Wednesday, April 28, 2010

Lit Bits: April 28, 2010

From the recent medical literature...

1. Computer Model May Improve Detection of Serious Bacterial Infection in Young Children with Fever

Laurie Barclay, MD. April 27, 2010 — Use of a computer model may improve detection of serious bacterial infection in young children with fever, according to the results of a 2-year, prospective cohort study reported in the April 20 issue of the BMJ.

"In most cases, the cause of a febrile illness is a self limiting, presumed viral, infection, but 5-10% of febrile children have serious bacterial infections such as pneumonia, urinary tract infection, meningitis, bacteraemia, or bone or joint infection (which usually present with fever)," write Jonathan C. Craig, MD, from the University of Sydney in Sydney, Australia, and colleagues. "These conditions can be difficult to distinguish from viral infections and benefit from early antibiotic therapy. The consequences of a delayed or missed diagnosis can be serious and, occasionally, fatal."

The goals of this study were to examine current methods for diagnosis and treatment of young children presenting with a febrile illness but suspected of having serious bacterial infection, and to develop and test a multivariable model aiming to differentiate serious bacterial infections from self-limiting nonbacterial illnesses.

Between July 1, 2004, and June 30, 2006, a total of 15,781 children younger than 5 years presented with a febrile illness to the emergency department of The Children's Hospital at Westmead, Australia. Physicians conducted a standardized clinical evaluation including mandatory entry of 40 clinical features into the hospital's electronic recordkeeping system. Standard radiologic and microbiological tests and follow-up confirmed or excluded serious bacterial infections.

Primary endpoints were diagnosis of 1 of 3 key types of serious bacterial infection (urinary tract infection, pneumonia, and bacteremia) and the diagnostic accuracy of the clinical computer-assisted decision-making model and clinician judgment. Follow-up rate was 93%.

For the 3 types of infections, the combined prevalence was 7.2% (95% confidence interval [CI], 6.7% - 7.5%). Among cases of febrile illness, urinary tract infection was diagnosed in 3.4% (95% CI, 3.2% - 3.7%), pneumonia in 3.4% (95% CI, 3.1% - 3.7%), and bacteremia in 0.4% (95% CI, 0.3% - 0.5%).

The appropriate test (urine culture, chest radiograph, or blood culture) was performed in more than 94% of children with serious bacterial infections. Antibiotics were prescribed for 66% of children with urinary tract infection; 69% of those with pneumonia; and 81% of those with bacteremia, as well as for 20% of those without bacterial infection.

Using multinomial logistic regression, the investigators developed a diagnostic model based on the data from the clinical evaluations and the confirmed diagnosis. Although sensitivity was low (10% - 50%) and specificity was high (90% - 100%) for physicians' diagnoses of bacterial infection, the clinical diagnostic model yielded a broad range of values for sensitivity and specificity.

"Emergency department physicians tend to underestimate the likelihood of serious bacterial infection in young children with fever, leading to undertreatment with antibiotics," the study authors write. "A clinical diagnostic model could improve decision making by increasing sensitivity for detecting serious bacterial infection, thereby improving early treatment."

Limitations of this study include lack of microbiological and radiologic verification in all children and uncertain validity of the physician estimates of disease.

In an accompanying editorial, Matthew J. Thompson, MBChB, DPhil, and Ann Van den Bruel, MD, PhD, from the University of Oxford, in Oxford, United Kingdom, note that measuring vital signs and evaluating the child's overall state of illness are key to proper diagnosis of febrile illness.

"In practice, clinicians use many different diagnostic strategies," Drs. Thompson and Van den Bruel write. "Calculating the probability of a condition on the basis of 28 predictors is only feasible with a computerised algorithm, for which popular handheld electronic devices and computerised records are invaluable. But before widespread implementation, we will need to have evidence showing the effect of using such a model on patient management and outcomes."

The National Health and Medical Research Council of Australia supported this study. The study authors and editorialists have disclosed no relevant financial relationships.

BMJ. 2010;340:c1594. Abstract:

2. Thirty-day Outcomes of ED Patients Undergoing Electrical Cardioversion for Atrial Fibrillation or Flutter

Scheuermeyer FX, et al. Acad Emerg Med 2010;17:408-415.

Objectives: While the short-term (less than 7-day) safety and efficiency of electrical cardioversion for emergency department (ED) patients with atrial fibrillation or flutter have been established, the 30-day outcomes with respect to stroke, thromboembolic events, or death have not been investigated.

Methods: A two-center cohort of consecutive ED patients undergoing cardioversion for atrial fibrillation or flutter between January 1, 2000, and September 30, 2007, was retrospectively investigated. This cohort was probabilistically linked with both a regional ED database and the provincial health registry to determine which patients had a subsequent ED visit or hospital admission, stroke, or thromboembolic event or died within 30 days. In addition, trained reviewers performed a detailed chart abstraction on 150 randomly selected patients, with emphasis on demographics, vital signs, medical treatment, and predefined adverse events. Hemodynamically unstable patients or those whose condition was the result of an underlying acute medical diagnosis were excluded. Data were analyzed by descriptive methods.

Results: During the study period, 1,233 patients made 1,820 visits for atrial fibrillation or flutter to the ED. Of the 400 eligible patients undergoing direct-current cardioversion (DCCV), no patients died, had a stroke, or had a thromboembolic event in the following 30 days (95% confidence interval [CI] = 0.0 to 0.8% for all outcomes). A total of 141 patients were included in the formal chart review, with five patients (3.5%, 95% CI = 0.5% to 6.6%) failing cardioversion, six patients (4.3%, 95% CI = 0.9% to 7.6%) having a minor adverse event that did not change disposition, and five patients (3.5%, 95% CI = 0.5% to 6.6%) admitted to hospital at the index visit.

Conclusions: Cardioversion of patients with atrial fibrillation or flutter in the ED appears to have a very low rate of long-term complications.

