Update on Automated Defibrillator Use for Children

The Pediatric Advanced Life Support Task Force of the International Liaison Committee on Resuscitation has updated its advisory statement on use of automated external defibrillators (AEDs) for children. “An Advisory Statement from the Pediatric Advanced Life Support Task Force” appears in the July 2003 issues of Pediatrics, Circulation, and Resuscitation, and is available online atwww.circ.ahajournals.org/cgi/content/full/107/25/3250.

According to the recommendations, newer models of AEDs can be used for children one to eight years of age who have no signs of circulation. Previously, health care professionals who treated children before admission to a hospital were told that AEDs should not be used on children eight years or younger because the older AEDs delivered adult doses of energy and were designed to read adult heart rhythms only. Newer AEDs can correctly analyze heart rhythms in children and deliver smaller shocks.

Conditions requiring defibrillation in children are rare, but include commotion cordis, a life-threatening condition caused by a ball or other object striking the chest.

The statement recommends first giving one minute of standard cardiopulmonary resuscitation to children one to eight years of age to see if that revives them. The Task Force also recommends that the newer AEDs be made available in public places, such as schools and airports.

AHRQ Reports on Coronary Heart Disease in Women

The Agency for Healthcare Research and Quality has released two evidence reports finding that insufficient studies on women limit the usefulness of coronary heart disease (CHD) research. The reports, “Results of Systematic Review of Research on Diagnosis and Treatment of Coronary Heart Disease in Women” and “Diagnosis and Treatment of Coronary Heart Disease in Women: Systematic Reviews of Evidence on Selected Topics,” are available online atwww.ahrq.gov/clinic/epcsums/chdwomsum.htm andwww.ahrq.gov/clinic/epcsums/chdwtopsum.htm, respectively. In addition, the information can be found on the National Guideline Clearinghouse Web site under “EPC Report” atwww.guideline.gov.

Although CHD causes more than 250,000 deaths in women annually, much of the research in the past 20 years on the diagnosis and treatment of CHD has excluded women entirely or included only limited numbers of women and minorities. As a result, many of the tests and therapies used to treat women for CHD are based on studies conducted predominately in men. Even in studies that include women, the research often does not provide findings specific to women.

In reviewing studies that did publish findings specific to gender or race/ethnicity, the researchers found the following:

• Good evidence suggests that treatment of hypertension lowers the risk for CHD events in women, and that these benefits may be greater in black women.

• Fair or good evidence suggests that the use of diagnostic tests and treatments may differ by gender. Men are more likely than women to undergo diagnostic testing and treatment for CHD, but women are more likely to be treated for hypertension.

• Fair or good evidence suggests that the use of beta blockers, aspirin, and angiotensin-converting enzyme inhibitors reduces risk for CHD events.

• Fair evidence suggests that smoking cessation after myocardial infarction lowers the risk for CHD in women.

• Fair evidence suggests that women who receive glycoprotein IIb/IIIa inhibitor drugs during coronary procedures seem to benefit from this treatment, but good evidence suggests that use of glycoprotein IIb/IIIa inhibitor drugs in women with acute coronary syndromes may be associated with an increased risk of death. This was the only treatment studied for which there was evidence that the outcomes may be different between men and women. Men treated with glycoprotein IIb/IIIa inhibitor drugs during acute coronary syndromes appeared to benefit.

The researchers conclude that even though funding agencies appear to have succeeded in ensuring that some women and minorities are included in recent randomized trials, data about these populations often are not made clear in the published findings. They recommend that funding and regulatory agencies request that outcome data by gender and race/ethnicity be published, or easily made available, in addition to requiring participation of women and minorities in research.

CDC/ATS Recommendations on Latent Tuberculosis

The Centers for Disease Control and Prevention (CDC) and the American Thoracic Society (ATS) have revised their recommendations on latent tuberculosis infection (LTBI). The revised recommendations are available online atwww.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm.

The CDC and ATS now recommend against using rifampin with pyrazinamide (RZ) because of high rates of hospitalization and death from liver injury associated with the combined use of these drugs. Previously, the CDC and ATS cautioned physicians on the use of this therapy and recommended additional monitoring.

Physicians are advised to use the recommended alternative regimens for the treatment of LTBI, which are available online at the Web page listed earlier. Rifampin and pyrazinamide (PZA) should continue to be administered in multidrug regimens for the treatment of persons with active tuberculosis.

