Wednesday, November 29, 2006

Lit Bits: November 29, 2006

From the latest medical literature...

1. Systolic BP Predicts Mortality in Acute Heart Failure

News Author: Steve Stiles. from Heartwire — a professional news service of WebMD

November 8, 2006 — Systolic hypertension is not only common in patients hospitalized with acute heart failure, but it may also help protect against death while in the hospital and for several months after discharge, regardless of left ventricular (LV) systolic function at admission, suggest data from a huge multicenter registry published in the November 8 issue of JAMA. The adjusted in-hospital mortality for more than 48,000 patients hospitalized with heart failure varied inversely with their admission systolic blood pressure (SBP) and was about 4 times higher when the SBP was lower than 120 mm Hg as compared with higher than 161 mm Hg.

"Hypertension is very frequent in patients hospitalized with heart failure, including those with reduced systolic function as well as those with preserved systolic function," Gregg C. Fonarow, MD, of the University of California, Los Angeles, Medical Center, a coauthor of the analysis, told heartwire. Half of the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry cohort — more than a third of patients with LV systolic dysfunction and more than half of those with preserved LV function — had an admission SBP of more than 140 mm Hg.

The inverse relationship between admission SBP and in-hospital mortality, Dr. Fonarow observed, applied to both groups of patients. Postdischarge mortality also rose significantly with declining admission SBP, regardless of any treatment with vasodilators or inotropic agents, in a subgroup of the cohort that was followed up for 2 to 3 months.

The OPTIMIZE-HF analysis by Mihai Gheorghiade, MD, of Northwestern University in Chicago, Illinois, and colleagues, not only suggests that admission SBP is independently prognostic in patients hospitalized with heart failure, they have implications for therapy, observed Dr. Fonarow. They suggest, he said, that "with the characteristics and outcomes so different among the patients by varied SBP levels, management will need to vary. Rather than grouping all of these patients together, we'll potentially need to stratify them."

The report states that "Elevated SBP appears to signal specific pathophysiological processes that differ from the underlying processes in patients with low SBP. Because the characteristics and outcomes are different among patients with heart failure with varying SBP levels, management may need to vary according to SBP at admission."

For the rest of the article:

2. Survey examines drivers of rising ED use in California

Source: AHA News Now. Date: October 26, 2006

Nearly half of emergency department users in California say their ED visits during the past year could have been handled by a primary care physician had one been available, according to a survey by Harris Interactive. Insured patients whose health conditions are not true emergencies are increasingly using the state’s EDs due to a lack of access to other forms of medical care and advice on how to handle sudden medical problems, the survey found.

ED users were considerably less likely to have a primary care doctor and more likely to state that their ED is their main source of care. Medicaid recipients were more than twice as likely as privately insured individuals to have visited the ED in the past year. Patients with chronic conditions also visited the ED more, indicating that their primary care physician may need to improve their care management. Harris surveyed insured consumers as well as primary care and emergency physicians.

3. Length of Stay by Route of Contrast Administration for Diagnosis of Appy by CT Scan

Evan R. Berg, MD, et al. Acad Emerg Med. 2006;13: 1040-1045.

INTRO: Appendicitis remains one of the leading surgical causes of acute abdominal pain in adults, with nearly 7% to 9% of the population experiencing this condition at some point in their lifetime. Timely diagnosis is important for improving clinical outcomes. Delays can result in higher rates of perforation, increased levels of patient discomfort, and decreased patient satisfaction with their emergency department (ED) visit. Computed tomography (CT) scanning of the abdomen has been reported to have high sensitivity, specificity, positive predictive value, and negative predictive value for the assessment of patients with suspected appendicitis and has emerged as the diagnostic test of choice in many EDs.

Various methods to enhance visibility of CT have been studied, including CT with any combination of oral, intravenous (IV), or rectal-contrast material. The most commonly used technique for evaluating the appendix is a scan of the entire abdomen and pelvis after administration of both oral and IV contrast. However, the administration of oral contrast is a time-consuming step, and the two-hour prep time for terminal ileal and cecal visualization can delay diagnosis and prolong the patient's ED length of stay.

Several studies have shown CT with rectal-contrast material to be as accurate (98%) and safe as CT with oral-contrast material. Rectal-contrast administration is performed quickly and requires only minutes to ensure visualization of the appendix. Therefore, CT scanning using rectal contrast instead of oral contrast may decrease time to diagnosis and disposition and may shorten patients' overall length of stay in the ED by reducing the time to obtain a CT. The goal of this study was to compare ED length of stay for patients receiving rectal contrast to length of stay for patients receiving the standard of care (oral contrast). In addition, we compared patient satisfaction, level of discomfort, and symptoms between patients receiving oral or rectal contrast.

