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?

For the REST of the paper, see http://download.journals.elsevierhealth.com/pdfs/journals/0196-0644/PIIS0196064406010110.pdf (Free, full-text).

Lit Bits: August 12, 2006

From the recent medical literature...

1. Treating Septic Shock: Does Every Minute Count?

Richard T. Ellison III, MD. Initiating antibiotic therapy within the first hour after the onset of hypotension appears to increase the likelihood of survival.

Summary
For patients with severe infections, earlier antibiotic therapy is generally believed to produce better outcomes. But how early is early? In a retrospective study partly supported by industry, investigators assessed the relation between time to initiation of effective antibiotic treatment and outcome in patients with septic shock. Subjects were 2731 adults who were treated for septic shock in 14 intensive care units in Canada and the U.S. between June 1989 and June 2004. Most patients had pneumonia (37%) or a gastrointestinal/intra-abdominal infection (29%); 56% of them died.

The survival rate was 83% in patients who received appropriate antibiotic treatment within the first 30 minutes after onset of documented hypotension, and 77% in patients who received appropriate treatment 30–60 minutes after onset. Over the next 5 hours, the survival rate decreased by approximately 8% per hour for each hour of delay in starting effective treatment. In multivariate analyses, time to initiation of effective antibiotic therapy was the factor most strongly associated with outcome, and the strong association held, regardless of the underlying pathogen or infection site.

Comment
These findings will likely have a major effect on clinical care, given the size of the patient population and the consistency of the results, even though the study suffers all the limitations of a retrospective analysis. The challenge for the future in treating septic shock is to develop effective strategies that allow clinicians to start effective antibiotics as quickly as possible yet still perform appropriate diagnostic evaluations and avoid indiscriminate use of antibiotics.
Source
Kumar A et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006 Jun; 34:1589-96.

2. One in Three Hospital Patients Is 65 or Older

Agency for Healthcare Research and Quality (AHRQ), Rockville, Maryland; http://hcup.ahrq.gov/HCUPnet.asp

The information in this article is from HCUPnet, an online query system that provides access to health statistics and information on hospital stays from the Healthcare Cost and Utilization Project (HCUP) sponsored by the Agency for Healthcare Research and Quality (AHRQ). This project includes the largest set of publicly available databases on all patients in the United States, regardless of type of insurance or whether the patients had insurance. To access HCUPnet, go to http://hcup.ahrq.gov/HCUPnet.asp.

Although only 12% of the US population was 65 years of age or older in 2003, the Department of Health and Human Services (HHS) Agency for Healthcare Research and Quality says that this group accounted for one third of all patients admitted to the nation's community hospitals in that year -- over 13 million hospital stays.

The elderly also accounted for 44% of all hospital charges -- nearly $329 billion.

The most common procedure performed on elderly patients was blood transfusion. Sixty percent of all blood transfusions -- almost 1.2 million -- were administered to the elderly. Nearly 1 in every 11 elderly patients in the hospital received a transfusion. The second, third, fourth, and fifth most commonly performed procedures in the hospital for the elderly were, respectively, diagnostic cardiac catheterization and coronary arteriography (852,300), upper gastrointestinal endoscopy and biopsy (690,700), respiratory intubation and mechanical ventilation (500,900), and percutaneous coronary angioplasty (401,900).

The 5 leading reasons why elderly patients were hospitalized, as measured by number of admissions, were congestive heart failure (839,300), pneumonia (770,400), coronary atherosclerosis or hardening of the arteries (675,700), cardiac dysrhythmias (484,200), and acute myocardial infarction or heart attack (449,000).

The proportion of elderly patients who died while hospitalized was 5 times higher than that of younger patients.

These and other data are included in Hospitalizations in the Elderly Population, 2003, HCUP Statistical Brief # 6 at http://www.hcup-us.ahrq.gov/reports/statbriefs.jsp The report uses statistics from the Nationwide Inpatient Sample, a database of hospital inpatient stays that is nationally representative of all short-term, nonfederal hospitals. The data are drawn from hospitals that comprise 90% of all discharges in the United States and include all patients, regardless of insurance type, as well as the uninsured.

