can result in treatment delays, increased medical errors, increased mortality, and patient and staff dissatisfaction. The study, which was conducted from January 2004 to January 2008, described the medical center's experience with transferring patients to in-patient hallways.

A physician identified admitted patients boarded in the emergency department who were appropriate for in-patient hallway boarding. Patients who need suctioning and those who require high flow oxygen or intensive care unit admissions were not admitted to in-patient hallways. Each hallway patient received a call bell and a privacy screen.

During the 4-year period, 278,975 people visited the emergency department, of which 57,487 were admitted, and 1798 patients died. "Of all admissions, 2036 went to hallways, 51,336 went to a standard bed (type of admit was unknown for 4115). Patients admitted to standard and hallway beds were similar in age (IQR [interquartile range], 55 [37 – 72 years]) and sex (48% female). The median (IQR) times from ED [emergency department] triage to actual admission in patients admitted to standard and hallway beds were 426 (306 - 600) and 624 (439 - 893), respectively."

Dr. Singer also told Medscape Emergency Medicine that 4% of the patients that were placed in hallways were similar in age and sex. The mortality rate was 2.6% for patients who went to a standard bed and 1.1% for patients who were first placed in the hallway. "There are no reported deaths to date while a patient was placed in the hallway while waiting for a room, as well as no safety concerns,” he said.

The researchers concluded emergency patients who were admitted to the hospital and held in an in-patient hallway to wait for a bed, instead of being "boarded" in the emergency department to wait, had mortality rates and intensive care unit admission rates of less than half that of patients in standard rooms. Boarding patients in the emergency department is harmful and harmful to the patients coming to the emergency department who experience delays in being seen by a physician who is attending to emergency department boarders.

Dr. Singer emphasized that overcrowding in the emergency department is not just an emergency department problem. "It is a hospital problem." He believes that by distributing in-patient hallway patients in the units does not affect patient care.

"I think this study is important in several ways," session moderator Jesse Pines, MD, assistant professor of emergency medicine and epidemiology at the University of Pennsylvania told Medscape Emergency Medicine. "It points out to hospital administrators the safety of a practice thought to be potentially unsafe is not and shows the ability of implementing a crowding solution. Other hospitals should consider trying it."

This study was funded by an EMF Grant given to the institution to assess overcrowding.

3. Controversy Swirls Around Early Goal-Directed Therapy in Sepsis: Pioneer Defends Ground-Breaking Approach to Deadly Disease

McKenna M. Ann Emerg Med. 2008;52:651-654 .

Plans to re-examine a research finding via a much larger set of clinical trials, a common event in medical research, have provoked an uncommon result: an unusually public airing in the mainstream media of allegations, financial questions and wounded professional pride.

The research finding at the center of the dispute is early goal-directed therapy for sepsis, formulated 7 years ago by Emanuel P. Rivers, MD, MPH, vice chairman and director of research in emergency medicine at Henry Ford Hospital in Detroit, MI. Dr. Rivers, who trained in critical care, emergency and internal medicine, proposed applying the “golden hour” to severe sepsis and septic shock.

His protocol identified patients and began treating them in the emergency department (ED), before they were admitted to intensive care. It deployed a bundle of conventional measures—early recognition of patients with a high risk of death using blood lactate levels or hypotension and giving antibiotics, fluid therapy titrated to central venous pressure, vasopressors if required to maintain blood pressure, hemoglobin concentration above 10 mg/dl using transfusions if required, and maintaining central venous blood oxygen saturation above 70% using medication (Inotropes) to improve perfusion.

And it had dramatic results. Dr. Rivers' protocol cut the mortality rate in the 130 patients who received it to 30.5%, compared to 46.5% among the 133 patients treated with the hospital's standard care—a drop in deaths so striking that the study's data safety monitoring board decided to end it early. That seemed a significant advance for a disease that affects 750,000 Americans each year and costs from $16.7 2 to $24 billion and that had had an intractable mortality rate for 3 decades. Rivers' protocol was adopted by the Surviving Sepsis Campaign, which is endorsed by the American College of Emergency Physicians and the Society of Critical Care Medicine, and is recommended by the Institute for Healthcare Improvement.

Early goal-directed therapy drew some criticism from the start,6 and EDs were slow to adopt it: 3 years after it was published, a survey of 30 academic medical center EDs, found only 2 using the protocol. (There is no registry of EDs that use early goal-directed therapy, but it has been adopted by several large health systems, and a July 2008 paper8 surveyed 40 hospitals now using it.)

Departments that have adopted it are enthusiastic. In a 2006 article in Chest, describing a yearlong trial at Cooper University Hospital in Camden, NJ, Stephen Trzeciak, MD, MPH, declared that early goal-directed therapy “could reliably be achieved in real-world clinical practice.” And later that year, authors from 9 institutions, including Trzeciak and Rivers, reported the outcomes of implementing early goal-directed therapy in 12 institutions other than Henry Ford; all 12 had comparable declines in sepsis mortality rates.

“Unnamed Sources”
Overall, at least 25 papers supporting the Rivers protocol have been published since 2001, according to the PubMed database. A recent meta-analysis of 9 studies covering 1,001 patients confirmed that the protocol reduces sepsis deaths.

But early goal-directed therapy has still faced questions. They range from the relatively small size of Rivers' original study, the fact that it was conducted at a single institution, and the reality that it remains the only randomized clinical trial of early goal-directed therapy; to the necessity of the specific monitoring catheter; to whether the protocol is reproducible in thinly staffed community hospitals and very crowded urban EDs.

In response, the National Institutes of General Medical Sciences, part of the National Institutes of Health, announced in late 200613 that it would grant $8.4 million over 5 years to test the Rivers protocol in a much larger randomized trial. The study, called ProCESS (Protocolized Care for Early Septic Shock), plans to enroll 1,935 patients at 24 institutions and will be directed by investigators at University of Pittsburgh Medical Center.

