Induction of Labor with Misoprostol

The Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists (ACOG) has issued an opinion paper (Committee Opinion no. 228) on the induction of labor with misoprostol. The opinion paper appears in the November 1999 issue of Obstetrics and Gynecology.

Induction of labor occurs in up to 15 percent of all pregnancies in the United States. ACOG supports labor induction as a worthwhile therapeutic option when the benefits of prompt delivery outweigh the risks of continuing the pregnancy. Recently, studies have examined the safety and effectiveness of misoprostol for labor induction. The drug is less expensive, more stable and easier to store than dinoprostone preparations. However, misoprostol is not currently approved by the U.S. Food and Drug Administration for use in labor induction, and the manufacturer has no plans to pursue approval for this indication.

In at least 19 clinical trials that used misoprostol in labor induction, the drug was found to be effective. When compared with placebo, misoprostol lowered oxytocin requirements. Higher rates of vaginal delivery were also seen within 24 hours of induction with misoprostol. Several studies suggest that misoprostol may reduce the rate of cesarean delivery; however, further clinical trials using the 25-μg dose are needed to confirm this observation.

Based on current evidence, intra-vaginal misoprostol tablets seem to be effective in inducing labor in women with unfavorable cervices. While higher doses (50 μg every six hours) may be appropriate in some patients, increased dosages appear to be linked with uterine tachysystole and possibly with uterine hyperstimulation and meconium staining of amniotic fluid. Further prospective trials are needed to define an optimal dosing regimen for misoprostol. The committee also warns that misoprostol should not be used in patients who have had uterine surgery because some of these patients have experienced uterine rupture.

New AHA Facts About Cardiovascular Disease

The American Heart Association (AHA) recently released the “2000 Heart and Stroke Statistical Update,” which covers various statistical aspects of cardiovascular disease and stroke. Statistical groups are broken down by age, sex, race and geographic location.

The update uses two sets of age-adjusted mortality rates for cardiovascular disease, following the recommendations of the U.S. Department of Health and Human Services. Age-adjusted mortality rates and prevalence are based on the 2000 and 1940 standards. For nearly 60 years, the government has used the 1940 standard as the basis of age adjustment. However, the populations of 1940 and today differ in size and the percentage of persons 65 years of age and older. To compensate for the aging and growth of the population, age-adjusted rates have been added so that any increases or decreases in rates can be more accurately monitored over time.

According to the report, almost 60 million Americans have one or more types of cardiovascular disease. One in three men and one in 10 women can expect to develop some major cardiovascular disease before age 60.

The following topics are covered in the AHA report: updated age-adjusted prevalence and mortality rates; information on heart disease and stroke in women; cardiovascular disease; coronary heart disease and angina pectoris; stroke; high blood pressure and end-stage renal disease; other cardiovascular diseases, including arrhythmias, arterial disease, bacterial endocarditis, cardiomyopathy, congenital cardiovascular defects, congestive heart failure, rheumatic fever, rheumatic heart disease and valvular heart disease; associated risk factors, such as tobacco smoke, cholesterol and other lipids, physical inactivity, overweight and obesity, and diabetes mellitus; medical procedures, facilities and costs; and economic cost of cardiovascular disease.

For more information on the AHA report, visit the AHA Web site at http://www.americanheart.org.

Vancomycin-Resistant Staphylococcus aureus

Staphylococcus aureus is one of the most common causes of hospital-and community-acquired infections, according to a report published in the January 7, 2000 issue of Morbidity and Mortality Weekly Report. Nosocomial methicillin-resistant S. aureus infections emerged in the 1980s and more recently community-acquired methicillin-resistant S. aureus infections have occurred. Increasingly, vancomycin has been used to treat suspected S. aureus infection.

According to the report, vancomycin-intermediate S. aureus has been reported in Europe, Asia and the United States in the past few years. The emergence of reduced vancomycin susceptibility in S. aureus increases the possibility that some strains will become completely resistant. It also means that available antimicrobial agents will become ineffective for the treatment of infections caused by such strains.

Laboratory staff may not know how to accurately identify vancomycin-intermediate S. aureus. The report suggests using a confirmatory testing protocol consistent with the interim guidelines of the Centers for Disease Control and Prevention (CDC). This protocol includes an algorithm to identify candidate strains for confirmatory testing. Correct, prompt identification of vancomycin-intermediate S. aureus is vital in preventing transmission.