3. C-Reactive Protein: Not Ready for Population-Wide CVD Risk Assessment.

Traditional risk factors alone are still the best predictors of CVD risk.

In two new studies, researchers have evaluated the predictive value of novel cardiovascular disease (CVD) risk markers, including C-reactive protein (CRP).
In one study, coauthored by a coinventor of a CRP assay, 15,048 women (age, 45) were followed for a mean of 10 years; 390 developed CVD. When CRP values were added to prediction models that included traditional risk factors (age, blood pressure, smoking status, and HDL and total cholesterol levels), prediction of which women would develop CVD was not improved. The researchers also examined how often women classified by traditional risk factors as having <5%, 5%–<10%, 10%–<20%, or 20% risk were recategorized when CRP results were incorporated: 12%–14% of women in each group were reclassified into the next lower category, and 2%–10% were transferred to the next higher category. The authors concluded that use of CRP assays could help direct preventive interventions.

In another prospective U.S. cohort study, researchers assessed whether adding measurements of CRP or any of 18 other novel risk factors to traditional risk factors (age, race, sex, HDL and total cholesterol levels, systolic BP, use of antihypertensive agents, and smoking and diabetes status) improved prediction of incident coronary heart disease among nearly 16,000 adults (age, 45). Only lipoprotein-associated phospholipase A2 showed a statistically significant increase in predictive value compared with traditional risk factors only; however, this increase was not clinically important.

Comment: The debate about the incremental value of measuring CRP and other novel markers will not end with these studies. Authors of a review that accompanies the Annals of Internal Medicine study determined that measuring CRP might add modest predictive ability for people at intermediate risk. But editorialists note that CRP might not be related causally to CVD and lowering CRP levels might not improve outcomes. Given that only one in three people with elevated BP or cholesterol levels achieves adequate control, we agree with Archives of Internal Medicine editorialists who recommend focusing on treatment and control of traditional risk factors. For now, routine screening of CRP levels appears unwarranted.

­ Jamaluddin Moloo, MD, MPH, and Richard Saitz, MD, MPH, FACP, FASAM

Citation(s): Cook NR et al. The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 2006 Jul 4; 145:21-9; Folsom AR et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: The atherosclerosis risk in communities study. Arch Intern Med 2006 Jul 10; 166:1368-73; Lloyd-Jones DM et al. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med 2006 Jul 4; 145:35-42; Davey Smith G et al. C-reactive protein and cardiovascular disease risk: Still an unknown quantity? Ann Intern Med 2006 Jul 4; 145:70-2; Lloyd-Jones DM and Tian L. Predicting cardiovascular risk: So what do we do now? Arch Intern Med 2006 Jul 10; 166:1342-4.

4. Selective radiography in 100 patients with suspected shoulder dislocation

Hendey GW, Chally MK, Stewart VB. J Emerg Med 2006;31:23-28.

Emergency Physicians frequently care for patients who have sustained a shoulder dislocation. Typically, pre-reduction radiographs are performed to confirm the dislocation and exclude fracture, and post-reduction films are ordered to confirm the reduction and exclude a fracture caused by the reduction. The notion that all such patients require both pre-reduction and post-reduction radiographs has been challenged by several authors. In two retrospective studies, no patient had a new fracture noted on post-reduction films, and both studies concluded that the routine practice of obtaining post-reduction films should be questioned. Three prospective studies reported that when physicians were clinically certain of joint position, their accuracy was 100%. A recent study found that 98% of fracture dislocations could be predicted using three clinical features, and could reduce pre-reduction films by 23%.

Based on the findings of many of the studies noted above, we previously derived a clinical decision rule for selective radiography in patients with a suspected shoulder dislocation (below). The algorithm suggests obtaining radiographs according to the mechanism of injury, previous dislocations, and the physician’s clinical certainty of joint position. The greatest potential savings in radiographs was noted in the subset of patients with recurrent dislocations by an atraumatic mechanism, where physicians were 100% accurate in their assessments of joint position, and there were no fractures or persistent dislocations. This suggests that this subgroup might be successfully managed without any radiographs in the Emergency Department (ED). The goal of the present study was to validate our previously derived clinical decision rule, and our specific objectives were: 1) to determine the actual reduction in X-ray utilization compared to the standard of pre- and post-reduction films for all dislocations, 2) to determine whether any fractures or dislocations were missed, 3) to compare the total ED time from triage to discharge, and 4) to assess patient satisfaction with an approach of selective radiography.

