Lit Bits: August 30, 2006

From the recent medical literature...

1. Paramedic Triage of AMI Patients Directly to Angioplasty: It's feasible and yields favorable outcomes.

Whether 911 ambulances carrying patients with acute myocardial infarction (AMI) ought to bypass hospitals without primary angioplasty capability and proceed directly to an interventional center is a subject of much controversy. Logistical issues commonly cause delays in implementing primary coronary angioplasty, and such delays have been linked to increased mortality and morbidity. These authors evaluated the feasibility of havingparamedics diagnose AMI, initiate therapy, and select patients for direct transport to a percutaneous coronary intervention (PCI) center, without physician intervention.

In a post hoc analysis of data from the Dutch On-TIME trial, the authors compared accuracy of diagnosis, time to treatment, left ventricular function, and clinical outcome in 209 patients who underwent diagnosis and triage by paramedics in the ambulance and in 258 patients who were triaged at a referral non-PCI hospital. Availability of a 12-lead ECG-equipped ambulance determined the location of initial diagnosis and triage.Participating paramedics received special training and used a computerized electrocardiographic algorithm for diagnosis.

The diagnosis of AMI was correct in 95% of patients in the prehospital group compared with 99% in the referred group; the difference was statistically significant. Pharmacologic pretreatment was initiated within 90 minutes after symptom onset in 59% and 43% of patients, respectively, also a significant difference. Multivariate analysis showed that prehospital triage was independently associated with a left ventricular ejection fraction >40% at discharge and a favorable outcome at 1 year.

Comment: These findings suggest that direct paramedic triage to PCI has advantages. Of note, however, the study's relatively small size and use of specially trained paramedics might limit its generalizability. As the search goes on for ways to streamline care during the golden hour of reperfusion therapy, initial diagnosis and triage by paramedics might be part of the answer. -

Aaron E. Bair, MD, FAAEM, FACEP. Citation(s): van 't Hof AW et al. Feasibility and benefit of prehospital diagnosis, triage, and therapy by paramedics only in patients who are candidates for primary angioplasty for acute myocardial infarction.

Am Heart J. 2006 Jun; 151:1255.e1-5. http://dx.doi.org/10.1016/j.ahj.2006.03.014

2. CDC releases new STD treatment guidelines

MMWR August 4, 2006;55:1-94

Full-text free on line: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5511a1.htm

3. Comparison of Fixed-Dose Weight-Adjusted SQ Unfractionated Heparin and LMWH for Acute Treatment of DVT

Clive Kearon, MB, PhD; et al. JAMA. 2006;296:935-942.

Context When unfractionated heparin is used to treat acute venous thromboembolism, it is usually administered by intravenous infusion with coagulation monitoring, which requires hospitalization. However, subcutaneous administration of fixed-dose, weight-adjusted, unfractionated heparin may be suitable for inpatient and outpatient treatment of venous thromboembolism.

Objective To determine if fixed-dose, weight-adjusted, subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for treatment of venous thromboembolism.

Design, Setting, and Patients Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients aged 18 years or older with acute venous thromboembolism from 6 university-affiliated clinical centers in Canada and New Zealand conducted from September 1998 through February 2004. Of the randomized patients, 11 were subsequently excluded from the analysis of efficacy and 8 from the analysis of safety.

Interventions Unfractionated heparin was administered subcutaneously as an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours (n = 345). Low-molecular-weight heparin (dalteparin or enoxaparin) was administered subcutaneously at a dose of 100 IU/kg every 12 hours (n = 352). Both treatments could be administered out of hospital and both were overlapped with 3 months of warfarin therapy.

Main Outcome Measures Recurrent venous thromboembolism within 3 months and major bleeding within 10 days of randomization.

Results Recurrent venous thromboembolism occurred in 13 patients in the unfractionated heparin group (3.8%) compared with 12 patients in the low-molecular-weight heparin group (3.4%; absolute difference, 0.4%; 95% confidence interval, ?2.6% to 3.3%). Major bleeding during the first 10 days of treatment occurred in 4 patients in the unfractionated heparin group (1.1%) compared with 5 patients in the low-molecular-weight heparin group (1.4%; absolute difference, ?0.3%; 95% confidence interval, ?2.3% to 1.7%). Treatment was administered entirely out of hospital in 72% of the unfractionated heparin group and 68% of the low-molecular-weight heparin group.

