Significant Decrease in AIDS Deaths in 1997

The National Center for Health Statistics (NCHS) reports that the number of deaths related to acquired immunodeficiency syndrome (AIDS) declined an unprecedented 47 percent from 1996 to 1997. The decrease in AIDS-related deaths from 1995 to 1996 was 29 percent. In addition, human immunodeficiency virus (HIV) infection fell from the eighth leading cause of death to the 14th leading cause of death in 1997. For persons aged 25 to 44 years, HIV infection declined from the leading cause of death in 1995 to the third leading cause in 1996 and to the fifth leading cause in 1997. Health and Human Services Secretary Donna Shalala emphasizes that the decline in AIDS deaths is primarily due to the continuing impact of highly active antiretroviral therapy. However, she cautions that efforts to prevent HIV should continue to be a priority.

Data from the report, “Births and Deaths: United States, 1997,” were collected through the National Vital Statistics System from over 90 percent of all birth and death records. Other findings from the report include the following:

• The overall infant mortality rate reached a new low of 7.1 deaths per 1,000 live births.

• The birth rate fell an estimated 3 percent in 1997, continuing a six-year downward trend.

• Little or no change in the number and percentage of births to unmarried women was shown in 1997.

• A slight increase was noted in the percentage of cesarean deliveries, up to 20.8 percent of all deliveries, suggesting a leveling off of the downward trend of recent years.

• Low-birth-weight infants accounted for 7.5 percent of all births, compared with 7.4 percent in 1996.

Copies of the report are available on the NCHS Web site at http://www.cdc.gov/nchswww/.

Estrogen Deficiency in Women with Breast Cancer

Women who have had breast cancer and women who are fearful of estrogen replacement therapy can receive alternative therapies that provide the benefits of estrogen without the risks, according to findings from a consensus conference sponsored by the Hormone Foundation, the Susan G. Komen Breast Cancer Foundation, the Canadian Breast Cancer Research Initiative, the National Cancer Institute of Canada, the Endocrine Society and the University of Virginia Cancer Center and Woman's Place. The consensus statement findings were presented at the 80th Annual Endocrine Society Meeting. The executive summary of the statement appears in the June 1998 issue of the Journal of Clinical Endocrinology and Metabolism.

According to the statement, alternative therapies to estrogen replacement bypass the need for estrogen by directly treating symptoms of estrogen deficiency. Estrogen alternatives can be used to prevent osteoporosis and coronary artery disease, and to treat the symptoms of menopause. The following types of alternative therapies are discussed in the statement:

• Antiresorptive agents, such as alendronate and calcitonin, can prevent osteoporosis by stopping the body's normal process of bone breakdown.

• Statin drugs, which are prescribed for high cholesterol levels, can reduce the risk of death from myocardial infarction by nearly 33 percent and lower the risk of coronary artery disease.

• Selective serotonin reuptake inhibitors are effective in treating post-menopausal depression and mood swings.

• Other treatments focus on specific postmenopausal symptoms. Vitamin E, megestrol acetate and clonidine prevent hot flushes. Estrogen creams and devices that provide a low-dose estrogen that will not be absorbed into the bloodstream can relieve vaginal dryness, pain and urinary tract infections.

Recommendations to Increase Vaccination Rates

The Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) recommend a programmatic strategy—the use of a reminder or recall system, or both, to increase the rates of vaccination. The recommendation appears in the September 4, 1998, issue of Morbidity and Mortality Weekly Report.

The reminder component of the strategy uses mail, telephone messages, or both, to remind parents of vaccination due dates for their children. The recall component uses mail, telephone messages, or both, to notify parents of children who are past due for one or more vaccinations. Both of these systems can be handled manually or can be automated. Messages from automated systems can be modified to address special needs, such as language.

Studies of the effectiveness of these systems generally have shown improvements in patient compliance for a variety of scheduled health care visits, including vaccinations. ACIP, AAFP and AAP believe that implementation of these recommendations will contribute substantially to improving vaccination coverage at the practice level.

Emergency Contraceptive Kit for Women

An emergency contraceptive kit (Preven Emergency Contraceptive Kit) containing oral contraceptive pills for postcoital use has been approved by the U.S. Food and Drug Administration (FDA). The kit has three components: a patient information booklet, a pregnancy test and a packet of four oral contraceptive pills. The pills contain progestin (0.25 mg of levonorgestrel) and estrogen (0.05 mg ethinyl estradiol). The regimen can prevent pregnancy when used within 72 hours of having sex. The pills work by preventing or delaying ovulation and will not affect an existing pregnancy.