ABSTRACT: OBJECTIVES: Studies show equivalent accuracy of abdominal computed tomography (CT) using rectal contrast compared with oral contrast for diagnosing appendicitis. The authors evaluated whether emergency department (ED) length of stay and satisfaction differed by route of contrast administration for abdominal CT.

METHODS: This before-and-after intervention evaluated adult patients in an urban academic ED who were undergoing abdominal CT to screen for suspected appendicitis. Phase 1 subjects had a CT after oral contrast. Phase 2 patients had a CT after rectal contrast infused by gravity drip. Patients were interviewed after CT scan to assess satisfaction and discomfort. The primary outcome was ED length of stay. Medians, 95% binomial confidence intervals (CI), and Wilcoxon rank sum test of differences were calculated.

RESULTS: One hundred twelve patients were enrolled; half received rectal contrast. There was a significant decrease in length of stay for patients who were administered rectal contrast (261 min, 95% CI = 236 to 305 min) vs. oral contrast (332 min, 95% CI = 299 to 362 min), p = 0.009. Although subjects in the rectal-contrast group waited 65 minutes longer than did oral-contrast patients before receiving contrast after the CT order, the time from contrast administration to CT was 13 minutes, vs. 150 minutes for patients receiving oral contrast (p less than 0.001). Patient satisfaction and discomfort did not differ by route of contrast administration.

CONCLUSIONS: Rectal contrast for patients undergoing abdominal CT to rule out appendicitis reduced ED length of stay by more than an hour and did not affect patient satisfaction or discomfort. Rectal-contrast administration for abdominal CT may significantly shorten patient throughput time for individuals undergoing evaluation for appendicitis.

4. "Checklist" Identifies Opioid Abuse in Chronic Pain Patients

NEW YORK (Reuters Health) Nov 10 - The Addiction Behaviors Checklist (ABC) is a useful assessment tool to measure inappropriate opioid use in patients with chronic pain, according to findings published in the October issue of the Journal of Pain and Symptom Management.

"Diagnosing addictive disease in patients with chronic nonmalignant pain has proven to be a clinical challenge," Dr. Bruce D. Naliboff, of the University of California, Los Angeles, and colleagues write. "Standardized diagnostic criteria for opioid addiction in pain-free populations have proven to be less than valid or difficult to apply in the context of chronic pain and therapeutic opioid prescription."

The ABC is a 20-item clinician-based assessment tool designed to track behaviors that are characteristic of addiction to prescription opioids in chronic pain populations. Items on the measure included observable behaviors recorded during and between clinic visits. The team reports on interrater reliability and sensitivity and specificity for cut-off scores for the ABC.

Included in the study were 136 consecutive veterans, with chronic pain and a mean age of 53 years, who were receiving long-term opioid medication treatment. The score as obtained based on subject responses, interviewer observations of behavior during the session, and information gathered from medical chart reviews.

Results of the study demonstrate strong interrater reliability for the ABC. This supported the reliability and objective nature of the individual items and total score. The team notes that the ABC total score showed good concurrent validity in terms of its relationship with global clinical judgments of appropriate opioid use.

Results of the sensitivity and specificity analysis showed that a cut-off score of 3 or more on the ABC is a good estimate of whether a patient is displaying inappropriate opioid use.

A total of 38 patients had their prescriptions discontinued because of objective misuse criteria established within the clinic setting. "The ABC mean score gradually increased, approaching a total mean score of 3, as the participants neared the final visit in which they were dropped due to problematic opioid medication use," Dr. Naliboff and colleagues explain.

"ABC mean scores for participants who either completed the study or were dropped due to non-problematic reasons tended to remain fairly stable around a mean score of about 1.2 to 1.3.

J Pain Symptom Manage 2006;32:342-351.

The 20 Items
Addiction behaviors since last visit
1. Patient used illicit drugs or evidences problem drinking. 2. Patient has hoarded meds.
3. Patient used more narcotic than prescribed. 4. Patient ran out of meds early.
5. Patient has increased use of narcotics. 6. Patient used analgesics PRN when prescription is for time contingent use.
7. Patient received narcotics from more than one provider. 8. Patient bought meds on the streets.