Conclusion Fixed-dose subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin in patients with acute venous thromboembolism and is suitable for outpatient treatment.

4. Furosemide is not effective in preventing and treating acute renal failure

Furosemide (frusemide) is not associated with any clinical benefits when used to prevent and treat acute renal failure in adults. In a meta-analysis of nine randomised trials, Ho and Sheridan investigated the potential beneficial and adverse effects of furosemide to prevent or treat acute renal failure.

They found that in-hospital mortality, risk of requiring renal replacement therapy or dialysis, number of dialysis sessions required, and proportion of patients with persistent oliguria were not significantly different after treatment with furosemide. However, high doses of furosemide may be associated with an increased risk of ototoxicity.

Abstract:

Objective To investigate the potential beneficial and adverse effects of frusemide to prevent or treat acute renal failure in adults.

Design Meta-analysis of randomised controlled trials.

Data sources Cochrane controlled trials register (2005 issue 4), Embase, and Medline (1966 to 1 February 2006), without language restrictions.

Review methods Two reviewers checked the quality of the studies and independently extracted data.

Results Nine randomised controlled trials totalling 849 patients with or at risk of acute renal failure were included.
Outcome measures not significantly different after frusemide treatment were in-hospital mortality (relative risk 1.11, 95% confidence interval 0.92 to 1.33), risk for requiring renal replacement therapy or dialysis (0.99, 0.80 to 1.22), number of dialysis sessions required (weight mean difference - 0.48 sessions, - 1.45 to 0.50), and proportion of patients with persistent oliguria.

5. Undesirable INRs Common Among Warfarin-Treated Patients in ER

NEW YORK (Reuters Health) Aug 28 - Nearly three quarters of warfarin-treated patients who present to the ER for any complaint have an INR that falls outside the therapeutic range and, in some cases, is dangerously high or low, new research indicates. The researchers were unable to identify any clinical factors that reliably predicted a non-therapeutic INR. As such, INR measurement may be indicated for all warfarin-treated patients who present to the ER, provided the current findings are replicated in other ER settings.

The new findings, which appear in the Annals of Emergency Medicine for August, are based on a study of 782 warfarin-treated patients seen in the ER of two academic medical centers between February 2003 and May 2004 and had their INR levels measured. Seventy-two percent of patients had an INR that fell outside the recommended range of 2 to 3, Dr. David H. Newman and Inna Zhitomirsky, from St. Luke's-Roosevelt Hospital Center in New York, report.

Forty-three percent of patients had values that were too low and 29% had values that were too high. An INR greater than 5 was noted in 11% of patients and 40% of these patients displayed gross bleeding, the report indicates. Twelve percent of patients required emergency therapy, including fresh frozen plasma in 7% and heparin in 5%. Twelve patients had an intracranial hemorrhage, including five with an INR above 3.

Conversely, stroke or thromboembolism was seen in 51 patients who had specifically been receiving warfarin to prevent such events. Roughly half of these patients had an INR below 2. Although gross hemorrhage and increasing duration of therapy were linked to an INR greater than 5, the authors found no group of features that could accurately predict a nontherapeutic INR.

"Given the prevalence and established danger of subtherapeutic and supratherapeutic levels, a low threshold should be maintained for testing and addressing INR levels in patients receiving warfarin in the ER," the authors conclude. Ann Emerg Med 2006;48:182-189.

6. Choosing Your Words Carefully: How Physicians Would Disclose Harmful Medical Errors to Patients

Gallagher TH, et al. Arch Intern Med. 2006;166:1585-1593.

Background A gap exists between patients' desire to be told about medical errors and present practice. Little is known about how physicians approach disclosure. The objective of the present study was to describe how physicians disclose errors to patients.

Methods Mailed survey of 2637 medical and surgical physicians in the United States (Missouri and Washington) and Canada (national sample). Participants received 1 of 4 scenarios depicting serious errors that varied by specialty (medical and surgical scenarios) and by how obvious the error would be to the patient if not disclosed (more apparent vs less apparent). Five questions measured what respondents would disclose using scripted statements.

