Saturday, July 12, 2008

Lit Bits: July 12, 2008

From the recent medical literature...

1. Emergency Department Visits Are Increasing for Elderly Patients

NEW YORK (Reuters Health) Jun 26 - The number of emergency department visits by elderly patients is increasing and will probably continue to increase as the population ages, according to findings published in the June issue of the Annals of Emergency Medicine.

"In 2005, the Centers for Disease Control and Prevention reported increasing emergency department (ED) visit rates per 100 people," write Dr. Mary Pat McKay and colleagues from George Washington University, Washington, DC. "The greatest increase in visit rate was among individuals 65 years and older," they note, adding that because older patients have longer ED stays, are more likely to be admitted, and represent a growing segment of the population, "this finding could have a significant negative effect on ED crowding."

Using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), the researchers analyzed ED visits by subjects older than 65 years during the years 1993 to 2003. They used annual census data to compute visit rates per 100 persons.

The rate of ED visits for subjects 65 to 74 years increased by 34% during the study period. Among black subjects, the visit rate increased by 90% to 77 visits per 100 persons per year. The rate for white subjects increased by 26% to 36 visits per 100 persons per year.

The researchers classified the ED patients' primary diagnostic codes into four categories: injury, acute noninjury, exacerbation of chronic condition, and "other" (including such ill-defined problems as weakness, dizziness, etc.). According to their report, 93% of the increase in ED visits was for diagnoses that fell into the "other/undefined" category. There was an increase of 44% in the number of visits at which three or more medications were administered.

No significant change was observed in the admission rate during the study period.

"If trends continue, the effects on ED and hospital crowding could be catastrophic, and planning should begin now," Dr. McKay and colleagues conclude.

Ann Emerg Med 2008;51:769-774.

2. One Epinephrine Dose May Not Suffice for Children With Multiple Food Allergies

NEW YORK (Reuters Health) Jul 09 - Nearly one in five food-induced anaphylactic reactions that occur in children with multiple food allergies will require two or more doses of epinephrine, new research suggests.

As reported in an upcoming issue of the Journal of Allergy and Clinical Immunology, Dr. Kirsi M. Jarvinen, from Mount Sinai School of Medicine in New York, and colleagues evaluated epinephrine usage in children with food allergies by surveying the families of 413 patients.

Overall, 78 children (median age = 4.5 years) were given epinephrine for a total of 95 reactions, the report indicates. Over 75% of these reactions involved peanut, tree nut, or cow's milk allergies.

Twelve (13%) of the reactions required two doses of epinephrine and an additional 6 (6%) required three doses, the researchers found.

Asthma was identified as a predictor of receiving multiple epinephrine doses, whereas the amount of food ingested and the delay in initial epinephrine treatment seemed to have no effect.

"Our survey performed in a highly selected patient population indicates that a significant number of respondents received a second dose of epinephrine," the authors conclude. "Prospective studies are needed to identify risk factors for severe anaphylaxis and to establish rational guidelines for prescribing multiple epinephrine autoinjectors for children with food allergy."

Järvinen KM, et al. J Allergy Clin Immunol 2008;122:133-138.

3. A Placebo in the Home Medicine Cabinet

A chewable, cherry-flavored dextrose tablet will soon be marketed to parents as a placebo treatment for children.

A placebo refers to a substance with no direct pharmacologic effect that is given to reinforce a patient’s expectation to get well. The New York Times reported that a chewable, cherry-flavored dextrose tablet will soon be marketed to parents as a placebo treatment for children. To capture the imagination of prospective parents, the name of the product — Obecalp — is the word placebo spelled backward. The developer of the placebo tablet, a parent of young children, promotes the product as a way to reduce potential harm from unnecessary medications. The Times quotes several physicians and bioethicists who point out that although placebos might be useful in some situations, ". . . giving children a ‘medicine’ for every ache and pain teaches that every ailment has a cure in a bottle."

Comment: After reading the article, I reviewed the index of several general pediatric textbooks and found only a single brief discussion about the ethical use of a placebo in clinical trials but no references to the use of a placebo in clinical practice. Use of placebos in the treatment of children deserves further examination.

Although I do not administer placebo pills to my patients on a regular basis, in some situations a placebo might be helpful. For example, some pediatricians prescribe a placebo for 1 week followed by a stimulant medication for new patients with ADHD to assess the need for medication. This use of a placebo is based on reports that 10% to 20% of children with ADHD have a positive response to a placebo trial. During a time when pediatricians practice the judicious use of antibiotics for respiratory infections and otitis media, the availability of a placebo pill could persuade parents to use the placebo and delay medical attention. Pediatricians should be prepared to discuss the benefits and risks of using a placebo at home.

— Martin T. Stein, MD. Published in JW Pediatrics and Adolescent Medicine July 2, 2008. Citation: Aschwanden C. Experts question placebo pill for children. New York Times. May 27 , 2008.

4. Does This Patient With Diabetes Have Osteomyelitis of the Lower Extremity?

Milne WK, et al. Ann Emerg Med 2008; in press.

An ulcer area larger than 2 square cm, a positive probe-to-bone test result, an ESR greater than 70 mm/hour, and an abnormal radiograph result are helpful in diagnosing the presence of lower extremity osteomyelitis in patients with diabetes. A negative MRI result makes the diagnosis much less likely when all of these findings are absent. No single historical feature or physical examination result reliably excludes osteomyelitis. The diagnostic utility of a combination of findings is unknown.

5. 18 of 28 Patients with SAH Report Preceding Sudden, Severe Headache

By Judith Moser, MD. NICE, France -- June 13, 2008 -- Specific warning signs, such as typical pulsatile headache, can be used as a diagnostic key to suspect presence of a cerebral aneurysm days before the occurrence of a spontaneous subarachnoidal haemorrhage (SAH), according to a study presented here at the 18th Meeting of the European Neurological Society (ENS).