So far, so normal: a creative researcher produces a path-breaking finding, and after a period of exploration and debate, the finding is re-examined for reproducibility. “It is a basic tenet of scientific investigation that you should be able to replicate a work in a different and bigger setting to make sure it is truly helpful,” said Donald Yealy, MD, of the University of Pittsburgh, one of the ProCESS trial's principal investigators. (Yealy is a deputy editor of Annals but was not involved in the preparation of this story.)

Dr. Rivers Responds
But the next step in the saga of early goal-directed therapy has been somewhat outside the norm. On August 14, the Wall Street Journal ran a front-page article that questioned both Rivers' analysis and his ethics.

Full-text: http://www.annemergmed.com/article/S0196-0644(08)01897-0/fulltext

4. Benefits of Prehospital Notification for Stroke Patients

Prehospital ED notification decreased door-to-CT time by 23% and doubled use of thrombolytic therapy.

Early identification and management of acute stroke are critical for improving outcomes. To examine the effects of advance notification of the arrival of stroke patients, researchers retrospectively analyzed data for 118 patients with acute stroke who were transported by emergency medical services directly from the scene to a single tertiary care emergency department within 6 hours of symptom onset during a 16-month period.

EMS staff provided advance notification to ED staff for 44 patients. No significant differences in age, sex, stroke history, or median National Institutes of Health Stroke Scale scores were noted between patients for whom prehospital notification was and was not given. Prehospital notification was associated with significantly shorter door-to-computed tomography (CT) time than no prehospital notification (median time, 40 vs. 47 minutes). In multivariable linear regression modeling, prehospital notification reduced door-to-CT time by 23%. Nine patients for whom prehospital notification was given and none for whom notification was not given had prolonged door-to-CT times (2–5 hours). All patients were evaluated by a vascular neurologist. Overall, 29% of patients received thrombolytic therapy (intravenous tissue plasminogen activator [TPA] in 20; IV TPA followed by intra-arterial thrombolysis in 12; and intra-arterial thrombolysis alone in 2). Patients who arrived at the ED after prehospital notification were twice as likely as those who arrived without advance notice to receive thrombolytic therapy (42% vs. 21%).

Comment: As expected, analogous to prehospital activation of the cath lab for patients with ST-segment-elevation myocardial infarction, prehospital notification of the ED allows mobilization of hospital resources for incoming stroke patients. Prehospital notification for stroke already is a class I recommendation of the American Heart Association. Why advance notification was not given for 63% of patients in this study is not known. Most disturbing is that even when advance notification was provided, patients did not get CT scans within the recommended 30 minutes. Although the window of time for stroke treatment is widening to 4.5 hours (JW Emerg Med Sep 15 2008 and Sep 24 2008), that is not a license for delay. Time to CT is a key driver of rapid thrombolytic therapy and requires close attention.

— Kristi L. Koenig, MD, FACEP. Published in Journal Watch Emergency Medicine November 7, 2008. Citation: Abdullah AR et al. Prehosp Emerg Care 2008; 12:426.

5. CT Important in Emergency Diagnosis of Appendicitis

NEW YORK (Reuters Health) Oct 30 - CT of the appendix has a significant impact on the management of emergency department patients who are suspected of having appendicitis, researchers report in the October issue of the American Journal of Roentgenology.

Dr. Robert O. Nathan of the University of Washington, Seattle, and colleagues note that despite the apparent value of CT under these circumstances, it has not been determined whether the approach should be used in all such patients.

To investigate further, the researchers studied data on 100 consecutive patients who attended a community hospital emergency department and underwent appendix CT.

In 3 of the 5 patients in whom appendicitis was considered very likely, CT determined that this was not the case. This was also true of 9 of 18 in whom appendicitis was considered to be likely.

However, in all 20 patients who considered to be unlikely to have appendicitis, CT results were in accordance.

Overall, CT scans led to a change in the treatment plans of 29% of the patients. The approach had a sensitivity of 94%, a specificity and positive predictive value of 100%, and a negative predictive value and accuracy of 99%.

"The data suggest that CT can be withheld in patients in whom emergency clinicians rate the likelihood of appendicitis as unlikely but that CT findings are often of benefit even when appendicitis is judged to be very likely," the researchers conclude.

Am J Roentgenol 2008;191:1102-1106.

6. Clinical Markers May Help Detect Abusive Head Trauma in Young Children

Clinical Context
Inflicted head injury is the leading cause of death in children who are abused. Characteristics of the child at risk for abusive injury include age younger than 1 year, prematurity at birth, and multiple birth, whereas family characteristics include younger mother, single mother, low socioeconomic status, and late or no prenatal care.

This is a retrospective chart review of children who underwent computed tomography scans, conducted at the National Center for Child Health and Development in Japan, to examine factors associated with AHT and factors that distinguish AHT from non-AHT.

Laurie Barclay, MD. October 30, 2008 — Several clinical markers evaluated at a medical visit may help detect abusive head trauma (AHT) of young children, according to findings of a comparative case series study reported in the October issue of Pediatrics.

"Distinguishing abusive head trauma in young children from other diseases by symptoms is difficult in practice," write Takeo Fujiwara, MD, PhD, MPH, from the National Institute of Public Health in Saitama, Japan, and colleagues. "Comparisons between abusive and nonabusive head trauma in young children in Japan, where computed tomography is widely and easily available, might contribute to identifying markers of abusive head trauma that differ from that in Western countries. The objective of this study was to compare the characteristics of abusive and nonabusive head trauma in young children in Japan."

A retrospective medical chart and social work record review identified 260 children who were aged 0 to 2 years, visited the National Center for Child Health and Development (Tokyo, Japan) from March 1, 2002, to December 31, 2005, and underwent computed tomography scanning because of suspected intracranial injury. Demographic and perinatal characteristics, injury history, clinical presentation, and outcomes were compared in patients with abusive or non-AHT, based on the published definition, using chi-square and Fisher's exact tests.

Compared with patients with non-AHT, those with AHT were significantly younger, with peak incidence at ages 2 to 4 months and ages 7 to 9 months. Other clinical markers associated with AHT were no injury history given by the caregiver (60.7%); neurologic symptoms such as unconsciousness, seizure (32%), or paralysis; subdural hemorrhage; and retinal hemorrhages.