Results Wide variation existed regarding what information respondents would disclose. Of the respondents, 56% chose statements that mentioned the adverse event but not the error, while 42% would explicitly state that an error occurred. Some physicians disclosed little information: 19% would not volunteer any information about the error's cause, and 63% would not provide specific information about preventing future errors.

Disclosure was affected by the nature of the error and physician specialty. Of the respondents, 51% who received the more apparent errors explicitly mentioned the error, compared with 32% who received the less apparent errors (P<.001); 58% of medical specialists explicitly mentioned the error, compared with 19% of surgical specialists (P<.001). Respondents disclosed more information if they had positive disclosure attitudes, felt responsible for the error, had prior positive disclosure experiences, and were Canadian. Conclusions Physicians vary widely in how they would disclose errors to patients. Disclosure standards and training are necessary to meet public expectations and promote professional responsibility following errors.

7. Sudden onset single floater symptom in one eye: is urgent dilated fundal examination by an ophthalmologist warranted?

Jaheed Khan, et al. Emergency Medicine Journal 2006;23:726-727

A shortcut review was carried out to establish whether patients with only symptom of a sudden onset uniocular floater warrant urgent referral to an ophthalmologist for specialist retinal examination to exclude retinal tears or detachment. Altogether 316 papers were found using the reported search, of which two presented the best evidence to answer the clinical question.

The clinical bottom line is that patients who complain of a sudden onset single floater with no photopsia or change in visual acuity in one eye should merit urgent referral to an ophthalmologist for a detailed fundal examination.

Clinical scenario

A 60 year old lady presents to the emergency department complaining of a 3 day history of a sudden onset single floater in her left eye with no history of flashing lights or other visual problems. Her visual acuity is 6/6 aided in each eye. Dilated fundal examination of her retina with a direct ophthalmoscope is unable to exclude peripheral retinal pathology. You wonder whether she needs specialist dilated fundal examination by an ophthalmologist to exclude a retinal tear or detachment.

Three part question
In [patients with an isolated floater, no photopsia, and no change in visual acuity] is [dilated fundoscopy by an ophthalmologist] required to [exclude retinal tear/detachment or other significant pathology]?

Search strategy (not included)

Search outcome: Altogether 361 papers were returned; two papers were found that addressed our particular question.

Comments: The symptom of a sudden onset single floater with or without flashing lights in one eye is a common presentation of posterior vitreous detachment. There is a small risk of retinal breaks associated with this condition. The two studies have highlighted a small risk of retinal break development in patients who have symptoms of a single floater in their vision but do not agree on the recommended management for this group of patients. The timing for development of retinal tears or detachment following posterior vitreous detachment can be variable. As a result there is no consensus as to whether this group of patients can be reviewed safely on a routine outpatient basis.

CLINICAL BOTTOM LINE

Patients who complain of a sudden onset single floater with no photopsia or change in visual acuity in one eye should merit urgent referral to an ophthalmologist for a detailed fundal examination.

8. Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis

Francois Dubos, MD, et al. J Pediatrics 2006;149: 72-76.

Objective
To identify the biologic tests that best distinguish between bacterial and aseptic meningitis in an emergency department (ED).

Study design
All children hospitalized for bacterial meningitis between 1995 and 2004 or for aseptic meningitis between 2000 and 2004 were included in a retrospective cohort study. Predictive values of blood (C-reactive protein, procalcitonin [PCT], white blood cell [WBC] count, neutrophil count) and cerebrospinal fluid (CSF) findings (protein, glucose, WBC count, neutrophil count) available in the ED were determined. Tests with the best predictive value were identified by using univariate and multivariate analyses and ROC curves comparison.

Results
Among the 167 patients included, 21 had bacterial meningitis. The CSF gram-stain and bacterial antigen test had 86% and 60% sensitivity rates, respectively. PCT ( 0.5 ng/mL) and CSF protein ( 0.5 g/L) were the best biologic tests, with 89% and 86% sensitivity rates, 89% and 78% specificity rates, adjusted odds ratios of 108 (95% CI, 15-772) and 34 (95% CI, 5-217), and areas under the ROC curves of 0.95 and 0.93, respectively.

