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Diagnostic Accuracy of Tests for Eradication of H. pylori

The treatment of duodenal ulcers has changed from reducing acid production to treating the underlying Helicobacter pylori infection. Various methods are used to detect the presence of H. pylori infection and determine the effectiveness of the treatment modalities. Rollán and associates compared the diagnostic accuracy of various invasive and noninvasive tests used to determine the presence of H. pylori infection after antibiotic therapy.

A total of 59 patients with active duodenal ulcer (defined as a circumscribed break in the duodenal mucosa that measured at least 5 mm in diameter) were enrolled in the study and were consecutively assigned to two treatment groups. One group received 40 mg of famotidine once a day for six weeks. During the first two weeks, 750 mg of amoxicillin and 500 mg of metronidazole three times daily were also added. The other group received 20 mg of omeprazole two times a day for four weeks. After the first two weeks, 750 mg of amoxicillin and 500 mg of tinidazole two times a day were added for the last 14 days.

Patients were assessed four to six weeks after completion of therapy. Modalities included carbon-14 urea breath test (UBT), determination of serum IgG antibody levels and multiple antral biopsies for rapid urea testing, histology, Warthin-Starry stain and polymerase chain reaction to detect H. pylori DNA. Infection status was determined by the concordance of test results.

H. pylori was eradicated in 80 percent of the patients studied. The UBT and the rapid urease test had the best sensitivity and specificity. Serology and histology had little diagnostic value because of the high rate of false-positive results.

The authors conclude that the carbon 14 urea breath test is as accurate in determining H. pylori status after antibiotic treatment as rapid urease testing and Warthin-Starry stain. They consider the urea breath test to be the gold standard for confirmation of eradication of H. pylori infection.

KARL MILLER, M.D.

Rollán A, et al. Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection after antibiotic treatment. Am J Gastroenterol 1997;92:1268-74.

Cervicography as Adjunct to Pap Smear Diagnosis

For the past 40 years, the use of Papanicolaou smears to screen women has substantially reduced the morbidity and mortality of cervical cancer. However, there remain significant concerns on the part of many women and physicians about the high false-negative rate associated with the sampling and reading of Pap smears. Even under ideal conditions, false-negative rates as high as 29 percent have been reported. Cervicography is a relatively new diagnostic technique in which a photograph of the cervix is taken after the application of acetic acid. The "cervigram" is examined carefully for evidence of dysplastic changes. If such changes are found, the patient is referred for colposcopy and directed biopsies. It has been hoped that cervicography could potentially spare many women colposcopy, which is more invasive, time-intensive and expensive to perform. Nuovo and associates performed a systematic review of the literature that looked at cervicography used as a diagnostic test in detecting cervical cancer or its precursors.

The authors conducted a MEDLINE search of published studies in English from 1966 through 1996 to retrieve articles that reported data on the use of cervicography for cervical cancer screening. A manual search of Index Medicus was also performed. The first author of all selected publications was contacted to obtain information on any further relevant studies not retrieved by the literature searches. Studies were selected only if they included cervicography as well as the standard reference test--colposcopy, with or without directed biopsy. The studies were evaluated using a quality assessment scale containing nine accepted methodologic standards for the evaluation of diagnostic tests. From each study, the percentage of unsatisfactory or technically defective cervigrams and the results of colposcopy (i.e., normal, any dysplasia, low-grade dysplasia, high-grade dysplasia, cancer) were extracted. In addition, sensitivity, specificity, positive and negative predictive values, disease prevalence and likelihood ratios were calculated. A true-positive cervigram was defined as one with histologic findings on colposcopy of any dysplasia or only high-grade dysplasia.

A total of 23 published studies were initially retrieved. However, after applying the criterion listed above (colposcopy performed on all participants), only seven studies were considered acceptable for inclusion. With regard to the quality assessment score, none of the studies received a score greater than three (the maximum possible was seven). Cervicography was found to have a high sensitivity for detecting high-grade dysplasia (89 to 100 percent). It also had a high false-positive rate, which ranged from 8.2 to 61 percent for any dysplasia and from 9.8 to 63.4 percent for high-grade dysplasia. The positive predictive value for detection of any dysplasia ranged from 22 to 45.5 percent, with a median of 41 percent. In detecting high-grade dysplasia, the positive predictive value ranged from 5.4 to 31.5 percent, with a median of only 10.9 percent.

The authors conclude from their systematic review that current available research on cervicography is generally poor. The majority of published studies to date did not use the reference standard of colposcopy. Moreover, none of the seven studies reviewed adequately met the nine methodologic standards for the evaluation of a diagnostic test. Additional, well-designed studies are needed to further evaluate cervicography before it can be recommended as either a screening test or a secondary triage test.

JEFFREY T. KIRCHNER, D.O.

Nuovo J, et al. Is cervicography a useful diagnostic test? A systematic overview of the literature. J Am Board Fam Pract 1997;10:390-7.

Prevalence and Recognition of Depression in Elderly Patients

Depression is the most common psychiatric disorder in the elderly population. The prevalence is from 8 to 10 percent in geriatric medical outpatients. Primary care physicians accurately recognize less than one half of patients with depression, resulting in potentially decreased function and increased length of hospitalization. Meldon and associates conducted a cross-sectional observational survey to determine the prevalence of depression in elderly patients presenting to the emergency department and to assess the recognition of depression by emergency physicians.

A total of 259 patients older than 65 years of age who presented to the emergency department of a large urban public hospital over a three-month period and who gave oral consent were included in the study. Each patient completed a verbally administered Koenig Scale to identify depression. This scale requires simple yes/no responses to 11 questions. A predetermined cutoff score of 4 was used to identify depression. Demographic data were also collected for each patient. Recognition of depression by the emergency physician was assessed by means of retrospective chart review. The patients' charts were also reviewed for any notation indicating that the emergency department physician recognized depression.

Seventy of the 259 patients (27 percent) who were tested scored at or above the cutoff score for depression. Demographic data correlating with depression included patients who categorized their health as poor and patients living in nursing homes. Emergency physicians failed to recognize depression in all 70 patients.

The Koenig Scale is easy to administer, and sensitive and specific in diagnosing major depressive disorder. The low rate of detection may have been the result of a lack of physician awareness of the high prevalence of depression among elderly patients and their concentration on somatic complaints.

Self-rated depression scales are limited because they do not reliably distinguish between depressive symptoms alone and major depressive disorder. This is probably not a critical point because depressive symptoms alone are a significant clinical and public health problem. Depressive symptoms have also been noted to be underreported by elderly black men.

The authors conclude that screening for depression in the emergency department is critical in subgroups of patients with a particularly high prevalence of depression, including elderly patients, especially those living in nursing homes or reporting poor general health. The Koenig Scale is a potential tool to help physicians rapidly identify depressed patients.

RICHARD SADOVSKY, M.D.

Meldon SW, et al. Depression in geriatric ED patients: prevalence and recognition. Ann Emerg Med 1997;30:141-5.