Despite the severity of clinical outcomes in patients with AHT, social welfare services separated only 32% of these patients from the caregiver.

"This study highlights the several clinical markers to detect abusive head trauma at a medical visit, including an absence of injury history, neurologic symptoms, subdural hemorrhage, and retinal hemorrhage," the study authors write. "These markers can be used to detect abusive head trauma cases by physicians and social welfare workers to protect children from additional abuse."

Limitations of the study include retrospective design, which may lead to misclassification; funduscopy and skeletal surveys not completed in some cases; criteria used might inflate the number of AHT cases; small sample size; and study performed only in 1 hospital, limiting generalizability.

"Similar clinical presentations of AHT with previous studies in Western culture (ie, the absence of an injury history, seizures, SDHs [subdural hemorrhages], and retinal hemorrhages) were also found in Japan," the study authors conclude. "The 2 peaks of age, at 2 to 4 months and 7 to 9 months, might be a characteristic unique to Japan....The CGC [Child Guidance Center] should be encouraged to consider these findings for making better informed decisions regarding children who are referred to CGC."

Pediatrics. 2008;122:e841-e847.

7. Being Difficult: For Some Patients, It's a Coping Mechanism

By Sandra G. Boodman. Special to The Washington Post. Tuesday, October 21, 2008; Page HE01

It's fashionable in health care to talk about the importance of being a knowledgeable, assertive patient and of forging a working partnership with a doctor, a relationship that will speed healing or improve the process of living with a chronic, even life-threatening, illness.

But as Michelle Mayer, a nurse with a doctorate in public health, discovered, the path to achieving such an alliance often is not an easy one.

Married to a Duke University physician, Mayer said she never set out to become difficult, the sort of patient who is the bane of many doctors. But as she wrote in the current issue of the journal Health Affairs and documented on her blog, http://diaryofadyingmom.blogspot.com, being com-pliant was bad for her health.

Challenging her doctors' advice and making decisions that at times diverged from their recommendations, she wrote, helped her wage a 12-year battle with scleroderma, an incurable and sometimes fatal autoimmune disorder that causes hardening of the skin. Mayer's illness was diagnosed when she was 27; her initial symptoms included extreme fatigue and uncontrollable itching.

"I tried being the 'good patient,' " said Mayer, who until illness forced her to retire was an assistant research professor in the school of public health at the University of North Carolina at Chapel Hill. Becoming difficult -- some, she said, might call it "empowered" -- was her "natural reaction" to doctors who were "incompetent, rude or domineering."

Full-text: http://www.washingtonpost.com/wp-dyn/content/article/2008/10/17/AR2008101702677.html

8. Images in EM

a. Adolescent With Rash and Cough

Heilbrunn BR, et al. Ann Emerg Med. 2008;52:606.

A 12-year-old girl from rural Indiana presented to the emergency department for temperature of 40°C (104°F), cough, and a painful rash on her legs. Her symptoms began 1 month previously with cough and fever, with subsequent development of rash.

Evaluation revealed a nontoxic, well-developed 12-year-old. She had a pulse of 142 beats/min, respiratory rate of 18 breaths/min, blood pressure of 110/67 mm Hg, and room air oxygen saturation of 99%. Her physical examination result was notable for anterior cervical adenopathy and tender erythematous nodular lesions on her lower extremities (Figure 1). Chest radiograph and chest computed tomographic scan are also included (Figure 2, Figure 3).

http://www.annemergmed.com/article/S0196-0644(08)01462-5/fulltext

b. Adult Female With Pink Nodules on Skin

Saleh M, et al. Ann Emerg Med. 2008;52:616

53-year-old healthy woman presented with a complaint of a painless pink nodule resembling an insect bite that started on her hand and progressed to the rest of her upper extremity (Figure 1, Figure 2). The symptoms started 3 weeks after gardening in her yard. She was treated with a 10-day course of antibiotics by her physician, without improvement. The patient began receiving antifungals, and a culture subsequently confirmed the diagnosis.

http://www.annemergmed.com/article/S0196-0644(08)01565-5/fulltext

9. Resistance to Fluoroquinolones Increasing in Outpatient Urinary E. Coli Isolates

By Will Boggs, MD. NEW YORK (Reuters Health) Nov 13 - Fluoroquinolone resistance in outpatient urinary Escherichia coli isolates has increased after recommendations for their use for empiric treatment of urinary tract infections, according to a report in the October issue of The American Journal of Medicine.

"Management of urinary tract infections, a common reason for antibiotic use in adults, is complicated by rising resistance of Escherichia coli to oral antibiotics," Dr. Connie Savor Price told Reuters Health. "Rapid emergence of fluoroquinolone resistance in E. coli following increased prescribing suggests further use would make fluoroquinolones unreliable for treatment within a short time."

Dr. Price, from Denver Health and Hospital Authority, Colorado, and colleagues examined the relationship between levofloxacin use and the emergence of fluoroquinolone-resistant E. coli in an adult outpatient population.

During a period when outpatient fluoroquinolone prescriptions increased from 3.8 prescriptions per 1000 outpatient visits (1998) to 12.8 prescriptions per 1000 outpatient visits (2005), levofloxacin resistance increased from 1% of all E. coli isolated in the outpatient setting to 9.4%, the authors report.

Virtually all levofloxacin-resistant E. coli were fully resistant, and 78% of isolates were resistant to two or more additional antimicrobial classes. Only a minority of isolates remained sensitive to trimethoprim-sulfamethoxazole (34.1%) or ampicillin (22.0%).

"Although antibiotic use predictably leads to resistance, we did not anticipate the pace of the emergence of resistance," the investigators say. "In just 6 years, levofloxacin resistance increased more than 5-fold."

"When possible," Dr. Price said, "as in most cases of simple cystitis, fluoroquinolone-sparing regimens should be utilized to preserve this important class of antibiotic. For simple cystitis, we are advocating nitrofurantoin for patients without contraindications."

Am J Med 2008;121:876-884

10. Procedural Sedation Is Safe for Children Younger Than 2 Years

About 6% of children who were sedated with combinations of ketamine, morphine, and midazolam experienced adverse events, all of which were minor, except for one case of respiratory failure.