Conclusion
PCT and CSF protein had the best predictive value to distinguish between bacterial and aseptic meningitis in children.

9. Selective nonoperative management of blunt abdominal trauma

Douglas Everett Gibson, MD, Christopher McKenna Canfield, MD (two Kaiser SAC docs!) J Emerg Med 2006;31:215-221.

The management of patients with blunt abdominal trauma has evolved over the past two decades with increasing reliance on a non-operative approach. An in-depth understanding of the clinical and radiographic parameters used to determine those who may be eligible for this form of treatment is an essential component of modern trauma care. This case-based review highlights critical aspects of non-operative management and provides a framework for the role of the emergency medicine provider. (To contact the primary author: Douglas.E.Gibson@kp.org)

10. Patterns and Outcomes Among Penetrating Trauma Recidivists: It Only Gets Worse.

Brooke BS, et al. Journal of Trauma-Injury Infection & Critical Care. 61(1):16-20, July 2006.

Abstract

Background: Trauma recidivism accounts for a significant proportion of visits to urban trauma centers. The current study was designed to characterize injury patterns among individual recidivists and analyze their impact on mortality.

Methods: Recidivists were identified within a trauma registry from an urban level-one trauma center from a period between 1997 and 2004. Demographic, injury type, and final disposition data were retrospectively reviewed. The primary outcomes measured were all-cause mortality and injury mechanism. The data were analyzed using the [chi]2 method, and logistic regression analysis.

Results: Among 15,973 total trauma visits, 2,511 (15.7%) were by recidivists, representing 1,528 unique patients. Of these recidivists, 794 (52%) had their first trauma admission during the period reviewed (84% male, 87% African-American, mean age 31 +/- 13 years). Blunt injuries only were identified in 43.8% patients, while 21.9% had penetrating injuries only, and 34.3% had a combination of injury patterns.

Recidivists presenting with penetrating trauma as their initial injury were more likely to return with penetrating injuries on their second (58% vs. 25% [p < p =" 0.002])"

11. Oral antihistamines for insect bites

Bernard A Fo and Caroline Lee. Emergency Medicine Journal 2006;23:721-722; doi:10.1136/emj.2006.040154

A short cut review was carried out to establish whether oral antihistamines are effective in the management of insect bites. In total, 994 citations were reviewed of which seven answered the three part question. The clinical bottom line is that antihistamines, used before and after, appear to be effective in reducing the immediate/early symptoms of mosquito bites in both adults and children. It is not clear whether the same antihistamine will be effective for both adults and children.

Three part question
In [patients with previous symptomatic reactions to insect bites] are [oral antihistamines] effective in [reducing symptoms]?

Clinical scenario

You are going on a family holiday to Scandinavia during the summer. You wonder what evidence there is that oral antihistamines will reduce the symptoms of the inevitable insect bites.

Search strategy (not included)

Search outcome
Medline search returned 214 citations, only seven of which were clinical trials addressing the question. CINAHL search returned 780 citations. None was a trial addressing the question. Search of the Cochrane database did not find any relevant reviews.

Comment(s)
Six of the seven trials were performed by a small group of researchers, addressing the problem of mosquito bites in Finland. Three mosquito species were studied. Inclusion criteria were not uniform; in some studies, subjects were known to have a significant reactions, in others they did not. Most studies used a crossover design; however, neither the treatment nor the washout periods were not uniform.

CLINICAL BOTTOM LINE

Antihistamines, used before and after, appear to be effective in reducing the immediate/early symptoms of mosquito bites in both adults and children. It is not clear whether the same antihistamine will be effective for both adults and children.

12. Hydromorphone Feasible First-line Emergency Treatment for Acute, Severe Pain

News Author: Karla Gale, MS. August 18, 2006

Hydromorphone (Dilaudid) is a safe and effective alternative to morphine for treating acute, severe pain in the emergency department (ED), according to results of a prospective study conducted at Montefiore Medical Center in the Bronx, New York.

"Inadequate treatment of pain is a big problem in many fields of medicine, including the ED," lead investigator Dr. Andrew K. Chang told Reuters Health. Inappropriate low dosing of morphine appears to have been "ingrained in the minds" of clinicians because of concerns about possible side effects, he and his colleagues suggest in their report in the Annals of Emergency Medicine for August.

