Lit Bits: April 2, 2010

From the recent medical literature...

1. Clinical Features from the H&P That Predict the Presence or Absence of Pulmonary Embolism in Symptomatic ED Patients: Results of a Prospective, Multicenter Study

Courtney DM, et al. Ann Emerg Med. 2010;55:307-315.e1.

Study objective
Prediction rules for pulmonary embolism use variables explicitly shown to estimate the probability of pulmonary embolism. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of pulmonary embolism. The objective of this study is to measure the predictive value of 13 implicit variables.

Methods
Patients were enrolled in a prospective cohort study from 12 centers in the United States; all had an objective test for pulmonary embolism (D-dimer, computed tomographic angiography, or ventilation-perfusion scan). Clinical features including 12 predefined previously validated (explicit) variables and 13 variables not part of existing prediction rules (implicit) were prospectively recorded at presentation. The primary outcome was venous thromboembolism (pulmonary embolism or deep venous thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with adjusted odds ratios from logistic regression with 95% confidence intervals not crossing unity were considered significant.

Results
Seven thousand nine hundred forty patients (7.2% venous thromboembolism positive) were enrolled. Mean age was 49 years (standard deviation 17 years) and 67% were female patients. Eight of 13 implicit variables were significantly associated with venous thromboembolism; those with an adjusted odds ratio (OR) greater than 1.5 included non-cancer-related thrombophilia (OR 1.99), pleuritic chest pain (OR 1.53), and family history of venous thromboembolism (OR 1.51). Implicit variables that predicted no venous thromboembolism outcome included substernal chest pain, female sex, and smoking. Nine of 12 explicit variables predicted a positive outcome of venous thromboembolism, including patient history of pulmonary embolism or deep venous thrombosis in the past, unilateral leg swelling, recent surgery, estrogen, hypoxemia, and active malignancy.

Conclusion
In symptomatic outpatients being considered for possible pulmonary embolism, non-cancer-related thrombophilia, pleuritic chest pain, and family history of venous thromboembolism increase probability of pulmonary embolism or deep venous thrombosis. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US emergency department patients.

Full-text (free): http://www.annemergmed.com/article/S0196-0644(09)01735-1/fulltext

2. Does Absence of Coronary Artery Calcification Exclude Obstructive Coronary Artery Disease?

In symptomatic patients, overall sensitivity of a CAC score of 0 for predicting absence of obstructive CAD was only 45%.

Gottlieb I, et al. J Am Coll Cardiol 2010; 55:627.

Objectives: This study was designed to evaluate whether the absence of coronary calcium could rule out 50% coronary stenosis or the need for revascularization.

Background: The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.

Methods: A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before.

Results: In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 ± 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of 50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 50% stenosis. The overall sensitivity for CS = 0 to predict the absence of 50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with 50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium.

Conclusions: The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification.

3. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts

Douma RA, et al. BMJ 2010;340:c1475

Objectives: In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed.
Design Retrospective multicentre cohort study.

Setting: General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland.

Patients: 5132 consecutive patients with clinically suspected pulmonary embolism.

Intervention: Development of a new D-dimer cut-off point in patients aged more than 50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets.

Main outcome measures: The proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates.

Results: The new D-dimer cut-off value was defined as (patient’s age x 10) µg/l in patients aged more than 50. In 1331 patients in the derivation set with an "unlikely" score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (below 500 µg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged more than 70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets.

Conclusions: The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded.

Full-text (free): http://www.bmj.com/cgi/content/full/340/mar30_3/c1475

4. Children with Food-Related Anaphylaxis Need Access to 2 Epinephrine Injections

Nancy Fowler Larson. April 1, 2010 — Keeping 2 doses of epinephrine on hand is recommended for children with life-threatening food allergies, according to a study published online March 22 in Pediatrics.

Approximately 3 million children in the United States have food allergies, and that number is growing. Food allergies are the chief cause of anaphylaxis, a sometimes-fatal allergic response, which progresses quickly to constrict the airway, irritate the skin and intestines, and/or affect heart rhythm. It is treated with an injection of epinephrine (adrenaline), which stimulates the heart, and elevates blood pressure, metabolic rate, and blood glucose concentration.

A number of small studies recommend that children who have experienced anaphylaxis brought on by food allergies should carry several doses of epinephrine. The suggestion brings up issues of cost and logistics.

"Therefore, we sought to more accurately define the likelihood of receiving dose of epinephrine for food-related anaphylaxis and to characterize the children for whom this was medically necessary," write Carlos A. Camargo Jr, MD, DrPH, from the Department of Emergency Medicine, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, and colleagues.

Using charts from Massachusetts General Hospital and Children's Hospital Boston, investigators reviewed 605 cases of 1255 patients whose mean age was 5.8 years. A total of 62% were boys. All subjects arrived at the emergency department (ED) between 2001 and 2006 with allergic reactions related to foods, typically nuts and milk. The investigators measured acute reactions using the International Classification of Diseases, Ninth Revision, Clinical Modification, criteria.