3. Why Expensive Placebos Work Better

It's long been recognized that the placebo effect is extremely powerful; anywhere between 35 and 75 percent of people get better after receiving pretend medical treatments, such as sugar pills. A few years ago, Tor Wager, a neuroscientist at Columbia University, wanted to figure out why placebos were so effective. His experiment was brutally straightforward: he gave college students electric shocks while they were stuck in an fMRI machine. (The subjects were well compensated, at least by undergraduate standards.) Half of the people were then supplied with a fake pain-relieving cream. Even though the cream had no analgesic properties—it was just a hand moisturizer—people given the pretend cream said the shocks were significantly less painful. The placebo effect eased their suffering. Wager then imaged the specific parts of the brain that controlled this psychological process. He discovered that the placebo effect depended entirely on the prefrontal cortex, the center of reflective, deliberate thought. When people were told that they'd just received pain-relieving cream, their frontal lobes responded by inhibiting the activity of their emotional brain areas (like the insula) that normally respond to pain. Because people expected to experience less pain, they ended up experiencing less pain. Their predictions became self-fulfilling prophecies.

The placebo effect is a potent source of self-help. It demonstrates the power of the prefrontal cortex to modulate even the most basic bodily signals. Once this brain area comes up with reasons to experience less pain—the cream is supposed to provide pain relief—those reasons become powerful distortions. Unfortunately, the same rational brain areas responsible for temporarily reducing suffering also mislead us about many daily decisions. The prefrontal cortex can turn off pain signals, but it can also cause a person to ignore the feelings that lead to choosing the best [option]. In these situations, conscious thoughts interfere with good decision-making.

Look, for example, at this witty little experiment. Baba Shiv, a neuroeconomist at Stanford, supplied a group of people with Sobe Adrenaline Rush, an "energy" drink that was supposed to make them feel more alert and energetic. (The drink contained a potent brew of sugar and caffeine that, the bottle promised, would impart "superior functionality.") Some participants paid full price for the drinks, while others were offered a discount. After drinking the product, participants were asked to solve a series of word puzzles. Shiv found that people who'd paid discounted prices consistently solved about 30 percent fewer puzzles than the people who'd paid full price for the drinks. The subjects were convinced that the stuff on sale was much less potent, even though all the drinks were identical. "We ran the study again and again, not sure if what we got had happened by chance or fluke," Shiv says. "But every time we ran it, we got the same results."

Why did the cheaper energy drinks prove less effective? According to Shiv, consumers typically suffer from a version of the placebo effect. Since they expect cheaper goods to be less effective, they generally are less effective, even if the goods are identical to more expensive products. This is why brand-name aspirin works better than generic aspirin and why Coke tastes better than cheaper colas, even if most consumers can't tell the difference in blind taste tests. "We have these general beliefs about the world—for example, that cheaper products are of lower quality—and they translate into specific expectations about specific products," said Shiv. "Then, once these expectations are activated, they start to really impact our behavior." The rational brain distorts the sense of reality, so the ability to properly assess the alternatives is lost. Instead of listening to the trustworthy opinions generated by our emotional brains, we follow our own false assumptions.

Researchers at Caltech and Stanford recently lifted the veil on this strange process. Their experiment was organized like a winetasting. Twenty people sampled five cabernet sauvignons that were distinguished solely by their retail prices, with bottles ranging in cost from five dollars to ninety dollars. Although the people were told that all five wines were different, the scientists weren't telling the truth: there were only three different wines. This meant that the same wines often reappeared, but with different price labels. For example, the first wine offered during the tasting—it was a bottle of a cheap California cabernet—was labeled both as a five-dollar wine (its actual retail price) and as a forty-five-dollar wine, a 900 percent markup. All of the red wines were sipped by each subject inside an fMRI machine.

Not surprisingly, the subjects consistently reported that the more expensive wines tasted better. They preferred the ninety­dollar bottle to the ten-dollar bottle and thought the forty-five­dollar cabernet was far superior to the five-dollar plonk. By conducting the winetasting inside an fMRI machine—the drinks were sipped via a network of plastic tubes—the scientists could see how the brains of the subjects responded to the different wines. While a variety of brain regions were activated during the experiment, only one brain region seemed to respond to the price of the wine rather than the wine itself: the prefrontal cortex. In general, more expensive wines made parts of the prefrontal cortex more excited. The scientists argue that the activity of this brain region shifted the preferences of the winetasters, so that the ninety-dollar cabernet seemed to taste better than the thirty-five­dollar cabernet, even though they were actually the same wine.

Of course, the wine preferences of the subjects were clearly nonsensical. Instead of acting like rational agents—getting the most utility for the lowest possible price—they were choosing to spend more money for an identical product. When the scientists repeated the experiment with members of the Stanford University wine club, they got the same results. In a blind tasting, these semi-experts were also misled by the made-up price tags. "We don't realize how powerful our expectations are," says Antonio Rangel, the neuroeconomist at Caltech who led the study. "They can really modulate every aspect of our experience. And if our expectations are based on false assumptions”—like the assumptions that more expensive wine tastes better—“they can be very misleading.”

Excerpted from Jonah Lehrer's fascinating book, How We Decide (Boston: Houghton Mifflin Harcourt, 2009), 146-149. Lehrer is a Rhodes scholar with a strong interest in neuroscience.

4. Accidental Injection of Epinephrine Into Fingers Not a Cause for Concern

NEW YORK (Reuters Health) Apr 09 - There are no significant local or systemic effects when an epinephrine autoinjector is accidentally discharged into a finger, according to an article in the Annals of Emergency Medicine on March 29.

Ischemia in the affected finger is rare, and when it does occur, it can be managed with vasodilators, Dr. Vikhyat S. Bebarta, from Wilford Hall Medical Center in San Antonio, Texas, and colleagues report.

These reassuring findings also show that contrary to what was once widely believed, epinephrine mixtures may be safe for digital nerve blocks during minor procedures, the researchers say. (Autoinjectors typically contain more epinephrine than is found in local anesthetic mixes, they note.)

The findings are based on a study of 127 accidental epinephrine injections into fingers. These cases were ones for which the researchers had follow-up data; their overall cohort consisted of 365 patients with accidental epinephrine injections to the hand who called a poison control center, including 213 with fingers involved.

No patient had any significant local or systemic side effects, and symptoms resolved completely in all cases. The researchers treated 29 patients (23%) with either topical nitroglycerin, local phentolamine injection, or local terbutaline. Forty patients used warm soaks alone.

Four patients (3.1%) were reported as having an ischemic finger and all were treated with vasodilator therapy and sent home. In two of the patients, symptoms resolved within 2 hours of injection.

