Saturday, September 22, 2007

Lit Bits: September 22, 2007

From the recent medical literature...

1. Patients with Possible ACS Can Be Safely Admitted to Non-Cardiology Units

By Martha Kerr. NEW YORK (Reuters Health) Sept 05 - Patients presenting to the emergency department (ED) with possible acute coronary syndrome (ACS) need not be held there until there is an available bed in the cardiology unit.

Patients with suspected ACS who are admitted to a family practice unit have similar outcomes as those admitted to a cardiology unit, according to a report published in the Annals of Emergency Medicine and available online.

The original study on the impact of implementation of the Agency for Healthcare Policy and Research's Unstable Angina Guidelines, conducted between 2000 and 2001, showed that the guidelines had no significant impact on emergency physicians' triage decisions.

In the current analysis, Dr. David A. Katz, of the University of Iowa, Iowa City, and colleagues determined whether systematic use of the Agency for Healthcare Policy and Research recommendations for risk stratification would improve physician decision making in 544 ED patients admitted with symptoms of possible ACS after a "nondiagnostic initial evaluation."

After 30 days, Dr. Katz's team reviewed the medical records and conducted telephone surveys of the patients to assess the incidence of adverse events and in-hospital and follow-up care.

One third (34%) of admitted patients had confirmed ACS.

"The incidence of ED revisits and rehospitalizations, functional status, and adverse cardiovascular events were similar" in patients admitted to the cardiology service and those who were admitted to another service, the investigators found.

Patients admitted to a cardiology service were 2.7 times more likely to undergo evaluation for ischemic heart disease than those admitted to a noncardiology service.

"Although patients admitted to a cardiology bed received more aggressive diagnostic testing than those admitted to a non-cardiology service bed in our study, the overall 30-day outcomes were very similar," Dr. Katz told Reuters Health. In addition, the patients on a cardiology unit "were not more likely to receive recommended therapies."

"According to a recent Institute of Medicine report, 'Hospital-based Emergency Care: At the Breaking Point,' the most common contributor to ED crowding is the inability to move admitted patients from the ED to inpatient hospital beds," Dr. Katz said.

"These results should be confirmed in larger studies with longer follow-up of patient outcomes," he noted. In the meantime," given the volume of patients with possible ACS treated in emergency departments - approximately 5 million every year - and the paucity of cardiology beds at certain times, emergency physicians can safely admit many of these patients to non-cardiology units and possibly reduce overcrowding in their emergency departments."

Full-text (free for now) from Ann Emerg Med, on-line articles in press: http://www.annemergmed.com/webfiles/images/journals/ymem/dkatz.pdf

2. Beta-Blockers Are Associated With Reduced Risk of AMI after Cocaine Use

Dattilo PB, et al. Ann Emerg Med. 2007; in press.

Study objective: Beta-Blocker use is associated with coronary artery spasm after cocaine administration but also decreases mortality in patients with myocardial infarction or systolic dysfunction. We conduct a retrospective cohort study to analyze the safety of beta-blockers in patients with positive urine toxicology results for cocaine.

Methods: The cohort consisted of 363 consecutive telemetry and ICU patients who were admitted to a municipal hospital and had positive urine toxicology results for cocaine during a 5-year period (307 patients). Fifteen patients with uncertain history of beta-blocker use before admission were excluded. The primary outcome measure was myocardial infarction; secondary outcome measure was inhospital mortality. Logistic regression analysis using generalized estimating equations models and propensity scores compared outcomes.

Results: Beta-Blockers were given in 60 of 348 admissions. The incidence of myocardial infarction after administration of beta-blocker was significantly lower than without treatment (6.1% versus 26.0%; difference in proportion 19.9%; 95% confidence interval [CI] 10.3% to 30.0%). One of 14 deaths occurred in patients who received beta-blockade (incidence 1.7% versus 4.5% without beta-blockade; difference in proportion 2.8%; 95% CI –1.2% to 6.7%). Multivariate analysis showed that use of beta-blockers significantly reduced the risk of myocardial infarction (odds ratio 0.06; 95% CI 0.01 to 0.61).

Conclusion: In our cohort, administration of beta-blockers was associated with reduction in incidence of myocardial infarction after cocaine use. The benefit of beta-blockers on myocardial function may offset the risk of coronary artery spasm. [Ann Emerg Med. 2007;xx:xxx.]

Full-text (free for now) from Ann Emerg Med, on-line articles in press: http://www.annemergmed.com/webfiles/images/journals/ymem/dattllo.pdf

3. TZDs: Good for the Glucose, but Bad for the Heart—Pioglitazone and Rosiglitazone: Different Effects on Heart Disease

Two new meta-analyses in JAMA confirm the increased risk for heart failure associated with pioglitazone and rosiglitazone, but they show disparate results for other cardiovascular outcomes.

In an analysis of data from 19 randomized controlled trials involving some 16,000 patients with type 2 diabetes, those randomized to pioglitazone showed an 18% reduced risk for the composite of death, MI, and stroke. There was also a nonsignificant reduction in risk for MI alone. The drug manufacturer contributed all data.

Another research group analyzed four long-term, randomized controlled trials of rosiglitazone in which cardiovascular safety was a prespecified endpoint; some 14,000 patients were included. Overall, rosiglitazone increased the risk for MI by 42%.

Editorialists note that the increased risk for MI observed with rosiglitazone is similar to the risk reported in a recent, much publicized meta-analysis. They add that "with many other available oral agents for diabetes, the potential benefit of [thiazolidinediones] requires reevaluation."

For these two JAMA abstracts, see TOC for Sept 12, 2007: http://jama.ama-assn.org/contents-by-date.0.dtl

4. FDA Issues Warning on Cardiovascular Effects of Haloperidol

The FDA is warning clinicians about the risks for cardiovascular side effects and sudden death from haloperidol.

The agency says there are "at least 28 case reports" of QT prolongation and Torsades de Pointes in the literature associated with the antipsychotic drug, "especially when given intravenously"; some cases have been fatal. A 2005 postmarketing study conducted for the Italian drug authority, but only recently submitted to the FDA by Johnson & Johnson, found 13 additional cases. The FDA notes that the drug is often used intravenously off-label, especially in intensive care units, to treat severe agitation.

Label warnings will be strengthened, the FDA says, and it recommends ECG monitoring if the drug is used intravenously. The FDA urges particular caution in patients with other QT-prolonging conditions, such as electrolyte imbalance (especially hypokalemia and hypomagnesemia).

FDA alert (Free): http://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm

5. Randomized Trial of Single-Dose IM Dex Compared With 5 days of Prednisolone for Children With Acute Asthma

Gordon S, et al. Pediatric Emergency Care. 2007;23:521-527.

Objectives: To compare the clinical efficacy of single-dose intramuscular (IM) dexamethasone phosphate (dex) to a 5-day course of oral prednisolone for the treatment of moderate asthma exacerbations in young children discharged from the emergency department (ED).

Methods: We performed a prospective, randomized trial in children aged 18 months to less than 7 years with asthma who presented to the ED with a clinical asthma score of 3 to 7 on a 9-point scale. Children were randomized to 1 dose of IM dex (0.6 mg/kg, maximum 15 mg) or oral prednisolone (2 mg/kg, maximum 50 mg) once daily for 5 days. The primary outcome, measured only for patients discharged from the ED, was change in asthma score from ED presentation to 4-day follow-up examination, as assessed by a physician masked to group assignment. We assessed secondary clinical course outcomes by a structured interview at 4 and 14 days.

Results: Eighty-eight patients were appropriately randomized to dex and 93 to prednisolone. Group characteristics were similar at baseline. Among those discharged from the ED, 62 (90%) of 69 and 64 (90%) of 74 patients in the dex and prednisolone groups, respectively, were reassessed at 4 days for the primary outcome. The mean change in total asthma score at 4-day follow-up was 3.6 in the dex group and 3.4 in the prednisolone group (difference, 0.2; 95% confidence interval, -0.4 to 0.7). Of patients initially discharged, 5.9% of dex patients and 4.1% of prednisolone patients were admitted before the 2-week follow-up (difference, 1.8%; 95% confidence interval, -5.4% to 9.0%).

Conclusions: A single dose of IM dex showed no clinically meaningful difference in outcomes compared with a 5-day course of oral prednisolone for the treatment of moderate acute asthma exacerbations in young children who are discharged from the ED.

6. Association of Overweight With Increased Risk of Coronary Heart Disease Partly Independent of Blood Pressure and Cholesterol Levels: A Meta-analysis of 21 Cohort Studies Including More Than 300,000 Persons

Bogers RP, et al. Arch Intern Med. 2007;167:1720-1728.

Background: The extent to which moderate overweight (body mass index [BMI], 25.0-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI, 30.0) are associated with increased risk of coronary heart disease (CHD) through adverse effects on blood pressure and cholesterol levels is unclear, as is the risk of CHD that remains after these mediating effects are considered.

Methods: Relative risks (RRs) of CHD associated with moderate overweight and obesity with and without adjustment for blood pressure and cholesterol concentrations were calculated by the members of a collaboration of prospective cohort studies of healthy, mainly white persons and pooled by means of random-effects models (RRs for categories of BMI in 14 cohorts and for continuous BMI in 21 cohorts; total N = 302 296).

Results: A total of 18 000 CHD events occurred during follow-up. The age-, sex-, physical activity–, and smoking-adjusted RRs (95% confidence intervals) for moderate overweight and obesity compared with normal weight were 1.32 (1.24-1.40) and 1.81 (1.56-2.10), respectively. Additional adjustment for blood pressure and cholesterol levels reduced the RR to 1.17 (1.11-1.23) for moderate overweight and to 1.49 (1.32-1.67) for obesity. The RR associated with a 5-unit BMI increment was 1.29 (1.22-1.35) before and 1.16 (1.11-1.21) after adjustment for blood pressure and cholesterol levels.

Conclusions: Adverse effects of overweight on blood pressure and cholesterol levels could account for about 45% of the increased risk of CHD. Even for moderate overweight, there is a significant increased risk of CHD independent of these traditional risk factors, although confounding (eg, by dietary factors) cannot be completely ruled out.

7. Do All Children with Pyelonephritis Require Hospital Admission?

Treatment with oral antibiotics alone is as effective as standard treatment with parenteral antibiotics followed by oral antibiotics.

Risk for sepsis and long-term renal scarring has led some authorities to recommend inpatient treatment with parenteral antibiotics for young children in whom pyelonephritis is suspected. In a multicenter open-label study, investigators in Italy randomized 502 children (age range, 1 month to 7 years) with pyelonephritis to receive either oral amoxicillin plus clavulanic acid (50 mg/kg amoxicillin in 3 divided doses daily) for 10 days or standard treatment with parenteral ceftriaxone (50 mg/kg in a single daily dose) for 3 days followed by oral amoxicillin plus clavulanic acid (50 mg/kg in 3 divided doses daily) for 7 days. All participants were admitted to the hospital until defervescence or for at least 3 days. Children with severe sepsis, dehydration, vomiting, or history of pyelonephritis or abnormal ultrasound were excluded.

About 20% of patients were lost to follow-up by 12 months. Among the remaining participants, the incidence of scarring as detected by scintigraphy did not differ significantly between the group that received standard treatment and the group that received oral treatment only (17.7% and 13.7%). Secondary outcomes — time to fever reduction, amount of reduction in inflammatory indices, and percentage of patients with sterile urine after 72 hours — also were similar in the two groups. Escherichia coli was identified as the pathogen in 94.4% of positive urine cultures.

This study suggests that children with first-time urinary tract infections with fever who are otherwise healthy, clinically stable, and not vomiting can be treated as outpatients, provided that local antibiotic sensitivities are considered, caretakers are reliable, and close follow-up can be arranged.

As a cannula is often in place for initial sampling of blood cultures and electrolytes, most sick children will probably receive initial parenteral treatment. Of note, 10% of the children in Montini's study who started oral treatment were switched to intravenous treatment due to diarrhoea or vomiting caused by antibiotics or intercurrent rotavirus gastroenteritis.

Montini G, et al. BMJ. 2007;335:386. Abstract: http://www.bmj.com/cgi/content/abstract/335/7616/386

8. Septic Shock — What’s the Best Vasopressor?

Epinephrine alone and norepinephrine plus dobutamine had similar efficacy and safety in this multicenter, randomized, controlled trial.

Background
International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock.

Methods
This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mmHg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat.