Cerebral aneurysms are the most common cause of spontaneous SAH, but only 10% to 20% of them are diagnosed before rupture. Despite recent advances in neurosurgical techniques, the overall outcome after SAH remains poor. Therefore, earlier diagnosis and further reductions of possible risk factors are desirable.

The reported incidence of warning signs in the literature ranges from 13.5% to 60%, with the majority of patients reporting sudden, unusually severe headache days, even weeks, before spontaneous SAH. A warning headache is often misdiagnosed as a migraine, sinusitis, tension headache, or cervical spine disorder.

The study, presented on June 11, aimed to identify the warning signs and symptoms of spontaneous SAH and evaluate the frequency of possible risk factors.

Investigators screened all patients who were admitted with spontaneous SAH between April 2004 and April 2005 to the department of neurology and neurosurgery at a university hospital. The study excluded patients with haemorrhage that definitely originated from trauma or intracerebral haemorrhage and those who died before an accurate diagnosis.

The researchers used prepared questionnaires in interviews with the patients or their relatives to gather data on possible warning signs.

Overall, 11 men and 17 women with spontaneous SAH were indentified during the study period. "In all of them, SAH was due to cerebral aneurysms, although arteriovenous malformation was also present in 3 of the cases," said principal investigator Mansooreh Togha, MD, Department of Neurology, Sina Hospital, Tehran University of Medical Science, Tehran, Iran.

A total of 64.3% (18 of 28) of patients recalled abrupt onset of atypical pulsatile headache prior to the event. "The most frequently indicated locations were frontotemporal and frontal," said Dr. Togha.

He noted that the localisation of headache is not related to the location of the aneurysm, in contrast to the usual findings in stroke patients.

Headache symptoms were bilateral in 63% of cases and combined with other neurological signs in most patients. There was a significant correlation with a sudden and unprecedented onset of ataxic gait, observed in 21.4% of patients.

Other, less frequent signs included hemiparesis (14.28%), palsy of the third cranial nerve (7.14%), and seizures (3.57%).

"The intervals between the warning symptoms and the SAH ranged between 24 hours to about 6 days," said Dr. Togha. "Transient losses of consciousness, which were reported in 42.85% of patients, occurred at shorter intervals of some hours to 5 days."

The 2 strongest modifiable risk factors were hypertension and smoking. Hypertension was reported in 39.3% of cases, and 32.1% of patients were smokers. After adjustment for factors such as age and sex, a smoking history of at least 5 years (20 cigarettes a day or more) was recognised as a risk factor, whereas hypertension was not.

Presentation title: Warning Signs and Symptoms of Subarachnoid Haemorrhage. Abstract P 769

6. Combination Vasopressin and Epinephrine Do Not Improve Cardiac Arrest Outcomes

Michael O'Riordan. From Heartwire — a professional news service of WebMD. July 3, 2008 — The combination of vasopressin and epinephrine in cardiopulmonary resuscitation (CPR) does not improve clinical outcomes, including survival to hospital admission or survival to the return of spontaneous circulation, compared with epinephrine alone, a new study has shown [1]. Investigators say there was no benefit of vasopressin treatment on any of the predefined subgroups and that the therapy is not likely to provide benefit when used in the resuscitation of patients who have cardiac arrest.

"The lack of superiority of combination therapy over epinephrine alone, regardless of the patient subgroup, suggests it may be futile to add vasopressin to epinephrine during cardiopulmonary resuscitation with advanced cardiac life support," writes Dr Pierre-Yves Gueugniaud (University of Lyon, France) and colleagues in the July 3, 2008 issue of the New England Journal of Medicine.

Although epinephrine remains the vasopressor agent of choice for CPR, the prognosis of patients with cardiac arrest is poor, regardless of the dose of epinephrine used. As previously reported by heartwire, vasopressin was postulated as an alternative to epinephrine when it was discovered that successfully resuscitated cardiac-arrest patients had higher endogenous vasopressin levels than those patients who died.

Although vasopressin is a possible alternative to epinephrine during CPR, limited clinical experience with the treatment has been documented. One study suggested that vasopressin as an adjunctive therapy to epinephrine might be more effective than epinephrine alone in the treatment of asystolic cardiac arrest, while other studies have shown equivocal benefit with the two drugs. Studies of CPR in animal models, Gueugniaud and colleagues write, showed that vasopressin increased blood flow to vital organs and cerebral oxygen delivery, as well as improved short-term survival.

For this reason, the French investigators performed a large, randomized, clinical trial to prospectively test whether the combination of vasopressin and epinephrine is superior to epinephrine alone in out-of-hospital cardiac arrest. Investigators assigned 1442 adults to 1 mg of epinephrine and 40 IU of vasopressin and 1452 adults to 1 mg of epinephrine alone, with the combination of drugs repeated if spontaneous circulation was not restored within three minutes after the first administration. Patients were subsequently given additional epinephrine alone if needed.

The combination therapy with vasopressin and epinephrine did not result in any significant improvement over epinephrine alone. The rates of survival to hospital admission, return of spontaneous circulation, survival to hospital discharge, survival at one year, and neurologic recovery at discharge were similar in both treatment arms.

Investigators also looked at a number of predefined patient subgroups, among them witnessed vs unwitnessed cardiac arrest, the initial cardiac rhythm, the number of drug injections, and the time to resuscitation before drug injection, and found no benefit with the combination of vasopressin and epinephrine.

Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine versus epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21-30. Abstract:

7. BNP Marker of Critical Heart Disease in Infants and Children

NEW YORK (Reuters Health) Jun 19 - Children presenting in emergency departments and intensive care units with hemodynamically significant cardiac disease have markedly elevated levels of B-type natriuretic peptide (BNP), researchers in Atlanta report in the June issue of Pediatrics.