In an editorial, Dr. Adam J. Singer of Stony Brook University, New York, summarizes "the take-home message": in the absence of signs of poor perfusion (pain, pallor, paresthesias, prolonged capillary refill, and cool temperature), patients with an accidental autoinjector stick require no treatment and can be discharged home. If digital ischemia is present, "dilute phentolamine in lidocaine should be injected subcutaneously into the site until the area turns pink."

Ann Emerg Med 2010.

5. Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department with Sepsis

Glickman SW, et al. Acad Emerg Med 2010;17:383-390.

Background: Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed.

Objectives: The objectives were to 1) describe the clinical presentation of ED sepsis, including types of infection and causative microorganisms, and 2) determine the incidence, patient characteristics, and mortality associated with early progression to septic shock among ED patients with infection.

Methods: This was a multicenter study of adult ED patients with sepsis but no evidence of shock. Multivariable logistic regression was used to identify patient factors for early progression to shock and its association with 30-day mortality.

Results: Of 472 patients not in shock at ED presentation (systolic blood pressure above 90 mm Hg and lactate less than 4 mmol/L), 84 (17.8%) progressed to shock within 72 hours. Independent factors associated with early progression to shock included older age, female sex, hyperthermia, anemia, comorbid lung disease, and vascular access device infection. Early progression to shock (vs. no progression) was associated with higher 30-day mortality (13.1% vs. 3.1%, odds ratio [OR] = 4.72, 95% confidence interval [CI] = 2.01 to 11.1; p ≤ 0.001). Among 379 patients with uncomplicated sepsis (i.e., no evidence of shock or any end-organ dysfunction), 86 (22.7%) progressed to severe sepsis or shock within 72 hours of hospital admission.

Conclusions: A significant portion of ED patients with less severe sepsis progress to severe sepsis or shock within 72 hours. Additional diagnostic approaches are needed to risk stratify and more effectively treat ED patients with sepsis.

6. A Clinical Decision Rule to Reduce Use of X-Rays in Patients with Chest Pain

A rule based on three criteria was 100% sensitive and 36% specific for determining which patients could forgo chest x-rays.

Hess EP, Stiell IG, et al. CJEM 2010;12(2):128-134

Objectif : Nous avons établi une règle de décision clinique pour déterminer qui, parmi les patients qui se présentent à l'urgence avec des douleurs thoraciques et un possible syndrome coronarien aigu (SCA), doit subir une radiographie pulmonaire.

These bilingual Canadians… Sorry about that. Let me repeat this in English.

Objective: We derived a clinical decision rule to determine which emergency department (ED) patients with chest pain and possible acute coronary syndrome (ACS) require chest radiography.
Methods: We prospectively enrolled patients over 24 years of age with a primary complaint of chest pain and possible ACS over a 6 month period. Emergency physicians completed standardized clinical assessments and ordered chest radiographs as appropriate. Two blinded investigators independently classified chest radiographs as "normal," "abnormal not requiring intervention" and "abnormal requiring intervention," based on review of the radiology report and the medical record. The primary outcome was abnormality of chest radiographs requiring acute intervention. Analyses included interrater reliability assessment (with κ statistics), univariate analyses and recursive partitioning.

Results: We enrolled 529 patients during the study period between Jul. 1, 2007, and Dec. 31, 2007. Patients had a mean age of 59.9 years, 60.3% were male, 4.0% had a history of congestive heart failure and 21.9% had a history of acute myocardial infarction. Only 2.1% (95% confidence interval [CI] 1.1%-3.8%) of patients had radiographic abnormality of the chest requiring acute intervention. The κ statistic for chest radiograph classification was 0.81 (95% CI 0.66-0.95). We derived the following rule: patients can forgo chest radiography if they have no history of congestive heart failure, no history of smoking and no abnormalities on lung auscultation. The rule was 100% sensitive (95% CI 32.0%-40.4%) and 36.1% specific (95% CI 32.0%-40.4%).

Conclusion: This rule has potential to reduce health care costs and enhance ED patient flow. It requires validation in an independent patient population before introduction into clinical practice.

7. The Risk of Intra-abdominal Injuries in Pediatric Patients with Stable Blunt Abdominal Trauma and Negative Abdominal Computed Tomography

Hom J. Acad Emerg Med. 2010; 17:469–475.

Objectives: This review examines the prevalence of intra-abdominal injuries (IAI) and the negative predictive value (NPV) of an abdominal computed tomography (CT) in children who present with blunt abdominal trauma.

Methods: MEDLINE, EMBASE, and Cochrane Library databases were searched. Studies were selected if they enrolled children with blunt abdominal trauma from the emergency department (ED) with significant mechanism of injury requiring an abdominal CT. The primary outcome measure was the rate of IAI in patients with negative initial abdominal CT. The secondary outcome measure was the number of laparotomies, angiographic embolizations, or repeat abdominal CTs in those with negative initial abdominal CTs.

Results: Three studies met the inclusion criteria, comprising a total of 2,596 patients. The overall rate of IAI after a negative abdominal CT was 0.19% (95% confidence interval [CI] = 0.08% to 0.44%). The overall NPV of abdominal CT was 99.8% (95% CI = 99.6% to 99.9%). There were five patients (0.19%, 95% CI = 0.08% to 0.45%) who required additional intervention despite their initial negative CTs: one therapeutic laparotomy for bowel rupture, one diagnostic laparotomy for mesenteric hematoma and serosal tear, and three repeat abdominal CTs (one splenic and two renal injuries). None of the patients in the latter group required surgery or blood transfusion.

Conclusions: The rate of IAI after blunt abdominal trauma with negative CT in children is low. Abdominal CT has a high NPV. The review shows that it might be safe to discharge a stable child home after a negative abdominal CT.

8. Naproxen, Sumatriptan Effective for Headache Recurrence after ED Discharge

By Michelle Rizzo. NEW YORK (Reuters Health) Apr 22 - Naproxen and sumatriptan are equally effective in relieving headache that recurs after emergency department (ED) discharge, according to findings published online March 22nd in the Annals of Emergency Medicine.

"Fifty-one percent of patients discharged from an ED after treatment for acute migraine, or other recurrent headache disorders, will use prescription medication to treat headache recurrence," Dr. Benjamin W. Friedman, of Albert Einstein College of Medicine, Bronx, New York, told Reuters Health by e-mail.