An allergic reaction to 2 or more organ systems or the presence of hypotension (below 70 mm Hg + [age x 2 years] for children under 10 years old, and below 90 mm Hg for children 10 - 18 years old) after exposure to an allergy-causing food was used to define anaphylaxis. Mean ± standard error and a 95% confidence interval (CI) were used to derive data. Statistical significance was achieved with a 2-sided P value of less than .05 in multivariable analysis, with use of unweighted numbers of visits to determine risk factors for a second dose of epinephrine.

Of Those Needing Epinephrine, 12% Required Second Dose

The results show that more than half (52%; 95% CI, 48% - 57%) of the subjects met the criteria for anaphylaxis stemming from foods, among other findings:

• Before their arrival at the ED, 31% of patients with anaphylaxis had received 1 dose of epinephrine, and 3% had received more than 1 dose.
• Once in the ED, 20% of those with anaphylaxis were treated with epinephrine; the others received antihistamines (59%) or corticosteroids (56%).
• During the entirety of their allergic episode, 44% of participants with anaphylaxis received epinephrine.
• Among those receiving epinephrine, 12% (95% CI, 9% - 14%) required more than 1 dose.

"This finding supports the recommendation that children at risk for food-related anaphylaxis carry 2 doses of self-injectable epinephrine," the study authors write.

Older age and having been transferred from another hospital were risk factors for a subsequent dose.

The study authors noted 3 limitations. First, the use of medical charts may have resulted in the inclusion of inaccurate or incomplete data. Second, the number of patients receiving epinephrine may have been overestimated because of the exclusive focus on ED cases. Finally, the hospital EDs in the study are in an academic, urban setting, possibly resulting in data that may not be nationally representative.

Pediatrics. Published online March 22, 2010.

5. Does diagnosis change as a result of repeat renal colic computed tomography scan in patients with a history of kidney stones?

Adam Goldstone A, et al. Amer J Emerg Med. 2010;28:291-295.

Study objective
We sought to determine the incidence of alternative diagnosis in patients with a history of kidney stones who experience recurrent symptoms and undergo repeat computed tomography (CT) imaging at their return to the emergency department (ED).

Methods
This was a retrospective chart review of ED patients at a tertiary care hospital. Inclusion criteria were all adult ED patients who received a repeat CT for renal colic, after having previously received the diagnosis of obstructive kidney stone confirmed by CT, in our ED. Patients were identified by reviewing the charts of those patients with repeat visits to the ED after January 1, 2004, in which they complained of symptoms suggestive of renal colic and received a CT scan. We determined the frequency of the same diagnosis on repeat CT scan in this population compared with the frequency of alternative diagnosis.

Results
Two hundred thirty-one patients met criteria for the study. Fifty-nine percent were male. One hundred eighty-nine (81.8%) patients had no change in diagnosis as a result of a repeat renal colic CT scan. Twenty-seven (11.6%) patients received an alternative diagnosis that did not require urgent intervention, and 15 (6.5%) patients received a diagnosis that did require an urgent intervention.

Conclusion
Repeat CT imaging of patients with known nephrolithiasis changed management in a minority of patients (6.5%). Knowing the frequency of alternative diagnosis in this population may help clinicians and patients balance the risks and benefits of repeat renal colic CT scans in patients with a history of kidney stones who return to the ED with similar symptoms.

6. Risk for Deep Venous Thrombosis in Patients with Superficial Venous Thrombosis

Among 600 patients with isolated superficial venous thrombosis, 10% experienced thromboembolic events within 3 months.

Decousus H, et al. Ann Intern Med 2010;152:218.

Background: Superficial venous thrombosis (SVT) is perceived to have a benign prognosis.

Objective: To assess the prevalence of venous thromboembolism in patients with SVT and to determine the 3-month incidence of thromboembolic complications.

Design: National cross-sectional and prospective epidemiologic cohort study. (ClinicalTrials.gov registration number: NCT00818688)

Setting: French office- and hospital-based vascular medicine specialists.

Patients: 844 consecutive patients with symptomatic SVT of the lower limbs that was at least 5 cm on compression ultrasonography.

Measurements: Incidence of venous thromboembolism and extension or recurrence of SVT in patients with isolated SVT at presentation.

Results: Among 844 patients with SVT at inclusion (median age, 65 years; 547 women), 210 (24.9%) also had deep venous thrombosis (DVT) or symptomatic pulmonary embolism. Among 600 patients without DVT or pulmonary embolism at inclusion who were eligible for 3-month follow-up, 58 (10.2%) developed thromboembolic complications at 3 months (pulmonary embolism, 3 [0.5%]; DVT, 15 [2.8%]; extension of SVT, 18 [3.3%]; and recurrence of SVT, 10 [1.9%]), despite 540 patients (90.5%) having received anticoagulants. Risk factors for complications at 3 months were male sex, history of DVT or pulmonary embolism, previous cancer, and absence of varicose veins.

Limitation: The findings are from a specialist referral setting, and the study was terminated before the target patient population was reached because of slow recruitment.