Decision Rule (paraphrased by DRV): You can safely skip radiographs in pts with recurrent shoulder dislocation, atraumatic mechanism, and physician certainty of diagnosis and relocation.

Abstract
We sought to prospectively validate an algorithm for selective radiography in the Emergency Department (ED) management of patients with suspected shoulder dislocation. Physicians ordered pre- and post-reduction radiographs based on an algorithm incorporating the mechanism of injury, previous dislocations, and the physician’s clinical certainty of joint position. Follow-up consisted of telephone calls and chart review. Of 100 patients, 94 had shoulder dislocation, and 59% were recurrent. Thirty percent had both pre- and post-reduction radiographs, 45% had pre- or post-reduction only, and 25% had no shoulder films, yielding an overall 46% reduction in X-ray utilization. Mean ED times were significantly shorter for patients managed without radiographs. On telephone follow-up (76%) and chart review (100%), we found no missed fractures or persistent dislocations. Use of a clinical decision rule for selective radiography reduced the number of radiographs and time spent in the ED, while missing no fractures or dislocations.

5. Vomiting of Liquid Corticosteroids in Children With Asthma.

Kim, Michael K. MD, et al. Pediatric Emergency Care. 22(6):397-401, June 2006.

Abstract
Background: Oral corticosteroids are an essential part of the management of children with acute asthma exacerbations. Vomiting is a frequently cited problem attributed to oral corticosteroids. A new formulation of prednisolone, Orapred, claims to have improved palatability that may decrease the incidence of vomiting.

Objective: To compare the incidence of vomiting and taste between patients who are given the generic preparation of prednisolone with those given Orapred.

Design/Methods: A randomized, double blind clinical trial was conducted at a tertiary care children s hospital emergency department. Children age 2 to 10 years presenting with acute asthma exacerbation were eligible. Patients with allergy to prednisolone, corticosteroid use within 2 weeks, history of vomiting in the last 24 hours, requirement for vascular access, and preference for other forms of corticosteroid were excluded. Enrolled patients were randomized and given either generic prednisolone (15 mg/5 ml) or Orapred (15 mg/5 ml). In children 6 years or older, a taste score was obtained using a 5 point hedonic face scale (1 = bad to 5 = great). After the administration, patients were observed for 30 minutes for vomiting. The Mann-Whitney U test was used to compare the median taste score between the two study groups. Relative risk (RR) of vomiting was calculated. Other confidence intervals were calculated when appropriate.

Results: During the study period, 211 eligible children were enrolled, of whom 23 were excluded. Of the remaining 188 subjects, 96 received generic prednisolone and 92 received Orapred. All baseline characteristics were similar in both groups. In the generic prednisolone group, 17 (17.7%) children vomited compared with 5 (5.4%) in the Orapred group (RR = 3.26, 95% CI, 1.25, 8.47). Taste scores were obtained from 18 children in the generic prednisolone group and from 19 children in the Orapred group. The median taste score was 2 for the generic prednisolone group and 4 for the Orapred group ([DELTA] = -2.0, 95% CI, -3.0, -1.0) (P = 0.0001).

Conclusions: In our study population, Orapred was associated with a significant less incidence of vomiting and better taste score compared to the generic prednisolone.

6. Risk factors for ectopic pregnancy in symptomatic first-trimester pregnancies

Barnhart KT, et al. Fertil Steril 2006;86:36-43.

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy.

Design: Nested case–control study. Setting: University medical center.

Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999.

Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions.

Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88–4.73] for one prior EP and 16.04 [5.39–47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11–2.05]), pain at presentation (1.42 [1.06–1.92]), vaginal bleeding at presentation (1.42 [1.04–1.93]), and hCG of 501–2,000 mIU/mL (1.73 [1.24–2.42]). Age younger than 25 years (0.59 [0.41–0.85]) and a history of abortion were protective from EP (0.58 [0.38–0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP.

Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis.