In a randomized trial, Dr. Friedman and his colleagues compared oral sumatriptan (100 mg) to naproxen (500 mg) for treating patients whose headaches were controlled in the ED but then recurred after discharge. All of the patients were contacted by phone 48 hours after discharge.

The main outcome was the change in pain intensity during the 2-hour period after treatment. The authors also assessed satisfaction with the medication and adverse effects.

The report includes data on 383 (93%) of the 410 patients who enrolled in the study. Overall, 280 patients (73%) had headache after discharge that was either mild (n = 89) or moderate to severe (n = 191). One hundred ninety-six (51%) took the investigational medication, including 88 with migraine.

The two groups had similar improvements in pain intensity, as measured on a validated 11-point verbal numeric rating scale, with a mean increase of 4.3 points in the naproxen group and 4.1 points in the sumatriptan group.

Findings were nearly identical among a subset of patients with acute migraine without aura (4.3 points for naproxen versus 4.2 points for sumatriptan). These patients were analyzed twice according to a-priori design: once as a homogenous subgroup and then again combined with all the patients.

The rate of adverse effects was 19% with naproxen and 26% with sumatriptan. Common adverse effects in both groups included gastrointestinal, dizziness/feeling lightheaded or weak, and drowsiness.

Overall, 71% of patients in the naproxen group and 75% in the sumatriptan group said they would want the same medication the next time.

"Although many medications are now available to treat acute migraine, the goal of complete and sustained headache relief remains elusive," Dr. Friedman said.

Ann Emerg Med 2010.

9. Do Brain-Training Programs Work?

by Greg Miller on April 20, 2010. Science Now. Play a computer game, boost your IQ—that's the claim made by some software companies pedaling so-called brain-training programs. It's probably an empty promise, according to the largest study to date of brain-training software, which finds no evidence of general cognitive benefits. Yet the study's limitations give brain-training advocates plenty to gripe about.

The idea for the study originated with a BBC science television show, Bang Goes the Theory. Producers contacted Adrian Owen at the MRC Cognition and Brain Sciences Unit in Cambridge, U.K., to help design an experiment to test the efficacy of computer brain training. Many of these programs are set up like a game, and playing along supposedly boosts memory, attention, and other cognitive functions. But few rigorous studies have been conducted on them, and many researchers question whether even the best programs do anything more than make people better at the game itself. For example, there's little solid research to suggest that using these programs has a beneficial effect on overall cognition that carries over into daily life.

In the new study, Owen and colleagues developed two online training programs and tested them in 11,430 healthy adults who registered on a Web site set up by the BBC. One group trained on a program that emphasized reasoning and problem-solving skills, and another group trained on a program that emphasized different skills, including short-term memory and attention. A third, control group, essentially did busywork, hunting for answers to general knowledge questions on the Internet. All participants were asked to "train" for at least 10 minutes, three times a week for 6 weeks, and all received a battery of cognitive tests before and after this 6-week period.

Not surprisingly, people in both training groups got better at the tasks they actually practiced. But that's as far as it went. "None of the brain-training tasks transferred to other mental or cognitive abilities beyond what had been specifically practiced," Owen's co-author and MRC colleague Jessica Grahn said at a press conference this morning announcing the results, which are published online today in Nature.

Brain-training advocates are not impressed, however. "This article makes big claims out of a single negative finding," says Torkel Klingberg, a neuroscientist at the Karolinska Institute in Stockholm and founder of a company that makes computer brain-training programs to improve working memory and other cognitive functions. Klingberg has published one of the few studies demonstrating that the benefits of training can generalize beyond a specific task. Among other qualms with the new study, he notes that subjects trained an average of only about 3 hours in total, and—for all the researchers know—may have done so with the TV blaring in the background or other distractions.

Although Klingberg says he agrees with the authors that many of the brain-training products on the market are probably ineffective, he argues that just because Owen and colleagues developed a training program and showed it didn't work doesn't mean that all such programs are worthless. "That does not mean that cognitive functions cannot be trained, or that all training paradigms lack effect," he says.

10. Some Success Fighting Heart Disease

Ron Winslow. Wall Street Journal, April 6, 2010. Good news from the front line in the battle against cardiovascular disease: The heart-attack rate among elderly Americans appears to be falling sharply.

The rate of hospital admissions for heart attack was 23% lower in 2007 than in 2002, according to a just-published analysis of Medicare data, with 228,170 fee-for-service Medicare patients admitted in 2007 compared with 297,653 in 2002. That suggests there were nearly 87,000 fewer heart-attack admissions in 2007 than would have been expected had the rate remained constant.

The report covers only the nearly 30 million Medicare beneficiaries in the traditional fee-for-service part of the federal health-care program for the elderly. If the findings are extrapolated based on 38 million Medicare participants, including those enrolled in so-called Medicare Advantage managed-care plans, researchers estimate a 2007 total of 319,063 heart-attack admissions, representing a reduction of 97,000 versus comparable figures in 2002.

"It's remarkable what has been accomplished," says Harlan Krumholz, a cardiologist at Yale University School of Medicine and principal investigator for the study. He terms the rapid decline in a major public health marker as "breathtaking."

Behind the drop, he and other heart experts believe, is the cumulative impact of a variety of prevention initiatives that public-health groups, professional organizations and payers of health care have mounted over the past two decades to change health habits and improve treatment of heart patients.

Quit-smoking campaigns, growing awareness of the importance of exercise and healthy diets, increasing use of medicines to control blood pressure and cholesterol and efforts to encourage doctors and hospitals to follow evidence-based guidelines when treating heart patients are among the potential contributing factors. "It looks like our effort with preventive medicine, with guidelines and a systematic approach to caring for patients, is paying off," says Sidney Smith, a cardiologist at University of North Carolina, Chapel Hill, and past president of the American Heart Association, who wasn't involved with the study.

Still, the progress comes with concerns…

Full-text (free):

11. Can CT Angiography of the Brain Replace Lumbar Puncture in the Evaluation of Acute-onset Headache after a Negative Noncontrast Cranial CT Scan?