Conclusion: A substantial number of patients with SVT exhibit venous thromboembolism at presentation, and some that do not can develop this complication in the subsequent 3 months.

7. Coffee Drinking and Caffeine Associated With Reduced Risk of Hospitalization for Heart Rhythm Disturbances

While it is not proven that coffee is protective, it is unlikely that moderate caffeine intake increases arrhythmia risk, Kaiser Permanente study finds

SAN FRANCISCO — Coffee drinkers may be less likely to be hospitalized for heart rhythm disturbances, according to a new study by the Kaiser Permanente Division of Research in Oakland, Calif. The researchers, who note the findings may be surprising because patients frequently report palpitations after drinking coffee, are presenting the study at the American Heart Association’s 50th Annual Conference on Cardiovascular Disease Epidemiology and Prevention in San Francisco on March 5, 2010.

While it has been established that very large doses of caffeine, the most active ingredient in coffee, can produce rhythm disturbances, there has been limited epidemiologic research about the caffeine doses people take. Previous data from a population study in Denmark compared heavy to light coffee drinkers with respect to risk of atrial fibrillation, the most common major rhythm disturbance, and found no statistically significant difference. This research presentation is believed to be the first large, multiethnic population study to look at all major types of heart rhythm disturbance, the researchers said.

The researchers followed 130,054 men and women and found that those who reported drinking four or more cups of coffee each day had an 18 percent lower risk of hospitalization for heart rhythm disturbances. Those who reported drinking one to three cups each day had a 7 percent reduction in risk, according to Arthur Klatsky, MD, the study’s lead investigator and a senior consultant in cardiology at Kaiser Permanente Division of Research in Oakland, Calif.

“Coffee drinking is related to lower risk of hospitalization for rhythm problems, but the association does not prove cause and effect, or that coffee has a protective effect,” Klasky said. Other explanations for the association might include other traits of coffee drinkers such as exercise or dietary habits. Additionally, some people with heart rhythm problems often are not hospitalized.

“However, these data might be reassuring to people who drink moderate amounts of coffee that their habit is not likely to cause a majorrhythm disturbance,” Klatsky said. While this report is not sufficient evidence to say that people should drink coffee to prevent rhythm problems, it supports the idea that people who are at risk for rhythm problems, or who have rhythm problems, do not necessarily need to abstain from coffee, emphasized Klatsky.

The long-term observational study involved 130,054 men and women, 18 to 90 years old, with the majority less than 50 years old. About 2 percent (3,317) were hospitalized for rhythm disturbances; 50 percent of those were for atrial fibrillation, the most common heart rhythm problem. The 18 percent reduction in risk was consistent among men and women, different ethnic groups, smokers and nonsmokers. It also was similar for various rhythm problems such as paroxysmal supraventricular tachycardia, atrial flutter, and atrial fibrillation.

In the study, 14 percent reported drinking less than one cup of coffee a day; 42 percent reported drinking one to three cups; and 17 percent reported drinking four cups or more each day. Only 27 percent were not coffee drinkers.

While emphasizing that these observational data do not establish causality and a protective mechanism is unclear, researchers speculate that moderate doses of caffeine may affect rhythm disturbances by antagonism of adenosine, a nucleoside compound widely distributed in the body. In the heart adenosine has several effects on conduction of electrical impulses, muscle cell energetics, and heart muscle cell recovery that might predispose to rhythm problems. Caffeine antagonizes adenosine effects by blocking its chemical sites of action.

The researchers examined hospitalization data by elapsed time after the initial examination. For hospitalization within 10 years, the reduction in hospitalizations for people who consumed four cups of coffee or more each day reached 28 percent.

The researchers also studied persons in the group with or without symptoms or history of heart and respiratory disease. For both groups, consuming four cups of coffee daily appeared to be associated with fewer hospitalizations for rhythm disturbances.

For more information on studies related to coffee consumption, go to: http://www.dor.kaiser.org/external/Arthur_Klatsky/

8. Images in Emergency Medicine

Elderly Woman With Abdominal Pain
http://www.annemergmed.com/article/S0196-0644(09)01133-0/fulltext

9. Good and Bad Health Habits in U.S.

Jennifer Warner. March 17, 2010 — Regular drinkers outnumber regular exercisers, says a new report on health behaviors in the U.S.

The CDC study shows that six in 10 American adults were regular drinkers in 2005-2007, but only about three in 10 regularly exercised.

The report details a range of good and bad health habits among American adults, including alcohol use, cigarette smoking, exercise, body weight, and sleep.

Overall, researchers say that since 1997, rates of cigarette smoking have declined by several percentage points, rates of obesity have climbed, and rates of alcohol use, exercise, and sleep have remained relatively unchanged.

The results are based on survey data collected from 79,096 interviews with U.S. adults between 2005-2007 and highlight differences between various gender, ethnic, and social groups when it comes to health behaviors.

Alcohol Use

• Men were more likely than women to be drinkers (68% vs. 55%), and women were more likely than men to abstain from alcohol (31% vs. 18%).
• White people were more likely than African-Americans, Asians, Native Americans, or Alaska Natives to be drinkers.
• The more educated people were, the more likely they were to drink. Seventy-four percent of people interviewed who have a graduate degree were drinkers, compared with 44% of people with a high school diploma.