Among potent analgesics, fentanyl has too short a half-life to be useful for treating acute, severe pain in the ED, Dr. Chang noted. "Up until 2003, meperidine (Demerol) was the most commonly used parenteral narcotic pain medication in emergency departments," he continued, "but it has fallen out of favor because of CNS toxicity. In fact, it has been removed from many hospital formularies." This leaves morphine and hydromorphone.

In a literature search, Dr. Chang's group found no studies comparing morphine to hydromorphone in the ED. "The National Hospital Ambulatory Medical Care Study tracks commonly used drugs, and in its section on pain medications in the ED, hydromorphone is not included in the list of the top 20 medications," the investigator added. "We were stunned when we saw that."

Dr. Chang's team has found that physicians appear to be more willing to administer adequate doses of hydromorphone than morphine. They attribute this to the fact that the initial dose of hydromorphone appears to be lower at 0.015 mg/kg (that is, about 1 to 1.5 mg), and thus seemingly less likely to induce serious adverse effects, as opposed to the equianalgesic dose of morphine 0.1 mg/kg (7 to 10 mg).

They therefore conducted a head-to-head, prospective, double-blind trial in which 94 subjects presenting to the ED with acute severe pain were randomly assigned to a single dose of IV morphine (0.1 mg/kg) and 97 were assigned to hydromorphone (0.015 mg/kg). Patients rated pain using a verbal numeric rating scale from 0 to 10. At 30 minutes, patients in the hydromorphone group rated the change in their pain as a mean of - 5.5, while morphine treatment resulted in a - 4.1 point change. Differences of a similar magnitude were reported at 5 minutes and at 2 hours.

The investigators did not expect to see that hydromorphone was more significantly effective at 5 minutes and at 30 minutes in patients who rated their initial pain as a 10. In fact, the average reduction in pain was - 5.9 in the hydromorphone group versus - 3.7 in the morphine group at 30 minutes. The researchers view this interaction between treatment and initial level of pain "as a hypothesis generated in this study, which should be explicitly stated a priori and tested in a future study."

The adverse event profiles were similar for the two drugs (for nausea, vomiting, hypotension, respiratory depression and oxygen desaturation).

13. MRSA Most Common Cause of Skin and Soft-Tissue Infections in Major US Cities

NEW YORK (Reuters Health) Aug 17 - Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has become the most frequent identifiable cause of skin and soft-tissue infections among patients treated at hospital emergency departments in several metropolitan areas across the US, investigators report.

Dr. Gregory J. Moran and colleagues conducted a prospective study from emergency departments in 11 US cities. Their study population encompassed 422 adults treated in August 2004 for an abscess, infected wound or cellulitis with purulent exudates. They report their findings in the New England Journal of Medicine for August 17.

S. aureus was isolated from 322 (76%) of the patients. Of these, 78% were MRSA. Thus, MRSA was isolated from 59% of the patients. Methicillin-sensitive S. aureus (MSSA) was the second most common cause, affecting 17% of patients. Streptococcal infections made up most of the remaining bacterial isolates. No organism was isolated from 9% of patients. Dr. Moran, from Olive View-UCLA Medical Center in Sylmar, California, and his team report that more than 90% of MRSA isolates were susceptible to trimethoprim-sulfamethoxazole, rifampin, clindamycin, and tetracycline. Resistance to macrolides and fluoroquinolones was common.

They observed that more than half of the patients with MRSA received empiric therapy to which the bacterium was not susceptible, such as cephalexin and dicloxacillin. Therefore, they write, "This finding suggests a need to reconsider empirical antimicrobial choices for skin and soft-tissue infections in areas where MRSA is prevalent."

Their limited follow-up showed no association between outcomes and susceptibility to the prescribed antimicrobial agents. The investigators propose that "most simple skin abscesses, even when caused by MRSA, can be cured with adequate drainage alone." In their patient cohort, 85% were treated by incision and drainage with or without antibiotics. However, lack of susceptibility is more likely to affect outcome among patients with cellulitis. Thus, Dr. Moran's group recommends that clindamycin or a combination of a beta-lactam plus trimethoprim-sulfamethoxazole be prescribed in order to cover both staphylococcal and streptococcal infections.