Findings
There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0·31; relative risk 0·86, 95% CI 0·65–1·14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0·69), at hospital discharge (84 [52%] vs 82 [49%], p=0·51), and by day 90 (84 [52%] vs 85 [50%], p=0·73), time to haemodynamic success (log-rank p=0·67), time to vasopressor withdrawal (log-rank p=0·09), and time course of SOFA score. Rates of serious adverse events were also similar.

Interpretation
There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

Annane D, et al. The Lancet 2007; 370:676-684.

9. Symptom Benefits, but no Life Savings with Noninvasive Ventilation for Acute Cardiogenic Pulmonary Edema

September 4, 2007 (Vienna, Austria) - Noninvasive ventilation, in the form of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NIPPV) may speed up the recovery of patients with acute cardiogenic pulmonary edema, but it doesn't help them live any longer, results from the 3CPO trial show. Both CPAP and NIPPV force air at different pressures into the patients' airways, thereby alleviating some of the effort of inhalation.

Presenting the results here at the European Society of Cardiology Congress 2007, Dr David Newby (Royal Infirmary, Edinburgh, Scotland) said that this is the first evidence from a sizable trial that a practice widely in use may not actually have an impact on hard clinical outcomes.

"Noninvasive ventilation does make the patient feel better in the acute setting, so in the first few hours, it is a very useful treatment, irrespective of which type you're using," Newby commented. "However, it is not a life-saving treatment."

No major benefits, no major harm

The 3CPO study was conducted at 26 sites in the UK, with patients presenting with acute cardiogenic pulmonary edema randomized to standard oxygen therapy, CPAP, or NIPPV, with physicians encouraged to use nitrates and diuretics. In all, 1156 patients were recruited and randomized to one of the three treatments.

While both noninvasive ventilation strategies were better than standard therapy for reducing several physiologic end points, including respiratory rate, heart rate, and acidosis, with no differences between the two types of ventilation approaches, neither therapy alone or in combination was better than standard oxygen therapy at reducing seven- or 30-day mortality.

There were no differences in subsequent MI or hospitalization rates across all three treatment strategies, Newby noted, and all forms of therapy were well tolerated.

Newby emphasized that previous randomized trials have all been very small, with a "plethora of meta-analyses"--many of which have suggested a mortality reduction with noninvasive ventilation--"dangerously close to outnumbering the randomized studies." The dearth of large randomized trials is conspicuous for a strategy whose use dates back 70 years, when investigators used a standard household vacuum cleaner and warned physicians of the need to make sure dust was adequately expelled from the vacuum before it was used to force air into a patient's lungs.

Seven decades later, the 3CPO trial should help put some of the misconceptions about administering higher-pressure oxygen to rest, he said.

"When patients come into the hospital with fluid on the lung, they're often in great distress, they're breathless, they're clammy: it's a very uncomfortable, unpleasant condition to be in. So the more rapid resolution of their symptoms is a beneficial thing. It's a simple treatment, just applying a mask, so it's a useful method for relieving suffering," Newby explained. "But in terms of the longer-term outcomes, it doesn't cause any harm, but it doesn't cause much benefit. My message is, use it to relieve suffering in the early hours of this severe illness, but don't overinterpret its overall benefit."

That message, however, goes against some solidly entrenched faith in the benefits of noninvasive ventilation in this patient group. Dr G Filippatos (Athens University Hospital, Attikon, Greece), the discussant for the study, said that when he first saw the results of the trial, he had trouble believing it was negative. He still believes there may be some patients who, in the right hands, might still experience hard clinical benefits from noninvasive ventilation.

But he also pointed out that the improvements in physiologic end points reported by Newby et al, while statistically significant, may not be clinically meaningful, because the absolute differences heart rate and ventilation between standard oxygen therapy and ventilation with pressure were very small.

"In clinical practice, it's hard to find clinical significance in a difference of one respiration per minute," Filippatos said.

10. Diagnosis and Guided Reduction of Forearm Fractures in Children Using Bedside Ultrasound

Chen L, et al. Pediatric Emergency Care. 2007;23:528-531.

Background: Forearm fractures are common injuries in children. Displaced and angulated fractures usually require reduction. Ultrasound diagnosis and guided reduction offer several potential advantages: (1) the procedure does not involve ionizing radiation; (2) compared with fluoroscopy units, the newer ultrasound units are more portable; and (3) repeated studies can be obtained easily and quickly.

Objective: The primary objective was to investigate the accuracy of emergency department (ED) physician-performed ultrasound in the diagnosis and guided reduction of forearm fractures in children.

Methods: Children suspected of having forearm fractures were enrolled prospectively in an urban pediatric ED from June 2004 to November 2004. A bedside ultrasound of the forearm bones was performed by a pediatric emergency medicine physician. Ultrasound findings were compared with radiograph findings. Reductions were performed under ultrasound guidance. Postreduction radiographs were performed. Any need for further reduction was recorded.

Results: During the study period, 68 patients were enrolled. Radiographs revealed forearm fractures in 48 patients. Twenty-nine subjects had fractures of the radius alone; 17 had fractures of both the radius and the ulna, and 2 had fractures of the ulna alone. Ultrasound revealed the correct type and location of the fracture in 46 patients. The sensitivity for the detection of forearm fractures was 97% (95% confidence interval [CI], 89%-100%) using ultrasound. The specificity was 100% (95% CI, 83%-100%). Twenty-six subjects underwent reduction of their fractures in the ED. Two subjects required re-reduction after the initial reduction. The initial success rate of ultrasound-guided reduction was 92% (95% CI, 75%-99%).

Conclusions: Bedside ultrasound performed by pediatric emergency medicine physicians is a reliable and convenient method of diagnosing forearm fractures in children. It is also useful in guiding the reduction of these fractures.

11. Rocephin Should Not Be Administered with Calcium in Patients of Any Age

Rocephin (ceftriaxone) and intravenous calcium-containing solutions should not be given within 48 hours of each other — "even via different infusion lines at different sites" — Roche has advised healthcare professionals in a letter to the FDA.

The warning applies to treatment in patients of any age. Previously, the manufacturer had warned about mixing ceftriaxone with calcium in newborns, given reports of at least eight fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys. To date, there have been no reports of such reactions in older patients.

FDA Safety Alert: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin

12. New CPR Promises Better Results by Compressing Abdomen, Not Chest

By Anthony J. Brown, MD. NEW YORK (Reuters Health) Sept 21 - Performing "only rhythmic abdominal compression" (OAC) rather than standard chest compressions may improve the coronary perfusion achieved during cardiopulmonary resuscitation (CPR), according to an animal study reported in the September issue of the American Journal of Emergency Medicine.

"The biggest finding is that OAC-CPR provides blood flow AND artificial respiration," lead author Dr. Leslie Geddes, from Purdue University in West Lafayette, Indiana, told Reuters Health. As such, "OAC-CPR does not require chest compression, nor does it require mouth-to-mouth breathing," which "eliminates the risk of rib fractures and transfer of infection."

Previous research has shown that conventional CPR has success rates of just 5% to 10%. Moreover, for every 1 minute that transpires before CPR is started, the chance of success falls 10%.

"In other words, at 10 minutes, the resuscitation is absolutely ineffective," Dr. Geddes said in a statement. "Any medical procedure that had that low a success rate would be abandoned right away. But the alternative is not very good, either: don't do CPR and the person is going to die."

With OAC CPR, the compressions work by forcing blood out of the vascular bed supplying the abdominal organs, which is known to contain about 25% of the total blood volume. This blood is then redirected to other sites, including the coronary circulation.

In their study, Dr. Geddes' team tested OAC CPR on pigs with experimentally induced ventricular fibrillation. The coronary perfusion index, which is calculated using aortic and right-atrial pressure curves, was used to assess perfusion effectiveness.

The researchers found that 60% more coronary perfusion was achieved with OAC CPR than with standard chest-compression CPR, using the same amount of effort. Moreover, there was no evidence that OAC damaged the visceral organs, and it naturally avoided the risk of rib fracture.

Geddes A, et al. Amer J Emerg Med 2007;25:786-790.

13. Do all fractures need full immobilisation? Evidence Based Case Report

Glasziou P. BMJ 2007;335:612-613 (22 September). Centre for Evidence-based Medicine, Department of Primary Health Care, University of Oxford, Oxford OX3 7LF

As I was about to start my morning general practice clinic, the receptionist told me of a patient who was coming in with an injury and handed me a faxed report from radiology, which stated: "possible fracture of the radial head." The "possible" suggested it was undisplaced or minimally displaced, so I wondered if it needed treating at all. While waiting for the first patient to arrive and sipping my tea, I checked the orthopaedics texts in my room and did a PubMed search.

I went to the Clinical Queries section of PubMed Central (which is bookmarked on my Firefox toolbar) and used the narrow version of the "therapy" filter (which filters for randomised trials). I entered search terms to describe the condition "fracture and radial and head," which brought up seven studies. Two of these studies were not trials and three were not relevant (two looked at different types of internal fixation, and one looked at different methods of reduction), which left two that were relevant. I used the most recent study (2002) [1] because it was more relevant to this patient's problem and I had access to the full text. I had access only to the abstract of the second trial, [2] but this seemed to be consistent with the findings of the first trial. My search took only a few minutes.

The trial [1] randomised 60 patients into two groups. One group was treated with rest in a broad sling for five days followed by mobilisation, and the other was treated with immediate mobilisation and an exercise programme that started 24 hours after injury. The randomisation process was haphazard rather than randomised, but baseline characteristics were not significantly different between the two groups (although the immediate mobilisation group seemed to have had more minor fractures). Follow-up assessments were done by an independent observer who was blinded to treatment, but the authors did not mention loss to follow-up. As is usual, the trial was not perfect, but none of the flaws seemed sufficient to invalidate the results.

All fractures in both groups united without problems. At the end of the first week, the early mobilisation group had slightly more pain (10 v 6 on a 25 point scale) but better range of motion (flexion of 112 degrees v 98 degrees). However, most measures showed no difference at that time or at further follow-up (four and 12 weeks).

When I saw the patient, it was clear that she had tenderness over the radial head but still had a full—though somewhat painful—range of elbow movement. I explained the choices to her—that immobilisation would help a little with the pain but make no long term difference, and it would mean that temporarily her arm would be a little stiffer. She opted for no immobilisation with a simple bandage for comfort. Of course, I could have called the local orthopaedic registrar, and that is often the wise thing to do. But once I had seen the patient I was sure that this was just a "minor" fracture that could be dealt with in primary care.

Clinical training and practice is replete with heuristics—rules of thumb—in both diagnosis and treatment. For example, "beware the unilateral red eye," "if a child fails to speak by 16 months then assume that the child is deaf until proved otherwise," and "where there is pus, let it out." One treatment rule we use for soft tissue injury is RICE (rest, ice, compression, and elevation). However, is this rule based on good research? Recently some colleagues and I questioned this advice, and did a systematic review of whether immobilisation is best for the treatment of limb injuries. We identified 49 trials, and we found that less rest and more mobility seemed to be better, even in the 14 studies of fractured limbs. [3] Subsequently, a trial showed that short arm plasters were preferable to long arm plasters for forearm fractures in children. Some people have suggested we change the rule from RICE to MICE (mobilisation, ice, compression, elevation). However, applying this general principle to individual patients and injuries is not always straightforward.

I was puzzled about exactly when I can apply the MICE heuristic to injuries, but a helpful reviewer suggested that, "The majority of hand fractures and radial head fractures are now treated by mobilisation. Many minor lower limb fractures are similarly treated. In many distal radial fractures and most proximal humeral and clavicle fractures, immobilisation is simply for pain relief." With that clarified, I am now left wondering how many other mnemonics provide misleading advice? Indeed, a colleague—Carl Heneghan—pointed out that the C of RICE is also questionable, with a trial in ankle sprains showing that compression bandages provide no advantage and lead to a greater use of analgesia. [4]


1. Liow RY, Cregan A, Nanda R, Montgomery RJ. Early mobilisation for minimally
displaced radial head fractures is desirable. A prospective randomised study of
two protocols. Injury 2002;33:801-6.
2. Unsworth-White J, Koka R, Churchill M, D'Arcy JC, James SE. The non-operative management of radial head fractures: a randomized trial of three treatments. Injury 1994;25:165-7.
3. Nash CE, Mickan SM, Del Mar CB, Glasziou PP. Resting injured limbs delays recovery: a systematic review. J Fam Pract 2004;53:706-12.
4. Watts BL, Armstrong B. A randomised controlled trial to determine the effectiveness of double Tubigrip in grade 1 and 2 (mild to moderate) ankle sprains. Emerg Med J 2001;18:46-50.
14. Self-reported Medication Adherence and Cardiovascular Events in Patients with Stable Coronary Heart Disease: The Heart and Soul Study

Gehi AK, et al. Arch Intern Med. 2007;167:1798-1803.