Cigarette Smoking

• One in five adults were smokers, and more than half (58.5%) had never smoked cigarettes.
• Four in 10 smokers tried to quit smoking in the last year.
• People who hold a GED were more likely than non-high school graduates and high school graduates to be smokers.

Exercise

• About six in 10 adults engaged in at least some leisure-time physical activity, and about three in 10 regularly engaged in some physical activity.
• Adults with higher levels of education were less likely to be smokers, be physically inactive, and be obese and to sleep six hours or less per night.
• Men were more likely than women to be physically active.

Body Weight

• Six in 10 adults were obese or overweight.
• Four in 10 adults were a healthy weight.
• Men were more likely to be overweight (67.9% vs. 53%), but men and women were equally likely to be obese (25.7% vs. 25.0%).

Sleep

• Six in 10 adults usually slept 7 to 8 hours in a 24-hour period.
• Three in 10 adults averaged 6 hours of sleep or fewer per night.
• Men aged 25-44 were more likely than women to sleep 6 hours or fewer, but women aged 65 and older were more likely than men to sleep fewer than 6 hours.

Schoenborn, C. “Health Behaviors of Adults: United States, 2005-2007,” March 17, 2010.

Free full-text (143 pages!): http://www.cdc.gov/nchs/data/series/sr_10/sr10_245.pdf

10. Insurance Companies Refusing Payment for Patients Who Leave the ED Against Medical Advice is a Myth

Wigder HN, et al. Ann Emerg Med. 2010;55:393.

Patients who request to leave emergency departments (EDs) against medical advice are sometimes told by health care providers that their insurance company will not pay their ED visit bill if they leave against medical advice. To test the validity of this assertion, we retrospectively reviewed 104 consecutive cases of patients with insurance leaving against medical advice in 2008 from a suburban level I trauma center that sees 57,000 ED visits per year. Our review included 19 insurance companies, including HMOs, PPOs, Medicare, Medicaid, and workman's compensation. We found that all 104 visits where the patient left against medical advice were fully reimbursed by their respective insurance company. Our review demonstrates that the admonishment by health care providers that insurance companies might not pay for a visit if patients leave the ED against medical advice is not well supported.

The belief that insurers will not reimburse ED visits when patients leave against medical advice is very prevalent among health care providers. We surveyed a convenience sample of 70 ED health care providers (emergency medicine residents and students n=40, attending physicians n=14, nurses n=16). Fifty-seven percent believe that insurance will not pay visits of patients leaving against medical advice. Fifty percent have told or would tell patients that insurance will not pay the bill if you leave against medical advice. Sixty-six percent have heard other health care providers tell patients that insurance will not pay the bill if you leave against medical advice.

In addition, the same belief is held by some consumers. For example, one consumer Web site states the same belief that your insurance company might not pay for the ED visit if you sign out against medical advice.

The problem of patients signing out against medical advice is commonly encountered by many physicians. In a recent study, an estimated 1 in 70 discharges in the United States are against medical advice.

Our study suggests that insurance companies not paying for ED visits of patients leaving against medical advice is a myth. Future studies may elucidate if physicians and nurses tell patients that leaving against medical advice will likely result in nonpayment by insurance to be helpful or to coerce patients to follow their medical recommendations.

11. Management of Early Spontaneous Pregnancy Loss

Procedures for managing early pregnancy loss are moving out of the operating room and into the office, safely and successfully.

Early pregnancy loss (EPL) is common: 15% to 20% of all recognized pregnancies end in spontaneous loss, and about one in four women will experience such pregnancy failure during her lifetime.

Although surgical treatment has been preferred historically, management strategies have evolved to encompass out-of-hospital care. Options for treating women with EPL now include expectant management, medical therapy, and surgical evacuation.

The rest of the (free) article is here: http://womens-health.jwatch.org/cgi/content/full/2010/401/1

12. Rate Control for Atrial Fibrillation: Can We Relax?

In a randomized trial, patients whose heart rates were strictly controlled fared no better than those treated more leniently — at least in the short term.

In many patients with relatively few symptoms, atrial fibrillation (AF) can be managed with heart rate control alone, without rhythm correction. Traditionally, the target in such cases has been the rate that would be expected in a similar patient in sinus rhythm. However, a retrospective analysis of data from two trials of rate versus rhythm control showed no clinical benefit from such strict control. In the current prospective Dutch trial, investigators randomized 614 patients with AF suitable for management with rate control alone to either strict control (below 80 beats/minute at rest and less than 110 beats/minute during moderate exercise) or lenient control (below 110 beats/minute at rest).

At the end of the dose-titration phase of the trial, the mean resting heart rate was markedly different in the strict- and lenient-control groups (76 vs. 93 beats/minute), but by 1 year, the difference had narrowed (75 vs. 86 beats/minute). At 3 years, the composite rate of death, hospitalization for heart failure, stroke, embolization, bleeding, and life-threatening arrhythmia did not differ significantly between the groups.