Misra S, et al. Int J Emerg Med 2008;1:173–177.

Introduction
Providing relief from pain and anxiety associated with diagnostic and therapeutic procedures has become an ethical imperative in children as well as a measured quality indicator from the family’s perspective. This, along with a tremendous increase in the number of procedures performed on children outside the operating room, has led to non-anesthesiologists, particularly emergency physicians, taking a key role in the administration of procedural sedation and analgesia (PSA) to children. It has been estimated that roughly a quarter million children will receive PSA in the emergency departments (EDs) annually and that children under 2 years of age constitute roughly 20–30% of those. It has been shown that pain in infants and toddlers is poorly recognized and documented, predisposing them to receive less analgesia when compared with older children.

Commonly used medications for PSA such as ketamine are relatively contraindicated in very young children (less than 6 months of age) because of an association with increased risk of airway complications. Inadequate sedation and analgesia predisposes to procedural failure, parental anxiety and dissatisfaction, and poor quality of care. The anatomic differences in the airway like smaller airway diameter, longer and floppy epiglottis, and the physiologic differences in drug metabolism between younger and older children could predispose younger children to a higher risk for adverse events related to sedation. Studies have shown contrasting results regarding association of age and adverse events related to PSA. While some studies have found children less than 2 years of age to be at an increased risk for adverse events related to PSA, other studies have found no association between age and adverse events related to PSA. To our knowledge, there have been no studies that have focused exclusively on PSA in children less than 2 years of age. The main objective of our study is to describe PSA in children less than 2 years of age in the ED of a tertiary care children’s hospital. Additionally, we will describe the indications for PSA, medications used, efficacy of sedation, and adverse events related to sedation in this group of children.

Full-text (pdf): http://www.springerlink.com/content/2v2q153557p1m741/fulltext.pdf

11. How Common Is Aspirin Resistance?

True resistance occurred in only 5% of patients; other "resistance" was attributed to dosing nonadherence.

Aspirin acetylates the cyclooxygenase (COX)-1 enzyme, thereby preventing the conversion of arachidonate to thromboxane A2 (TxA2), a powerful platelet-aggregating agent. Based on this and other antithrombotic properties of aspirin (attenuation of fibrin cross-linking and augmentation of clot permeability and lysis), this agent has become a mainstay in the management of patients with atherothrombotic disorders. However, disturbing reports of aspirin resistance have weakened confidence in the effectiveness of this inexpensive and readily accessible drug. Patients are considered resistant to aspirin if ex vivo tests of platelet function show lack of inhibition, if production of TxA2 continues during aspirin therapy, or if thrombosis recurs. Yet another — largely unexplored — reason for aspirin resistance might be lack of adherence in taking the drug.

To evaluate the relation between aspirin resistance and adherence, Italian investigators performed a prospective study of 100 consecutive patients who had been undergoing continuous aspirin therapy for 6 months. In 69 participants, platelet aggregation and thromboxane metabolite concentration measures were consistent with the expected effects of aspirin. The remaining 31 "aspirin-resistant" patients were entered into a controlled program in which they were given 100 mg of aspirin daily for 7 days and carefully monitored for adherence.

Repeat laboratory testing after 7 days showed full aspirin effect in 26 of these patients, which suggested that they were not resistant but rather were nonadherent with their previous aspirin therapy. The five remaining patients also demonstrated resistance after receiving a second 7-day course of aspirin at a higher dose (325 mg daily), thus verifying that they were truly aspirin-resistant. The three groups (aspirin-sensitive, aspirin-nonadherent, and aspirin-resistant patients) had similar histories of cardiovascular disease and risk factors. Further analyses revealed that patients who were taking more than six tablets of prescribed medications daily were significantly more likely to be nonadherent than were those taking fewer medications (P less than 0.001). The number of prescribed medications predicted poor adherence independent of patient age; gender; or history of previous stroke, myocardial infarction, hypertension, diabetes, or dyslipidemia.

Comment: The authors found that true aspirin resistance occurred in only 5% of patients. Poor adherence with dosing — which was more likely among patients taking more than six tablets of various medications daily — accounted for 84% of presumed drug resistance. The message of this study might be applicable to many other situations in which patients are instructed to take several drugs concomitantly: Failure to observe a positive response might be due to poor adherence rather than to drug resistance. Explaining why a drug is being given, stressing the importance of adhering to instructions, and monitoring patients carefully for dosing adherence are necessary to ensure optimal outcomes.

— David Green, MD, PhD. Published in Journal Watch Oncology and Hematology November 18, 2008. Citation: Pignatelli P et al. J Thromb Haemost 2008;6:1832.

12. CT Perfusion Scan Spots Acute Stroke in the Emergency Setting

By Megan Rauscher. NEW YORK (Reuters Health) Nov 11 - Computed tomography (CT) perfusion imaging can be used to diagnose acute ischemic stroke in the emergency department more rapidly than magnetic resonance imaging (MRI), the standard for stroke diagnosis, according to results of a large single-center study.

"We looked at over 400 patients and found CT perfusion scans to be very accurate and rapid -- within 5 minutes of the patient getting on the CT scanner table you can have an answer, as opposed to MRI, which takes half an hour," Dr. Ansaar T. Rai noted in a telephone interview with Reuters Health.

"Our study reveals that the widespread use of CT perfusion is a practical way to help busy emergency departments save precious time in stroke diagnosis, target treatment and reduce the risks of inappropriate thrombolytic use," Dr. Rai added in a university statement.

Dr. Rai, from the department of radiology, West Virginia University Health Sciences Center in Morgantown, and colleagues retrospectively reviewed 422 patients who underwent CT perfusion for suspected stroke. CT perfusion abnormalities were correlated with subsequent diffusion weighted image (DWI) abnormalities seen on MRI performed within 1 week of CT.

Of 157 acute ischemic strokes confirmed by MRI, 78 showed CT perfusion abnormalities (sensitivity 49.7%).

