Lit Bits: February 28, 2007

From the recent medical literature...

1. Multislice CT Angiography Offers Effective Evaluation of Chest Pain in ED

from Heartwire — a professional news service of WebMD. February 21, 2007 — For patients presenting to emergency departments with chest pain, multislice computed tomography angiography (CTA) using a 64-slice scanner can definitively establish or rule out coronary disease, a randomized trial suggests.

"The problem with the traditional stress-test approach is that it's time-consuming, expensive, and it's not always definitive," James Goldstein, MD, of the William Beaumont Hospital in Royal Oak, Michigan, explained to heartwire. "We showed that CTA was extremely accurate and helpful in deciding, in the vast majority of patients, whether their chest pain was potentially attributable to blockages in the arteries. And in terms of efficiency we demonstrated that multislice CTA reduced the time it took to make a diagnosis by about 75% and also reduced cost."

Goldstein and colleagues report the results of their study online in the February 20 Rapid Access issue of the Journal of the American College of Cardiology. The article will also appear in the February 27 print issue of the journal.

Time and Money
For their study, Goldstein and colleagues randomized 197 patients presenting to the emergency department with chest pain to either multislice CTA or standard of care (diagnostic algorithms based on serial electrocardiograms, cardiac enzyme tests, and nuclear stress testing). In the CTA group, patients with few or no signs of coronary disease were discharged, and those with stenoses higher than 70% were sent for cardiac catheterization.

In all, 75% of patients were either discharged or sent on for cardiac catheterization based on the CTA results; the remainder — those with intermediate lesions or those in whom the scans could not be interpreted — were sent for stress testing, according to the study protocol. Compared with patients treated according to the standard of care, diagnostic times were significantly shorter and cheaper in the multislice CTA group. During 6 months of follow-up, the number of patients deemed "normal" during their initial visits who returned to the hospital for reevaluation was numerically higher in the standard-of-care group, although this difference was not statistically significant. There were no safety issues between groups.

A "significant limitation" of the CTA strategy is that it does not offer information on cardiac function — the rest/stress imaging protocol used in the standard-of-care algorithm, in contrast, might help minimize catheterizations and unnecessary revascularization procedures, the authors note.

Radiation and Noncardiac Causes
In an accompanying editorial, Pim J. de Feyter, MD, and Niels van Pelt, MD, of the University Hospital Rotterdam, the Netherlands, point to 2 other problems with the use of multislice CTA. One is radiation exposure: the editorialists note that the effective radiation dose for a nonpulsing 64-slice scanner is between 9.6 and 21.4 mSv and is reduced to 4.8 to 14 mSv if electrocardiogram pulsing is used. In comparison, technetium nuclear testing entails 10.6 to 12 mSv, whereas traditional coronary angiography entails 4 to 6 mSv. For a patient exposed first to a CTA test that proves inconclusive, followed by a stress test that might indicate a need for invasive coronary angiography, the effective radiation dose would be at least double and possibly triple that of a patient referred directly for a nuclear stress test.

They also point out that patients presenting with chest pain in the emergency department should be checked for other potentially fatal causes, including aortic dissections and pulmonary emboli. "This would require a CT-scan protocol with a large field of view allowing global evaluation of thoracic structures, but that would compromise the evaluation of the coronary arteries and might lead to misinterpretation of coronary lesions."

To heartwire, Goldstein agreed that effective radiation dose could be high if nuclear stress testing is used after an inconclusive CTA — one solution would be to use a stress echocardiogram instead to verify indeterminate results, he said. Goldstein also agreed with de Feyter and van Pelt on the need to evaluate noncardiac structures and suggested that this is another one of the attractive features of cardiac computed tomography. But most attractive, he emphasized, is the increased efficiency in the larger proportion of patients with no previous history of coronary heart disease found to have a normal electrocardiogram and normal cardiac enzyme tests.

"We see at least 15 patients like that every day in our emergency room and they're undergoing these laborious tests," Goldstein said, noting that results from the various tests can sometimes take several days. "Then, if they have recurrent chest pain two weeks later we go through the whole rigmarole again.... Whereas if a patient comes in now, at 4:15 PM, I can send them to the CT scanner and we'll have the diagnosis by 5:00 PM and if the heart looks fine they'll be out having dinner that night."

J Am Coll Cardiol. 2007;49:863-871.

2. ED Co-Pay Decreases Visits

The largest-ever study on the effects of health care co-payment costs on emergency department visits has revealed that requiring patients to pay for a portion of the cost can reduce the number of visits. The study also finds that this decrease does not negatively affect health.

The population-based experiment followed over two million commercially insured (with Kaiser Permanente–Northern California, a prepaid integrated delivery system) and 250,000 Medicare insured patients.

"The results of this study are encouraging in that these modest co-payments appeared to reduce health care use, and therefore overall costs, without harming patients," says Dr. John Hsu, lead author of the study.

While emergency visit rates decrease substantially as the co-payment increases, the findings show no increase in the rate of unfavorable clinical events (hospitalization, intensive care admission) and no increase in deaths.

Hsu J, et al. Cost-Sharing for Emergency Care and Unfavorable Clinical Events: Findings from the Safety and Financial Ramifications of ED Copayments Study. Health Services Research 2006;41:1801–1820.

Abstract: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1475-6773.2006.00562.x

3. Simple Clinical Predictors May Obviate Urgent Endoscopy in Selected Patients With Nonvariceal UGI Bleeding

Romagnuolo R, et al. for the Registry for Upper GI Bleeding and Endoscopy Investigator Group. Arch Intern Med. 2007;167:265-270.

Background: The validated Blatchford risk score (BRS) predicts outcomes in patients with nonvariceal upper gastrointestinal tract bleeding, before endoscopy; completion of the Rockall score requires endoscopy. The aims of this study were to predict whether the modified BRS (mBRS) can predict (1) endoscopic high-risk stigmata (HRS) and (2) rebleeding and mortality.

Methods: Clinical and demographic characteristics on 1869 patients from 6 Canadian provinces were prospectively entered into the Registry for Upper GI Bleeding and Endoscopy database, recording 30-day rebleeding and mortality. The Rockall score and mBRS (hemoglobin level, hemodynamic instability, and presence of melena, liver disease, or cardiac failure; urea and syncope were not recorded) were calculated. Logistic regression was used to assess the association between an mBRS of 1 or less with HRS and with rebleeding and mortality.

Results: The mean (SD) age of the patients was 66 (17) years, with 62% men and a mean of 2.5 comorbidities. Of the 1860 patients with 30-day rebleeding data, 334 (18.0%) rebled; 5.3% died. The mBRS was 0 in 3% and 1 or less in 9.8% of patients; HRS were seen in 31.0% of patients. An mBRS of 1 or less was associated with lower rebleeding (5% vs 19%; P less than .001) and mortality (0.5% vs 5.8%; P=.003), and was significant in multivariate analysis for rebleeding (odds ratio, 0.24; 95% confidence interval, 0.12-0.48) and mortality (odds ratio, 0.12; 95% confidence interval, 0.02-0.90). The HRS were less frequent when the mBRS was 1 or less (16.9% vs 32.7%; odds ratio, 0.4; 95% confidence interval, 0.3-0.6). Patients with a low mBRS with HRS had a low rebleeding rate (3.3%) and a lower apparent benefit from endoscopic therapy.

Conclusions: A modified Blatchford risk score of 1 or less identifies approximately 10% of patients with gastrointestinal tract bleeding with a low likelihood of having HRS and a low risk of adverse outcomes. A prospective randomized study is required to examine whether this subgroup of patients presenting after hours could be discharged safely from emergency departments with arrangements for (urgent) outpatient endoscopy.

4. Empirical Ophthalmic Antibiotics indicated for Pediatric Conjunctivitis

Patel PB, et al. Clinical Features of Bacterial Conjunctivitis in Children. Acad Emerg Med 2007; 14:1-5.

INTRO: Conjunctivitis is a common cause of pediatric primary care visits and is a common ophthalmologic complaint in the pediatric emergency department (ED). Conjunctivitis can be extremely contagious. It is feared that it may be easily spread in day care centers and school classrooms, leading to absences and lost time from work for parents.

The most common causes of conjunctivitis are bacterial and viral infections. In the primary care setting, treatment is based solely on the clinical examination. A 1981 study showed that in the pediatric population, approximately 54% of cases of acute infectious conjunctivitis are caused by a bacterial pathogen.1 However, physicians prescribe antibiotics nearly 80%–95% of the time. Ocular antibiotics, therefore, are considered to be frequently overprescribed, and concerns for increased cost of health care, antibiotic resistance, and adverse reactions are often raised. The objective of our study was to describe the point prevalence and clinical features associated with bacterial conjunctivitis in children and to determine if and when empirical topical antimicrobial therapy for conjunctivitis is indicated.

DISCUSSION (excerpt): Conjunctivitis is a common pediatric diagnosis made in both the primary care and ED settings. Its prevalence is significant to the general population, because it is a leading cause of day care and school absences. Even though most cases of bacterial conjunctivitis are self-limited, it can take up to three weeks for the infection to clear. Treatment of acute conjunctivitis helps to shorten the clinical course, reduces spread of the contagion and discomfort, and allows the patient to resume activities earlier. The etiology is difficult to delineate on clinical grounds alone, and there is much pressure on physicians to prescribe antibiotics due to the social impact the diagnosis holds. Thus, physicians are faced with the dilemma of potentially overprescribing antibiotics in an era of increasing bacterial resistance and increased awareness of cost.

Pediatric and emergency medicine literature lacks clinical diagnostic indicators to assist practitioners in making a more informative decision about the need for ocular antibiotics because results from a culture of the conjunctiva may be delayed by several days. Most cases of acute infectious conjunctivitis are self-limited, and 64% resolve in two to five days. Untreated, acute bacterial conjunctivitis is clinically cured within three to five days in 28% of cases, and by eight to ten days there is a 72% clinical cure rate. There is bacteriologic cure of 19% and 31% of the same untreated groups. If treated with antibiotics, these numbers improve to 62% clinical cure at three to five days and 91% at eight to ten days, with bacteriologic cure of 71% and 79%, respectively. Recent studies have shown that topical antibiotics impact microbiologic remission by six to ten days. Thus, there is support for treating bacterial conjunctivitis because it leads to more rapid and improved rates of clinical remission.