Comment: This study is the third to show no outcome improvement in patients with atrial fibrillation treated with strict versus lenient rate control. However, these were relatively short-term trials, and remodeling associated with rapid heart rates might not become evident for many more years. Furthermore, even the patients in the lenient-control group achieved reasonably low heart rates. Nonetheless, as an editorialist reminds us, adverse drug effects may outweigh what we believe to be the benefits of strict rate control. It is, indeed, "better to treat the patient and not the electrocardiogram."

— Mark S. Link, MD. Published in Journal Watch Cardiology March 15, 2010. Citation(s):
Van Gelder IC et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010 Mar 15; [e-pub ahead of print]. Dorian P. Rate control in atrial fibrillation. N Engl J Med 2010 Mar 15; [e-pub ahead of print].

13. Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses

Merlin MA, et al. Amer J Emerg Med. 2010;28:296-303.

Introduction
This study proposes that intranasal (IN) naloxone administration is preferable to intravenous (IV) naloxone by emergency medical services for opioid overdoses. Our study attempts to establish that IN naloxone is as effective as IV naloxone but without the risk of needle exposure. We also attempt to validate the use of the Glasgow Coma Scale (GCS) in opioid intoxication.

Methods
A retrospective chart review of prehospital advanced life support patients was performed on confirmed opioid overdose patients. Initial and final unassisted respiratory rates (RR) and GCS, recorded by paramedics, were used as indicators of naloxone effectiveness. The median changes in RR and GCS were determined.

Results
Three hundred forty-four patients who received naloxone by paramedics from January 1, 2005, until December 31, 2007, were evaluated. Of confirmed opioid overdoses, change in RR was 6 for the IV group and 4 for the IN group (P = .08). Change in GCS was 4 for the IV group and 3 for the IN group (P = .19). Correlations between RR and GCS for initial, final, and change were significant at the 0.01 level (ρ = 0.577, 0.462, 0.568, respectively).

Conclusion
Intranasal naloxone is statistically as effective as IV naloxone at reversing the effects of opioid overdose. The IV and IN groups had similar average increases in RR and GCS. Based on our results, IN naloxone is a viable alternative to IV naloxone while posing less risk of needle stick injury. Additionally, we demonstrated that GCS is correlated with RR in opioid intoxication.

14. A New Diagnostic Test for Acute Appendicitis?

Preliminary data look promising.

A screening test with high negative predictive value could improve diagnostic accuracy for acute appendicitis and reduce the number of patients needing imaging studies and consultation. In a prospective pilot study, researchers evaluated whether S100A8/A9, a calcium-binding protein that is secreted in inflammatory conditions, is a useful biomarker for acute appendicitis. The study was conducted by the manufacturer of the biomarker assay.

Plasma levels of S100A8/A9 and total white blood cell (WBC) counts were measured in 181 adults and children who presented to three emergency departments with right-sided or infraumbilical acute abdominal pain of less than 2 weeks' duration and no dysuria or recent trauma. The prevalence of acute appendicitis was 23%. For predicting acute appendicitis, S199A8/A9 (at a cutoff of 20 units) had a sensitivity of 93%, specificity of 54%, negative predictive value of 96%, and positive predictive value of 37%. Corresponding values for total WBC count (at a cutoff of 10 to the third power) were 62%, 67%, 86%, and 36%.

Comment: These preliminary data show promise for the S100A8/A9 test in patients with possible acute appendicitis, but the findings of this pilot study must be validated in a prospective trial. This study also shows, yet again, the futility of the outdated and discredited — but surprisingly persistent — practice of using WBC count to diagnose appendicitis.

— Diane M. Birnbaumer, MD, FACEP. Published in Journal Watch Emergency Medicine March 26, 2010. Citation: Bealer JF and Colgin M. S100A8/A9: A potential new diagnostic aid for acute appendicitis. Acad Emerg Med 2010;17:333.

15. Needle tip visualization during ultrasound-guided vascular access: short-axis vs long-axis approach

Stone MB, et al. Amer J Emerg Med. 2010;28:343-347.

Objectives
Ultrasound guidance for central venous catheterization improves success rates and decreases complications when compared to the landmark technique. Prior research has demonstrated that arterial and/or posterior vein wall puncture still occurs despite real-time ultrasound guidance. The inability to maintain visualization of the needle tip may contribute to these complications. This study aims to identify whether long-axis or short-axis approaches to ultrasound-guided vascular access afford improved visibility of the needle tip.

Methods
A prospective trial was conducted at a level I trauma center with an emergency medicine residency. Medical students and residents placed needles into vascular access tissue phantoms using long-axis and short-axis approaches. Ultrasound images obtained at the time of vessel puncture were then reviewed. Primary outcome measures were visibility of the needle tip at the time of puncture and total time to successful puncture of the vessel.