However, after excluding small non-vascular territory strokes, there were 77 acute ischemic strokes with total volume of infarcted tissue of more than 5 cc by DWI. Of these, 71 showed CT perfusion abnormalities, yielding a sensitivity of 92.2%, the investigators report in the October issue of the Journal of Emergency Medicine.

Of the 265 patients without acute ischemic stroke, none showed CT perfusion abnormalities, yielding a specificity for detecting ischemic stroke of 100%.

It's worth noting, the researchers say, that the average time between emergency room neurological exam and CT scan was only 35 minutes.

They conclude that CT perfusion imaging is effective for diagnosing major strokes "that result in more devastating outcome."

"Every hospital has a CT scanner -- that's why we chose this modality," Dr. Rai commented, "and by doing this test, we can tell with a very fair degree of certainty whether a person is having a major ischemic stroke -- the kind that if treated quickly can really help the patient avoid major disability."

J Emerg Med 2008;35:287-292.

13. The Management of STEMI Patients

a. The Accuracy of an Out-of-Hospital 12-Lead ECG for the Detection of ST-Elevation Myocardial Infarction Immediately After Resuscitation

Müller D, et al. Ann Emerg Med. 2008;52:658-664.

Study objective
Severe myocardial ischemia is the leading cause of arrhythmic sudden cardiac death. It is unclear, however, in which percentage of patients sudden cardiac death is triggered by ST-elevation myocardial infarction (STEMI) and whether the diagnosis of STEMI can be reliably established immediately after resuscitation from out-of-hospital sudden cardiac death.

Methods
A 12-lead ECG was registered after return of spontaneous circulation after cardiac arrest. After hospital admission, further ECG, creatine kinase MB, and troponin measures; results of coronary angiograms; and autopsies were evaluated to confirm the definitive diagnosis of STEMI.

Results
Seventy-seven patients were included in our study (67% men, age 64 [14 to 93] years). STEMI was diagnosed in 44 patients. The diagnosis of myocardial infarction was confirmed in 84% of the 77 patients who survived to hospital admission. The sensitivity of the out-of-hospital ECG was 88% (95% confidence interval [CI] 74% to 96%), the specificity 69% (95% CI 51% to 83%), the positive predictive value 77% (95% CI 62% to 87%), and the negative predictive value 83% (95% CI 64% to 87%). The accuracy of the out-of-hospital ECG and that registered on admission was the same.

Conclusion
The diagnosis of STEMI can be established in the field immediately after return of spontaneous circulation in most patients. This may enable an early decision about reperfusion therapy, ie, immediate out-of-hospital thrombolysis or targeted transfer for percutaneous coronary intervention.

b. Transferring Patients With ST-Segment Elevation Myocardial Infarction for Mechanical Reperfusion: A Meta-Regression Analysis of Randomized Trials

De Luca G, et al. Ann Emerg Med. 2008;52:665-676.

Study objective
Primary angioplasty is associated with benefits in survival as compared with thrombolysis among patients with ST-segment elevation myocardial infarction (STEMI). However, in daily practice only a minority of STEMI patients are admitted to 24-hour primary percutaneous coronary intervention hospitals. A previous meta-analysis failed to show significant benefits in terms of survival, potentially because of a limited statistical power. Thus, the aim of the current study is to perform an updated meta-analysis of randomized trials to evaluate whether transfer for primary angioplasty provides significant benefits in terms of survival compared with on-site thrombolysis among STEMI patients.

Methods
The literature was scanned by formal searches of electronic databases (MEDLINE, CENTRAL, EMBASE) and the Cochrane Central Register of Controlled trials (http://www.mrw.interscience.wiley.com/cochrane/Cochrane_clcentral_articles_%20fs.html) from January 1990 to April 2008. The following key words were used: “randomized trial;” “myocardial infarction;” “reperfusion;” “thrombolysis;” “primary angioplasty;” “angioplasty;” “mechanical reperfusion;” “facilitation;” “transfer;” “transportation;” “mortality;” and “survival.” Inclusion criteria were (1) randomized comparison between on-site thrombolysis and transferring for primary angioplasty; and (2) complete data on mortality. We did not exclude trials or trial arms that specifically addressed transfer for percutaneous coronary intervention after thrombolysis. Crude data were extracted by 2 investigators. No language restrictions were enforced. The relationship between benefits in mortality and reinfarction, baseline mortality of the thrombolytic group in each study (study level variable), and percutaneous coronary intervention-related time delay was evaluated by using a weighted least-square regression.

Results
A total of 11 randomized trials were identified, including 5,741 patients (51.8% transferred for primary angioplasty and 48.2% treated with thrombolysis). Transfer for primary angioplasty was associated with a significant reduction in mortality (5.6% versus 6.8%; P=.02), reinfarction (2.1% versus 4.7%; P less than .0001 and stroke (0.7% versus 1.7%, P=.0005) at 30-day follow-up. The benefits in mortality and reinfarction of transfer for primary percutaneous coronary intervention over thrombolysis were not significantly related to baseline mortality of the lytic group or to percutaneous coronary intervention-related time delay.

Conclusion
This meta-analysis demonstrates that, among STEMI patients, transfer for mechanical reperfusion is associated, in addition to benefits in reinfarction and stroke, with a significant reduction in mortality at 30-day follow-up.

14. Does this work for you?

Christakis NA. BMJ 2008;337:a2281

To say a drug "works" is only half the story

Doctors say that a drug "works" if, in comparison with the control arm of a clinical trial, significantly more people in the treatment arm respond. Unfortunately, this is a naive oversimplification, and it breeds complacency among patients and physicians alike.

Criticisms of this perspective have been lodged before. One is that researchers often pick outcomes that are not patient centred—patients do not care if a tumour shows "shrinkage upon radiological visualisation" but rather whether they are in less pain. Another criticism is that when side effects of drugs are factored in, many patients do not think that a drug works very well at all, even as the doctor or drug company extols its virtues; drop-out rates in the active agent arm of trials often exceed those of the placebo arm, providing evidence of patients’ distaste for the overall effects of a drug.

But one problem that has received far less attention is that when patients say a drug "works" they typically mean something quite different from what doctors mean. Patients mean that most patients respond to the drug. This, however, is rarely the case. In fact, some of the most prescribed drugs today have no effect in most patients who take them.

