Acute otitis media (AOM) is currently the most prevalent bacterial disease affecting children today. AOM is an inflammation of the middle ear that presents a rapid onset of signs and symptoms such as pain, fever, irritability, anorexia, or vomiting. Complications of AOM include damage to the middle ear, perforations, ossicular erosion, cholesteatoma, and other intratemporal and intracranial problems. The annual cost of medical and surgical treatment of this condition is estimated between $3 billion and $4 billion. Inappropriate antibiotic treatment of AOM encourages the emergence of multidrug-resistant strains of bacterial pathogens.

There are several errors that can lead to overdiagnosis of this condition. For the most part, they include a bias on the part of physicians and parents toward treating the child with antibiotics as a safety net. Given the current difficulty in diagnosing AOM, physicians may be tempted to diagnose a child with the condition without adequate visualization of the tympanic membrane. Even if the ear is examined with a pneumatic otoscope and an adequate view of the tympanic membrane is obtained, it may be difficult to assess the mobility of the membrane and a simple middle ear effusion might be mistaken as AOM.

Several recent studies have given clinically-substantiated support of the use of spectral gradient acoustic reflectometry (SG/AR) as a breakthrough in technology to enhance the diagnostic accuracy of acute otitis media. The studies demonstrated SG/AR to be equivalent to trypanometry in detecting middle ear effusion, yet the method is less expensive. If practitioners are able to accurately detect middle ear effusion, misdiagnosis of AOM will be greatly reduced as will the related overprescription of antibiotics to treat the disease.

Diagnosing AOM with greater accuracy will avoid up to an estimated 8 million unnecessary prescriptions of antibiotics every year (1). In an age where bacterial resistance may severely compromise health care, physicians, providers and parents must be more active in eliminating resistance wherever possible. Chronic illnesses with far-reaching consequences such as AOM are an important area in which to concentrate. In addition to aiding health professionals in accurately diagnose AOM, SG/AR is a reliable means to track the persistent middle ear effusion that often follows the treated AOM infection. Practitioners may thus reduce the use of antibiotics to treat ordinary resolving fluid levels that can be mistaken for a recurrence of the infection.

There is ample evidence that SG/AR is an accurate, easy-to-use, cost-effective means of diagnosing middle ear effusion. This technology can easily be implemented into medical practice, allowing a higher degree of accuracy in the diagnosis of AOM, a reducation in unnecessary antibiotic prescriptions, and a hindrance of the development of antimicrobial resistant bacteria. By adopting this means, physicians will have a more effective means of controlling the most prevalent bacterial disease affecting children today.

CURRENT TREATMENT OF PEPTIC ULCER DISEASE

Peptic ulcer disease is a worldwide problem. The lifetime risk of peptic ulcer disease is about 10%, and two percent of the U.S. population has the disease at any given time. The two primary causes of the condition are infection with the bacterium H pylori and complications from the use of non-steroidal anti-inflammatory drugs (NSAIDs). Profound changes in the diagnosis and treatment of peptic ulcer disease over the past few years have recast peptic ulcer as a curable disease rather than a chronic condition requiring ongoing dietary and lifestyle changes.

Scope: Peptic ulcer disease is a ubiquitous world-wide illness. Treatment of the disease causing pathogen, H pylori usually prevents a recurrence. H pylori’s success as a pathogen stems from its ability to cope with a wide range of gastric environments and to evade immune defenses and pharmaceutical agents. The primary route of contamination is through the fecal-oral route, but there is little evidence for water-borne transmission in the developed world. The bacterium invariably damages the gastric mucosa causing structural and functional abnormalities. Elimination of the bacteria results in healing of gastritis or peptic ulcer disease.

Diagnosis: The presence of peptic ulcer disease is generally detected on the basis of patient history and clinical findings. The classic presentation of the condition is a burning or deep epigastric pain that occurs 1 to 3 hours after eating and is relieved by the ingestion of antacids or mild food. Noninvasive testing such as serologic tests, urea breath test, or stool test for H pylori antigens is recommended in symptomatic patients who have no alarm symptoms for cancer. It is important to inquire about how often patients use NSAIDs as risk of complications is 5 to 20 times higher in such patients.