McCormack RF, et al. Acad Emerg Med. 2010;17: 444–451

Objectives: The primary goal of evaluation for acute-onset headache is to exclude aneurysmal subarachnoid hemorrhage (SAH). Noncontrast cranial computed tomography (CT), followed by lumbar puncture (LP) if the CT is negative, is the current standard of care. Computed tomography angiography (CTA) of the brain has become more available and more sensitive for the detection of cerebral aneurysms. This study addresses the role of CT/CTA versus CT/LP in the diagnostic workup of acute-onset headache.

Methods: This article reviews the recent literature for the prevalence of SAH in emergency department (ED) headache patients, the sensitivity of CT for diagnosing acute SAH, and the sensitivity and specificity of CTA for cerebral aneurysms. An equivalence study comparing CT/LP and CT/CTA would require 3,000 + subjects. As an alternative, the authors constructed a mathematical probability model to determine the posttest probability of excluding aneurysmal or arterial venous malformation (AVM) SAH with a CT/CTA strategy.

Results: SAH prevalence in ED headache patients was conservatively estimated at 15%. Representative studies reported CT sensitivity for SAH to be 91% (95% confidence interval [CI] = 82% to 97%) and sensitivity of CTA for aneurysm to be 97.9% (95% CI = 88.9% to 99.9%). Based on these data, the posttest probability of excluding aneurysmal SAH after a negative CT/CTA was 99.43% (95% CI = 98.86% to 99.81%).

Conclusions: CT followed by CTA can exclude SAH with a greater than 99% posttest probability. In ED patients complaining of acute-onset headache without significant SAH risk factors, CT/CTA may offer a less invasive and more specific diagnostic paradigm. If one chooses to offer LP after CT/CTA, informed consent for LP should put the pretest risk of a missed aneurysmal SAH at less than 1%.

12. Fever as nature’s engine?

Fowler AW. BMJ 2009;339:b3874

Data suggest that the use of paracetamol (aka acetaminophen) to reduce the body temperature and alleviate the symptoms of flu is counterproductive.

Infectious organisms are adapted to the temperature of the part of the body they colonise. Rhinoviruses, which infect the cooler upper airway and sinuses, grow best at 33-35ºC, so inhaling air at about 45ºC for 20 minutes significantly improves the symptoms of a common cold. Conversely, treating the common cold with aspirin causes a significant increase in the rate of production of the virus. Moreover, if fever is suppressed in ferrets infected with flu virus, illness is prolonged.

The effect of lowering or raising body temperatures in humans with flu has not been studied, but there are good reasons to treat flu by encouraging the temperature to rise to 40ºC for at least 24 hours. The lack of such research may be due to a deep seated fever phobia stemming from pre-scientific medicine, when fever was perceived as an illness in itself. However, in the 17th century Thomas Sydenham said, "Fever is nature’s engine which she brings into the field to remove her enemy," the potential of which remains unrecognised by the public and the medical profession.

13. Heat or Cold Packs for Neck and Back Strain: A Randomized Controlled Trial of Efficacy

Garra G, et al. Acad Emerg Med. 2010; 17:484–489.

Objectives: Acute back and neck strains are very common. In addition to administering analgesics, these strains are often treated with either heat or cold packs. The objective of this study was to compare the analgesic efficacy of heat and cold in relieving pain from back and neck strains. The authors hypothesized that pain relief would not differ between hot and cold packs.

Methods: This was a randomized, controlled trial conducted at a university-based emergency department (ED) with an annual census of 90,000 visits. ED patients older than 18 years old with acute back or neck strains were eligible for inclusion. All patients received 400 mg of ibuprofen orally and then were randomized to 30 minutes of heating pad or cold pack applied to the strained area. Outcomes of interest were pain severity before and after pack application on a validated 100-mm visual analog scale (VAS) from 0 (no pain) to 100 (worst pain), percentage of patients requiring rescue analgesia, subjective report of pain relief on a verbal rating scale (VRS), and future desire for similar packs. Outcomes were compared with t-tests and chi-square tests. A sample of 60 patients had 80% power to detect a 15-mm difference in pain scores.

Results: Sixty patients were randomized to heat (n = 31) or cold (n = 29) therapy. Mean (±standard deviation [SD]) age was 37.8 (±14.7) years, 51.6% were female, and 66.7% were white. Groups were similar in baseline patient and pain characteristics. There were no differences between the heat and cold groups in the severity of pain before (75 mm [95% CI = 66 to 83] vs. 72 mm [95% CI = 65 to 78]; p = 0.56) or after (66 mm [95% CI = 57 to 75] vs. 64 mm [95% CI = 56 to 73]; p = 0.75) therapy. Pain was rated better or much better in 16/31 (51.6%) and 18/29 (62.1%) patients in the heat and cold groups, respectively (p = 0.27). There were no between-group differences in the desire for and administration of additional analgesia. Twenty-five of 31 (80.6%) patients in the heat group and 22 of 29 (75.9%) patients in the cold group would use the same therapy if injured in the future (p = 0.65).

Conclusions: The addition of a 30-minute topical application of a heating pad or cold pack to ibuprofen therapy for the treatment of acute neck or back strain results in a mild yet similar improvement in the pain severity. However, it is possible that pain relief is mainly the result of ibuprofen therapy. Choice of heat or cold therapy should be based on patient and practitioner preferences and availability.

14. Generalized Petechial Rashes in Children with Parvovirus B19

Parvovirus was the most common cause of generalized petechial rashes during a 2007 pediatric parvovirus B19 outbreak.

Edmonson MB et al. Pediatrics 2010 Apr; 125: e787-e792.

Objectives: Human parvovirus B19 infection is associated not only with erythema infectiosum (fifth disease) but also, rarely, with purpuric or petechial rashes. Most reports of these atypical rashes describe sporadic cases with skin lesions that have distinctively focal distributions. During a community outbreak of fifth disease, we investigated a cluster of illnesses in children with generalized petechial rashes to determine whether parvovirus was the causative agent and, if so, to describe more fully the clinical spectrum of petechial rashes that are associated with this virus.

METHODS: Systematic evaluation was conducted by general pediatricians of children with petechial rashes for evidence of acute parvovirus infection.