Results
All subjects were able to successfully obtain simulated blood from the tissue phantom. Mean time to puncture was 14.8 seconds in the long-axis group and 12.4 seconds in the short-axis group (P = .48). Needle tip visibility at the time of vessel puncture was higher in the long-axis group (24/39, 62%) as opposed to the short-axis group (9/39, 23%) (P = .01).

Conclusions
In a simulated vascular access model, the long-axis approach to ultrasound-guided vascular access was associated with improved visibility of the needle tip during vessel puncture. This approach may help decrease complications associated with ultrasound-guided central venous catheterization and should be prospectively evaluated in future studies.

See also: Veysman BD. The Vein Teardrop Sign: A Story of Ultrasound-Guided Vascular Access.
J Emerg Med. 2010;38:406-407.

16. Inaccuracies Common in Diagnostic X-Rays for Hip and Pelvic Fractures

Nancy Fowler Larson. March 23, 2010 — Standard X-rays are not a reliable indicator of hip and pelvic fractures, according to an article published in the April issue of the American Journal of Roentgenology.

"Hip fractures cause high morbidity and mortality, especially in the elderly population, in which the 1-year mortality has been reported to be 12-37%," write Matthew Kirby, MD, and Charles Spritzer, MD from the Department of Radiology, Duke University Medical Center, Durham, North Carolina. "The patient population among whom this problem often arises is elderly women with a history of minor trauma."

In a retrospective study, investigators sought to determine the accuracy of hip and pelvic X-rays in patients who arrived at the Duke emergency department with pain or suspected trauma, and who later had a magnetic resonance imaging scan (MRI). The researchers studied the records of 92 patients whose treatment occurred between July 2005 and June 2008. Seventy-seven were women and 15 were men, with an average age of 70.8 years. Sixty-five had a history of trauma, typically a fall or automobile accident.

X-ray Has False Positives and False Negatives

The results showed that X-ray missed a number of fractures and that MRI revealed many fractures undetected by X-ray. Among other findings:

• 13 patients (14%) had 23 fractures (6 hip, 17 pelvic) undetected by X-ray but confirmed by MRI
• 11 patients (12%) whose X-ray suggested the presence of fractures had MRIs that showed none
• 15 patients (16%) with X-rays that did reveal fractures had MRIs that depicted additional breaks missed by X-ray

Of the 59 patients whose MRIs showed no fractures, 43 (73%) had other conditions revealed by MRI, including muscle edema and tears, trochanteric bursitis, and hamstring tendinopathy. An area under the curve of 0.74 was calculated for receiver operating characteristics analysis for hip fracture detection through X-ray.

The researchers concluded that MRI paves the way for better patient care.

"We found a large number of both false-positive and false-negative diagnoses based on radiographic findings alone," the authors write. "Use of MRI has a substantial advantage in the detection of pelvic and femoral fractures, helping to steer patients to appropriate medical and surgical therapy."

Several limitations were noted by the investigators. First, the retrospective study design offers innate limitations, including the fact that work-up bias may have existed, as only patients who underwent MRI were evaluated. Second, no separate examination was done for trauma patients alone. Third, the study included no cost analysis for the added expense of MRI and other factors that might offset it. Finally, variation existed among MRI protocols and requested X-rays.

Future implications for the study include benefits for patients as well as healthcare management, according to the study authors.

"Accurate diagnosis of hip and pelvic fractures in the emergency department can speed patients to surgical management, if needed, and reduce the rate of hospital admissions among patients who do not have fractures," Dr. Spritzer said in a press release. "This distinction is important in terms of health care utilization, overall patient cost, and patient inconvenience."

Duke University Medical Center supported the study. The study authors have disclosed no relevant financial relationships.

AJR Am J Roentgenol. 2010;94:1054-1060.

17. Treating Urinary Tract Infections in Healthy Women — Less Is More

Treatments based on dipstick results are as good as — and less expensive than — those based on culture.

Empirical therapy for urinary tract infections (UTIs) in a primary care setting is effective because most people with symptoms have bacterial infections. Unfortunately, this treatment strategy results in antibiotic prescription for about 10% of the healthy adult female population in the U.K. each year. In four linked studies conducted in southern England, researchers evaluated various approaches to therapy, trying to balance effectiveness with a reduction in unnecessary antibiotic use.

Little and colleagues examined the effectiveness of five strategies commonly used to eliminate UTI symptoms. A total of 309 nonpregnant women aged 18 to 70 were randomized to empirical therapy, begun immediately or delayed by 48 hours, or to targeted antibiotics based on a UTI symptom score, dipstick results (leucocytes, or both nitrites and blood), or culture results from a midstream urine sample. No significant differences were seen among the strategies in time to amelioration of symptoms.

Turner and co-workers evaluated the cost-effectiveness of these five approaches. The dipstick strategy was less costly than urine culture but more costly than empirical therapy. Compared with immediate antibiotics, the dipstick strategy cost about £10 for each day of symptoms avoided. The authors considered only duration of symptoms and cost of care to the National Health Service — not the additional benefit of reducing unnecessary antibiotic use.