If candidate strains are identified, the CDC can perform expedited confirmatory susceptibility testing. Information on confirmatory testing, investigation therapy and infection-control guidelines are available from the CDC Hospital Infections Program at the National Center for Infectious Diseases by calling 404-639-6413. This information is also available on the Web (http://www.cdc.gov/ncidod/hip/vanco/vanco.htm) or by e-mail (SEARCH@cdc.gov).

The report emphasizes that recovery of S. aureus with reduced susceptibility to vancomycin should be reported immediately to state and local health departments and the CDC, infection-control precautions should be implemented and an epidemiologic investigation should be conducted.

Individual Education Plan Development

The Committee on Children with Disabilities of the American Academy of Pediatrics (AAP) has issued a statement on the role of the physician in the development and implementation of an Individual Education Plan (IEP) and/or an Individual Family Service Plan (IFSP). The statement appears in the July 1999 issue of Pediatrics.

The committee reports that IEP and IFSP are legally mandated documents developed by a multidisciplinary team assessment. This assessment specifies goals and services for each child who is eligible for special education services or early intervention services. Federal legislation requires that every child who has a disability that interferes with learning be given a written plan of service. The IEP is for children between three and 21 years of age. The IFSP is for infants and toddlers up to three years of age. The Transitional Services Outcome Plan is for young adults at 16 years of age.

The AAP committee recommends that each child with a disability have access to the following services: a medical home; screening, surveillance and diagnosis; referral; diagnosis and eligibility; participation in assessment; counsel and advice; creation of the IEP and IFSP; coordinated medical services; and advocacy.

According to the AAP committee, when physicians participate in interdisciplinary efforts for children with disabilities, they are able to focus more on the children's needs. This participation may also improve the coordination of all forms of service and care for the child and the child's family.

The role of the physician in the development and implementation of these programs includes knowledge of federal statutes, and state and local mandates and regulations; helping families to find early intervention and education professionals and parental support groups in their area; and collaborating with the team serving each child. Such efforts can help children with disabilities to have a better quality of life.

FDA Advisory on Influenza Medications

The U.S. Food and Drug Administration (FDA) has issued a public health advisory to remind physicians and other health care professionals of important therapeutic considerations when treating patients who have influenza-like symptoms.

Influenza has been a widespread health concern in recent months. Four medications are currently approved for antiviral therapy in uncomplicated influenza. Amantadine and rimantadine have been available for years in the United States for the treatment of influenza A. The recent approval of two new drugs, zanamivir (Relenza) and oseltamivir (Tamiflu), that act against influenza A and B has increased interest in the role of specific antiviral medications for treatment of this disease.

The FDA advisory recommends that health care professionals consider the following when treating patients with influenza:

• Vaccination is the primary method of influenza prevention and control.

• Patients with influenza-like illness, especially patients with chronic medical conditions, may have significant bacterial infections with or without influenza. Antiviral medications such as those approved for the treatment of influenza have no activity against bacterial infections. Therefore, patients should be treated with appropriate antibacterial therapy whenever bacterial infection is suspected. Physicians should also know that antiviral medications have not been proven to prevent or effectively treat viral complications of influenza, such as viral pneumonia. Antiviral therapy for influenza is only effective if started in the first two days of symptoms and causes only a modest increase in the rate of symptom improvement.

• Physicians should use special caution when prescribing zanamivir to patients with underlying asthma or chronic obstructive pulmonary disease. The FDA has received reports of respiratory problems following inhalation of zanamivir. The drug package insert contains precautionary information regarding the risk of bronchospasm in patients with respiratory disease. If patients with airway disease use zanamivir, they should be carefully supervised and short-acting bronchodilators should be made available.

The FDA requests that health care professionals report any serious adverse event associated with the use of antiviral drugs for influenza to the FDA's MedWatch program at 800-FDA-1088 (fax: 800-FDA-0178), or to the manufacturer of the drug. The FDA Web site address is http://www.fda.gov.

Diagnosis of Attention-Deficit/Hyperactivity Disorder

The Agency for Healthcare Research and Quality (AHRQ), formerly the Agency for Health Care Policy and Research (AHCPR), has developed a technical report on the diagnosis of attention-deficit/hyperactivity disorder (ADHD). The review, titled “Diagnosis of Attention-Deficit/Hyperactivity Disorder,” was released in August 1999.