METHODS: This was a prospective study in a children's hospital ED. Conjunctival swabs for bacterial culture were obtained from patients aged 1 month to 18 years presenting with red or pink eye and/or the diagnosis of conjunctivitis.

RESULTS: A total of 111 patients were enrolled over one year. Patients had a mean (±SD) age of 33.2 (±37.5) months, and 55% were male. Eighty-seven patients (78%) had positive bacterial cultures. Nontypeable Haemophilus influenzae accounted for 82% (71/87), Streptococcus pneumoniae for 16% (14/87), and Staphylococcus aureus for 2.2% (2/87). Five clinical variables were significantly associated with a positive bacterial culture. Regression analysis revealed that the combination of a history of gluey or sticky eyelids and the physical finding of mucoid or purulent discharge had a posttest probability of 96% (95% CI = 90% to 99%). Subjective scoring by physicians for a positive culture was 50.6%.

CONCLUSIONS: Conjunctivitis in children is predominantly bacterial, with nontypeable H. influenzae being the most common organism. A history of gluey or sticky eyelids and physical findings of mucoid or purulent discharge are highly predictive of bacterial infection. Based on the above data, empirical ophthalmic antibiotic therapy may be appropriate in children presenting with conjunctivitis.

5. The Effect of Low-Complexity Patients on ED Waiting Times

Schull MJ, et al. Ann Emerg Med 2007;49: 257-264.e1.

Study objective
The extent to which patients presenting to emergency departments (EDs) with minor conditions contribute to delays and crowding is controversial. To test this question, we study the effect of low-complexity ED patients on the waiting times of other patients.

Methods
We obtained administrative records on all ED visits to Ontario hospitals from April 2002 to March 2003. For each ED, we determined the association between the number of new low-complexity patients (defined as ambulatory arrival, low-acuity triage level, and discharged) presenting in each 8-hour interval and the mean ED length of stay and time to first physician contact for medium- and high-complexity patients. Covariates were the number of new high- and medium-complexity patients, mean patient age, sex distribution, hospital teaching status, work shift, weekday/weekend, and total patient-hours. Autoregression modeling was used given correlation in the data.

Results
One thousand ninety-five consecutive 8-hour intervals at 110 EDs were analyzed; 4.1 million patient visits occurred, 50.8% of patients were women, and mean age was 38.4 years. Low-, medium-, and high-complexity patients represented 50.9%, 37.1%, and 12% of all patients, respectively. Mean (median) ED length of stay was 6.3 (4.7), 3.9 (2.8), and 2.2 (1.6) hours for high-, medium-, and low-complexity patients, respectively, and mean (median) time to first physician contact was 1.1 (0.7), 1.3 (0.9), and 1.1 (0.8) hours. In adjusted analyses, every 10 low-complexity patients arriving per 8 hours was associated with a 5.4-minute (95% confidence interval [CI] 4.2 to 6.0 minutes) increase in mean length of stay and a 2.1-minute (95% CI 1.8 to 2.4 minutes) increase in mean time to first physician contact for medium- and high-complexity patients. Results were similar regardless of ED volume and teaching status.

Conclusion
Low-complexity ED patients are associated with a negligible increase in ED length of stay and time to first physician contact for other ED patients. Reducing the number of low-complexity ED patients is unlikely to reduce waiting times for other patients or lessen crowding.

6. Algorithm More Accurately Predicts Cardiovascular Risk in Women

Researchers have developed an improved algorithm for predicting 10-year cardiovascular risk in women, according to a report in a recent issue of JAMA.

The Reynolds Risk Score algorithm was created using data from nearly 25,000 healthy women, aged 45 or older, who were monitored for cardiovascular events over a median of about 10 years. Researchers derived the algorithm using data from two-thirds of the cohort, then validated it in the remainder. The algorithm incorporates two variables not used by the current ATP-III algorithm: family history of premature coronary heart disease and C-reactive protein.

An editorial calls the study an "important contribution" and observes: "Overall, approximately 20% of women will have different lipid treatment goals based on the Reynolds model than recommended by the ATP-III guidelines."

Ridker PM, et al. JAMA. 2007;297:611-619.

JAMA abstract: http://jama.ama-assn.org/cgi/content/abstract/297/6/611

Reynolds Risk Score: http://www.reynoldsriskscore.org/

7. FDA Notes Cases of Intussusception After New Rotavirus Vaccine

The FDA issued a public health notice yesterday regarding 28 cases of intussusception that have occurred over the past year following receipt of live, oral, pentavalent rotavirus vaccine (RotaTeq).

Whether any of these cases is related to the vaccine is unknown. Premarketing studies did not identify an increased risk; however, an earlier rotavirus vaccine was withdrawn because of concerns about higher rates of intussusception. The manufacturer and the CDC are conducting further studies to assess the risk.

The FDA said that it issued the notice "to remind people that intussusception is a potential complication of RotaTeq" and to encourage reporting of any further cases of intussusception that may have occurred to the Vaccine Adverse Event Reporting System.

FDA Public Health Notice: http://www.fda.gov/cber/safety/phnrota021307.htm

8. Pitfalls in the Diagnosis of Cerebellar Infarction

BACKGROUND: Cerebellar infarction is an important cause of acute neurologic disease and accounts for 2%–3% of the 600,000 ischemic stroke cases annually in the United States. Delayed or missed diagnosis of cerebellar infarction may result in serious morbidity and mortality due to hydrocephalus, mass effect, and brain stem compression. Misdiagnosis also delays detecting the underlying cause of brain ischemia such as cardiac disorders and vascular occlusive lesions within the intracranial and extracranial circulation, leaving patients at continued risk for further strokes. There are only scattered case reports about misdiagnosis of cerebellar strokes and no information about the causes and consequences of failure to recognize this condition. To identify sources of preventable medical errors, we analyzed 15 cases of cerebellar infarcts that were initially misdiagnosed in the emergency department (ED). We report the clinical features, diagnostic tests, and outcome of these cases.

OBJECTIVES: To identify sources of preventable medical errors, the authors obtained pilot data on cerebellar ischemic strokes that were initially misdiagnosed in the emergency department.

METHODS: Fifteen cases of misdiagnosed cerebellar infarctions were collected, all seen, or reviewed by the authors during a five-year period. For each patient, they report the presenting symptoms, the findings on neurologic examination performed in the emergency department, specific areas of the examination not performed or documented, diagnostic testing, the follow-up course after misdiagnosis, and outcome. The different types of errors leading to misdiagnosis are categorized.

RESULTS: Half of the patients were younger than 50 years and presented with headache and dizziness. All patients had either incomplete or poorly documented neurologic examinations. Almost all patients had a computed tomographic scan of the head interpreted as normal, and most of these patients underwent subsequent magnetic resonance imaging showing cerebellar infarction. The initial incorrect diagnoses included migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and polyneuropathy. The overall mortality in this patient cohort was 40%. Among the survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis involved the clinical evaluation, diagnostic testing, and establishing a diagnosis and disposition.

CONCLUSIONS: This study demonstrates how the diagnosis of cerebellar infarction can be missed or delayed in patients presenting to the emergency department.

Savitz SI, et al. Acad Emerg Med 2007;14:63-68.

9. Kawasaki Disease's Cardiovascular Effects Not Ameliorated by Corticosteroid Pulse

Patients with Kawasaki disease did not benefit from the addition of a pulsed dose of corticosteroid to standard therapy, researchers report in the Feb 15 issue of the New England Journal of Medicine.

Some 200 children with the disease were randomized to receive either a pulsed intravenous dose of methylprednisolone given over 2 to 3 hours or placebo infusion. All patients also received standard therapy with immune globulin and aspirin.

At weeks 1 and 5 after randomization, measurements of the patients' coronary arteries -- the primary outcome of the study -- showed no differences between groups. Corticosteroid-treated children had slightly shorter initial hospital stays and a lower median erythrocyte sedimentation rate at week 1.

The author of an accompanying perspective writes that "the failure of corticosteroids to benefit these patients underscores the difference between Kawasaki disease and other chronic vasculitides, for which corticosteroids are the foundation of most treatment strategies."
______________

By the way, just what are the symptoms of Kawasaki disease?

Here’s a review (written with parents in mind): The first phase, which can last for up to 2 weeks, usually involves a persistent fever that is higher than 104 F, and lasts for at least 5 days. Other typical symptoms include: severe redness in the eyes; a rash on the child's stomach, chest, and genitals; red, dry, cracked lips; swollen tongue with a white coating and big red bumps; sore, irritated throat; swollen palms of the hands and soles of the feet with a purple-red color; swollen lymph nodes. During the second phase of the illness, which usually begins within two weeks of when the fever first begins, the skin on the child's hands and feet may begin to peel in large pieces. The child may also experience joint pain, diarrhea, vomiting, or abdominal pain.

10. Combination Therapy for COPD Offers No Survival Benefit

Combination therapy with a long-acting beta-agonist plus a corticosteroid offers some benefits for COPD patients, but not survival benefits, according to a study in the Feb 22 issue of the New England Journal of Medicine.

In the international, industry-supported TORCH trial, researchers randomized more than 6000 COPD patients to receive either inhaled salmeterol and fluticasone propionate, each drug alone, or placebo. At 3 years, rates of all-cause mortality (the primary outcome) were 12.6% with combination therapy, 13.5% with salmeterol, 16.0% with fluticasone, and 15.2% with placebo. The mortality difference between the combination-therapy and placebo groups fell just short of statistical significance (P=0.052). However, combination therapy was associated with significant improvements in health status, lung function, and the frequency of COPD exacerbations. Patients taking fluticasone, alone or in combination, had an increased rate of pneumonia.

An editorialist writes that although the combination therapy results are difficult to interpret, "monotherapy with corticosteroids should not be advocated for patients with COPD," while "monotherapy with a long-acting bronchodilator appears to be safe."