EDITOR'S NOTE:Recognition of the high incidence of depression in elderly patients is an obligation of the family physician. The morbidity associated with depression in this population includes decreased ability to function, feelings of poor health, increase in frequency and length of hospitalizations, and changes in mental status. Having the patient complete a brief questionnaire helps cue the physician to inquire further about depression, as should clinical presentations that include typical symptoms of depression or multiple, difficult-to-explain somatic complaints. Screening for depression can be performed by clinical staff members other than the physician. Pharmacologic treatment for depression is safe and successful in most of these patients.

--R.S.

Efficacy of Pramipexole in Early Parkinson's Disease

Pramipexole is a full dopamine agonist that has strong specificity for D₃ receptors of the D₂ receptor family. A previous study showed that this agent decreased the amount of time patients had symptoms of Parkinson's disease and improved motor function among patients with advanced disease treated with levodopa. The Parkinson Study Group evaluated the safety and efficacy of four doses of pramipexole in patients with early Parkinson's disease.

A total of 264 patients with Parkinson's disease entered the placebo-controlled, randomized study. Patients had had Parkinson's disease for no more than seven years and were classified as having stage I, stage II or stage III disease. Amantadine, selegiline and anticholinergic medications were permitted during the study period, but none of the patients was receiving other dopamine agonists. Exclusion criteria were dementia, atypical parkinsonism or severe illness. Patients under 30 years of age and those who had taken antipsychotic medications in the previous six months were also excluded.

Patients were randomized to receive either placebo or pramipexole in a daily dosage of 1.5 mg, 3.0 mg, 4.5 mg or 6.0 mg in three divided doses. Patients were seen at baseline and then at two, four, six, eight, 10 and 11 weeks after baseline. Unified Parkinson Disease Rating Scale (UPDRS) scores and the occurrence of adverse events were determined at each follow-up visit. Specific outcomes measured in the study included how well the drug was tolerated and the change in the UPDRS score between baseline and 10 weeks of treatment.

Nearly all of the placebo group (98 percent) completed the study, compared with 81 percent of the patients in the 1.5-mg group, 92 percent of the 3.0-mg group, 78 percent of the 4.5-mg group and 67 percent of the 6.0-mg group. Twenty-five patients withdrew from the study, usually because of adverse reactions such as fatigue, dyspnea, confusion or dizziness. The 6.0-mg dosage group showed a trend toward more adverse reactions, particularly somnolence. At all dosages, the improvement in UPDRS scores between baseline and 10 weeks was statistically significant when compared with placebo. The overall improvement in UPDRS scores was approximately 20 percent over the 10 weeks of treatment.

The authors conclude that pramipexole in dosages of 1.5 mg, 3.0 mg and 4.5 mg per day is safe and effective in improving UPDRS scores in patients with early Parkinson's disease. The long-term effect of pramipexole in forestalling disease progression requires further study.

GRACE BROOKE HUFFMAN, M.D.

Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson disease. A randomized dose-ranging study. JAMA 1997;278:125-30.

Clinical Detection of Left-Sided Heart Failure

The diagnosis and management of left-sided heart failure can be difficult. Badgett and associates reviewed the literature to assess how well clinicians diagnose this condition clinically and to identify clinical findings that may signify decreased ejection fraction, increased filling pressure and systolic or diastolic dysfunction.

Since left-sided heart failure can be defined as decreased ejection fraction or increased filling pressure, patients may fit into one of three categories: those with decreased ejection fraction and normal filling pressure, those with decreased ejection fraction and increased filling pressure, and those with normal ejection fraction and increased filling pressure (diastolic dysfunction). A MEDLINE search was conducted, and 34 studies were found that examined the ability of the clinical findings or clinical examination to predict filling pressure or ejection fraction. Clinical findings were classified as "very helpful," "somewhat helpful" or "helpful only when present" (see the accompanying table).

Clinical Findings Helpful in the Detection of Heart Failure Helpfulness of the findings Increased filling pressure Ejection fraction <40% Diastolic dysfunction Very helpful findings* Radiographic redistribution, jugular venous distention Radiographic cardiomegaly, or redistribution, anterior Q waves, left bundle branch block, abnormal apical impulse Current hypertension † Somewhat helpful findings ‡ Dyspnea,§ orthopnea, tachycardia,// low SBP,// PPP <25%, S3, rales, abnormal abdominojugular reflux, radiographic cardiomegaly¶ Pulse >90, or >100 bpm, SBP <90 mm Hg, PPP <33%, S3, rales, dyspnea, any previous infarction, CPK >200 or >1,000 IU Obesity,§ no tachycardia,§// elderly,// no smoking, no coronary disease Findings helpful only when present# Edema Jugular venous distention, edema Normal radiographic heart size SBP=systolic blood pressure; bpm=beats per minute; PPP=proportional pulse pressure (pulse pressure/systolic pressure); S3=third heart sound; CPK=creatine phosphokinase in postinfarction patient. *--Very helpful findings are significant in all studies and have been studied at least twice. The findings of radiographic cardiomegaly or current hypertension are always independently significant. †--Current hypertension is defined as systolic pressure >160 mm Hg or diastolic pressure >100 mm Hg or >105 mm Hg. ‡--Somewhat helpful findings are significant in at least one half of studies. For systolic dysfunction, only findings significant in over one half of studies are listed. §--Only studied once. //--No cutoff to define abnormal. ¶--Cardiomegaly is somewhat helpful in initially detecting increased filling pressure. However, cardiomegaly may remain after reduction of the filling pressure. #--Findings helpful only when present are consistently reported as highly specific, although they are not usually statistically significant. Reprinted with permission from Badgett RG, Lucey CR, Mulrow CD. Can the clinical examination diagnose left-sided heart failure in adults? JAMA 1997;277:1712-9.

The diagnosis of increased left ventricular filling pressure cannot be made on the basis of a single clinical finding. Radiographic redistribution (also known as cephalization or pulmonary venous hypertension) and jugular venous distention were found to be very helpful findings but are best used to confirm increased filling pressure in a patient with known severe systolic dysfunction. Lack of radiographic redistribution or jugular venous distention, however, does not exclude increased filling pressure. Dyspnea and abnormal vital signs were found to be somewhat helpful in the detection of increased filling pressure. Dependent edema was helpful in making the diagnosis only when present.

Since the detection of increased filling pressure is difficult, the authors suggest that the number of abnormal findings on examination may correlate with a probability of increased filling pressure. In the absence of known severe systolic dysfunction, patients with no more than one abnormal finding are likely to have a normal filling pressure, whereas those with at least three abnormal findings may have increased filling pressure.

Certain clinical findings may help identify patients with an ejection fraction of less than 40 percent. These findings are as follows: cardiomegaly (radiographically determined), abnormal apical impulse, radiographic redistribution, left bundle branch block and anterior Q waves. Tachycardia, decreased blood pressure and a third heart sound may be somewhat helpful findings. Insignificant clinical findings include the patient's age, orthopnea, left ventricular hypertrophy, a history of hypertension and a history of heart failure. Again, patients may be classified as having a high, an indeterminate or a low probability of decreased ejection fraction. A decreased ejection fraction is much more likely if three or more abnormal clinical findings are present. Patients with a low probability of decreased ejection fraction have none of the abnormal clinical findings associated with a decreased ejection fraction.