Risk factors for MRSA infection included antibiotic use in the previous month, the presence of an abscess, a lesion attributed to a spider bite, history of MRSA, and recent close contact with another person with a similar infection. The latter risk factor "highlights the importance of educating patients about methods to prevent further transmission of infection, including keeping lesions covered with clean, dry bandages; practicing good hand hygiene; and avoiding the sharing of contaminated items." Because MRSA is so prevalent, the research team recommends that standard precautions, including use of gowns and gloves, "should be considered for all patients with purulent skin and soft-tissue infections in areas with a high prevalence of MRSA."

They also advise clinicians to obtain cultures from such patients and test them for susceptibility in order to ensure that the infection is treated with the appropriate antibiotic. In a related editorial, Dr. M. Lindsay Grayson, from the University of Melbourne in Australia, describes this report as "a landmark study that defines the amazing extent to which community-associated MRSA...has spread through the US population" by means of "a delightfully simple study design and thorough attention to detail."

N Engl J Med 2006;355:666-674,724-726.

14. Morphine-Ketorolac Combo Beats Monotherapy for Acute Renal Colic

NEW YORK (Reuters Health) Aug 22 - The combination of intravenous ketorolac and morphine provides superior pain relief to either agent alone and results in a reduced need for rescue analgesia with morphine, according to a new report. Dr. Basmah Safdar, of the Yale University School of Medicine in New Haven, Connecticut, and colleagues randomized 130 patients with acute renal colic to intravenous infusions of morphine, ketorolac or a combination of the two drugs. Patients were between the ages of 48 and 55 years old. Pain was measured using a 10 cm visual analog scale. Scores were assessed at baseline and again at 40 minutes.

Mean difference between combination therapy and morphine monotherapy in visual analog pain scores after analgesia was 1.8 cm. Pain score difference between the combination and ketorolac alone was 2.2 cm. There was no statistical difference in pain status between morphine and ketorolac. Rescue morphine was required in 30% of patients overall, in 42.5% of patients on morphine, in 33% of those on ketorolac and in only 16% of those receiving combination therapy. Patients receiving combination therapy also had fewer adverse effects, such as nausea and vomiting, than in patients receiving either drug alone. Dr. Safdar's group notes that use of the combination analgesia could reduce time in the emergency department for acute renal colic.

Ann Emerg Med 2006;48:173-181.

15. FDA Approves OTC Sale of Emergency Contraception Plan B

By Lisa Richwine. WASHINGTON (Reuters) Aug 24 - Adult women now have access to the emergency contraception called "Plan B," also referred to as the "morning-after" pill, without a prescription, U.S. health officials said on Thursday after a 3-year political battle over wider access. Barr Pharmaceuticals Inc.'s Plan B must stay behind pharmacy counters, the Food and Drug Administration said. Women must show proof they are at least 18 to buy the emergency contraceptive pills and younger girls still need a doctor's order. "When used as directed, Plan B effectively and safely prevents pregnancy," the FDA said in a statement. Two Plan B pills can prevent pregnancy when taken within 72 hours of sexual intercourse.

Backers and opponents had fiercely lobbied the agency with arguments about Plan B's impact on abortion rates and teen sex; and the feud stalled the nominations of two FDA commissioners. Women's groups and other supporters argued easier access would reduce the number of unwanted pregnancies and abortions. Conservative opponents said wider availability would lead to more teen-age promiscuity and sexually transmitted diseases.

Barr agreed to monitor enforcement of the age limit and to limit Plan B's distribution to health clinics and stores with pharmacies, the FDA said. The pills should be available in dual nonprescription and prescription packages by the end of the year. Prescription packages are available now.

"While we still feel that Plan B should be available to a broader age group without a prescription, we are pleased that the agency has determined that Plan B is safe and effective for use by those 18 years of age and older as an over-the-counter product," Barr Chief Executive Bruce Downey said in a statement. The company originally had sought permission to sell Plan B over the counter without age limits.