For example, sildenafil (Viagra) works less than half the time: even when used in a dose optimised fashion (where the dose is titrated from 25 mg to 200 mg), and when effectiveness is gauged by the number of men who report that at least 60% of attempts at sexual intercourse are successful, only 48% of men are found to respond to the drug (compared with 11% who respond to a placebo) (BMC Urology 2002;2:6, doi:10.1186/1471-2490-2-6). When the 25 mg dose of the drug is used, 28% of the men report success (compared with 10% in the placebo arm). Most patients taking sildenafil should thus not expect it to "work." In fact, we could quite honestly tell patients that the 25 mg dose does not work 72% of the time.

The use of pregabalin to treat post-herpetic neuralgia provides a similar example. Roughly 50% of patients report that their pain scores drop by half or more, compared with 20% of patients who received a placebo (Neurology 2003;60:1274-83). At least half of patients, in other words, would not think that this drug has worked by this measure of success.

An alternative way of seeing the same phenomenon is to ask how often placebo "works." Consider the use of atorvastatin to prevent cardiovascular disease. The ASCOT trial, which followed more than 10 000 patients for an average of 3.3 years, found that 1.9% of people who were taking the drug had a heart attack, whereas among the patients taking a placebo the figure was 3% (Lancet 2003;361:1149-58, doi:10.1016/S0140-6736(03)12948-0). This is an impressive difference, yet many patients might not want to take the drug if they were told that a placebo worked at least 97% of the time.

Countless drugs that have been shown in randomised controlled trials to be effective work in only a minority of patients. Imagine that a drug worked 20% of the time in a trial, compared with 5-10% for a placebo. This is the case for drugs ranging from antihypertensives to minoxidil to cancer chemotherapy. Such a difference in a trial corresponds to an enormous effect size. However, most patients taking such drugs would not benefit—they would hardly think that the drugs "worked."

If you buy a toaster you expect it to be able to toast bread every time it is used. If it does not, you say it does not work and return or discard it. You do not take solace from the claim that, in fact, 30% of the time in the manufacturer’s laboratory the toaster did a better job in browning bread than sunshine alone.

My point is not that drugs evaluated in randomised controlled trials are not terrific. They are. And the scientific evidence for their efficacy is impressive. Rather, the problem is that patients and doctors lose sight of what trials actually show and either have false expectations of drugs’ effectiveness or are unaware that they should be vigilant about the possibility that the drug may have no effect whatsoever in any one person and hence fail to consider the need to switch or stop taking the drug.

Attention to variation in a patient’s response is thus essential for any drug that does not affect nearly 100% of patients. The variation in response involves two parts: that related to observable factors (such as age or clinical status) and unpredictable variation. Because the original clinical trials showing that drugs work are rarely powered to look at variation in observable factors, post-marketing observational studies are needed to determine which patients, on average, do or do not respond.

As for the unpredictable variation, one appropriate reaction is to have a protocol of administration that evaluates a patient’s response. Doctors sometimes already do this in a systematic way (such as when titrating the administration of highly active antiretroviral treatment). But this practice should be more widespread and more formal—and should especially be implemented in the case of drugs that have been shown to benefit only a minority of patients.

Just because drugs work in trials does not mean they will work in our patients. In fact, we can often expect that they will not work at all.

15. CPR by Paramedics for Cardiac Arrest: First Focus Is to Restore Pulse in the Field

from Heartwire — a professional news service of WebMD. November 4, 2008 (Chicago, IL) — Significantly more adult patients with cardiac arrest had their heartbeats restored by emergency-medical service (EMS) personnel in Los Angeles after adoption of cardiopulmonary-resuscitation (CPR) guidelines that emphasize treatment at the scene before any effort to transport to a hospital, investigators reported here last week at the American College of Emergency Physicians Scientific Assembly 2008 [1]. Their prospective study was limited to bystander-witnessed out-of-hospital cardiac arrest not associated with trauma.

The rate of return of spontaneous circulation (ROSC) was about 70% higher (p less than 0.0001) in 2007 compared with 2000 before adoption of the new protocol, which downplays restoration of ventilation in favor of uninterrupted chest compressions and advanced life-support efforts sustained for at least 20 minutes.

And thanks to a refined procedure for calling an end to resuscitation efforts in the field, there were significantly fewer "futile transports" in 2007, study presenter Dr Marc Eckstein (University of Southern California, Los Angeles), told heartwire.

If no pulse is restored after 20 minutes, the city's fire-department–based EMS personnel can remotely contact a physician for authorization to terminate the resuscitation effort, said Eckstein, who is medical director of the Los Angeles Fire Department and was previously a New York City paramedic.

For the most part, he said, "the only patients who will have a neurologically intact survival are going to be those who get a pulse back in the field." By definition, prepping the patient for transport interrupts chest compressions, which diminishes chances for survival. "If the patient is delivered [to the hospital] with CPR in progress, that patient probably isn't going to survive."

Revamped procedures in the protocol in 2007 compared with 2000 included two minutes of chest compressions as the first action taken, followed by a defibrillator shock, and then immediate resumption of compressions--without taking time for a pulse check, according to Eckstein. Less priority is given to intubation, and care is taken to avoid hyperventilation. "The point is to minimize interruptions in chest compressions, because that's a critical component for maintaining coronary perfusion pressure," he said.

"Obviously change is difficult in a very large system like ours, but the preliminary data are very encouraging."

Patients who regain a pulse undergo 12-lead electrocardiography, Eckstein said; those with likely infarction are transported to the closest "STEMI receiving center" for catheterization and possible intervention.

Futile transports were fewer due to the significant increases in cases in which resuscitation efforts were terminated in the field. The rate in 2000 was 9% of the 1700 patients with out-of-hospital cardiac arrest that were either witnessed or not witnessed, compared with 27% of the 1607 such patients in 2007 (p less than 0.0001).

With recent guidelines' emphasis on chest-compression-only CPR for the public, which do not recommend assisted breathing, "we hope we'll see a big increase in the rate of bystander CPR, because that's been a big impediment to improving the survival rate all these years," according to Eckstein.