7. Famciclovir: A Single-Dose Treatment for Herpes Labialis

Single-dose, patient-initiated famciclovir: A randomized, double-blind, placebo-controlled trial for episodic treatment of herpes labialis. Spruance SL, et al. J Amer Acad Dermatol 2006;55: 47-53.

Background
The brief period of viral replication in recurrent herpes labialis lesions suggests shorter therapeutic regimens are a logical episodic treatment strategy.

Objective
We sought to assess the efficacy and safety of single-dose and single-day famciclovir treatments.

Methods
In all, 701 randomly assigned patients self-initiated therapy with famciclovir (1500 mg once [single dose] or 750 mg twice a day for 1 day [single day]) or placebo within 1 hour of onset of the prodromal symptoms of an episode of herpes labialis. Lesion healing was monitored by diaries and frequent clinic visits.

Results
Median healing times of primary (first to appear) vesicular lesions in the famciclovir single-dose, famciclovir single-day, and placebo groups were 4.4, 4.0, and 6.2 days, respectively. There was no significant difference between the famciclovir regimens. Adverse events in the famciclovir groups were similar to placebo.

Limitations
The active arms of this trial were not directly compared to other antiviral regimens.

Conclusion
Single-dose famciclovir reduced time to healing of herpes labialis lesions by approximately 2 days compared with placebo.

8. Epinephrine May Edge Vasopressin in Cardiac Arrest

NEW YORK (Reuters Health) Jul 20 - Vasopressin offers no advantages over epinephrine for treatment of out-of-hospital cardiac arrest and may even be of less help neurologically, according to a review of the subject in the July issue of the Annals of Emergency Medicine.

"Vasopressin," lead author Dr. Peter C. Dwyer told Reuters Health "appears to be one of several powerful cardioactive drugs that may restart the heart after cardiac arrest in some patients without increasing survival to hospital discharge."

One study, he added, "suggested that it might increase likelihood of longer term survival in patients with cardiac ... asystole. Our analysis indicates that this observation was likely a result of chance."

In order to determine whether either agent increased survival to discharge, Dr. Wyer of Columbia University College of Physicians and Surgeons, Pelham Manor, New York and colleagues reviewed data from three "high-quality" randomized trials and one "rigorous" meta-analysis.

None of the findings, they note, confirmed a consistent benefit of vasopressin over epinephrine in increasing survival or improving neurological outcome in survivors.

Furthermore, continued Dr. Wyer, there is "a suggestion that the drug may worsen neurological outcome in those who do survive."

"We believe," he concluded, "that further research is necessary before this drug is recommended for widespread use in cardiac resuscitation patients."

Ann Emerg Med 2006;48:86-97.

9. NSAIDs Slightly Increase Risk of MI

NEW YORK (Reuters Health) Aug 01 - All nonsteroidal anti-inflammatory agents (NSAIDs), those that inhibit cyclo-oxygenase-2 (COX)-2 or the conventional, nonselective agents, raise the risk of myocardial infarction (MI), according to the results of a population-based, matched case-control study conducted in Finland.

"Our results do not support the view that COX-selectivity alone determines the cardiovascular adverse effects of NSAIDs, at least concerning MI," lead investigator Dr. Arja Helin-Salmivaara and colleagues note in their report, published in the July issue of the European Heart Journal.

Accumulating data on the cardiovascular risks associated with COX-2 inhibitors have called into question the safety of nonselective NSAIDs, they note. Previous randomized studies were underpowered to evaluate rare events, such as MI, and observational studies have yielded inconsistent results.

The investigators evaluated data for 33,309 patients with a first MI entered into the Finnish Hospital Discharge Register between 2000 and 2003. These subjects were compared with 138,949 control subjects matched by age, sex, and hospital catchment area.

The NSAIDs used included: conventional NSAIDs (diclofenac, ibuprofen, indomethacin, ketoprofen, naproxen, mefenamic acid, piroxicam, tenoxicam, tolfenamic acid, aceclofen, tiaprofenic acid); semiselective NSAIDs (etodolac, nabumetone, nimesulide and meloxicam); and COX-2 inhibitors (rofecoxib, celecoxib, valdecoxib and etoricoxib).