Addiction behaviors within current visit
1. Patient appears sedated or confused (e.g., slurred speech, unresponsive). 2. Patient expresses worries about addiction.
3. Patient expressed a strong preference for a specific type of analgesic or a specific route of administration. 4. Patient expresses concern about future availability of narcotic.
5. Patient reports worsened relationships with family. 6. Patient misrepresented analgesic prescription or use.
7. Patient indicated she or he ‘‘needs’’ or ‘‘must have’’ analgesic meds. 8. Discussion of analgesic meds was the predominant issue of visit.
9. Patient exhibited lack of interest in rehab or self-management. 10. Patient reports minimal/inadequate relief from narcotic analgesic.
11. Patient indicated difficulty with using medication agreement.

Other: 1. Significant others express concern over patient’s use of analgesics

5. Adenosine vs. IV Ca--channel antagonists for the treatment of PSVT

Holdgate A; Foo A. Cochrane Database Syst Rev. 2006; (4):CD005154 (ISSN: 1469-493X)

BACKGROUND: Patients with paroxysmal supraventricular tachycardia frequently present to the Emergency Department. Where vagal manoeuvres fail, the two most commonly used drugs are adenosine and calcium channel antagonists. Both are known to be effective but both have a significant side-effect profile.

OBJECTIVES: To examine the relative effects of adenosine and calcium channel antagonists and, if possible, to determine which is most appropriate for the management of supraventricular tachycardia.

MAIN RESULTS: Eight trials were identified. In the pooled analysis there was no significant difference in reversion rate or relapse rate between the two drugs. Time to reversion was slower for verapamil than adenosine in all studies that reported this outcome, but the data were not suitable for combining. Minor adverse events such as nausea, chest tightness, shortness of breath and headache were reported much more frequently in patients treated with adenosine with 10.8 % of patients reporting at least one of these events, compared with 0.6% of those treated with verapamil (OR 0.15, 95% CI 0.09 to 0.26, P less than 0.001). There was no significant difference in the rate of major adverse events between the two groups, although hypotension was reported exclusively in the verapamil treatment group (3/166 patients treated with verapamil, 0/171 treated with adenosine).

AUTHORS' CONCLUSIONS: Adenosine and verapamil are both effective treatments for supraventricular tachycardia in the majority of patients. However, given the high incidence of minor but unpleasant side effects in patients treated with adenosine and the potential for hypotension with verapamil, patients should be fully informed of these risks prior to treatment.

6. Tamiflu May Be Linked to Risk for Self-Injury and Delirium

November 14, 2006 — The US Food and Drug Administration (FDA) and Roche Laboratories Inc have notified healthcare professionals regarding safety labeling revisions for oseltamivir phosphate (Tamiflu capsules and suspension) that warn of the potential risk for neuropsychiatric events associated with its use.

The warning was based on postmarketing reports (primarily from Japan) suggesting that patients with influenza receiving oseltamivir, particularly children, may be at increased risk for self-injury and delirium.

Although the role of the drug remains unclear, patients receiving oseltamivir should be closely monitored for signs of abnormal behavior, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.

Oseltamivir is indicated for the prophylaxis of influenza and treatment of uncomplicated acute illness in those who have been symptomatic for no longer than 2 days. It is approved for use in patients aged 1 year and older.

Adverse events potentially related to use of oseltamivir should be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

7. Presence of Calcium of EBCT Leads to Improved Use of Statins, Aspirin in Asymptomatic Men

from Heartwire — a professional news service of WebMD. November 13, 2006 (Chicago, IL) - Finding coronary artery calcium (CAC) on an EBCT (EB= electron beam) scan appears to improve use of preventive medicine in asymptomatic men above and beyond presence of traditional risk factors, new results from the Prospective Army Coronary Calcium Project suggest. Whether better use of preventive drugs leads to improved outcomes remains unknown, but according to Dr Allen J Taylor (Walter Reed Army Medical Center, Washington, DC), appreciating the impact of scans on patient management is an important piece of the puzzle.

"We've learned that calcium scans are an independent predictor of risk, but the knock against calcium scanning has been that it hasn't previously been shown that the scan leads to improved management decisions or outcomes," Taylor told heartwire during a poster session at the AHA 2006 Scientific Sessions. "This is the first time we've seen that management is shifted by a calcium scan."

Taylor and colleagues looked at use of aspirin, statins, and both medications among 1640 men between the ages of 40 and 50 participating in the PACC project, a community-based screening initiative among asymptomatic, otherwise healthy men. All study participants underwent risk factor assessment and an EBCT scan at study outset.