Leydon and colleagues used interviews to explore trial participants' views about UTI management. Although the 21 participants generally favored decreasing their exposure to antibiotics, they reacted somewhat more ambiguously to a suggested 48-hour delay in antibiotic therapy. Without careful and caring discussion by the physician, patients who were asked to delay antibiotics were apt to think that their symptoms were not being considered seriously.

Finally, Little and colleagues examined the natural course of uncomplicated UTIs in 839 nonpregnant women aged 18 to 70, of whom 511 had complete symptom diaries and laboratory results. Among patients with infections caused by microbes sensitive to the antibiotic prescribed, severe symptoms lasted an average of 3.32 days. Such symptoms lasted 56% longer in women with resistant organisms (P less than 0.001), 62% longer when no antibiotics were prescribed (P=0.008), and 33% longer in patients with "urethral syndrome" (symptoms, but no laboratory confirmation; P less than 0.001). In multivariate analysis, antibiotic resistance and no antibiotics were the most important factors in prolongation of symptoms.

Comment: These studies, conducted in various private practice settings, suggest that urine culture offers no benefit over empirical therapy in women with uncomplicated UTIs. Although the dipstick strategy is slightly more expensive than empirical therapy, the increased cost may be justified by the reduction in unnecessary antibiotic use. An editorialist notes the need to achieve a balance between individual benefits (alleviation of distress caused by prolonged symptoms, decrease in lost productivity) and population benefits (reduced antibiotic use). The physician's approach to explaining management and allaying fears is an important element in treating women with such infections.

— Stephen G. Baum, MD. Published in Journal Watch Infectious Diseases March 10, 2010. Citation: Little P et al. Effectiveness of five different approaches in management of urinary tract infection: Randomised controlled trial. BMJ 2010; 340:c199.

Full-text: http://www.bmj.com/cgi/content/full/340/feb05_1/c199

18. Emergency Department Workload Increase: Dependence on Primary Care?

Tranquada KE, et al., J Emerg Med. 2010;38:279-285.

Background: Increasing demand for emergency care and crowded emergency departments (EDs) lead some planners to conclude that inconvenient primary care scheduling increases the number of “unnecessary” ED visits. The reasons that the planners argue for more primary care are: to increase funding for primary care; the unfounded notion that it is less expensive to see a primary care physician (PCP) than an Emergency Physician; and the impractical goal that the ED should be used only by intellectually interesting life- or limb-threatened patients or “true emergencies.”

Objective: To explore the rates of patient-reported access to primary care in ambulatory presentations to a rural tertiary care ED.

Methods: An observational study was performed in which an anonymous survey was given to a convenience sample of patients who presented by walking into the ED. Results: Overall, 70.4% (686/975) of respondents stated that they had a PCP, and 38.1 % (252/661) of the sample had attempted to contact their physicians before presenting to the ED. Of the group who attempted to contact their physicians, 62.8% (130) were neither spoken to nor seen by any doctor. These rates did not change by time of presentation or by day of the week.

Conclusion: The results suggest that it is neither a lack of primary care, nor the time of day or night that drives patients to come to the ED.

19. Cardiovascular Benefits of Statins vs. Risk for Incident Diabetes

One additional case of incident diabetes occurred for every 255 patients who received statins for 4 years.

Does statin therapy raise risk for incident diabetes? When statins were compared with placebo (or usual care), mixed signals have emerged, with statins seeming to raise diabetes incidence in some trials and to lower it in others.

In a collaborative meta-analysis, investigators reviewed data from 13 trials in which 90,000 stable nondiabetic patients were randomized to receive a statin or placebo (or usual care) and were followed for a mean of 4 years. The rate of incident diabetes was slightly but significantly higher in patients who took statins than in those who received placebo or usual care (4.9% vs. 4.5%; odds ratio, 1.09). In absolute terms, one additional case of incident diabetes occurred for every 255 patients who received statins for 4 years. No variations in diabetes risk were noted among different statins. The association of statin use and incident diabetes was stronger in trials that involved older patients.

Comment: Although statins might cause one additional case of diabetes per 255 nondiabetic patients treated for 4 years, data from another meta-analysis indicate that statins would prevent five major coronary events in those 255 patients. Therefore, the authors recommend that risk for diabetes should not deter therapy with statins in patients at moderate-to-high cardiovascular risk, but they suggest that older patients who take statins be monitored for hyperglycemia.

— Bruce Soloway, MD. Published in Journal Watch General Medicine March 4, 2010. Citation:
Sattar N et al. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet 2010; 375:735.

20. SCAN Rule May Reduce Misdiagnosis of ICH in Patients with Minor Stroke

Emma Hitt, PhD. March 22, 2010 — A rule involving 4 symptoms — severe hypertension (S), confusion (C), anticoagulation (A), and nausea and vomiting (N) — appears to be specific and sensitive at identifying intracerebral hemorrhage (ICH) in patients with minor stroke.

The SCAN rule states that if at least 1 of these 4 predictive variables is present in a patient with minor stroke, the patient is likely to have ICH. The rule may help determine which patients can be safely treated immediately with antiplatelet agents compared with those who might have ICH and would need further brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) before treatment.