Background: Nonadherence to physician treatment recommendations is an increasingly recognized cause of adverse outcomes and increased health care costs, particularly among patients with cardiovascular disease. Whether patient self-report can provide an accurate assessment of medication adherence in outpatients with stable coronary heart disease is unknown.

Methods: We prospectively evaluated the risk of cardiovascular events associated with self-reported medication nonadherence in 1015 outpatients with established coronary heart disease from the Heart and Soul Study. We asked participants a single question: "In the past month, how often did you take your medications as the doctor prescribed?" Nonadherence was defined as taking medications as prescribed 75% of the time or less. Cardiovascular events (coronary heart disease death, myocardial infarction, or stroke) were identified by review of medical records during 3.9 years of follow-up. We used Cox proportional hazards analysis to determine the risk of adverse cardiovascular events associated with self-reported medication nonadherence.

Results: Of the 1015 participants, 83 (8.2%) reported nonadherence to their medications, and 146 (14.4%) developed cardiovascular events. Nonadherent participants were more likely than adherent participants to develop cardiovascular events during 3.9 years of follow-up (22.9% vs 13.8%, P = .03). Self-reported nonadherence remained independently predictive of adverse cardiovascular events after adjusting for baseline cardiac disease severity, traditional risk factors, and depressive symptoms (hazards ratio, 2.3; 95% confidence interval, 1.3-4.3; P = .006).

Conclusions: In outpatients with stable coronary heart disease, self-reported medication nonadherence is associated with a greater than 2-fold increased rate of subsequent cardiovascular events. A single question about medication adherence may be a simple and effective method to identify patients at higher risk for adverse cardiovascular events.

15. Febrile seizures in young children: What role is played by excess fluids?

Cann SAH. Med Sci Monit 2007; 13(9): RA159-167.

Febrile seizures are a common occurrence in young children with incidence rates varying from 3–14%, depending on the geographic region. Studies have suggested that an elevated temperature is a factor in their development, though other factors may synergistically lower the seizure threshold. While it is recognized that excessive or rapid dilute fluid intake can cause seizures in young children, and in adults during strenuous physical activity, less focus has been paid to its involvement during febrile illnesses.

Young children are more vulnerable to the development of febrile seizures due to their small skull size relative to brain volume. In animals, reduced serum sodium levels have been shown to lower the threshold to convulsive stimuli, while hypertonic saline has been shown to rapidly reverse these effects. Similarly vasopressin, frequently elevated during acute infections, enhances fluid retention and may also be a precipitating factor for febrile seizures. Although an elevated temperature may augment seizure risk, antipyretics have not been shown to prevent them. In fact, some may increase seizure risk through a reduction in urine output. It has long been observed that fluid retention occurs during febrile infections, followed by diuresis during convalescence. This characteristic observation led to recommendations for restricted fluid intake during acute infections dating back more than 2,000 years.

Only recently has there been a return to restricted fluid intake for patients with potentially reduced free water excretion. Further studies are required to determine the role of the overall fluid balance in the etiology of childhood febrile seizures.

Full-text (free) through this link: http://www.medscimonit.com/medscimonit/modules.php?name=Current_Issue&d_op=summary&id=9908

16. Efficacy and Impact of IV Morphine before Surgical Consultation in Children with RLQ Pain Suggestive of Appendicitis: A Randomized Controlled Trial

Bailey B, et al. Ann Emerg Med 2007; 50:371-378.

Although many studies have demonstrated that opioids do not interfere with the diagnosis of acute abdomen, early analgesia is not yet routine practice, particularly for children. In 8- to 18-year-old children with moderate to severe right lower quadrant abdominal pain, does morphine (0.1 mg/kg intravenously) delay the surgical disposition decision? In this 90-person randomized trial, intravenous morphine did not delay surgical decision-making, a particularly compelling finding, given the high prevalence of appendicitis in the sample (66%). Placebo effect was unusually strong in this study, resulting in pain relief similar to that of morphine.

This study provides persuasive evidence that physicians should routinely provide analgesia to children with possible appendicitis. Research we’d like to see: Now that it seems well established that lower doses of opioids are safe in acute abdominal pain, it appears justified to study analgesic titration to a greater degree of pain relief.

17. Is Epinephrine Harmful When Used With Anesthetics for Digital Nerve Blocks?

Waterbrook AL, et al. Ann Emerg Med 2007; 50:472-475

Patients with injuries to the fingers and toes commonly present to the emergency department. These injuries tend to be painful, and anesthesia is often achieved by digital nerve blocks. There is an established dogma that the use of epinephrine with local anesthetics for digital blocks is dangerous because it may lead to vascular insufficiency and necrosis. Most emergency medicine textbooks recommend against using epinephrine in digital blocks, despite several prospective trials and comprehensive reviews of the literature that show evidence to the contrary. One study using color Doppler ultrasonography demonstrated that blood flow to the digit was fully restored in 60 to 90 minutes, without any local or systemic complications after digital anesthesia with epinephrine. We reviewed the available evidence to evaluate the safety of using epinephrine in conjunction with local anesthetics for digital blocks.

The Bottom Line
There are 2 published prospective, randomized, clinical trials evaluating the use of epinephrine in conjunction with local anesthetics for digital blocks. Although these studies report no complications, improved hemostasis, decreased pain, increased duration of anesthesia, and decreased anesthetic requirement in subjects receiving epinephrine, the investigations were small. There is also a small prospective study evaluating digital blood flow after local anesthesia with epinephrine was administered. This study reveals full return of blood flow to the digits at 60 or 90 minutes and resulted in no local or systemic complications.

In addition, there are 3 comprehensive literature reviews that fail to report any cases of digital necrosis caused by the use of commercial lidocaine-epinephrine anesthetic. Cases in which digital necrosis did occur were attributable to other causes, such as nonstandardized epinephrine concentrations, use of expired and possibly acidic procaine, inappropriate usage of tourniquets, overdistention of the tissues, and poor surgical technique. According to current evidence, we conclude that the use of epinephrine with lidocaine in standard commercial concentrations for digital blocks is not harmful and is likely advantageous.

18. Emergency Treatment of Hemorrhagic Complications of Thrombolysis

Rasler F. Ann Emerg Med.2007;50:485.

Symptomatic intracerebral hemorrhage following intravenous thrombolysis for stroke occurred in 6% of patients, with a 3% risk of death during the original NINDS study. Higher rates of bleeding have been found with deviations from the study protocol. This understandably causes hesitation when recommending thrombolysis for acute stroke. Despite the known risk, many emergency departments (EDs) and intensive care/coronary care units are not prepared to treat hemorrhagic complications with the urgency they require. Although specific reversal agents are available, when a critical hemorrhage happens you don’t have time to begin thinking about treatment options or call a hematologist for advice.

Whether thrombolysis is used for stroke, heart attack or pulmonary embolism, every hospital would benefit from having written guidelines immediately available in the ED and intensive care/coronary care units for the complications. A specific table of treatment guidelines was created at our institution (see URL below), which may be copied. We keep the table in a visible location with our “thrombolytic box,” rather than just being attached to a manual with other hospital protocols.

Nurses and physicians must be diligent in watching for early signs of intracranial and other bleeding complications, and ready to initiate the guidelines. Based on clinical signs alone, it may be necessary to stop the thrombolytic infusion and begin thawing cryoprecipitate even before an immediate computed tomographic scan is done. Time is the critical issue when beginning thrombolysis, and this same urgency is essential to help limit damage if hemorrhage occurs.

Elevated blood pressure following intracranial hemorrhage must also be addressed to potentially limit hematoma expansion. Avoid rapid blood pressure reduction and use 30° head elevation. Acute treatment goals have not yet been established and each patient should be individualized. Recommendations for treating spontaneous intracerebral hemorrhagic (bleeding not caused by thrombolysis), suggest a systolic blood pressure less than 180 and mean arterial pressure less than 130 mm. Bleeding associated with thrombolysis, however, may benefit from lower pressure.

Seizure prophylaxis should be considered because there is a 10% risk of early seizure, usually with an early onset, and especially with lobar hemorrhage. If intubation is performed, the usual measures to minimize its acute effect on intracranial pressure should be used. Activated Factor VII theoretically offers an option to treating bleeding associated with thrombolysis, but will require study before any recommendations can be made.

For the Table, see: http://www.annemergmed.com/article/PIIS0196064407006804/fulltext

19. Use of a triage pain protocol in the ED

Fosnocht DE, et al. Amer J Emerg Med. 2007;25:791-793.

Purposes
This study was designed to evaluate the ability of a triage pain protocol to improve frequency and time to delivery of analgesia for musculoskeletal injuries in the emergency department (ED).

Basic Procedures
Frequency and time to analgesic administration were measured before and after use of a triage pain protocol. The protocol allowed analgesic medications to be given at the time of triage.

Main Findings
Time to medication administration was 76 minutes (95% confidence interval [CI], 68-84 minutes) before and 40 minutes (95% CI, 32-47 minutes) after the protocol. Five hundred fifty-nine (70%) of 800 patients received analgesics using the protocol compared with 212 of 471 (45%) patients prior.

Principal Conclusions
Use of a triage pain protocol increased the number of patients with musculoskeletal injury who received pain medication in the ED. Use of the protocol also resulted in a decrease in the time to analgesic medication administration.

20. Ophthalmic diagnoses in the ED: optic neuritis

Germann CA, et al. Amer J Emerg Med. 2007;25:834-837.

Optic neuritis is the most common cause of decreased vision due to optic nerve dysfunction in patients who are 20 to 40 years of age. Optic neuritis, or inflammation of the optic nerve, is primarily due to idiopathic demyelination. Demyelinative lesions seen in optic neuritis are not unlike those seen in plaque associated with multiple sclerosis. In fact, acute inflammatory demyelination of the optic nerve commonly occurs as an initial manifestation of multiple sclerosis.

Key features of optic neuritis include a vision loss occurring over 1 to 10 days, color vision impairment, eye pain with motility, and an afferent pupillary defect. This significant diagnosis can be challenging to an emergency physician as it is relatively infrequently observed.

21. In Treating Migraine in the ED, What Influences our Drug Choices?

Hurtado T, et al. Headache. 2007;47:1134-1143.

Study Objective.—To evaluate the factors that influence clinicians' choices of parenteral medications in the emergency department (ED) management of migraine headache.

Background.—Migraine headache is a common problem in the United States. Many migraineurs require periodic ED management. Though a large variety of parenteral medications are used by ED clinicians in the treatment of migraine, little research has been directed to the reasons why providers use the medications they do.

Methods.—This study used a self-administered questionnaire for providers from 3 geographically distinct EDs to evaluate their pharmacotherapeutic preferences in the treatment of uncomplicated migraine based on a fictitious scenario. Factors influencing medication choices were rated on a 5-point Likert scale and analyzed descriptively. Hypothetical practice patterns from the questionnaires were compared with actual practice patterns from a prior study from the same institutions.

Results.—Eighty-three percent of surveys were returned, the majority from attending physicians (71%), as their initial drugs-of-choice providers preferred dopaminergic antiemetics (93%) and parenteral NSAIDs (22%). If initial therapy failed, opioids (40%) with nonspecific antiemetics (24%) were preferred as second-line agents. Choice of therapy was influenced (in descending order) by medication availability and its antimigraine properties, the providers' training, current departmental practice patterns, and national practice guideline recommendations. Opioid use was influenced by patients' failure to respond to ED and outpatient alternatives and the presence of contraindications/intolerances to non-opioids. When these results were compared to a prior study of actual practice patterns, a range of discordance was observed, which varied significantly by institution.

Conclusion.—Emergency clinicians report that a variety of factors influence their parenteral pharmacotherapy in the management of patients with migraine headache. The comparison of hypothetical practice patterns with actual practice patterns reveals a range of institution-specific discordance. There is discordance between providers' responses to a fictitious scenario and their previously recorded practice patterns with regional variation.

22. Spinal Cord Injury Improves Mental Health?

Perceived quality of life was better than normal among men with spinal cord injuries.

Spinal cord injury (SCI) can have devastating consequences for physical functioning, related to the level of injury. Most of us assume that the emotional and social consequences are similarly severe. Researchers recruited subjects at two Veterans Administration hospitals to examine whether men’s self-perceived quality of life was linked to injury severity.