"Many cardiac disease states can mimic the more common illnesses of childhood, such as bronchiolitis, reactive airway disease, and sepsis," lead author Dr. Kevin O. Maher and colleagues point out.

To examine its potential as a marker to diagnose heart disease in children, Dr. Maher's group measured BNP levels in 33 pediatric patients newly diagnosed with congenital or acquired heart disease and in 70 pediatric patients with respiratory or infectious disease.

The cardiac patients (ages 2 days to 17.5 years) had presented to emergency departments or intensive care units and were subsequently transferred to Children's Healthcare of Atlanta for diagnosis and management of critical heart disease.

Prior to this event, there had been numerous health care visits for symptoms of "fussiness, fatigue, poor feeding, shortness of breath, swelling of the lower extremities, weakness, and 'not looking well,'" the authors note. Initial diagnoses were viral illness, nephrotic syndrome, colic, sepsis, and pneumonia. Two patients died before severe heart disease was diagnosed.

Chief complaints in the noncardiac group (ages 3 days to 72 months) were fever, cough, shortness of breath, congestion, fatigue, vomiting/diarrhea, dizziness, abdominal pain, and cold symptoms. None were diagnosed with heart disease.

Mean BNP level was 3290 pg/mL in the cardiac patients and 17.4 pg/mL in the noncardiac group. Using 100 pg/mL as a cutoff value to identify heart disease, the sensitivity was 100% and specificity was 98%.

The authors caution that BNP levels can be elevated in neonates without cardiac disease, whereas patients with milder forms or earlier presentation of heart disease may have lower BNP levels than in this cohort of cardiac patients.

"We have not proved that a normal BNP level rules out cardiac disease," they state.

Regardless, Dr. Maher and his associates recommend BNP as "a useful marker to aid in the emergency diagnosis of pediatric critical heart disease in the acute care setting."

Pediatrics 2008;121:e1484-e1488.

8. Sixty-four–slice CT of the Coronary Arteries: Cost–Effectiveness Analysis of Patients Presenting to the ED with Low-risk CP

Khare RK, et al. Acad Emerg Med. 2008;15:623-632.

Objectives: The aim was to use a computer model to estimate the cost–effectiveness of 64-slice multidetector computed tomography (MDCT) of the coronary arteries in the emergency department (ED) compared to an observation unit (OU) stay plus stress electrocardiogram (ECG) or stress echocardiography for the evaluation of low-risk chest pain patients presenting to the ED.

Methods: A decision analytic model was developed to compare health outcomes and costs that result from three different risk stratification strategies for low-risk chest pain patients in the ED: stress ECG testing after OU care, stress echocardiography after OU care, and MDCT with no OU care. Three patient populations were modeled with the prevalence of symptomatic coronary artery disease (CAD) being very low risk, 2%; low risk, 6% (base case); and moderate risk, 10%. Outcomes were measured as quality-adjusted life years (QALYs). Incremental cost–effectiveness ratios (ICERs), the ratio of change in costs of one test over another to the change in QALY, were calculated for comparisons between each strategy. Sensitivity analyses were conducted to test the robustness of the results to assumptions regarding the characteristics of the risk stratification strategies, costs, utility weights, and likelihood of events.

Results: In the base case, the mean (±standard deviation [SD]) costs and QALYs for each risk stratification strategy were MDCT arm $2,684 (±$1,773 to $4,418) and 24.69 (±24.54 to 24.76) QALYs, stress echocardiography arm $3,265 (±$2,383 to $4,836) and 24.63 (±24.28 to 24.74) QALYs, and stress ECG arm $3,461 (±$2,533 to $4,996) and 24.59 (±24.21 to 24.75) QALYs. The MDCT dominated (less costly and more effective) both OU plus stress echocardiography and OU plus stress ECG. This resulted in an ICER where the MDCT arm dominated the stress echocardiography arm (95% confidence interval [CI] = dominant to $29,738) and where MDCT dominated the ECG arm (95% CI = dominant to $7,332). The MDCT risk stratification arm also dominated stress echocardiography and stress ECG in the 2 and 10% prevalence scenarios, which demonstrated the same ICER trends as the 6% prevalence CAD base case. The thresholds where the MDCT arm remained a cost-saving strategy compared to the other risk stratification strategies were cost of MDCT, less than $2,097; cost of OU care, above $1,092; prevalence of CAD, less than 70%; MDCT specificity, above 65%; and a MDCT indeterminate rate, less than 30%.

Conclusions: In this computer-based model analysis, the MDCT risk stratification strategy is less costly and more effective than both OU-based stress echocardiography and stress ECG risk stratification strategies in chest pain patients presenting to the ED with low to moderate prevalence of CAD.

9. Actual Financial Comparison of Four Strategies to Evaluate Patients with Potential Acute Coronary Syndromes

Chang AM, et al. Acad Emerg Med. 2008;15:649-655.

Objectives: Small studies have shown that a negative computed tomography coronary angiogram (CTA) in low-risk chest pain patients predicts a low rate of 30-day adverse events. The authors hypothesized that an immediate CTA strategy would be as effective but less costly than alternative strategies for evaluation of patients with potential acute coronary syndrome (ACS).

Methods: The authors retrospectively compared four strategies for evaluation of patients after initial physician determination that the patient required admission and testing to rule out ACS. Patients were frequency-matched by age, race, gender, thrombolysis in myocardial infarction (TIMI) score, and initial electrocardiogram (ECG). The four groups were immediate CTA in the emergency department (ED) without serial markers (n = 98); clinical decision unit/observation unit (CDU) with biomarkers and CTA (n = 102); CDU evaluation with serial cardiac biomarkers and stress testing (n = 154); and usual care, defined as admission with serial biomarkers and hospitalist-directed evaluation (n = 289). The main outcomes were actual cost of care (facility direct and indirect fixed, facility variable direct labor and supply costs), length of stay (LOS), diagnosis of coronary artery disease (CAD), and safety (30-day death or myocardial infarction [MI]).