Prior to non-invasive testing for H pylori, the clinician must differentiate peptic ulcer disease from gastroesophogeal reflux disease (GERD) and recognize the alarm signs of gastric cancer, both of which are indications for early endoscopy. As a general rule, physicians should choose the most accurate test for the level of expertise available. In patients who continue on for treatment, it is important to test again to confirm a cure and thus prevent further morbidity or transmission of infection.

Treatment: The link between H pylori infection and peptic ulcer is now universally accepted, and the illness is known to be curable. Spicy foods and stress are not causative agents as they were once thought, although they can intensify the symptoms. In most cases, cure of the H pylori infection results in the cure of peptic ulcer disease as long as the use of NSAIDs has been discontinued. The persistence of symptoms after appropriate treatment of H pylori is rare, but suggests a cause other than bacterial infection.

Over-the-counter antacids are effective in relieving the symptoms of peptic ulcers. However, histamine blockers (cimetidine, famotidine, and ranitidine) and proton pump inhibitors (omeperazole and lansoperazole) are now the agents most widely used to treat symptoms and expose H pylori to antimicrobial compounds. Antibiotics proven effective against H pylori include amoxicillin, clarithromycin, metronidazole, and tetracycline. Strains resistant to each of these agents has been described, though they are extremely rare for tetracycline and amoxicillin. Clarithromycin resistance raises the largest concern due to the incresing general use of macrolides.

The most important factors in choosing the appropriate therapy are success in eradicating the bacteria, preventing bacterial resistance, minimizing adverse effects and cost, and maintaining patient compliance. The most effective regimens currently are an H2 blocker or proton pump inhibitor combined with two antibiotics administered for 14 days. These triple drug combinations are more likely to eradicate H pylori and less likely to produce resistant strains. Cure of infection should be confirmed 4 weeks after completion of treatment.

Compliance with drug therapy is one of the most important considerations in this and most other treatment modalities. Physicians can help patients comply by helping them understand the rationale behind the treatment and the possible consequences of incomplete or inadequate regimens. It is important that patients comprehend the roles of H pylori, outcomes with concomitant NSAID use, and proper medications in peptic ulcer disease. Above all, give patients encouragement that taking these medications and tolerating the side effects will lead to an elimination of the pain and discomfort in less than two weeks time.

GINSENG AND QUALITY OF LIFE

Panax ginseng, also known as Korean ginseng is one of the oldest, most popular, and most expensive herbs in the world. Siberian ginseng is of a different genus than panax but carries with it the same indications. Purported uses of panax ginseng include a huge range of effects, from raising overall vitality and quality of life to anticancer and aphrodisiac. The Chinese believe it to be a panacea, hence the name panax. The common uses of the plant are currently under investigation, though none of them have yet been proven conclusively.

An estimated 6 million Americans use this root to enhances physical performance (including sexual), improve vitality, and increases resistance to stress and aging. Though some animal and in vitro studies suggest that ginseng has beneficial effects on immune and endocrine functions, evidence of its effects on humans is limited and contradictory. Despite extensive use of the herb, adverse reactions are rare and ginseng is on the FDA's GRAS list. However, at least 1 fatality has been attributed to a ginseng product contaminated with the herbal stimulant ephedra. Ginseng can act as a mild stimulant and should probably be avoided in association with other stimulants or in patients with cardiovascular disease. Common side effects of ginseng are tachycardia and hypertension. Rare endocrinologic effects include mastalgia and postmenopausal bleeding, both of which cease with discontinuation of ginseng.