Dr. Helin-Salmivaara from the University of Turku, in Helsinki, and colleagues determined the adjusted odds ratio associated with current use of each drug, after adjusting for comorbidities, hormone therapy and other drugs that reduce MI risk.

They found that current use of any NSAID was associated with an adjusted odds ratio of 1.40. The risk of MI was significantly increased for all classes of NSAIDS, with adjusted odds ratios ranging from 1.3 to 1.5.

The mean adjusted odds ratios for MI tended to decline over time after discontinuation of NSAID, but this association reached statistical significance only for conventional NSAIDs.

Neither age nor gender appeared to modify the risk of MI in any NSAID category. However, significantly elevated risks for indomethacin, diclofenac, naproxen, nimesulide, or rofecoxib were observed only in subjects 76 years old or older.

Although "the risk was elevated regardless of the duration of therapy," Dr. Helin-Salmivaara's group concludes, it was "considerably less than the (2- to 5-fold greater) risk of serious upper gastrointestinal events."

Still, "even if the risk increase was modest, any risk of serious adverse event is important at the population level if a drug is not life-saving and is widely used, as is the case with NSAIDs," the authors conclude.

In a related editorial, Dr. Deepak L. Bhatt, from Cleveland Clinic Foundation in Ohio, points out that the report by Dr. Helin-Salmivaara's team is the largest population-based, matched case-control study of NSAIDs performed to date.

Because other studies have yielded different results, and some researchers have hypothesized that NSAIDs are cardioprotective, a large randomized trial is needed. To that end, Dr. Bhatt and his associates have launched a prospective trial to evaluate the safety of celecoxib, ibuprofen and naproxen among 20,000 patients with arthritis, either with cardiovascular disease or at high risk.

Eur Heart J 2006;27:1635-1636,1657-1663.

10. Termination of Out-of-Hospital Resuscitation Rule May Help EMTs

NEW YORK (Reuters Health) Aug 02 - A new three-item clinical prediction rule may help emergency medical personnel decide when to terminate basic life support resuscitative efforts in cases of out-of-hospital cardiac arrest.

The prediction rule recommends, in the absence of advanced cardiac life support, EMTs may consider the termination of basic life support resuscitative efforts: if there is no return of spontaneous circulation before transportation to the ED is initiated; if the patient received no shocks before transportation is initiated; and if the cardiac arrest was not witnessed by EMS personnel, clinicians report in August 3 issue of The New England Journal of Medicine.

Dr. Laurie J. Morrison of the University of Toronto and colleagues validated this rule by testing it in 24 emergency medical systems in Ontario, which included 1240 adults with presumed cardiac arrest who were treated by EMTs trained in the use of an automated external defibrillator.

Of the 776 patients for whom the prediction rule called for termination of basic life support, 4 survived (0.5%). "The rule had a specificity of 90.2 percent for recommending transport of survivors to the emergency department and had a positive predictive value for death of 99.5 percent when termination was recommended," the authors report.

"Implementation of this rule would result in a decrease in the rate of transportation from 100 percent of patients to 37.4 percent," they add.

Dr. Morrison and colleagues note that "substantial numbers" of out-of-hospital cardiac arrest patients with little or no potential for survival are regularly transported to emergency departments.

Guidelines to help EMTs identify which patients would truly benefit from resuscitation efforts would be "extremely useful" and economical.

N Engl J Med 2006;355:478-487.

11. Point-Of-Care USs May Be Better Than Landmark Identification to Place Central Lines

News Author: Laurie Barclay, MD. Aug. 24, 2005 ­ Point-of-care ultrasound (US) is superior to landmark identification for the placement of central venous cannulas, according to the results of a randomized trial published in the August 2005 issue of Critical Care Medicine. The investigators suggest that all central lines should be placed with US assistance.

"A 2001 Agency for Healthcare Research and Quality Evidence Report [AHRQ] on patient safety addressed point-of-care limited ultrasonography guidance for central venous cannulation and strongly recommended real-time, dynamic guidance for all central cannulas," write Truman J. Milling, Jr, MD, from the New York Methodist Hospital, and colleagues. "However, on the basis of one limited study, the report dismissed static assistance, a 'quick look' with ultrasound to confirm vein location before preparing the sterile field, as unhelpful."