Results: Patients in each group were of similar age (mean ± standard deviation [SD] 46 ± 9 years), race (62% African American), and gender (57% female) and had similar TIMI scores (100% between 0–2). Comparing immediate CTA versus CDU CTA versus CDU stress versus usual care, median costs were less ($1,240 vs. 2,318 vs. 4,024 vs. 2,913; p less than 0.01), and LOS was shorter (8.1 hr vs. 20.9 hr vs. 26.2 hr vs. 30.2 hr; p < 0.01). Diagnosis of CAD was similar (5.1% vs. 5.9% vs. 5.8% vs. 6.6%; p = 0.95), but fewer patients had 30-day death/MI (0% vs. 0% vs. 0.7% vs. 3.1%; p = 0.04) or 30-day readmission (0% vs. 3.2% vs. 2.3% vs. 12.2%; p less than 0.01).

Conclusions: Compared to the other strategies, immediate CTA was as safe, identified as many patients with CAD, had the lowest cost, had the shortest LOS, and allowed discharge for the majority of patients. Larger prospective studies should confirm safety before immediate CTA replaces other strategies to rule out possible ACS.

10. Where is the Safest Place in the Hospital to have a Cardiac Arrest?

Kaysera RG, et al. Resuscitation. 2008 May 26. [Epub ahead of print]

Various hospital units exist to meet the clinical needs of different populations, including the risk of unexpected life threatening events such as sudden cardiac arrest (CA). Location of CA events has been studied in the out-of-hospital arena, and comparisons have been made between in-hospital and out-of-hospital settings. However, detailed analysis of the location of in-hospital events has so far been limited to single centers. The primary purpose of this analysis was to determine the characteristics and outcomes of Emergency Department (ED) CA events, and to compare them to CA events occurring in other units (ICU, general floor and telemetry floor).

Additionally, little is known about the characteristics of patients who develop CA in the ED, as a "primary" event vs. "recurrent" event (after successful resuscitation from out-of-hospital CA) and about the characteristics of patients who develop CA after a major traumatic injury. Secondary analyses profiled the characteristics and outcomes of these two subsets of ED CA patients (primary vs. recurrent, and trauma vs. non-trauma).

60,852 adult, in-patient CA events in the National Registry of Cardiopulmonary Resuscitation were included. Multiple regression analysis compared ED CA with those occurring in the ICU, telemetry, or general floors. Subgroup analysis examined traumatic vs. non-traumatic ED CA and ED CA occurring after a successful pre-hospital resuscitation (recurrent) vs. primary ED event.

In multivariate analysis, ED location predicted improved survival to discharge (OR 0.74, 95%CI [0.67–0.82]). ED CAs had higher survival to discharge rates (ED 22.2, ICU 15.5, Tele 19.8, Floor 10.8, p less than 0.0001), better cerebral performance category scores (ED 1.59, ICU 1.73, Tele 1.96, Floor 1.69, p less than 0.0001), and shorter post-event length of stays (ED 8.6, ICU 17.5, Tele 16.5, Floor 14.2 days, p less than 0.0001) than other locations. Recurrent ED CAs were less likely to survive to discharge (10.1% vs. 24.6%, p less than 0.0001) than primary events. Trauma-related ED CAs had a lower survival to discharge rate (7.5% vs. 23.8%, p less than 0.0001), were less likely to be caused by an arrhythmia (23.6% vs. 32.5%, p less than 0.0008), and more likely to be preceded by hypotension or shock (41.6% vs. 29.0%, p less than 0.0001) than non-trauma ED events.

ED CAs have unique characteristics, and better survival and neurologic outcomes compared to other hospital locations. Primary ED CAs have a better chance of survival to discharge than recurrent events. Traumatic ED CAs have worse outcomes than non-traumatic CA.

11. Is Noninvasive Ventilation Improving Outcomes in Decompensated HF?

In a large randomized trial, noninvasive ventilation provided no survival advantage to patients with cardiogenic pulmonary edema.

Noninvasive methods of ventilation are being used in patients with acute heart failure, even though the evidence for a net benefit of such a strategy is not very strong. Investigators in the U.K. conducted a large, randomized, multicenter trial to determine if noninvasive ventilation, compared with oxygen administration alone, improves survival in patients with cardiogenic pulmonary edema. Two methods of noninvasive ventilation were compared: continuous positive airway pressure (CPAP) and noninvasive positive-pressure ventilation (NIPPV). The primary endpoint was death or intubation within 7 days after treatment initiation.

A total of 1069 patients with cardiogenic pulmonary edema were randomized to standard oxygen therapy, CPAP, or NIPPV. The patients’ mean age was 78, and about one fifth of them had symptoms of MI. Mean heart rate in all three groups was about 113 beats per minute, and mean systolic blood pressures were about 161 mm Hg.

At 7 days, there was no difference in mortality between noninvasive-ventilation recipients and oxygen-therapy recipients. The composite of death or intubation at 7 days was not significantly different among the three groups, nor was length of hospital stay. More patients discontinued noninvasive ventilation than standard oxygen therapy because of discomfort. By contrast, standard oxygen therapy was discontinued because of worsening blood gas values or respiratory distress more frequently than was noninvasive ventilation.

Comment: The results of this open randomized trial of noninvasive ventilation failed to show a reduction in the risk for death or intubation. The finding that fewer noninvasive-ventilation recipients than oxygen-therapy recipients experienced respiratory distress or metabolic abnormalities did not translate into any clinically meaningful change in outcome. The authors conclude with a "glass-is-half-full" assessment of their findings; nonetheless, this trial provides little support for noninvasive ventilation as an initial approach to patients with acute heart failure.