Baseline use of statins and of aspirin was greater in patients found to have coronary calcium than in patients with no calcium (approximately 10% vs 5% for statins and 18% vs 10% for aspirin)--reflecting more complex risk factor profiles. Over six years of follow-up, both statin and aspirin use increased to a greater degree in patients found to have coronary calcium on baseline EBCT, with the curves for both drugs diverging clearly after the baseline scan.

"There's something that's being recognized as risk, over and above standard risk factors, and that's leading to more use of preventive medication," Taylor told heartwire. What the study can't answer is what's driving the increase in medication use, whether it's patient-driven or physician decision-making, he added. Still, he says, "the bottom line is that this is the first community-based screening study to show that management of patients after calcium screening is improved . . . so it's an important advance in our understanding of this test as a tool in preventive cardiology."

As for whether management decisions lead to improved outcomes, "that's only really addressable by a randomized trial, but I don't think that trial is ever going to be done," Taylor said. "You can reasonably infer that if patients are using statins and aspirin, their outcomes should be better, but that's a leap of faith. This is an important step in the right direction."

8. Tdap from the CDC: to be used only once and limited to those aged 11- 65 years.

Tdap was licensed in 2005. It is the first vaccine for adolescents and adults that protects against all three diseases.

Who should get Tdap vaccine and when?

Adolescents 11 through 18 years of age should get one booster dose of Tdap.
• A dose of Tdap is recommended for adolescents who got DTaP or DTP as children but have not yet gotten a dose of Td. The preferred age is 11-12.
• Adolescents who have already gotten a booster dose of Td are encouraged to get a dose of Tdap as well, for protection against pertussis. Waiting at least 5 years between Td and Tdap is encouraged, but not required.
• Adolescents who did not get all their scheduled doses of DTaP or DTP as children should complete the series using a combination of Td and Tdap.

Adults 19 through 64 years of age should substitute Tdap for one booster dose of Td. Td should be used for later booster doses.
• Adults who expect to have close contact with an infant younger than 12 months of age should get a dose of Tdap. Waiting at least 2 years since the last dose of Td is suggested, but not required.
• Healthcare workers who have direct patient contact in hospitals or clinics should get a dose of Tdap. A 2-year interval since the last Td is suggested, but not required.

An adolescent or adult who gets a severe cut or burn might need protection against tetanus infection. Tdap may be used if the person has not had a previous dose.

If vaccination is needed during pregnancy, Td usually is preferred over Tdap. Ask your doctor. New mothers who have never received a dose of Tdap should get a dose as soon as possible after delivery.

Tdap may be given at the same time as other vaccines.

Td should be used rather than Tdap if Tdap is not available, and for:
- Anybody who has already gotten Tdap,
- Adults 65 years of age and older,
- Children 7 through 9 years of age.

9. Do we really need plain and soft-tissue radiographies to detect radiolucent foreign bodies in the ED?

Turkcuer I, et al. Amer J Emerg Med 2006;24:763-768.

Objective: The objective of this study was to compare 3 imaging techniques—plain radiography, soft-tissue radiography, and ultrasonography—in detecting nonradiopaque foreign bodies in soft tissue.

Methods: In this randomized, blinded, and descriptive in vitro study, 40 chicken thighs with 2 types of nonradiopaque foreign bodies (wood and rubber) and 40 chicken thighs as part of a control group were evaluated to detect soft-tissue foreign bodies with plain radiography, soft-tissue radiography, and high-frequency ultrasonography.

Results: The overall sensitivity, specificity, as well as positive predictive and negative predictive values of plain radiography for both nonradiopaque foreign bodies were 5%, 90%, 33%, and 48%, respectively; those of soft-tissue radiography for both nonradiopaque foreign bodies were 5%, 90%, 33%, and 48%, respectively; and those of ultrasonography for both nonradiopaque foreign bodies were 90%, 80%, 81%, and 89%, respectively.

Conclusions: In this experimental model, the results show that high-frequency ultrasonography is superior to plain and soft-tissue radiographies and that the latter 2 techniques are similarly poor at detecting nonradiopaque foreign bodies.

10. Study Raises Questions on Safety of Naproxen

Aleve (naproxen) may increase the risk for cardiovascular and cerebrovascular events, according to research published in Public Library of Science Clinical Trials.