The study population consisted of 20 men with "high SCI" with lesions at or above T6 (some were quadriplegics), 10 with "low SCI" with lesions below T7, and 11 nondisabled men (controls). Injuries occurred many years previously (mean: high-SCI group, 27.9 years; low-SCI group, 16.5 years). Some controls had mononeuropathies or mild polyneuropathies. Subjects rated their life satisfaction, quality of life, and depression.

As expected, the high-SCI group had the lowest mean rating for physical functioning. The three groups rated their overall satisfaction with life similarly, including physical role, general health, and social functioning. The high-SCI group had the highest perceived emotional role in society and vitality. In further analysis, the worse the physical disability, the better was the overall mental health, especially in the high-SCI group. Depression levels did not differ among the groups. Analyses in patients without histories of traumatic brain injury had similar results.

Comment: More "severe" SCI was associated with better perceived quality of life, even compared with control group ratings. Although the controls were not completely healthy (some had neuropathies, which are often treated with psychiatric medications), this finding appears paradoxical. The authors hold that the finding may have a neurophysiologic basis, related to changes in sympathetic pathways and somatic sensory input. This study challenges our notions about the consequences of physical disability and highlights the need for empirical data rather than reliance on "logical" assumptions.

— Jonathan Silver, MD. Published in Journal Watch Psychiatry. September 17, 2007. Citation:
Abrantes-Pais F de N et al. Psychological or physiological: Why are tetraplegic patients content? Neurology 2007 Jul 17; 69:261.

Sunday, September 09, 2007

Lit Bits: September 9, 2007

From the recent medical literaure...

1. Cardioverting AF in Patients with Pacemakers

Aims: External cardioversion (ECV) of atrial fibrillation (AF) may damage implanted pacemaker and cardioverter-defibrillator (ICD) systems. This prospective study evaluated the safety and efficacy of ECV comparing mono- to biphasic shock waveforms in patients with implanted rhythm devices.

Methods and results: Patients with pacemaker or ICD systems and an indication for ECV were randomized to receive mono- or biphasic shocks. Systems were tested immediately before and after ECV, 1 h and 1 week later with respect to device and lead integrity. Forty-four patients (71 ± 10 years, 31 male; 29 pacemakers, 12 ICDs, three cardiac resynchronization systems) underwent ECV with antero-posterior paddle orientation (monophasic in 21 and biphasic in 23 patients). Pacing impedances were reduced immediately after ECV (atrial 402–392 , P less than 0.001; ventricular 517–496 , P = 0.001) and returned to baseline values within 1 week. Ventricular sensing was reduced immediately after ECV (12.4–11.6 mV, P = 0.004). There was no device or lead dysfunction in any patient. ECV was successful in 42/44 patients (95%), cumulative energy was significantly lower for biphasic compared with monophasic shocks (P = 0.001).

Conclusion: ECV for AF seems to be safe and effective in patients with implanted rhythm devices.

Manegold JC, et al. Eur Heart J 2007 28: 1731-1738.

2. Move Over Ranson: The Pancreatitis Outcome Prediction (POP) Score: A new prognostic index for patients with severe acute pancreatitis

Objective: Severe acute pancreatitis, defined as pancreatitis with distant organ dysfunction, is a condition carrying a high mortality and morbidity. Current outcome prediction scores are based on small populations, usually from single specialist centers. Some scores cannot be applied until several days into hospital admission. We thus sought to develop a new and more sensitive outcome prediction score-the Pancreatitis Outcome Prediction (POP) Score-for these high-risk patients.

Design: Retrospective cohort study of a large multicenter intensive care database. Setting: One hundred fifty-nine U.K. intensive care units. Patients: Participants were 2,462 patients admitted to intensive care units with severe acute pancreatitis.

Measurements and Main Results: Demographic, physiologic, and biochemical data collected within the first 24 hrs of intensive care unit admission were used to develop a risk prediction score using logistic regression. The six variables with the strongest relationship to hospital outcome-arterial pH, age, serum urea, mean arterial pressure, Pao2/Fio2 ratio, and total serum calcium (in order of decreasing impact)-produced a model with a prognostic discrimination (area under the receiver operating characteristic curve = 0.838) superior to other models. These six factors were used to develop an objectively weighted multivariate prognostic score ranging from 0 to 40 points.

Conclusions: Prognostic stratification of patients with severe acute pancreatitis requiring intensive care offers a useful audit tool to gauge unit performance and improve delineation of subsets for prospective trials. Prospective validation of this new outcome prediction score is required, preferably in different countries. The validity of the POP Score for either hospital or intensive care admission could also be tested and assessed for superiority over existing scores.

Harrison DA, et al. Critical Care Medicine. 35:1703-1708.

3. Bilateral and Unilateral Acute Otitis Media: Different Clinical Entities? Bilateral involvement is associated with more-severe disease.

Expectant management is an acceptable treatment approach for selected children with acute otitis media (AOM) and avoids overuse of antibiotics (Journal Watch Emergency Medicine Oct 20 2006). In two recent studies, researchers hypothesized that bilateral and unilateral AOM might have different clinical, demographic, and microbiologic features. Such features might assist clinicians in determining which patients are likely to benefit from antimicrobial therapy.

A study from Texas included 1216 cases with clinical characteristics of AOM in children up to age 16 years; 566 underwent tympanocentesis and culture of middle ear fluid. Fifty-eight percent of the cohort had bilateral disease. Children younger than 2 years were significantly more likely to have bilateral than unilateral disease, but bilateral or unilateral disease was not associated with ethnicity, gender, history of prior AOM, fever, or day-care attendance. Age and severity of tympanic membrane inflammation were independent predictors of bilateral disease. Viruses did not show a significant relation to laterality, but bacterial pathogens, in particular Haemophilus influenzae, were significantly more likely to be isolated from subjects with bilateral disease.

A study from Israel included 1026 children aged 3 months to 3 years; all underwent tympanocentesis. Sixty-one percent had bilateral AOM. Patients with bilateral disease were younger than those with unilateral disease (mean age, 10.6 vs. 11.8 months), but no differences in gender, ethnicity, or history of previous AOM were noted. Bacteria were more commonly isolated from cultures of middle ear fluid in patients with bilateral AOM than in those with unilateral AOM (83% vs. 67%). The microbiologic spectrum was similar to that in the other study, and again, H. influenzae was more common in bilateral than unilateral disease (63% vs. 42%). Clinical/otologic scores used for determining disease severity were higher in patients with bilateral AOM, and bilateral disease was an independent risk factor for more-severe disease.

Comment: These data provide no big surprises, but the consistency between the findings of the two studies strengthens the conclusions. Bilateral disease is strongly associated with age (less than 2 years) and degree of tympanic membrane inflammation/disease severity, two factors that clinicians already consider when deciding whether to start antimicrobial therapy. Based on these two studies, it is reasonable for clinicians to also consider bilateral ear involvement as indicative of more-severe disease that requires antimicrobial therapy.

— Jill M. Baren, MD, MBE, FACEP, FAAP. Published in Journal Watch Emergency Medicine August 10, 2007. Citation: McCormick DP et al. Pediatr Infect Dis J 2007 Jul; 26:583-8.

4. Simple Score Aids Pulmonary Embolism Therapy Decisions: Some Might be Candidates for Exclusive Outpt Therapy

By David Douglas. NEW YORK (Reuters Health) Aug 07 - Comparison of two prognostic models shows that one appears to be particularly effective in predicting short-term mortality in patients with acute pulmonary embolism (PE), and thus can aid selection of candidates for outpatient therapy, according to Spanish researchers.

"Our findings suggest that a simple clinical score identifies a subgroup of patients with acute symptomatic PE and a very low risk of short-term complications with standard anticoagulation," lead investigator Dr. David Jimenez told Reuters Health.

In the July issue of Chest, Dr. Jimenez, of Alcala di Henares University, Madrid, and colleagues note that they used the PE severity index (PESI) classes I to V and the Geneva low-risk and high-risk strata to categorize 599 patients with confirmed PE.

The PESI classified 36% of the patients as being low-risk, compared to 84% when the Geneva prediction score was used.

At 30 days, there were statistical similarities in the proportion of purportedly low-risk patients who experienced non-fatal recurrent thromboembolism or major bleeding. This amounted to 2.8% of PESI patients versus 4.2% of Geneva patients.

However, at 30 days, mortality in the PESI-selected low-risk group was 0.9% compared to 5.6% via Geneva scoring.

Thus, concluded Dr. Jimenez, the usefulness of PESI "for selecting low-risk patients for out-of-hospital treatment of acute PE should be addressed in a well-designed clinical trial."

Dr. Lisa K. Moores, author of an accompanying editorial, told Reuters Health that "the PESI includes objective, easily identifiable factors, which can be ascertained within minutes of presentation -- without the use of sophisticated diagnostic testing."

"If these results are further confirmed, we might avoid hospital admission in as many as 25% of patients with acute PE," Dr. Moores, of the Uniformed Services University of the Health Sciences, Bethesda, Maryland, added.

Chest 2007;132:24-30.

5. Corticosteroids Reduce Relapse After Asthma Attack

By Anne Harding. NEW YORK (Reuters Health) Aug 06 - A new Cochrane Collaboration review confirms that asthma patients fare better after an emergency department visit for an exacerbation if they receive corticosteroids upon discharge.

Dr. Brian Rowe of the University of Alberta in Edmonton and colleagues found patients given corticosteroids were 62% less likely to require additional care in the week after discharge, and 53% less likely to relapse within 21 days.

However, Dr. Rowe told Reuters Health, prescribing corticosteroids is just "one of a variety of things that physicians should be doing at discharge," including working with the patient to develop a management plan for their asthma.

Up to 16% of people who undergo emergency treatment for an asthma exacerbation will relapse within two weeks, the researchers note in their report.

While Canadian, US and UK guidelines recommend corticosteroids after asthma exacerbations, Dr. Rowe and his team point out, "there remains significant debate about the use, dosage, route and length of corticosteroid (or glucocorticoid) treatment of the asthmatic in the in- and out-patient setting."

To clarify the potential benefits of corticosteroids, the researchers looked at six trials including 374 adults and children who were treated with the drugs or placebo after being discharged from acute care, most frequently the emergency department.

The RR for relapse in the first week after discharge for patients given corticosteroids was 0.38, and 0.47 in the first three weeks. Patients were also 65% less likely to require hospitalization, while they used an average of 3.3 fewer activations of beta-2 agonists daily. There was no significant difference in pulmonary function or side effects between the two groups.

The review was unable to answer the question of which route of administration is preferable, Dr. Rowe noted, and could also not address the issue of the best dosage. He pointed out that Canadian doctors typically use 50 mg for seven to 10 days, while US doctors prescribe 40 mg for the same time period, largely because 50 mg pills are available in Canada while 40 mg tablets are the US standard.

"Our feeling is that it's probably not so important how much you give but whether you give it or not," Dr. Rowe said.

Cochrane Database Syst Rev 2007;3.

6. A Prospective Evaluation of Shortened Course Oral N-Acetylcysteine for the Treatment of Acute Acetaminophen Poisoning

Betten DP, et al. Ann Emerg Med. 2007;50:272-279.

Study objective
Treatment with a shortened duration of oral N-acetylcysteine (20 to 48 hours) after acute acetaminophen poisoning is effective in the prevention of subsequent hepatic failure and death when administered to individuals meeting appropriate laboratory criteria.

Methods
Individuals with a potentially toxic acetaminophen ingestion according to serum acetaminophen levels were identified prospectively using a large statewide poison control system database throughout a 12-month period. N-acetylcysteine was administered for a minimum of 6 doses (20 hours), after which laboratory studies were obtained. Discontinuation of N-acetylcysteine was recommended by the poison center when 2 criteria were met: serum acetaminophen was undetectable (less than10 μg/mL) and liver test results were normal (serum aminotransferase, international normalized ratio). A follow-up questionnaire was administered to individuals treated with N-acetylcysteine for 48 hours or less to ascertain the presence of symptoms consistent with progressive hepatotoxicity.

Results
Of 205 acutely poisoned individuals treated with N-acetylcysteine for 48 hours or less, 195 were successfully contacted after discharge, and 187 of 195 (95.9%) reported no symptoms consistent with hepatic failure. Eight individuals (4.1%) reported abdominal pain or vomiting; however, none received further N-acetylcysteine treatment or additional hospitalization.

Conclusion
A shortened duration of treatment with N-acetylcysteine (20 to 48 hours) may be an effective treatment option in individuals considered to be at no further risk of developing liver toxicity according to the fulfillment of appropriate laboratory criteria before N-acetylcysteine discontinuation.