— Harlan M. Krumholz, MD, SM. Published in JW Cardiology July 9, 2008. Citation:
Gray A et al. for the 3CPO Trialists. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med 2008 Jul 10; 359:142.

12. Alfuzosin Stone Expulsion Therapy for Distal Ureteral Calculi: A Double-Blind, Placebo Controlled Study

Pedro RN, et al. J Urol 2008;179:2244-2247.

We evaluated the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage.

Materials and Methods
A total of 76 patients with a distal ureteral calculus provided consent for the study. Patients were randomized between placebo and study medication, and investigators and patients were blinded to the randomization scheme. Followup was done on a weekly basis and continued until the patient was rendered stone-free. The patient blood pressure, discomfort level, stone position on imaging, number of remaining pills and any adverse events were assessed. Statistical analysis was performed with the Student t test with p less than 0.05 considered significant.

The overall spontaneous stone passage rate was 75%, including 77.1% for placebo and 73.5% for alfuzosin (p = 0.83). Mean ± SD time needed to pass the stone was 8.54 ± 6.99 days for placebo vs 5.19 ± 4.82 days for alfuzosin. (p = 0.003). There was no difference in the size or volume of stones that passed spontaneously between the placebo and alfuzosin arms, as measured on baseline computerized tomography (4.08 ± 1.17 and 3.83 ± 0.95 mm, p = 0.46) and by a digital caliper after stone expulsion (3.86 ± 1.76 and 3.91 ± 1.06 mm, respectively, p = 0.57). When comparing the improvement from the baseline pain score, the alfuzosin arm experienced a greater decrease in pain score in the days after the initial emergency department visit to the date of stone passage (p = 0.0005).

Alfuzosin improves the patient discomfort associated with stone passage and decreases the time to distal ureteral stone passage but it does not increase the rate of spontaneous stone passage.

13. Oral Prednisolone for NSAID-Intolerant Gout Patients

Oral prednisolone is as safe and effective as naproxen.

Current standard treatments for gout (colchicine and nonsteroidal anti-inflammatory drugs [NSAIDs]) can have significant side effects. In a randomized, double-blind trial, Dutch researchers compared treatment with either oral naproxen (500 mg twice daily) or oral prednisolone (35 mg once daily plus placebo) for 5 days in 120 patients (89% men; mean age, 57) with microscopically confirmed monoarticular gout. Patients were referred by their family doctors within 24 hours of initial presentation. Another 96 patients with microscopically confirmed gout were excluded, mostly because of current use of NSAIDs or colchicine or contraindications to NSAIDs.

At 90 hours, mean reductions in pain (assessed on a validated visual analog scale [VAS]) were similar in the naproxen and prednisolone groups. Mean reductions in disability related to use of the affected joint and related to walking (both scored on unvalidated VASs) also were similar in the two groups. Adverse effects during treatment were minor and comparable between groups. At 3-week follow-up, all patients reported complete resolution of pain and disability.

Comment: A 5-day course of prednisolone is as effective as traditional treatment with an NSAID (in this case, naproxen) for acute gout. Prednisolone is both a sound alternative for patients with an NSAID contraindication and an alternative first-line therapy.

— Kristi L. Koenig, MD, FACEP. Published in JW EM. June 13, 2008. Citation: Janssens HJEM et al. Lancet 2008 May 31; 371:1854.

Medline abstract (Free):

14. Coffee drinking linked to lower mortality, particularly in women

Lopez-Garcia E, et al. Ann Intern Med 2008;148:904-14.

Many observational studies have tried to find out whether coffee is bad for your health. It can be hard to tell, because people who drink lots of coffee also tend to smoke, drink alcohol, and take little exercise. In the latest study, researchers carefully controlled for all these factors and a few more. They found a clear association between drinking coffee and lower mortality that was stronger in women than men.

The researchers analysed data from two long running cohorts. One included 41,736 male health professionals. The other included 86,214 female nurses. In both cohorts the risk of death from all causes went down as coffee consumption went up. Both trends were significant. In the female cohort, however, most categories of coffee consumption were associated with significantly lower risk of death compared with no coffee. The reductions ranged from 7% (relative risk 0.93, 95% CI 0.87 to 0.98) among nurses drinking five to seven cups a week, to 26% (0.74, 0.68 to 0.81) among nurses drinking four or five cups a day.

Coffee seemed to protect both men and women against cardiovascular death but not death from cancer. The authors think caffeine is unlikely to be responsible since they also observed lower mortality among women drinking decaffeinated coffee.

This study was not funded by Starbucks.

15. Ultrasound-guided supraclavicular brachial plexus nerve block vs procedural sedation for the treatment of upper extremity emergencies

Stone MB, et al. Amer J Emerg Med. 2008;26:706-710.

Emergency physicians often treat patients who require procedural sedation for the management of upper extremity fractures, dislocations, and abscesses (upper extremity emergencies). Unfortunately, procedural sedation is associated with several rare but potentially serious adverse effects and requires continuous hemodynamic monitoring and several dedicated staff members. The purpose of this study was to determine the role of ultrasound-guided supraclavicular brachial plexus nerve blocks in the emergency department (ED) as an alternative to procedural sedation for the management of upper extremity emergencies.

In a prospective trial, a convenience sample of ED patients with upper extremity emergencies that would normally require procedural sedation were assigned to receive either procedural sedation or an ultrasound-guided supraclavicular brachial plexus nerve block. Emergency department length of stay (ED LOS) was the primary outcome measure and was analyzed using a paired 2-tailed Student t test.

A total of 12 subjects were enrolled. Average ED LOS for subjects receiving the brachial plexus nerve block was 106 minutes (95% confidence interval, 57-155 minutes). Average ED LOS for subjects receiving procedural sedation was 285 minutes (95% confidence interval, 228-343 minutes). The ED LOS was significantly shorter in the nerve block group (P < .0005). Patient satisfaction was high in both groups, and no significant complications occurred in either group.