A major reason for the lack of clinical data regarding ginseng's effects on health is the inherent difficulty of quantifying intangible benefits such as "vitality" and "quality of life." A 3-month randomized trial demonstrated a significant increase in subjective "quality-of-life" scores among 625 ginseng users. In an randomized-double-blinded-placebo-controlled study, college-aged volunteers who took 100 mg of ginseng twice daily for 3 months experienced a statistical improvement in the speed at which they were able to perform mathematical calculations. They did not experience any improvement in motor function or other cognitive functions; no adverse effects were seen in this study.₍₁₎No studies to date compare ginseng's effect with that of widely available and inexpensive cognitive stimulants such as caffeine. There has also been no controlled confirmation of the aphrodisiac effects of the herb in humans. A case-control study suggests an association, but not necessarily a causal relationship, between the use of ginseng and lower cancer rates.₍₂₎

Patients who consume ginseng are risking a high price for little proven benefit. Commercial preparations of ginseng cost as much as $20 per ounce and, due to the current state of herbal regulation, vary tremendously in quality. In a recent analysis of 54 available ginseng products, 85% were determined "worthless," containing little or no ginseng.₍₃₎ E senticosis, which is marketed as "Siberian ginseng,” was found to contain no true ginseng.₍₄₎ To assure the appropriate quality and efficacy, only preparations containing standardized levels of ginsenoside should be taken. Children and pregnant or lactating women should avoid taking ginseng until safety and efficacy are adequately proven in scientifically controlled studies.

1. D'Angelo R, Grimaldi M, Caravaggi M, et al. A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers. J Ethnopharmacol. 1986;16:15-22.
2. Taik-Koo Y, Soo-Yong C. Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 1995;4:401-408.
3. Castleman M. Ginseng. Herb Q. 1990;48:17-24.
4. O 'Hara M, et al. A Review of 12 Commonly Used Medicinal. Arch Fam Med. 1998;7:523-536

RECENT FDA ACTIONS

Marketing approval has been granted for orlistat (Xenical®/Roche) in combination with a low-fat diet for the treatment of severe obesity. The drug has been since the summer of 1998 in Europe, Mexico, and some countries in South America. It acts by inhibiting lipase enzymes which facilitate the breakdown of dietary lipids. Although the drug was delayed due to concerns about breast cancer; however, due to additional data, the new package insert does not mention any correlation with breast cancer. In clinical trials, 57% of patients treated with orlistat lost at least 5% of original body weight as compared to 31% of patients on placebo. Adverse effects include intestinal cramping, oily spotting, flatulence, fecal urgency and oily or loose stools.

The Arthritis Advisory Committee of the FDA has recommended approval of rofecoxib (Vioxx®/Merck) for the treatment of osteoarthritis and acute short-term pain. This will be the second drug with selective COX-2 inhibition and will compete with celeboxib (Celebrex®/Searle & Pfizer). The committee recommended that the drug labeling carry the NSAID class warning for possible GI toxicity. Final FDA action may happen by June.

The FDA has approved levalbuterol (Xopenex®/Sepracor) inhalation in two strengths for use iwh a nebulizer in the treatment and prevention of bronchospasm.

An FDA approvable letter has been received for dofetilide (Tikosyn®/Pfizer) for the restoration of normal heart rhythm in patients with atrial fibrillation/atrial flutter therapy.

Ebastine (Rhone-Poulenc Rorer) an antihistamine, has been found “not approvable” by the FDA. The agency did not elaborate on its decision.

RESEARCH RECOMMENDATIONS

Researchers believe that the current RDA for Vitamin C should be raised from 60 mg/day to 100-200 mg/day. However, they report that ingesting greater that 100 mg/day may be associated with adverse events such as diarrhea, abdominal bloating or hyperoxalemia. They state that Vitamin C should be obtained from eating fruits and vegetables (5 servings / day).

1. JAMA 1999; 281:1415-1423.

Stanford University researchers (March 2 issue of Proceedings of the National Academy of Sciences) report that a methodology used by bacteria to destroy other microorganisms may potentially be utilized to enhance the effectiveness and diminish the side effects of many different drugs. This may be especially true with agents used to treat immunosuppression, inflammation and hypertension.

The American Society of Anesthesiologists strongly recommend that patients discuss their use of dietary supplements prior to surgery. They should also discontinue their use at least 2 to 3 weeks prior to the procedure. This new recommendation is based on a number of reports of significant changes in heart rate and/or blood pressure during surgery in some patients taking herbal medications.

The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of any sponsoring organizations.