NEJM abstract: http://content.nejm.org/cgi/content/short/356/8/775

11. Thrombolysis for Pulmonary Embolus: How Good Is It?

THE ROLE OF THROMBOLYTIC therapy in acute pulmonary embolism has long been debated. Compared with heparin sodium alone, the addition of thrombolytic therapy improves hemodynamic and scintigraphic outcomes within 24 hours of administration, but these benefits diminish over time. For patients with pulmonary embolism and arterial hypotension, thrombolysis is considered to be the standard of care because prognosis in this group is so poor without thrombolytic therapy that the potential benefits are thought to far outweigh the risks. The controversy centers on treatment of hemodynamically stable patients with pulmonary embolism, especially those with right ventricular dysfunction. Right ventricular dysfunction is thought to be a sign of possible impending hemodynamic instability. It is present in 40% to 50% of patients with pulmonary embolism who are hemodynamically stable at the time of presentation, and right heart failure is a common cause of death in these patients. Patients with submassive pulmonary embolism and right ventricular dysfunction have mortality rates that are 2 times higher than those with normal right ventricular function.

Proponents of thrombolytic therapy argue that its potential benefits justify the greater cost and the increased risk of intracerebral hemorrhage and other major bleeding complications in hemodynamically stable patients with right ventricular dysfunction. A recent randomized controlled trial 14 in this population demonstrated that primary thrombolysis with alteplase and heparin was more effective than treatment with heparin alone in preventing the combined end point of death or the requirement for treatment escalation, including the need for catecholamine infusion, mechanical ventilation, or secondary thrombolysis. However, mortality rates were lower than expected and similar in both treatment groups. The authors concluded that their results supported the use of primary thrombolysis based on the less-frequent requirement for treatment escalation in the intervention group.

Methods: We performed a cost-effectiveness analysis to compare health effects and costs of treatment with alteplase plus heparin sodium vs heparin alone in hemodynamically stable patients with pulmonary embolism and right ventricular dysfunction by developing a Markov model and using data from clinical trials and administrative sources.

Results: Based on data from a recent randomized trial, we assumed that the risk of clinical deterioration requiring treatment escalation was almost 3 times higher in patients who received heparin alone (23.2% vs 7.6%) but that the risk of death was equal in the 2 cohorts (2.7%). Based on registry data, we assumed that the risk of intracranial hemorrhage was approximately 3 times higher in patients who received alteplase plus heparin (1.2% vs 0.4%). Under these and other assumptions, thrombolysis resulted in marginally higher total lifetime health care costs ($43 900 vs $43 300) and was slightly less effective (10.52 vs 10.57 quality-adjusted life-years) than treatment with heparin alone. Thrombolysis was more effective and cost less than $50 000 per quality-adjusted life-year gained when we assumed that the baseline risk of death in the heparin group was 3 times the base-case value (8.1%) and that alteplase reduced the relative risk of death by at least 10%.

Conclusions: Available data do not support the routine use of thrombolysis to treat patients with submassive pulmonary embolism. However, thrombolysis may prove to be cost-effective in selected subgroups of hemodynamically stable patients in whom the risk of death is higher.

Perlroth DJ, et al. Arch Intern Med. 2007;167:74-80.

12. AHA Prevention Guidelines for Women Recommend Aspirin for All

Updated American Heart Association guidelines for prevention of cardiovascular disease in women say routine low-dose aspirin should be considered for women of all ages to prevent strokes.

The guidelines, last revised in 2004, were released online Feb 19th by Circulation. For women under age 65 who are healthy or at moderate risk, they suggest aspirin (81 mg daily or 100 mg every other day), as long as the benefit of preventing an ischemic stroke appears to outweigh the risk for gastrointestinal bleeding and hemorrhagic stroke. They offer the same advice for women over 65 to prevent both MI and stroke if their blood pressure is controlled.

Other changes include the following:

-- Physicians should consider other factors besides the Framingham global risk score -- such as medical, lifestyle, and family histories -- when making decisions about women's preventive therapy.

-- The guidelines no longer recommend hormone replacement therapy, antioxidant supplements, or folic acid to prevent cardiovascular disease.

-- Women who need to lose or keep off weight should get a minimum of 60 to 90 minutes of moderate-intensity physical activity on most days.

AHA Guideline in Circulation: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.181546v1

13. Concerns Raised Over Studies supporting Mannitol for Head Injury

Excerpt from the BMJ article: Each year, worldwide, many thousands of people are treated in emergency departments for head injuries. Mannitol is an osmotic diuretic that is believed to reduce intracranial pressure after head injury and may improve patient outcome. Between 2001 and 2004, a Brazilian neurosurgeon Julio Cruz and colleagues published three clinical trials comparing high dose and conventional dose mannitol in the treatment of head injury. No other trials had examined this question.

The results showed that high dose mannitol greatly reduced death and disability six months after the head injury. A Cochrane systematic review that included these trials concluded: "high dose mannitol seems to be preferable to conventional dose mannitol in the acute management of comatose patients with severe head injury." However, one of the trials was accompanied by an editorial that questioned the reliability and validity of the results, calling for further multicentre studies. A subsequent investigation by the Cochrane Collaboration was unable to confirm that the studies took place.

Doubts over the data
In May 2006, Dr Jorge Mejia, the Colombian national coordinator of the CRASH-2 (clinical randomisation of an antifibrinolytic in significant haemorrhage; www.crash2.Lshtm.ac.uk) trial, wrote to IR (who is editor of the Cochrane Injuries Group) after attending a meeting of the Latin American Brain Injury Consortium in Brazil. He was concerned about the inclusion of the Cruz trials in the Cochrane review:

"During the discussion some Brazilian physicians expressed some surprise with the inclusion of Julio Cruz' paper in the meta-analysis (Cruz 2004; J Neurosurgery, 100:376) ... Cruz had no patients at his arrival to Brasil, back from USA where he had developed his research career."

Dr Mejia was clearly shocked by this revelation: "I do not know what to do, but I feel betrayed. I guess that someone should contact the others authors and ask them. I feel that I can not stay passive, but I have no evidence."

Dr Cruz, the lead author, had killed himself in 2005. However, the reports had coauthors from Italy and Japan, and we contacted them for further information…

NEW YORK (Reuters Health) Feb 22 - Using high-dose mannitol to treat head injuries may not be a sound strategy as the three main studies supporting this practice may not have even taken place, according to a report in British Medical Journal for February 24.

Between 2001 and 2004, a research group led by Brazilian neurosurgeon Dr. Julio Cruz published three trials showing that high-dose mannitol is preferable to the conventional dose in treating head injury. In particular, a reduction in death and disability was noted at 6 months by using high- rather than standard-dose mannitol.

However, concerns over the data began to surface. In an editorial accompanying one of the studies, the validity and reliability of the findings were called into question, largely because the research was conducted "at only one institution." A later investigation by the Cochrane Collaboration was unable to verify that any of the studies had actually occurred.

In the present report, appearing in the British Medical Journal for February 24, Dr. Ian Roberts, coordinating editor of the Cochrane Injuries Group, and colleagues describe the numerous unsuccessful efforts they took to verify the data from Cruz's studies.

One major problem in confirming the data was that Dr. Cruz committed suicide in 2005. Another problem was that Dr. Roberts' team could not determine where the patients included in the studies had come from. The Federal University of Sao Paulo, which was listed as Dr. Cruz's affiliation on the papers, later told the investigators that it had never employed Dr. Cruz.

Dr. Roberts' team contacted the living co-authors in an effort to retract the reports. These authors declined to seek retraction and supported Dr. Cruz, commenting that "he would never have been able to do something false."

After considerable efforts to confirm the data, Dr. Roberts and colleagues conclude, "We are left with serious doubt about important studies but with no way of determining with confidence whether the results are fabricated or real. The main author is dead. There is no institution to investigate. The implications for patients are serious."

BMJ 2007;334:392-394.

14. Can aggressively lowering BP in hypertensive patients with CAD be dangerous?

Messerli FH, et al. Ann Intern Med 2006;144:884–93.

Extensive literature exists regarding control of hypertension in patients with coronary artery disease (CAD). However, debate continues with respect to the effects of excessive lowering of the diastolic blood pressure. This study is a secondary analysis of a large cohort of patients from the International Verapamil-Trandolapril Study (INVEST), in which the authors examined the data to determine if low diastolic blood pressure is associated with increased morbidity and mortality in patients with CAD and hypertension.

In this study, 22,576 patients were included. Data from averaged systolic and diastolic pressures was pooled into 10 mm Hg subsets. The primary outcome was defined as the first occurrence of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke. The rates of these outcomes were distributed along the systolic and diastolic blood pressure strata, and the relationship was determined to be a J-shaped pattern. The J-curve for diastolic pressure was more pronounced, and the findings led the authors to conclude that diastolic pressures below 70 mm Hg increased the risk for primary outcome events, particularly death from all causes and from MI, both fatal and nonfatal.

Comment: These data suggest that patients with hypertension and CAD are at increased risk for complications (defined by mortality, MI, or stroke) when their diastolic pressures were lowered below 70 to 80 mm Hg.

15. MRI Contrast Agents Linked to Skin Disorder in Renal Disease Patients

The CDC this month warned physicians to avoid using gadolinium-containing MRI contrast agents when possible in patients with advanced renal failure because of the risk for a serious skin disease.

In an article in MMWR, gadolinium agents were linked to nephrogenic fibrosing dermopathy (NFD), which can cause thickening and hardening of the skin. Researchers conducted a matched case-control study that included 19 cases from a St. Louis hospital. In multivariate analysis, patients with renal disease who developed NFD were nearly nine times as likely to have been exposed to gadolinium contrast agents in the previous year as those who did not develop the skin condition. Patients receiving peritoneal dialysis appeared to be at greater risk than those receiving hemodialysis.

MMWR article: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5607a1.htm

16. A Randomized Controlled Trial Comparing Intranasal Fentanyl to IV Morphine for Managing Acute Pain in Children in the ED

Borland M, et al. Ann Emerg Med 2007;49:335-340.

In the pediatric emergency department (ED), rapid, effective, and painless delivery of analgesia is desired. As a consequence, it is routine in many facilities to give intravenous (IV) morphine to children presenting to the ED in moderate to severe pain. However, the insertion of an IV cannula can, at times, require special skills, is time and staff dependent, and is painful and anxiety provoking for some children. Alternative methods of providing safe and effective analgesia include the intranasal route for the administration of opiates such as fentanyl and diamorphine. A study in a tertiary pediatric ED illustrated the safety and efficacy of intranasal fentanyl in a pediatric population. Two other ED studies have compared an intranasal opiate with intramuscular morphine as their criterion standard.