In our population, ultrasound-guided brachial plexus nerve blocks resulted in shorter ED LOS compared to procedural sedation for patients with upper extremity fractures, dislocations, or abscesses.

16. A 10% Prevalence of Silent Stroke Found in "Healthy" Adults

Caroline Cassels. June 27, 2008 — About 10% of apparently healthy middle-aged adults have experienced silent cerebral infarcts (SCI), according to the latest results from the Framingham Offspring Study. Furthermore, the study found risk factors typically associated with clinical stroke, including hypertension, elevated serum homocysteine, and carotid artery disease, are also associated with midlife SCI.

The study's findings are consistent with previous community-based studies, which have estimated the prevalence of SCI between 5.8% and 17.7%, depending on age, ethnicity, presence of comorbidities, and imaging techniques.

"Our study shows that, in a middle-aged population free of clinical disease, there is a distressingly high prevalence of subclinical disease, as evidenced by these silent infarcts, which we know increase the risk of clinical stroke and cognitive impairment," study investigator Sudha Seshadri, MD, from Boston University School of Medicine, in Massachusetts, told Medscape Neurology & Neurosurgery.

"These findings also reinforce the need for clinicians to aggressively detect and manage cardiovascular risk factors, perhaps even earlier than midlife," she added.

Atrial Fibrillation Link

In addition to the prevalence data, the investigators also found that stroke risk factors, including hypertension, elevated plasma homocysteine, carotid stenosis, and increased carotid artery intimal medial thickness, are also significantly associated with silent infarcts.

Another, somewhat surprising, finding, said Dr. Seshadri, was a significant link between atrial fibrillation (AF) and SCI, with the data revealing that AF increased the risk for prevalent SCI more than 2-fold.

According to Dr. Seshadri, this finding may be an indication that AF is a simultaneous outcome, rather than a cause of SCI.

"While it is possible that tiny emboli resulting from atrial fibrillation may be causing these silent infarcts, it is probable that some of the risk factors for AF are the same as those for SCI. Therefore, it may be that atrial fibrillation is a marker for silent infarcts, rather than a cause, and that the 2 conditions are occurring together," she said.

An offshoot of the Framingham Heart Study, a longitudinal study that began in 1948 with the goal of identifying common risk factors for cardiovascular disease, the Framingham Offspring Study, which began in 1971, includes the children and children's spouses of the original cohort.

With an average age of 62 years, the current sample included 2040 offspring who attended the sixth examination (1996-1998) and underwent volumetric brain magnetic resonance imaging (MRI) in 2001 and were free of clinical stroke.

In addition, subjects were assessed using the Framingham Stroke Risk Profile (FSRP), a validated instrument that predicts 10-year probability of incident stroke and includes age, systolic blood pressure, antihypertensive therapy, diabetes mellitus, cigarette smoking, cardiovascular disease, AF, and left ventricular hypertrophy.

Subjects also underwent carotid imaging and measurement of cholesterol concentrations as well as plasma homocysteine.

Need to Follow Guidelines

Among the 10.7% of study subjects who had MRI evidence of silent infarcts, 84% had a single lesion, most commonly located in the basal ganglia (52%). One third of the lesions were subcortical, and 10% were cortical lesions.

According to the study, the aggregate FSRP score was significantly associated with prevalent SCI. Of the FRSP variables, AF, hypertension, and systolic blood pressure were all associated with an increased risk for silent infarct.

Of the variables not included in the FRSP, plasma homocysteine, carotid stenosis of 25% or greater, and increased intimal medial thickness were also associated with a higher risk for prevalent SCI. Neither age nor sex modified the effect of any of the risk factors on SCI prevalence.

The finding that there is a link between elevated homocysteine may warrant consideration of including SCI as an outcome in future studies looking at the potential benefit of vitamin supplementation.

While the study's findings are not necessarily surprising, said Dr. Seshadri, they do underscore the need to follow guidelines for the early diagnosis and prevention of hypertension and atherosclerosis and their risk factors.

Unfortunately, she said, such guidelines have not been optimally implemented for a variety of reasons. "For instance, we know that over a lifetime, 9 out of 10 people will develop hypertension. When a condition is that common it tends to be regarded as the 'norm.' But we also know that the 10% of people who do not develop high blood pressure are healthier and live longer, better-quality lives. I would argue that even though a condition is regarded as the norm it should still be treated aggressively," she said.

The study was supported by the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke. The study authors have disclosed no relevant financial relationships.

Stroke. Published online June 26, 2008.

17. Women With Low-Risk Non-STEMI ACS: The Case for Conservative Care

Steve Stiles. From Heartwire — a professional news service of WebMD. July 2, 2008 — In the setting of unstable angina or non-ST-elevation MI (NSTEMI), women considered high risk, but not those at lower risk, benefit about as much as men from an early invasive management strategy—that is, routine referral for angiography with percutaneous coronary intervention (PCI) as appropriate—suggests a meta-analysis said to strengthen recent recommendations to use a more conservative approach in low-risk women [1]. Increased risk in the analysis of eight clinical trials was defined by elevations in levels of cardiac biomarkers, either creatine kinase MB (CK-MB) or troponin.

Men and high-risk women managed with the early invasive approach showed similar one-year reductions in the composite risk of death, MI, or rehospitalization for acute coronary syndrome (ACS), according to the authors, led by Dr Michelle O'Donoghue (Brigham and Women's Hospital, Boston, MA). "In contrast, an invasive strategy does not appear to substantially benefit women in the absence of biomarker elevation and moreover may potentially increase the risk of death or MI [myocardial infarction]," they write in the July 2, 2008 issue of the Journal of the American Medical Association.

Conservative management, as is typical in such analyses, consisted of optimal medical therapy as the primary approach, with coronary angiography only for patients with ongoing symptoms or myocardial ischemia at stress testing.