Caroline E. Lovelock, MBChB, DPhil, FRACP, formerly with the John Radcliffe Hospital in Oxford, United Kingdom, and now with the Department of Neurology at St. George's Hospital Medical School in London, United Kingdom, and colleagues published their findings in the March issue of Journal of Neurology, Neurosurgery & Psychiatry.

"Because CT brain imaging becomes insensitive to an acute bleed after only a few days, the SCAN rule is particularly useful for identifying which late-presenting patients need priority access to MRI brain imaging so that the risk of misdiagnosing an ICH can be minimized," Dr. Lovelock told Medscape Neurology.

The researchers sought to identify clinical factors associated with ICH in 334 consecutive patients with minor stroke, defined as a National Institutes of Health Stroke Scale score of 3 or less. The predictive model derived in this cohort was then further validated in a separate cohort of 280 patients. Approximately 5% of patients in the initial and validation cohorts had ICH.

"In the hospital clinic validation cohort, at least 1 clinical predictor was present in 24% of patients but in 93% of patients with ICH," the study authors write. "If 2 or more clinical predictors were present, 25% of patients had evidence of ICH on scan."

Data pooled from the derivation and validation cohorts indicated that the SCAN rule had a sensitivity of 97% (95% confidence interval [CI], 84% – 99%) and a specificity of 74% (95% CI, 70% – 77%) for the detection of ICH.

Utility in Various Healthcare Settings

The SCAN rule, which is applicable to late-presenting patients with minor stroke, should be useful in both the US and UK healthcare systems, Dr. Lovelock said. Even in a highly resourced healthcare system, she noted, "patients with minor stroke may still present late to medical attention, particularly if they are relatively socially or geographically isolated."

According to Dr. Lovelock, the SCAN rule may also be useful in poorer countries, "where it can be used to identify which patients with minor stroke need priority access to early CT imaging to rule out ICH," although it still requires validation in different healthcare settings.

Dr. Lovelock noted, though, that the SCAN rule should not be used as an alternative to brain imaging to diagnose ICH. "Instead it is a guide to help plan appropriate investigations and treatment for patients with minor stroke, in whom the possibility of an underlying ICH always needs to be considered."

Not an Alternative to Brain Imaging

According to a related editorial by Enda Kerr and Rustam Al-Shahi Salman with the University of Edinburgh, United Kingdom, "the most useful attribute of the SCAN rule might be its negative predictive value of 99.8% (95% CI, 99% – 100%).

"For the 70% of patients with minor stroke who had a SCAN score of zero, ICH was almost completely ruled out," they point out.

Still, although the SCAN rule almost "rules out ICH in patients with minor strokes and a SCAN score of zero, it is insufficient to completely refute the need for timely and appropriate brain imaging."

Brain imaging can also do more than exclude hemorrhage by identifying the vascular territory of an ischemic stroke, ruling out stroke "mimics" and potentially influencing prognosis estimates or management strategies, they add. "So, where brain imaging facilities permit, immediate brain scanning for all strokes remains the policy that is most cost-effective and results in the greatest gain in quality-adjusted life-years."

Dr. Lovelock, Dr. Kerr, and Dr. Al-Shahi Salman have disclosed no relevant financial relationships. The study used data from the Oxford Vascular Study (OXVASC), which is funded by the UK Medical Research Council, the Dunhill Medical Trust, the Stroke Association, the BUPA Foundation, the National Institute for Health Research (NIHR), the Thames Valley Primary Care Research Partnership, and the NIHR Oxford Biomedical Research Centre.

J Neurol Neurosurg Psychiatry. 2010;81:271-275, 239.

21. ED overcrowding is associated with an increased frequency of medication errors

Kulstad EB, et al. Amer J Emerg Med 2010;28:304-309.

Objectives
Despite the growing problems of emergency department (ED) crowding, the potential impact on the frequency of medication errors occurring in the ED is uncertain. Using a metric to measure ED crowding in real time (the Emergency Department Work Index, or EDWIN, score), we sought to prospectively measure the correlation between the degree of crowding and the frequency of medication errors occurring in our ED as detected by our ED pharmacists.

Methods
We performed a prospective, observational study in a large, community hospital ED of all patients whose medication orders were evaluated by our ED pharmacists for a 3-month period. Our ED pharmacists review the orders of all patients in the ED critical care section and the Chest Pain unit, and all admitted patients boarding in the ED. We measured the Spearman correlation between average daily EDWIN score and number of medication errors detected and determined the score's predictive performance with receiver operating characteristic (ROC) curves.

Results
A total of 283 medication errors were identified by the ED pharmacists over the study period. Errors included giving medications at incorrect doses, frequencies, durations, or routes and giving contraindicated medications. Error frequency showed a positive correlation with daily average EDWIN score (Spearman's ρ = 0.33; P = .001). The area under the ROC curve was 0.67 (95% confidence interval, 0.56-0.78) with failure defined as greater than 1 medication error per day.

Conclusions
We identified an increased frequency of medication errors in our ED with increased crowding as measured with a real-time modified EDWIN score.