There has not been a study comparing an intranasal opiate with a drug with a similar onset of action. Intramuscular morphine would be expected to take up to 30 minutes to achieve adequate analgesia, whereas intranasal formulations take 5 to 10 minutes. In addition, if it were possible to provide adequate analgesia without IV access, then the administration of
analgesia would be hastened, which would equate to greater patient comfort and satisfaction.

Study objective
We compare the efficacy of intranasal fentanyl versus intravenous morphine in a pediatric population presenting to an emergency department (ED) with acute long-bone fractures.

Methods
We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in a tertiary pediatric ED between September 2001 and January 2005. A convenience sample of children aged 7 to 15 years with clinically deformed closed long-bone fractures was included to receive either active intravenous morphine (10 mg/mL) and intranasal placebo or active intranasal concentrated fentanyl (150 µg/mL) and intravenous placebo. Exclusion criteria were narcotic analgesia within 4 hours of arrival, significant head injury, allergy to opiates, nasal blockage, or inability to perform pain scoring. Pain scores were rated by using a 100-mm visual analog scale at 0, 5, 10, 20, and 30 minutes. Routine clinical observations and adverse events were recorded.

Results
Sixty-seven children were enrolled (mean age 10.9 years [SD 2.4]). Fractures were radius or ulna 53 (79.1%), humerus 9 (13.4%), tibia or fibula 4 (6.0%), and femur 1 (1.5%). Thirty-four children received intravenous (IV) morphine and 33 received intranasal fentanyl. Statistically significant differences in visual analog scale scores were not observed between the 2 treatment arms either preanalgesia or at 5, 10, 20, or 30 minutes postanalgesia (P=.333). At 10 minutes, the difference in mean visual analog scale between the morphine and fentanyl groups was -5 mm (95% confidence interval -16 to 7 mm). Reductions in combined pain scores occurred at 5 minutes (20 mm; P=.000), 10 minutes (4 mm; P=.012), and 20 minutes (8 mm; P=.000) postanalgesia. The mean total INF dose was 1.7 µg/kg, and the mean total IV morphine dose was 0.11 mg/kg. There were no serious adverse events.

Conclusion
Intranasal fentanyl delivered as 150 µg/mL at a dose of 1.7 µg/kg was shown to be an effective analgesic in children aged 7 to 15 years presenting to an ED with an acute fracture when compared to intravenous morphine at 0.1 mg/kg.

17. Prehypertension Is “On the Map” of Cardiovascular Risk Factors

DALLAS, TX -- February 20, 2007 -- According to researchers studying postmenopausal women in the Women's Health Initiative, prehypertension exists in about 40% of postmenopausal women and it is associated with a 58% higher risk of cardiovascular death, regardless of ethnicity, compared to normal blood pressure.

Using the most recent definitions for hypertension, normal blood pressure is systolic pressure (the top number in a blood pressure reading) less than 120 mm Hg and diastolic (bottom number) less than 80 mm Hg; prehypertension is systolic pressure of 120-139 or diastolic 80-89 mm Hg; and hypertension is systolic pressure of 140 mm Hg or higher, or diastolic pressure of 90 mm Hg or higher or currently taking antihypertensive medication.

"Is the cardiovascular risk with blood pressures slightly above 120/80 mm Hg clinically important enough to justify the label of prehypertension?" asked the study authors. "The increased cardiovascular risk with prehypertension is certainly smaller than the risk associated with having diabetes (158% higher risk), but is greater than that associated with smoking (34% higher). Since smoking is pretty much unchallenged as a cardiovascular risk factor, perhaps prehypertension should be afforded the same acceptance."

Researchers studied 60,785 postmenopausal women in the Women's Health Initiative during a 7.7-year follow-up. At the start of the study, 26% had normal blood pressure, 39% had prehypertension and 35% had hypertension. Prehypertension rates among women of different ethnic groups were 39.5% for whites, 32.1 for blacks, 42.6 for Hispanics, 38.7 for American Indians and 40.3% for Asians.

Women with higher blood pressures were more likely to be older, have higher body mass index, diabetes or high cholesterol. Smoking was more common among women with normal blood pressure (10%). The 10-year incidence of cardiovascular events was 3.63% for women with normal blood pressure, 7.11% for women with prehypertension; and 14.16% for women with high blood pressure.

Compared to women with normal blood pressure, prehypertensive women of any ethnicity had a 58% higher risk of cardiovascular death: 76% higher risk of heart attack; 93% higher risk of stroke; 36% higher risk for being hospitalized with heart failure; and 66% higher risk for any cardiovascular event. Even after adjusting for age, body mass index, diabetes, high cholesterol and smoking status, prehypertension was independently associated with a higher risk of cardiovascular events.

Hsia J, et al. Circulation. 2007;115:855-860.

Abstract: http://circ.ahajournals.org/cgi/content/abstract/115/7/855

18. Frequent Use of Nonnarcotic Analgesics Associated with Hypertension in Men

Near-daily use of nonnarcotic analgesics, including acetaminophen, confers a moderate increase in the risk for developing hypertension, researchers report in the current Archives of Internal Medicine.

The study group comprised some 16,000 men with an average age of 65 and no history of hypertension. They were subjects in the Health Professionals Follow-up Study. Participants reported the frequency of their use of acetaminophen, NSAIDS, and aspirin at baseline; on two questionnaires over the subsequent 4 years they also reported whether they'd been diagnosed with hypertension.

Compared with nonusers, those who took NSAIDS, aspirin, or acetaminophen 6 or 7 days a week had a multivariable relative risk for incident hypertension of 1.38, 1.26, and 1.34, respectively. The authors suggest the acetaminophen link might be mediated through vasodilatory prostaglandins, oxidative stress, and endothelial function.

The authors say their findings echo others' and "suggest that these agents be used with greater caution."

Archives abstract: http://archinte.ama-assn.org/cgi/content/abstract/167/4/394

19. Board-type Questions

Compared to patients with permanent atrial fibrillation, patients with paroxysmal atrial fibrillation have a risk of stroke that is

A) 50% less
B) 25% less
C) 25% greater
D) 50% greater
E) similar

A 62-year-old white male has a history of coronary artery disease, hypertension, and osteoarthritis. He is on lovastatin (Mevacor) for hypercholesterolemia. You are choosing a medication to treat his hypertension. Which one of the following could increase this patient’s risk of rhabdomyolysis?

A) Carvedilol (Coreg)
B) Quinapril (Accupril)
C) Losartan (Cozaar)
D) Atenolol (Tenormin)
E) Verapamil (Calan, Isoptin)

Answers follow item 20.

20. Ultrasound Guided Hematoma Block: A Novel Use of US in the Traumatized Patient

Crystal C, et al. J Trauma. 2007;62:532-533.

The procedure is best performed with a high-frequency linear probe, such as the 5.0- to 10-MHz transducer used in this instance. The site is prepared in the usual sterile fashion. A generous amount of sterile conducting gel is placed over the suspected fracture site to allow the transducer to be gently placed upon it. We have found that laying the transducer sagittally over the long axis of the bone provides the best images. By placing the fracture site in the center of the image, one can easily place a needle into the hematoma by entering the skin in the middle of the transducer. Similar to ultrasound-guided venous access, the needle often will not be directly visualized.

The hematoma block is an effective and safe means to provide analgesia before the reduction of fractures. Orthopedic surgeons and emergency physicians have long recognized its value in the management of fractures commonly seen in the ED. It has been used in a variety of fracture sites including wrist, forearm, ankle, and femur. It is safe and effective in both adults and children, with the typical injected dose of local anesthetic not resulting in toxic blood levels. Although it is usually a relatively simple procedure to perform, it may at times be difficult. In our experience, some of this difficulty occurs when body habitus or traumatic soft-tissue swelling precludes the accurate palpation of the exact fracture site.

Emergency physicians now recognize the utility of ultrasound in the emergency department. Recently, its use for fracture identification has been suggested. We could find no citations in the literature on its use in assisting with hematoma blocks. We have found that this technique has enhanced our ability to successfully perform this procedure. Our group has used this technique over 30 times, with many of us performing every hematoma block under ultrasound guidance. Our anecdotal experience suggests that although hematoma block is generally a very safe procedure, ultrasound provides a means to make it even safer because the procedure may be performed successfully on the first attempt, without the risk of placing the anesthetic in an incorrect location requiring repeated attempts with the concomitant risk of complications. Although further study is needed, this may be similar to other areas of medicine (e.g., central venous lines) where ultrasound guidance has been proven safer and more efficacious than a “blind” approach.

______________________

Answers to board questions

E to both questions

Patients with paroxysmal atrial fibrillation (i.e., self-terminating) and persistent atrial fibrillation (i.e., that lasts more than 7 days or requires elective cardioversion) appear to have a risk of stroke that is similar to that of patients with permanent atrial fibrillation.

Ref: Page RL: Newly diagnosed atrial fibrillation. N Engl J Med 2004;351:2408-2416.

Lovastatin, as well as other statin cholesterol-lowering medications, is primarily metabolized through the cytochrome P-450 system. Medications that inhibit the enzyme CYP 3A4, such as verapamil, increase serum concentrations of selected statins and subsequently increase the risk of rhabdomyolysis.

Ref: Thompson PD, Clarkson P, Karas RH: Statin-associated myopathy. JAMA 2003;289:1681-1690.

Lit Bits: February 14, 2007

From the recent medical literature…

1. Myth: Parenteral ketorolac provides more effective analgesia than oral ibuprofen

Arora S, Herbert M, et al (from UCLA). Can J Emerg Med 2007;9:30-2

Introduction
Acute pain is an extremely common presenting symptom to the emergency department (ED), making it imperative that emergency physicians provide adequate, safe and cost-effective analgesia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often first-line treatments for moderate to severe pain. Physicians can choose between intramuscular (IM) or intravenous (IV) ketorolac and an oral NSAID. The mechanism of action (reversible inhibition of prostaglandin synthesis at the level of cyclooxygenase) is identical irrespective of the route the medication is given.1 Despite the similar pharmacodynamics, many physicians believe that parenteral ketorolac is more efficacious, despite a greater cost and a more invasive route of administration. To investigate this myth (i.e., that parenteral ketorolac provides greater analgesic effect than an oral NSAID), we conducted a review of the literature, with specific focus on ibuprofen as the prototypical — and least expensive — oral NSAID.