Recently updated guidelines [2] recommend a conservative strategy in lower-risk women and early invasive management in most other cases, O'Donoghue explained to heartwire. "This was primarily based on a signal of potential harm in earlier trials when an early invasive strategy was used in low-risk women," she said. "However, too few women were enrolled in each individual trial to reliably examine this strategy within subgroups."

The current analysis, based on eight trials that had randomized patients with unstable angina or NSTEMI to one of the two management strategies, strengthens the case made in the recent guidelines using a database of more than 10 000 patients, including about 3000 women, according to O'Donoghue.

Over all patients, the 12-month odds ratio for death, MI, or ACS rehospitalization with the invasive approach, compared with conservative management, was 0.78 (95% CI, 0.61-0.98); among those who showed elevations in either of the two biomarkers (ie, they were biomarker-positive), it was 0.59 (0.51-0.69), and among those who were biomarker-negative, 0.79 (0.58-1.06). Women showed only a modest risk reduction that didn't reach significance overall; those who were biomarker-positive showed a significant benefit, however, that was comparable to that among men.

Independent of sex, reductions in the ACS-rehospitalization rate accounted for most of the gain in the primary end point with the invasive strategy.

According to O'Donoghue, women who went to cardiac catheterization were significantly less likely than men to show obstructive coronary disease, even when they were positive for one of the biomarkers. Almost a quarter of women, but only 8% of men, showed no epicardial coronary disease. The observation that women seem to have less of the very thing PCI is intended to treat, O'Donoghue observed, may help explain why the invasive strategy appears less effective in women.

"Women were also more likely to have preexisting medical conditions, including diabetes, hypertension, and hyperlipidemia, that may place them at higher risk of complications after catheterization or bypass surgery," she said.

Their analysis has some limitations, the authors note, including their lack of access to patient-level data and heterogeneity across the trials with respect to standard therapies for ACS. The eight studies' publication dates ranged from 1994 to 2005, a time of great change in available antiplatelet agents and the rise of coronary stents in the US. Also, O'Donoghue observed, none were performed in the era of high-sensitivity troponin assays; how they might influence the risk stratification of women, she said, would have to be explored in prospective studies.

The meta-analysis seems to have had at least one unusual advantage, however. The principal investigators of all eight trials were enlisted to participate in the analyses and are listed as coauthors of the paper. "One advantage to having all of these terrific investigators on board was getting their feedback at every step along the way. They provided a lot of valuable insight," O'Donoghue said. "I believe this kind of collaborative approach strengthened the study and adds to the validity of the results."


[1] O'Donoghue M, Boden WE, Braunwald E, et al. Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: A meta-analysis. JAMA 2008; 300:71-80.

[2] Anderson JL, Adams CD, Antman EM, et al. ACC /AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines…J Am Coll Cardiol 2007; 50(7): e1-e157.

18. Inaccuracies Common in Medication Histories of Trauma Patients

NEW YORK (Reuters Health) Jun 24 - Results of a study published in the June 9 online issue of the Annals of Emergency Medicine suggest that inaccuracies are common in medication histories of trauma patients.

"The majority of inaccuracies were related to incomplete medical information available to or obtained by health care providers at the initial evaluation and resuscitation...and did not seem related to severity of injury," write Dr. S. Lee Miller and colleagues from Conemaugh Memorial Medical Center, Johnstown, Pennsylvania.

In a prospective study on 234 patients admitted to their rural level 1 trauma center, the researchers compared the accuracy of medication histories obtained in the emergency department with results of a medication reconciliation process performed by a clinical pharmacist after admission. In addition, they examined whether trauma-associated factors affected medication accuracy.

The authors report that medication lists recorded by the trauma team were accurate only 4% of the time. Medication lists recorded by admitting nurses were more accurate than those recorded by the trauma team (11% versus 4%). The clinical pharmacist found errors in medication name, strength, route, and frequency.

Of 20 patients admitted with Glasgow Coma Scale scores less than 13, none had accurate medication lists. Of 84 patients with Injury Severity Scores greater than 15, 70 had inaccurate medication lists. The wrong medications were ordered for 10 patients, and one adverse drug event (hypoglycemia) was identified.

"Medication-related adverse effects are the most expensive single 'disease' in this country at $76 billion," Dr. Miller said in an interview with Reuters Health. "Trauma is number 2 at $74 billion," he added. "It is only going to get more costly, both in human and dollar terms as the US population ages, until we develop a central repository of healthcare information."

Dr. Miller suggested that people should "always carry an accurate list of the medications (name, dose, route, frequency) [they] are on and, if possible, use only one pharmacy with a pharmacist you can actually speak with and have them review all of your meds (including samples, herbals, and OTC)."

Also, he said, "make sure your primary care physician is informed in a timely fashion of all of the medications that any specialist started you on."

"We need an accurate, secure, electronic medical record that can be accessed easily when we need care, but secure from unauthorized viewers," Dr. Miller concluded.

Ann Emerg Med 2008.

19. Predictive Value of T-wave Abnormalities at the Time of ED Presentation in Patients with Potential ACS

Lin KB, et al. Acad Emerg Med. 2008;15:537–543.

Objectives: T-wave abnormalities on electrocardiograms (ECGs) are common, but their ability to predict 30-day cardiovascular outcomes at the time of emergency department (ED) presentation is unknown. The authors determined the association between T-wave abnormalities on the presenting ECG and cardiovascular outcomes within 30 days of presentation in patients with potential acute coronary syndromes (ACSs).

Methods: This was a secondary analysis of a prospective cohort study of ED patients that presented with a potential ACS. Patients were excluded if they had a prior myocardial infarction, ST-segment elevation or depressions, right or left bundle branch block, or Q-waves on the initial ECG. Data included demographics, medical and cardiac history, and ECG findings including the presence or absence of T-wave flattening, inversions of 1–5 mm, and inversions >5 mm. Investigators followed the hospital course for admitted patients, and 30-day follow-up was performed on all patients. The main outcome was a composite of death, acute myocardial infarction, revascularization, coronary stenosis greater than 50%, or a stress test with reversible ischemia.