The data are from the NIH's Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), which was halted early because of concerns about the heart risks of NSAIDS in the wake of the Vioxx withdrawal. At that time, the NIH issued a warning about the risks associated with naproxen, but the results were not previously available.

For the composite outcome of MI, heart failure, stroke, TIA, or cardiovascular death, the researchers found a hazard ratio of 1.63 for naproxen versus placebo, just reaching statistical significance.

The authors conclude that -- although not definitive -- the data suggest an increased risk for cardiovascular and cerebrovascular events with naproxen. However, an editorialist notes that the trial was stopped by the NIH, not the study's data safety monitoring board; this "resulted in data that cannot be reliably interpreted."

PLoS clinical trial:

11. Oral medroxyprogesterone acetate and combination OCs for acute uterine bleeding: a RCT.

Munro MG, et al. Obstet Gynecol. 2006; 108(4):924-9 (ISSN: 0029-7844)

OBJECTIVE: To compare the efficacy of multidose medroxyprogesterone acetate and a multidose monophasic combined oral contraceptive (OC) for hemodynamically stable women with nongestational, acute uterine bleeding.

METHODS: Hemodynamically stable patients with acute uterine bleeding sufficient to justify immediate medical or surgical intervention were enrolled in an open-label, randomized trial comparing oral medroxyprogesterone acetate 20 mg and a monophasic combination OC containing 1 mg norethindrone and 35 mug of ethinyl estradiol, each administered TID for one week. Doses were reduced after 1 week to 20 mg per day and one tablet per day for the next 3 weeks for the medroxyprogesterone acetate and OC groups, respectively. Following baseline assessment, patients completed daily treatment and symptom logs collected at 14 and 28 days after initiation of therapy.

RESULTS: Forty patients were randomly assigned, 20 in each group; 33 were evaluated at the 14-day visit. Emergency surgical procedures were avoided in 100% of those women taking medroxyprogesterone acetate and 95% of the OC group. Cessation of bleeding had occurred in 88% of the OC group and 76% of those receiving medroxyprogesterone acetate, with a median time to bleeding cessation of 3 days for both groups. Compliance with therapy was higher in the medroxyprogesterone acetate group than the OC group, but there was no overall difference in the incidence of treatment-related nausea and bloating.

CONCLUSION: This randomized trial is limited by sample size but suggests that both regimens may be effective and reasonably well tolerated.

12. Herniated Disk Improves With Either Surgical or Nonsurgical Treatment

News Author: Laurie Barclay, MD. November 21, 2006 — Patients with herniated disks had improved outcomes during 2 years whether treated surgically or nonsurgically, according to the results of a randomized trial with an accompanying observational cohort reported in the November 22/29 issue of JAMA.

"Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients, but the efficacy of the procedure relative to nonoperative care remains controversial," write James N. Weinstein, DO, MSc, of the Dartmouth Medical School in Hanover, New Hampshire, and colleagues from the Spine Patient Outcomes Research Trial (SPORT).

Based on intent-to-treat analyses, both treatment groups had substantial improvements for all primary and secondary outcomes. Between-group differences in improvements were consistently in favor of surgery, but these were small and not statistically significant for the main endpoints.

"Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period," the authors write. "Because of the large numbers of patients who crossed over in both directions, conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis."

The second report describes outcomes in the observational cohort of patients who met the SPORT eligibility criteria but declined randomization between March 2000 and March 2003. Of the 743 patients enrolled, 528 patients received surgery, and 191 received usual nonoperative treatment.

At 3 months, patients who opted for surgery had greater improvement in the primary outcome measures of bodily pain (mean change: surgery, 40.9 vs nonoperative care, 26.0; treatment effect, 14.8; 95% confidence interval [CI], 10.8 - 18.9), physical function (mean change: surgery, 40.7 vs nonoperative care, 25.3; treatment effect, 15.4; 95% CI, 11.6 - 19.2), and Oswestry Disability Index (mean change: surgery, -36.1 vs nonoperative care, -20.9; treatment effect, -15.2; 95% CI, -18.5. to -11.8). These differences were less pronounced at 2 years.

"Patients with persistent sciatica from lumbar disk herniation improved in both operated and usual care groups," the authors write. "Those who chose operative intervention reported greater improvements than patients who elected nonoperative care. However, nonrandomized comparisons of self-reported outcomes are subject to potential confounding and must be interpreted cautiously."