Distinguishing between diastolic and systolic dysfunction may be aided by the finding of elevated blood pressure during an episode of increased filling pressure. Obesity, lack of tachycardia, absence of smoking and no history of coronary artery disease may be somewhat helpful findings. Patients with a normal heart size are unlikely to have diastolic dysfunction.

The authors conclude that, while it is difficult to clinically diagnose left-sided heart failure, certain findings make such a diagnosis more or less likely.

GRACE BROOKE HUFFMAN, M.D.

Badgett RG, et al. Can the clinical examination diagnose left-sided heart failure in adults? JAMA 1997;277:1712-9.

Accuracy of the Electronic Pacifier Thermometer

Rectal temperature measurement is considered the most accurate way of assessing temperature in infants, but it may be difficult to obtain correctly. Axillary temperature is easily obtained but is often inaccurate. Tympanic temperature devices are commonly used, but some studies have indicated doubt about their accuracy, especially in infants and young children. Press and Quinn evaluated the accuracy of the electronic pacifier thermometer.

Temperatures obtained rectally and with the pacifier thermometer were compared in 100 children between seven days and 24 months of age who were seen in an emergency department or an inpatient pediatric unit. Sublingual and rectal temperatures were taken sequentially, one immediately after the other. The initial site of measurement was altered from patient to patient. Fever was defined as a rectal temperature of 38.0°C (100.4°F) or greater.

The time for the pacifier to reach a steady-state temperature was measured in the first 30 children and ranged from two minutes and 15 seconds to four minutes and 15 seconds. The mean supralingual temperature was 37.5°C (99.9°F), and the mean rectal temperature was 38.0°C (100.4°F). The mean difference of 0.49°F between the two thermometers was significant. However, when the mean difference between the two readings was adjusted upward by 0.5°F for the pacifier thermometer, the difference was not statistically significant.

Fifty patients had a rectal temperature of 38.0°C (100.4°F) or greater, and fever was identified by the pacifier thermometer in 36 of these 50 children. This number increased to 46 when 0.5°F was added to the supralingual reading. None of the remaining four children in whom fever was missed by the oral reading had a fever of greater than 38.5°C (100.8°F) rectally. The pacifier thermometer was 72 percent sensitive and 97 percent specific in the detection of fever. The sensitivity increased to 92 percent when oral readings were adjusted upward by 0.5°F, but the specificity decreased to 76 percent.

The authors state that the rectal temperature should remain the gold standard for recording temperature, especially in infants younger than three months. However, the pacifier thermometer seems to be a reasonable and easier alternative for parents of older infants and children, especially when exact temperature measurements are less crucial. A disadvantage of the pacifier thermometer is the mean time of more than three minutes that is necessary to reach a steady state. This feature may make it a more feasible option for home use or use in low-volume ambulatory care settings, as opposed to the emergency department or a busy office.

JEFFREY T. KIRCHNER, D.O.

Press S, Quinn BJ. The pacifier thermometer: comparison of supralingual with rectal temperatures in infants and young children. Arch Pediatr Adolesc Med 1997;151:551-4.

Family Opinions About End-of-Life Medical Care

How good a job, in the opinion of family members, do physicians do in providing end-of-life care? Hanson and colleagues interviewed recently bereaved family members about the terminal care given their relative to determine what their perceptions were and what suggestions they had to improve end-of-life care.

Death certificates were obtained for people who were older than 65 years of age when they died and whose cause of death was listed as chronic lung disease, cancer, cirrhosis, congestive heart failure or stroke. A family member was interviewed to determine if the decedent had had cardiopulmonary resuscitation (CPR), had been on a ventilator or had been in an intensive care unit during the final month of life. The family member was asked about conversations with the physician concerning the use of these treatments and the existence of living wills or similar advanced directives. The family member was also asked, "Do you believe that more medical treatments should have been used to keep [your relative] alive as long as possible?" and "Do you believe that more medical treatments should have been used to relieve [your relative's] pain?"

A total of 461 telephone interviews were completed. About one half of the decedents had died of cancer. Nine percent of patients had received CPR, 11 percent had been on a ventilator and 24 percent had been in an intensive care unit during the last month of life. In less than one half (46 percent) of cases, a capable patient had discussed end-of-life treatments with a physician. In 6 percent of cases, capable patients did not discuss end-of-life decisions with their physicians, although family members had such discussions. Family members generally did not disagree with the final treatments ordered, although 6 percent of patients or interviewees had wanted treatment not recommended by the physician, and 8 percent of family members thought that more treatment should have been used to prolong life. Most respondents (78 percent) thought that the decedent had pain at the end of life, and 12 percent thought more pain relief had been needed; 18 percent thought more relief had been needed for other symptoms. Almost all comments (91 percent) about hospice care were positive, and 69 percent were pleased with hospital care. Nursing home care generated the lowest percentage of positive comments (51 percent). Staff there were thought to be inattentive and poorly trained, and physicians were thought to be remote.

The authors conclude that some of the suggestions provided by the participants could help efforts to improve end-of-life medical care. In general, the recommendations involved improved communication; specifically, families wanted more information about prognoses, less medical jargon and greater access to physicians.

GRACE BROOKE HUFFMAN, M.D.

Hanson LC, et al. What is wrong with end-of-life care? Opinions of bereaved family members. J Am Geriatr Soc 1997;45:1339-44.

Ardeparin and Danaparoid for Prevention of DVT

Without anticoagulation prophylaxis, deep venous thrombosis occurs in up to 30 percent of patients after abdominal surgery and in 40 to 70 percent of patients after major orthopedic surgery on the lower limbs. Ardeparin sodium, a low-molecular-weight heparin, and danaparoid sodium, a heparinoid, have received approval from the U.S. Food and Drug Administration for use in the prevention of deep venous thrombosis. Danaparoid is approved in the United States only for use in patients who have had hip replacement, and ardeparin is approved only for use in those who have had knee replacement. Consultants for the Medical Letter on Drugs and Therapeutics reviewed the evidence for the use of these two agents.

Low-molecular-weight heparins are produced by depolymerizing standard heparin. These heparins inactivate factor Xa and thrombin (factor IIa). They are more bioavailable than standard heparin after subcutaneous injection and have a longer half-life, resulting in the need for fewer doses per day. The plasma heparin concentrations are more predictable, permitting use of fixed dosages without routine monitoring of heparin activity.

Danaparoid sodium is a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate derived from porcine intestinal mucosa. It has a higher anti-Xa:anti-IIa ratio and a longer half-life than low-molecular-weight heparins. It can be given in fixed weight-adjusted doses once or twice daily and generally does not require laboratory monitoring. Few controlled trials of danaparoid have been published. One randomized controlled trial found that deep venous thrombosis occurred after hip replacement in 17 percent of the patients treated with danaparoid and in 32 percent of the patients treated with heparin and dihydroergotamine. One patient in each group developed pulmonary embolus.