For surveillance purposes, a case of severe liver injury was defined as one leading to the hospitalization or death of a patient being treated for LTBI with RZ. Between October 2000 and June 2003, the CDC received reports of 48 patients with confirmed cases; 33 cases (69 percent) occurred in the second month of treatment. A total of 11 patients (23 percent) died, including two persons known to have human immunodeficiency virus infection.

A two-phase retrospective survey was conducted to estimate the incidence of severe liver injury among persons receiving RZ for LTBI. Of 7,737 patients who were reported to have started RZ therapy during the survey period, 5,980 (77 percent) received daily doses, and 1,757 (23 percent) received twice-weekly doses. A total of 204 patients discontinued using RZ because of aspartate transaminase concentrations greater than five times the upper limit of normal. An additional 146 patients discontinued using RZ because of symptoms of hepatitis.

Of the 48 cases of severe liver injury reported to the CDC through passive surveillance, 30 were detected in the second phase of the survey. Of the 18 patients whose cases were not detected, six patients had liver injuries outside the survey period, the physicians of five patients did not respond to the questionnaire, and seven (six of whom were in a private practice) were not identified in the first phase of the survey. Of the 30 patients whose cases were detected, 23 (77 percent) recovered, and seven (23 percent) died. On the basis of these 30 cases, the estimated rates of hospitalization and death during the survey period were 3.0 and 0.9 per 1,000 treatment initiations, respectively.

On the basis of the investigation of potential cofactors in the 48 patients with serious liver injury, the RZ regimen should never be offered to patients who (1) are concurrently taking other medications associated with liver injury; (2) routinely drink excessive amounts of alcohol, even if alcohol use is discontinued during treatment; (3) have underlying liver disease; or (4) have a history of isoniazid (INH)-associated liver injury.

If the potential benefits of this regimen outweigh the risk for severe liver injury and death associated with it, use of RZ might be considered in carefully selected patients, but only if the preferred or alternative regimens (i.e., nine months of daily or biweekly INH, six months of daily or biweekly INH, or four months of daily rifampin) are judged not likely to be completed, and oversight by a physician with expertise in the treatment of LTBI can be provided. In addition, patients should be asked whether they have had liver disease or adverse effects from taking INH or other drugs, informed of potential hepatotoxicity of the RZ regimen, and advised against the concurrent use of potentially hepatotoxic drugs, including over-the-counter drugs such as acetaminophen.

The recommendations against the use of RZ for LTBI treatment do not apply to the appropriate use of rifampin and PZA in multidrug regimens for the treatment of persons with active TB disease. In these circumstances, the risk for morbidity and mortality from TB disease is substantially greater than with LTBI.

NIA Releases Publications on Alzheimer's Disease

The National Institute on Aging (NIA) of the U.S. Department of Health and Human Services has released two publications on Alzheimer's disease (AD). “2001–2002 Alzheimer's Disease Progress Report” and “Alzheimer's Disease: Unraveling the Mystery” are available free of charge by calling the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center at 800-438-4380, or online atwww.alzheimers.org.

The progress report offers a comprehensive overview of recent advances in AD research, including new findings on the causes and mechanisms of AD, risk factors, promising protective measures, and caregiving.

The companion piece to the progress report, “Alzheimer's Disease: Unraveling the Mystery,” provides basic science background on the brain and AD, and offers an educational video and graphics on an accompanying CD-ROM.

FDA Approval

• Seasonale. The U.S. Food and Drug Administration (FDA) has approved Seasonale, a 91-day oral contraceptive regimen for women. Seasonale contains a progestin (levonorgestrel) and an estrogen (ethinyl estradiol), which are active ingredients in already approved oral contraceptives. Tablets containing the active hormones are taken for 12 weeks (84 days), followed by one week (7 days) of placebo tablets.

Under the dosing regimen, the number of expected menstrual periods reduce from once a month to about once every three months. As with the conventional 28-day regimen, women will have a period while taking the placebo tablets. Although users have fewer menstrual cycles, data from clinical trials show that many women, especially in the first few cycles of use, had more unplanned bleeding and spotting between the expected menstrual periods than women taking a conventional 28-day regimen.

Risks of Seasonale use are similar to other oral contraceptive use and include an increased risk of blood clots, myocardial infarction, and stroke. Cigarette smoking increases the risk of serious cardiovascular side effects.