ADHD is one of the most common psychiatric disorders to affect children. Currently, the cause of ADHD is unknown, although investigators have studied the relation of ADHD to such conditions as elevated blood lead levels, abnormal thyroid function, morphologic brain differences and electroencephalograph patterns.

AHRQ sponsored the development of this technical review to summarize current scientific evidence from the medical literature on the prevalence of ADHD and the value of various evaluation methods. The report included 97 studies that had been peer reviewed and published in English between 1980 and 1997.

Two types of diagnostic screening tests were evaluated: behavioral rating scales and medical screening tests. The behavior rating scales consisted of ADHD-specific scales and “broadband” scales that were designed to screen for various symptoms. The medical screening tests included commonly recommended tests that are often used in the evaluation of children with suspected ADHD: electroencephalography, lead concentration level screening, thyroid hormone level testing, hearing and vision screening, imaging tests, neurologic screening and continuous performance tests.

Significant findings that were derived from the literature analysis include the prevalence of ADHD in the general population; the prevalence of comorbid ADHD in the general population; the prevalence of comorbid ADHD in the pediatric clinic setting; behavioral rating scales specific to ADHD; broad-band behavioral rating scales; and medical screening tests. The report also discusses the need for and goals of future research.

Copies of the report (Technical Review No. 3, AHCPR Publication No. 99-0050) may be obtained at no charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. The review is also available online at http://www.ahcpr.gov/clinic/index.html#evidence.

Previous Breast Cancer and Hormone Therapy

The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists (ACOG) has issued a committee opinion paper on the role of hormone replacement therapy in women with previously treated breast cancer. ACOG Opinion Paper no. 226 was published in November 1999. It replaces ACOG Opinion Paper no. 135 that was published in April 1994. The purpose of this committee opinion is to review the available evidence and its limitations and to provide recommendations for the use of hormone replacement therapy in women with previously treated breast cancer.

The use of hormone replacement therapy in women previously treated for breast cancer remains controversial. Researchers are concerned that estrogen use in these women may reactivate residual cancer, and mammary cells that have undergone malignant transformation may be stimulated to grow. The ACOG committee makes the following recommendations for postmenopausal women with previously treated breast cancer:

• The use of hormone replacement therapy may be considered.

• Because no specific data exist regarding particular stages or histologic types of breast cancer in which hormone replacement therapy may have a greater or lesser effect on breast cancer progression, caution must be exercised in all instances.

• Treatment plans that include hormone replacement therapy should also include dietary control, exercise, and, when appropriate, weight reduction and behavior modification (e.g., cessation of smoking, reduction of alcohol intake).

• Women with breast cancer who use hormone replacement therapy should be monitored for recurrent disease. If malignancy recurs, the use of hormone replacement therapy should be reevaluated.

• In consultation with the patient's oncologist, physicians should educate patients about the extent of current knowledge and potential benefits of hormone replacement therapy.

Enbrel for Juvenile Rheumatoid Arthritis

The Arthritis Foundation estimates that nearly 50,000 children in the United States have some type of juvenile rheumatoid arthritis. After a six-month review, the U.S. Food and Drug Administration (FDA) has approved Enbrel, a rheumatoid arthritis drug, for use in children. According to the drug labeling, the new indication is defined as a “reduction in signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more [disease-modifying antirheumatic drugs].” The drug was first approved in late 1998 to treat moderate to severe rheumatoid arthritis in adults.

Immunex, the manufacturer of Enbrel, will collect data on the safety and efficacy of the drug in at least 500 patients with juvenile rheumatoid arthritis. The expected duration of the study will be a minimum of three years, according to an approval letter from the FDA for the new arthritis indication.

Previous labeling contained a summary of a trial of 69 patients with juvenile rheumatoid arthritis, but the product was not specifically indicated for use in children. The results of that trial are fully explained in the new labeling.

The new three-year study “will include detailed efficacy and safety data collection on 200 patients with more limited data collection in an additional 300 patients.” The manufacturer will initiate the study or registry by April 1, 2000. More information on the study appears in the May 31, 1999 issue of “The Pink Sheet.” Information can also be obtained on the FDA Web site at http://www.fda.gov.