Friday, January 26, 2007

Lit Bits: January 26, 2007

From the recent medical literature...

1. Combination Therapy Reduces Exacerbations in Severe COPD

NEW YORK, NY -- January 15, 2007 -- For patients with severe chronic obstructive pulmonary disease (COPD), combining a long-acting bronchodilator with an inhaled corticosteroid reduced the number of exacerbations by 35%.

The research appears in the second issue for January 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society. Peter Kardos, MD, of the Respiratory Medicine Section of Maingau Hospital in Frankfurt am Main, Germany, and three associates treated patients with moderate to severe COPD from 92 respiratory centers across Germany. All had less than a 50% predicted lung function capability for their age group.

The researchers treated 487 patients with salmeterol, a long-acting bronchodilator, and gave 507 a combination therapy of salmeterol and fluticasone propionate, an inhaled corticosteroid. Of the total cohort, 792 patients completed all phases of the 44-week study. In the combined therapy group, 324 patients experienced moderate to severe exacerbations, as compared to 464 in the control group. The authors believe that this reduction in exacerbations is likely of clinical importance for patients with severe COPD.

"Exacerbations are a major cause of disease-related problems," said Dr. Kardos. "In particular, they greatly contribute to the decline of the health-related quality of life, increase symptoms and breathlessness, speed progression of the disease and increase the risk of mortality. In addition, exacerbations induce enormous economic costs. They can occur at any stage of the disease, but become more frequent as lung function impairment worsens."

In the United States, COPD is the fourth leading cause of death, killing 122,283 Americans in 2003. In 2004, more than 11 million U.S. adults were estimated to suffer from the disease, which results from chronic bronchitis and emphysema, two lung diseases that frequently co-exist and interferes with normal breathing. Smoking is the primary cause of COPD.

To date, no medication has been effective in halting long-term decline in lung function, which is the hallmark of the disease. Medications can only be used to provide relief from symptoms and prevention complications.

In an editorial on the research in the same issue of the journal, Dennis E. Niewoehner, MD, and Timothy J. Wilt, MD, of the Veterans Affairs Medical Center and the University of Minnesota, wrote: "As in all previous large inhaled corticosteroid (ICS) trials, Dr. Kardos administered relatively high doses of fluticasone. High dose ICS causes localized adverse effects in the upper airway and on the skin, but only infrequently do these complications cause discontinuation of therapy."

"Of greater concern is the systemic absorption of small amounts of ICS and the potential for long-term sequelae, particularly involving the bones and eyes," the editorialists continued. "The largely elderly population of patients with COPD may be at greater risk, and, as discussed in a recent review, the extent of the relationship between long-term ICS and bone and eye complications has yet to be fully clarified."

"Dr. Kardos and associates identify an additional safety concern with ICS not mentioned in previous publications. Based on adverse event reporting, 23 cases of pneumonia occurred in the combined-treatment group compared with only seven in the salmeterol arm. This difference is statistically significant and represents an excess pneumonia rate of about 3 per 100 patient years in patients given fluticasone."

The authors noted that similar results were obtained in patients who received fluticasone in TOwards a Revolution in COPD Health (TORCH), a survival study that aimed to determine the impact of salmeterol/fluticasone propionate combination and the individual components on the survival of COPD patients. "In light of the known immunosuppressive properties of corticosteroids, an excess pneumonia rate from a high local concentration of ICS is not particularly surprising," the editorialists wrote.

The authors also pointed out that only a small minority of patients treated with ICS would achieve "clinically noticeable improvement in health status." They concluded: "Therefore, decisions to initiate ICS combined with a long-acting beta agonist should focus on severely symptomatic and exacerbation-prone patients and balance the recently demonstrated benefits against increased drug costs and adverse effects."

SOURCE: American Thoracic Society

2. Clinical Prediction Rule for Identifying Children With CSF Pleocytosis at Very Low Risk of Bacterial Meningitis

Nigrovic LE, at al. JAMA. 2007;297:52-60.

Context: Children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. We previously developed a clinical prediction rule, the Bacterial Meningitis Score, that classifies patients at very low risk of bacterial meningitis if they lack all of the following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/µL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10 000 cells/µL, and a history of seizure before or at the time of presentation.

Objective: To validate the Bacterial Meningitis Score in the era of widespread pneumococcal conjugate vaccination.

Design, Setting, and Patients: A multicenter, retrospective cohort study conducted in emergency departments of 20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. All children aged 29 days to 19 years who presented at participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells 10 cells/µL) and who had not received antibiotic treatment before LP.

Main Outcome Measure: The sensitivity and negative predictive value of the Bacterial Meningitis Score.