In an accompanying editorial, Eugene Carragee, MD, of the Stanford University Medical Center in California, notes that "these findings suggest that in most cases there is no clear reason to advocate strongly for surgery apart from patient preference. For the patient with emotional, family, and economic resources to handle mild or moderate sciatica, surgery may have little to offer."
A second editorial, by David R. Flum, MD, MPH, of the University of Washington in Seattle, describes the difficulty in interpreting surgical trials with subjective outcomes. "Because of limitations in design and study operation, the proper role and benefits of these competing interventions are still unclear," Dr. Flum concludes. "Given the large number of patients potentially exposed to the risks of these strategies, a sham surgical trial may be the only effective and ethical next step."

JAMA. 2006;296:2441-2450, 2451-2459, 2483-2485, 2485-2487

JAMA editorials:

13. Target Expands $4 Generic Program to All Pharmacies

Target announced on Monday that all of its nearly 1300 pharmacies will now offer $4 generic prescriptions. Wal-Mart recently expanded its own $4 generic program to cover about 3000 of its pharmacies in 38 states.

Which drugs are offered?

14. Late PCI Found to Be of No Clinical Benefit After MI

Reopening persistently occluded arteries after myocardial infarction does not produce an additional clinical benefit over optimal medical therapy, concludes an article released online in the New England Journal of Medicine.

In the study, 2166 stable patients were randomized either to undergo PCI and receive medical therapy, or to receive medical therapy alone. The patients had all suffered infarction and had confirmed total occlusion of the infarct-related artery 3 to 28 days later.

The estimated 4-year cumulative event rate (a composite of death from any cause, nonfatal reinfarction, or NYHA class IV heart failure) did not differ between the groups.

An editorial, offering advice on incorporating these results into care of patients after MI, says that repeated angiography is not warranted in most such patients and that all survivors of infarction should receive a beta-blocker indefinitely.

NEJM editorial:

15. Benefit of early invasive therapy in ACS: a meta-analysis of contemporary randomized clinical trials.

Bavry AA, et al. J Am Coll Cardiol. 2006; 48(7):1319-25 (ISSN: 1558-3597)

OBJECTIVES: This study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Although early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown.

METHODS: Clinical trials that randomized non-ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis.

RESULTS: In all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p less than 0.0001).

CONCLUSIONS: Managing non-ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina.

16. Canadian Study Indicates BNP Test for Suspected Heart Failure is Cost-Effective

from Heartwire — a professional news service of WebMD

November 16, 2006 (Chicago, IL) – The use of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) testing in conjunction with clinical assessment improves the overall management of patients presenting to the emergency room with suspected acute heart failure, and saves around $1000 per patient, according to the results of the IMPROVE-CHF study presented in a late-breaking clinical trials session here by Dr Gordon W Moe (St Michael's Hospital, Toronto, Canada).

"In the Canadian system, this test is not reimbursed by the government and its use is still limited in spite of the data," Moe told heartwire. "Canadian doctors are already very good at making a diagnosis [of heart failure] so we did the test to see if it provided incremental benefit. The test saved money because a low level is very specific at ruling out heart failure, so doctors were able to discharge patients faster. On the other hand, if you have a high level, you know the patient is going to be very sick and you can administer therapy faster."

Discussant of the trial, Dr Margaret M Redford (Rochester, MN) said the results of IMPROVE-CHF, taken together with previous studies in this area, "provide consistent and compelling proof-of-concept evidence that the use of BNP testing in the evaluation of patients with dyspnea does improve cost savings without any adverse effects on outcomes."

Reduction in duration of ER stay. Moe and colleagues randomized 501 patients presenting with shortness of breath to seven emergency departments across Canada to usual care or BNP testing. All patients actually received a BNP test, but the results were not disclosed to doctors treating the usual care group.

Physicians immediately committed to a diagnosis for each patient based on their professional opinion, and these diagnoses were later judged and confirmed by cardiologists blinded to the BNP results, which were measured in the emergency room and again at 72 hours in those who were hospitalized.

There was a significant reduction in duration of emergency room visit in the BNP group compared with the usual care patients (5.6 hours vs 6.3 hours; p=0.038), but no differences between the groups in terms of ICU admission, duration of ICU stay or initial hospitalization from the emergency department.

There were cost savings, however, of $961 per patient ($4631 per patient in the BNP group overall compared with $5592 in the usual-care group). There was also significantly reduced rehospitalization within 60 days in the BNP group (33 patients vs 51).