Results of a double-blind randomized trial comparing ardeparin with placebo in patients undergoing knee surgery demonstrated that deep vein thrombosis occurred in 30 percent of the patients taking ardeparin and in 59 percent of the patients receiving placebo, a significant difference. Rates of major bleeding events were similar in both groups. Another study demonstrated that bleeding was more common with use of ardeparin. The incidence of bleeding complications with low-molecular-weight heparins or danaparoid appears to be similar to the rates with standard heparin. Heparin-induced thrombocytopenia may occur with any of these agents but appears to be less common with low-molecular-weight heparin and has not been reported with short-term use of danaparoid. Although the low-molecular-weight heparins are approved only for use in specific procedures, many experts believe that they could be used interchangeably for any of these major surgeries.

The Medical Letter consultants conclude that ardeparin and danaparoid appear to be slightly more effective than warfarin or standard heparin but have a similar incidence of bleeding complications and a lower incidence of thrombocytopenia. Unlike standard heparin, they can be given once or twice a day in fixed weight-adjusted dosages and do not usually require laboratory monitoring.

BARBARA APGAR, M.D., M.S.

Medical Letter consultants. Ardeparin and danaparoid for prevention of deep vein thrombosis. Med Lett Drugs Ther 1997;39(1011): 94-5.

Effect of Aspirin on Preventing Stroke in Atrial Fibrillation

Placebo-controlled studies have demonstrated the efficacy of oral anticoagulant therapy for prevention of stroke in patients with atrial fibrillation. Since oral anticoagulant therapy is inconvenient and increases the risk of bleeding, three randomized placebo-controlled trials have evaluated the use of aspirin for stroke prevention in patients with atrial fibrillation. One study revealed a nonsignificant relative risk reduction of 18 percent, one found a nonsignificant 15 percent relative risk reduction and one found a 44 percent relative risk reduction of stroke. The Atrial Fibrillation Investigators performed a meta-analysis of pooled data from these three studies to identify any subgroups of patients who might be particularly responsive to aspirin therapy.

The three studies included the Atrial Fibrillation, Aspirin, Anticoagulation Study (AFASAK), the European Atrial Fibrillation Trial (EAFT) and the Stroke Prevention in Atrial Fibrillation 1 Study (SPAF1). A total of 1,985 patient-years were assigned to the aspirin group and 1,867 patient-years were assigned to the placebo group. The daily dose of aspirin varied, from 75 mg in AFASAK, to 300 mg in EAFT, to 325 mg in SPAF1. The primary end point in the meta-analysis was occurrence of ischemic stroke.

When data from all three studies were combined, the relative risk reduction with aspirin therapy was 21 percent. Disabling stroke was decreased by 17 percent and nondisabling stroke was reduced by 27 percent with aspirin use. Aspirin therapy did not appear to be efficacious in patients without risk factors for stroke.

Patients with a history of hypertension had a 36 percent relative reduction in the risk of stroke, although the analysis did not reveal a conventional statistical significance. When patients with a previous stroke or transient ischemic attack were evaluated, aspirin therapy was associated with a relative risk reduction of 19 percent. The data did not show convincing evidence of particular efficacy in any subgroup of patients.

The authors conclude that aspirin appeared to have a slightly protective effect against stroke in patients with atrial fibrillation, but no subgroup was identified that was particularly responsive to aspirin. Other analyses have shown that oral anticoagulant therapy offers a larger and more predictable reduction in the risk of ischemic stroke for patients with atrial fibrillation.

BARBARA APGAR, M.D., M.S.

The Atrial Fibrillation Investigators. The efficacy of aspirin in patients with atrial fibrillation: analysis of pooled data from 3 randomized trials. Arch Intern Med 1997;157: 1237-40.

Role of Hepatitis G Virus in Acute and Chronic Liver Disease

Viral hepatitis is known to be caused by at least five distinct viruses (A, B, C, D and E) that can result in acute infection. Hepatitis B, C and D viruses can result in chronic infection. A novel agent called hepatitis F has been described but has not yet been confirmed. Another hepatitis virus, the hepatitis G virus, has been identified, confirmed and cloned. Hepatitis G virus has been reported to be associated with other diseases such as aplastic anemia. Cheung and colleagues reviewed the literature to examine the association between hepatitis G virus and various liver diseases.

Hepatitis G is an RNA virus similar to other viruses in the Flaviviridae family. Currently, serologic testing for hepatitis G is not available. Hepatitis G virus infection can only be diagnosed by polymerase chain reaction assay, which detects viral RNA in serum. Hepatitis G antibody assays to detect evidence of past infection are not available. An enzyme-linked immunosorbent assay for detection of antibodies has recently been described as a potent serologic marker for immunity to hepatitis G virus infection, but further studies are needed.

Studies indicate that the prevalence of hepatitis G virus among blood donors ranges from 0.9 to 10.0 percent. The prevalence among populations receiving multiple blood products has been found to be 5.4 to 18.6 percent among patients with hemophilia and 18.0 percent among anemic patients requiring multiple transfusions. Hepatitis G virus is a blood-borne virus that is parenterally transmitted. However, as in hepatitis C, many patients who are positive for hepatitis G have no identifiable parenteral risk factors.

The role of hepatitis G virus in post-transfusion hepatitis is uncertain. The correlation between the presence of the virus and chronic liver disease is poor. Hepatitis G is rarely a cause of post-transfusion hepatitis.

Some evidence indicates that hepatitis G virus is a causative factor in acute community-acquired non-A­E hepatitis, but hepatitis G is not a major cause of acute community-acquired hepatitis in the United States. Most cases of hepatitis G virus infection occur in the setting of coinfection with other hepatitis viruses, such as hepatitis B and C. Hepatitis G virus seems to have little effect on the course of infection or the response to interferon therapy, and the clinical course is largely determined by the coinfecting virus.

The role of hepatitis G virus in hepatocellular carcinoma is unclear. Serum hepatitis G RNA, usually along with hepatitis B or C, has been found in patients with hepatocellular carcinoma. In an Austrian study, hepatitis G RNA was the only infectious viral agent identified in 8 percent of 85 patients with hepatocellular carcinoma. It is believed that hepatitis G is unlikely to be a major etiologic agent in hepatocellular carcinoma.

No data exist on the treatment of patients with hepatitis G virus alone, since the role of hepatitis G in chronic viral hepatitis has not yet been determined. Treatment response in patients coinfected with hepatitis G virus and another hepatitis virus is similar to that of the other hepatitis virus.

The authors conclude that although hepatitis G virus appears to be a hepatotrophic virus, its independent role in acute and chronic liver disease is unclear. Correlation is poor between serum hepatitis G RNA and elevation of alanine transaminase levels, and viremia frequently occurs without alanine transaminase elevation. Therapy for hepatitis G virus is not yet recommended, since its role as an etiologic agent in liver disease is unclear. Interferon could be used if hepatitis G virus infection were to be demonstrated as a cause of liver disease.

In a related editorial, Bonkovsky points out that the most striking association to cause concern is between hepatitis G virus and aplastic anemia following acute hepatitis, although even this relationship requires further substantiation. He states that the type and severity of hepatitis that hepatitis G virus might cause is so minor as to put doubt on the categorization of this virus as a hepatitis virus.

RICHARD SADOVSKY, M.D.

Cheung RC, et al. Hepatitis G virus: is it a hepatitis virus? West J Med 1997;167:23-33, and Bonkovsky HL. The alphabet soup of viral hepatitis: is G a new flavi(or) in the mix? [Editorial]. West J Med 1997;167:50-1.