Results: Among 3295 patients with CSF pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the 1714 patients categorized as very low risk for bacterial meningitis by the Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%; 95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and both were younger than 2 months old. A total of 2518 patients (80%) with aseptic meningitis were hospitalized.

Conclusions: This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to EDs with CSF pleocytosis.

3. Getting our terminology up-to-date

A. 2005: “Near-drowning” is out.

For over a year now, “drowning” has been the proper term to describe all liquid submersion events, whether the victim dies or walks away from it. To describe an event as a “near-drowning” is as out of vogue as describing a car crash as a “MVA” (see below).

A new definition of drowning: towards documentation and prevention of a global public health problem

van Beeck EF, at al. Bull World Health Organ vol.83 no.11 Genebra Nov. 2005

Drowning is a major global public health problem. Effective prevention of drowning requires programmes and policies that address known risk factors throughout the world. Surveillance, however, has been hampered by the lack of a uniform and internationally accepted definition that permits all relevant cases to be counted. To develop a new definition, an international consensus procedure was conducted. Experts in clinical medicine, injury epidemiology, prevention and rescue from all over the world participated in a series of "electronic" discussions and face-to-face workshops. The suitability of previous definitions and the major requirements of a new definition were intensely debated. The consensus was that the new definition should include both cases of fatal and nonfatal drowning.

After considerable dialogue and debate, the following definition was adopted: "Drowning is the process of experiencing respiratory impairment from submersion/immersion in liquid." Drowning outcomes should be classified as: death, morbidity, and no morbidity. There was also consensus that the terms wet, dry, active, passive, silent, and secondary drowning should no longer be used. Thus a simple, comprehensive, and internationally accepted definition of drowning has been developed. Its use should support future activities in drowning surveillance worldwide, and lead to more reliable and comprehensive epidemiological information on this global, and frequently preventable, public health problem.

B. Remember when MVAs gave way to MVCs?

About 10 years ago, the term MVC (Motor Vehicle Crash) was to replace MVA. The more recent literature reflects this. “Accident” suggests that these crashes are unavoidable, outside of human influence or control. But many times, MVCs are predictable and preventable events. The change was made official by Ricardo Martinez, Administrator, National Highway Traffic Safety Administration, June 8, 1997.

4. Free Online Fitness Tools from the AHA

With an eye on Americans who spend too much time sitting behind computer screens and not enough time getting exercise, the American Heart Association is pitching fitness with an online nutrition tracker. Just in time to rescue waning New Year's resolutions, the AHA has launched several online tools to help users eat right and exercise. The tools, all part of the AHA's new "Start!" program, include:

-- A fitness tracker that tells users how many calories they net based on daily food intake and exercise. Users can also sign up for recorded celebrity wake-up calls.

-- An eating guide that offers low-fat recipes, tips for buying healthier food, and recommendations for the number of calories to eat to maintain a healthy weight.

-- A request form for the AHA to set up a walking program in a user's workplace.

All the tools are free, but some require online registration. Go to

5. Pneumonia Severity Index Guides Care Decisions in the ED

NEW YORK (Reuters Health) Jan 09 - When patients present to the emergency department with pneumonia, the Pneumonia Severity Index (PSI) is a useful aid in making initial site-of-treatment decisions, a multicenter, prospective study conducted in 16 French hospitals confirms.

"Our results confirm previous interventional studies, and bring additional evidence for incorporating the PSI in the ED policies and its more widespread clinical use in the ED setting," Dr. Bertrand Renaud from Centre Hospitalier Universitaire Henri Mondor, Paris, France told Reuters Health.

Over the 3- to 5-month study period, eight participating EDs used the PSI to guide site-of-treatment decisions and eight study EDs did not. The outcomes examined included the proportion of "low risk" patients treated as outpatients, all-cause 28-day mortality, admission of inpatients to the ICU, and subsequent hospitalization of outpatients.

According to the team's report in Clinical Infectious Diseases for January 1, the proportion of patients at low risk who were treated as outpatients was nearly twice as high with routine use of the PSI as that for nonuse of the PSI (42.8% vs 23.9%), "without compromising their safety."

"The actual rate of outpatient care was 18.9% higher for patients who were treated in EDs that routinely used the PSI," they note.

In analyses adjusted for pneumonia severity, short-term mortality was lower in patients from EDs using the PSI, whereas subsequent hospitalization for outpatients and ICU admissions for inpatients did not differ between patients from PSI-user and PSI-nonuser EDs.

According to Dr. Renaud, this study marks the first "real life" assessment of the value of the PSI in guiding hospitalization decisions in patients presenting with community-acquired pneumonia.

Clin Infect Dis 2007;44:41-49.

For the PSI calculator:

6. Cough and Cold Medications May Be Lethal to Infants

NEW YORK (Reuters Health) Jan 11 - After investigating the deaths of three infants between 1 and 6 months of age linked to cough and cold medication use, officials with the US Centers for Disease Control and Prevention are emphasizing that these drugs should be used only after talking with a physician.