He also said the next step in the research is to compare outcomes data from hospitals that received the patients who were successfully resuscitated, to determine whether the updated CPR protocol increased the percentage who were discharged neurologically intact.

Eckstein M. Impact of new CPR/advanced cardiac life support guidelines on outcome from out-of-hospital cardiac arrest. American College of Emergency Physicians Scientific Assembly 2008; October 28, 2008; Chicago, IL. Abstract 87.

16. Counseling May Reduce Clinician Burnout and Stress

Laurie Barclay, MD. November 18, 2008 — A short-term counseling intervention was effective in reducing burnout and stress in a cohort of Norwegian clinicians, according to the results of a study published online November 12 in the British Medical Journal.

"Research on the mental health of doctors has led to a call for preventive interventions to lower the risk of burnout and mental distress," write Karin E. Isaksson Rø, MDr, from the Research Institute, Modum Bad, in Vikersund, Norway, and colleagues. "Early intervention programmes could ensure that practising doctors in trouble get help in time, before their problems interfere with care of patients and give rise to medical errors, but such programmes have been poorly investigated."

At a Norwegian resource center, 227 physicians participated in a counseling intervention during 2003 to 2005 and completed a self-reported assessment at 1 year. The intervention consisted of individual counseling lasting 1 day or group-based counseling lasting 1 week, aimed at motivating reflection on and acknowledgement of the physicians' situation and personal needs. Primary endpoints were levels of burnout, measured with the Maslach burnout inventory, and predictors of reduced emotional exhaustion, based on linear regression.

Of 185 physicians (81%) who completed 1-year follow-up, 88 were men and 97 were women. On a scale of 1 to 5, the mean level of emotional exhaustion significantly decreased from 3.00 ± 0.94 to 2.53 ± 0.76 (t = 6.76; P less than .001), which was similar to the level found in a representative sample of 390 Norwegian physicians. In addition, participants had decreased their working hours by 1.6 ± 11.4 hours/week.

The proportion of physicians on full-time sick leave decreased from 35% (63 of 182 physicians) at baseline to 6% (10 of 182 physicians) at follow-up, and the proportion that had undergone psychotherapy increased from 20% (36 of 182 physicians) to 53% (97 of 182 physicians). After adjustment for sex, age, and personality dimensions, reduction in emotional exhaustion in the overall cohort was independently associated with reduced number of work hours per week (β = 0.17; P = .03). Among men, "satisfaction with the intervention" was an independent predictor of reduced emotional exhaustion (β = 0.25; P = .04).

"A short term counselling intervention could contribute to reduction in emotional exhaustion in doctors," the study authors write. "This was associated with reduced working hours for the whole cohort and, in men, was predicted by satisfaction with the intervention."

Study limitations include an inability to determine causality, lack of further analyses of subgroups possibly causing a false negative finding (type 2 error), regression analyses for each sex also subject to possible type 2 errors, and possible recall bias.

"Considering doctors' reluctance to seek help, despite high levels of distress, it is important to offer interventions that facilitate access and that can enhance motivation to reconsider personal and professional priorities when necessary," the study authors write. "The indications of factors possibly contributing to reduction in emotional exhaustion need to be further investigated with a more controlled design."

The Norwegian Women's Public Health Association and Modum Bad psychiatric hospital supported this study. Dr. Rø has been employed at the resource center, Villa Sana, and was reimbursed for a presentation of preliminary results at an internal meeting of the Norwegian Medical Association.

BMJ. Published online November 12, 2008.

17. The Relative Efficacy of Meperidine for the Treatment of Acute Migraine: A Meta-analysis of Randomized Controlled Trials

Friedman BW, et al. Ann Emerg Med. 2008;52:705-713.

Study objective
Despite guidelines recommending against opioids as first-line treatment for acute migraine, meperidine is the agent used most commonly in North American emergency departments. Clinical trials performed to date have been small and have not arrived at consistent conclusions about the efficacy of meperidine. We performed a systematic review and meta-analysis to determine the relative efficacy and adverse effect profile of opioids compared with nonopioid active comparators for the treatment of acute migraine.

Methods
We searched multiple sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and LILACS, emergency and headache medicine conference proceedings) for randomized controlled trials comparing parenteral opioid and nonopioid active comparators for the treatment of acute migraine headache. Our primary outcome was relief of headache. If this was unavailable, we accepted rescue medication use or we transformed visual analog scale change scores by using an established procedure. We grouped studies by comparator: a regimen containing dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated an odds ratio (OR) of headache relief and then assessed clinical and statistical heterogeneity for the group of studies. We then pooled the ORs of headache relief with a random-effects model.

Results
From 899 citations, 19 clinical trials were identified, of which 11 were appropriate and had available data. Four trials involving 254 patients compared meperidine to dihydroergotamine, 4 trials involving 248 patients compared meperidine to an antiemetic, and 3 trials involving 123 patients compared meperidine to ketorolac. Meperidine was less effective than dihydroergotamine at providing headache relief (OR=0.30; 95% confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to 14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57). Meperidine and ketorolac use resulted in similar rates of gastrointestinal adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23 to 12.72).

Conclusion
Clinicians should consider alternatives to meperidine when treating acute migraine with injectable agents.

18. Reversal of Profound Rocuronium-induced Blockade with Sugammadex: A Randomized Comparison with Neostigmine

Jones RK, et al. Anesthesiology. 2008;109:816-824.

Profound neuromuscular blockade reversal with 4 mg/kg sugammadex administered at 1-2 posttetanic counts after rocuronium is approximately 17 times faster than after 70 μg/kg neostigmine. Sugammadex may have unique ability to reverse profound neuromuscular blockade.

Abstract: http://www.anesthesiology.org/pt/re/anes/abstract.00000542-200811000-00014.htm

19. Aspirin for prevention of cardiovascular events is only effective in established cardiovascular disease

Hiatt WR. BMJ 2008;337:a1806

In the linked randomised controlled trial (doi:10.1136/bmj.a1840), Belch and colleagues assess whether aspirin and antioxidants, given together or separately, reduce cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.