Changes in the Incidence of Bacterial Meningitis

Before the development of an effective vaccine, Haemophilus influenzae type b was a common pediatric pathogen. The incidence of H. influenzae meningitis or invasive disease in children under the age of five years was one in 200 cases. Moreover, H. influenzae accounted for 70 percent of cases of bacterial meningitis in this age group. Since the vaccine's introduction in 1990, a growing body of data has suggested a dramatic decline in the incidence of H. influenzae meningitis in children. Schuchat and colleagues at the Centers for Disease Control and Prevention reported the results of laboratory-based surveillance for bacterial meningitis completed in 1995, five years after the vaccine was licensed.

Surveillance for invasive disease caused by H. influenzae, Neisseria meningitidis, group B streptococcus, Listeria monocytogenes and Streptococcus pneumoniae was performed in four states: Georgia, Tennessee, Maryland and California. The 22 counties studied represented approximately 10 million persons, or 3.9 percent of the United States population. Twenty-four percent of the study population was black. Invasive disease was defined as a disease in which a specific organism had been isolated from a sterile site, such as blood or cerebrospinal fluid. A case of invasive disease was considered to be meningitis if the patient's medical record listed meningitis as a diagnosis.

During 1995, bacterial meningitis was identified in 248 residents in the surveillance areas. The most common agent identified was S. pneumoniae (47 percent), followed by N. meningitidis (25 percent), group B streptococcus (12 percent), L. monocytogenes (8 percent) and H. influenzae (7 percent). The median age of the patients found to have meningitis was 25 years. The main pathogen causing meningitis in the neonatal patient group was group B streptococcus, and in those aged two to 18 years, N. meningitidis was the predominant pathogen. In patients over the age of 19 years, S. pneumoniae caused 62 percent of the reported cases of meningitis. Only one third of all cases of meningitis occurred in children under the age of five years. When invasive infections caused by H. influenzae in all age groups were totaled, 181 cases were reported, and meningitis was associated with 18 cases.

The authors conclude that the median age of patients with meningitis caused by one of these five pathogens has changed dramatically over a nine-year period. In 1986 the median age was 15 months, and by 1995 it was 25 years. In 1986, two thirds of patients with bacterial meningitis were between the ages of one month and five years. However, by 1995 meningitis had decreased by 87 percent in this age group. In addition, cases of meningitis in all age groups declined 55 percent.

Widespread use of the H. influenzae type b vaccine is primarily responsible for producing this major change in the epidemiology of bacterial meningitis. A formidable goal is to continue to develop effective vaccines for use in children, especially against group B streptococcus and pneumococcus, which are now the two predominant organisms causing invasive disease.

JEFFREY T. KIRCHNER, D.O.

Schuchat A, et al. Bacterial meningitis in the United States in 1995. N Engl J Med 1997;337:970-6.

AIDS, Unexplained Fever and Value of Bone Marrow Biopsy

Patients with acquired immunodeficiency syndrome frequently develop fever and other nonspecific symptoms that elude diagnosis despite laboratory tests and imaging studies. In the general population, bone marrow biopsy is a safe and useful diagnostic test for investigating fever of unknown origin. Benito and associates studied the role of bone marrow biopsy in patients with human immunodeficiency virus (HIV) infection and fever of unknown origin.

Bone marrow biopsy was performed in 123 consecutive patients with 137 episodes of fever that persisted for 10 or more days. Biopsy was performed after patients had been hospitalized for one week. One or more AIDS-defining conditions were present in 113 (91.9 percent) of the patients before evaluation of fever began.

A specific etiology of fever of unknown origin was identified in 52 (38 percent) of the 137 episodes of fever by means of bone marrow culture and/or pathologic examination. Pathologic examination of the bone marrow alone led to diagnosis of a specific condition in 43 episodes of fever of unknown origin, representing 31.4 percent of all episodes.

Three types of disease were diagnosed by bone marrow biopsy: mycobacterial infection (36 patients), non-Hodgkin's lymphoma (12 patients) and visceral leishmaniasis (four patients). Bone marrow culture was more sensitive than microscopic examination in the diagnosis of mycobacterial infection. Tuberculosis was found in 18 patients and was confirmed by culture in 17 patients (10 from culture of bone marrow, three from blood, three from sputum and one from stool).

Mycobacterium avium­intracellulare complex (MAC) infection was diagnosed in 14 patients. The authors note that bone marrow biopsy was not sensitive for the diagnosis of MAC; more than one third of these patients had only nonspecific cytologic abnormalities. Bone marrow cultures were positive for organisms in five patients in whom the pathologic study was not diagnostic. All of the patients with MAC infection diagnosed by bone marrow examination subsequently had positive blood cultures in less than two weeks. In all 12 patients with non-Hodgkin's lymphoma, bone marrow biopsy was the hallmark of the presence of the tumor.

The authors conclude that bone marrow biopsy is a useful procedure for identifying the etiology of fever of unknown origin in patients with HIV disease, particularly in those who live in areas where tuberculosis and leishmaniasis are prevalent. Bone marrow biopsy is also useful in the diagnosis of extranodal non-Hodgkin's lymphoma when mass lesions are not accessible. In the diagnosis of MAC infection, bone marrow biopsy is no more valuable than blood culture.

BARBARA APGAR, M.D., M.S.

Benito N, et al. Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome. Arch Intern Med 1997; 157:1577-80.

Use of Prednisone and Aspirin for Recurrent Fetal Loss

Recurrent fetal loss is a manifestation of several autoimmune diseases, including systemic lupus erythematosus. The lupus anticoagulant, an inhibitor of in vitro coagulation, and several other autoantibodies have been detected in otherwise healthy women with a history of recurrent fetal loss. The mechanism of spontaneous abortion in these patients is not known. Moderate to high doses of prednisone and aspirin have been recommended as therapy on the rationale that most of these women have a subtle autoimmune disorder that is manifested by recurrent fetal loss. Laskin and associates evaluated the use of aspirin and prednisone in women with autoantibodies and a history of unexplained fetal loss with respect to maternal morbidity and fetal mortality.

Patients included in the study were 18 to 39 years of age with a history of at least two consecutive fetal losses before 32 weeks' gestation, and at least one of the following laboratory findings on two of three occasions: antinuclear antibodies, anti-DNA antibodies (double- or single-stranded), antilymphocyte IgM, anticardiolipin IgG or lupus anticoagulant. Exclusion criteria included diabetes mellitus, systemic lupus erythematosus, luteal phase defect, chromosomal abnormality, diastolic blood pressure greater than 90 mm Hg and previous prednisone therapy. Those selected for the study were randomized to receive placebo or 100 mg per day of aspirin until 36 weeks' gestation, plus prednisone, 0.8 mg per kg daily (maximum: 60 mg) for four weeks, followed by 0.5 mg per kg per day (maximum: 40 mg) until delivery.

A total of 202 women were enrolled in the study, and 101 were randomized into each group. Each woman was followed throughout her pregnancy and for at least two years postpartum, regardless of the outcome of the pregnancy. There were no baseline differences between the groups in age, number of prior fetal losses, number of live births, percentages with a specific type of autoantibody or lupus anticoagulant, and smoking history.