For the missing middle portion of this evidence-based article, see the link below.

Conclusion
The higher cost of ketorolac, the pain and difficulty associated with its administration, the risk of extravasation, and the exposure of practitioners to possible needle-stick injuries, all argue that there is no use for IM or IV ketorolac over oral ibuprofen in the ED for routine analgesia, unless oral administration of ibuprofen is unfeasible or contraindicated. Only in specific acute pain syndromes associated with nausea and vomiting, like renal colic, may its use be warranted. The belief that IM/IV medications are perceived as being stronger than oral medications and therefore result in a more powerful placebo effect has also been shown to be false. With the exception of 1 study in post-op patients with a significantly flawed study design, the evidence overwhelmingly shows that inexpensive and relatively safe oral ibuprofen has equal efficacy to the more expensive and potentially dangerous IM or IV ketorolac.

The full-text (free!) can be found here: http://caep.ca/template.asp?id=167EB6F10A6E433D95DED55F7E876043

2. Lancet Focuses on Stroke

Stroke is the focus of several studies in the Jan 27th issue of the Lancet.

A. MRI beats CT for acute CVA. One study found MRI better than CT for detecting acute stroke in a sample of 356 patients who underwent both procedures. MRI had an accuracy of 89%, compared with CT's 54%. (Both were equally effective in detecting acute intracranial hemorrhage.) The authors write that MRI "should be the preferred test for accurate diagnosis of patients with suspected acute stroke."

B. tPA in “routine clinical practice.” In a second study, designed to evaluate the effectiveness of alteplase in routine clinical practice, European investigators followed up on some 6500 patients who had received the drug in almost 300 treatment centers. They report that alteplase -- which must be used within 3 hours -- has a safety profile at least as good as that seen in randomized trials and that "thrombolysis should now be considered a part of routine care."

C. Risk-stratifying our TIA patients. The third study helps clinicians predict which TIA patients are at risk for short-term stroke.

Unified Score Improves Prediction of Stroke After TIA

January 30, 2007 — Researchers of the California and ABCD risk scores have collaborated on a new unified score, dubbed ABCD2, that appears to improve the prediction of stroke risk after a previous transient ischemic attack (TIA) over either score alone.

Their findings, a collaboration between researchers at the Radcliffe Infirmary, Oxford in the United Kingdom; the University of California, San Francisco; and Kaiser Permanente Northern California in Oakland, are published in the January 27 issue of The Lancet.

"The purpose here was rather than to have competing scores out there, to work together with our colleagues across the Atlantic to come up with the best possible score," S. Claiborne Johnston, MD, of the University of California, San Francisco, and Kaiser Permanente Northern California told Medscape. In particular, he noted, they wanted, "a score that would tell treating physicians what the 2-day stroke risk is, when the decision to admit or to treat a TIA as an emergency is particularly relevant."

ABCD-Squared
Currently, patients with a TIA are treated differently between hospitals in various medical settings, Dr. Johnston said. "For instance, some hospitals admit the majority of patients with TIA, as high as 80% or more; others admit very few patients — fewer than 20% or 10% — and in the UK, really none."

The ABCD2 score is meant to help clinicians make more rational decisions about who to admit and who requires other urgent interventions or evaluations to prevent a stroke in patients with TIA, Dr. Johnston said. The unified score draws together elements of the California score, previously published but not ultimately validated by Dr. Johnston's group (Johnston SC, et al. JAMA. 2000;284:2901-2906), and of the ABCD score, published and validated in their own population by Peter Rothwell, MD, and colleagues at Oxford (Rothwell PM, et al. Lancet. 2005;366:29-36).

"We combined our various cohorts into one large study, developed a new rule that really combines the prior 2 rules and then validated that on 4 independent cohorts and came up with ABCD2," Dr. Johnston said.

The 2 existing scores predicted the risk for stroke similarly in the 4 validation cohorts, totaling 2893 patients, for stroke risk at 2, 7, and 90 days with c statistics ranging from 0.60 to 0.81, the authors note. However, the combined score was more accurate than either of these in the groups where the tools had been derived, some 1916 patients.

The main difference between the California and ABCD scores was that the California score included diabetes but not hypertension as a cofactor while the Oxford score included hypertension but not diabetes, Dr. Johnston noted. The new tool includes both diabetes and hypertension and is based on points summed from 5 clinical factors: age older than 60 years (1 point), blood pressure of 140/90 mm Hg or higher (1 point), clinical features including unilateral weakness (2 points), speech impairment without weakness (1 point), duration of 60 minutes or higher (2 points) or 10 to 59 minutes (1 point), and diabetes (1 point).

"It's a more comprehensive score than either of the prior ones, and so not surprisingly, it works better," he said.

The ABCD2 score validated well, was more accurate than either of the previous scores in the 2 groups where they had been derived, and generally performed better in the 4 validation cohorts. In the 4799 patients with complete data in the combined validation groups, the 2-day risk for stroke was 1.0% with a score of 0 to 3 seen in 1012 patients or 21% who were deemed low risk, 4.1% with a score of 4 or 5 in 2169 or 45% considered at moderate risk, and 8.1% with a score of 6 or 7 in 1628 patients or 34% who were deemed at high risk.

Unified Score
The hope with the score is to set 1 clinical standard that can then be used consistently for guidelines and teaching purposes, Dr. Johnston said. This has been an issue for other prognostic scores, he noted. "For instance there are several that predict risk of stroke in patients with atrial fibrillation, and that's not helpful to anyone," he said. "That shouldn't happen here, because we have now a score that has been embraced by the 2 groups that have done the most work in this, and in all our studies now include over 4,000 patients so it should hold up."

Recent guidelines from the National Stroke Association anticipate this new rule based on a previous presentation of these data at a scientific meeting, he noted, but future guidelines will hopefully be able to be more explicit about the role of aggressive interventions and hospitalization in patients at different levels of the score.

"Dealing in Futures"
In an accompanying comment, Walter N. Kernan, MD, of Yale University School of Medicine in New Haven, Connecticut, writes that "patients who present soon after a TIA should be evaluated for short-term stroke risk and the ABCD2 system is currently the best available method."

However, Dr. Kernan raised a couple of points about the tool that otherwise, he writes, "holds up well to scrutiny." First, the diagnosis of TIA was not made according to a uniform definition, such as that proposed by the TIA Working Group. "Diagnostic standardization helps to assure that a clinical prediction instrument is applied to populations for which it has been developed (and in which it would be expected to work best)."

Second, he notes, the tool was tested in the same population areas where the systems from which it was derived were developed. "Additional testing will ascertain whether it successfully stratifies risk beyond San Francisco and Oxfordshire and in the hands of different users."

ABCD2 reminds us that an effective clinician "deals in futures," Dr. Kernan states. The "great virtue" of the system as an aid to prognosis is "its simplicity and easy applicability," he concludes. "We should consider it now for communication and triage, but recognize that prognosis is dynamic and can be affected by clinical data and treatment. The day after initial evaluation, the ABCD2 score might be old news, but the patient could have a brighter future."

As Dr. Kernan anticipates in his editorial, Dr. Johnston responded that the ABCD2 group sees the lack of a strict definition for TIA, but rather relying on the clinician's diagnosis in the field as a strength, not a weakness, that increases the generalizability of the score. As for the populations in which the prediction tool was tested, while technically it is true that it was tested in the same populations where it was derived, the populations are vastly different from each other.

"The score works well in a system in Oxford where almost everybody's white and it's fairly affluent, and no one gets admitted to the hospital, and in a system in California where patients are getting admitted to the hospital, where only 50% are white and the rest are all different races, and where a broader spectrum of socioeconomic status is represented," Dr. Johnston pointed out.

S Claiborne Johnston, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369:251-252, 283-292.

3. The Role of Cardiac Risk Factor Burden in Diagnosing ACS in the ED Setting

Han JH, et al. Ann Emerg Med 2007; 49:145-152.e1.

Background
Clinicians commonly assume that the more cardiac risk factors a patient has (cardiac risk factor burden), the higher the risk of acute coronary syndromes in those with suspected acute coronary syndromes. In the emergency department (ED) setting, Jayes et al observed that individual risk factors were not useful for diagnosing acute coronary syndromes but did not study the role of cardiac risk factor burden on clinical decision-making. As a result, the role of cardiac risk factor burden in the ED setting remains unclear. Recently, the Framingham Heart Study found that patients with 2 or more cardiac risk factors had a substantially higher lifetime risk for cardiovascular disease, but this was a population-based longitudinal study, limiting this study’s generalizability to the ED population. Additionally, associations between cardiac risk factors and acute coronary syndromes are not uniform across the entire population. Different cardiac risk factors are associated with acute coronary syndromes in men and women. However, the effect modification of age on the relationship between cardiac risk factor burden and acute coronary syndromes is not well studied.

Editor’s Summary
What question this study addressed: Whether cardiac risk factors as defined for the general population are useful in identifying acute coronary syndrome in patients undergoing ED evaluation for acute coronary syndrome.

We found that in ED patients with suspected acute coronary syndromes, the greater the number of cardiac risk factors identified, the greater the odds of acute coronary syndromes being present, but the relationship between cardiac risk factor burden and acute coronary syndromes was significantly modified by age. In this retrospective analysis of a clinical registry with 10,806 eligible ED patients with suspected acute coronary syndrome, cardiac risk factor burden was moderately predictive of acute coronary syndrome in those younger than 40 years but was not helpful in older patients. For patients older than 65 years, cardiac risk factor burden was less useful for the prediction of acute coronary syndromes. These findings reflect that older age is a powerful risk for acute coronary syndromes in and of itself.

How this might change clinical practice: These data suggest that clinicians should not use cardiac risk factor burden to define the probability of acute coronary syndrome in ED patients who are older than 40 years and are being evaluated for this condition.