Throughout the process, two Democratic senators blocked votes on President George W. Bush's nominees to run the FDA. After the FDA decision, Sens. Patty Murray of Washington and Hillary Rodham Clinton of New York dropped their objections to a Senate vote on the confirmation of Bush's current pick, acting FDA Commissioner Andrew von Eschenbach, a Murray spokeswoman said.Since Barr's initial application in April 2003 to allow sales of the contraceptive without a prescription, repeated delays sparked charges that the FDA let politics override science. In December 2003, a panel of outside advisers voted 23-4 to recommend switching Plan B from a prescription to over-the-counter drug. FDA staff scientists agreed, but a senior official rejected approval over concerns that young girls might not be able to use the pills safely. Barr submitted a new application for over-the-counter sales to women 16 years of age or older. The FDA deferred a decision on that plan and last month proposed limiting sales to women 18 years or older.

Plan B pills contain high doses of progestin. Women are directed to take two tablets 12 hours apart. The drugs block the release or fertilization of the ovum. Some research suggests Plan B also may keep a fertilized egg from attaching to the womb, with some opponents considering this equivalent to abortion. Plan B is different from RU-486, a pill that induces abortion early in pregnancy by blocking implantation of a fertilized egg. RU-486 also is known as Mifeprex (mifepristone).

16. Lower Blood Pressure Better for CAD Patients

By Will Boggs, MD. NEW YORK (Reuters Health) Aug 16 - The progression of coronary atherosclerosis is lowest for patients with blood pressure below 120/80 mm Hg, according to a report in the August 15th issue of the Journal of the American College of Cardiology. "We think that now it is the time to discover the optimal standards for blood pressure reduction for patients with coronary disease," Dr. Ilka Sipahi of the Cleveland Clinic Foundation, Ohio told Reuters Health. "It is likely that within the next few years we will realize that we have been treating blood pressure too conservatively."

Dr. Sipahi and colleagues evaluated the effects of normal blood pressure, prehypertension, and hypertension on the progression of coronary atherosclerosis (as measured by intravascular ultrasound) in 274 patients taking part in a clinical trial. Both mean systolic blood pressure and mean pulse pressure were significant predictors of change in atheroma volume in a multivariable analysis that controlled for lipid levels and other recognized coronary artery disease risk factors. The increase in adjusted atheroma volume was 12.0 mm for hypertensive patients and a non-significant 0.9 mm for prehypertensive subjects. Patients with normal blood pressure experienced a decrease in atheroma volume of 4.6 mm over the 2-year study.

Patients who moved from prehypertensive to normal blood pressure levels during the study had a decrease in atheroma volume (mean, 6.2 mm), the researchers note. Patients whose blood pressure remained at prehypertensive levels had a mean 1.5-mm increase in atheroma volume. Thus, said Dr. Sipahi, blood pressure levels below 120/80 mm Hg "are the best to slow progression of atherosclerosis." These normal levels, he added, "were even associated with a strong trend for reversal of coronary disease."

In an accompanying editorial, Drs. Jonathan Tobis and Gregg C. Fonarow of the University of California, Los Angeles note that the findings point to "a critical need to reassess the guidelines for managing blood pressure in patients with coronary artery disease." J Am Coll Cardiol 2006;48:833-838,839-840.

17. Clinical Features of Head Injury Patients Presenting With a Glasgow Coma Scale Score of 15 and Who Require Neurosurgical Intervention

Catherine M. Clement, RNc, Ian G. Stiell, MD, MSca, Michael J. Schull, MD, MSce, et al. Ann Emerg Med 2006;48: 245-251.

Editor's Capsule Summary

What is already known on this topicA small group of head injury patients who present with a Glasgow Coma Scale (GCS) score of 15 subsequently require urgent neurosurgical intervention. What question this study addressed

How often is 'urgent' neurosurgical intervention (defined liberally as requiring craniotomy within 7 days of injury) needed in GCS 15 patients, and what clinical features might warn of this?

What this study adds to our knowledge: Urgent neurosurgical intervention occurred in only about 1 of 500 patients (upper limit of 95% confidence interval about 1 of 250 patients). 'Precipitous' deterioration occurred in only 2 individuals, or about 1 of 2,500 patients. GCS score decrease, confusion, severe headache, vomiting, restlessness, and focal temporal blow may represent warning signs of impending deterioration.