RESULTS: During the outbreak, acute parvovirus infection was confirmed in 13 (76%) of 17 children who were evaluated for petechial rash. Confirmed case patients typically had mild constitutional symptoms, and most (11 [85%] of 13) had fever. Petechiae were typically dense and widely distributed; sometimes accentuated in the distal extremities, axillae, or groin; and usually absent from the head/neck. Most case patients had leukopenia, and several had thrombocytopenia. Parvovirus immunoglobulin M was detected in 8 (73%) of 11 acute-phase serum specimens, and immunoglobulin G was detectable only in convalescent specimens. Parvovirus DNA was detected in all 7 tested serum specimens, including 2 acute-phase specimens that were immunoglobulin M–negative. All case patients had brief, uncomplicated illnesses, but 6 were briefly hospitalized and 1 underwent a bone marrow examination. Two case patients developed erythema infectiosum during convalescence.

CONCLUSIONS: During an outbreak of fifth disease, parvovirus proved to be a common cause of petechial rash in children, and this rash was typically more generalized than described in case reports. Associated clinical features, hematologic abnormalities, and serologic test results are consistent with a viremia-associated illness that is distinct from and occasionally followed by erythema infectiosum.

15. Unplanned ICU Transfers Often Preventable but Are Not Typically Due to Clinical Error

Terry Hartnett. April 12, 2010 (Washington, DC) — Transfers to the intensive care unit (ICU) that occur within 24 hours of presentation at the emergency department (ED) are primarily the result of a worsening of the initial condition or the development of a new problem. Very few of these transfers are due to diagnostic error or inappropriate treatment, according to a report presented here at Hospital Medicine 2010: Society of Hospital Medicine Annual Meeting.

The general consensus is that these transfers can be avoided, but a study presented by lead investigator Srinivas Bapoje, MD, MPH, a hospitalist at the Denver Health Medical Center in Colorado, suggests that improving triage and monitoring in the ED might result in immediate appropriate transfer from the ED to the ICU.

Dr. Bapoje told Medscape Internal Medicine that the accepted thinking on why so many patients end up in the ICU when they were not originally triaged there from the ED has been that clinical errors lead to unplanned transfers.

"Most of the patients in our study went to the ICU within 24 hours, and many within the first 6 hours," he said. "It seems clear that these patients likely met ICU criteria in the ED," said Dr. Bapoje. "We need to screen patients better."

The study involved 152 patients. The 2 most common diagnoses were respiratory failure (24%) and acute coronary syndrome (11%).

"Errors in care accounted for the transfer of 29 patients (19%), but in 15 of 29 patients (52%) the errors were in triage, because 14 of 15 (93%) met ICU admission criteria while still in the emergency department," Dr. Bapoje and his colleagues reported.

The study found 4 primary reasons for unplanned ICU transfers:

• Triage errors from the ED. This occurred in 15 cases (10% of the total), 14 of which (9%) were due to overlooked severity; only 1 (0.7%) of the unplanned ICU transfers was due to a diagnostic error. None of the transfers were the result of inadequate assessment.
• Worsening of the presenting condition. This was true for close to half of the patients in the study, with 73 patients (48%) experiencing worsening (68 of which were spontaneous). There were only 5 errors in assessment or treatment (3%).
• Development of a new problem. A significant number (59 patients [39%]) experienced this situation.
• Critical lab values. Only 5 cases (3%) fell into this category.

Dr. Bapoje told Medscape Internal Medicine that a rapid response team was used in the management of 106 of the study patients, but there was no recognized difference in outcome from those managed conventionally.

The researchers also found that mortality decreased for patients transferred to the ICU in the first 24 hours of hospital admission, compared with patients transferred after the initial 24 hours (4% vs 22%).

Still, Dr. Bapoje found that 29 (19%) transfers might have been prevented. "If the transfer occurs from the floor to the ICU, it adds to the cost and lengthens the stay," he said. "When the transfer occurs directly from the ED, it allows us to manage resources better," he noted.

A faculty member at the conference, Mary Jo Gorman, MD, FHM, founder and chief executive officer of Advances ICU Care, based in St. Louis, Missouri, told Medscape Internal Medicine that the results are not surprising, but she agreed that they point to the need for better observation and a quicker response to changes in the patient's condition.

"Hospitalists are increasingly being asked to fill the gap of intensivists in the ICU," said Dr. Gorman. "We need to closely monitor these patients and proactively intervene when necessary," she said.

Dr. Gorman's company monitors patients through a telemedicine system that puts a monitor and camera in each patient's room. The data feeds are monitored around the clock and allow for a quick response to any worsening or change in condition.

Dr. Bapoje said that although the deterioration of a patient's condition cannot be alleviated, the hospitalist who is based in the hospital around the clock can do a better job of monitoring and providing a quick response.

The study did not receive commercial support. Dr. Bapoje and Dr. Gorman have disclosed no relevant financial relationships.

Hospital Medicine 2010: Society of Hospital Medicine (SHM) Annual Meeting: Abstract 19. Presented April 9, 2010.

16. Is Risk for Venous Thromboembolism Affected by Route and Type of Menopausal Hormone Therapy?

Results of a large observational study suggest that transdermal (in contrast with oral) estrogens do not raise risk.

Although hormone therapy (HT) now is recommended only for short-term relief of menopausal symptoms, risk for idiopathic venous thromboembolism (VTE) is greatest during the first year of treatment. To determine if route of administration or type of concomitant progestogen affects risk for VTE, investigators analyzed data from a prospective cohort study of more than 80,000 French women (mean age at entry, 54) who completed biennial questionnaires for a mean of 10 years. The study was partially funded by a manufacturer of transdermal delivery systems.

During follow-up, 549 first idiopathic VTEs (134 pulmonary emboli and 415 deep venous thromboses) occurred. Past users (i.e., those with no use within 3 months before questionnaire completion) and never users of HT had similar VTE risk. Analysis adjusted for potential confounders showed that users of oral, but not transdermal (patch or gel), estrogen had substantially higher risk for VTE than did never users (hazard ratio, 1.7). No significant associations were found between VTE and concomitant micronized progesterone (Prometrium), pregnane derivatives including medroxyprogesterone acetate (Provera), or nortestosterone derivatives (including norethindrone acetate). However, the norpregnane derivatives nomegestrol acetate and promegestone (not marketed in the U.S.) were associated with significantly higher VTE risk (HR, 1.8).