Dr. A. Srinivasan and colleagues at the CDC note in the January 12th issue of the Morbidity and Mortality Weekly Report that during 2004 and 2005, approximately 1500 children less than 2 years old were treated in US emergency departments for adverse events associated with cough and cold medications.

For each of the three dead infants, a medical examiner or coroner determined that the cough and cold medications were the underlying causes of death.

Blood levels of the decongestant pseudoephedrine at autopsy ranged from 4700 to 7100 ng/mL; that compares to plasma concentrations of 180-500 ng/mL expected after therapeutic dosing in children ages 2 to 12 years old.

"Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children aged less than 2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting a health-care provider and should follow the provider's instructions precisely," the authors advise.

In an editorial note, the CDC says controlled trials indicate that cough and cold medications are no more effective than placebo in children younger than 2 years of age.

Furthermore, the American College of Chest Physicians in 2006 released clinical practice guidelines for management of cough, advising clinicians to refrain from recommending cough suppressants.

Safer and probably more effective treatments for young patients' symptoms include softening nasal secretions with saline nose drops or a cool-mist humidifier, then clearing nasal congestion with a rubber suction bulb.

Mor Mortal Wkly Rep CDC Surveill Summ 2007;56:1-4.
Full free-text article:

7. (Poor) Association Between Performance Measures and Clinical Outcomes for Patients Hospitalized With Heart Failure

Fonarow GC, et al. JAMA. 2007;297:61-70.

Context: Assessment of quality of care in heart failure has focused on the development and use of process-based performance measures, with the presumption that these processes are associated with improved clinical outcomes. However, this link remains largely untested.

Objective: To examine the relationship between current American College of Cardiology/American Heart Association (ACC/AHA) performance measures for patients hospitalized with heart failure and relevant clinical outcomes.

Design, Setting, and Patients: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, a registry and performance improvement program for patients hospitalized with heart failure. Sixty- to ninety-day postdischarge follow-up data were prospectively collected from 5791 patients at 91 US hospitals in a prespecified 10% sample between March 2003 and December 2004. Mean patient age was 72.0 years, 51% were male, 78% were white, and 42% had ischemic etiology. Multivariable and propensity-adjusted analyses were performed to assess the process-outcome relationship for each performance measure in eligible patients. Additionally, we evaluated the process-outcome link of a potential performance measure for -blockade at discharge among eligible patients hospitalized with heart failure.

Main Outcome Measures: Sixty- to ninety-day mortality and combined mortality/rehospitalization rates.

Results: Mortality during follow-up was 8.6% and mortality/rehospitalization was 36.2%. None of the 5 ACC/AHA heart failure performance measures was significantly associated with reduced early mortality risk, and only angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use at discharge was associated with 60- to 90-day postdischarge mortality or rehospitalization. -Blockade at the time of hospital discharge, currently not a heart failure performance measure, was strongly associated with reduced risk of mortality (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .004) and mortality/rehospitalization during follow-up.

Conclusions: Current heart failure performance measures, aside from prescription of an ACE inhibitor or an ARB at discharge, have little relationship to patient mortality and combined mortality/rehospitalization in the first 60 to 90 days after discharge. Additional measures and better methods for identifying and validating heart failure performance measures may be needed to accurately assess and improve care of patients with heart failure.

8. The Future: Emerging Therapies for the Management of Decompensated Heart Failure: From Bench to Bedside

deGoma EM, at al. J Am Coll Cardiol. 2006;48:2397-409

While pharmaceutical innovation has been highly successful in reducing mortality in chronic heart failure, this has not been matched by similar success in decompensated heart failure syndromes. Despite outstanding issues over definitions and end points, we argue in this paper that an unprecedented wealth of pharmacologic innovation may soon transform the management of these challenging patients. Agents that target contractility, such as cardiac myosin activators and novel adenosine triphosphate-dependent transmembrane sodium-potassium pump inhibitors, provide inotropic support without arrhythmogenic increases in cytosolic calcium or side effects of more traditional agents.

Adenosine receptor blockade may improve glomerular filtration and diuresis by exerting a direct beneficial effect on glomerular blood flow while vasopressin antagonists promote free water excretion without compromising renal function and may simultaneously inhibit myocardial remodeling. Urodilatin, the renally synthesized isoform of atrial natriuretic peptide, may improve pulmonary congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators such as perhexiline may optimize myocardial energy utilization by shifting adenosine triphosphate production from free fatty acids to glucose, a unique and conceptually appealing approach to the management of heart failure. These advances allow optimism not only for the advancement of our understanding and management of decompensated heart failure syndromes but for the translational research effort in heart failure biology in general.