There were a total of 66 live births in the treatment group and 57 live births in the placebo group. However, after adjusting for maternal age and the week of gestation at which the previous fetal losses occurred, the aspirin and prednisone had no beneficial effect. Preterm delivery, premature labor and premature rupture of the membranes all occurred significantly more often in the treatment group. The majority of these births occurred between 32 and 38 weeks of gestation. However, the birth weights of all infants, including those in the placebo group, were appropriate for gestational age (between the 10th and 90th percentiles). There was no difference between the two groups with respect to congenital anomalies or incidence of infection.

Hypertension occurred in 13 percent of patients in the treatment group compared with 5 percent of patients in the placebo group. Gestational diabetes was also more common in patients in the treatment group (15 percent versus 5 percent in the placebo group). Two women in the treatment group developed cataracts, compared with none in the placebo group.

The authors conclude that in women with a history of recurrent fetal loss and the presence of autoantibodies, aspirin and prednisone are no more effective than placebo in preventing fetal loss during a subsequent pregnancy. They also found a higher incidence of preterm delivery in patients treated with aspirin and prednisone compared with those treated with placebo. Had this therapy been effective in improving pregnancy outcome in women with recurrent fetal loss, the few instances of hypertension and gestational diabetes would not be sufficient to warrant withholding treatment.

JEFFREY T. KIRCHNER, D.O.

Laskin CA, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med 1997;337:148-53.

Psychiatric Disorders and Teenage Parenthood

The first report of the National Comorbidity Survey revealed that early-onset psychiatric disorders are predictors of truncated educational attainment. The second study was conducted to evaluate whether these disorders are associated with subsequent teenage parenthood. Results indicated that women who give birth as adolescents are more likely to become welfare recipients and to have a difficult time establishing independence from government assistance. Over 50 percent of the Aid to Families with Dependent Children budget goes to families started by adolescents. Kessler and associates evaluated the National Comorbidity Survey to determine the relationship between early-onset psychiatric disorders and subsequent teenage pregnancy.

Researchers surveyed 8,098 persons 15 to 54 years of age. Psychiatric disorders consisting of anxiety, affective and conduct disorders, and addiction were positively related to subsequent teenage pregnancy in females, with addictive disorders being the strongest predictors. Male teenage premarital parenthood was significantly associated with conduct disorder. There was no evidence that history of prior psychiatric disorders predicted subsequent abortion or miscarriage. There was a consistently positive association between prior psychiatric disorders and having at least one sexual partner during the previous 12 months. The association between psychiatric disorders and failure to use consistent contraception was nonsignificant, with the exception of conduct disorder among females.

Results of this study suggest that adolescents with psychiatric disorders are at higher risk of teenage pregnancy. These results have important implications for the policy debate on national health care insurance. Results reported in this study add to the growing body of evidence that early-onset psychiatric disorders are associated with important societal costs.

The authors conclude that these findings also have important implications for mental health professionals treating adolescents with psychopathology; the higher risk for pregnancy in this group should be noted. These results should also alert family physicians who treat adolescent mothers or their children to be aware of possible psychopathology and adverse life consequences in this group. Planners of interventions aimed at preventing adolescent pregnancy should consider including a mental health treatment component in the treatment intervention package.

BARBARA APGAR, M.D., M.S.

Kessler RC, et al. Social consequences of psychiatric disorders, II: teenage parenthood. Am J Psychiatry 1997; 154:1405-11.

Chronic Fatigue Syndrome: Not a Diagnosis in Children

Revised Criteria for the Diagnosis of Chronic Fatigue Syndrome* Major criteria Unexplained, persistent or relapsing chronic fatigue that is of new or definite onset (not lifelong) Fatigue is not due to ongoing exertion. Fatigue is not substantially alleviated by rest. Fatigue results in substantial reduction in previous levels of occupational, educational, social or personal activities. Minor criteria Self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social or personal activities Sore throat Tender cervical or axillary lymph nodes Muscle pain Multiple joint pain without joint swelling or redness Headaches of a new type, pattern or severity Unrefreshing sleep Postexertional malaise lasting more than 24 hours *--Criteria were developed by the Centers for Disease Control and Prevention, the National Institutes of Health and the International Chronic Fatigue Syndrome Study Group. A case of chronic fatigue syndrome must fulfill all the major criteria, plus four or more of the minor criteria. Each minor criterion must have persisted or recurred during six or more consecutive months of illness and must not have predated the fatigue. A patient who does not fully meet the criteria for chronic fatigue syndrome may be diagnosed as having idiopathic chronic fatigue. Reprinted with permission from Plioplys AV. Chronic fatigue syndrome should not be diagnosed in children. Pediatrics 1997;100:270-1.

Although chronic fatigue syndrome has no known diagnostic markers, a standardized set of diagnostic criteria has been proposed by the International Chronic Fatigue Syndrome Study Group, the Centers for Disease Control and Prevention, and the National Institutes of Health (see the accompanying table). Plioplys reviews the reasons that this disorder should not be diagnosed in children and adolescents.

Fatigue-producing diseases are more common in children and adolescents than in adults. Among the illnesses that should be excluded in children who present with fatigue are central nervous system disorders (including degenerative illnesses and space-occupying lesions), infectious diseases, myopathies, neuropathies and mitochondrial disorders. Psychiatric disorders must also be considered. Depression, anxiety and somatization are most likely, but the possibility of school phobia and family dysfunction should also be considered.

The author emphasizes that the problems involved with diagnosing chronic fatigue syndrome in children are numerous. The most important problem may be that a diagnosis of chronic fatigue syndrome may prevent recognition of a condition that may be treatable (chronic fatigue syndrome is not treatable). Also, if chronic fatigue syndrome is diagnosed after a "standard" medical work-up, rare conditions may be overlooked if the diagnostic work-up is stopped too soon. Psychologic problems may be neglected if chronic fatigue syndrome is diagnosed in children and adolescents and, finally, a diagnosis of chronic fatigue syndrome may promote a "disabled" mindset in the patient.

The author stresses that the internationally developed guidelines for chronic fatigue syndrome should not be applied to children, and that chronic fatigue syndrome should not be diagnosed in these patients.

GRACE BROOKE HUFFMAN, M.D.

Plioplys AV. Chronic fatigue syndrome should not be diagnosed in children. Pediatrics 1997;100:270-1.

Abciximab and Long-Term Protection from Restenosis

Percutaneous coronary procedures are frequently followed by the need for repeat procedures or bypass surgery for coronary artery renarrowing. Abciximab is a monoclonal antibody fragment directed against beta₃ integrin and is known to have short-term protective effects against restenosis in patients undergoing coronary intervention procedures. Topol and colleagues performed a long-term follow-up study of patients who received abciximab during coronary angioplasty or directional atherectomy to evaluate its prolonged protective effects.

Patients who were at increased risk for ischemia during angioplasty or directional atherectomy were included in the study. At the time of the initial revascularization procedure, patients received 325 mg of aspirin, and intravenous heparin. They were then randomized to receive one of three regimens: placebo bolus and placebo infusion, abciximab bolus and placebo infusion, or abciximab bolus and abciximab infusion. The outcomes observed were death, myocardial infarction or need for urgent coronary revascularization. The authors performed the follow-up study 2.5 years after the index percutaneous coronary revascularization procedure. Questionnaires administered by study coordinators were used to collect long-term follow-up data.