Comment: This observational study cannot provide irrefutable evidence that transdermal estrogens do not raise VTE risk, but it is the largest study to date that suggests the possibility; moreover, the findings mirror those of earlier studies (JW Womens Health Apr 5 2007). Given that oral, but not transdermal, estrogens can raise levels of factors that lead to clotting, these findings are biologically plausible. The data also provide reassurance that progestogens marketed in this country (when prescribed with transdermal estrogen) do not raise VTE risk.

— Robert W. Rebar, MD

Published in Journal Watch Women's Health April 8, 2010. Citation: Canonico M et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: Results from the E3N cohort study. Arterioscler Thromb Vasc Biol 2010 Feb; 30:340.

17. A Descriptive Comparison of Ultrasound-guided Central Venous Cannulation of the Internal Jugular Vein to Landmark-based Subclavian Vein Cannulation

Theodoro D, et al. Acad Emerg Med. 2010;17: 416–422.

Objectives: The safest site for central venous cannulation (CVC) remains debated. Many emergency physicians (EPs) advocate the ultrasound-guided internal jugular (USIJ) approach because of data supporting its efficiency. However, a number of physicians prefer, and are most comfortable with, the subclavian (SC) vein approach. The purpose of this study was to describe adverse event rates among operators using the USIJ approach, and the landmark SC vein approach without US.

Methods: This was a prospective observational trial of patients undergoing CVC of the SC or internal jugular veins in the emergency department (ED). Physicians performing the procedures did not undergo standardized training in either technique. The primary outcome was a composite of adverse events defined as hematoma, arterial cannulation, pneumothorax, and failure to cannulate. Physicians recorded the anatomical site of cannulation, US assistance, indications, and acute complications. Variables of interest were collected from the pharmacy and ED record. Physician experience was based on a self-reported survey. The authors followed outcomes of central line insertion until device removal or patient discharge.

Results: Physicians attempted 236 USIJ and 132 SC cannulations on 333 patients. The overall adverse event rate was 22% with failure to cannulate being the most common. Adverse events occurred in 19% of USIJ attempts, compared to 29% of non–US-guided SC attempts. Among highly experienced operators, CVCs placed at the SC site resulted in more adverse events than those performed using USIJ (relative risk [RR] = 1.89, 95% confidence interval [CI] = 1.05 to 3.39).

Conclusions: While limited by observational design, our results suggest that the USIJ technique may result in fewer adverse events compared to the landmark SC approach.

18. Are Acetaminophen/NSAID Combinations More Effective Than One Drug Alone?

A systematic review indicates that combinations are more effective for relieving acute pain.

Although many clinicians recommend combining acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) for acute pain management, the evidence for this practice has been mixed. An international team of investigators performed a systematic review of all randomized controlled trials (RCTs) in which paracetamol/NSAID combinations were compared to either class of drug alone for managing acute postoperative pain. The study was funded by the manufacturer of a paracetamol/ibuprofen combination tablet.

Twenty RCTs involving 1852 patients compared paracetamol/NSAID combinations with paracetamol alone. An analgesic combination was more effective than acetaminophen alone for at least one of three measures (pain score, need for supplemental analgesia, globally assessed pain relief) in 16 studies (80%). The mean reduction in pain intensity was 35%, and the mean reduction in need for supplemental analgesics was 39%. Fourteen studies involving 1129 patients compared the efficacy of an analgesic combination to that of an NSAID alone. Nine studies (64%) demonstrated that the combination was more effective. The mean reduction in pain intensity was 38%, and the mean reduction in need for analgesic supplementation was 31%. The incidence of side effects did not differ significantly between combination therapy and either single-drug therapy.

Comment: This systematic review supports the use of a combination of acetaminophen and NSAIDs for acute pain. The postoperative pain models used in these studies (orthopedic; ear, nose, and throat; gynecological; general; and dental surgery) likely translate well to other acute pain contexts.

— Emily L. Brown, MD, and Ron M. Walls, MD, FRCPC, FAAEM. Published in Journal Watch Emergency Medicine April 9, 2010. Citation: Ong CK et al. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: A qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010 Apr; 110:1170.

19. Changes in Rabies Postexposure Prophylaxis Regimen

The CDC recommends changing the vaccination schedule from five to four doses.

Rupprecht CE et al. MMWR Recomm Rep 2010 Mar 19; 59:1


20. Thrombolytic Therapy Appears Safe Even in Stroke Mimics

Susan Jeffrey. April 6, 2010 — A new retrospective study suggests prompt treatment with tissue plasminogen activator (tPA) within 3 hours of symptom onset is safe even for patients who ultimately are found not to have had a stroke.

Outcomes showed that patients with conditions that simulate acute ischemic stroke, so-called stroke mimics, underwent treatment without any symptomatic intracerebral hemorrhage (ICH), the most feared complication of treatment.

"It may be that when you give tPA to people who don't have a stroke, the [hemorrhage] risk is much lower," lead study author Sean I. Savitz, MD, from the Department of Neurology at the University of Texas Medical School at Houston, speculated.

Time is brain, he said, and the pressure is on in the emergency department to make a decision on whether or not to treat. "That kind of approach can miss other things and lead you to treating things that are not actually stroke. There's not enough time to determine that this really is a seizure, or really is a migraine, or might be something else," he told Medscape Neurology.

The indication from this retrospective study at least is that that approach is safe even for patients who don’t have stroke, but prospective studies would help to better establish the safety of treating stroke mimics, he added.

Their findings were published online March 24 and will appear in the April 27 issue of Neurology.
Clock Is Ticking

Newer imaging modalities, such as computed tomographic (CT) angiography, magnetic resonance angiography, or transcranial Doppler, can show large artery occlusions, and diffusion-weighted imaging is very sensitive for ischemic stroke, the study authors write, but these techniques are not universally available.

No large study has looked at the outcomes of patients treated with tPA who were ultimately found to have a stroke mimic, such as seizure, complicated migraine, or functional deficits, or those assumed to have an averted stroke, that is, those without an infarct on magnetic resonance imaging (MRI) but who were not found to have another diagnosis. This latter group was called neuroimaging-negative cerebral ischemia (NNCI) in this analysis.