9. Randomized Clinical Trial of Etomidate Versus Propofol for Procedural Sedation in the ED

Miner JR, et al. Ann Emerg Med 2007;49:

Patients undergoing painful procedures in the emergency department (ED), such as orthopedic manipulations or abscess drainage, often require moderate or deep procedural sedation for successful performance of the procedure. This sedation is achieved with the use of a sedative agent administered at a dose that allows patients to maintain airway reflexes and have some response to verbal stimuli (moderate sedation) or to pain (deep sedation). The ideal sedative agent for this purpose would provide adequate sedation to perform the procedure successfully, with a minimum of cardiorespiratory adverse effects, and have a short duration of action. Etomidate and propofol are 2 ultrashort-acting sedative agents thought to provide these characteristics. Despite their common use in procedural sedation, the performance and safety of these 2 agents have not been compared in a randomized controlled fashion.

Propofol has an onset of action of approximately 45 seconds and begins to redistribute from the blood to fat and muscle in 3 to 5 minutes, with a rapidly resolving clinical effect. Propofol provides reliable amnesia and rapid recovery when used for procedural sedation. Etomidate has an onset of action of approximately 1 minute and duration of action of 5 to 15 minutes. It is considered to have the least homodynamic effect of any of the agents available for procedural sedation. A number of studies have found that etomidate provides effective, reliable sedation with minimal adverse effects.

Both of these agents are frequently used for procedural sedation in the ED, but it is not yet known whether one of these agents is more effective or safe than the other. Determining differences in the effectiveness and safety of these agents will allow the development of more specific guidelines about their use.

Study objective
We compare the efficacy, adverse events, and recovery duration of etomidate and propofol for use in procedural sedation in the emergency department (ED).

This was a randomized nonblinded prospective trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients received either propofol or etomidate. Doses, vital signs, nasal end-tidal CO2 (etco2), pulse oximetry, and bispectral electroencephalogram analysis scores were recorded. Subclinical respiratory depression was defined as a change in etco2 greater than 10 mm Hg, an oxygen saturation of less than 92% at any time, or an absent etco2 waveform at any time. Clinical events related to respiratory depression, including an increase in supplemental oxygen, the use of a bag-valve-mask apparatus, airway repositioning, or stimulation to induce breathing, were noted during the procedure. After the procedure, patients completed visual analog scales about perceived pain during the procedure and recall of the procedure.

Two hundred twenty patients were enrolled; 214 underwent sedation and were analyzed. One hundred five patients received etomidate and 109 received propofol. No clinically significant complications were noted. Subclinical respiratory depression was observed in 36 of 105 (34.3%) patients in the etomidate group and 46 of 109 (42.2%) in the propofol group (difference –7.9%; 95% confidence interval [CI] –20.9% to 5.1%). Myoclonus was noted in 21 of 105 (20.0%) patients in the etomidate group and 2 of 109 (1.8%) in the propofol group (difference 18.2%; 95% CI 10.1% to 26.2%). The mean difference between baseline systolic blood pressure and the nadir was 3.8% (95% CI 2.3% to 5.3%) for etomidate and 7.9% (95% CI 6.1% to 9.7%) for propofol. Clinical events related to respiratory depression included an increase in supplemental oxygen in 6.7% of etomidate patients and 5.5% of propofol patients (difference 1.2%; 95% CI –5.2% to 7.6%), the use of bag-valve-mask apparatus in 3.8% of patients in the etomidate groups and 4.6% in the propofol group (difference –0.8%; 95% CI –6.1% to 4.6%), airway repositioning in 13.3% of etomidate patients and 11.0% of propofol patients (effect size 2.3%; 95% CI –6.4% to 11.1%), and stimulation to induce breathing in 11.4% of etomidate patients and 11.9% of propofol patients (difference –0.5%; 95% CI –9.1% to 8.1%). The procedures were successful in 93 of 105 (88.6%) for etomidate and 106 of 109 (97.2%) for propofol (difference –7.4%; 95% CI –14.3% to –1.1%).

Etomidate and propofol appear equally safe for ED procedural sedation; however, etomidate had a lower rate of procedural success and induced myoclonus in 20% of patients.

10. A Prospective Evaluation of “Ketofol” (Ketamine/Propofol Combination) for Procedural Sedation and Analgesia in the ED

Willman EV, et al. Ann Emerg Med 2007;49:28-30.

Study objective
We evaluate the effectiveness and consider the safety of intravenous ketamine/propofol combination (“ketofol”) in the same syringe for procedural sedation and analgesia in the emergency department (ED).