7. ACEP’s New Clinical Policy on Acetaminophen Poisoning

Full-text (free): http://www.annemergmed.com/article/PIIS0196064407007317/fulltext

8. Implantable Cardioverter Defibrillators Efficacious in Real-World Practice

Implantable cardioverter defibrillators reduce mortality associated with left ventricular systolic dysfunction, a systematic review in Annals of Internal Medicine concludes.

The federally funded review, undertaken to measure the effectiveness of ICDs "under usual clinical practice conditions," examined observational studies as well as randomized controlled trials. Randomized-trial data comprising over 8500 participants showed the devices lowered all-cause mortality by 20%; observational studies, including some 9450 subjects, showed an even greater reduction, 46%. (According to the authors, the higher benefit in observational studies may be due to physicians choosing healthier patients to receive ICDs.)

The authors say their investigation also affirms the current recommendation to "delay ICD implantation after acute coronary events or coronary revascularization."

Annals abstract: http://www.annals.org/cgi/content/abstract/147/4/251
Relevant ACC Guidelines: http://content.onlinejacc.org/cgi/content/full/48/5/1064#SEC13

9. Longer Ambulance Rides Linked with Increased Mortality

For patients with certain life-threatening emergencies, mortality increases with increasing distance from the emergency department, reports the Emergency Medicine Journal.

Researchers gathered data on some 10,300 ambulance calls in the U.K. over 5 years. All patients were unconscious, were not breathing, or had acute chest pain.

About 6% of patients died. Overall, the relative risk for death increased by 2% with each additional kilometer traveled. The association between mortality and distance was strongest for patients with respiratory problems. Adjustment for confounders such as age and illness severity did not significantly affect the findings.

The authors say their results support "an approximate 1% absolute increase in mortality associated with each 10-km increase in straight-line distance" from the emergency department, and they note that "closing local EDs could result in an increase in mortality for a small number of patients with life-threatening emergencies."

EMJ Abstract: http://emj.bmj.com/cgi/content/abstract/24/9/665

10. Very High-Dose IV Nitroglycerin Effective in Decompensated Heart Failure

By Martha Kerr. NEW YORK (Reuters Health) Aug 21 - Patients presenting to the emergency department with hypertensive, severely decompensated heart failure respond well to high-dose intravenous nitroglycerin. The strategy results in a lower risk of ICU admission and of endotracheal intubation, a team at Wayne State University in Detroit, Michigan, reports in the August issue of the Annals of Emergency Medicine.

Twenty-nine patients with severe decompensated heart failure were enrolled in an open-label, non-randomized trial of high-dose IV nitroglycerin. Eligible patients had a systolic pressure of 160 mm Hg or higher or a mean arterial pressure of 120 mm Hg or higher.

Patients received a 2 mg bolus of nitroglycerin, followed by a 20 micrograms/minute infusion every three to five minutes, with a maximum of ten doses. "This is 200 times the typical dose," lead investigator Dr. Phillip Levy told Reuters Health. The mean total dose of nitroglycerin administered in this study was 6.5 mg.

Endotracheal intubation was required in 13.8% of cases, bilevel positive airway pressure (BiPAP) ventilation in 6.9%, and ICU admission in 37.9%. Symptomatic hypotension developed in one patient and biomarker evidence of myocardial infarction was seen in 17.2% of patients.

An analysis of 45 historical controls with similar symptoms who did not receive high-dose nitroglycerin showed that 26.7% underwent endotracheal intubation, 20% had BiPAP and 80% were admitted to the ICU. MI biomarkers were observed in 28.9% of patients.

Ventricular filling is impaired in heart failure with hypertension, Dr. Levy explained. "High-dose nitroglycerin decreases preload enough so that ventricular filling is improved and the heart pumps more effectively."

Dr. Levy said that cardiac output is increased by about one-third. The short half-life allows any nitroglycerin-induced episodes of severe hypotension to self-correct, he noted.

"We think that the improved ventricular filling allows the fluid to get off the lung more quickly," which would explain the reduction in endotracheal intubation seen in the study group compared with controls, Dr. Levy surmised.

"The next step is a randomized, controlled trial conducted at multiple centers ... We need to ensure that the results are generalizable to all patients with heart failure." Approximately 90% of patients in this study were black, which is a group at high risk for hypertension and which may skew the findings, he pointed out.

Ann Emerg Med 2007;50:144-152.

11. Antibiotic Use for ED Patients With URIs: Prescribing Practices, Patient Expectations, and Patient Satisfaction

Ong S, et al. Ann Emerg Med. 2007;50:213-220.

Study objective
Physicians often prescribe antibiotics to patients even when there is no clear indication for their use. Previous studies examining antibiotic use in acute bronchitis and upper respiratory infections have been conducted in primary care settings. We evaluate the factors that physicians in the emergency department (ED) consider when prescribing antibiotics (eg, patient expectations) and the factors associated with patient satisfaction.

Methods
Ten academic EDs enrolled adults and children presenting with symptoms consistent with upper respiratory infection. Enrolled patients were interviewed before their physician encounter and were reinterviewed before discharge and 2 weeks later. Physicians were interviewed about factors that influenced their management decisions, including their perceptions of patients’ expectations. Patients with a single diagnosis of uncomplicated acute bronchitis or upper respiratory infection were included for analysis.

Results
Of 272 patients enrolled, 68% of bronchitis patients and 9% of upper respiratory infection patients received antibiotics. Physicians were more likely to prescribe antibiotics when they believed that patients expected them (odds ratio [OR] 5.3; 95% confidence interval [CI] 2.9 to 9.6), although they were able to correctly identify only 27% of the patients who expected antibiotics. Satisfaction with the ED visit was reported by 87% of patients who received antibiotics and 89% of those not receiving antibiotics. Satisfaction with the visit was reported by 92% of patients who believed they had a better understanding of their illness but only by 72% of those who thought they had no better understanding (OR 4.4; 95% CI 2.0 to 8.4).

Conclusion
Physicians in our academic EDs prescribed antibiotics to 68% of acute bronchitis patients and to fewer than 10% of upper respiratory infection patients. Physicians were more likely to prescribe antibiotics to patients who they believed expected them, although they correctly identified only about 1 in 4 of those patients. Patient satisfaction was not related to receipt of antibiotics but was related to the belief they had a better understanding of their illness.

12. “Poachers and Dabblers?”: ASA President’s Incautious Comment Riles Emergency Physicians

Salaries and sedation were a central theme of the “21st Century Anesthesiology – Preparing for the Future Paradigm” presentation at the Practice Management Conference of the American Society of Anesthesiologists (ASA) last January.

Slide illustrations reflected the warnings ASA president Mark J. Lema issued to his colleagues. “What are the Current Issues Challenging the Status Quo?” one slide asked, followed by this list of answers:

“Provider Shortage/Aging Population”;

“Salary/Payment Problems”; and

“Poachers and Dabblers.”

Elaborating on the final point, another slide named the perpetrators eroding the anesthesiologists’ profession by administering propofol sedation.

“Dabblers” were the endoscopists, dentists and cosmetic surgeons.

But what group topped Lema’s “Poacher” list? “ER MDs (emergency surgery).”

Other “Poachers” were hospitalists and critical care physicians. Emergency physicians have been aware of the long-running ASA disputes with elective surgery specialties, and even dentists, over who should be administering propofol and under what conditions.

Emergency physicians, though, did not expect to find themselves as the new top target in the campaigns by the ASA and related groups to make propofol sedation the exclusive domain of anesthesiologists…

For the rest of the article (free): http://www.annemergmed.com/article/PIIS0196064407013066/fulltext

13. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations

Canani RB, et al. BMJ 2007;335.

Objective: To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children.

Design: Randomised controlled clinical trial in collaboration with family paediatricians over 12 months. Setting: Primary care. Participants Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.

Intervention: Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.

Main outcome measures: Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.

Results: 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P less than 0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P less than 0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.

Conclusions: Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.

14. How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis

Shojania KG, et al. Ann Intern Med. 2007;147:224-233.

Clinicians often use systematic reviews to obtain current evidence to guide clinical decisions and health care policy. Shojania and coworkers studied 100 quantitative systematic reviews to see how quickly the conclusions changed as new evidence became available. Conclusions about the effectiveness or harms of therapies frequently changed soon after publication of the systematic review. The median survival time without a change in the conclusions was 5.5 years. Significant new evidence had become available within 2 years for 23%. The evidence supporting preferred clinical practices is unstable.

Abstract: http://www.annals.org/cgi/content/abstract/147/4/224

15. Physician Scores on a National Clinical Skills Examination as Predictors of Complaints to Medical Regulatory Authorities

Tamblyn R, et al. JAMA. 2007;298:993-1001.

Context: Poor patient-physician communication increases the risk of patient complaints and malpractice claims. To address this problem, licensure assessment has been reformed in Canada and the United States, including a national standardized assessment of patient-physician communication and clinical history taking and examination skills.

Objective: To assess whether patient-physician communication examination scores in the clinical skills examination predicted future complaints in medical practice.

Design, Setting, and Participants: Cohort study of all 3424 physicians taking the Medical Council of Canada clinical skills examination between 1993 and 1996 who were licensed to practice in Ontario and/or Quebec. Participants were followed up until 2005, including the first 2 to 12 years of practice.

Main Outcome Measure: Patient complaints against study physicians that were filed with medical regulatory authorities in Ontario or Quebec and retained after investigation. Multivariate Poisson regression was used to estimate the relationship between complaint rate and scores on the clinical skills examination and traditional written examination. Scores are based on a standardized mean (SD) of 500 (100).

Results: Overall, 1116 complaints were filed for 3424 physicians, and 696 complaints were retained after investigation. Of the physicians, 17.1% had at least 1 retained complaint, of which 81.9% were for communication or quality-of-care problems. Patient-physician communication scores for study physicians ranged from 31 to 723 (mean [SD], 510.9 [91.1]). A 2-SD decrease in communication score was associated with 1.17 more retained complaints per 100 physicians per year (relative risk [RR], 1.38; 95% confidence interval [CI], 1.18-1.61) and 1.20 more communication complaints per 100 practice-years (RR, 1.43; 95% CI, 1.15-1.77). After adjusting for the predictive ability of the clinical decision-making score in the traditional written examination, the patient-physician communication score in the clinical skills examination remained significantly predictive of retained complaints (likelihood ratio test, P less than .001), with scores in the bottom quartile explaining an additional 9.2% (95% CI, 4.7%-13.1%) of complaints.

Conclusion: Scores achieved in patient-physician communication and clinical decision making on a national licensing examination predicted complaints to medical regulatory authorities.

16. Paramedics Overinflate Endotracheal Tube Cuffs

Every paramedic in this study inflated the cuff above the safe limit, and 87% could not detect an overinflated cuff by palpation of the pilot balloon.

Overinflation of an endotracheal tube (ETT) cuff can lead to severe complications, including tracheal necrosis, laryngeal nerve palsy, and tracheo-esophageal fistula, whereas underinflation can lead to inadequate ventilation from air leaks and aspiration. In a prospective, observational, cross-sectional simulation study, researchers assessed paramedics’ ability to inflate an ETT cuff to a safe pressure and to estimate the pressure of previously inflated cuffs by palpation of the pilot balloon.

After performing a simulated intubation, each participant assessed cuff pressure, and then a researcher measured actual pressure using a cuff inflation device. In a second phase of the study, participants palpated, in random order, nine ETT pilot balloons with pressures ranging from 0 to 120 cm H2O and indicated whether the pressure was too low, appropriate, or too high.

The 53 participating paramedics had an average career length of 6.6 years and performed endotracheal intubation an average of 3.6 times per year. Every participant inflated the ETT cuff above the safe pressure limit of 25 cm H2O, and, in 66% of cases, ETT cuff pressure was greater than the upper limit of measurement (120 cm H2O). Most participants (87%) could not detect an overinflated ETT cuff by palpation, and no participant identified all overinflated cuffs. The authors suggest that clinicians consider using a commercial ETT cuff inflator to achieve optimal pressures and a manometer to assess for safe results.

Comment: Although these dismal results might not be reproduced in larger samples or in an emergency department setting, they should remind us to pay attention to the dangers of overinflation or underinflation of an endotracheal tube cuff. Next time you intubate a patient or receive a patient who was intubated in the field, add assessment of the intracuff pressure to your postintubation algorithm of checking breath sounds, end-tidal carbon dioxide, and chest x-ray!