Results: Of 8,298 patient visits, 5,582 met criteria for inclusion: 4,166 (74.6%) had no T-wave abnormalities, 721 (12.9%) had T-wave flattening in two or more leads, 659 (11.8%) had T-wave inversions of 1–5 mm, and 36 (0.64%) had T-wave inversions beyond 5 mm. The composite endpoint was more common in patients with T-wave flattening (8.2% vs. 5.7%; p = 0.0001; relative risk [RR] = 1.4; 95% confidence interval [CI] = 1.1 to 1.9), T-wave inversions 1–5 mm (13.2% vs. 5.7%; p = 0.0001; RR = 2.4; 95% CI = 1.8 to 3.1), and T-wave inversions more than 5 mm (19.4% vs. 5.7%; p = 0.0001; RR = 3.4; 95% CI = 1.7 to 6.1), or any T-wave abnormality (10.8% vs. 5.7%; p = 0.0001; RR = 1.9; 95% CI = 1.6 to 2.3), even after adjustment for initial troponin. This association also existed in the subset of patients without known coronary artery disease.

Conclusions: In patients with potential ACS presenting to the ED, T-wave abnormalities are associated with higher rates of 30-day cardiovascular events.

20. Carboxyhemoglobin levels in carbon monoxide poisoning: do they correlate with the clinical picture?

Hampson NB, et al. Amer J Emerg Med. 2008;26:665-669.

It is commonly written that carboxyhemoglobin (COHb) measurements correlate with the clinical presentation of patients poisoned with carbon monoxide (CO). However, the evidence supporting this concept is scanty. The present study was performed to analyze COHb measurements in a large population of patients with CO poisoning to determine whether clinically significant correlates exist.

Records of all patients treated with hyperbaric oxygen for acute CO poisoning at a single private academic medical center from 1978 to 2005 were reviewed. The COHb measurements were analyzed with regard to sex, age, source of CO, loss of consciousness, endotracheal intubation, arterial pH, and death.

Data from 1603 CO-poisoned patients were reviewed, and 1407 were included in the final analysis. Statistically higher COHb measurements were associated with male sex (24.2% ± 11.2% vs 21.5% ± 11.6), adult age range (24.0% ± 11.0% vs 19.5% ± 10.3%), poisoning by CO from fires (25.7% ± 12.1%) or motor vehicles (22.7% ± 24.7%), loss of consciousness (24.3% ± 12.2% vs 22.3% ± 9.4%), lower arterial pH, and death (32.1% ± 12.8% vs 23.1% ± 0.9%).

Despite the fact that statistically significant differences in average COHb measurements were seen with regard to a number of variables, the clinical significance of these differences appeared to be minimal. Moreover, the utility of COHb measurements as predictors of clinical status in CO poisoning was not apparent. At least in part, this likely relates to delay and interval oxygen administration before obtaining COHb measurements.

21. Oral Cannabis Is an Ineffective Analgesic: Another good idea goes up in smoke

CHICAGO – A study published in the July issue of the Journal Anesthesiology discovered that oral cannabis (a form of medical marijuana) not only failed to alleviate certain types of pain in human volunteers but, surprisingly, it instead caused increased sensitivity to some forms of pain.

In their research, Birgit Kraft, M.D., and her colleagues from the Medical University of Vienna evaluated the analgesic potency of orally administered cannabis extract that included its main psychoactive component, Tetrahydrocannabinol (THC).

“The surprising result of our study was the absence of any kind of analgesic activity of THC-standardized cannabis extract on experimentally induced pain using well-established human model procedures,” said Dr. Kraft. “Our results also seem to support the impression that high doses of cannabinoids may even cause increased sensitivity in certain pain conditions.”

In Dr. Kraft’s study, 18 healthy female volunteers were given oral cannabis extract or active placebo and then evaluated for heat and electrical pain thresholds in skin areas of experimentally induced sun burn, an accepted approach to assessing responses to acute pain.

Previous studies have suggested that cannabis and THC may be effective in treating chronic pain, such as in cancer patients, patients with spinal cord injury, or those with multiple sclerosis. And, though inconsistent, some studies on patients with acute pain have suggested beneficial effects.

Consistent with the uncertainty about oral cannabis ingestion evaluated in this study, there is also uncertainty in the research community as to whether inhaled cannabis might prove more efficacious for pain relief than orally ingested cannabis.

Dr. Kraft’s results concerning oral cannabis for acute pain were seemingly conclusive. “From comparisons with previous clinical data, the lack of pain relief from the cannabis dosage and oral administration in our study cannot be considered the result of inadequate dosage or insufficient gastrointestinal absorption,” said Dr. Kraft. “The high levels of THC detected in the blood of our subjects as well as the occurrence of typical THC side effects argue for sufficient availability, and thus we draw the conclusion that THC was not effective in treating acute pain.”

Dr. Kraft stressed, however, that cannabis may still remain a viable option for certain types of chronic pain patients.

“Pain is a very complex and subjective phenomena,” she said. “Chronic pain has not only been shown to lead to changes in peripheral and central neuronal processing, but also to be associated with psychosocial problems, physical disorders, and functional disabilities. Recent studies have indicated that cannabis can be effective in treating certain types of chronic pain and helping patients to cope by improving quality of life.”

Dr. Kraft and her colleagues concluded that contemporary treatment strategies that rely on experimentally proven therapies still remain the best option for most patients suffering acute pain.

“In patients with acute pain, other analgesic drugs such as narcotics and non-steroidal anti-inflammatory drugs (NSAIDs) produce more reliable and potent analgesia,” she said.