A prospective case series of consecutive ketofol procedural sedation and analgesia events in the ED of a trauma-receiving community teaching hospital from July 2005 to February 2006 was studied. Patients of all ages, with any comorbid conditions, were included. Ketofol (1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was administered intravenously at the discretion of the treating physician by using titrated aliquots. The presence or absence of adverse events was documented, as were procedural success, recovery time, and physician, nurse, and patient satisfaction. Physiologic data were recorded with established hospital procedural sedation and analgesia guidelines.

One hundred fourteen procedural sedation and analgesia events using ketofol were performed for primarily orthopedic procedures. The median dose of medication administered was ketamine at 0.75 mg/kg and propofol at 0.75 mg/kg (range 0.2 to 2.05 mg/kg each of propofol and ketamine; interquartile range [IQR] 0.6 to 1.0 mg/kg). Procedures were successfully performed without adjunctive sedatives in 110 (96.5%) patients. Three patients (2.6%; 95% confidence interval [CI] 0.6% to 7.5%) had transient hypoxia; of these, 1 (0.9%; 95% CI 0.02% to 4.8%) required bag-valve-mask ventilation. Four patients (3.5%; 95% CI 1.0% to 8.7%) required repositioning for airway malalignment, 4 patients (3.5%; 95% CI 1.0% to 8.7%) required adjunctive medication for sedation, and 3 patients (2.6%; 95% CI 0.6% to 7.5%) had mild unpleasant emergence, of whom 1 (0.9%; 95% CI 0.02% to 4.8%) received midazolam. No patient had hypotension or vomiting or received endotracheal intubation. Median recovery time was 15 minutes (range 5 to 45 minutes; IQR 12 to 19 minutes). Median physician, nurse, and patient satisfaction scores were 10 on a 1-to-10 scale.

Ketofol procedural sedation and analgesia is effective and appears to be safe for painful procedures in the ED. Few adverse events occurred and were either self-limited or responded to minimal interventions. Recoveries were rapid, and staff and patients were highly satisfied.

11. Physician Organizations Offer Principles for Reform of US Healthcare System

By Martha Kerr. NEW YORK (Reuters Health) Jan 11 - In what they call an historic move, ten large American professional medical associations have banded together to issue principles for the reform of the country's healthcare system.

The eleven Principles for the Reform of the U. S. Health Care System were issued today, and are "intended to help provide the impetus for bipartisan Congressional action to cover the uninsured," according to a statement from the alliance.

The associations involved in crafting the principles are the American Medical Association; the American Academy of Family Physicians; the American Association of Orthopedic Surgeons; the American College of Cardiology; the American College of Emergency Physicians; the American College of Obstetricians and Gynecologists; the American College of Physicians; the American College of Surgeons; the American College of Osteopathic Family Physicians; and the American Osteopathic Association.

"Healthcare coverage for all is needed to ensure quality of care and to improve the health status of Americans," the first principle states. Healthcare should be provided "without unreasonable financial barriers to care." The associations also call for catastrophic health coverage for all to protect Americans from financial ruin. Access to and financing for appropriate health services "must be a shared public/private cooperative effort," the reformers say. Cost management "by all stakeholders ... is critical to attaining a workable, affordable and sustainable healthcare system."

The coalition also stipulates a reduction of administrative systems, which is essential to reduce costs, improve efficiency and maximize funding for healthcare services. Quality and safety must also be improved. Sufficient funding must also be earmarked for research and education, for preventive and trauma care and for mental health services. The final principle is for "comprehensive medical liability reform," which is "essential to ensure access to quality healthcare."

President of the American Academy of Family Physicians, Dr. Rick Kellerman told Reuters Health that the coalition is "historic" and encompasses the majority of physicians practicing in the US. "Physicians see how dysfunctional our healthcare system is," said Dr. Kellerman, who is on the faculty of the University of Kansas School of Medicine and a family physician in Wichita.

The states are serving as incubators of a variety of approaches to healthcare reform, such as seen with Gov. Arnold Schwarzenegger's proposal for California and laws covering healthcare coverage in Massachusetts and Virginia. "We are seeing a convergence of thought processes," Dr. Kellerman commented. "Forty-seven million Americans are without healthcare insurance...and the vast majority of those individuals work. Many have two jobs," Dr. Kellerman pointed out.

He said other associations, including health insurance companies, are also working to propose solutions to healthcare system and a statement from them may be issued as early as next week.

12. Algorithm Identifies Patients Likely to Respond to Later Thrombolysis After Stroke

By Will Boggs, MD. NEW YORK (Reuters Health) Jan 01 - The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) can be used to select patients likely to respond to thrombolysis 3 to 6 hours after stroke onset, according to a report in the December issue of Stroke.

"Our work shows that, even if the Stroke-TPI works imperfectly in this later time window, it can still identify patients who get substantial clinical benefit, though they are currently ineligible for therapy," Dr. David M. Kent told Reuters Health.