Abstract: http://www.annemergmed.com/article/PIIS0196064406024024/abstract

4. Pay for Performance Shows Modest Benefit on Quality Measures

An experimental Centers for Medicare and Medicaid Services pay-for-performance hospital plan modestly improved compliance with several quality measures in a controlled study released early online by the New England Journal of Medicine.

Researchers compared compliance with quality measures for heart failure, acute MI, and pneumonia at hospitals with and without pay for performance. Bonuses for good performance were 1% to 2%, and the program similarly levied small penalties for poor performance.

After adjustment for several factors, pay for performance was associated with a roughly 2.5% to 4.0% improvement in compliance compared with the control hospitals over the 2-year study period. The improvement was significantly greater in hospitals with a weak baseline performance.

Both the authors and an editorialist note several limitations of this study. The editorialist concludes that the CMS will gain "from recognizing that pay for performance is ... likely to have only modest incremental value."

NEJM abstract (free): http://content.nejm.org/cgi/content/abstract/356/5/486

5. Thrombolysis (Tissue Plasminogen Activator-tPA) in Stroke: A Medical-Legal Perspective

Here is a note from Steven C. Gabaeff, M.D., President CalAAEM. He writes: “Here is an article from the Legal Medicine Perspectives, November/December 2006 Vol. 15, No. 6. This is a publication of the American College of Legal Medicine, an excellent organization of which I am a member. I encourage others to consider joining at www.aclm.org. This article describes the legal issues currently surrounding the use or non-use of thrombolytics in the ED setting. It creates quite a conundrum.”

Only the Intro and one selected paragraph are appended below. The remainder of the article can be found here: http://www.drvinson.net/g6/115/116.html

Introduction

This issue’s Colleagues’ Corner examines the medical-legal quagmire that exists when physicians are faced with the decision to use thrombolytics in the treatment of acute strokes. This article is an edited version of the recently published article in Stroke on the subject by Michael I. Weintraub, MD, FACP, FAAN. As. Dr. Weintraub makes clear despite the success of the 1995 National Institutes of Neurological Disorders and Stroke (NINDS) study using IV recombinant tissue plasminogen activator (tPA) within 3 hours in acute stroke and its subsequent FDA approval, there has been a reluctance to use tPA because of safety and efficacy issues with high incidence of intracerebral hemorrhage, and protocol violations. This article and the cases will illustrate the increased number of malpractice lawsuits generated by the controversy over the “standard of care” and educate clinicians regarding several specific issues surrounding tPA and how to avoid the legal pitfalls.

Overall, his extensive review has led Dr. Weintraub to conclude that neurologists, emergency room physicians and hospitals are at increased liability risk if they use or do not use tPA. Detailed documentation, informed consent or timely transfer should reduce threat of legal action. This article is likely to generate opinions pro and con. Accordingly, the editors of LMP encourage the Fellows and Members of the ACLM on file their concurring and dissenting opinions on LEGALMEDNET so that we may all benefit from our collective knowledge.

Elements of a Malpractice Claim

Currently, there is a marked increase in the number of lawsuits regarding stroke and tPA. PHYSICIANS RECIPROCAL INSURERS. DOCUMENTATION OF MEDICALREASONING/ JUDGEMENT. ALERT: 2006; 1. Physicians are currently being sued if they treat or do not treat with tPA. This topic is somewhat complex but usually revolves around several issues relating to documentation, informed consent, etc. Inherent in this is the fact that there are protocol deviations noted with absence of National Institutes of Health Stroke Scale (NIHSS) in 84%, and a recent retrospective analysis study revealed that one major protocol deviation in 67% and 97% had combined major and minor protocol deviations. When protocol deviations arise, there is increased mortality and morbidity.

6. Infectious Diseases Society Seeks Mandatory Flu Shots for Healthcare Workers

The Infectious Diseases Society of America is recommending that the government increase its efforts to encourage healthcare workers to receive annual influenza vaccinations.

In a statement released Thursday, the society said the U.S. should strengthen policies to include mandatory annual vaccinations while allowing healthcare workers to decline only if they specify in writing that they have religious or philosophical objections or medical contraindications. It also recommended that:

-- Influenza vaccine coverage rates be a quality measure for hospitals and individual practices;

-- Annual flu shots be given onsite to all healthcare workers with patient contact at hospitals, clinics, and other facilities;

-- The vaccinations be paid for by employers or by the employees' health insurance.

ISDA Statement: http://www.idsociety.org/Content/NavigationMenu/News_Room1/Pandemic_and_Seasonal_Influenza/IDSA_flufinalAPPROVED1.24.07.pdf

7. Is Informed Consent Required in the ED for the Administration of IV Contrast?

Iverson K. Ann Emerg Med 2007;49:231-233.

An excerpt from the essay:

We know that a wide variation exists in the practice of obtaining informed consent before the administration of intravenous contrast, and the need to obtain such consent remains controversial. Information about the risks of intravenous contrast material is not common knowledge among the general population, and most patients want some information before contrast injection; about half view such information as essential. Yet in many hospitals and physician groups, obtaining such consent is not routine: physicians associated with larger hospitals (greater than 250 beds); larger physician groups (greater than 10 physicians), no matter what their specialty; and university hospitals use written informed consent less often than those in smaller groups, those associated with smaller hospitals, or those in private practice. In university settings, radiology technologists are most likely to inform patients about nonemergency computed tomography (CT) and the possible risks, whereas ordering physicians are most likely to inform patients about a CT scan’s purpose.

The question remains: Should all emergency physicians be required to obtain informed consent before their patients have studies with intravenous contrast or any other specific procedure? The answer depends, as noted above, on applicable law and local customary practice. However, so that variation in obtaining formal written informed consent does not exist within an institution, or at least within the ED, each department (following any institutional guidelines) should develop brief lists of frequently performed procedures that require written informed consent. If possible, separate consent forms for common procedures that list substantive risks should be available to help clinicians provide all necessary information.

Once the decision is made to obtain formal informed consent, the individual responsible for the procedure, usually the physician, should provide the information, answer questions, and obtain the consent, although others may help complete the documentation. When necessary, a trained translator should be available to ensure accurate information transmission.

The key points about formal written informed consent in the ED are that differences in local custom, hospital policies, and state law lead to a wide variability in which procedures require written informed consent and who obtains it. Yet, since patients often don’t know information about procedures that we consider common knowledge, obtaining patient cooperation and consent for procedures, whether or not one obtains formal written informed consent, is a vital part of practicing elegant emergency medicine. Basing an ED requirement for informed consent on the relative risk of procedures is fraught with hazards because scant data are available. Therefore, the best practice continues to be emphasizing excellent physician-patient communication.

Full-text (requires subscription): http://www.annemergmed.com/article/PIIS019606440602138X/fulltext

8. New Guidelines for Thromboembolism Issued

There are new guidelines for venous thromboembolism. Issued jointly by the American College of Physicians and the American Academy of Family Physicians, the guidelines include the following recommendations:

-- Use validated prediction rules (such as the Wells prediction rules) to estimate pretest probabilities of disease.

-- In patients with low pretest probabilities, use a D-dimer test to rule out deep-venous thrombosis and pulmonary embolism.

-- Use ultrasound to investigate those with intermediate to high pretest probabilities of deep-venous thrombosis in lower extremities.

-- In suspected pulmonary embolism, patients with intermediate or high pretest probabilities of disease require imaging studies.

-- Use low-molecular-weight heparin for the initial inpatient treatment of deep venous thrombosis (either unfractionated or low-molecular-weight forms may be used for pulmonary embolism).

-- Outpatient treatment of deep venous thrombosis (and possibly pulmonary embolism) with low-molecular-weight heparin is safe for selected patients.

-- Either unfractionated heparin or LMWH is appropriate for the initial treatment of pulmonary embolism.

-- Use compression stockings within a month of diagnosis and continue for at least a year.

AIM Guidelines (free): http://www.annals.org/cgi/content/full/0000605-200702060-00149v1

9. Hyperglycemic Crises in Adult Patients With Diabetes: A consensus statement from the American Diabetes Association (ADA)

Kitabchi AE, et al. Diabetes Care 2006;29:2739-2748.

In December 2006 the ADA released their latest guidelines. The full-text (free): can be found here: http://care.diabetesjournals.org/cgi/content/full/29/12/2739. Below is just a small sampling.

INTRO
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infection. Table 1 outlines the diagnostic criteria and electrolyte and fluid deficits for both disorders. The mortality rate in patients with DKA is less than 5% in experienced centers, whereas the mortality rate of patients with HHS still remains high at 11%. Death in these conditions is rarely due to the metabolic complications of hyperglycemia or ketoacidosis but rather relates to the underlying precipitating illness. The prognosis of both conditions is substantially worsened at the extremes of age and in the presence of coma and hypotension. [DRV: note the terminology—hyperosmolar “state” is in, “coma” is out, like the passé terms “near-drowning” and “MVA”]

This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review and more recently published peer-reviewed articles since 2001, which should be consulted for further information.

-- DKA diagnostic criteria: serum glucose over 250 mg/dl, arterial pH below 7.3, serum bicarbonate less than 18 mEq/l, and moderate ketonuria or ketonemia.

-- HHS diagnostic criteria: serum glucose greater than 600 mg/dl, arterial pH above 7.3, serum bicarbonate greater than 15 mEq/l, and minimal ketonuria and ketonemia.

-- The two most common precipitating factors in the development of DKA or HHS are inadequate or inappropriate insulin therapy or infection.

-- During the past decade, an increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes.

-- Not all patients with ketoacidosis have DKA.

-- Unless the episode of DKA is uncomplicated and mild/moderate, regular insulin by continuous intravenous infusion is the treatment of choice. In adult patients, once hypokalemia (K+ less than 3.3) is excluded, an intravenous bolus of regular insulin at 0.1 unit/kg, followed by a continuous infusion of regular insulin at a dose of 0.1 unit/kg should be administered.