Once a woman has used the pregnancy test in the kit and determines she is not pregnant, the first dose of two pills is taken within 72 hours of having sex in which there was a known or suspected birth control failure or after sex without birth control; the second dose of pills is taken 12 hours later. When used in this manner, the treatment is about 75 percent effective, according to the FDA.

The most commonly reported side effects were nausea, vomiting, dizziness, menstrual irregularities, breast tenderness, headache, and abdominal pain and cramps.

Preventing Medication Errors in Children

The American Academy of Pediatrics (AAP) has issued a statement on the prevention of medication errors in the pediatric inpatient setting. In the statement, medication errors are defined by the AAP as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, the patient or the consumer. Steps are recommended to reduce these medication errors in the following areas: hospital-wide actions and policies, ordering medication, prescriber actions, pharmacy actions and nursing staff actions. The following steps are recommended by the AAP to ensure that medication orders are communicated safely and effectively:

• Confirm that the patient's weight is correct for weight-based dosages.

• Identify drug allergies in patients.

• Write out instructions rather than using abbreviations.

• Avoid vague instructions.

• Specify exact dosage strength.

• Avoid use of a terminal zero to the right of the decimal point (e.g., use 5 rather than 5.0) to minimize 10-fold dosing errors.

• Use a zero to the left of a dose less than 1 (e.g., use 0.1 rather than .1) to avoid 10-fold dosing errors.

• Avoid abbreviations of drug names.

• Spell out dosage units rather than using abbreviations.

• Ensure that prescriptions and signatures are legible.

Once-Daily Drug for Persons with HIV

The U.S. Food and Drug Administration has approved efavirenz (Sustiva), a once-daily nonnucleoside reverse transcriptase inhibitor for the treatment of both adults and children with human immunodeficiency virus (HIV) infection. It is the first anti-HIV drug to be approved for once-daily dosing with or without food, and it should be used in combination with other anti-HIV drugs. Efavirenz is the second drug in the nonnucleoside reverse transcriptase inhibitor class of antiviral agents to be approved for use in children.

Results from clinical trials that lasted up to 24 weeks indicate that, when used in two-, three- and four-drug combinations, efavirenz reduces plasma HIV RNA to below quantifiable levels in most treatment-naive and treatment-experienced patients with HIV infection. According to the manufacturer, efavirenz penetrates into the cerebrospinal fluid, a common viral sanctuary.

In studies, efavirenz was generally well tolerated. The most significant adverse events were nervous system symptoms, which were reported in about one half of patients (e.g., dizziness, insomnia, somnolence). The discontinuation rate for nervous system symptoms was about 2.6 percent. Although rare, more serious side effects included mood changes or an inability to think clearly. Mild to moderate skin rash was reported in 25 percent of patients. The incidence of severe rash was rare. Efavirenz is contraindicated in pregnant women or women who may become pregnant.

The drug is available in 200-mg capsules for adult dosing of 600 mg per day, and in 100-mg capsules and 50-mg capsules for pediatric dosing. The wholesale cost for one day of therapy is about $10.95.

Updated Guidelines for Parkinson's Disease

In the face of new therapeutic options and treatment strategies that have developed over the past several years, a group of neurology experts met earlier this year to update a 1994 treatment guideline for the management of patients with Parkinson's disease. The updated treatment algorithm was published as a supplement to the March 1998 issue of Neurology. New information has been incorporated into the guidelines. In particular, the guidelines have more information on the nonpharmacologic management of Parkinson's disease (education, support, exercise and nutrition), the potential for obtaining neuroprotection, the pharmacologic approach to early treatment and the emerging role of surgery as a restorative therapy for patients with advanced disease.

The algorithm is designed to aid the physician in identifying treatment options for patients in the various stages of Parkinson's disease and to provide a rationale for selecting one of these options.

Topical Adhesive for Skin Wound Closure

A topical skin adhesive (Dermabond) for holding the edges of superficial wounds closed has been approved by the U.S. Food and Drug Administration. The quick-setting glue forms a film over the wound and gradually falls off as the skin heals. It is indicated for topical application to close easily approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery, and simple, thoroughly cleansed trauma-induced lacerations. The adhesive should be used in conjunction with, but not in place of, subcuticular sutures, when they are required.

In a controlled randomized, prospective trial including 818 patients, the adhesive was shown to be equivalent to sutures, staples and skin strips in both wound healing and cosmetic result. The advantages of the adhesive were shorter treatment time, easier application technique, and less patient pain and discomfort.