Dr. Kent from Tufts University School of Medicine, Boston, Massachusetts and colleagues investigated whether their multivariable predictive instrument for thrombolysis in stroke might be useful for identifying patients with a favorable risk-benefit profile for treatment beyond 3 hours after stroke onset.

Among all patients treated 3 to 6 hours after symptom onset, the authors report, there was no significant difference in good outcomes between patients treated with recombinant tissue plasminogen activator (rt-PA) and those not treated.

However, patients selected by Stroke-TPI as treatment-favorable showed an absolute margin of benefit from rt-PA of 9.8%, the results indicate. Those selected as treatment-unfavorable were more likely to suffer harm from rt-PA.

"Whether the Stroke-TPI can select such treatment-favorable patients in the period after the 3 hour window needs to be validated on an independent population," Dr. Kent said. "Ongoing trials in this later time window, such as ECASS-3 or IST-3, may provide a substrate to test this."

Stroke 2006;37:2963-2969.

13. Effect of Intoxication Among Blunt Trauma Patients Selected for Head CT Scanning

Bracken ME, Hoffman JR, et al. Ann Emerg Med 2007;49:45-51.

Study objective
We examine the prevalence and types of intracranial injuries sustained by intoxicated blunt trauma patients.

The study was conducted as a secondary analysis of National Emergency X-Radiography Utilization Study II head injury database. Treating physicians prospectively assessed presenting signs and symptoms on all blunt trauma patients who underwent head computed tomography (CT). Intoxication status was determined by the examining physician and was based on a history of intoxication, positive toxicologic screen result, or physical evidence suggesting intoxication. Intracranial injury diagnoses were based on final CT interpretations provided by attending radiologists.

Intracranial injury was detected in 1,193 of the 13,728 enrolled patients (8.7%), and intoxication was evident in 3,356 (24.4%) patients. Physicians were unable to assess intoxication status in 620 individuals. Intracranial injury was present in 231 intoxicated patients (231/3,356; 6.9%; 95% confidence interval [CI] 6.0 to 7.8), 789 of 9,752 nonintoxicated patients (8.1%; 95% CI 7.6% to 8.6%), and 173 of the 620 patients who could not be assessed for intoxication (prevalence 27.9%; 95% CI 24.4% to 31.6%). Intracranial injury was identified in only 5 of 299 intoxicated patients (1.7%) who had normal neurological examination results and no evidence of trauma to the calvarium.

The prevalence of intracranial injury among intoxicated blunt trauma patients who are selected for head CT is lower than among nonintoxicated patients selected for imaging, which likely represents heightened concern in the presence of intoxication, even without other findings suggestive of intracranial injury. This conclusion is supported by the fact that few intoxicated patients with normal neurologic findings and no evidence of trauma to the calvarium had positive findings on CT imaging.

14. White Blood Cell Ratio Differentiates Tonsillitis from Mononucleosis

The ratio between lymphocytes and the total number of white blood cells can help quickly distinguish between bacterial tonsillitis and mononucleosis, according to a study in Archives of Otolaryngology -- Head and Neck Surgery.

Researchers retrospectively analyzed white counts in 100 patients with tonsillitis and 120 with mononucleosis (diagnosed with the mononucleosis spot test). Patients with tonsillitis had a lower mean ratio of lymphocytes to total white blood cells (0.1) than did patients with mononucleosis (0.5). All tonsillitis cases fell below a 0.35 cutoff, while most mononucleosis cases measured above. The authors say that their data suggest that a ratio higher than 0.35 has a 90% sensitivity and a 100% specificity for detecting mononucleosis.

Physicians should use the cell ratio, the authors conclude, "as an indicator to decide whether mononucleosis spot tests are required."


15. Antiplatelet Therapy Necessary at Least a Year with Drug-Eluting Stents

An advisory from the American Heart Association and four other organizations recommends that patients receive dual antiplatelet therapy for at least a year after receiving drug-eluting stents.

The recommended treatment is aspirin plus either clopidogrel (Plavix) or ticlopidine (Ticlid). The statement, published online in Circulation, said such therapy is sometimes stopped prematurely by patients or healthcare providers who do not realize the "potentially severe consequences" -- a greatly increased risk for stent thrombosis, which leads to myocardial infarction or death in about two-thirds of cases. In particular, it urged against interrupting therapy for dental procedures.

The statement also recommends:

-- Telling patients before discharge to contact their cardiologist before ceasing therapy, even if instructed to stop by another healthcare provider;

-- Deferring elective procedures with a significant risk for bleeding until patients finish their year of therapy;

-- Foregoing use of drug-eluting stents in patients who are unlikely to comply with therapy or who will need surgery in the next year.