-- ED Management? Prospective and randomized studies have reported on the efficacy and cost effectiveness of subcutaneous rapid-acting insulin analogs in the management of patients with uncomplicated DKA. Patients treated with subcutaneous rapid-acting insulin received an initial injection of 0.2 units/kg followed by 0.1 unit/kg every hour or an initial dose of 0.3 units/kg followed by 0.2 units/kg every 2 h until blood glucose was less than 250 mg/dl, then the insulin dose was decreased by half to 0.05 or 0.1 unit/kg, respectively, and administered every 1 or 2 h until resolution of DKA. There were no differences in length of hospital stay, total amount of insulin administration until resolution of hyperglycemia or ketoacidosis, or number of hypoglycemic events among treatment groups. In addition, the use of insulin analogs allowed treatment of DKA in general wards or in the emergency department, avoiding admission to an intensive care unit. By avoiding intensive care admissions, these investigators reported a reduction of 30% in the cost of hospitalization

-- Check the K before you start the insulin. Rarely, DKA patients may present with significant hypokalemia. In such cases, potassium replacement should begin with fluid therapy, and insulin treatment should be delayed until potassium concentration is restored to greater than 3.3 mEq/l to avoid arrhythmias or cardiac arrest and respiratory muscle weakness.

-- Bicarbonate use in DKA remains controversial. At a pH greater than 7.0, administration of insulin blocks lipolysis and resolves ketoacidosis without any added bicarbonate. However, the administration of bicarbonate may be associated with several deleterious effects including an increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema

-- The routine use of phosphate in the treatment of DKA or HHS has resulted in no clinical benefit to the patient.

10. Early Detection of Cerebral Edema during Treatment of Pediatric DKA

Muir AB, et al. Diabetes Care 2004; 27:1541-1546.

INTRO
Most children with diabetic ketoacidosis (DKA) exhibit abnormal neurological function. Therefore, evidence-based guidance for discerning the patients who require lifesaving intervention is needed. Cerebral dysfunction in DKA is usually a manifestation of metabolic derangement, but cerebral edema (CE) arises in 1% of episodes and is a complication that frequently causes irreversible brain damage and death. Neurological collapse from CE is typically described as having sudden onset and progressing rapidly, with recovery depending on prompt reduction of intracranial pressure. The object of this study was to delineate the signs and symptoms of neurological compromise that predict progression to severe CE in children with DKA.

CE occurs rarely in patients older than age 20 years, despite the presence of asymptomatic CE in most adults and children with DKA. This age dependence may point to developmental changes in cerebral metabolism as critical elements in the pathogenesis of CE. For example, children’s brains are reported to have higher fuel and oxygen requirements than those of adults. Hypoxia is further implicated because the brains of patients with DKA may extract blood oxygen less efficiently than healthy individuals and the reported association of symptomatic CE with low partial pressures of carbon dioxide in arterial blood may reflect harmful cerebral vasoconstriction. Exuberant rehydration with hypotonic fluid and bicarbonate administration may aggravate the CE; however, the evidence that CE is primarily iatrogenic is not compelling. In the absence of an understanding of the pathogenesis of CE and its prevention, emphasis must be on early recognition of the disease to permit quick intervention, with the hope of reducing morbidity and mortality.

OBJECTIVE—Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA.

RESEARCH DESIGN AND METHODS—A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed. Signs of neurological disease were incorporated into a bedside evaluation protocol that was applied to an independent test sample of 17 patients previously reported to have developed symptomatic CE during treatment for DKA. Head computed tomograms and their reports were reviewed.

RESULTS—The protocol allowed 92% sensitivity and 96% specificity for the recognition of CE sufficiently early for intervention. The diagnostic criteria were fulfilled in two temporal patterns, defining early- and late-onset CE. Although initial computed tomograms were often normal, the findings also included diffuse CE and focal brain injury, the latter only in patients with an early onset of abnormal neurological signs.

CONCLUSIONS—CE may occur in the absence of acute changes on head computed tomograms. Early detection of CE at the bedside using an evidence-based protocol permits intervention in time to prevent permanent brain damage.

What were the signs? Consult the full-text (free): http://care.diabetesjournals.org/cgi/content/full/27/7/1541

11. TV Drug Ads Play on Emotions, U.S. Study Says

By Susan Heavey. WASHINGTON (Reuters) Jan 30 - Television drug advertisements rely heavily on emotional appeals rather than comprehensive disease information to attract consumers' attention, according to one of the first studies to analyze such commercials.

The study, published in the Annals of Family Medicine Monday, investigated dozens of TV drug ads for some of the nation's top-selling drugs at those times when most viewers tune in.

Researchers analyzed the ads based on how they portrayed the medication and disease, emotions and lifestyles changes. They found companies used various tactics to appeal to viewers with limited facts that could oversimplify their decisions. "The benefits of prescription drugs are rarely that black and white," lead author Dominick Frosch, an assistant professor of medicine at the University of California in Los Angeles, told Reuters.

"Choosing the wrong prescription drug can cause serious health problems and it can also be very costly to the larger society," he added. While such strategies are frequently used for other consumer products, they raise questions when it comes to pharmaceuticals, Frosch and other researchers wrote.

"Our findings suggest the need to reconsider the distinction between selling soap or other consumer products and selling prescription drugs," they said.

In their review, researchers analyzed 38 commercials that aired over the course of four weeks of prime-time television in mid-2004. They coded ads for common themes such as humor or product information, then rated how often each was used. While all the ads met regulations, they often made vague claims, the researchers said. About one-quarter offered details on the cause of a disease or who was at risk.

They also found that nearly all ads relied on characters who seemed happy after taking a drug or otherwise showed positive emotions. Some mentioned changing habits in addition to medication, but none offered such change as an alternative. Print drug ads have been analyzed before, but this study is one of the first aimed at televised versions and comes as Congress prepares to consider allowing drugmakers to pay U.S. regulators to have their commercials screened before airing.

Prescription drug ads have raised concerns since the Food and Drug Administration loosened restrictions on them in 1997. Since then critics have charged both TV and print ads are misleading and encourage consumers to seek drugs they don't need. Companies and other supporters have said they can educate consumers about possible treatments.

Industry lobbying group the Pharmaceutical Researchers and Manufacturers of America (PhRMA) released voluntary guidelines in 2005 to address the concerns, but some say they fall short. PhRMA criticized the study for using ads that aired before its guidelines were implemented. Early indications show "that advertisements airing since the Principles took effect have tended to be more educational and informative," said the group's senior vice president, Ken Johnson.

Still, Frosch said the guidelines don't offer specifics and avoid the issue of emotional appeals. "I don't think prescription drug advertising needs to be banned, but it does need to be more responsible," he told Reuters. This spring Frosch will launch a related study on consumers' reaction to TV drug ads, with results expected next year.

12. New Treatment for Diabetes type 2: DPP-4 Inhibitors

In October 2006, the U.S. Food and Drug Administration (FDA) approved Januvia as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve glucose control in patients with type 2 diabetes when diet and exercise are not enough. The recommended dose of Januvia is 100 mg once daily. Januvia should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

Januvia (Sitagliptin Phosphate) is an oral, once-daily, selective DPP-4 inhibitor. DPP-4 inhibitors work by enhancing a natural body process that lowers blood sugar, the incretin system. When blood sugar is elevated, incretins work in two ways to help the body regulate high blood sugar levels: they trigger the pancreas to increase the release of insulin and signal the liver to reduce its production of glucose. DPP-4 inhibitors enhance the body's own ability to control blood sugar levels by increasing the active levels of these incretin hormones in the body, helping to decrease blood sugar levels in patients with type 2 diabetes.

In clinical trials, Januvia demonstrated an overall incidence of side effects comparable to placebo. The most common side effects reported with Januvia (more than 5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection, and headache. The incidence of selected gastrointestinal adverse reactions in patients treated with Januvia was as follows: abdominal pain (2.3 percent; placebo, 2.1 percent), nausea (1.4 percent; placebo, 0.6 percent) and diarrhea (3.0 percent; placebo, 2.3 percent).

13. Myth: Interpretation of a single ammonia level in patients with chronic liver disease can confirm or rule out hepatic encephalopathy

Arora S, et al. Can J Emerg Med 2006;8:433-5.

Although the exact pathophysiology of hepatic encephalopathy (HE) is not fully understood, for more than a century ammonia has been thought to play a critical role. However, the interpretation and utility of ammonia levels in patients with chronic liver disease (CLD) presenting with HE has been a long-standing source of confusion. It is a common belief in the emergency department and on the wards that a single elevated ammonia level in a patient with CLD can confirm the diagnosis of HE, and a normal level essentially rules it out. This confusion stems from the fact that early studies showed a correlation between degree of encephalopathy and the ammonia level, but numerous subsequent studies have shown that severely encephalopathic patients often have normal ammonia levels.

The degree of the correlation between ammonia levels and the severity of hepatic encephalopathy continues to be controversial. What is evident from the literature is that a single normal ammonia level does not rule out HE in a patient with CLD, and serial levels may not correlate with the evolving clinical picture. An ammonia level is merely a data point among the constellation of variables that may contribute to the development of HE and, for now, the final diagnosis remains a clinical one. Reliance on ammonia levels to make the diagnosis of HE is inappropriate and perhaps dangerous if it results in failure to seek other causes of altered mentation in ED patients with CLD.

Full-text: http://caep.ca/template.asp?id=675B8D2F423146EC928E8C9DFE501121

14. Atypical Clinical Features of Pediatric Appendicitis

Becker T, et al. Acad Emerg Med 2007; 14, 124-129.

INTRO: In classic descriptions of appendicitis, the first symptom is periumbilical pain, followed by nausea, right lower quadrant pain, and later, vomiting with fever. This sequence of events is noted in only 50% of adults, and it is even less common in children. The classic symptoms are often not present in children, making the diagnosis difficult and sometimes leading to missed diagnoses with significant morbidity and mortality, as well as professional liability. In addition to making the correct diagnosis, it is imperative to make the diagnosis in a timely manner. Delay in diagnosis ultimately leads to an increase in the perforation rate, with associated complications. Recently, the medical literature has emphasized the use of advanced radiologic imaging (computed tomography [CT] or ultrasound [US]) to aid in the diagnosis of appendicitis, especially in cases in which examination findings or history are atypical. These interventions can lead to delays in care as well as unnecessary radiation exposure. Often, patients with atypical findings are not candidates for immediate triage to the operating room. It would be helpful to know the frequency of atypical findings and which, if any, are strong negative predictors.