— Kristi L. Koenig, MD, FACEP. Published in Journal Watch Emergency Medicine August 30, 2007. Citation: Parwani V et al. Prehosp Emerg Care 2007; 11:307-11.

17. Thrombolysis for Acute Stroke: Much Talk, Little Action

From 1999 to 2004, tPA was administered to only 1.2% of acute ischemic stroke patients in the U.S.

Myriad studies have demonstrated the effectiveness and safety of tissue plasminogen activator (tPA) when administered under the appropriate circumstances and its deleterious effects when administered improperly or in small, nonacademic, nonstroke-center hospitals without specific policies and procedures for its use. These studies have given rise to two vocal camps of emergency physicians — one for and one against use of tPA — largely split according to the type of center in which the EP practices.

To identify hospital and patient characteristics associated with administration of tPA, researchers analyzed data from the Nationwide Inpatient Sample for 1999 through 2004. Of nearly 370,000 patients with acute ischemic stroke who were admitted through an emergency department, 4104 (1.12%) received tPA (intravenously in 90.1% and intra-arterially in 9.9%). Most hospitals (69.5%) did not use tPA. Among hospitals that did use tPA, the mean number of patients treated with it annually per hospital was 3.06 (range, 1 to 76). Patient factors that significantly decreased the chances of a patient being treated with tPA were older age (odds ratio, 0.43 for patients 85 compared with those less than 55), female sex (OR, 0.77), increased severity of illness (OR, 0.44 for patients with modified Charlson Index score 3 compared with those with score of 0), and black or Hispanic race/ethnicity (ORs, 0.54 and 0.79, respectively, compared with whites).

Comment: The database did not provide information about reasons for not giving tPA, other than presentation after the acceptable 3-hour window. The rate of tPA administration reported in this study is very low, with the hospitals divided mostly into those that rarely if ever use it and those that give it comparatively more often. The time has come for implementing systems of care that allow rapid screening and transport of eligible patients directly to centers that can safely administer tPA.

— Richard D. Zane, MD, FAAEM. Published in Journal Watch Emergency Medicine, August 24, 2007. Citation: Schumacher HC et al. Ann Emerg Med 2007; 50:99-107.

18. Survey Finds Significant Statistical Insecurity: Most physicians have no confidence in their own ability to use medical statistics.

The era of evidence-based medicine means that physicians are continuously exposed to statistical concepts, but a survey from Mayo Clinic documents how insecure most of us feel about using them.

Of 301 medical students, internal medicine residents, and internal medicine faculty members who completed a questionnaire (for a response rate of 64%), only a small minority agreed they had had adequate training in medical statistics (17%), could tell when the correct statistical methods were used in a study (23%), could conduct their own statistical analyses with confidence (15%), or could design their own research with confidence (28%). Although faculty were more likely to report confidence than trainees, even they were seldom confident using statistics independently, and even among respondents with extensive self-reported research experience, only 55% were confident conducting their own statistical analyses. Almost 80% of respondents felt a biostatistician should be centrally involved in most research.

Comment: This study's results certainly ring true: It seems only the rare physician is truly fluent in statistics and in the language of medical research. Further, while researchers may collaborate with biostatisticians on their projects, clinicians struggling to explain new studies to patients are on their own and often make big mistakes. The authors suggest that evidence-based medicine become the vehicle for more-effective training in biostatistics for all.

— Abigail Zuger, MD. Published in Journal Watch General Medicine August 29, 2007. Citation:
West CP and Ficalora RD. Mayo Clin Proc 2007; 82:939-43.

19. Admissions for Early MI Provide Opportunity to Flag High-Risk Relatives

Hospital admissions of patients with premature myocardial infarction could provide an opportunity to flag first-degree relatives for family counseling and heart disease screening, according to an analysis in BMJ.

Using data from previous case-control and cohort studies, researchers estimated that aggressively treating middle-aged people with a family history of early MI could have prevented 40% of premature MIs in England and Wales in 2004. In one study, the relative risk for early MI was 4.3 for male siblings of MI patients and 2.2 for female siblings; the researchers estimated that screening and treating these siblings could prevent about 1000 premature MIs over 5 years in England and Wales.

Previously, high-risk families had been targeted through questionnaires. The authors write that "wide coverage could be achieved by identifying relatives whenever someone is admitted to hospital for premature myocardial infarction. Such people may be motivated by their relative's illness to modify their lifestyle."

BMJ Abstract: http://www.bmj.com/cgi/content/extract/335/7618/481

20. Food Additives Associated with Hyperactivity in Children

Common food additives may cause hyperactivity in children in the general population, according to a study published online in Lancet.

In a randomized crossover trial, 137 three-year-olds and 130 eight- or nine-year-olds consumed daily drinks of placebo, mix A (sodium benzoate and artificial food coloring), or mix B (similar to mix A, but with additional food coloring) for 6 weeks. Hyperactivity was evaluated using teacher and parent ratings, direct observation, and a computerized test.

Compared with placebo in adjusted analyses, mix A was associated with elevated hyperactivity scores among three-year-olds, while mix B was associated with elevated scores among eight- or nine-year-olds.

The authors write, "These findings show that adverse effects are not just seen in children with extreme hyperactivity (ie, ADHD), but can also be seen in the general population and across the range of severities of hyperactivity."

Lancet article (Free abstract with one-time registration; full text requires subscription): http://www.thelancet.com/journals/lancet/article/PIIS0140673607613063/abstract?iseop=true

21. Patient-Physician Communication Scores Predict Patient Complaints

Low communication scores on physician licensing exams predict patient complaints years later, reports a new study in JAMA.

In a longitudinal study, Canadian researchers looked at some 3400 physicians who took the Medical Council of Canada clinical skills examination from 1993 to 1996. Physicians could receive low scores on the communication portion by exhibiting "condescending, offensive, or judgmental behaviors, or ignoring patient responses."

Physicians who scored in the lowest quartile for communication had 4.26 patient complaints to the regulatory authority per 100 practice-years, compared with 2.51 per 100 practice-years for clinicians scoring in the top quartile. The communication score remained predictive of complaints after adjustment for the written clinical decision-making section of the test.

The authors recommend changing examinations to test communication skills more efficiently and earlier in a physician's training, and they suggest a minimum passing standard for communication skills.

JAMA article (Free abstract; full text requires subscription): http://jama.ama-assn.org/cgi/content/short/298/9/993

Monday, August 20, 2007

Lit Bits: August 20, 2007

From the recent medical literature...

1. ACC/AHA Update Guidelines for Unstable Angina, NSTEMI

Shelley Wood. August 14, 2007 — The American College of Cardiology (ACC) and the American Heart Association (AHA) have updated their 2002 Guidelines for the Management of Patients with Unstable Angina (UA)/Non-ST-Elevation Myocardial Infarction (NSTEMI), introducing a number of recommendations for initial diagnostic tests, choice and duration of antiplatelet therapy, and new anticoagulants.[1] The new document also highlights strategies and agents that are no longer considered valuable in the treatment or diagnosis of patients with unstable coronary artery disease (CAD). The guidelines are published online August 6, 2007 in the Journal of the American College of Cardiology and Circulation.

In an interview with heartwire, writing group chair Dr Jeffrey Anderson (University of Utah Hospital, Salt Lake City) highlighted some of the key changes in the updated guidelines. "There have been a lot of new trials, new drugs, new anticoagulants, and new issues, so there are a moderate number of changes," he said. "I don't think there are a lot of things that are completely reversed, but there's certainly been an evolution and fine-tuning of the 2002 guidelines."

One of the overarching themes, according to Anderson, is a slight pullback in terms of the emphasis on an initial invasive strategy for all UA/NSTEMI patients. "In these guidelines we've sort of swung the pendulum back a little bit from the initial invasive strategy from 2002," he said. Instead, the 2007 update urges physicians to first establish whether patients are high or low risk and then apply the guidelines according to that initial risk assessment. "In low-risk patients, particularly low-risk women, an initially conservative strategy is more appropriate.... Low-risk patients should first be noninvasively risk-stratified and treated medically, but not all sent to the lab." Based on the Invasive Versus Conservative Treatment in Unstable Coronary Syndome (ICTUS) trial, the guidelines also state that an initially conservative strategy can also be considered in stabilized patients, he said.

But Dr Eric Peterson (Duke University, Durham, NC), another member of the writing group, sees this slightly differently. "I take it almost the other way around," he told heartwire. "The guidelines give a 1a recommendation for use of an early invasive strategy in patients who match any of these risk factors, including those who have positive markers, but there is some latitude that's given to physicians — a 2b recommendation — that they can consider a conservative strategy if they initially stabilize the patient."

Peterson acknowledged there was "tension inside the guideline committee" about how to balance some of the conflicting trials in this area — for example, ICTUS vs [Intracoronary Stenting with Antithrombotic Regimen Cooling Off] ISAR-COOL or [Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction] TACTICS-TIMI 18. "When it comes to the issue of invasive vs conservative strategies, there is evidence that goes both ways, depending on which study you choose to look at.... Following that evidence, there are differences in clinician opinion as to what the right strategy would be, and I think in part the guidelines reflect that."

What the guidelines do urge, says Peterson, is for physicians to first make the decision as to what treatment strategy they're going to take, then follow the recommended pathways according to what they've decided. "These guidelines give clinicians the mandate to make that decision up front and then to tailor the therapy that would go along with that, depending on what strategy you choose."

In with the new, out with the old
As expected, bivalirudin and fondaparinux have made it into the 2007 update. Both agents have a class 1 indication for use on top of antiplatelet therapy for patients in whom an invasive strategy is selected. Unfractionated heparin (UFH) and enoxaparin are given class 1 indications in patients undergoing an invasive strategy or a conservative strategy, but fondaparinux is preferred over these other agents in patients at an increased risk of bleeding for whom a conservative strategy is selected. In UA/NSTEMI patients for whom an initial conservative strategy is selected (with the possibility of converting to an invasive strategy other than coronary artery bypass grafting [CABG]), enoxaparin or fondaparinux are recommended over UFH.

Also new to the guidelines are recommendations for the use of multislice computed tomographic (CT) angiography and cardiac MRI, reflecting other recent appropriateness criteria and scientific statements dealing with imaging. Brain-type natriuretic peptide (BNP) makes its debut in the updated guidelines as a biomarker test that can be considered to supplement global risk assessment in ACS patients. Otherwise, a cardiac-specific troponin is now recommended as the "preferred marker."

"Troponin has continued to rise and really everything else has fallen way behind," Anderson explained. "In 2002, there was more attention paid to alternative markers; now we've sort of pushed those down the list."

Other notable changes or tweaks in the 2007 update include a fresh emphasis on reducing delays to initial evaluation and facilitated emergency-department (ED) diagnosis and triage, including the use of a 12-lead ECG ideally within 10 minutes of ED arrival. For patients treated invasively, recommended duration of clopidogrel therapy has been extended. "The guidelines now recommend that clopidogrel therapy be continued for at least one year after drug-eluting stent placement and ideally up to one year with a bare-metal stent or even with medical therapy, because we think the additional antiplatelet therapy seems to be beneficial," Anderson commented.

The new guidelines also give the option of using a higher loading dose of clopidogrel. "A lot of the more recent studies use 600 mg, and even though we need more studies in terms of larger numbers and hard outcomes, those studies look very promising. So we offer that as an option," Anderson said.

According to Anderson, recommendations for glycoprotein (GP) IIb/IIIa inhibitors are largely unchanged from the 2002 guidelines. "The only thing that's come along is whether, with high-risk ACS patients, you can just give clopidogrel alone without adding a GP IIb/IIIa inhibitor," Anderson explained. "There's one study that has showed that adding on a GP IIb/IIIa inhibitor did seem to benefit patients, so in higher-risk patients we're still suggesting you use a GP IIb/IIIa inhibitor if you're doing an invasive strategy, even if you're using clopidogrel. In the lower-risk patients, you can use either one or the other; at least one and possibly both."

Finally, the guidelines also drive the final nail into the coffin for strategies that have proved nonbeneficial or harmful over the past five years, including the use of supplements such as beta-carotene, vitamins E and C, and folic acid. Also singled out as harmful in the new guidelines are hormone replacement therapy in postmenopausal women and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), except for aspirin, for UA/NSTEMI patients during hospitalization.

"If one looks at what has happened over the past five to 10 years, adverse outcomes in NSTEMI have really fallen dramatically," Anderson said. "The bottom line is, the guidelines seem to be working. In the past 10 years we've pushed the envelope in terms of evidence-based medicine for diagnostics and treatment, and we do seem to be having an impact on the risks associated with ACS. With that in mind, the message would be to push ahead and fine-tune what we do and hopefully get even better outcomes."