The use of aspirin for secondary prevention of cardiovascular events in patients with coronary or cerebrovascular disease is well established and is based on extensive evidence from the Antithrombotic Trialists’ Collaboration. That meta-analysis found that aspirin was beneficial in patients with acute myocardial infarction or ischaemic stroke; unstable or stable angina; and those with previous myocardial infarction, stroke, or cerebral ischaemia. However, not all patients with cardiovascular disease respond to aspirin, as shown by a recent meta-analysis of aspirin trials in peripheral artery disease.

In contrast, studies evaluating the possible benefits of aspirin for primary prevention in patients without cardiovascular disease have been consistently negative. A review by the United States Food and Drug Administration (FDA) of the proposed labelling of aspirin for primary prevention in 2003 evaluated five primary prevention trials and found that they were all negative for their primary end point. Further examination of those trials in the higher risk subgroups (Framingham risk score greater than 8-10% a decade) and in patients with diabetes also failed to show a benefit of aspirin. On the basis of this assessment, the FDA did not extend the labelling of aspirin for primary prevention.

Subsequent to the FDA meeting, the women’s health study—a randomised trial of 39 876 healthy women treated with aspirin or placebo—also failed to show a significant improvement for the primary end point (prevention of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes; P=0.13). But rather than emphasising this negative conclusion, the authors focused on a subgroup analysis that led them to conclude that aspirin reduced the risk of stroke in women.

The physicians’ health study randomised 22 071 healthy men to aspirin or placebo and found no benefit for the primary end point of cardiovascular mortality, although a subgroup analysis found that aspirin prevented non-fatal myocardial infarction in men. The major cardiovascular event rates in these two key primary prevention studies were less than 1% a year.

Despite the consistently negative evidence from trials, guidelines provide inconsistent recommendations on the use of aspirin to prevent cardiovascular events in healthy subjects at higher risk who do not have existing cardiovascular disease, particularly patients with diabetes. The assumption is that the positive findings of aspirin in patients with symptomatic coronary or cerebrovascular disease can be extrapolated to these high risk populations without clinical evidence of cardiovascular disease.

In this context, Belch and colleagues’ trial compared the effects of aspirin and antioxidants (using a factorial design) on the primary prevention of fatal and non-fatal major cardiovascular events in a high risk population. Patients were eligible if they had type 1 or type 2 diabetes and evidence of asymptomatic peripheral artery disease, defined by an ankle brachial index less than 1.00. More than 1200 patients were enrolled and followed up to eight years. At baseline, participants had a mean age of 60 years and an average ankle brachial index of 0.90. The observed risk of a major cardiovascular event was 2.9% a year, much higher that that seen in the previously noted primary prevention trials (driven by age of the population and the presence of diabetes and peripheral artery disease). Patients randomised to aspirin had 116 primary fatal and non-fatal cardiovascular events compared with 117 in the control group (hazard ratio 0.98, 95% confidence interval 0.76 to 1.26). No significant difference in major cardiovascular events was seen between the antioxidant treatment group and the placebo group. Although no significant difference was seen between the rate of gastrointestinal bleeding in each group, there was a trend for a greater incidence of gastrointestinal symptoms, including dyspepsia, in patients randomised to aspirin.

Belch and colleagues’ study supports the observations from six well conducted randomised control trials that found no benefit of aspirin for primary prevention, even in higher risk groups. The findings are also consistent with the previous report of no benefit of aspirin in patients with peripheral artery disease. What is striking about the negative effect of aspirin is that people in Belch and colleagues’ study were at particularly high risk given their age and the presence of diabetes and asymptomatic peripheral artery disease, with an event rate of about 3% a year.

These result support the concept that risk assessment alone cannot predict which patients will benefit from aspirin. In fact, the only predictor of clinical response to aspirin is a history of a major coronary or cerebral ischaemic event, as defined by the previous meta-analysis. The mechanisms of this differential response to aspirin are not known but clearly suggest that patients who respond to aspirin must have a history of clinical, symptomatic cardiovascular disease. This is in sharp contrast to the evidence that statins, for reducing concentrations of low density lipoprotein cholesterol, and drugs for treating hypertension have clinical benefit that extends to all risk groups, including those with and without cardiovascular disease. In these examples, the difference between primary and secondary prevention is only in the absolute reduction in risk because primary prevention populations have a lower absolute risk of cardiovascular events but receive the same relative benefit from the treatment.

A total of seven well controlled trials now show that aspirin has no benefit for primary prevention of cardiovascular events, even in people at higher risk. Although aspirin is cheap and universally available, practitioners and authors of guidelines need to heed the evidence that aspirin should be prescribed only in patients with established symptomatic cardiovascular disease.

20. Head Injury Policy Statement by the American College of Emergency Physicians

Abstract
This clinical policy provides evidence-based recommendations on select issues in the management of adult patients with mild traumatic brain injury (TBI) in the acute setting. It is the result of joint efforts between the American College of Emergency Physicians and the Centers for Disease Control and Prevention and was developed by a multidisciplinary panel. The critical questions addressed in this clinical policy are:

(1) Which patients with mild TBI should have a noncontrast head computed tomography (CT) scan in the emergency department (ED)?
(2) Is there a role for head magnetic resonance imaging over noncontrast CT in the ED evaluation of a patient with acute mild TBI?
(3) In patients with mild TBI, are brain specific serum biomarkers predictive of an acute traumatic intracranial injury?
(4) Can a patient with an isolated mild TBI and a normal neurologic evaluation result be safely discharged from the ED if a noncontrast head CT scan shows no evidence of intracranial injury? Inclusion criteria for application of this clinical policy's recommendations are nonpenetrating trauma to the head, presentation to the ED within 24 hours of injury, a Glasgow Coma Scale score of 14 or 15 on initial evaluation in the ED, and aged 16 years or greater. The primary outcome measure for questions 1, 2, and 3 is the presence of an acute intracranial injury on noncontrast head CT scan; the primary outcome measure for question 4 is the occurrence of neurologic deterioration.

Full-text: http://www.acep.org/workarea/downloadasset.aspx?id=8814