A total of 2,099 patients were initially assigned to one of the three treatment groups. Long-term data were available in 662 patients in the placebo group, 663 patients in the abciximab bolus group and 678 in the abciximab bolus plus infusion group. Patients were followed for up to three years.

When all outcomes were considered together at one year, the abciximab bolus plus infusion group had a 19 percent reduction compared with the placebo group. The data indicate that during the first two years of follow-up, 12 coronary revascularization procedures were prevented in the group that received abciximab as a bolus and infusion, compared with the placebo group.

After three years of follow-up, the abciximab bolus plus infusion group had a 13 percent reduction in these outcomes compared with the placebo group. The abciximab bolus plus placebo infusion group did not have similar reductions. Similar beneficial results were apparent when each of the three outcomes was considered separately. Death occurred in 6.8 percent of patients receiving abciximab bolus plus infusion, in 8.0 percent of patients receiving abciximab bolus plus placebo and in 8.6 percent of patients receiving placebo. Myocardial infarction occurred in 10.7 percent of the study subjects receiving abciximab bolus plus infusion, in 12.2 percent of those receiving abciximab bolus plus placebo, and in 13.6 percent of those receiving placebo. Another revascularization procedure was needed in 34.8 percent of the patients who received abciximab bolus plus infusion, compared with 38.6 percent of those who received abciximab bolus only and 40.1 percent of those who received placebo only.

The authors conclude that abciximab is associated with an extended protective effect against death, myocardial infarction and the need for coronary revascularization in patients who receive this medication as a bolus and infusion before their initial coronary revascularization procedure.

GRACE BROOKE HUFFMAN, M.D.

Topol EJ, et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin b₃ blockade with percutaneous coronary intervention. JAMA 1997;278:479-84.

Use of Antibiotics for Acute Otitis Media in Children

Although antibiotics are the standard therapy for acute otitis media in most developed countries, in the Netherlands and Iceland the routine initial approach to therapy is symptomatic treatment. This strategy has been credited with a decrease in antimicrobial resistance. In contrast, about 30 percent of British children less than three years of age visit their family physician because of otitis media every year, and 97 percent receive antibiotics. Between 1990 and 1995, British strains of Streptococcus pneumoniae have shown increasing rates of resistance to penicillin (from 1.5 to 3.9 percent) and erythromycin (from 2.8 to 8.6 percent). An international network of primary care researchers reviewed previous studies to evaluate whether the use of antimicrobial therapy for the management of otitis media should be reassessed.

The researchers were unable to find compelling evidence to support recommendations that antibiotic treatment in children with acute otitis media improved outcomes, although the great variations in study design and quality made this analysis very complex. They were also unable to confirm that antibiotic treatment prevented complications, particularly mastoiditis or meningitis. Previous studies have shown that children younger than two years of age and those attending day care centers are at increased risk of adverse consequences from otitis media; however, no studies have shown that antibiotic treatment improves outcome in children at risk. Studies of different types of antibiotics and regimens have also been inconclusive. Treatment periods ranging from two to 10 days have been shown to be comparable.

The researchers found that the use of antibiotics in patients with otitis media does not appear to dramatically relieve the duration of symptoms, reduce the number of recurrences or improve long-term outcomes when compared with patients who do not receive them.

The Dutch protocol for the treatment of acute otitis media includes use of acetaminophen for at least the first 24 hours (longer in older children without risk factors) and frequent re-evaluation. This approach has resulted in significantly lower rates of resistance to common antibiotics in isolates of S. pneumoniae and Haemophilus influenzae in the Netherlands, compared with other European countries. Similarly, there has been a documented decline in antibiotic resistance in children attending day care centers in Iceland since the country adopted the Dutch protocols for treatment of acute otitis media. When initial management of otitis media emphasizes pain and symptom relief with careful follow-up as in the Dutch system, less than 3 percent of children had persistent symptoms after three days and the outcomes at two months were similar when compared with outcomes in other countries where physicians routinely use antibiotic therapy.

The researchers conclude that more than 80 percent of children with acute otitis media recover with the use of symptomatic treatment and good follow-up care. Measures to prevent otitis media infection in children include breast feeding, avoidance of tobacco smoke and good hygiene to reduce viral transmission. The researchers recommend that the routine use of antibiotics be reconsidered and, if antibiotics are used, that the duration of therapy should be less than 10 days.

ANNE D. WALLING, M.D.

Froom J, et al. Antimicrobials for acute otitis media? A review from the International Primary Care Network. BMJ 1997;315:98-102.

Relationship Between Estrogen Therapy and Cervical Cancer

Although several studies have found an association between the use of oral contraceptives and an increased risk of cervical cancer, little is known about whether similar risks exist when estrogen is used for postmenopausal hormone replacement therapy. Parazzini and colleagues conducted a case-control study to determine whether the use of hormone replacement therapy is associated with an increased risk of cervical cancer.

The study included 645 women from 40 to 75 years of age who were hospitalized between 1981 and 1993 because of histologically confirmed invasive cervical cancer. Control patients included 749 women of the same age admitted for trauma or orthopedic, surgical and dental conditions. None of the women in the control group were admitted because of gynecologic conditions, and none had undergone hysterectomy. Extensive data were obtained from all study participants through the use of structured questionnaires that evaluated lifestyle, risk factors for cervical and other cancers, history of screening for cervical cancer and use of oral contraceptives or hormone replacement therapy.

Estrogen use was reported by 40 women with cervical cancer and 86 women in the control group, for an odds ratio of 0.5 (95 percent confidence interval: 0.3 to 0.8), indicating a possible protective effect. The odds of having cervical cancer fell with the duration of estrogen use. The authors calculated the odds ratio to be 0.6 (0.4 to 1.1) for use of less than 12 months' duration and 0.5 (0.2 to 1.0) for use of 12 months' duration or more when compared with women who had never received estrogen therapy. Protection tended to be stronger in women with 10 or more years of estrogen use and in women who started estrogen therapy before 50 years of age.

Although the use of estrogen replacement therapy in this population was low, the authors conclude that use of exogenous estrogens does not appear to increase the risk of cervical cancer and may have a protective effect. The biologic explanation for this effect is not clear. Some of the differences may be attributable to factors such as the increased use of screening and the lower number of sexual partners reported by women in the control group. However, these results confirm those of an earlier, Swedish study and provide some indication that estrogen replacement therapy does not increase the risk of cervical cancer.

ANNE D. WALLING, M.D.

Parazzini F, et al. Case-control study of oestrogen replacement therapy and risk of cervical cancer. BMJ 1997; 315:85-8.

Nizatidine for Prevention of Postprandial Heartburn

Nizatidine is a selective histamine H₂-receptor antagonist that inhibits histamine-mediated gastric acid secretion. Dosages of 150 mg and 300 mg administered twice a day or at bedtime are approved for the treatment of active duodenal and gastric ulcers, and erosive esophagitis. A lower-dose, over-the-counter formulation is now available for the prevention of postprandial heartburn. Spiegel and associates compared the effectiveness of three different dosages of nizatidine (225 mg, 75 mg and 25 mg) in preventing postprandial heartburn.