Full-text: http://content.onlinejacc.org/cgi/content/full/50/7/e1 and
Exec summary: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.185752

2. The Role of Post-Reduction Radiographs after Shoulder Dislocation

To determine whether post-reduction radiographs add clinically important information to what is seen on prereduction X-rays in ED patients with shoulder dislocation, a prospective observational study was conducted. Clinicians recorded pre-reduction and post-reduction X-ray readings, and the films were subsequently reviewed by a blinded attending radiologist. While the majority of fractures associated with shoulder dislocations were seen on pre-reduction radiographs, more than one-third of fractures were visible only on post-reduction X-rays.

Kahn JH, et al. J Emerg Med 2007;33:169-173.

3. Midazolam vs. Diphenhydramine for the Treatment of Metoclopramide-induced Akathisia: A Randomized Controlled Trial

Parlak I, et al. Acad Emerg Med. 2007;8:715-721.

Objectives: To compare the effects of midazolam, which is a fast and short-acting benzodiazepine, and diphenhydramine, which is a widely used anticholinergic agent, in clinical practice for the treatment of metoclopramide-induced akathisia.

Methods: All adults older than 17 years given metoclopramide for nausea and vomiting or for headache and who had akathisia were eligible for this clinical, randomized, double-blind trial. Patients were randomized to receive diphenhydramine or midazolam. Subjective, objective, and total akathisia scores and modified Ramsay Sedation Scale scores were recorded. Repeated-measures analysis of variance was used to compare the efficacy and side effects of the medications.

Results: Forty-one (73.3%) of the 56 enrolled patients were women. The mean (±SD) age was 39.9 (±15.7) years in the diphenhydramine group and 40.9 (±16.2) years in the midazolam group. Mean subjective, objective, and total akathisia scores in the first 5 minutes declined considerably in the midazolam group compared with the diphenhydramine group (p less than 0.001). However, the mean Ramsay Sedation Scale score in the first 15 minutes increased significantly in the midazolam group compared with the diphenhydramine group (p less than 0.001).

Conclusions: Midazolam can correct the symptoms of metoclopramide-induced akathisia faster than diphenhydramine, but it causes more sedation.

4. Epilepsy Can Cause Isolated Transient Amnesia

Consider the diagnosis of nonconvulsive epilepsy in patients with unexplained episodic memory loss.

When a patient presents with an episode of transient memory loss without other neurologic symptoms, the diagnosis "transient global amnesia" (TGA) is often made, but the etiology is often unclear. Researchers in the U.K. describe 50 patients, recruited over 18 months, in whom epilepsy was thought to be the cause of otherwise unexplained transient amnesia, resulting in the more specific diagnosis of "transient epileptic amnesia" (TEA).

All patients had recurrent episodes of amnesia in which other cognitive functions were judged by witnesses to have remained intact. Diagnostic criteria for epilepsy were presence of at least one of these conditions: (1) epileptiform abnormalities on electroencephalogram (EEG), (2) presence of other clinical features of epilepsy such as lip-smacking or olfactory hallucinations, and (3) clear response to anticonvulsant therapy. Each of the three conditions was met by 18, 36, and 48 patients, respectively. Mean age at onset was 62, median attack frequency was 12 per year, and median duration of amnestic episodes was 30 to 60 minutes. Compared with age-matched controls, patients had subtle long-term memory problems on standardized tests. A diagnosis of epilepsy was initially considered in only 12 of these patients.

Comment: This is the largest published case series to date of patients with TEA. Because only 18 of the patients had documented epileptiform activity on EEG, one might challenge whether the diagnosis of TEA was certain in all cases. Nevertheless, this report demonstrates that clinicians should consider the diagnosis of nonconvulsive epilepsy in patients with unexplained episodic memory loss.

— Allan S. Brett, MD. Published in JW Gen Med July 24, 2007. Citation: Butler CR et al. Ann Neurol 2007 Jun; 61:587-98.

5. Average patient spends 4 hours in ED

The average time spent in emergency departments rose in 2006, but so did patient satisfaction, according to a new report by Press Ganey Associates. Based on the firm’s patient surveys in 1,500 hospitals, patients spent an average of 4 hours in the ED, 18 minutes more than in 2005. The more patients an ED saw over the year, the longer the average visit, which increased by 30 minutes for every additional 10,000 patients annually. Patient satisfaction dropped as time in the ED increased, with the lowest satisfaction reported from 3-11 p.m. and highest from 7 a.m.-3 p.m.

To view the report, go to: http://www.pressganey.com/ER-report.pdf

6. In the Elderly A Fibber, Warfarin Superior to Aspirin for Preventing Stroke

Warfarin is more effective than aspirin in preventing stroke, intracranial hemorrhage, and arterial embolism among elderly patients with atrial fibrillation, the Lancet reports.

Researchers randomized 973 patients over 75 years of age with atrial fibrillation either to warfarin (target INR, 2 to 3) or to 75 mg of aspirin daily. After an average follow-up of 2.7 years, the warfarin group had an annual relative risk of 0.48 for stroke, intracranial hemorrhage, or embolism. The number needed to treat for 1 year to prevent a primary event was 50. There was no difference between the groups in the risk for major hemorrhage — a result the authors called "surprising."

Editorialists, citing the study's "unprecedented number of patients in an age group that has been largely under-represented in randomised trials," say it "firmly establishes the superior efficacy of warfarin as a stroke-prevention strategy in elderly patients with atrial fibrillation."

Mant J, et al. The Lancet 2007; 370:493-503.

7. Antibiotic Prophylaxis Does Not Lower Rate of Recurrent UTI in Children

Conway PH, et al. JAMA. 2007;298:179-186.

Context: The evidence regarding risk factors for recurrent urinary tract infection (UTI) and the risks and benefits of antimicrobial prophylaxis in children is scant.

Objectives: To identify risk factors for recurrent UTI in a pediatric primary care cohort, to determine the association between antimicrobial prophylaxis and recurrent UTI, and to identify the risk factors for resistance among recurrent UTIs.

Design, Patients, and Setting: From a network of 27 primary care pediatric practices in urban, suburban, and semirural areas spanning 3 states, a cohort of children aged 6 years or younger who were diagnosed with first UTI between July 1, 2001, and May 31, 2006, was assembled. Time-to-event analysis was used to determine risk factors for recurrent UTI and the association between antimicrobial prophylaxis and recurrent UTI, and a nested case-control study was performed among children with recurrent UTI to identify risk factors for resistant infections.

Main Outcome Measures: Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens.

Results: Among 74 974 children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22-3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37-5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19-5.12), and grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; 95% CI, 1.26-15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.50-2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antibimicrobial resistance among children with recurrent UTI (HR, 7.50; 95% CI, 1.60-35.17).

Conclusion: Among the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections.

8. Cognitive Impairment from H2 Blockers for 1 in 5 Older Patients

INDIANAPOLIS, IN -- August 2, 2007 -- Long-term use of histamine2 receptor antagonists (H2A), one class of drugs that blocks stomach acid, may be associated with cognitive impairment in older African-American adults. According to an Indiana University School of Medicine and Regenstrief Institute study published in August issue of the Journal of the American Geriatrics Society, the risk for showing signs of cognitive impairment is 2.5 times greater for patients using these medications long-term.

These acid blockers, including ranitidine and famotidine, are among the most popular medications prescribed in the United States. More than 16 million prescriptions were dispensed in 2005 and several of these medications are also available over-the-counter. The drugs are sold under brand names such as Axid, Pepcid, Tagamet and Zantac, and are used to treat ulcers, acid reflux and other gastrointestinal disorders.

The 5-year observational study included 1,558 cognitively normal African-Americans aged 65 and older. After controlling for other possible factors, nearly 18% of H2A users studied exhibited signs of cognitive impairment.

"Taking these medications continuously appears to put older African-Americans at greater risk for the development of cognitive impairment," said Malaz Boustani, MD, MPH, lead author of the study. "We need to study this further to determine how acid blockers might be causing or creating this effect and if it occurs only in African-Americans."

9. Emergency Angioplasty Use Rises, But Some Patients Still Miss Out

NEW HAVEN, CT -- August 3, 2007 -- Compared with their counterparts a decade ago, today's heart attack patients are receiving emergency angioplasty or clot-busting drugs to re-open clogged arteries at a far greater rate, but 10% of patients who could benefit from this life-saving treatment still do not receive it, according to a study published in The American Journal of Medicine by Yale and University of Michigan researchers.

The results also showed that the chance of missing out on lifesaving emergency treatment was highest among patients without typical symptoms like chest pain, patients who did not arrive at the hospital until 6 or more hours after the heart attack began, female patients, those over age 75 and non-whites.

The 10-year study was based on data from 238,291 heart attack patients between 1994 and 2003 who were listed in the National Registry of Myocardial Infarction. The patients had a particular kind of heart attack called ST-elevated myocardial infarction (STEMI). It is the most current and comprehensive look at the use of emergency reperfusion, a treatment that can restore blood flow to the heart muscle. To track the changes in emergency reperfusion therapy over time, the researchers divided the study data into three time periods: June 1994 through May 1997, June 1997 through May 2000, and June 2000 through May 2003.

"This study has good and bad news," said senior author Harlan M. Krumholz, MD, the Harold H. Hines, Jr. Professor of Medicine at Yale School of Medicine. "We have definitely made progress in treating appropriate patients, but our findings indicate that we need to improve further to be sure that no patient who could benefit from treatment is missed."

"We may never be able to get to 100%, but 10% of eligible patients going untreated is still too many," said first author Brahmajee Nallamothu, MD, assistant professor of cardiovascular medicine at the University of Michigan Medical School. "We hope our study highlights the opportunities to improve care and particularly some of the "at risk" subgroups still less likely to receive reperfusion therapy despite eligibility, so that we can focus our clinical efforts on them."

Hospitals around the nation, including Yale-New Haven and University of Michigan, are taking part in a national campaign to reduce "door-to-balloon" times -- the time from when a STEMI patient enters hospital doors to the time blood flow is restored to the heart by opening a blockage with angioplasty.

The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study. Genentech, Inc. provided researchers with access to the registry.

10. U.S. Life Expectancy Ranking Is Falling

Although Americans are living longer than ever, U.S. life expectancy ranks 42nd in the world — down from 11th two decades ago — according to an Associated Press story.

The report, based on data from the U.S. Census Bureau and National Center for Health Statistics, says the U.S. is now surpassed by most of Europe, Jordan, Guam, the Cayman Islands, and Japan, among other countries.

The article cites lack of health insurance, high obesity rates, and racial disparities among the reasons for the country's falling ranking. Many more countries are included in the standings now than 20 years ago, which also contributes to the U.S.'s lower placement.

11. Seldinger Cricothyrotomy Kit Slower, but Preferred, Compared to New Tube-over-Needle Device

Assmann HM, et al. Anesth Anal 2007; 105:148-154.

BACKGROUND: Percutaneous cricothyroidotomy may be a life-saving procedure in cannot intubate–cannot ventilate situations. In this study we compared the insertion times of a new indicator-guided cricothyroidotomy device and a wire-guided device in mannequins.

METHODS: This study was a crossover trial comparing the insertion times and success rates of an indicator-guided tube-over-needle device and a wire-guided cricothyroidotomy device in a mannequin. After an audiovisual training session, 64 anesthesiologists performed five cricothyroidotomies with each of the two devices. Successful insertion was defined as insertion of a device into the correct anatomic location. The insertion times and success rates between the two techniques for the five attempts were compared using repeated measures ANOVA, paired t-test, and 2 analyses.

RESULTS: Insertion times were faster (32.6 ± 14.9 s vs 42.3 ± 12.5 s, P less than 0.001) while success rates were similar (95% vs 93.1%) with the indicator-guided device when compared with the wire-guided device. For both devices, performance improved with repeated attempts. Four insertion attempts (1.3%) were positioned anterior or posterior to the trachea lumen with the indicator-guided device compared to none with the wire-guided device (P = 0.12) Subjectively, more participants chose to use the wire-guided than the indicator-guided device (59% vs 31%, P less than 0.001) in a clinical emergency situation.

CONCLUSION: In a mannequin model, cricothyroidotomy insertion times were faster for the indicator-guided technique than for the wire-guided technique, but success rates were similar. Subjectively, more participants chose to use the wire-guided device in a clinical emergency situation.