The investigators performed a retrospective review of patients treated with intravenous tPA within 3 hours of symptom onset between June 2004 and October 2008, identified from their stroke registry. They recorded admission National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin score, length of stay, any incidence of symptomatic ICH, and discharge diagnosis.

In all, 512 patients received tPA during that period of which 21% were found not to have an infarct on imaging.

Stroke mimics, those in whom another diagnosis was established, accounted for 14%. Their average age was 55 years, median admission NIHSS score was 7, median discharge NIHSS score was 0, median length of stay was 3 days, and none of these patients had symptomatic ICH after treatment. The most common alternate diagnoses among these patients were seizure, complicated migraine, and conversion disorder.

The remaining 7% fell into the NNCI group. The average age in this group was 61 years, median admission NIHSS score again was 7, median discharge NIHSS score again was 0, median length of stay was identical at 3 days, and, again, none had symptomatic ICH.
Their data, and those of others, they conclude, support treatment with tPA in those with suspected acute ischemic stroke, even when alternate diagnoses are being considered.

"Because the risk of emergently treating [stroke mimics], such as migraine, are low, and there is a loss of potential benefit in withholding treatment if the patient is indeed having a stroke, we favor intravenous tPA treatment if the patient meets Food and Drug Administration and American Heart Association criteria for thrombolysis," the study authors write.

"Subsequent studies after tPA initiation can be performed to better clarify the etiology in cases where the diagnosis is uncertain," they add. "Further prospective investigations are needed to establish the safety of thrombolysis in [stroke mimics] and NNCI."

"Swift and Sure"

In an editorial accompanying the publication, Jeffrey L. Saver, MD, from the University of California, Los Angeles, and William G. Barsan, MD, from the University of Michigan, Ann Arbor, point out that the new study shows the outcome of lytic exposure in mimic patients was "benign, with no cases reported of intracranial hemorrhage (0/82), systemic hemorrhage (0/69), or orolingual edema (0/76)."

The rate of mimics in this series, though, is higher than in prior studies, they note, "reflecting the distinctive and explicit policy of the Houston group to treat patients early, even if the diagnosis is still uncertain." Most other centers, they write, prefer more diagnostic certainty even though it could mean worsening neurologic outcomes.

Between the poles of diagnostic certainty and rapid treatment "lie happy mediums," they write. Although investigation continues, they suggest that a "reasonable target" based on previous studies would be a door-to-needle time of 60 minutes or less, with a neurovascular mimic rate of 3% or less where noncontrast CT alone is used, and 1% or less with more advanced modalities.

"Many tools are available to improve hyperacute stroke diagnosis and reduce mimic treatment rates, including formal assessment tools for prehospital personnel and emergency physicians, telestroke consultation by remote stroke expert physicians, and multimodal CT and MRI," Dr. Saver and Dr. Barsan conclude. "As these approaches are more widely implemented in regional stroke systems of care, thrombolytic treatment decisions can increasingly be both swift and sure."

Neurology. Published online March 24, 2010.

21. Airway Obstructions in Children Are Uncommon but Often Fatal

Nancy Fowler Larson. April 20, 2010 — Although only a small percentage of children incur airway obstruction from foreign bodies (FBs), a significant proportion of those cases result in death, according to a study published in the April issue of the Archives of Otolaryngology—Head & Neck Surgery.

Each year, approximately 2.5 million American children experience airway FBs (A-FBs) or esophageal FBs (E-FBs), which lead to as many as 2000 fatalities. Previous studies have demonstrated that half of such patients had no causal history, and 20% were misdiagnosed and mismanaged for at least 1 month.

"Delay of proper treatment inevitably increases the risk of complications and mortality in these patients," write Rahul Shah, MD, from the Division of Otolaryngology, Children's National Medical Center, George Washington University Medical Center, Washington, DC, and colleagues.
To pinpoint national trends regarding treatment of A-FBs and E-FBs in pediatric patients, the investigators studied information from the national Kids' Inpatient Database (KID) 2003 for those younger than 20 years.

The KID data that year came from close to 3 million pediatric discharges from 3438 hospitals. Of those, 2771 children had been admitted for FB airway obstructions. Fifty-nine percent were boys, 55% were younger than 2 years, and the mean age was 3.5 years. Other findings were as follows:

• 3.4% (n = 94) of children with FBs died in the hospital
• 25% of objects involved in all deaths met standards set by the Consumer Products Safety Commission
• 58% of FBs in fatal and nonfatal cases were nonorganic; 42% were food, with similar fatality numbers in each group (Χ2P = .65)
• Treatment procedures included bronchoscopy (52%), esophagoscopy (28%), and tracheotomy (1.7%)

Teaching hospitals were the treatment location for 71% of cases. The average charges were $34,652, with regional differences (P less than .001) and with greater expense at children's hospitals (P = .03). The mean hospital stay was 6.4 days and entailed 2.4 procedures.

The researchers noted that although children younger than 3 years were involved in most obstructions from edible objects, older children accounted for many of the nonfood cases.

"Prior studies have shown that children younger than 3 years are at higher risk for A-FBs and E-FBs. Our data corroborate this finding, as 80% of children with recovered organic FBs were younger than 3 years," the authors write. "However, only about 60% of children with inorganic FBs were younger than this age."

The mean age of pediatric patients whose FBs were caused by nonfoods was 4.3 years. That prompted an alert for physicians to more frequently suspect FBs when faced with an older child in respiratory distress.

Several limitations to the study were noted. First, any inaccurate data from the KID would have been included in the study. Second, biases may exist for 2 reasons: the researchers' decision to use E911 (inhalation and ingestion of food causing obstruction of respiratory tract or suffocation) and E912 (inhalation and ingestion of other object causing obstruction of respiratory tract or suffocation) International Classification of Diseases, Ninth Revision, Clinical Modification, codes only, and because a portion of the data-use agreement prevented discussion of a variable when its frequency was less than 10 sampled admissions.

The investigators called on teaching hospitals to increase and diversify training for the removal of airway obstructions.

"Bronchoscopic removal of FBs is standard in the treatment of these children; however, the dearth of actual cases makes this skill difficult to learn and to assess in trainees," the authors write. "To resolve this deficiency, alternative educational paradigms for FB retrieval may need to be considered."

The study authors have disclosed no relevant financial relationships.

Arch Otolaryngol Head Neck Surg. 2010;136:373-379.