How this might change clinical practice: This secondary analysis quantifies, with greater precision than previously available, the rarity of need for 'urgent' or 'precipitous' neurosurgical intervention among head injury patients presenting with GCS 15. Although the features listed above as indicative of impending deterioration seem clinically sensible, their independent predictive value requires confirmation.

Study objective
Emergency physicians are concerned about minor head injury patients who present with a Glasgow Coma Scale (GCS) score of 15 yet require neurosurgical intervention. Our objectives are to determine the accuracy of the Canadian CT Head Rule (CCHR) in this important subset, the prevalence of patients requiring urgent intervention, and their clinical course and possible warning signs.

Methods
We conducted a secondary data analysis of the CCHR study cohorts from 10 hospital emergency departments (EDs). We included head trauma patients with witnessed loss of consciousness, disorientation, or definite amnesia and who presented with an initial GCS score of 15. Records were reviewed and specific variables added to the database. The primary outcome was need for urgent neurosurgical intervention.

Results
Among the 4,551 study patients, only 26 (0.6%; 95% confidence interval [CI] 0 to 1.0%) required neurosurgical intervention, and the CCHR identified all 26 cases with 100% sensitivity. Eleven patients required ?urgent? craniotomy within 7 days, and of those, 2 patients deteriorated precipitously. These 11 (0.2%; 95% CI 0.1% to 0.3%) cases had additional signs: GCS score decrease within 6 hours (82%), GCS score decrease within 3 hours (73%), confusion (64%), any vomiting (36%), focal temporal blow (36%), restlessness (36%), and severe headache (45%).

Conclusion
For patients with minor head injury and GCS score of 15, urgent neurosurgical intervention and precipitous deterioration are rare. The CCHR accurately identified all patients requiring neurosurgical intervention. Warning signs that may portend need for urgent intervention include any vomiting, restlessness, any GCS score decrease, severe headache, confusion, and focal temporal blow.

18. ACEP Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients with Non-ST-Segment Elevation Acute Coronary Syndromes

Francis M. Fesmire, MD, et al. Ann Emerg Med 2006; 48:270-301.

Introduction
Patients with chest pain and other symptoms suggestive of acute coronary syndromes are among the most common reasons for which patients seek emergency department (ED) care. The etiologies for these symptoms range from minor disease processes such as chest wall strain, bronchitis, or indigestion to life-threatening conditions such as acute myocardial infarction (AMI), pulmonary embolism, or aortic dissection. Not only does missing a life-threatening condition result in potential serious morbidity and mortality to the patient, but this represents a frequent cause of malpractice suits against emergency physicians and the most dollars awarded. For these reasons, the American College of Emergency Physicians (ACEP) chose chest pain as the topic of the first clinical policy that was published in 1990, and revised in 1995.

Over the last decade there has been an exponential growth in published research and development of new diagnostic modalities and therapies relating to evaluation and treatment of patients with acute coronary syndromes. These newer diagnostic and therapeutic modalities are being developed at a pace that far exceeds the ability of one physician to keep track. This current policy represents the first part of a 2 part revision of the 2000 ACEP clinical policy on AMI and unstable angina. The second part will focus on critical issues in reperfusion therapy in patients with ST-segment elevation AMI. This policy focuses on critical issues in patients with non-ST-segment elevation acute coronary syndromes.

This clinical policy was created after careful review and critical analysis of the peer-reviewed literature. A writing subcommittee knowledgeable in acute coronary syndromes-related literature was selected to review the 2000 ACEP clinical policy5 and other recent acute coronary syndromes clinical guidelines in order to select key areas on which to focus this current policy.

Four critical questions of current interest and/or controversy were chosen by the subcommittee:
1. Are serial ECGs useful during the ED evaluation of patients with suspected acute coronary syndromes?
2. Is there a preferred regimen of serum marker testing in the ED for the exclusion of non?ST-segment elevation AMI?
3. What are the indications for ED administration of glycoprotein IIb/IIIa inhibitors in patients with non?ST-segment elevation acute coronary syndromes?
4. What are the indications for ED administration of clopidogrel in patients with non?ST-segment elevation acute coronary syndromes?

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