12. Cannabis Use Linked to Later Psychosis

A Lancet meta-analysis on the late effects of cannabis use finds that the drug is associated with a 40% increase in the risk for psychotic symptoms, with more use leading to greater risk.

The authors assessed the studies with particular attention to bias and confounding factors, such as intoxication effects and subjects' having experienced psychosis at baseline. In the seven studies evaluated for a link with psychosis, the odds ratio for psychosis in those who had ever used cannabis versus nonusers was 1.41. Among the most frequent users, the odds ratio was 2.09.

The authors say the question is not so much whether cannabis causes psychosis as it is "whether the evidence ... now available can justify policy implications, such as public education campaigns to alert people to the possible risks."

A commentator calls the study "the most comprehensive meta-analysis to date" and concludes that cannabis' "long-term hazardous effects ... with regard to psychosis seem to have been overlooked."

Abstract: http://www.thelancet.com/journals/lancet/article/PIIS0140673607611623/abstract

13. Are One or Two Dangerous? Calcium Channel Blocker Exposure in Toddlers

Pediatric ingestions of calcium channel blocking medications are becoming more frequent. A literature review revealed that although most accidental pediatric ingestions are asymptomatic, a small number do result in cardiovascular instability or even death. The dihydropyridines, particularly nifedipine, and the phenylalkylamine verapamil are most often implicated in symptomatic ingestions.

There are no adequate data to identify which children are predisposed to illness, or to determine cutoffs for toxic dosages. However, ingestions of only one pill have been documented to cause severe symptoms, including death. Thus, emergency evaluation to assess potential toxicity is necessary, and gastrointestinal decontamination and in-hospital observation of at least 6 h after toxic ingestion for regular release medications, and 12–24 h after toxic ingestion for sustained release medications is recommended for all cases of unintentional calcium channel blocker ingestion in children younger than 6 years of age.

Ranniger C, et al. J Emerg Med 2007;33:145-154.

14. Prognostic Factors in Heat Wave–Related Deaths: A Meta-analysis

Bouchama A, et al. Arch Intern Med. 2007;167:(doi:10.1001/archinte.167.20.ira70009).

Background: Although identifying individuals who are at increased risk of dying during heat waves and instituting protective measures represent an established strategy, the evidence supporting the components of this strategy and their strengths has yet to be evaluated. We conducted a meta-analysis of observational studies on risk and protective factors in heat wave–related deaths.

Methods: Using the OVID interface, we searched Medline (1966-2006) and CINHAL (1982-2006) databases. The Web sites of the World Health Organization, Institut National de Veille Sanitaire, and Centers for Disease Control and Prevention were also visited. The search terms included heat wave, heat stroke, heatstroke, sunstroke, and heat stress disorders. Eligible studies were case-control or cohort studies. Odds ratios (ORs) and information on study quality were abstracted by 2 investigators independently. Six case-control studies involving 1065 heat wave–related deaths were identified.

Results: Being confined to bed (OR, 6.44; 95% confidence interval [CI], 4.5-9.2), not leaving home daily (OR, 3.35; 95% CI, 1.6-6.9), and being unable to care for oneself (OR, 2.97; 95% CI, 1.8-4.8) were associated with the highest risk of death during heat waves. Preexisting psychiatric illness (OR, 3.61; 95% CI, 1.3-9.8) tripled the risk of death, followed by cardiovascular (OR, 2.48; 95% CI, 1.3-4.8) and pulmonary (OR, 1.61; 95% CI, 1.2-2.1) illness. Working home air-conditioning (OR, 0.23; 95% CI, 0.1-0.6), visiting cool environments (OR, 0.34; 95% CI, 0.2-0.5), and increasing social contact (OR, 0.40; 95% CI, 0.2-0.8) were strongly associated with better outcomes. Taking extra showers or baths (OR, 0.32; 95% CI, 0.1-1.1) and using fans (OR, 0.60; 95% CI, 0.4-1.1) were associated with a trend toward lower risk of death.

Conclusion: The present study identified several prognostic factors that could help to detect those individuals who are at highest risk during heat waves and to provide a basis for potential risk-reducing interventions in the setting of heat waves.

15. Diabetes Linked to Higher Mortality After Acute Coronary Syndromes

Patients with acute coronary syndromes experience higher mortality if they also have diabetes, according to a JAMA study.

Researchers pooled data on some 62,000 patients with acute coronary syndromes who were participants in 11 independent randomized trials from 1997 to 2006. About 17% of the patients had diabetes.

After controlling for other factors, the researchers found that diabetes was independently linked with higher mortality 30 days after ST-segment elevation myocardial infarction (odds ratio, 1.40) and after unstable angina/non-STEMI (OR, 1.78). After 1 year, the risk for death in patients with diabetes who had UA/NSTEMI approached that of patients without diabetes who had STEMI (7.2% vs. 8.1%).

The authors conclude: "Despite modern therapies for [acute coronary syndromes], diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease."

JAMA article (Free abstract; full text requires subscription): http://jama.ama-assn.org/cgi/content/short/298/7/765

16. Parents Warned Cough Medicines Imperil Infants

By Gardiner Harris. NY Times. Published: August 16, 2007

WASHINGTON, Aug. 15 — Hoping to halt the growing number of injuries to infants and toddlers, the Food and Drug Administration issued an advisory Wednesday warning parents never to give cough and cold medicines to children under the age of 2 unless instructed to do so by a doctor.

The warning is part of a broad reassessment by the agency of the safety of the popular medicines, which have been blamed for hundreds of adverse reactions and a handful of deaths in children under the age of 2.

The F.D.A. will convene a panel of independent experts on Oct. 18 to discuss whether more prohibitions or warnings are warranted. Such meetings often signal that the agency is seriously concerned about the safety of the drugs under review. The drugs’ labels currently advise parents to see a doctor before giving the medicines if their child is under the age of 2, but too many parents are failing to heed this advice, the agency said. “We continue to see adverse effects associated with the medicines because people are not using them properly,” said Susan Cruzan, an F.D.A. spokeswoman.

If, despite label warnings, parents continue to use the drugs inappropriately in young children, the agency could take more serious action, like restricting the drugs’ wide availability.Most drugs that have been withdrawn in the past 15 years were taken off the market because doctors and patients failed to heed prominent warnings.

Some prominent pediatricians and public health experts said that the drug agency’s advisory did not go far enough. One group petitioned the agency to ban the marketing of the drugs for children under the age of 6, and some said that the medicines should no longer be sold over-the-counter for use in children at all.

“Unless convincing evidence shows that these medications are effective for children, their easy availability to families should be re-examined,” said Dr. Ian M. Paul, a pediatrician at Penn State Children’s Hospital in Hershey, Pa.

But the drugs’ makers say that the F.D.A. approved the drugs because they are safe and effective. Virginia Cox, a spokeswoman for the Consumer Healthcare Products Association, said that the drugs’ labels already advised against their use in children under the age of 2 unless a doctor approved. Ms. Cox said there was no need to raise this age limit to 6. Some of the drugs have drawings or pictures of infants in diapers on their labels.

The debate results because the standards for drug approvals have changed sharply in the decades since many of the medicines in children’s cough and cold products were approved. If those drugs were currently up for review, they would not be approved for use in children because the manufacturers never tested them thoroughly in children.

Instead, the drugs’ makers performed studies in adults and then simply assumed that they would work in children. Such assumptions, once common, are no longer acceptable. Indeed, a growing number of studies in children suggest that cough and cold medicines work no better than placebos. Among the ingredients that have caused concern are anticough medicines including dextromethorphan, which is the DM in many preparations. They can cause neurological problems, including abnormal movements and hallucinations, even in standard doses. Another is pseudoephedrine, which is a decongestant that has been associated with infant deaths, increased blood pressure and arrhythmias.

Some of the injuries and deaths associated with these products have resulted when parents gave two different products to their child, not realizing that both contained identical medicines, resulting in an overdose. In rare cases, children have been injured when given recommended doses.

Everyone agrees that more studies in children are needed, but companies have little incentive to undertake new trials because the medicines’ patents long ago expired. So the F.D.A. must decide how to regulate drugs that it knows very little about — a position in which it frequently finds itself. In such circumstances, it often turns to advisory boards.

Despite the growing worries, sales of the drugs are booming. Most major pharmacies carry a dozen or more brands. The medicines are popular largely because children have an average of 6 to 10 colds each year, far more than adults.

17. FDA Warns Nursing Mothers on Codeine-Containing Drugs

Mothers with a rare metabolic genotype may risk morphine overdose in themselves and their breastfeeding babies from prescription-strength doses of codeine, the FDA warns.

The problem arises in people with duplications in the CYP2D6 gene, which allows unusually fast and complete metabolism of codeine into morphine, which can cause high levels of the metabolite in breast milk. The agency's alert cites a case of infant death thought to be due to ultrarapid metabolism.

The agency says that clinicians should warn nursing women to be watchful of signs of morphine overdose in themselves and their babies. Unusual sleepiness, difficulties in breathing, and decreased muscular tone in infants should prompt immediate medical attention.

There is a test for determining a patient's CYP2D6 genotype, although it is not frequently used clinically.

FDA alert (Free): http://www.fda.gov/cder/drug/infopage/codeine/default.htm

19. Emergency Physician Activation of the Cardiac Cath Lab: Door-to-balloon time decreased significantly, with few false positives.

Time from presentation to revascularization influences infarct size and mortality in ST-segment–elevation myocardial infarction (STEMI). These authors prospectively assessed door-to-balloon times before and after implementation of a protocol mandating that emergency physicians (EPs) activate the cath lab without cardiology consultation and that a team of three registered nurses immediately transfer each patient from the emergency department to the cath lab.

Sixty consecutive STEMI patients were catheterized during the 11 months before implementation of the protocol, and 86 were catheterized during the 10 months after. Median door-to-balloon time decreased significantly overall (113.5 vs. 75.5 minutes), during regular hours (83.5 vs. 64.5 minutes), during off-hours (123.5 vs. 77.5 minutes), and in cases transferred from an outside affiliated ED (147 vs. 85 minutes). Mean infarct size decreased significantly (peak creatinine kinase during first 24 hours, 2623 vs. 1517 IU/L), as did mean hospital stay (5 vs. 3 days) and total hospital costs per admission (US$26,826 vs. $18,280). Mortality rates did not differ significantly (7.4% vs. 5.2%). One patient was misrouted to the cath lab rather than to the critical care unit because of a communication error between the EP and the cardiologist.

Comment: This study is one of several demonstrating that door-to-balloon time is improved when EPs, not cardiologists, activate the cath lab (Journal Watch Emergency Medicine Nov 17 2006). The observed decreases in length of stay and cost seem too good to be true, and the authors provide insufficient detail to determine whether they fully accounted for the cost of the three nurses for patient transfer. Nonetheless, even if the authors overestimated the benefits, the only reason to require cardiologists to activate the lab would be if EPs did so unnecessarily, which didn’t happen in this study. If this finding is generalizable to other hospitals, we can conclude that qualified EPs, not cardiologists, should activate the cath lab for ED STEMI patients.

— Daniel J. Pallin, MD, MPH. Published in Journal Watch Emergency Medicine August 17, 2007. Citation: Khot UN, et al. Circulation 2007; 116:67-76.

20. FDA Announces Boxed Warnings on All Thiazolidinediones (TZDs)

The entire class of thiazolidinedione drugs used to treat type 2 diabetes must carry boxed warnings about the drugs' ability to cause or worsen heart failure, the FDA announced late yesterday.

The affected drugs are Avandia (rosiglitazone), Actos (pioglitazone), Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin), and Duetact (pioglitazone and glimepiride).

The action addresses the FDA's worry that "despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure," says the agency's chief of drug evaluation and research.

FDA announcement (Free): http://www.fda.gov/bbs/topics/NEWS/2007/NEW01683.html

21. Obesity Seems to Spread Through Social Networks

Obesity appears to spread from person to person through social ties, according to a New England Journal of Medicine study.

The research evaluated a network of about 12,000 people over 32 years. All were members of the Framingham Heart Study. Researchers found, for example, that a person's chances of becoming obese increased by 57% in a given period if a friend became obese, 40% if a sibling did, and 37% if a spouse did. The effects were seen even if the obese acquaintance lived far away.

The authors speculate that someone who sees a friend gain weight may regard putting on weight as more acceptable. An editorialist says the work suggests that "friends have an even more important effect on a person's risk of obesity than genes do."

NEJM article (Free): http://content.nejm.org/cgi/content/full/357/4/370