The objective of the Third Sonography Outcomes Assessment Program (SOAP-3) Trial was to compare the overall success rate of central cannula placement with use of dynamic US, static US, and anatomical landmarks.

From September 2003 to February 2004 in a U.S. urban teaching hospital, 201 patients undergoing internal jugular vein central venous cannulation were randomized to placement with dynamic US (n = 60), static US (n = 72), or anatomical landmark (n = 69). All imaging was performed with iLook25 SonoSite (SonoSite, Bothell, Washington). Outcome measures were cannulation success, first attempt success, number of attempts, vein size, and clarity of anatomical landmarks. After adjustment for pretest difficulty assessment, results are expressed as odds improvement (95% confidence interval [CI]) over anatomical landmark for dynamic US and static US.

Dynamic US had an odds 53.5 (95% CI, 6.6 - 440) times higher for success than anatomical landmark, and static US had an odds 3 (95% CI, 1.3 - 7) times higher for success than anatomical landmark. Unadjusted success rates were 98% for dynamic US, 82% for dynamic ultrasound, and 64% for anatomical landmark. For dynamic US, odds for first success were 5.8 (95% CI, 2.7 - 13) times higher than for anatomical landmark, and for dynamic ultrasound, odds were 3.4 (95% CI, 1.6 - 7.2) times higher than for anatomical landmark. Unadjusted first-attempt success rates were 62% for dynamic US, 50% for static US, and 23% for anatomical landmark. The US groups had low complication rates.

Study limitations were that the study population did not include all central cannula recipients in the hospital during the study period; inclusion of study investigators in the group of US operators; lack of data on the urgency of cannula placement; and lack of blinding of investigators.

"Ultrasound assistance was superior to anatomical landmark techniques," the authors write. "D [dynamic US] outperformed S [static US] but may require more training and personnel. All central cannula placement should be conducted with ultrasound assistance. The 2001 Agency for Healthcare Research and Quality Evidence Report dismissing static assistance was incorrect."

The authors report no financial conflicts of interest.

Crit Care Med. 2005;33:1764-1769

12. Antibiotics for acute purulent rhinitis---wait and watch

Antibiotics should not be used as first line treatment for acute purulent rhinitis because of their gastrointestinal toxicity, even though they are probably effective. Arroll and Kenealy (BMJ 2006;333:279; 5 August) conducted a meta-analysis of seven randomised controlled trials in adults and children. The relative risks for benefits and harms with the antibiotics were 1.18 and 1.46 respectively. Antibiotics may be used when the symptoms continue long enough to concern patients, the authors add.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7562/279

13. Safety and effectiveness of intravenous regional anesthesia (Bier block) for outpatient management of forearm trauma

Bruce Mohr, MD. Whistler Health Care Centre, Whistler, BC. Can J Emerg Med 2006;8(4):247-50

ABSTRACT
Objective: To assess the safety and effectiveness of intravenous regional anesthesia (Bier block) in the management of forearm injuries (i.e., forearm, wrist or hand) by primary care physicians at a diagnostic and treatment facility.

Methods: A retrospective review was conducted of all patients at a single centre who underwent a Bier block for forearm injuries between September 2000 and March 2005.

Results: 1816 Bier blocks were performed on 1804 patients (64% male) during the study period. Patient age ranged from 4–70 (mean 25) years. Wrist fractures requiring reduction were the most common diagnosis. Adverse events were recorded in 9 cases (0.50%, 95% confidence interval 0.23%–0.94%): 1 case of medication error (0.06%); 3 of improper cuff inflation (0.17%); and 5 of inadequate analgesia (0.28%). None of the adverse events resulted in failure to complete the procedure or in serious morbidity or mortality.

Conclusion: Bier block anesthesia is a safe, effective and reliable technique in an outpatient primary care setting. This technique is a useful modality for physicians who manage acute upper-extremity injuries.

14. Radioisotopes Can Trigger Airport Radiation Detectors

[Though not immediately clinically relevant to many of our practices, this report was nevertheless fascinating.­DRV]

NEW YORK (Reuters Health) Aug 04 - The findings from a case report illustrate how treatment with radioisotopes can make patients radioactive for several weeks and capable of activating radiation detectors at airports.