Most literature surrounding childhood appendicitis extrapolates the presenting signs and symptoms from adult patients. Presenting symptoms and signs will vary by age and the ability to achieve a reliable, but often limited, examination. In one small case series, approximately one third of children with appendicitis have atypical findings.

The objectives of this investigation were to determine the frequency of atypical clinical features among pediatric patients with appendicitis and to investigate which atypical features are the strongest negative predictors for appendicitis.

BACKGROUND: The diagnosis of appendicitis remains challenging in children. Delays in diagnosis, or misdiagnosis, have important medical and legal implications. The typical, or classic, presentation of pediatric appendicitis has been modeled after adult disease; however, many children present atypically with subtle findings or unusual signs.

OBJECTIVES: To determine the frequency of atypical clinical features among pediatric patients with appendicitis and to investigate which atypical features are the strongest negative predictors for appendicitis among patients being evaluated for appendicitis.

METHODS: Children and adolescents with suspected appendicitis were enrolled over 20 consecutive months. Pediatric emergency physicians completed standardized data collection forms on eligible patients. Final diagnosis was determined by pathology or follow-up telephone call. Typical and atypical findings were defined strictly a priori.

RESULTS: Seven hundred fifty-five patients were enrolled. The median age was 11.9 years (interquartile range [IQR]: 8.5, 14.9 yr); 36% of patients were diagnosed with appendicitis. Among patients with appendicitis, the most common atypical features included absence of pyrexia (83%), absence of Rovsing's sign (68%), normal or increased bowel sounds (64%), absence of rebound pain (52%), lack of migration of pain (50%), lack of guarding (47%), abrupt onset of pain (45%), lack of anorexia (40%), absence of maximal pain in the right lower quadrant (32%), and absence of percussive tenderness (31%). Forty-four percent of patients with proven appendicitis had six or more atypical characteristics. The median number of atypical features for patients with proven appendicitis was five (IQR: 4.0, 7.0). The greatest negative predictors, on the basis of likelihood ratios, were as follows: white blood cell count (WBC) of less than 10,000 per cubic millimeter (likelihood ratios [LR], 0.18), absolute neutrophil count (ANC) of less than 7,500 per cubic millimeter (LR, 0.35), lack of percussive tenderness (LR, 0.50), lack of guarding (LR, 0.63), and no nausea or emesis (LR, 0.65).

CONCLUSIONS: Appendicitis in pediatric patients is difficult to diagnose because children present with a wide variety of atypical clinical features. Forty-four percent of patients with appendicitis presented with six or more atypical features. Two atypical features are the strongest negative predictors of appendicitis in children: WBC of less than 10,000 per cubic millimeter and an ANC of less than 7,500 per cubic millimeter.

15. FDA Warns on Potentially Lethal Side Effects of Topical Anesthetics

The FDA is warning consumers that improper use of topical anesthetics can cause serious side effects, including irregular heart beat, seizures, difficulty breathing, and death. The products, available over the counter or by prescription, contain agents such as lidocaine, tetracaine, benzocaine, or prilocaine. Compounded versions that combine agents or use high concentrations of the drugs are often used after cosmetic procedures and have been linked with two deaths.

Two women in their 20s died after applying large amounts of compounded topical anesthetic cream to their legs and then wrapping them in plastic. Such wrapping, along with applying the products to a large area, keeping the products on too long, heating the skin, or applying to irritated skin may increase the risk.

FDA Advisory: http://www.fda.gov/cder/drug/advisory/topical_anesthetics.htm

16. Wanna lose weight? FDA Approves OTC Orlistat

The FDA approved an over-the-counter version of the weight loss drug Xenical (orlistat) on Wednesday. The lipase inhibitor will be sold under the name Alli as a 60 mg capsule -- a lower dose than the prescription version of the drug.

Alli is meant to be used by adults with a BMI of 27 or more, in conjunction with a reduced-calorie diet and exercise plan. Users can take up to three capsules a day, one with each fat-containing meal, and should take a multivitamin at bedtime, as the drug can block the absorption of some vitamins.

The most common side effects are diarrhea and other changes in bowel habits, which can be reduced by eating a low-fat diet. The drug is contraindicated in transplant recipients. Patients on anticoagulants or who are being treated for diabetes or thyroid disease should only use the product under physician supervision.

Here’s the manufacturer’s spin: http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=965

17. As Asthma Inhalers Are Phased Out, Shortages Expected; Physicians Must Prepare Patients for Switch to Ozone-Friendly Inhalers

Physicians should be aware that asthma rescue medications are in short supply as prescription drug manufacturers begin phasing out metered-dose inhalers containing ozone-depleting chlorofluorocarbons (CFCs). The FDA in 2005 ordered drugmakers to stop making inhalers with CFC propellants by the end of 2008.

Beginning in 2008, only hydrofluoroalkane (HFA) propellants may be used in metered-dose inhalers. Several manufacturers have already slowed or halted production of CFC inhalers in preparation for the switch to HFA products. This shortage is expected to become more pronounced in coming months, as Schering-Plough, through its Warrick Pharmaceutical Division, announced it would stop production of CFC inhalers this spring.

Because of the shortage, patients with nonspecific prescriptions may unknowingly be switched to alternative HFA agents. Even though HFA propellant formulations are not generically interchangeable with their CFC counterparts, there have been some reports of substitutions being made without physician approval. Accordingly, physicians writing prescriptions for bronchodilators should be sure to indicate specifically which medication they are prescribing.

Physicians should also be aware that HFA propellants may “feel different” to patients accustomed to CFC inhalers. Physicians and pharmacists should educate patients about what to expect when making the switch to avoid potential overuse, product waste, or patient dissatisfaction.

Medi-Cal has added HFA agents to its list of covered drugs and will only cover CFC inhalers with prior authorization. Many health plans, however, still do not cover HFA inhalers without prior authorization.

18. Clinical prediction rule to distinguish PID from acute appendicitis in women of childbearing age

Morishita K, et al. Amer J Emerg Med 2007;25:152-157.

Abstract
Objective
We aimed to develop a clinical prediction rule to distinguish pelvic inflammatory disease (PID) from acute appendicitis in women of childbearing age.

Methods
We reviewed medical records over a 4-year period of female patients of childbearing age who had presented with abdominal pain at an urban emergency department and had either appendicitis (n = 109) or PID (n = 72). A prediction rule was developed by use of recursive partitioning based on significant factors for the discrimination.

Results
The significant factors to favor PID over appendicitis were (1) no migration of pain (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.5-11.5), (2) bilateral abdominal tenderness (OR, 16.7; 95% CI, 5.3-50.0), and (3) absence of nausea and vomiting (OR, 8.4; 95% CI, 2.8-24.8). The prediction rule could rule out appendicitis from PID with sensitivity of 99% (95% CI, 94-100%) when classified as a low-risk group by the following factors: (1) no migration of pain, (2) bilateral abdominal tenderness, and (3) no nausea and vomiting.

Conclusion
We developed a prediction rule for childbearing-aged women presenting with acute abdominal pain to distinguish acute appendicitis from PID based on 3 simple, clinical features: migration of pain, bilateral abdominal tenderness, and nausea and vomiting. Prospective validation is needed in other settings.

19. Acute Stroke Management: News from the American Stroke Association International Stroke Conference 2007

A. No Benefit of Glucose-Lowering on Stroke Morbidity, Mortality

February 12, 2007 (San Francisco) — Aggressive lowering of blood glucose levels following acute stroke does not improve patient outcomes, a new study suggests.

Here at the American Stroke Association International Stroke Conference 2007, researchers presented the results of the UK Glucose Insulin in Stroke Trial (GIST-UK), the first-ever randomized clinical trial to compare intensive glucose modulation following acute stroke with conventional care.

The study found no evidence to support acute management of raised blood glucose following stroke. Furthermore, an IV infusion of glucose/potassium/insulin (GKI) had a significant impact on blood pressure lowering that may be potentially harmful.

"The bottom line is that in the majority of patients there is no need to intensively reduce blood glucose levels. For stroke patients with extreme glucose elevation, treatment may be worthwhile. But in the absence of this, there is absolutely no demonstrable benefit of glucose-lowering treatment with respect to outcome in stroke patients," principal investigator Dr. Christopher Gray, MD, from the Newcastle University School of Clinical Medical Sciences, in the United Kingdom, told Medscape.

Full story: http://www.medscape.com/viewarticle/552049

B. Intra-Arterial Thrombolysis Prompts "Lazarus" Phenomenon

February 12, 2007 (San Francisco) — A new study shows almost 25% of patients with acute ischemic stroke experience significant and immediate improvement following intra-arterial (IA) thrombolytic therapy.

Presented here at the American Stroke Association International Stroke Conference 2007, investigators from the Ohio State University College of Medicine, in Columbus, looked at factors influencing the so-called "Lazarus phenomenon" (LP), in which ischemic stroke patients experience a decrease in National Institutes of Health Stroke Scale (NIHSS) score by at least 50% within 24 hours following treatment.

Investigators found the most significant predictors of LP were shorter time to IA thrombolytic treatment, good pial collateral formation, and reperfusion flow of greater than 50%.

"Some people experience a dramatic improvement [with IA] and some people don't, and we're trying to figure out the reasons for this. Based on these results, it is clear time is a major factor and every minute counts," the study's principal investigator, Dr. Gregory A. Christoforidis, told Medscape.

Full-story: http://www.medscape.com/viewarticle/552046

20. FDA Warns on Look-Alike Heparin Vials

The FDA and Baxter International warned of potentially dangerous medication errors involving two heparin products with similar labels. Three infants died when they were given the higher dose Heparin Sodium Injection 10,000 units/mL instead of the lower dose HEP-LOCK U/P 10 units/mL. Both products use blue as the primary background color on their labels, though in different shades.

Baxter is looking for ways to vary the packaging to prevent future errors. In the meantime, it suggests that healthcare workers check their inventory to ensure no mix-up has occurred; notify staff of the problem; be sure not to rely solely on package color to identify a product; and always read the label and verify that the correct dose and product are being used.

Manufacturer’s letter: http://www.fda.gov/medwatch/safety/2007/heparin_DHCP_02-06-2007.pdf