For a test that costs Can $21, these findings are pretty good, Moe said. In a healthcare system like that of Canada that mandates judicious use of resources, " the use of the BNP test will improve the overall management of these patients and . . . should be part of the routine management," he commented.

Findings consistent with other studies. Redford said the study had some strengths--including the fact that it excluded patients with obvious causes of dyspnea and looked at whether BNP testing adds incremental value (which few other studies have done). But it also had some limitations, she noted, such as relatively small numbers of patients, which limited the power for mortality assessment and subgroup analyses.

Also, the researchers were not really able to say whether the savings in cost were related to better and more rapid treatment of patients or due to less use of diagnostic testing, nor were they able to determine whether the assay was most helpful in ruling out, or ruling in, heart failure, she noted.

Several studies have now compared the ability of BNP to make a diagnosis of heart failure, she said, including PRIDE, BASEL, the BNP trial, and the New Zealand one. When comparing the area under the receiver operating curve (AUC) for the BNP assay with the AUC for clinical diagnosis of heart failure, the current study's findings are quite consistent with those of the other trials for both indices, she said.

In terms of cost savings, the 15% savings in cost at 60 days in IMPROVE-CHF is consistent with the other studies in which economic data were reported, such as the BASEL study, which described a 25% saving in hospital costs with the BNP test vs no test, which was maintained out to six months, she concluded.

17. Statins Lower Risks in Patients Without CVD

Statins can take a role in the primary prevention of major coronary and cerebrovascular events in patients at moderate to moderately high risk, a meta-analysis in Archives of Internal Medicine finds. Statins did not, however, significantly reduce all-cause mortality or coronary heart disease mortality in these patients.

Researchers analyzed seven randomized, controlled trials comprising 42,848 subjects who either took statins for primary prevention or received a placebo. Ninety percent of the patients had no evidence of cardiovascular disease at enrollment.

Subjects taking statins for a mean of 4.3 years had a lower incidence of heart attack, stroke, revascularization, and other events than controls. The authors estimate the following numbers needed to treat for 4.3 years: 60, to prevent one major coronary event; 268 for stroke; 61 for nonfatal myocardial infarction and 93 for revascularization.

Thavendiranathan P, et al. Arch Intern Med. 2006;166:2307-2313.

18. Discordant Cardiac Biomarkers: Frequency and Outcomes in ED Patients With CP

Storrow AB, et al. Ann Emerg Med 2006;48:660-665.

Editor’s Capsule Summary
What is already known on this topic: Cardiac biomarkers are important in diagnosis and risk stratification of patients with suspected acute coronary syndrome. How to interpret discordant biomarkers is unclear.

What question this study addressed: Among patients with suspected non–ST-segment elevation acute coronary syndrome, how should emergency department (ED) clinicians interpret the following pairs of discordant cardiac biomarkers: increased CKMB+normal creatine kinase levels, increased troponin+normal CKMB levels, and normal troponin+increased CKMB levels?

What this study adds to our knowledge: In an ED population with suspected non–ST-segment elevation acute coronary syndrome, increase of either cardiac troponin or CKMB levels appears to increase the odds of acute coronary syndrome compared with that of patients with normal concordant cardiac biomarkers. Because of the constraints of incorporation and evaluation bias, these conclusions should be viewed as tentative at this time.

How this might change clinical practice: Until more information becomes available, it appears wise to regard increase of either cardiac troponin or CKMB as a true positive result and proceed accordingly.

Abstract: Study objective
We evaluate associations between pairs of discordant cardiac biomarkers (positive MB band of creatine kinase [CKMB] with negative creatine kinase, positive CKMB with negative cardiac troponin, and positive troponin with negative CKMB) and the presence of acute coronary syndromes in emergency department (ED) chest pain patients.

This was a secondary analysis of a prospective registry. Data were obtained from the multicenter Internet Tracking Registry of Acute Coronary Syndromes, which included 17,713 ED visits for possible acute coronary syndrome between June 1999 and August 2001. First visits and first ED cardiac biomarker results from the 9 sites, 8 in the United States and 1 in Singapore, were included. Subjects were excluded for incomplete information or an initial ECG consistent with ST-segment elevation myocardial infarction. Acute coronary syndrome was defined by diagnosis-related group code indicating myocardial infarction, positive invasive or noninvasive diagnostic testing, revascularization, or death during hospitalization or within 30 days.