"Patients receiving radioactive isotopes should be warned that they may trigger radiation alarms," lead author Dr. Kalyan Kumar Gangopadhyay and colleagues from City Hospital in Birmingham, UK, emphasize.

The case report, which appears in the August 5th issue of the British Medical Journal, involved a 46-year-old man with hyperthyroidism. Medical therapy was initially successful in treating his symptoms, but recurrences of thyrotoxicosis eventually led to treatment with radioactive iodine.

The nuclear medicine department gave the man a card describing the precautions to be taken following his treatment. However, the card made no mention of the possibility of setting off radiation detectors.

Six weeks later, the patient made a trip to the US, where he activated security alarms upon check-in at the airport in Orlando, Florida. The man was detained, strip-searched, and sniffer dogs were called to investigate. After a prolonged interrogation, the patient was eventually released after producing the card given to him by the nuclear medicine department.

Based on the type of radioisotope used, patients may be capable of triggering a radiation alarm for up to 95 days, the report indicates.

"Doctors show a worrying lack of awareness about such potential problems," the researchers note. "A literature search found only four case reports and this further highlights the problem."

The authors note that with more sensitive radiation detectors being installed at airports worldwide, there is a good chance that alarms caused by radioisotope-treated patients will increase.

BMJ 2006;333:293-294.

15. TPA Is Safe in Elderly Patients With Acute Ischemic Stroke

By Michelle Rizzo. NEW YORK (Reuters Health) Jul 28 - Results of a study published in the July issue of the Journal of Neurology, Neurosurgery, and Psychiatry suggest that thrombolysis can be safely applied in carefully selected elderly patients with acute ischemic stroke.

"Ischemic stroke patients over 80 can be successfully and safely treated with tPA," lead author Dr. Michael D. Hill, of the University of Calgary, Alberta, Canada, told Reuters Health. "Hopefully...practitioners will be less 'afraid' of the older age group and treat them just as aggressively with thrombolysis as they treat younger patients."

The researchers reviewed data prospectively collected from the Canadian Alteplase for Stroke Effectiveness Study (n = 1135). Two hundred seventy patients at least 80 years of age who were treated with tPA for acute ischemic stroke were compared with 865 patients younger than 80 years.

No significant differences were observed in the risk of symptomatic intracerebral hemorrhage between patients aged 80 years and older and those younger than 80 years (4.4% versus 4.6%).

Forty percent of patients younger than 80 years of age had a favorable outcome (defined as a modified Rankin Score of 0 to 1) at 90 days, compared to 25% of those 80 years and older (p < 0.001). At 3 months' follow-up, 35% of patients older than 80 were dead, compared with 18% of those younger than 80 years (p = 0.001).

Patients 80 years of age and older were more likely than those younger than 80 years to have atrial fibrillation (37% versus 18%, p < 0.001), congestive heart failure (11% versus 6%, p = 0 .004), hypertension (59% versus 48%, p = 0.002), and ischemic heart disease (30% versus 23%, p = 0.05).

The older patients were also more likely to have greater stroke severity than the younger patients. In patients 80 years and older, predictors of death included baseline serum glucose level and congestive heart failure.

"In carefully selected elderly patients, the use of intravenous tPA was not found to be associated with an increased risk of symptomatic intracerebral hemorrhage," the authors conclude.

J Neurol Neurosurg Psychiatry 2006;77:826-829.

16. Delay prescribing of antibiotics for acute conjunctivitis

Delayed prescribing of topical antibiotics is probably the best strategy for managing acute conjunctivitis in primary care, say Everitt and colleagues in the BMJ this week. They randomised more than 300 adults and children with acute infective conjunctivitis from 30 general practices to one of three prescribing strategies­immediate antibiotics (chloramphenicol eye drops), no antibiotics (controls), or delayed antibiotics (prescription to be collected at patients' discretion after three days). Prescribing strategies did not affect the severity of symptoms, but duration of moderate symptoms was less with antibiotics (immediate or delayed). However, delayed prescribing reduced antibiotic use and reattendance compared with immediate prescribing.

Abstract: http://bmj.bmjjournals.com/cgi/content/abstract/333/7563/321