The adhesive is applied in thin layers (a minimum of three) with a light brushing stroke after the wound has been cleaned and its edges approximated. A flexible bond is formed in 45 to 60 seconds, reaching full strength in about two and one-half minutes. Healing typically occurs in five to 10 days. The chemical compound used in Dermabond is octylcyanoacrylate adhesive.

Infliximab for Crohn's Disease

The U.S. Food and Drug Administration has approved a monoclonal antibody called infliximab (Remicade) for use in patients with moderate to severe Crohn's disease. Infliximab, the first approved treatment for Crohn's disease, is a genetically engineered antibody against a protein called tumor necrosis factor alpha that promotes inflammation in the body. The product is indicated for the reduction of symptoms of moderate to severe Crohn's disease in patients who have not responded well to traditional treatments, including antibiotics, corticosteroids and other immunosuppressant agents.

In clinical trials, the improvement in patients receiving infliximab was measured in terms of the number of liquid or soft stools, the number and severity of abdominal cramps, and the overall sense of well-being. Most patients benefited from the treatment within a two- to four-week period following a single intravenous infusion of infliximab. Data are limited on the long-term effectiveness of infliximab.

The most common side effects were related to the intravenous infusion itself and included pruritis or urticaria, low blood pressure, fever or chills, and chest pain. These symptoms were usually temporary. The manufacturer estimates the cost to be about $2,000 for a single-dose infusion.

Local Anesthetic System for Needle Insertions

A new topical adhesive system (EMLA Anesthetic Disc), 2.5 percent lidocaine and 2.5 percent prilocaine cream, has been approved by the U.S. Food and Drug Administration for use on normal intact skin for local analgesia in children over the age of one month. The “peel-and-stick” topical anesthetic, applied to intact skin under a closed dressing, provides dermal pain relief by the release of lidocaine and prilocaine into the epidermal and dermal layers of the skin and the accumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. Satisfactory numbing is achieved one hour after application, reaching a maximum point at two to three hours after removal from the skin. The anesthetic can be applied at home before an office visit.

In placebo-controlled studies, application of the anesthetic cream for at least one hour before needle insertion provided significantly more pain reduction than placebo. It was also effective in providing pain relief during laser treatment for removal of facial port-wine stains. Local reactions included paleness, redness, alteration in temperature sensations, edema, itching and rash. These local reactions were generally mild and transient.

Use of Combination Vaccine in Infants

The U.S. Food and Drug Administration (FDA) has issued a statement reminding physicians that the only approved combination vaccine containing Haemophilus influenzae type b (Hib) conjugate vaccine and diphtheria and tetanus toxoid and acellular pertussis (DTaP) vaccine is for use in toddlers (ages 15 to 18 months). The FDA emphasizes that the approved Hib conjugate vaccines and DTaP vaccines have not been approved for combination use in the primary immunization series in infants at two, four and six months of age. Clinical studies in infants have shown that using some combination products may induce a suboptimal immune response to the Hib component.

For the immunization of children younger than 15 months, any licensed Hib conjugate vaccine may be given concurrently in separate sites with DTaP or diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP), according to the manufacturer. Alternatively, any of the licensed combination products containing DTP and Hib conjugate vaccine may be used. The FDA notes that the Advisory Committee on Immunization Practices has stated a preference for products containing an acellular pertussis component.

For further information on actions that may be needed for infants who received an unlicensed DTaP/Hib combination product, contact the Immunization Hotline of the Centers for Disease Control and Prevention at 800-232-2522.

Treatment for Rheumatoid Arthritis in Adults

Leflunomide (Arava) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of active rheumatoid arthritis in adults. Leflunomide is indicated for the treatment of active rheumatoid arthritis in adults to reduce signs and symptoms and to slow structural damage as evidenced by erosions and joint space narrowing on radiographs.

The efficacy of leflunomide was demonstrated in clinical trials by improvement in end point measures such as counts of tender and swollen joints, physician and patient global assessments, a function/disability measure, and pain intensity. The dosage is 10 or 20 mg once a day.

The most common side effects noted in clinical trials included diarrhea, rash, alopecia and elevated liver function values. Leflunomide is contraindicated in pregnant women, in women of childbearing potential who are not using reliable contraception and in women who are nursing. It is also not recommended in patients with significant liver disease or hepatitis B or C. The FDA has requested studies to determine if leflunomide induces any male-mediated effects on reproduction.