AHA Press Release:

16. Patient Satisfaction: It’s All a Matter of Meeting Expectations

The disconfirmation paradigm: Throughput times and emergency department patient satisfaction

Cassidy-Smith TN, et al. J Emerg Med 2007;32:7-13.

This study examined the relationship between throughput times, expectations, and patient satisfaction using the Disconfirmation Paradigm (DP), which proposes that dissatisfaction arises when service expectations are not met.

Before discharge or admission, adult emergency department (ED) patients estimated how long they waited for three intervals (Perceived Times): triage to patient care area, patient care area placement to physician evaluation, and physician evaluation to disposition. Acceptable waiting times and satisfaction for the same intervals were then provided by the subject (Acceptable Times and Throughput Time Satisfaction, respectively). Perceived Times were subtracted from Acceptable Times to yield an index of Expectancy Disconfirmation.

There were 1118 (72%) of 1550 eligible patients interviewed. Throughput Time Satisfaction predicted overall satisfaction (r = 0.56 to 0.62, p less than 0.001). In turn, Expectancy Disconfirmation predicted Wait Time Satisfaction (r = 0.42 to 0.64, p less than 0.001).

Consistent with the DP, when throughput times exceeded expectations, dissatisfaction with those throughput times arose, leading to general dissatisfaction with the ED visit.

17. Do Children Require ECG Evaluation and Inpatient Telemetry After Household Electrical Exposures?

Chen EH, et al. Ann Emerg Med. 2007;49:64-67

Emergency physicians must often make decisions about patient management without clear-cut data of sufficient quality to support clinical guidelines or evidence-based reviews. Topics in the Best Available Evidence section must be relevant to emergency physicians, are formally peer reviewed, and must have a sufficient literature base to draw a reasonable conclusion but not such a large literature base that a traditional “evidence-based” review, meta-analysis, or systematic review can be performed.

Electrical injuries in children often occur in the home and are associated with electrical cords (60% to 70%) and wall outlets (10% to 15%); by contrast, adults are typically injured in the workplace. Electrical power sources are characterized as high-voltage exposures or low-voltage exposures. The National Electric Code defines high-voltage exposure as greater than 600 V, although in the medical literature, high-voltage exposures are considered to be greater than 1,000 V. Utility power lines are typically greater than 13,800 V, whereas common household circuits (in the United States and Canada) provide 240 V for high-power appliances and 120 V for general use (220 to 260 V in Australia, Europe, and Asia).

The pathway of the current through the body determines which organs are damaged; a transthoracic current increases the risk of a cardiac injury. Moreover, the extent of tissue injury depends on source voltage, current type (alternating versus direct), current intensity (amperage), pathway of current flow, duration of contact, and local tissue resistance. The most serious cardiac complication of electrical injury is ventricular fibrillation causing cardiac arrest, although electricity can also cause direct myocardial necrosis, which can affect the myocardium, conduction pathways, and coronary arteries. Other nonfatal arrhythmias have been reported (eg, sinus tachycardia, QT prolongation, variable heart block, and nonspecific ST-segment abnormality) but are often transient.

As early as the 1960s, the international medical community published case series describing the life-threatening cardiac manifestations of electrical injury, so it became the standard of care to admit all patients for routine cardiac monitoring for 24 hours. The first studies that questioned this practice were performed primarily in adults and suggested that asymptomatic patients with a low-voltage exposure and a normal initial ECG do not benefit from inpatient cardiac monitoring. We therefore searched the literature to determine whether we can identify a group of pediatric patients at very low risk for a cardiac injury who might not require an ECG evaluation or inpatient telemetry and be safely discharged from the emergency department (ED).

The bottom line
Healthy children exposed to common household currents (120 to 240 V, no water contact), if asymptomatic at ED presentation and without a ventricular arrhythmia or cardiac arrest in the field, are at very low risk for developing cardiac arrhythmias. Patients with a normal initial ECG result do not develop late dysrhythmias, and those with nonfatal arrhythmias or nonspecific ECG abnormalities typically resolve spontaneously within 24 hours. Therefore, this review of available literature supports the practice of safely discharging these children without an initial ECG evaluation or inpatient cardiac monitoring after a common household current exposure. Our recommendations do not pertain to patients who might require admission for other injuries.

18. Utility of LP in the Afebrile vs. Febrile Elderly Patient with AMS: a Pilot Study

Shah K, et al. J Emerg Med 2007;32:15-18.

We conducted a pilot study to compare the diagnostic utility of a lumbar puncture (LP) in febrile vs. afebrile elderly patients with altered mental status (AMS). Our null hypothesis was that there is no utility of performing an LP on the afebrile elderly patient with AMS.