A total of 413 subjects were randomized to receive one of the three dosages or placebo. They were given the drug 30 minutes before a meal of chili, cheese-flavored nacho chips and cola. Only 2.9 percent of the subjects receiving placebo had complete prevention of heartburn. In the nizatidine groups, 14.4 percent of the subjects receiving the 225-mg dose and 14.9 percent of those receiving the 75-mg dose had complete prevention of heartburn. The results in the treatment group that received 25 mg of nizatidine were not distinguishable from those in the placebo group.

The longest duration of complete heartburn relief following the meal was significantly greater for all nizatidine treatment groups, compared with the placebo group. All three dosages of nizatidine significantly reduced the average severity of heartburn, compared with placebo. In those subjects whose heartburn was not completely prevented, all dosages of nizatidine were equally superior to placebo in reducing the average severity and peak severity of heartburn. All dosages of nizatidine were well tolerated.

The authors conclude that 75-mg and 225-mg dosages of nizatidine administered 30 minutes before eating a meal that provokes heartburn are effective in providing complete heartburn relief. These two dosages were significantly better than placebo and the 25-mg dosage in preventing postprandial heartburn. The authors conclude that the 75-mg and 225-mg dosages of nizatidine are effective in preventing postprandial heartburn, despite the fact that these dosages are lower than that available in the prescription formulation.

BARBARA APGAR, M.D., M.S.

Spiegel JE, et al. A double-blind, placebo-controlled study of the effectiveness and safety of nizatidine in the prevention of postprandial heartburn. Arch Intern Med 1997;157:1594-9.

An Otic Solution for the Treatment of Acute Ear Pain

Most children with acute otitis media have ear pain. Along with discomfort, otalgia results in fussiness, sleep disturbance and parental anxiety. However, the management of ear pain has been inadequately studied. Physicians commonly recommend acetaminophen, which has a slow onset of action and produces mixed results. A proprietary otic solution, consisting of a mixture of antipyrine, benzocaine and oxyquinolone sulfate dissolved in dehydrated glycerin, has been developed for instillation into the ear canal. It reputedly induces analgesia immediately after coming into contact with the tympanic membrane and has no reported side effects. Hoberman and associates compared the efficacy of this otic solution with an olive oil placebo for the management of pain in children with acute otitis media.

Children between five and 19 years of age presenting to the emergency department with ear pain and acute otitis media were eligible for the study. Children who had received analgesia at home or in the emergency department within the preceding five hours were excluded. The diagnosis of otitis media required the presence of pain with a middle ear effusion and at least one other indicator of acute inflammation, including marked redness, distinct bulging or fullness of the tympanic membrane. Two visual analog scales were used to assess ear pain and were first administered at the time of diagnosis to determine a baseline level of pain. Children receiving a score of 3 or greater were eligible for the study. A total of 54 children were enrolled in the study, with an equal number randomized to receive either five drops of the otic solution or five drops of olive oil. All of the children also received acetaminophen, 15 mg per kg, in a single dose. The visual analog scales were re-administered at 10, 20 and 30 minutes after the instillation of ear drops.

At entry, both groups had essentially the same baseline pain scores. After 10 minutes, 33 percent of the treatment group and 15 percent of the placebo group reported a 50 percent reduction in pain. At 20 minutes, 50 percent of patients in the treatment group versus 44 percent of patients in the placebo group reported a 50 percent reduction in pain. At 30 minutes, the difference was 78 percent for the group receiving the otic solution and 56 percent for the group receiving placebo. None of these differences were statistically significant. When ear pain reduction of 25 percent was assessed, the results also favored the group receiving the otic solution at 10, 20 and 30 minutes. The only difference that reached statistical significance was the number of patients (96 versus 70 percent) who achieved ear pain reduction of 25 percent at 30 minutes. A small number of children did report dramatic and immediate pain relief with the otic solution, whereas pain relief with the olive oil, when attained, was gradual. One patient receiving the otic solution and six patients receiving placebo reported no pain relief at the end of the evaluation period.

The authors conclude that in children with acute ear pain associated with otitis media, a topical otic solution provides adequate analgesia within 30 minutes of administration and, in some instances, much sooner, and appears to be superior to olive oil for this purpose.

JEFFREY T. KIRCHNER, D.O.

Hoberman A, et al. Efficacy of Auralgan for treating ear pain in children with acute otitis media. Arch Pediatr Adolesc Med 1997;151:675-8.

EDITOR'S NOTE: Acute ear pain results in many telephone calls to family physicians, not infrequently during the middle of the night or on weekends. Acetaminophen is usually recommended but has a slow onset of action (usually from 30 to 60 minutes) and thus often does not adequately relieve the child's pain or the parent's anxiety. A potential benefit to using a topical analgesic with a rapid onset of action for ear pain might be fewer phoned-in prescriptions for amoxicillin until the child can be examined. There may even be spontaneous remission in the interim, allowing the physician to forgo antibiotic therapy altogether.

--J.K.

Physicians' Efforts to Help Patients Stop Smoking

Approximately 70 percent of smokers contact a physician each year, and each smoker averages more than four visits to a physician annually. Primary care physicians have an ongoing opportunity to help patients stop smoking. Even brief interventions have been shown to increase smoking abstinence at one year of follow-up. Although most physicians believe they are providing smoking cessation advice to their patients, it is reported that only about 51 percent of smokers remember being advised to quit. Goldstein and associates evaluated patients' perceptions of their physicians' efforts to help them stop smoking.

Study subjects were asked to complete a telephone survey. Data were collected for 3,037 smokers who had visited a health care setting during the past 12 months.

Smokers were more likely to report being spoken to about smoking, being advised to quit, being offered help in quitting or having a follow-up visit arranged if they received care in a private physician's office, if they rated their health status as fair or poor, if they had smoked more than a pack a day for a long duration or if they were thinking about quitting. Women were more likely than men and employed persons were more likely than unemployed persons to receive advice to quit. Smokers who rated their health status as fair or poor were more likely to be prescribed medication to help them quit smoking than were those who rated their health as good.

As few as 14.9 percent of the persons surveyed reported being offered help to quit smoking, and 3.0 percent said they were given a follow-up appointment. The data showed that physicians were more likely to offer advice when the smoker expressed a willingness to quit. Thus, primary care physicians who only intervene with smokers who are motivated to quit are missing opportunities to provide counseling about smoking cessation strategies to the majority of their patients who smoke.

The authors suggest that there is considerable room for improvement in physicians' efforts to encourage patients to quit smoking and to provide follow-up visits. The authors note that office systems should be used to enhance identification and treatment of smokers, as recommended in guidelines from the Agency for Health Care Policy and Research.

BARBARA APGAR, M.D., M.S.

Goldstein MG, et al. Physicians counseling smokers. A population-based survey of patients' perceptions of health care provider­delivered smoking cessation interventions. Arch Intern Med 1997;157:1313-9.

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"Tips from Other Journals" are written by the medical editors of American Family Physician.

Copyright © 1998 by the American Academy of Family Physicians.
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