Of 8,769 eligible patients, 1,614 (18.4%) had acute coronary syndrome. The CKMB and cardiac troponin results were discordant in 7% of patients (CKMB+/cardiac troponin–, 4.9%, CKMB–/cardiac troponin+ 2.1%), whereas increased CKMB with normal creatine kinase levels occurred in 239 (3.1%) patients. The unadjusted odds ratios with 95% confidence intervals for acute coronary syndrome in patients with and without discordant markers were: CKMB+/CK− 5.7 (4.4-7.4), CKMB+/CK+ 4.4 (3.6-5.2), CKMB−/cTn+ 4.8 (3.4-6.8), CKMB+/cTn− 2.2 (1.7-2.8), CKMB+/cTn+ 26.6 (18.0-39.3). For the group with cardiac troponin, the reference category was negative troponin and negative CKMB; for the group with creatine kinase, the reference category was negative CKMB but either a positive or negative creatine kinase.

Among the spectrum of ED patients with chest pain, an increased CKMB level with a normal creatine kinase level identifies patients at increased risk for acute coronary syndrome. Similarly, an increased troponin level regardless of CKMB level and an increased CKMB level regardless of troponin level identify patients at higher risk for acute coronary syndrome than those with uniformly normal cardiac biomarker levels. Our data suggest that discordant cardiac biomarkers may identify patients at increased risk for acute coronary syndrome.

19. The Internet Tracking Registry of Acute Coronary Syndromes (i*trACS): A Multicenter Registry of Patients With Suspicion of ACS Reported Using the Standardized Reporting Guidelines for ED Chest Pain Studies

Lindsell CJ, et al. Ann Emerg Med 2006;48:666-677.

Editor’s Capsule Summary
What is already known on this topic: Randomized controlled trials can demonstrate the effectiveness of therapies but do not focus on the complex clinical presentations of acute coronary syndrome. Observational data sets that contain systematically recorded information on every patient who could have an acute coronary syndrome can help examine interactions between patient characteristics, presentations, practice patterns, and outcomes.

What question this study addressed: The investigators established a 9-emergency department network that collected standardized information on a convenience sample of patients in whom acute coronary syndrome was considered. They present information on more than 17,000 patient encounters.
What this study adds to our knowledge: This study provides information about these patients’ demographics, cardiac enzyme patterns, and 30-day outcomes.

How this might change clinical practice: This study alone will not change clinical practice but provides a model for clinical networks whose data might eventually lead to better strategies for the risk stratification of patients to different diagnostic and therapeutic regimens.

Study objective
Observational studies of well-described patient populations presenting to emergency departments (EDs) with suspicion of acute coronary syndrome are necessary to understand the relationships between patients’ signs and symptoms, cardiac risk profile, test results, practice patterns, and outcomes. We describe the methods for data collection and the ED population enrolled in a multicenter registry of patients with chest pain.

Patients older than 18 years, presenting to one of 8 EDs in the United States or 1 ED in Singapore, and with possible acute coronary syndrome were enrolled in the Internet Tracking Registry of Acute Coronary Syndromes between June 1999 and August 2001. Prospective data, including presenting signs and symptoms, ECG findings, and the ED physician’s initial impression of risk, were systematically collected. Medical record review or daily follow-up was used to obtain cardiac biomarker results, invasive and noninvasive testing, treatments, procedures, and inhospital outcomes. Thirty-day outcomes were determined by telephone follow-up and medical record review.

The registry includes 15,608 patients, with 17,713 visits. Chest pain was the chief complaint in 71% of visits. The ECG was diagnostic of ischemia or infarction in 10.1% and positive cardiac biomarkers were observed in 10% of visits. Forty-three percent of patients were sent home directly from the ED. Of admitted patients, 5% died by 30 days, and 3% had documented coronary artery disease or had undergone percutaneous coronary intervention or coronary artery bypass grafting within 30 days. For patients discharged directly from the ED, 0.4% died or had a documented myocardial infarction within 30 days. Coronary artery bypass graft surgery, percutaneous coronary intervention, or a diagnosis of coronary artery disease was found in 0.5% of discharged patients.

A unique description of undifferentiated ED chest pain patients with suspected acute coronary syndrome is provided. The data set can be used to generate and explore hypotheses to improve understanding of the complex relationships between presentation, treatment, testing, intervention and outcomes.

20. A score for predicting salvage and outcome in Gustilo type-IIIA and type-IIIB open tibial fractures.

J Bone Joint Surg Br. 2006 Oct;88(10):1351-60.

Wait a minute—I don’t even know what a Gustilo fracture is…so I think we’ll skip this one.