A retrospective study was conducted at an urban, university tertiary care referral center. The study population included all elderly patients (age 65 years and older) who had cerebrospinal fluid (CSF) samples sent to the laboratory over 1 year. A structured chart review was performed. Exclusion criteria were normal mental status, recent neurosurgical procedure or presence of a ventricular shunt, and missing medical records. An LP was considered diagnostically useful if it yielded a diagnosis.

Of the 125 patients who met the study criteria, 84 patients were afebrile and 41 patients were febrile. Of the 84 afebrile patients with AMS, 15 patients (18%; 95% confidence interval [CI] 10–26%) had an abnormal LP. Ten (12%) had some form of meningitis and five (6%) had unclear diagnoses. Of the 41 febrile patients with AMS, 10 patients (24%; 95% CI 11–38%) had an abnormal LP. Three (7%) had some form of meningitis or encephalitis. Comparing the elderly patient group without fever with the elderly patient group with fever, there was no statistical difference in the incidence of abnormal LPs or diagnostically useful LPs.

Based on the results of this pilot study, we were unable to reject the null hypothesis that there is no utility of performing LP on afebrile elderly patients with altered mental status. We would advocate not relying solely on the presence or absence of fever to determine management in the elderly.

19. Dietary Supplements Linked to Serious Adverse Incidents

The American Association of Poison Control Centers keeps data that indicate dietary supplements are more dangerous than many believe -- particularly for children, according to an essay in the New York Times (by Dan Hurley, Jan 16, 2007).

The database collected about 1.6 million reports of adverse reactions to vitamins, minerals, essential oils, herbs, and other supplements over a 23-year period, the essayist writes. More than 250,000 of those incidents required hospitalization and there were 257 deaths. Nearly 75% of the reported incidents occurred in children younger than 6 years.

In 2005, ordinary vitamins were linked to the most poisonings in the category, followed by minerals. Of the herbs and other products, melatonin and homeopathic remedies caused the most problems. But common and popular products, such as St. John’s wort and echinacea, were also linked to hundreds of incidents, many of them serious enough to require hospitalization.

20. Does the Presence of Crystal Arthritis rule out Septic Arthritis?

Shah K, et al. J Emerg Med 2007;32:23-26.

The objective of this study was to determine the incidence of septic arthritis in the presence of joint crystals.

A retrospective study was conducted at a university tertiary care referral center. The study population included all patients with synovial fluid crystals in the joint aspirate sent to the laboratory during the 7-year study period. Septic arthritis was defined as a positive synovial culture.

Of the 265 joint aspirates containing crystals, 183 (69.0%) contained gout crystals, 81 (30.6%) contained pseudogout crystals, and 1 (0.4%) contained both. Four (1.5%) of the aspirates had positive cultures. The mean synovial WBC of the 4 samples with concomitant crystals and septic arthritis was 113,000 (95% confidence interval [CI] 72,700–153,200), which was significantly higher than the entire population at 23,200 (95% CI 19,400–27,000; p less than 0.01). Of note, all 4 patients with concomitant disease had significant co-morbidities and synovial WBC counts greater than 50,000.

Septic arthritis and acute crystal-induced arthritis can occur simultaneously; there were 4 cases (1.5%) of concomitant disease in our study population. The presence of crystals cannot exclude septic arthritis with certainty.

21. Minimally-angulated Pediatric Wrist Fractures: Is Immobilization without Manipulation Enough?

Al-Ansari K, et al. Can J Emerg Med 2007;9:9-15

Background: Emergency department (ED) manipulation of complete minimally angulated distal radius fractures in children may not be necessary, due to the excellent remodeling potential of these fractures.

Objectives: The primary objective of this study was to determine the proportion of minimally angulated distal radius fractures managed in the ED with plaster immobilization that subsequently required manipulation. Our secondary objective was to document, at follow-up, changes in angulation for each wrist fracture.

Methods: This retrospective cohort study reviewed consecutive records of all children with bi-cortical minimally angulated (≤ 15º of angulation in the sagittal plane and ≤ 0.5 cm of displacement) distal metaphyseal radius fractures, alone or in combination with distal ulnar fracture. Details of treatment, radiographic findings, and clinical outcomes during the subsequent orthopedic follow up were recorded.

Results: Of 124 patients included in the analysis, none required manipulation after their ED visit. All but 14 (11.3%) fractures were angulated ≤ 20° within the follow-up period. Two (1.6%) fractures that were initially angulated ≤ 15° progressed to 30°-35°, but remodeled within 2 years to nearly perfect anatomic alignment. By 6 weeks post-injury, no patients had clinically apparent deformity and all had normal function.

Conclusions: Minimally angulated fractures of the distal metaphyseal radius managed in plaster immobilization without reduction in the ED are unlikely to require future surgical intervention.